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|
||
<a href="/help/"
|
||
data-ga-category="featured_link"
|
||
data-ga-action="user_guide">
|
||
User Guide
|
||
</a>
|
||
</span>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
|
||
</form>
|
||
|
||
|
||
<div id="article-page-header">
|
||
<div id="article-top-actions-bar" class="article-top-actions-bar">
|
||
<div class="inner-wrap">
|
||
<div class="actions-container">
|
||
<div class="return-to-search">
|
||
|
||
|
||
</div>
|
||
|
||
<div class="multiple-results-actions " role="region" aria-label="save, email, send to">
|
||
<button id="save-results-panel-trigger"
|
||
type="button"
|
||
class="save-results save-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="save-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="open">
|
||
Save
|
||
</button><button id="email-results-panel-trigger"
|
||
type="button"
|
||
class="email-results email-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="email-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="open">
|
||
Email
|
||
</button><div class="more-actions dropdown-block"><button id="more-actions-trigger"
|
||
type="button"
|
||
class="trigger more-actions-trigger"
|
||
ref="linksrc=show_moreactions_btn"
|
||
aria-label="Send to"
|
||
aria-controls="more-actions-dropdown">Send to</button><div id="more-actions-dropdown" class="dropdown dropdown-container" hidden><div class="content"><ul class="more-actions-links"><li><a class="clipboard-panel-trigger dropdown-block-link "
|
||
href="#"
|
||
role="button"
|
||
data-ga-category="save_share"
|
||
data-ga-action="clipboard"
|
||
data-ga-label="send">
|
||
Clipboard
|
||
</a></li><li><a role="button" class="dropdown-block-link bibliography-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F35362222%2F%23open-bibliography-panel">My Bibliography</a></li><li><a role="button" class="dropdown-block-link collections-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F35362222%2F%23open-collections-panel">Collections</a></li><li><a role="button" class="citation-manager-panel-trigger dropdown-block-link citation-manager-trigger-target" href="#">Citation manager</a></li></ul></div></div></div>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region">
|
||
<button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog">
|
||
<span class="button-label">Display options</span>
|
||
</button>
|
||
|
||
<div class="dropdown" hidden>
|
||
<div class="title">
|
||
Display options
|
||
</div>
|
||
|
||
<div class="content">
|
||
|
||
<div class="format-container">
|
||
<span class="option-label">
|
||
Format
|
||
</span>
|
||
<select name="format" data-initial-value="abstract" aria-label="Display format" id="article-display-format">
|
||
<option value="abstract">Abstract</option>
|
||
|
||
<option value="pubmed">PubMed</option>
|
||
|
||
<option value="pmid">PMID</option>
|
||
|
||
</select>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
</div>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="QXfZMElUFThE8KRgJmDy8HOXLBnkuouL7KZ4puOgfu482bX6mFgACPkBjF5wnZ25">
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="article-panels-container" class="article-panels-container">
|
||
<div id="save-action-panel" class="save-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Save citation to file
|
||
</h2>
|
||
<form id="save-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="QXfZMElUFThE8KRgJmDy8HOXLBnkuouL7KZ4puOgfu482bX6mFgACPkBjF5wnZ25">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="save-action-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="save-action-format" name="results-format" class="action-panel-selector">
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="pubmed-text">PubMed</option>
|
||
<option value="pmid">PMID</option>
|
||
<option value="abstract">Abstract (text)</option>
|
||
<option value="csv">CSV</option>
|
||
</select>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Save citations to file' panel"
|
||
ref="linksrc=close_save_panel"
|
||
aria-controls="save-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="email-action-panel"
|
||
class="email-action-panel action-panel"
|
||
aria-hidden="true"
|
||
data-recaptcha-script-url="https://www.recaptcha.net/recaptcha/enterprise.js?render=explicit&onload=onloadCaptchaCallback"
|
||
data-recaptcha-enabled="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Email citation
|
||
</h2>
|
||
<form id="email-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/send-email/"
|
||
data-by-search-action="/results-export-email-by-search-data/"
|
||
data-by-ids-action="/send-email/"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post"
|
||
method="post"
|
||
>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="QXfZMElUFThE8KRgJmDy8HOXLBnkuouL7KZ4puOgfu482bX6mFgACPkBjF5wnZ25">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<span class="action-panel-label">
|
||
Subject:
|
||
</span>
|
||
<span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 35362222 - PubMed</span>
|
||
<input type="hidden" name="email-subject" value="1 selected item: 35362222"/>
|
||
<input type="hidden" name="email-subject-hash" value="8f0b0ac1bd638fd44a1432b45dca64794724e5c45ff1cbe3a31a18d4faf8394a"/>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-to" class="action-panel-label required-field-asterisk">
|
||
To:
|
||
</label>
|
||
<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-from" class="action-panel-label">
|
||
From:
|
||
</label>
|
||
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
|
||
</div>
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-citation-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
|
||
<option selected="selected" value="summary">Summary</option>
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="abstract">Abstract</option>
|
||
<option value="abstract-text">Abstract (text)</option>
|
||
|
||
</select>
|
||
</div>
|
||
<div class="include-supplemental-container">
|
||
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
|
||
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="form-field recaptcha ">
|
||
|
||
|
||
|
||
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
|
||
|
||
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="send">
|
||
Send email
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Email citations' panel"
|
||
ref="linksrc=close_email_panel"
|
||
aria-controls="email-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
<input type="hidden" name="email-search-details" value="" />
|
||
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="collections-action-panel"
|
||
class="collections-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-collections-open-panel-enabled="false"
|
||
data-collections-open-panel-url-hash="#open-collections-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to Collections
|
||
</h3>
|
||
|
||
|
||
<form id="collections-action-panel-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-add-to-collection-max-amount="1000"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="QXfZMElUFThE8KRgJmDy8HOXLBnkuouL7KZ4puOgfu482bX6mFgACPkBjF5wnZ25">
|
||
|
||
|
||
|
||
<div class="choice-group" role="radiogroup">
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_new">
|
||
<label for="collections-action-panel-new">Create a new collection</label>
|
||
</li>
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_existing">
|
||
<label for="collections-action-panel-existing">Add to an existing collection</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
|
||
<div class="controls-wrapper">
|
||
<div class="action-panel-control-wrap new-collections-controls">
|
||
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label>
|
||
<input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-panel-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="save_share"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection">
|
||
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div>
|
||
</div>
|
||
<div class="action-panel-control-wrap existing-collections-controls">
|
||
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label>
|
||
<select id="collections-action-panel-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="save_share"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
|
||
</select>
|
||
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="add">
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="bibliography-action-panel"
|
||
class="bibliography-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-bibliography-open-panel-enabled="false"
|
||
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to My Bibliography
|
||
</h3>
|
||
<form id="bibliography-action-panel-form"
|
||
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-add-to-bibliography-max-amount="100"
|
||
data-add-to-bibliography-batch-size="10"
|
||
data-bibliography-delegates-url="/list-bibliography-delegates/"
|
||
data-add-to-bibliography-url="/add-to-bibliography/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="QXfZMElUFThE8KRgJmDy8HOXLBnkuouL7KZ4puOgfu482bX6mFgACPkBjF5wnZ25">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap bibliographies-controls">
|
||
<div class="choice-group">
|
||
<ul class="bibliographies-action-add radio-group-items">
|
||
<li>
|
||
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
|
||
<label for="my-bibliography">My Bibliography</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your delegates due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore>
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to bibliography' panel"
|
||
ref="linksrc=close_bibliography_panel"
|
||
aria-controls="bibliography-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="mybib"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
|
||
data-saved-search-open-panel-enabled="false"
|
||
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your saved search
|
||
</h2>
|
||
|
||
<form id="saved-search-action-panel-form"
|
||
class="saved-search-action-panel-form action-panel-content action-form"
|
||
data-create-saved-search-url="/create-saved-search/"
|
||
data-try-search-terms-url="/try-search-term/"
|
||
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="QXfZMElUFThE8KRgJmDy8HOXLBnkuouL7KZ4puOgfu482bX6mFgACPkBjF5wnZ25">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
|
||
Name of saved search:
|
||
</label>
|
||
<input maxlength="200"
|
||
type="text"
|
||
name="saved-search-name"
|
||
id="saved-search-name"
|
||
class="saved-search-name"
|
||
value=""
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
|
||
Search terms:
|
||
</label>
|
||
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
|
||
</div>
|
||
<div class="test-search-term-wrap">
|
||
<a href="#" class="try-search-term">Test search terms</a>
|
||
</div>
|
||
<div class="choice-group action-panel-extra-margin-top">
|
||
<span class="action-panel-label" id="fieldset-label">
|
||
Would you like email updates of new search results?
