{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:46:03Z","timestamp":1787705163818,"version":"build-2784847793"},"reference-count":22,"publisher":"Wiley","issue":"49","license":[{"start":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T00:00:00Z","timestamp":1761350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100013365","name":"West China Hospital, Sichuan University","doi-asserted-by":"publisher","award":["ZYGD23030"],"award-info":[{"award-number":["ZYGD23030"]}],"id":[{"id":"10.13039\/501100013365","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Alcoholic liver disease (ALD) represents a formidable global health challenge with limited effective therapeutic interventions. This study investigates the therapeutic potential and underlying mechanisms of xenogeneic neonatal liver\u2010derived extracellular vesicles in ALD. EV\n                    <jats:italic>neo<\/jats:italic>\n                    (neonatal rat liver\u2010derived extracellular vesicle) and EV\n                    <jats:italic>adult<\/jats:italic>\n                    (adult rat liver\u2010derived extracellular vesicle) are isolated via differential centrifugation and rigorously characterized. A preclinical ALD mouse model is established using the National Institute on Alcohol Abuse and Alcoholism model, with comparative therapeutic assessment of intravenously administered EV\n                    <jats:italic>neo<\/jats:italic>\n                    vs EV\n                    <jats:italic>adult<\/jats:italic>\n                    . Proteomic profiling of liver tissues and EVs \uff08extracellular vesicles\uff09, integrated with immunohistochemical analyses, fluorescence imaging, mitochondrial functional assays, and quantification of inflammatory\/regenerative markers, elucidated therapeutic mechanisms. Key findings demonstrate that EV\n                    <jats:italic>neo<\/jats:italic>\n                    \u2010specific enrichment of mitochondrial biogenesis, anti\u2010inflammatory, and anti\u2010apoptotic pathways. EV\n                    <jats:italic>neo<\/jats:italic>\n                    administration significantly attenuates hepatic steatosis and inflammatory responses, restores mitochondrial homeostasis through redox balance modulation, induces macrophage polarization toward an M2 reparative phenotype, enhances hepatocyte proliferation, and suppresses apoptotic signaling. Comparative analysis revealed EV\n                    <jats:italic>neo \u2019s<\/jats:italic>\n                    superior therapeutic efficacy over EV\n                    <jats:italic>adult<\/jats:italic>\n                    , attributable to its developmentally programmed cargo that orchestrates mitochondrial resilience, immunometabolic reprogramming, and parenchymal regeneration. These findings establish developmental stage\u2010specific EV therapeutics as a paradigm for ALD treatment, emphasizing their multimodal mechanistic advantages in counteracting alcohol\u2010induced hepatopathology.\n                  <\/jats:p>","DOI":"10.1002\/smll.202509351","type":"journal-article","created":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T08:36:12Z","timestamp":1761381372000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neonatal Liver\u2010Derived Extracellular Vesicle: Unlocking Mitochondrial Repair and Regenerative Mechanisms in Alcoholic Liver Disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Xin","family":"Zeng","sequence":"first","affiliation":[{"name":"Center of Infectious Diseases Department of Liver Transplantation Center and National Health Commission (NHC) Key Laboratory of Transplant Engineering and Immunology West China Hospital Sichuan University  Chengdu 610000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases West China Hospital of Sichuan University  Chengdu Sichuan 610041 China"},{"name":"Laboratory of Infectious and Liver Diseases Institution of Infectious Diseases West China Hospital of Sichuan University  Chengdu Sichuan 610041 China"},{"name":"Division of Infectious Diseases State Key Laboratory of Biotherapy Sichuan University  Chengdu Sichuan 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shisheng","family":"Wang","sequence":"additional","affiliation":[{"name":"West China Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqiang","family":"Hu","sequence":"additional","affiliation":[{"name":"West China\u2010California Research Center for Predictive Intervention Medicine West China Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaojia","family":"Zhou","sequence":"additional","affiliation":[{"name":"Animal experimental center of West China hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingmin","family":"Zeng","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases West China Hospital of Sichuan University  Chengdu Sichuan 610041 China"},{"name":"Laboratory of Infectious and Liver Diseases Institution of Infectious Diseases West China Hospital of Sichuan University  Chengdu Sichuan 610041 China"},{"name":"Division of Infectious Diseases State Key Laboratory of Biotherapy Sichuan University  Chengdu Sichuan 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Pei","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases West China Hospital of Sichuan University  Chengdu Sichuan 610041 China"},{"name":"Laboratory of Infectious and Liver Diseases Institution of Infectious Diseases West China Hospital of Sichuan University  Chengdu Sichuan 610041 China"},{"name":"Division of Infectious Diseases State Key Laboratory of Biotherapy Sichuan University  Chengdu Sichuan 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingping","family":"Liu","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases Department of Liver Transplantation Center and National Health Commission (NHC) Key Laboratory of Transplant Engineering and Immunology West China Hospital Sichuan University  Chengdu 610000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Cao","sequence":"additional","affiliation":[{"name":"Centre for Transplant and Renal Research Westmead Institute for Medical Research The University of Sydney 176 Hawkesbury Rd Westmead Sydney NSW 2145 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Tang","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases West China Hospital of Sichuan University  Chengdu Sichuan 610041 China"},{"name":"Laboratory of Infectious and Liver Diseases Institution of Infectious Diseases West China Hospital of Sichuan University  Chengdu Sichuan 610041 China"},{"name":"Division of Infectious Diseases State Key Laboratory of Biotherapy Sichuan University  Chengdu Sichuan 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongbo","family":"Wu","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases West China Hospital of Sichuan University  Chengdu Sichuan 610041 China"},{"name":"Laboratory of Infectious and Liver Diseases Institution of Infectious Diseases West China Hospital of Sichuan University  Chengdu Sichuan 610041 China"},{"name":"Division of Infectious Diseases State Key Laboratory of Biotherapy Sichuan University  Chengdu Sichuan 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0650-4109","authenticated-orcid":false,"given":"Chengshi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Laboratory of Diabetes and Metabolism Research West China Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,25]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.03.018"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23258"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15701"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1465-3362.2009.00153.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.16969"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10565-024-09954-6"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25126604"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202300602"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.156187"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.70011"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-024-02452-6"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12133"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.06.006"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aav8521"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2020.11.001"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2022.107983"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1200708"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-44057-6"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-018-0082-x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.02.026"},{"key":"e_1_2_9_21_1","first-page":"72","volume":"11","author":"Fatty Liver and Alcoholic Liver Disease Study Group","year":"2003","journal-title":"Chin. J. Hepatol."},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.032"}],"container-title":["Small"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smll.202509351","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T11:34:17Z","timestamp":1765452857000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/smll.202509351"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,25]]},"references-count":22,"journal-issue":{"issue":"49","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/smll.202509351"],"URL":"https:\/\/doi.org\/10.1002\/smll.202509351","archive":["Portico"],"relation":{},"ISSN":["1613-6810","1613-6829"],"issn-type":[{"value":"1613-6810","type":"print"},{"value":"1613-6829","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,25]]},"assertion":[{"value":"2025-08-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e09351"}}