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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="5klorUn8zxitIfb06PsMOTJIE8eUuKknm75t4KQu985XCGhQJ85Oi1fmccW6nlSH">
<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="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
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="5klorUn8zxitIfb06PsMOTJIE8eUuKknm75t4KQu985XCGhQJ85Oi1fmccW6nlSH">
<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="5klorUn8zxitIfb06PsMOTJIE8eUuKknm75t4KQu985XCGhQJ85Oi1fmccW6nlSH">
<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="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</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="5klorUn8zxitIfb06PsMOTJIE8eUuKknm75t4KQu985XCGhQJ85Oi1fmccW6nlSH">
<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="5klorUn8zxitIfb06PsMOTJIE8eUuKknm75t4KQu985XCGhQJ85Oi1fmccW6nlSH">
<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="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</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="25741767">
<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://www.mdpi.com/resolver?pii=ijms16034814"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=6383&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=25741767&amp;db=pubmed&amp;nlmid=101092791"
title="See full text options at MDPI"
data-ga-category="full_text"
data-ga-action="MDPI"
data-ga-label="25741767"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--res.mdpi.com-data-pubmed-linkout.png" alt="MDPI full text link"><span class="text">
MDPI
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/25741767/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=25741767&amp;db=pubmed&amp;nlmid=101092791"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="25741767"
><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="/25741767/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/25741767/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="25741767" 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%2F25741767%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="5klorUn8zxitIfb06PsMOTJIE8eUuKknm75t4KQu985XCGhQJ85Oi1fmccW6nlSH"><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="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
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"
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</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Shanghai Collaborative Innovation Center for Biomanufacturing Technology, Shanghai 200237, China. meor@ecust.edu.cn." href="#short-view-affiliation-6" ref="linksrc=author_aff">
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data-ga-label="Ji-Dong Gu">Ji-Dong Gu</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, China. jdgu@hkucc.hku.hk." href="#short-view-affiliation-7" ref="linksrc=author_aff">
7
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data-ga-label="Bo-Zhong Mu">Bo-Zhong Mu</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="State Key Laboratory of Bioreactor Engineering and Institute of Applied Chemistry, East China University of Science and Technology, Shanghai 200237, China. bzmu@ecust.edu.cn." href="#short-view-affiliation-8" ref="linksrc=author_aff">
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</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Shanghai Collaborative Innovation Center for Biomanufacturing Technology, Shanghai 200237, China. bzmu@ecust.edu.cn." href="#short-view-affiliation-9" ref="linksrc=author_aff">
9
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<li data-affiliation-id="short-view-affiliation-1"
id="short-view-affiliation-1"
><sup class="key">1</sup> State Key Laboratory of Bioreactor Engineering and Institute of Applied Chemistry, East China University of Science and Technology, Shanghai 200237, China. ljf@ecust.edu.cn.</li>
<li data-affiliation-id="short-view-affiliation-2"
id="short-view-affiliation-2"
><sup class="key">2</sup> Shanghai Collaborative Innovation Center for Biomanufacturing Technology, Shanghai 200237, China. ljf@ecust.edu.cn.</li>
<li data-affiliation-id="short-view-affiliation-3"
id="short-view-affiliation-3"
><sup class="key">3</sup> State Key Laboratory of Bioreactor Engineering and Institute of Applied Chemistry, East China University of Science and Technology, Shanghai 200237, China. smmbadinga@ecust.edu.cn.</li>
<li data-affiliation-id="short-view-affiliation-4"
id="short-view-affiliation-4"
><sup class="key">4</sup> Shanghai Collaborative Innovation Center for Biomanufacturing Technology, Shanghai 200237, China. smmbadinga@ecust.edu.cn.</li>
<li data-affiliation-id="short-view-affiliation-5"
id="short-view-affiliation-5"
><sup class="key">5</sup> State Key Laboratory of Bioreactor Engineering and Institute of Applied Chemistry, East China University of Science and Technology, Shanghai 200237, China. meor@ecust.edu.cn.</li>
