{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T16:35:07Z","timestamp":1792773307329,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","issue":"59","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82525068"],"award-info":[{"award-number":["82525068"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370643"],"award-info":[{"award-number":["82370643"]}],"id":[{"id":"10.13039\/501100001809","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":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hepatic ischemia\u2013reperfusion injury (HIRI) is a frequent and severe complication after liver transplantation and hepatectomy, driven by sterile inflammation and lacking effective therapies. Regulator of G\u2010protein signaling 16 (RGS16) is an inflammatory modulator, but its role in HIRI remains unclear. We found that RGS16 expression was markedly increased in the livers of post\u2010hepatectomy patients and positively correlated with neutrophil extracellular trap formation (NETosis). Using hepatocyte\u2010specific\n                    <jats:italic>Rgs16<\/jats:italic>\n                    knockout and transgenic mouse models, we demonstrated that Rgs16 deficiency attenuated hepatic inflammation and apoptosis after HIRI, whereas Rgs16 overexpression significantly exacerbated liver injury. Integrated multi\u2010omics analyses, including RNA\u2010seq, MeRIP\u2010seq, and mass spectrometry, identified C\u2010X\u2010C motif chemokine ligand 1 (CXCL1) as a key downstream effector of RGS16. Mechanistically, RGS16 competitively binds YTH domain family protein 3 (YTHDF3), displacing poly(A)\u2010nuclease deadenylation complex subunit 3 (PAN3) and stabilizing m\n                    <jats:sup>6<\/jats:sup>\n                    A\u2010modified Cxcl1 mRNA, thereby enhancing CXCL1 expression. Elevated CXCL1 promotes hepatocyte apoptosis and inflammation through C\u2010X\u2010C chemokine receptor 2 (CXCR2)\u00a0and drives neutrophil recruitment and NETosis. Pharmacological inhibition of CXCL1 or degradation of NETs with DNase I significantly alleviated RGS16\u2010induced liver injury. Collectively, RGS16 aggravates HIRI by amplifying hepatocyte\u2010intrinsic CXCL1\u2013CXCR2 signaling and CXCL1\u2010mediated neutrophil recruitment and NETosis, suggesting RGS16 and its downstream pathways as potential therapeutic targets for HIRI.\n                  <\/jats:p>","DOI":"10.1002\/advs.76817","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:20:41Z","timestamp":1785241241000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RGS16 Aggravates Hepatic Ischemia\u2010Reperfusion Injury via Hepatocyte\u2010Intrinsic Apoptosis\/Inflammation &amp; Neutrophil Recruitment\/NETosis"],"prefix":"10.1002","volume":"13","author":[{"given":"Xinglong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Minimally Invasive Hepatic Surgery The First Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"Key Laboratory of Hepatosplenic Surgery Ministry of Education The First Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"Department of General Surgery The Fourth Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanzhi","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive Hepatic Surgery The First Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"Key Laboratory of Hepatosplenic Surgery Ministry of Education The First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjun","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive Hepatic Surgery The First Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"Key Laboratory of Hepatosplenic Surgery Ministry of Education The First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongliang","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive Hepatic Surgery The First Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"Department of Pediatric Surgery The Sixth Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4040-8188","authenticated-orcid":false,"given":"Zihao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive Hepatic Surgery The First Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"Key Laboratory of Hepatosplenic Surgery Ministry of Education The First Affiliated Hospital of Harbin Medical University  Harbin 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Surgery The First Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"The First Department of General Surgery Affiliated Hospital of Inner Mongolia Minzu University  Tongliao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shounan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive Hepatic Surgery The First Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"Key Laboratory of Hepatosplenic Surgery Ministry of Education The First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanjia","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive Hepatic Surgery The First Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"Key Laboratory of Hepatosplenic Surgery Ministry of Education The First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaoyu","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive Hepatic Surgery The First Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"Key Laboratory of Hepatosplenic Surgery Ministry of Education The First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3843-3835","authenticated-orcid":false,"given":"Yao","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Ultrasound The First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Tang","sequence":"additional","affiliation":[{"name":"International Health Care Center National Center for Global Health and Medicine  Tokyo Japan"},{"name":"Hepato\u2010Biliary\u2010Pancreatic 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