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In this study, we isolated 4-hydroxyphenylacetic acid (HPA) from the marine-derived fungus Emericellopsis maritima Y39\u20132. The antithrombotic activity and mechanism of HPA were reported for the first time. Using a zebrafish model, we found that HPA had a strong antithrombotic activity because it can significantly increase cardiac erythrocytes, blood flow velocity, and heart rate, reduce caudal thrombus, and reverse the inflammatory response caused by Arachidonic Acid (AA). Further transcriptome analysis and qRT\u2013PCR validation demonstrated that HPA may regulate autophagy by inhibiting the PI3K\/AKT\/mTOR signaling pathway to exert antithrombotic effects.<\/jats:p>","DOI":"10.3390\/md22040148","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T12:41:57Z","timestamp":1711543317000},"page":"148","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Marine-Fungus-Derived Natural Compound 4-Hydroxyphenylacetic Acid Induces Autophagy to Exert Antithrombotic Effects in Zebrafish"],"prefix":"10.3390","volume":"22","author":[{"given":"Shaoshuai","family":"Xin","sequence":"first","affiliation":[{"name":"Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Agro-Products Processing Technology of Shandong Province, Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, 23788 Gongye North Road, Jinan 250100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peihai","family":"Li","sequence":"additional","affiliation":[{"name":"Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4743-6939","authenticated-orcid":false,"given":"Lizhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1873-1533","authenticated-orcid":false,"given":"Xuanming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenqiang","family":"Mu","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of High Active Traditional Chinese Medicine Delivery System & Chongqing Engineering Research Center of Pharmaceutical Sciences, Chongqing Medical and Pharmaceutical College, Chongqing 410331, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7097-0876","authenticated-orcid":false,"given":"Houwen","family":"Lin","sequence":"additional","affiliation":[{"name":"Research Center for Marine Drugs, State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacy, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3775-7694","authenticated-orcid":false,"given":"Xiaobin","family":"Li","sequence":"additional","affiliation":[{"name":"Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kechun","family":"Liu","sequence":"additional","affiliation":[{"name":"Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Barzkar, N., Jahromi, S.T., and Vianello, F. 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