|
||
</span>
|
||
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
|
||
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
|
||
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
|
||
</li>
|
||
<li>
|
||
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
|
||
<label for="saved-search-alert-no" class="action-panel-label">No</label>
|
||
</li>
|
||
</ul>
|
||
</fieldset>
|
||
</div>
|
||
|
||
<div class="alert-schedule-wrap">
|
||
<div class="action-panel-control-wrap">
|
||
<label class="action-panel-label">
|
||
Email:
|
||
</label>
|
||
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
|
||
</div>
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="saved-search-frequency" class="action-panel-label">
|
||
Frequency:
|
||
</label>
|
||
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
|
||
<option value="monthly">Monthly</option>
|
||
<option value="weekly">Weekly</option>
|
||
<option value="daily">Daily</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-monthly-additional">
|
||
<label for="saved-search-monthly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
|
||
<option value="Sunday">The first Sunday</option>
|
||
<option value="Monday">The first Monday</option>
|
||
<option value="Tuesday">The first Tuesday</option>
|
||
<option value="Wednesday">The first Wednesday</option>
|
||
<option value="Thursday">The first Thursday</option>
|
||
<option value="Friday">The first Friday</option>
|
||
<option value="Saturday">The first Saturday</option>
|
||
<option value="day">The first day</option>
|
||
<option value="weekday">The first weekday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-weekly-additional">
|
||
<label for="saved-search-weekly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
|
||
<option value="Sunday">Sunday</option>
|
||
<option value="Monday">Monday</option>
|
||
<option value="Tuesday">Tuesday</option>
|
||
<option value="Wednesday">Wednesday</option>
|
||
<option value="Thursday">Thursday</option>
|
||
<option value="Friday">Friday</option>
|
||
<option value="Saturday">Saturday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-report" class="action-panel-label">
|
||
Report format:
|
||
</label>
|
||
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
|
||
<option value="DocSum">Summary</option>
|
||
<option value="DocSumText">Summary (text)</option>
|
||
<option value="Abstract">Abstract</option>
|
||
<option value="AbstractText">Abstract (text)</option>
|
||
<option value="MEDLINE">PubMed</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-amount" class="action-panel-label">
|
||
Send at most:
|
||
</label>
|
||
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
|
||
<option value="1">1 item</option>
|
||
<option value="5" selected>5 items</option>
|
||
<option value="10">10 items</option>
|
||
<option value="20">20 items</option>
|
||
<option value="50">50 items</option>
|
||
<option value="100">100 items</option>
|
||
<option value="200">200 items</option>
|
||
</select>
|
||
</div>
|
||
<div>
|
||
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
|
||
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
|
||
Send even when there aren't any new results
|
||
</label>
|
||
</div>
|
||
<div class="action-panel-control-wrap option-text-in-email-wrap">
|
||
<label for="saved-search-email-text" class="action-panel-label">
|
||
Optional text in email:
|
||
</label>
|
||
<textarea name="saved-search-email-text"
|
||
id="saved-search-email-text"
|
||
class="saved-search-email-text"></textarea>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Save
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your saved search' panel"
|
||
ref="linksrc=close_saved_search_panel"
|
||
aria-controls="saved-search-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Create a file for external citation management software
|
||
</h2>
|
||
<form id="citation-manager-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="QXfZMElUFThE8KRgJmDy8HOXLBnkuouL7KZ4puOgfu482bX6mFgACPkBjF5wnZ25">
|
||
|
||
|
||
|
||
<input name="results-format" type="hidden" value="pubmed"/>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Send citations to citation manager' panel"
|
||
ref="linksrc=close_citation_manager_panel"
|
||
aria-controls="citation-manager-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your RSS Feed
|
||
</h2>
|
||
|
||
<form id="rss-action-panel-form"
|
||
class="rss-action-panel-form action-panel-content action-form"
|
||
data-create-rss-feed-url="/create-rss-feed-url/"
|
||
data-search-form-term-value="">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="QXfZMElUFThE8KRgJmDy8HOXLBnkuouL7KZ4puOgfu482bX6mFgACPkBjF5wnZ25">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="rss-name" class="action-panel-label required-field-asterisk">
|
||
Name of RSS Feed:
|
||
</label>
|
||
<input maxlength="200"
|
||
placeholder="Name"
|
||
type="text"
|
||
name="rss-name"
|
||
id="rss-name"
|
||
class="rss-name"
|
||
value=''
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="rss-limit-wrap">
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="rss-limit" class="action-panel-label">
|
||
Number of items displayed:
|
||
</label>
|
||
<select id="rss-limit" class="no-border-panel-selector rss-limit">
|
||
<option value="5">5</option>
|
||
<option value="10">10</option>
|
||
<option value="15" selected="selected">15</option>
|
||
<option value="20">20</option>
|
||
<option value="50">50</option>
|
||
<option value="100">100</option>
|
||
</select>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Creating..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Create RSS
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your RSS' panel"
|
||
ref="linksrc=close_rss_panel"
|
||
aria-controls="rss-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap rss-link-copy-wrap">
|
||
<label for="rss-link" class="usa-sr-only">RSS Link</label>
|
||
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
|
||
<button
|
||
type="button"
|
||
disabled
|
||
class="rss-link-copy-button disabled"
|
||
data-ga-category="save_share"
|
||
data-ga-action="rss"
|
||
data-ga-label="copy">
|
||
Copy
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="article-page" id="article-page" data-article-pmid="35362222">
|
||
<aside class="page-sidebar">
|
||
<div class="inner-wrap">
|
||
|
||
<div class="full-text-links">
|
||
<div class="full-view">
|
||
<h3 class="title">
|
||
Full text links
|
||
</h3>
|
||
<div class="full-text-links-list">
|
||
<a class="link-item
|
||
|
||
dialog-focus"
|
||
href="https://doi.org/10.15252/emmm.202114904"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=3094&itool=Abstract-def&log$=linkouticon&uid=35362222&db=pubmed&nlmid=101487380"
|
||
title="See full text options at Nature Publishing Group"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="Nature Publishing Group"
|
||
data-ga-label="35362222"
|
||
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.embopress.org-pb-assets-embo-site-images-pubmed-embomm.gif" alt="Nature Publishing Group full text link"><span class="text">
|
||
|
||
Nature Publishing Group
|
||
|
||
</span></a><a class="link-item
|
||
pmc
|
||
"
|
||
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/35362222/"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=35362222&db=pubmed&nlmid=101487380"
|
||
title="Free full text at PubMed Central"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="PMC"
|
||
data-ga-label="35362222"
|
||
><span class="text">
|
||
|
||
Free PMC article
|
||
|
||
</span></a>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="short-view">
|
||
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
|
||
Full text links
|
||
</a>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
|
||
aria-label="Open dialog with citation text in different styles"
|
||
data-ga-category="save_share"
|
||
data-ga-action="cite"
|
||
data-ga-label="open"
|
||
data-all-citations-url="/35362222/citations/"
|
||
data-citation-style="nlm"
|
||
data-pubmed-format-link="/35362222/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="35362222" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
|
||
aria-label="Save article in MyNCBI collections."