<li data-affiliation-id="short-view-affiliation-6"
id="short-view-affiliation-6"
><sup class="key">6</sup> Shanghai Collaborative Innovation Center for Biomanufacturing Technology, Shanghai 200237, China. meor@ecust.edu.cn.</li>
<li data-affiliation-id="short-view-affiliation-7"
id="short-view-affiliation-7"
><sup class="key">7</sup> School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, China. jdgu@hkucc.hku.hk.</li>
<li data-affiliation-id="short-view-affiliation-8"
id="short-view-affiliation-8"
><sup class="key">8</sup> State Key Laboratory of Bioreactor Engineering and Institute of Applied Chemistry, East China University of Science and Technology, Shanghai 200237, China. bzmu@ecust.edu.cn.</li>
<li data-affiliation-id="short-view-affiliation-9"
id="short-view-affiliation-9"
><sup class="key">9</sup> Shanghai Collaborative Innovation Center for Biomanufacturing Technology, Shanghai 200237, China. bzmu@ecust.edu.cn.</li>
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<p>
Lipopeptides produced by microorganisms are one of the five major classes of biosurfactants known and they have received much attention from scientific and industrial communities due to their powerful interfacial and biological activities as well as environmentally friendly characteristics. Microbially produced lipopeptides are a series of chemical structural analogues of different families and, among them, 26 families covering about 90 lipopeptide compounds have been reported in the last two decades. This paper reviews the chemical structural characteristics and molecular behaviors of surfactin, one of the representative lipopeptides of the 26 families. In particular, two novel surfactin molecules isolated from cell-free cultures of Bacillus subtilis HSO121 are presented. Surfactins exhibit strong self-assembly ability to form sphere-like micelles and larger aggregates at very low concentrations. The amphipathic and surface properties of surfactins are related to the existence of the minor polar and major hydrophobic domains in the three 3-D conformations. In addition, the application potential of surfactin in bioremediation of oil spills and oil contaminants, and microbial enhanced oil recovery are discussed.
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<img class="figure-thumb" itemprop="thumbnail"
id="article-image-0"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d5e/4394451/ffdf5707bd5e/ijms-16-04814-g001.gif"
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<p> Figure 1 </p>
</strong>
<div class="figure-caption-contents"><p> Tandem MS of C15-surfactin-O-methyl ester… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 1 </p>
</strong>
<div class="figure-caption-contents"><p> Tandem MS of C15-surfactin-O-methyl ester ( <b> A </b> ) TOF MS/MS; ( <b> B </b> )… </p></div>
</div>
<figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 1
</strong>
<div class="figure-caption-contents">Tandem MS of C15-surfactin-O-methyl ester (<b>A</b>) TOF MS/MS; (<b>B</b>) Fragment ions after simple cleavage; (<b>C</b>,<b>D</b>) fragment ions produced after the double hydrogen transfer of lipopeptides in TOF MS/MS. Reprinted from <i>Process Biochem</i> 44: 1144 [23]. Copyright (2009), with permission from Elsevier.</div>
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<img class="figure-thumb" itemprop="thumbnail"
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<p> Figure 2 </p>
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<div class="figure-caption-contents"><p> Basic chemical structure of C15-surfactin-… </p></div>
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<strong class="figure-label">
<p> Figure 2 </p>
</strong>
<div class="figure-caption-contents"><p> Basic chemical structure of C15-surfactin- <i> O </i> -methyl ester. Reprinted from <i> Process Biochem </i> 44:1144… </p></div>
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<figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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Figure 2
</strong>
<div class="figure-caption-contents">Basic chemical structure of C15-surfactin-<i>O</i>-methyl ester. Reprinted from <i>Process Biochem</i> 44:1144 [23]. Copyright (2009), with permission from Elsevier.</div>
</figcaption>
</figure>
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data-figure-id="ijms-16-04814-f003">
<img class="figure-thumb" itemprop="thumbnail"
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<p> Figure 3 </p>
</strong>
<div class="figure-caption-contents"><p> Snapshots of the representative arrangement… </p></div>
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<strong class="figure-label">
<p> Figure 3 </p>
</strong>
<div class="figure-caption-contents"><p> Snapshots of the representative arrangement of surfactin molecules at ( <b> a </b> ) 2.20… </p></div>
</div>
