{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:05:01Z","timestamp":1786122301186,"version":"build-2736575974"},"reference-count":60,"publisher":"Wiley","issue":"44","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515012419"],"award-info":[{"award-number":["2023A1515012419"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Alcohol\u2010associated liver disease (ALD) progresses from steatosis to steatohepatitis, but the underlying mechanisms remain unclear. Here, we investigated SETDB1's role in ALD progression involving LC3B\u2010mediated LC3\u2010associated phagocytosis (LAP). SETDB1 expression was progressively downregulated in livers of alcohol\u2010fed mice and ethanol\u2010treated hepatocytes, correlating with disease severity.\n                    <jats:italic>Setdb1<\/jats:italic>\n                    HKO mice exhibited accelerated ALD progression, developing severe steatosis, inflammation, and fibrosis even under pair\u2010fed conditions, indicating SETDB1 deficiency enhances disease susceptibility to nutritional stressors. Mechanistically, SETDB1 acted as a transcriptional cofactor for ERG to promote\n                    <jats:italic>Map1lc3b<\/jats:italic>\n                    transcription. SETDB1 deficiency impaired LAP by disrupting Rubicon membrane localization, causing defective lipid droplet clearance and enhanced cGAS\u2010STING activation. The ATG16L1 WD40 domain was essential for this LAP\u2010mediated protection. LC3B restoration in\n                    <jats:italic>Setdb1<\/jats:italic>\n                    HKO mice ameliorated steatosis, inflammation, and liver injury. Notably, the lipidation\u2010deficient LC3B\u2010G120A mutant failed to rescue steatosis but partially suppressed inflammation, revealing a lipidation\u2010independent LC3B function. We demonstrate lipidated LC3B mediates cytoplasmic LAP\u2010dependent lipid clearance, while non\u2010lipidated LC3B translocates to the nucleus, reducing R\u2010loop accumulation, preserving genomic stability, and restraining cGAS\u2010STING\u2010driven inflammation. Collectively, these findings define a protective SETDB1\u2010ERG\u2010LC3B axis restraining ALD progression and reveal dual LC3B functions, offering mechanistic insight and a potential therapeutic strategy for intercepting steatosis\u2010to\u2010steatohepatitis transition.\n                  <\/jats:p>","DOI":"10.1002\/advs.202513189","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T14:32:04Z","timestamp":1779201124000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LC3B Mediated SETDB1\u2010Accounted Alcoholic Steatohepatitis via Lipidation\u2010Dependent LAP and Lipidation\u2010Independent Nuclear Stabilization"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7329-5079","authenticated-orcid":false,"given":"Yi","family":"Zhang","sequence":"first","affiliation":[{"name":"KingMed School of Laboratory Medicine Guangzhou Medical University  Guangzhou China"},{"name":"Engineering Technology Research Center of Intelligent Diagnosis For Infectious Diseases in Guangdong Province  Guangzhou China"},{"name":"Guangdong Provincial Engineering Research Center For Early Warning and Diagnosis of Respiratory Infectious Diseases  Guangzhou China"},{"name":"Guangzhou Key Laboratory For Clinical Rapid Diagnosis and Early Warning of Infectious Diseases  Guangzhou China"},{"name":"Departments of Laboratory Diagnosis The Fifth Affiliated Hospital of Harbin Medical University  Daqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tan","family":"Wei","sequence":"additional","affiliation":[{"name":"KingMed School of Laboratory Medicine Guangzhou Medical University  Guangzhou China"},{"name":"Engineering Technology Research Center of Intelligent Diagnosis For Infectious Diseases in Guangdong Province  Guangzhou China"},{"name":"Guangdong Provincial Engineering Research Center For Early Warning and Diagnosis of 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