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_button"
|
||
data-collections-open-dialog-enabled="false"
|
||
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F35362222%2F%23open-collections-dialog"
|
||
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
|
||
class="dialog collections-dialog"
|
||
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="QXfZMElUFThE8KRgJmDy8HOXLBnkuouL7KZ4puOgfu482bX6mFgACPkBjF5wnZ25"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
|
||
id="collections-action-dialog-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
|
||
id="collections-action-dialog-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label><input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-dialog-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label><select id="collections-action-dialog-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="add">
|
||
Add
|
||
</button><button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger"
|
||
title="Open dialog with more actions to take"
|
||
ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region"><button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title">
|
||
Display options
|
||
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</a></li></ul></div></div></div><span class="period">. </span><span class="cit">2022 May 9;14(5):e14904.</span>
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<h1 class="heading-title">
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S1P defects cause a new entity of cataract, alopecia, oral mucosal disorder, and psoriasis-like syndrome
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S1P defects cause a new entity of cataract, alopecia, oral mucosal disorder, and psoriasis-like syndrome
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|
||
</div>
|
||
|
||
|
||
|
||
<span class="citation-doi">
|
||
doi: 10.15252/emmm.202114904.
|
||
</span>
|
||
|
||
|
||
|
||
<span class="secondary-date">
|
||
Epub 2022 Apr 1.
|
||
</span>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<div class="expanded-authors" id="short-view-expanded-authors">
|
||
|
||
<div class="authors">
|
||
<h3 class="title">
|
||
Authors
|
||
</h3>
|
||
|
||
|
||
|
||
<div class="authors-list">
|
||
<span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Chen+F&cauthor_id=35362222"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Fuying Chen">Fuying Chen</a><sup class="equal-contrib-container"><span class="author-sup-separator"> </span><a class="equal-contrib" title="Contributed equally" href="#short-view-equal-contrib-explanation" ref="linksrc=author_equal_contrib">#</a></sup><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China." href="#short-view-affiliation-1" ref="linksrc=author_aff">
|
||
1
|
||
</a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, China." href="#short-view-affiliation-2" ref="linksrc=author_aff">
|
||
2
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Ni+C&cauthor_id=35362222"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Cheng Ni">Cheng Ni</a><sup class="equal-contrib-container"><span class="author-sup-separator"> </span><a class="equal-contrib" title="Contributed equally" href="#short-view-equal-contrib-explanation" ref="linksrc=author_equal_contrib">#</a></sup><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China." href="#short-view-affiliation-1" ref="linksrc=author_aff">
|
||
1
|
||
</a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, China." href="#short-view-affiliation-2" ref="linksrc=author_aff">
|
||
2
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Wang+X&cauthor_id=35362222"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Xiaoxiao Wang">Xiaoxiao Wang</a><sup class="equal-contrib-container"><span class="author-sup-separator"> </span><a class="equal-contrib" title="Contributed equally" href="#short-view-equal-contrib-explanation" ref="linksrc=author_equal_contrib">#</a></sup><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China." href="#short-view-affiliation-1" ref="linksrc=author_aff">
|
||
1
|
||
</a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, China." href="#short-view-affiliation-2" ref="linksrc=author_aff">
|
||
2
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Cheng+R&cauthor_id=35362222"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Ruhong Cheng">Ruhong Cheng</a><sup class="equal-contrib-container"><span class="author-sup-separator"> </span><a class="equal-contrib" title="Contributed equally" href="#short-view-equal-contrib-explanation" ref="linksrc=author_equal_contrib">#</a></sup><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China." href="#short-view-affiliation-1" ref="linksrc=author_aff">
|
||
1
|
||
</a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, China." href="#short-view-affiliation-2" ref="linksrc=author_aff">
|
||
2
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Pan+C&cauthor_id=35362222"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Chaolan Pan">Chaolan Pan</a><sup class="equal-contrib-container"><span class="author-sup-separator"> </span><a class="equal-contrib" title="Contributed equally" href="#short-view-equal-contrib-explanation" ref="linksrc=author_equal_contrib">#</a></sup><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China." href="#short-view-affiliation-1" ref="linksrc=author_aff">
|
||
1
|
||
</a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, China." href="#short-view-affiliation-2" ref="linksrc=author_aff">
|
||
2
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Wang+Y&cauthor_id=35362222"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Yumeng Wang">Yumeng Wang</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China." href="#short-view-affiliation-1" ref="linksrc=author_aff">
|
||
1
|
||
</a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, China." href="#short-view-affiliation-2" ref="linksrc=author_aff">
|
||
2
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Liang+J&cauthor_id=35362222"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Jianying Liang">Jianying Liang</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China." href="#short-view-affiliation-1" ref="linksrc=author_aff">
|
||
1
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Zhang+J&cauthor_id=35362222"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Jia Zhang">Jia Zhang</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China." href="#short-view-affiliation-1" ref="linksrc=author_aff">
|
||
1
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Cheng+J&cauthor_id=35362222"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Jinke Cheng">Jinke Cheng</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China." href="#short-view-affiliation-3" ref="linksrc=author_aff">
|
||
3
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Chin+YE&cauthor_id=35362222"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Y Eugene Chin">Y Eugene Chin</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Instituteof Health Sciences, Chinese Academy of Sciences, Shanghai Jiaotong University School of Medicine, Shanghai, China." href="#short-view-affiliation-4" ref="linksrc=author_aff">
|
||
4
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Zhou+Y&cauthor_id=35362222"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
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data-ga-action="author_link"
|
||
data-ga-label="Yi Zhou">Yi Zhou</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China." href="#short-view-affiliation-5" ref="linksrc=author_aff">
|
||
5
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Wang+Z&cauthor_id=35362222"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Zhen Wang">Zhen Wang</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Dermatology, Children's Hospital of Shanghai Jiaotong University, Shanghai, China." href="#short-view-affiliation-6" ref="linksrc=author_aff">
|
||
6
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Guo+Y&cauthor_id=35362222"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Yiran Guo">Yiran Guo</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Center for Data Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, PA, USA." href="#short-view-affiliation-7" ref="linksrc=author_aff">
|
||
7
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Chen+S&cauthor_id=35362222"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="She Chen">She Chen</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China." href="#short-view-affiliation-8" ref="linksrc=author_aff">
|
||
8
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Htun+S&cauthor_id=35362222"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Stephanie Htun">Stephanie Htun</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Division of Genetics, Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA." href="#short-view-affiliation-9" ref="linksrc=author_aff">
|
||
9
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Mathes+EF&cauthor_id=35362222"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Erin F Mathes">Erin F Mathes</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Departments of Dermatology and Pediatrics, University California, San Francisco, CA, USA." href="#short-view-affiliation-10" ref="linksrc=author_aff">
|
||
10
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=de+Alba+Campomanes+AG&cauthor_id=35362222"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Alejandra G de Alba Campomanes">Alejandra G de Alba Campomanes</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Ophthalmology, University of California, San Francisco, CA, USA." href="#short-view-affiliation-11" ref="linksrc=author_aff">
|
||
11
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Slavotinek+AM&cauthor_id=35362222"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Anne M Slavotinek">Anne M Slavotinek</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Division of Genetics, Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA." href="#short-view-affiliation-9" ref="linksrc=author_aff">
|
||
9
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Zhang+S&cauthor_id=35362222"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Si Zhang">Si Zhang</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China." href="#short-view-affiliation-8" ref="linksrc=author_aff">
|
||
8
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Li+M&cauthor_id=35362222"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Ming Li">Ming Li</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China." href="#short-view-affiliation-1" ref="linksrc=author_aff">
|
||
1
|
||
</a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, China." href="#short-view-affiliation-2" ref="linksrc=author_aff">
|
||
2
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Yao+Z&cauthor_id=35362222"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Zhirong Yao">Zhirong Yao</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China." href="#short-view-affiliation-1" ref="linksrc=author_aff">
|
||
1
|
||
