{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T20:46:22Z","timestamp":1782938782040,"version":"3.54.5"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cerebral ischemia\u2010reperfusion injury (CIRI) is a critical pathological process following ischemic stroke, with ferroptosis being increasingly recognized as a key contributor to neuronal damage. However, the regulatory mechanisms, particularly the role of specific transcription factors like E26 transformation\u2010specific variant 4 (ETV4), remain poorly understood. This study aimed to investigate the function and underlying mechanism of ETV4 in neuronal ferroptosis during CIRI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In vitro, SH\u2010SY5Y cells subjected to oxygen\u2010glucose deprivation\/reoxygenation (OGD\/R) were used to model CIRI. Cell viability and ferroptosis markers (Fe\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sup>+<\/jats:sup>\n                      , malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), reactive oxygen species (ROS)) were assessed. Molecular expressions were measured by Real\u2010time Quantitative PCR (RT\u2010qPCR) and\/or western blot. In vivo, a rat model of middle cerebral artery occlusion\/reperfusion (MCAO\/R) was established, and brain injury was evaluated via 2% solution of 2,3,5\u2010triphenyl tetrazolium chloride (TTC), hematoxylin\u2010eosin (HE), and TdT\u2010mediated dUTP nick\u2010end labeling (TUNEL) staining. Chromatin immunoprecipitation (ChIP), dual\u2010luciferase reporter, RNA pull\u2010down, RNA immunoprecipitation (RIP), and actinomycin D assays were employed to validate the molecular interactions within the ETV4\/Y\u2010box binding protein 1 (YBX1)\/glutathione peroxidase\u20104 (GPX4) axis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ETV4 was significantly down regulated in both the MCAO\/R model and OGD\/R\u2010treated cells. Overexpression of ETV4 markedly attenuated OGD\/R\u2010induced oxidative stress, ferroptosis in vitro, and ameliorated brain injury in vivo. Mechanistically, ETV4 transcriptionally activated YBX1 by directly binding to its promoter. YBX1, in turn, stabilized GPX4 mRNA, which was modified by NSUN2\u2010mediated methylation. Crucially, the protective effects of ETV4 in vitro were abolished upon YBX1 or GPX4 knockdown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings demonstrate that ETV4 transcriptionally up regulates YBX1 to stabilize GPX4 mRNA in an NSUN2\u2013m5Cmethylation dependent manner, thus suppressing neuronal ferroptosis. This reveals a novel ETV4\/YBX1\/GPX4 axis as a potential therapeutic target for CIRI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71548","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:52:17Z","timestamp":1781671937000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ETV4 Improves Cerebral Ischemia\u2010Reperfusion Injury by Restraining YBX1\u2010GPX4\u2010Ferroptosis Cascades"],"prefix":"10.1002","volume":"16","author":[{"given":"Qian","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Neurology Haikou Affiliated Hospital of Central South University Xiangya School of Medicine  Haikou Hainan China"},{"name":"Department of Emergency, Hainan General Hospital Hainan Affiliated Hospital of Hainan Medical University  Haikou Hainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faming","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Dermatology Haikou Affiliated Hospital of Central South University Xiangya School of Medicine  Haikou Hainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology Haikou Affiliated Hospital of Central South University Xiangya School of Medicine  Haikou Hainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes10020102"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2025.111996"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.042"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhw372"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.137235"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427\u2010021\u20102047\u20108"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1717319"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11658\u2010024\u201000605\u20106"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2023.114630"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.633681"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.5114\/fn.2022.120101"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2022.110137"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2022.10.020"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.70270"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2024.111375"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202507254"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/1587922"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0269\u201024.2024"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.172345"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2024.111210"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2016.02.010"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064\u2010024\u201004161\u20105"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2024.217064"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975\u2010023\u201001210\u2010z"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12482"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2025.108316"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422\u2010020\u201000441\u20101"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018\u2010024\u201005119\u20107"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.14712\/fb2021067040150"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2021.13159"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/01616412.2025.2530215"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2021.0216"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2023.188872"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951\u2010023\u201001862\u2010x"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.24976\/Discov.Med.202436187.143"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2023.02.021"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064\u2010022\u201003789\u20105"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.12.010"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001688\u2010x"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064\u2010022\u201003697\u20108"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1635209"}],"container-title":["Brain 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