N-Methylparoxetine Blocked Autophagic Flux and Induced Apoptosis by Activating ROS-MAPK Pathway in Non-Small Cell Lung Cancer Cells
Identifieur interne : 000A82 ( Pmc/Checkpoint ); précédent : 000A81; suivant : 000A83N-Methylparoxetine Blocked Autophagic Flux and Induced Apoptosis by Activating ROS-MAPK Pathway in Non-Small Cell Lung Cancer Cells
Auteurs : Kun Wang [République populaire de Chine] ; Bonan Chen [République populaire de Chine] ; Ting Yin [République populaire de Chine] ; Yujuan Zhan [République populaire de Chine] ; Yuhua Lu [République populaire de Chine] ; Yilin Zhang [République populaire de Chine] ; Jiawei Chen [République populaire de Chine] ; Weijie Wu [République populaire de Chine] ; Shikun Zhou [République populaire de Chine] ; Wenli Mao [République populaire de Chine] ; Yuhui Tan [République populaire de Chine] ; Biaoyan Du [République populaire de Chine] ; Xiaodong Liu [République populaire de Chine] ; Hiuting Idy Ho [République populaire de Chine] ; Jianyong Xiao [République populaire de Chine]Source :
- International Journal of Molecular Sciences [ 1422-0067 ] ; 2019.
Abstract
The main mechanistic function of most chemotherapeutic drugs is mediated by inducing mitochondria-dependent apoptosis. Tumor cells usually respond to upregulate autophagy to eliminate impaired mitochondria for survival. Hypothetically, inhibiting autophagy might promote mitochondria-dependent apoptosis, thus enhancing the efficacy of chemotherapeutic therapies. We previously identified
Url:
DOI: 10.3390/ijms20143415
PubMed: 31336784
PubMed Central: 6678301
Affiliations:
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-Methylparoxetine Blocked Autophagic Flux and Induced Apoptosis by Activating ROS-MAPK Pathway in Non-Small Cell Lung Cancer Cells</title>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>N</italic>
-Methylparoxetine Blocked Autophagic Flux and Induced Apoptosis by Activating ROS-MAPK Pathway in Non-Small Cell Lung Cancer Cells</title>
<author><name sortKey="Wang, Kun" sort="Wang, Kun" uniqKey="Wang K" first="Kun" last="Wang">Kun Wang</name>
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<author><name sortKey="Liu, Xiaodong" sort="Liu, Xiaodong" uniqKey="Liu X" first="Xiaodong" last="Liu">Xiaodong Liu</name>
<affiliation wicri:level="4"><nlm:aff id="af4-ijms-20-03415">Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong SAR 999077, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong SAR 999077</wicri:regionArea>
<orgName type="university">Université chinoise de Hong Kong</orgName>
<placeName><settlement type="city">Sha Tin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ho, Hiuting Idy" sort="Ho, Hiuting Idy" uniqKey="Ho H" first="Hiuting Idy" last="Ho">Hiuting Idy Ho</name>
<affiliation wicri:level="4"><nlm:aff id="af4-ijms-20-03415">Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong SAR 999077, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong SAR 999077</wicri:regionArea>
<orgName type="university">Université chinoise de Hong Kong</orgName>
<placeName><settlement type="city">Sha Tin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Xiao, Jianyong" sort="Xiao, Jianyong" uniqKey="Xiao J" first="Jianyong" last="Xiao">Jianyong Xiao</name>
<affiliation wicri:level="1"><nlm:aff id="af1-ijms-20-03415">Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea>
<placeName><settlement type="city">Jiangmen</settlement>
<region type="province">Guangdong</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af3-ijms-20-03415">Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006</wicri:regionArea>