</a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, China." href="#short-view-affiliation-2" ref="linksrc=author_aff">
|
||
2
|
||
</a></sup></span>
|
||
</div>
|
||
|
||
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<div class="affiliations">
|
||
<h3 class="title">
|
||
Affiliations
|
||
</h3>
|
||
<ul class="item-list">
|
||
|
||
<li data-affiliation-id="short-view-affiliation-1"
|
||
id="short-view-affiliation-1"
|
||
><sup class="key">1</sup> Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-2"
|
||
id="short-view-affiliation-2"
|
||
><sup class="key">2</sup> Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, China.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-3"
|
||
id="short-view-affiliation-3"
|
||
><sup class="key">3</sup> Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-4"
|
||
id="short-view-affiliation-4"
|
||
><sup class="key">4</sup> Instituteof Health Sciences, Chinese Academy of Sciences, Shanghai Jiaotong University School of Medicine, Shanghai, China.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-5"
|
||
id="short-view-affiliation-5"
|
||
><sup class="key">5</sup> Department of gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-6"
|
||
id="short-view-affiliation-6"
|
||
><sup class="key">6</sup> Department of Dermatology, Children's Hospital of Shanghai Jiaotong University, Shanghai, China.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-7"
|
||
id="short-view-affiliation-7"
|
||
><sup class="key">7</sup> Center for Data Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, PA, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-8"
|
||
id="short-view-affiliation-8"
|
||
><sup class="key">8</sup> NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-9"
|
||
id="short-view-affiliation-9"
|
||
><sup class="key">9</sup> Division of Genetics, Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-10"
|
||
id="short-view-affiliation-10"
|
||
><sup class="key">10</sup> Departments of Dermatology and Pediatrics, University California, San Francisco, CA, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-11"
|
||
id="short-view-affiliation-11"
|
||
><sup class="key">11</sup> Department of Ophthalmology, University of California, San Francisco, CA, USA.</li>
|
||
|
||
</ul>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
<div class="equal-contrib-block">
|
||
<div class="equal-contrib-explanation" id="short-view-equal-contrib-explanation"><sup class="key">#</sup> Contributed equally.</div>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<ul class="identifiers" id="short-view-identifiers">
|
||
|
||
<li>
|
||
<span class="identifier pubmed">
|
||
<span class="id-label">
|
||
|
||
PMID:
|
||
|
||
</span>
|
||
|
||
|
||
<strong class="current-id" title="PubMed ID">35362222</strong>
|
||
|
||
|
||
|
||
</span>
|
||
|
||
</li>
|
||
|
||
<li>
|
||
<span class="identifier pmc">
|
||
<span class="id-label">
|
||
|
||
PMCID:
|
||
|
||
</span>
|
||
|
||
|
||
<a class="id-link"
|
||
target="_blank"
|
||
rel="noopener"
|
||
ref="linksrc=article_id_link&article_id=PMC9081911&id_type=PMC"
|
||
href="https://pmc.ncbi.nlm.nih.gov/articles/PMC9081911/"
|
||
data-ga-category="full_text"
|
||
data-ga-action="PMCID"
|
||
>
|
||
PMC9081911
|
||
</a>
|
||
|
||
|
||
|
||
</span>
|
||
|
||
</li>
|
||
|
||
<li>
|
||
<span class="identifier doi">
|
||
<span class="id-label">
|
||
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In this report, we discovered a new entity named cataract, alopecia, oral mucosal disorder, and psoriasis-like (CAOP) syndrome in two unrelated and ethnically diverse patients. Furthermore, patient 1 failed to respond to regular treatment. We found that CAOP syndrome was caused by an autosomal recessive defect in the mitochondrial membrane-bound transcription factor peptidase/site-1 protease (MBTPS1, S1P). Mitochondrial abnormalities were observed in patient 1 with CAOP syndrome. Furthermore, we found that S1P is a novel mitochondrial protein that forms a trimeric complex with ETFA/ETFB. S1P enhances ETFA/ETFB flavination and maintains its stability. Patient S1P variants destabilize ETFA/ETFB, impair mitochondrial respiration, decrease fatty acid β-oxidation activity, and shift mitochondrial oxidative phosphorylation (OXPHOS) to glycolysis. Mitochondrial dysfunction and inflammatory lesions in patient 1 were significantly ameliorated by riboflavin supplementation, which restored the stability of ETFA/ETFB. Our study discovered that mutations in MBTPS1 resulted in a new entity of CAOP syndrome and elucidated the mechanism of the mutations in the new disease.
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CAOP; MBTPS1; electron transfer flavoprotein; mitochondrial respiratory chain reaction.
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© 2022 The Authors. Published under the terms of the CC BY 4.0 license.
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<p> Figure 1. CAOP syndrome patients carry <i> MBTPS1… </i> </p>
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<p> Figure 1. CAOP syndrome patients carry <i> MBTPS1 </i> variants and inflammatory disorders </p>
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<div class="figure-caption-contents"><ol style="list-style-type:none"> <li> <span class="label"> A </span> <p> Representative clinical picture… </p> </li> </ol></div>
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Figure 1. CAOP syndrome patients carry <i>MBTPS1</i> variants and inflammatory disorders
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<div class="figure-caption-contents"><ol style="list-style-type:none"><li><span class="label">A</span><p>Representative clinical picture of two patients with CAOP syndrome (14‐year‐old patient 1 and 5‐year‐old patient 2).</p></li><li><span class="label">B</span><p>Hematoxylin and eosin (H&E) staining of skin biopsies from patient 1 and healthy controls. Scale bars: 200 µm.</p></li><li><span class="label">C, D</span><p>Gene sequencing revealed heterozygous <i>MBTPS1</i> p.Val355Gly (c.1064T>G) and p.Ter1053Arg (c.3157T>C) variants in patient 1 and heterozygous <i>MBTPS1</i> p.Ter1053Cys (c.3159A>T) and c.2072‐2A>T variants in patient 2. The arrows indicate the variants.</p></li><li><span class="label">E</span><p>Schematic diagram of the S1P domain structure. The p.Val355Gly variant is localized in the peptidase S8 domain, the c.2072‐2A>T variant is located in the ABC transp‐aux domain, and p.Ter1053Arg and p.Ter1053Cys are found in the cytoplasmic domain.</p></li></ol></div>
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<p> Figure EV1. Variants of <i> MBTPS1 </i> in CAOP… </p>
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<p> Figure EV1. Variants of <i> MBTPS1 </i> in CAOP syndrome </p>
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<div class="figure-caption-contents"><ol style="list-style-type:upper-alpha"> <li> <p> Whole‐exome sequencing analysis of patient 1. No… </p> </li> </ol></div>
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Figure EV1. Variants of <i>MBTPS1</i> in CAOP syndrome
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<div class="figure-caption-contents"><ol style="list-style-type:upper-alpha"><li><p>Whole‐exome sequencing analysis of patient 1. No meaningful new variants were detected based on the autosomal dominant pattern, X‐linked hemizygous genetic model, or autosomal recessive inheritance pattern. The analysis according to an autosomal recessive genetic mode detected compound heterozygous variants of the <i>MBTPS1</i> gene.</p></li><li><p>Protein expression of S1P in skin biopsies of patient 1 and healthy controls. The heterozygous variants in the <i>MBTPS1</i> gene resulted in two bands of S1P protein: one band was similar to the S1P band of the healthy control, and the other band was markedly larger than that of the healthy control.</p></li><li><p>Ethidium bromide‐stained agarose gel of the cDNA products resulting from the splicing assay of the wild‐type (WT) and variant (c.2072‐2A>T) pSPL3<i>‐MBTPS1</i> minigenes. The 491‐base‐pair (bp) product represents the mutant RNA transcript lacking <i>MBTPS1</i> exon 16, and the 648‐bp band corresponds to a wild‐type transcript that includes <i>MBTPS1</i> exon 16. The identity of the PCR fragments was confirmed by sequencing.</p></li></ol> Source data are available online for this figure.</div>
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<p> Figure 2. S1P dysfunction impairs mitochondrial import and results in mitochondrial abnormalities </p>
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Figure 2. S1P dysfunction impairs mitochondrial import and results in mitochondrial abnormalities
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<div class="figure-caption-contents"><ol style="list-style-type:none"><li><span class="label">A, B</span><p>Representative transmission electron microscopy (TEM) images showing keratinocyte mitochondria (red arrow) in patient 1 (A) and in the <i>Mbtps1</i>‐conditional knockout (cKO) mouse model (B). Scale bars: 2 µm.</p></li><li><span class="label">C, D</span><p>Quantification of the mitochondrial number and morphology in patient 1 (C) and the <i>Mbtps1</i>‐cKO mouse model (D). (C) Left panel: <i>n</i> = 13 biological replicates of normal individuals, <i>n</i> = 10 biological replicates of patient 1. Middle and right panel: <i>n</i> = 121 biological samples of normal individuals and patient 1. (D) Left panel: <i>n</i> = 23 biological replicates of <i>Mbtps1‐</i>loxP mice; <i>n</i> = 15 biological replicates of <i>Mbtps1</i>‐cKO mice. Middle panel and right panel: <i>n</i> = 113 biological replicates of <i>Mbtps1‐</i>loxP mice and <i>Mbtps1</i>‐cKO.</p></li><li><span class="label">E</span><p>Immunofluorescence experiments showed that mutant S1P (p.Val355Gly and p.Ter1053Arg) was diffusely localized in the cytosol and showed lower mitochondrial localization compared with wild‐type S1P, which suggested that these variants disrupt its mitochondrial import. The white arrowheads indicate the colocation (yellow) of S1P (green) and the mitochondrial tracer (red). Scale bars: 20 μm (panels 1–4); scale bars: 2 μm (panel 5).</p></li><li><span class="label">F</span><p>Cellular component separation assay showing that S1P was enriched in mitochondria. Biochemical fractionation of the whole‐cell lysate (WCL), cytosol (Cyto, tubulin), mitochondria (Mito, COX IV), lysosomes (Lyso, LAMP1), Golgi apparatus (Golgi, GM130), endoplasmic reticulum (ER, ERp72), and nucleus (Nue, Lamin B) from HaCaT cells.</p></li><li><span class="label">G</span><p>A component separation assay revealed a lower expression of mutant S1P (p.Val355Gly and p.Ter1053Arg) than wild‐type S1P in mitochondria.</p></li><li><span class="label">H</span><p>The impaired binding of mutant S1P (p.Val355Gly and p.Ter1053Arg) to translocase of the outer membrane (TOM) 70 and translocase of the inner membrane (TIM) 23 was detected by a coimmunoprecipitation (Co‐IP) assay.</p></li></ol> Data information: The data are presented as the means ± SDs. Statistical significance was assessed by the Mann–Whitney two‐tailed <i>U</i> test (C and D). ***<i>P</i> < 0.001. Three biological replicates were included in the study (E–H). Source data are available online for this figure.</div>
