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After gain\u2010 or loss\u2010of\u2010function manipulation of IRF\u20101 and DYRK1\u03b1, we quantified glutathione peroxidase 4 (GPX4) and acyl\u2010CoA synthetase long\u2010chain family member 4 (ACSL4), reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH). In\u00a0vivo, wild\u2010type (WT) mice, IRF\u20101 knockout (Irf1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) mice, and WT mice treated with the DYRK1\u03b1 inhibitor harmine underwent a 70% warm LIRI model. Liver and blood were collected for histology, serum transaminases, cytokine ELISA, protein analyses, and flow cytometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>IRF\u20101 knockdown attenuated LIRI, accompanied by suppression of hepatocellular ferroptosis. DYRK1\u03b1 inhibition reversed IRF\u20101\u2013mediated decreases in GSH and GPX4 and prevented increases in MDA, ROS, and ACSL4 in AML12 cells, indicating DYRK1\u03b1 participation in IRF\u20101\u2013driven ferroptosis. In mice, pharmacologic inhibition of DYRK1\u03b1 with harmine reduced hepatic ferroptosis and ameliorated LIRI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>IRF\u20101 aggravates LIRI, at least in part, by promoting hepatocellular ferroptosis via DYRK1\u03b1. Targeting the IRF\u20101\u2013DYRK1\u03b1 axis may offer a therapeutic strategy to limit perioperative liver injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70194","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T07:03:11Z","timestamp":1781593391000},"page":"1587-1601","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>IRF<\/scp>\n                    \u20101 modulates hepatic ferroptosis and aggravates liver ischemia\/reperfusion injury via\n                    <scp>DYRK1\u03b1<\/scp>"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7407-1969","authenticated-orcid":false,"given":"Jinping","family":"Zhang","sequence":"first","affiliation":[{"name":"General Surgery Department, Xuanwu Hospital Capital Medical University  Beijing 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