<placeName><settlement type="city">Jiangmen</settlement>
<region type="province">Guangdong</region>
</placeName>
</affiliation>
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</analytic>
<series><title level="j">International Journal of Molecular Sciences</title>
<idno type="eISSN">1422-0067</idno>
<imprint><date when="2019">2019</date>
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<front><div type="abstract" xml:lang="en"><p>The main mechanistic function of most chemotherapeutic drugs is mediated by inducing mitochondria-dependent apoptosis. Tumor cells usually respond to upregulate autophagy to eliminate impaired mitochondria for survival. Hypothetically, inhibiting autophagy might promote mitochondria-dependent apoptosis, thus enhancing the efficacy of chemotherapeutic therapies. We previously identified <italic>N</italic>
-methylparoxetine (NMP) as an inducer of mitochondrial fragmentation with subsequent apoptosis in non-small cell lung cancer (NSCLC) cells. We discovered that ROS was accumulated in NMP-treated NSCLC cells, followed by c-Jun <italic>N</italic>
-terminal kinase (JNK) and p38 MAP kinase (p38) activation. This was reversed by the application of a reactive oxygen species (ROS) scavenger, <italic>N</italic>
-acetylcysteine (NAC), leading to a reduction in apoptosis. Our data suggested that NMP induced apoptosis in NSCLC cells by activating mitogen-activated protein kinase (MAPK) pathway. We further speculated that the remarkable increase of ROS in NMP-treated NSCLC cells might result from an inhibition of autophagy. Our current data confirmed that NMP blocked autophagy flux at late stage wherein lysosomal acidification was inhibited. Taken together, this study demonstrated that NMP could exert dual apoptotic functions—mitochondria impairment and, concomitantly, autophagy inhibition. NMP-related excessive ROS accumulation induced apoptosis by activating the MAPK pathway in NSCLC cells.</p>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Int J Mol Sci</journal-id>
<journal-id journal-id-type="iso-abbrev">Int J Mol Sci</journal-id>
<journal-id journal-id-type="publisher-id">ijms</journal-id>
<journal-title-group><journal-title>International Journal of Molecular Sciences</journal-title>
</journal-title-group>
<issn pub-type="epub">1422-0067</issn>
<publisher><publisher-name>MDPI</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">31336784</article-id>
<article-id pub-id-type="pmc">6678301</article-id>
<article-id pub-id-type="doi">10.3390/ijms20143415</article-id>
<article-id pub-id-type="publisher-id">ijms-20-03415</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title><italic>N</italic>
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</contrib>
<contrib contrib-type="author"><name><surname>Mao</surname>
<given-names>Wenli</given-names>
</name>
<xref ref-type="aff" rid="af1-ijms-20-03415">1</xref>
<xref ref-type="aff" rid="af2-ijms-20-03415">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tan</surname>
<given-names>Yuhui</given-names>
</name>
<xref ref-type="aff" rid="af3-ijms-20-03415">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Du</surname>
<given-names>Biaoyan</given-names>
</name>
<xref ref-type="aff" rid="af2-ijms-20-03415">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Liu</surname>
<given-names>Xiaodong</given-names>
</name>
<xref ref-type="aff" rid="af4-ijms-20-03415">4</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0001-9897-3780</contrib-id>
<name><surname>HO</surname>
<given-names>Hiuting Idy</given-names>
</name>