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Figure EV2. S1P dysfunction results in abnormalities in lipid metabolism and lysosomes
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<div class="figure-caption-contents"><ol style="list-style-type:upper-alpha"><li><p>Deposited lipid vesicles (green arrowheads, lower panel) and increased amounts of lysosomes (red arrowheads, lower panel) were observed in patient 1, but no ER abnormalities were detected (white arrowheads, upper panel). Scale bars: 1 μm (upper panel) and 5 μm (lower panel).</p></li><li><p>Volcano plot showing abnormalities in cholesterol and triglyceride biosynthesis in <i>MBTPS1‐</i>knockout (<i>MBTPS1</i>‐KO) HaCaT cells. The fold changes were calculated as log2 (expression in <i>MBTPS1‐</i>KO/expression in <i>MBTPS1‐</i>Ctrl) (<i>n</i> = 4 biological replicates).</p></li><li><p>Hematoxylin and eosin (H&E) staining showed psoriasiform perivasculitis in <i>Mbtps1‐</i>conditional knockout (cKO) mice. Scale bars: 100 μm.</p></li><li><p>Oil red O staining showed lipid accumulation in <i>Mbtps1</i>‐cKO mice. Scale bar: 100 μm.</p></li><li><p>The encapsulation of mitochondria in lysosomes (red arrowhead) was observed in <i>Mbtps1‐</i>cKO mice. Scale bars: 2 μm.</p></li></ol></div>
|
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id="article-image-4"
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6db8/9081911/64a1420a4ee4/EMMM-14-e14904-g004.gif"
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|
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<p> Figure EV3. S1P knockdown results in growth… </p>
|
||
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<strong class="figure-label">
|
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<p> Figure EV3. S1P knockdown results in growth limitations, spinal curvature, and skin abnormalities in zebrafish </p>
|
||
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|
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<strong class="figure-label">
|
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Figure EV3. S1P knockdown results in growth limitations, spinal curvature, and skin abnormalities in zebrafish
|
||
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|
||
|
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|
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|
||
<div class="figure-caption-contents"><ol style="list-style-type:upper-alpha"><li><p>
|
||
<i>Mbtps1</i>‐morpholino (MO) zebrafish exhibited obvious growth limitations and spinal curvature.</p></li><li><p>Skin abnormalities (red arrows) were observed in <i>mbtps1</i>‐MO zebrafish. Scale bars: 10 μm.</p></li><li><p>The encapsulation of mitochondria in lysosomes (red arrows) was observed in <i>mbtps1</i>‐MO zebrafish at 48 hpf. Scale bars: 2 μm.</p></li><li><p>Increases in the mitochondrial number and morphological alterations of mitochondria were observed in the <i>mbtps1</i>‐MO zebrafish model. Mitochondria were induced into multilamellar globules, and the folds of cristae in the inner membrane extended to onion‐like circles in the <i>mbtps1</i>‐MO zebrafish model (red arrows). Scale bars: 2 µm.</p></li><li><p>Quantification of the mitochondrial number and morphology in the zebrafish model. Left panel: Quantification of the mitochondrial number per cell in the zebrafish model (<i>n</i> = 12 biological replicates of control‐MO (Ctrl‐MO) zebrafish; <i>n</i> = 10 biological replicates of <i>mbtps1</i>‐MO zebrafish, biological replicates). Middle panel: Quantification of the mitochondrial length in the zebrafish model (<i>n</i> = 93 biological replicates). Right panel: Quantification of the length‐to‐width ratio of mitochondria in the zebrafish model (<i>n</i> = 93 biological replicates).</p></li></ol> Data information: The data are presented as the means ± SDs. Statistical significance was assessed by unpaired two‐tailed Student’s <i>t</i>‐test (E, left panel) or the Mann–Whitney two‐tailed <i>U</i> test (E, middle panel and right panel). **<i>P</i> < 0.01, ***<i>P</i> < 0.001. Source data are available online for this figure.</div>
|
||
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|
||
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|
||
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|
||
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|
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id="article-image-5"
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6db8/9081911/149d9c8c241e/EMMM-14-e14904-g014.gif"
|
||
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|
||
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||
<strong class="figure-label">
|
||
<p> Figure 3. S1P forms a trimetric complex… </p>
|
||
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|
||
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||
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|
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||
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||
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||
|
||
<strong class="figure-label">
|
||
<p> Figure 3. S1P forms a trimetric complex with electron transfer flavoprotein (ETF) A and ETFB… </p>
|
||
</strong>
|
||
|
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||
|
||
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||
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||
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||
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||
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||
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||
<strong class="figure-label">
|
||
Figure 3. S1P forms a trimetric complex with electron transfer flavoprotein (ETF) A and ETFB proteins
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><ol style="list-style-type:upper-alpha"><li><p>LC–MS/MS analysis of S1P‐binding proteins. Total protein lysate was subjected to coimmunoprecipitation (Co‐IP) with normal IgG or S1P antibody. The purified protein complex was separated by SDS–PAGE and then subjected to silver staining. The arrows indicate the bands containing S1P, ETFA, and ETFB. The differential bands were then analyzed by liquid chromatography‐tandem mass spectrometry (LC–MS/MS).</p></li><li><p>Role of the S1P‐ETFA‐ETFB interaction network in mitochondrial and nonmitochondrial protein systems.</p></li><li><p>S1P interacts with endogenous ETFA and ETFB in HaCaT cells. Total protein lysate was subjected to Co‐IP with normal IgG, ETFA (left panel), or ETFB (right panel) antibody. The interaction between S1P and ETFA/ETFB was then detected by immunoblotting.</p></li><li><p>The direct interaction between S1P and ETFA‐ETFB was validated by a GST pull‐down assay. Left panel: <i>in vitro</i>‐translated S1P was pulled down by purified GST‐ETFA fusion protein. Right panel: <i>in vitro</i>‐translated S1P was pulled down by purified GST‐ETFB fusion protein.</p></li><li><p>Confocal immunofluorescence demonstrated that S1P colocalized with ETFA and ETFB in HaCaT cells. The black arrowheads indicate the colocalization (white) of S1P (green), ETFA (red), and ETFB (purple). Scale bars: 20 μm (panels 1–5); scale bars: 2 μm (panel 6).</p></li><li><p>Three‐dimensional structure of the S1P‐ETFA‐ETFB‐FAD complex <i>in stereo</i>. The structures of S1P (magenta), ETFA (light blue), ETFB (green), and FAD (red) are depicted in carbon.</p></li></ol></div>
|
||
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||
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||
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||
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|
||
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||
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||
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|
||
data-image-alt="Figure 4"
|
||
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|
||
data-figure-id="emmm202114904-fig-0004">
|
||
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|
||
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|
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6db8/9081911/94b84e0755db/EMMM-14-e14904-g005.gif"
|
||
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|
||
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||
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|
||
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||
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||
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||
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|
||
<p> Figure 4. S1P dysfunction impairs ETF flavination… </p>
|
||
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|
||
|
||
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||
|
||
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||
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||
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||
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|
||
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|
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||
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|
||
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||
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||
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||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 4. S1P dysfunction impairs ETF flavination and stability </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><ol style="list-style-type:upper-alpha"> <li> <p> Representative immunohistochemical images of S1P, ETFA,… </p> </li> </ol></div>
|
||
|
||
|
||
|
||
|
||
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|
||
|
||
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||
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||
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||
<strong class="figure-label">
|
||
Figure 4. S1P dysfunction impairs ETF flavination and stability
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><ol style="list-style-type:upper-alpha"><li><p>Representative immunohistochemical images of S1P, ETFA, and ETFB in normal controls and patient 1. Scale bars: 100 μm.</p></li><li><p>Unchanged mRNA levels and decreased protein levels of ETFA and ETFB were observed in the skin biopsy of patient 1. Quantitative RT–PCR analysis (upper panel, <i>n</i> = 6 biological replicates of normal controls; <i>n</i> = 6 technical replicates of patient 1) and immunohistochemistry (lower panel, <i>n</i> = 6 biological replicates; <i>n</i> = 3 technical replicates) of the S1P, ETFA, and ETFB levels.</p></li><li><p>Representative immunohistochemistry images of S1P, ETFA, and ETFB in both <i>Mbtps1</i>‐conditional knockout (cKO) and <i>Mbtps1</i>‐loxP mice. Scale bars: 100 μm.</p></li><li><p>
