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Here, in an ALF mouse model, metabolites were identified that promote the formation of neutrophil extracellular traps (NETs) in the liver, subsequently influencing macrophage differentiation and disease progression. ALF occurs with abnormalities in hepatic and intestinal metabolites. Abnormal metabolites (LTD4 and glutathione) can directly, or indirectly <jats:italic>via<\/jats:italic> reactive oxygen species, promote NET formation of infiltrating neutrophils, which subsequently regulate macrophages in a pro\u2010inflammatory M1\u2010like state, inducing an amplification of the destructive effects of inflammation. Together, this study provides new insights into the role of NETs in the pathogenesis of ALF.<\/jats:p>","DOI":"10.1002\/1873-3468.14971","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T01:29:15Z","timestamp":1724030955000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Metabolic dysregulation\u2010triggered neutrophil extracellular traps exacerbate acute liver failure"],"prefix":"10.1002","author":[{"given":"Kangnan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Shanghai Tongren Hospital Shanghai Jiaotong University School of Medicine  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rongrong","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Tongren Hospital Shanghai Jiaotong University School of Medicine  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