<xref ref-type="aff" rid="af4-ijms-20-03415">4</xref>
<xref rid="c1-ijms-20-03415" ref-type="corresp">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Xiao</surname>
<given-names>Jianyong</given-names>
</name>
<xref ref-type="aff" rid="af1-ijms-20-03415">1</xref>
<xref ref-type="aff" rid="af3-ijms-20-03415">3</xref>
<xref rid="c1-ijms-20-03415" ref-type="corresp">*</xref>
</contrib>
</contrib-group>
<aff id="af1-ijms-20-03415"><label>1</label>
Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</aff>
<aff id="af2-ijms-20-03415"><label>2</label>
Department of Pathology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</aff>
<aff id="af3-ijms-20-03415"><label>3</label>
Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006, China</aff>
<aff id="af4-ijms-20-03415"><label>4</label>
Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong SAR 999077, China</aff>
<author-notes><corresp id="c1-ijms-20-03415"><label>*</label>
Correspondence: <email>b144156@cuhk.edu.hk</email>
(H.I.H.); <email>jianyongxiao@gzucm.edu.cn</email>
(J.X.)</corresp>
<fn id="fn1-ijms-20-03415"><label>†</label>
<p>These authors contributed equally to this work.</p>
</fn>
</author-notes>
<pub-date pub-type="epub"><day>11</day>
<month>7</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection"><month>7</month>
<year>2019</year>
</pub-date>
<volume>20</volume>
<issue>14</issue>
<elocation-id>3415</elocation-id>
<history><date date-type="received"><day>29</day>
<month>6</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>10</day>
<month>7</month>
<year>2019</year>
</date>
</history>
<permissions><copyright-statement>© 2019 by the authors.</copyright-statement>
<copyright-year>2019</copyright-year>
<license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
).</license-p>
</license>
</permissions>
<abstract><p>The main mechanistic function of most chemotherapeutic drugs is mediated by inducing mitochondria-dependent apoptosis. Tumor cells usually respond to upregulate autophagy to eliminate impaired mitochondria for survival. Hypothetically, inhibiting autophagy might promote mitochondria-dependent apoptosis, thus enhancing the efficacy of chemotherapeutic therapies. We previously identified <italic>N</italic>
-methylparoxetine (NMP) as an inducer of mitochondrial fragmentation with subsequent apoptosis in non-small cell lung cancer (NSCLC) cells. We discovered that ROS was accumulated in NMP-treated NSCLC cells, followed by c-Jun <italic>N</italic>
-terminal kinase (JNK) and p38 MAP kinase (p38) activation. This was reversed by the application of a reactive oxygen species (ROS) scavenger, <italic>N</italic>
-acetylcysteine (NAC), leading to a reduction in apoptosis. Our data suggested that NMP induced apoptosis in NSCLC cells by activating mitogen-activated protein kinase (MAPK) pathway. We further speculated that the remarkable increase of ROS in NMP-treated NSCLC cells might result from an inhibition of autophagy. Our current data confirmed that NMP blocked autophagy flux at late stage wherein lysosomal acidification was inhibited. Taken together, this study demonstrated that NMP could exert dual apoptotic functions—mitochondria impairment and, concomitantly, autophagy inhibition. NMP-related excessive ROS accumulation induced apoptosis by activating the MAPK pathway in NSCLC cells.</p>
</abstract>
<kwd-group><kwd><italic>N</italic>
-Methylparoxetine</kwd>
<kwd>NSCLC</kwd>
<kwd>autophagy inhibition</kwd>
<kwd>ROS</kwd>
<kwd>MAPK</kwd>
<kwd>apoptosis</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group><fig id="ijms-20-03415-f001" orientation="portrait" position="float"><label>Figure 1</label>