|
||
<i>MBTPS1</i> gene knockout led to decreases in the ETFA and ETFB protein levels <i>in vivo</i>. Quantitative RT–PCR analysis (upper panel, <i>n</i> = 6 biological replicates) and immunohistochemistry (lower panel, <i>n</i> = 6 biological replicates) of the S1P, ETFA, and ETFB levels in <i>Mbtps1</i>‐cKO mice and <i>Mbtps1</i>‐loxP mice.</p></li><li><p>Cycloheximide (CHX) chase analysis showed that <i>MBTPS1</i> knockout induced rapid degradation of ETFA and ETFB proteins in HaCaT cells. Left panel: Representative western blotting images of the ETFA and ETFB protein levels during CHX chase. Right panel: Quantification of the immunoblotting results corresponding to the left panel (<i>n</i> = 3 biological replicates).</p></li><li><p>Mutant S1P (p.Val355Gly and p.Ter1053Arg) only weakly interacted with ETFA and ETFB. We constructed Flag‐tagged wild‐type and mutant S1P HaCaT cell lines and then performed a Co‐IP assay with Flag antibody, and the interaction between S1P and ETFA/ETFB was detected by immunoblotting.</p></li><li><p>Wild‐type S1P, but not mutant S1P (p.Val355Gly and p.Ter1053Arg), decreased the association between ETFA and ETFB. We performed a Co‐IP assay with an ETFA antibody, and the interaction between ETFA and ETFB was detected by immunoblotting.</p></li><li><p>Wild‐type S1P, but not mutant S1P (p.Val355Gly and p.Ter1053Arg), enhanced the incorporation of FAD into the ETF complex. The visible spectra of flavin show two shoulder peaks at 420 and 460 nm, indicating the incorporation of FAD in the ETF complex. In the presence of the wild‐type S1P protein, the two peaks were shifted by 0.02 OD units, whereas the additional mutant S1P (p.Val355Gly and p.Ter1053Arg) weakly shifted the two peaks by 0.005–0.01 OD units.</p></li></ol> Data information: The data are presented as the means ± SDs. Statistical significance was assessed by unpaired two‐tailed Student’s <i>t</i>‐test (B: upper panel, B: lower panel for S1P and ETFB, D: upper panel, D: lower panel for S1P and ETFB, E: right panel) or the Mann–Whitney two‐tailed <i>U</i> test (B: lower panel for ETFA, D: lower panel for ETFA). ns, not significant, *<i>P</i> < 0.05, **<i>P</i> < 0.01, ***<i>P</i> < 0.001. Three biological replicates were included in the experiment (F, G). Source data are available online for this figure.</div>
|
||
|
||
|
||
|
||
|
||
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|
||
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||
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||
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|
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|
||
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|
||
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|
||
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|
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|
||
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|
||
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|
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||
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|
||
<p> Figure EV4. S1P knockout decreases the protein… </p>
|
||
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|
||
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|
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|
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|
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<p> Figure EV4. S1P knockout decreases the protein levels of ETF </p>
|
||
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|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><ol style="list-style-type:none"> <li> <span class="label"> A, B </span> <p> S1P knockout decreased… </p> </li> </ol></div>
|
||
|
||
|
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|
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Figure EV4. S1P knockout decreases the protein levels of ETF
|
||
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|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><ol style="list-style-type:none"><li><span class="label">A, B</span><p>S1P knockout decreased the levels of ETF and the complex II subunit SDHA and increased the protein levels of the complex I subunit NDUFS3 in HaCaT cells. A: Representative immunoblots of S1P, ETFA, ETFB, and mitochondrial electron transport chain proteins in control (Ctrl) and <i>MBTPS1‐</i>knockout (KO) HaCaT cells. B: Quantification of the immunoblotting results shown in (A) (<i>n</i> = 3 biological replicates).</p></li><li><span class="label">C, D</span><p>Loss of S1P led to a decrease in ETFA and ETFB proteins <i>in vivo</i>. C: Representative immunoblots of S1P, ETFA, and ETFB in <i>Mbtps1</i>‐cKO and <i>Mbtps1</i>‐loxP mice. D: Quantification of the immunoblotting results shown in (C) (<i>n</i> = 3 biological replicates).</p></li><li><span class="label">E</span><p>Loss of S1P did not affect the mRNA expression of <i>ETFA</i> and <i>ETFB</i> in HaCaT cells. Quantitative RT–PCR analysis of the S1P, <i>ETFA,</i> and <i>ETFB</i> mRNA levels in Ctrl and <i>MBTPS1</i>‐knockout (KO) HaCaT cells (<i>n</i> = 6 biological replicates).</p></li></ol> Data information: The data are presented as the means ± SDs (B, D, and E). Statistical significance was assessed by unpaired two‐tailed Student’s <i>t</i>‐test (B, D, and E). ns, not significant, *<i>P</i> < 0.05, **<i>P</i> < 0.01, ***<i>P</i> < 0.001. Source data are available online for this figure.</div>
|
||
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|
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|
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|
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|
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|
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|
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<p> Figure EV5. S1P regulates ETF stability independent… </p>
|
||
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<p> Figure EV5. S1P regulates ETF stability independent of its proteolytic activity </p>
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<div class="figure-caption-contents"><ol style="list-style-type:upper-alpha"> <li> <p> Both wild‐type and protease‐inactive… </p> </li> </ol></div>
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Figure EV5. S1P regulates ETF stability independent of its proteolytic activity
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<div class="figure-caption-contents"><ol style="list-style-type:upper-alpha"><li><p>Both wild‐type and protease‐inactive mutant S1P (p.Ser414Ala) increased the ETFA and ETFB protein levels, indicating that S1P regulates ETF stability independent of its protease activity. Three biological replicates were included in this study.</p></li><li><p>S1P increased global ATP production independent of its protease activity (<i>n</i> = 4 biological replicates).</p></li><li><p>S1P enhanced the incorporation of FAD into the ETF complex independent of its protease activity.</p></li></ol> Data information: The data are presented as the means ± SDs. Statistical significance was assessed by ordinary one‐way ANOVA. ns, not significant, ***<i>P</i> < 0.001. Source data are available online for this figure.</div>
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<p> Figure 5. S1P dysfunction impairs cellular OXPHOS… </p>
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<p> Figure 5. S1P dysfunction impairs cellular OXPHOS and increases glycolysis </p>
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Figure 5. S1P dysfunction impairs cellular OXPHOS and increases glycolysis
|
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<div class="figure-caption-contents"><ol style="list-style-type:upper-alpha"><li><p>Mitochondrial respiration (OCR) in control (Ctrl) and <i>MBTPS1‐</i>knockout (KO) HaCaT cells were quantified in real time using a Seahorse extracellular flux analyzer. Right subpanels: Quantification of basal respiration, maximal respiration, and OCR‐coupled ATP production in mitochondrial respiration (<i>n</i> = 5 biological replicates).</p></li><li><p>Quantification of relevant metabolites in mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis in Ctrl and <i>MBTPS1‐</i>KO HaCaT cells (<i>n</i> = 4 biological replicates).</p></li><li><p>Nonmitochondrial respiration (ECAR) was quantified in real time using a Seahorse extracellular flux analyzer. Quantification of non‐glycolytic acidification, glycolysis, glycolytic capacity, and glycolytic reserve in Ctrl and <i>MBTPS1‐</i>KO HaCaT cells (<i>n</i> = 4 biological replicates).</p></li><li><p>
|
||
<i>MBTPS1</i> knockout led to a decrease in global ATP production in HaCaT cells. Control and <i>MBTPS1</i>‐KO HaCaT cells were cultured in six‐well dishes. A standard curve was generated to calculate the sample ATP concentrations using an ATP Lite Luminescence Assay kit (<i>n</i> = 4 biological replicates).</p></li><li><p>
|
||
<i>MBTPS1</i> knockout significantly increased the generation of mitochondrial reactive oxygen species (Mito SOX) in HaCaT cells. Left panel: Representative immunofluorescence images of Mito SOX in HaCaT cells. Scale bars: 100 µm. Right panel: The immunofluorescence intensity was quantified to calculate the relative Mito ROS level in HaCaT cells (<i>n</i> = 4 biological replicates).</p></li><li><p>Schematic representation of OXPHOS and glycolysis upon S1P dysfunction.</p></li></ol> Data information: The data are presented as the means ± SDs. Statistical significance was assessed by unpaired two‐tailed Student’s <i>t</i>‐test (A–E). ns, not significant; *<i>P</i> < 0.05; **<i>P</i> < 0.01; ***<i>P</i> < 0.001. Source data are available online for this figure.</div>
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<p> Figure 6. Riboflavin therapy rescues the OXPHOS… </p>
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<p> Figure 6. Riboflavin therapy rescues the OXPHOS defect by restoring ETF stability </p>
|
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<div class="figure-caption-contents"><ol style="list-style-type:upper-alpha"> <li> <p> The S1P deficiency‐induced… </p> </li> </ol></div>
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Figure 6. Riboflavin therapy rescues the OXPHOS defect by restoring ETF stability