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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Figure 3
</strong>
<div class="figure-caption-contents">Snapshots of the representative arrangement of surfactin molecules at (<b>a</b>) 2.20 and (<b>b</b>) 1.20 nm<sup>2</sup>·molecule<sup>1</sup> (The atom coloring scheme is C, green; N, blue; O, red; and H, white). Reprinted with permission from Gang <i>et al.</i> [38]. Copyright (2011) American Chemical Society.</div>
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<img class="figure-thumb" itemprop="thumbnail"
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<strong class="figure-label">
<p> Figure 4 </p>
</strong>
<div class="figure-caption-contents"><p> Normalized probability distribution of CC… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 4 </p>
</strong>
<div class="figure-caption-contents"><p> Normalized probability distribution of CC and NN magnitudes (ad corresponds to the interfacial… </p></div>
</div>
<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 4
</strong>
<div class="figure-caption-contents">Normalized probability distribution of CC and NN magnitudes (ad corresponds to the interfacial concentration of 2.20, 1.50, 1.20, and 0.95 nm<sup>2</sup>·molecule<sup></sup><sup>1</sup>, respectively; CC, the vector connecting the β carbon atom of the fatty acid residue and the α carbon atom in Val<sup>4</sup>; NN, the vector connects the nitrogen atom of Leu<sup>2</sup> and the nitrogen atom of Leu<sup>6</sup>). Reprinted with permission from Gang <i>et al.</i> [38]. Copyright (2011) American Chemical Society.</div>
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<strong class="figure-label">
<p> Figure 5 </p>
</strong>
<div class="figure-caption-contents"><p> The S1 ( <b> top </b> )… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 5 </p>
</strong>
<div class="figure-caption-contents"><p> The S1 ( <b> top </b> ) and S2 ( <b> bottom </b> ) structure (only Glu… </p></div>
</div>
<figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 5
</strong>
<div class="figure-caption-contents">The S1 (<b>top</b>) and S2 (<b>bottom</b>) structure (only Glu<sup>1</sup> and Asp<sup>5</sup> residues have been represented, S1 and S2 exhibit a particular horse saddle folding mode (left) and acidic residues show a claw topology). Reprinted with permission from Bonmatin <i>et al.</i> [45]. Copyright (2004) John Wiley &amp; Sons, Inc.</div>
</figcaption>
</figure>
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data-figure-id="ijms-16-04814-f006">
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d5e/4394451/ea8fdcc51b6b/ijms-16-04814-g006.gif"
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<strong class="figure-label">
<p> Figure 6 </p>
</strong>
<div class="figure-caption-contents"><p> The 3-D structure ( <b> a… </b> </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 6 </p>
</strong>
<div class="figure-caption-contents"><p> The 3-D structure ( <b> a </b> ) and Electrostatic potentials associated to solvent-accessible surfaces… </p></div>
</div>
<figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 6
</strong>
<div class="figure-caption-contents">The 3-D structure (<b>a</b>) and Electrostatic potentials associated to solvent-accessible surfaces (<b>b</b>) of surfactin (The backbone is in blue, the two negatively charged side chains are in red, the FA8 fatty acid in yellow, and the other hydrophobic residues in green). Reprinted with permission from Tsan <i>et al.</i> [46]. Copyright (2007) American Chemical Society.</div>
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<strong class="figure-label">
<p> Figure 7 </p>
</strong>
<div class="figure-caption-contents"><p> Surface tension of surfactins with… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 7 </p>
</strong>
<div class="figure-caption-contents"><p> Surface tension of surfactins with different fatty acid chain length [51]. </p></div>
</div>
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Figure 7
</strong>
<div class="figure-caption-contents">Surface tension of surfactins with different fatty acid chain length [51].</div>
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<p> Figure 8 </p>
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<div class="figure-caption-contents"><p> Micelle size distribution of surfactin-C13,… </p></div>
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<p> Figure 8 </p>
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<div class="figure-caption-contents"><p> Micelle size distribution of surfactin-C13, -C14 and -C15 [51]. </p></div>
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Figure 8
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<div class="figure-caption-contents">Micelle size distribution of surfactin-C13, -C14 and -C15 [51].</div>
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