<caption><p>NMP inhibited human NSCLC cell proliferation. (<bold>A</bold>
) Molecular structure of NMP. (<bold>B</bold>
) Inhibition rates of proliferation in NMP-treated NCI-H1299 and NCI-H1650 cells (24 h) quantified by CCK-8 viability assay. Median inhibitory concentrations (IC50) were estimated by log(inhibitor) vs. normalized response of non-linear regression analysis. (<bold>C</bold>
) Inhibition rates of proliferation in NMP-treated NCI-H1299, NCI-H1650 and BEAS-2B cells (24 h) quantified by CCK-8 viability assay. (<bold>D</bold>
) Colony formation assay of NCI-H1299 and NCI-H1650 cells, treated with serial concentrations of NMP for 7 days. (<bold>E</bold>
) Flow cytometry analyses of 24 h NMP (0–60 μM) treatment of CFDA-SE-labelled NCI-H1299 and NCI-H1650 cells (<bold>F</bold>
) Fluorescence micrographs of NMP (0–60 μM, 24 h)-treated NCI-H1299 and NCI-H1650 cells with EdU incorporation. <italic>Green</italic>
, EdU-positive cells; <italic>blue</italic>
, Hoechst 33342 for nuclear staining. Scale bar, 20 μm. Error bars, means ± S.D. of three independent experiments; * <italic>p</italic>
< 0.05, ** <italic>p</italic>
< 0.01,*** <italic>p</italic>
< 0.001, compared to the control group.</p>
</caption>
<graphic xlink:href="ijms-20-03415-g001"></graphic>
</fig>
<fig id="ijms-20-03415-f002" orientation="portrait" position="float"><label>Figure 2</label>
<caption><p>NMP induced apoptosis in NSCLC cells. (<bold>A</bold>
) Flow cytometry analyses of NMP-treated NCI-H1299, NCI-H1650, and BEAS-2B cells that were subjected to PI/Annexin V staining assay for apoptosis detection. Error bars means ± S.D. of three independent experiments; *** <italic>p</italic>
< 0.001, compared to the control group. (<bold>B</bold>
,<bold>C</bold>
) Western blots of whole cell lysates in NCI-H1299 and NCI-H1650 cells which were treated with NMP (60 µM) or cisplatin(Cis, 35 µM) at the indicated doses for 24 h (<bold>B</bold>
) or for the indicated time courses (<bold>C</bold>
).</p>
</caption>
<graphic xlink:href="ijms-20-03415-g002"></graphic>
</fig>
<fig id="ijms-20-03415-f003" orientation="portrait" position="float"><label>Figure 3</label>
<caption><p>NMP induced apoptosis through a mitochondria-dependent pathway in NSCLC cell lines. (<bold>A</bold>
,<bold>B</bold>
) Fluorescence micrographs of mitochondria in a vehicle or 40 µM NMP-treated NCI-H1299 and NCI-H1650 cells with MitoTracker Red CMXRos staining. The length of mitochondria was quantified with ImageJ (US National Institutes of Health, Bethesda, MD, USA). Scale bar, 5 μm. Error bars mean ± S.D. of three independent experiments; *** <italic>p</italic>
< 0.001, compared to the control group. (<bold>C</bold>
) Western blot assay for mitochondria-dependent apoptosis of different cellular fractions obtained from NMP treated NCI-H1299 cells. The intensity of bands was quantified by using Gelpro32 Analyzer (Media Cybernetics, Inc., MD, USA). One-way analysis of variance (ANOVA), ** <italic>p</italic>
< 0.01,*** <italic>p</italic>
< 0.001, compared to the control group. <italic>Cyto</italic>
, cytosolic fractions; <italic>Mito</italic>
, mitochondrial fractions; <italic>WCL</italic>
, whole cell lysates.</p>
</caption>
<graphic xlink:href="ijms-20-03415-g003"></graphic>
</fig>
<fig id="ijms-20-03415-f004" orientation="portrait" position="float"><label>Figure 4</label>
<caption><p>NMP induced ROS accumulation and activated MAPK pathways. (<bold>A</bold>
,<bold>B</bold>