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<div class="figure-caption-contents"><ol style="list-style-type:upper-alpha"><li><p>The S1P deficiency‐induced decrease in ETFA and ETFB was significantly reversed by riboflavin (Rib) in a concentration‐dependent manner in <i>MBTPS1‐</i>KO HaCaT cells. GAPDH was used as a loading control. <i>MBTPS1</i>‐KO cells were initially cultured in DMEM for 24 h and supplemented with 0, 2.5, 5, or 10 µM riboflavin for 3 days. The expression of ETFA and ETFB was then detected by immunoblotting.</p></li><li><p>The S1P deficiency‐induced abnormalities in mitochondrial respiration can be significantly reversed by riboflavin supplementation and ETFA/B overexpression in HaCaT cells. Left panel: Mitochondrial respiration (OCR) was quantified in real time using a Seahorse extracellular flux analyzer. Right panel: Quantification of nonglycolytic acidification, glycolysis, glycolytic capacity, and glycolytic reserve in HaCaT cells (<i>n</i> = 3 biological replicates).</p></li><li><p>The decreased global ATP production caused by S1P deficiency could be significantly reversed by riboflavin supplementation and ETFA/B overexpression in HaCaT cells (<i>n</i> = 4 biological replicates).</p></li><li><p>Inflammatory lesions in CAOP syndrome were significantly improved by riboflavin supplementation. The representative head image of patient 1 before therapy is shown in Fig 1A (panel 1).</p></li></ol> Data information: The data are presented as the means ± SDs. Statistical significance was assessed by unpaired two‐tailed Student’s <i>t</i>‐test (B, C). *<i>P</i> < 0.05; **<i>P</i> < 0.01; ***<i>P</i> < 0.001. Three biological replicates were included in the experiment (A). Source data are available online for this figure.</div>
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<p> Figure 7. Putative mechanism through which S1P… </p>
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<p> Figure 7. Putative mechanism through which S1P regulates cellular respiration </p>
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<div class="figure-caption-contents"><p> S1P acts as a novel… </p></div>
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Figure 7. Putative mechanism through which S1P regulates cellular respiration
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<div class="figure-caption-contents">S1P acts as a novel mitochondria‐localized electron transfer flavoprotein (ETF)‐binding partner and is involved in the mitochondrial respiration chain reaction. S1P dysfunction disrupts its translocation to mitochondria, impairs the flavination and stability of ETF, and shifts mitochondrial oxidative phosphorylation (OXPHOS) to glycolysis. OXPHOS, oxidative phosphorylation; ROS, reactive oxygen species. ETF, electron transfer flavoprotein; FAD, flavin adenine dinucleotide; FADH2, reduced flavin adenine dinucleotide; ADP, adenosine diphosphate; ATP, adenosine triphosphate; Q, ubiquinone; TCA cycle, tricarboxylic acid cycle.</div>
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href="/32409196/"
|
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ref="linksrc=references_link&ordinalpos=1"
|
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data-ga-category="reference"
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data-ga-action="32409196"
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>
|
||
PubMed
|
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|
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|
||
</li>
|
||
|
||
</ol>
|
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</li>
|
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</ol>
|
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|
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<div class="actions-bar">
|
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<button
|
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class="show-all"
|
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ref="linksrc=show_all_references_link"
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Show all 62 references
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|
||
</div>
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
<div id="publication-types" class="publication-types keywords-section">
|
||
<h2 class="title">
|
||
Publication types
|
||
</h2>
|
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<ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Case Reports"
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aria-expanded="false"
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data-pinger-ignore>
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Case Reports
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</button><div id="keyword-actions-publication-types-0"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword Case Reports"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Case+Reports%22%5Bpt%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Case+Reports%22%5Bpt%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Case Reports"[pt]"
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data-ga-category="search"
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data-ga-action="pub_type"
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data-ga-label="Case Reports">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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ref="linksrc=search_in_mesh_link"
|
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Case+Reports"
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data-ga-category="search_mesh"
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data-ga-action="pub_type_link"
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data-ga-label="Case Reports">
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Case Reports"[pt]"
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data-ga-label=""Case Reports"[pt]"
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Add to Search
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</a></li></ul></div></div></div></li></ul>
|
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</div>
|
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|
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|
||
|
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<div id="mesh-terms" class="mesh-terms keywords-section">
|
||
<h2 class="title">
|
||
MeSH terms
|
||
</h2>
|
||
|
||
<ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Alopecia / genetics"
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tabindex="0"
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aria-controls="keyword-actions-mesh-terms-0"
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aria-expanded="false"
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data-pinger-ignore>
|
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Alopecia / genetics
|
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</button><div id="keyword-actions-mesh-terms-0"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Alopecia / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Alopecia%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Alopecia%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Alopecia/genetics"[MeSH]"
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data-ga-category="search"
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data-ga-action="mesh_term"
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data-ga-label="Alopecia / genetics">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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ref="linksrc=search_in_mesh_link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Alopecia"
|
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data-ga-category="search_mesh"
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data-ga-action="mesh_term_link"
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data-ga-label="Alopecia / genetics">
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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ref="linksrc=add_to_search_link"
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role="button"
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data-search-term=""Alopecia/genetics"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Alopecia/genetics"[MeSH]"
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href="#">
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
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aria-label="Toggle dropdown menu for keyword Cataract* / genetics"
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-major-1"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Cataract* / genetics
|
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</button><div id="keyword-actions-mesh-terms-major-1"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Cataract* / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Cataract%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Cataract%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Cataract/genetics"[MAJR]"
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data-ga-category="search"
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data-ga-action="mesh_term"
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data-ga-label="Cataract* / genetics">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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ref="linksrc=search_in_mesh_link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Cataract"
|
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data-ga-category="search_mesh"
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data-ga-action="mesh_term_link"
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data-ga-label="Cataract* / genetics">
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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role="button"
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data-search-term=""Cataract/genetics"[MAJR]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Cataract/genetics"[MAJR]"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Electron-Transferring Flavoproteins / genetics"
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tabindex="0"
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aria-controls="keyword-actions-mesh-terms-2"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Electron-Transferring Flavoproteins / genetics
|
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</button><div id="keyword-actions-mesh-terms-2"
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Electron-Transferring Flavoproteins / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Electron-Transferring+Flavoproteins%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Electron-Transferring+Flavoproteins%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Electron-Transferring Flavoproteins/genetics"[MeSH]"
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data-ga-category="search"
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data-ga-action="mesh_term"
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data-ga-label="Electron-Transferring Flavoproteins / genetics">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
|
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ref="linksrc=search_in_mesh_link"
|
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Electron-Transferring+Flavoproteins"
|
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data-ga-category="search_mesh"
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data-ga-action="mesh_term_link"
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data-ga-label="Electron-Transferring Flavoproteins / genetics">
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Search in MeSH