) Flow cytometry analyses of intracellular ROS in NMP-treated NCI-H1299 and NCI-H1650 labeled with green DCFDA fluorescent dye. Error bars mean ± S.D. of three independent experiments; *** <italic>p</italic>
< 0.001, compared to the control group. (<bold>C</bold>
) Western blot assay for MAPK pathways in NMP-treated NCI-H1299 cells.</p>
</caption>
<graphic xlink:href="ijms-20-03415-g004"></graphic>
</fig>
<fig id="ijms-20-03415-f005" orientation="portrait" position="float"><label>Figure 5</label>
<caption><p>ROS clearance reversed JNK/p38 activation and attenuated NMP-induced apoptosis. (<bold>A</bold>
) CCK-8 viability assay of NCI-H1299 cells treated with different concentrations of NMP with or without NAC (2 mM) for 24 h. (<bold>B</bold>
) Flow cytometry analyses of the treated cells with Annexin V/PI labeling. (<bold>C</bold>
) Western blot analysis for MAPK pathways of the treated cells. Error bars, means ± S.D. of three independent experiments; ** <italic>p</italic>
< 0.01; *** <italic>p</italic>
< 0.001, compared to the control group.</p>
</caption>
<graphic xlink:href="ijms-20-03415-g005"></graphic>
</fig>
<fig id="ijms-20-03415-f006" orientation="portrait" position="float"><label>Figure 6</label>
<caption><p>NMP induced the accumulation of autophagosomes in NSCLC Cells. (<bold>A</bold>
,<bold>B</bold>
) Western blot analyses for LC3II of dose-dependent (24 h treatment, (<bold>A</bold>
)) or time-dependent responses (<bold>B</bold>
) in NCI-H1299 and NCI-H1650 cells treated with NMP (60 µM) or bafilomycin A1 (Baf, 0.1 µM). (<bold>C</bold>
) Fluorescence micrographs of LC3-stably-expressed NCI-H1299 and NCI-H1650 cells treated with vehicle, rapamycin (Rapa, 0.5 µM), bafilomycin A1 (Baf, 0.1 µM) or NMP (40 µM). Scale bar, 20 μm. Error bars mean ± S.D. of three independent experiments; *** <italic>p</italic>
< 0.001, compared to the control group.</p>
</caption>
<graphic xlink:href="ijms-20-03415-g006"></graphic>
</fig>
<fig id="ijms-20-03415-f007" orientation="portrait" position="float"><label>Figure 7</label>
<caption><p>NMP impaired NSCLC cell late-staged autophagic flux. (<bold>A,B</bold>
) Western blot analysis for p62 of NMP- of Baf-treated NCI-H1299 and NCI-H1650 cells at the indicated doses for 24 h (<bold>A</bold>
), or 60 µM NMP- or 0.1 µM Baf-treated cells for the indicated time courses (B). (<bold>C</bold>
) Flow cytometry analyses of GFP-LC3 mean fluorescence intensities in NCI-H1299 cells treated with NMP (40 µM), Baf (0.1 µM) or in combination. (<bold>D</bold>
) <italic>Left</italic>
, typical fluorescence micrographs of mCherry-GFP-LC3-expressing NCI-H1299 or NCI-H1650 cells treated with vehicle, NMP (40 µM), or Baf (0.1 µM) for 24 h; or HBSS for 6 h. Scale bar, 5 μm. <italic>Right</italic>
, Pearson’s correlation analyses of GFP/mCherry colocalization. Error bars, means ± S.D. of three independent experiments; ** <italic>p</italic>
< 0.01, ***<italic>p</italic>
< 0.001, compared to the control group.</p>
</caption>
<graphic xlink:href="ijms-20-03415-g007"></graphic>
</fig>
<fig id="ijms-20-03415-f008" orientation="portrait" position="float"><label>Figure 8</label>
<caption><p>NMP altered lysosomal pH and inhibited lysosomal cathepsins maturation. (<bold>A</bold>
,<bold>B</bold>
) Typical fluorescence micrograph of vehicle-, Baf (0.1 µM)- or NMP (40 µM)-treated NCI-H1299 and NCI-H1650 cells subjected to pH-dependent fluorescent dyes acridine orange (AO) and Lysotracker Red DND-99 stainings to detect lysosomal acidification. Scale bar, 20 μm. (<bold>C</bold>
,<bold>D</bold>
) Western blot analysis for mature cathepsin B and D detection in treated cells in dose- (<bold>C</bold>