|
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</a></li><li><a class="add-to-search-link dropdown-block-link"
|
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ref="linksrc=add_to_search_link"
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role="button"
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data-search-term=""Electron-Transferring Flavoproteins/genetics"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Electron-Transferring Flavoproteins / metabolism"
|
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tabindex="0"
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aria-controls="keyword-actions-mesh-terms-3"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Electron-Transferring Flavoproteins / metabolism
|
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</button><div id="keyword-actions-mesh-terms-3"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Electron-Transferring Flavoproteins / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Electron-Transferring+Flavoproteins%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Electron-Transferring+Flavoproteins%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Electron-Transferring Flavoproteins/metabolism"[MeSH]"
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data-ga-category="search"
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data-ga-action="mesh_term"
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data-ga-label="Electron-Transferring Flavoproteins / metabolism">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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ref="linksrc=search_in_mesh_link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Electron-Transferring+Flavoproteins"
|
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data-ga-category="search_mesh"
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data-ga-action="mesh_term_link"
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data-ga-label="Electron-Transferring Flavoproteins / metabolism">
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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ref="linksrc=add_to_search_link"
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role="button"
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data-search-term=""Electron-Transferring Flavoproteins/metabolism"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Humans"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-4"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Humans
|
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</button><div id="keyword-actions-mesh-terms-4"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Humans"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Humans"[MeSH]"
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data-ga-category="search"
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data-ga-action="mesh_term"
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data-ga-label="Humans">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Humans"
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data-ga-category="search_mesh"
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data-ga-action="mesh_term_link"
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data-ga-label="Humans">
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Humans"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Humans"[MeSH]"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
|
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aria-label="Toggle dropdown menu for keyword Psoriasis*"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-major-5"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Psoriasis*
|
||
</button><div id="keyword-actions-mesh-terms-major-5"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Psoriasis*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
||
href="/?term=%22Psoriasis%22%5BMAJR%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Psoriasis%22%5BMAJR%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Psoriasis"[MAJR]"
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data-ga-category="search"
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data-ga-action="mesh_term"
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data-ga-label="Psoriasis*">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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ref="linksrc=search_in_mesh_link"
|
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Psoriasis"
|
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data-ga-category="search_mesh"
|
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data-ga-action="mesh_term_link"
|
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data-ga-label="Psoriasis*">
|
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Search in MeSH
|
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</a></li><li><a class="add-to-search-link dropdown-block-link"
|
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ref="linksrc=add_to_search_link"
|
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role="button"
|
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data-search-term=""Psoriasis"[MAJR]"
|
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data-ga-category="search"
|
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data-ga-action="add_to_search"
|
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data-ga-label=""Psoriasis"[MAJR]"
|
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href="#">
|
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Add to Search
|
||
</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
||
aria-label="Toggle dropdown menu for keyword Riboflavin / metabolism"
|
||
tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-6"
|
||
aria-expanded="false"
|
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data-pinger-ignore>
|
||
Riboflavin / metabolism
|
||
</button><div id="keyword-actions-mesh-terms-6"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Riboflavin / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
||
href="/?term=%22Riboflavin%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
|
||
data-href="/?term=%22Riboflavin%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
|
||
ref="linksrc=search_in_pubmed_keyword_link&mesh="Riboflavin/metabolism"[MeSH]"
|
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data-ga-category="search"
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data-ga-action="mesh_term"
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data-ga-label="Riboflavin / metabolism">
|
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Search in PubMed
|
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
|
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ref="linksrc=search_in_mesh_link"
|
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Riboflavin"
|
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data-ga-category="search_mesh"
|
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data-ga-action="mesh_term_link"
|
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data-ga-label="Riboflavin / metabolism">
|
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Search in MeSH
|
||
</a></li><li><a class="add-to-search-link dropdown-block-link"
|
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ref="linksrc=add_to_search_link"
|
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role="button"
|
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data-search-term=""Riboflavin/metabolism"[MeSH]"
|
||
data-ga-category="search"
|
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data-ga-action="add_to_search"
|
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data-ga-label=""Riboflavin/metabolism"[MeSH]"
|
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href="#">
|
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Add to Search
|
||
</a></li></ul></div></div></div></li></ul>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
<div id="substances" class="substances keywords-section">
|
||
<h2 class="title">
|
||
Substances
|
||
</h2>
|
||
|
||
<ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
||
aria-label="Toggle dropdown menu for keyword Electron-Transferring Flavoproteins"
|
||
tabindex="0"
|
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aria-controls="keyword-actions-substances-0"
|
||
aria-expanded="false"
|
||
data-pinger-ignore>
|
||
Electron-Transferring Flavoproteins
|
||
</button><div id="keyword-actions-substances-0"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
||
hidden
|
||
aria-label="Dropdown menu for keyword Electron-Transferring Flavoproteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
||
href="/?term=%22Electron-Transferring+Flavoproteins%22%5Bnm%5D&sort=date&sort_order=desc"
|
||
data-href="/?term=%22Electron-Transferring+Flavoproteins%22%5Bnm%5D&sort=date&sort_order=desc"
|
||
ref="linksrc=search_in_pubmed_keyword_link&keyword="Electron-Transferring Flavoproteins"[nm]"
|
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data-ga-category="search"
|
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data-ga-action="substance"
|
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data-ga-label="Electron-Transferring Flavoproteins">
|
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Search in PubMed
|
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
|
||
ref="linksrc=search_in_mesh_link"
|
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href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Electron-Transferring+Flavoproteins%22"
|
||
data-ga-category="search_mesh"
|
||
data-ga-action="substance_link"
|
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data-ga-label="Electron-Transferring Flavoproteins">
|
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Search in MeSH
|
||
</a></li><li><a class="add-to-search-link dropdown-block-link"
|
||
ref="linksrc=add_to_search_link"
|
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role="button"
|
||
data-search-term=""Electron-Transferring Flavoproteins"[nm]"
|
||
data-ga-category="search"
|
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data-ga-action="add_to_search"
|
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data-ga-label=""Electron-Transferring Flavoproteins"[nm]"
|
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href="#">
|
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Add to Search
|
||
</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
||
aria-label="Toggle dropdown menu for keyword Riboflavin"
|
||
tabindex="0"
|
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aria-controls="keyword-actions-substances-1"
|
||
aria-expanded="false"
|
||
data-pinger-ignore>
|
||
Riboflavin
|
||
</button><div id="keyword-actions-substances-1"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
||
hidden
|
||
aria-label="Dropdown menu for keyword Riboflavin"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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