) or time-dependent manners (<bold>D</bold>
).</p>
</caption>
<graphic xlink:href="ijms-20-03415-g008"></graphic>
</fig>
<fig id="ijms-20-03415-f009" orientation="portrait" position="float"><label>Figure 9</label>
<caption><p>NMP induced apoptosis in NSCLC cells by dual pathways. An illustration demonstrating the summary of NMP actions on apoptosis in NSCLC cells. (<bold>Left</bold>
) NMP inhibited late-staged autophagy flux by inhibiting acidification of early lysosome. (<bold>Right</bold>
) NMP stimulated mitochondrial fission and fragmentation, leading to ROS and cytochrome C leakage. Cytochrome C is a risk factor to promote apoptosis. Excessive ROS accumulation further damages mitochondria, thus NMP could induce an effective apoptotic effect on tumor cells by promoting mitochondrial-dependent apoptosis and inhibiting autophagy in NSCLC cells in parallel.</p>
</caption>
<graphic xlink:href="ijms-20-03415-g009"></graphic>
</fig>
</floats-group>
</pmc>
<affiliations><list><country><li>République populaire de Chine</li>
</country>
<region><li>Guangdong</li>
</region>
<settlement><li>Jiangmen</li>
<li>Sha Tin</li>
</settlement>
<orgName><li>Université chinoise de Hong Kong</li>
</orgName>
</list>
<tree><country name="République populaire de Chine"><region name="Guangdong"><name sortKey="Wang, Kun" sort="Wang, Kun" uniqKey="Wang K" first="Kun" last="Wang">Kun Wang</name>
</region>
<name sortKey="Chen, Bonan" sort="Chen, Bonan" uniqKey="Chen B" first="Bonan" last="Chen">Bonan Chen</name>
<name sortKey="Chen, Bonan" sort="Chen, Bonan" uniqKey="Chen B" first="Bonan" last="Chen">Bonan Chen</name>
<name sortKey="Chen, Jiawei" sort="Chen, Jiawei" uniqKey="Chen J" first="Jiawei" last="Chen">Jiawei Chen</name>
<name sortKey="Du, Biaoyan" sort="Du, Biaoyan" uniqKey="Du B" first="Biaoyan" last="Du">Biaoyan Du</name>
<name sortKey="Ho, Hiuting Idy" sort="Ho, Hiuting Idy" uniqKey="Ho H" first="Hiuting Idy" last="Ho">Hiuting Idy Ho</name>
<name sortKey="Liu, Xiaodong" sort="Liu, Xiaodong" uniqKey="Liu X" first="Xiaodong" last="Liu">Xiaodong Liu</name>
<name sortKey="Lu, Yuhua" sort="Lu, Yuhua" uniqKey="Lu Y" first="Yuhua" last="Lu">Yuhua Lu</name>
<name sortKey="Mao, Wenli" sort="Mao, Wenli" uniqKey="Mao W" first="Wenli" last="Mao">Wenli Mao</name>
<name sortKey="Mao, Wenli" sort="Mao, Wenli" uniqKey="Mao W" first="Wenli" last="Mao">Wenli Mao</name>
<name sortKey="Tan, Yuhui" sort="Tan, Yuhui" uniqKey="Tan Y" first="Yuhui" last="Tan">Yuhui Tan</name>
<name sortKey="Wang, Kun" sort="Wang, Kun" uniqKey="Wang K" first="Kun" last="Wang">Kun Wang</name>
<name sortKey="Wu, Weijie" sort="Wu, Weijie" uniqKey="Wu W" first="Weijie" last="Wu">Weijie Wu</name>
<name sortKey="Xiao, Jianyong" sort="Xiao, Jianyong" uniqKey="Xiao J" first="Jianyong" last="Xiao">Jianyong Xiao</name>
<name sortKey="Xiao, Jianyong" sort="Xiao, Jianyong" uniqKey="Xiao J" first="Jianyong" last="Xiao">Jianyong Xiao</name>
<name sortKey="Yin, Ting" sort="Yin, Ting" uniqKey="Yin T" first="Ting" last="Yin">Ting Yin</name>
<name sortKey="Yin, Ting" sort="Yin, Ting" uniqKey="Yin T" first="Ting" last="Yin">Ting Yin</name>
<name sortKey="Zhan, Yujuan" sort="Zhan, Yujuan" uniqKey="Zhan Y" first="Yujuan" last="Zhan">Yujuan Zhan</name>
<name sortKey="Zhang, Yilin" sort="Zhang, Yilin" uniqKey="Zhang Y" first="Yilin" last="Zhang">Yilin Zhang</name>
<name sortKey="Zhou, Shikun" sort="Zhou, Shikun" uniqKey="Zhou S" first="Shikun" last="Zhou">Shikun Zhou</name>
</country>
</tree>
</affiliations>
</record>
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