{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T16:39:19Z","timestamp":1784133559417,"version":"3.55.0"},"reference-count":82,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"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":["82300279"],"award-info":[{"award-number":["82300279"]}],"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":["82500972"],"award-info":[{"award-number":["82500972"]}],"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":["82200406"],"award-info":[{"award-number":["82200406"]}],"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":["82300497"],"award-info":[{"award-number":["82300497"]}],"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":["82130014"],"award-info":[{"award-number":["82130014"]}],"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":["82321001"],"award-info":[{"award-number":["82321001"]}],"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":["82430013"],"award-info":[{"award-number":["82430013"]}],"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":["82200345"],"award-info":[{"award-number":["82200345"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["226\u20102024\u201000132"],"award-info":[{"award-number":["226\u20102024\u201000132"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2025QC1668"],"award-info":[{"award-number":["ZR2025QC1668"]}],"id":[{"id":"10.13039\/501100007129","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":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Excessive macrophage\u2010mediated inflammation following myocardial infarction (MI) exacerbates infarct expansion and impairs cardiac repair; however, the regulatory mechanisms remain poorly understood. Here, it is reported that ubiquitin\u2010specific peptidase 9 X\u2010linked (USP9X) was significantly downregulated in macrophages during early post\u2010MI inflammation. Macrophage\u2010specific deficiency of USP9X enhanced expression of pro\u2010inflammatory genes, thereby impeding cardiac functional recovery. Mechanistically, USP9X deubiquitinated and stabilized tumor necrosis factor receptor\u2010associated factor (TRAF)\u2010type zinc finger domain containing 1 (TRAFD1), a negative regulator of Toll\u2010like receptor (TLR) signaling, thereby restraining inflammatory responses. Moreover, inflammatory stimuli triggered acetylation of USP9X at K2414, exposing a latent KFERQ motif that promoted its recognition by the molecular chaperone heat shock cognate protein 70 (HSC70) and facilitated subsequent lysosomal degradation via chaperone\u2010mediated autophagy (CMA). Consistently, both genetic inhibition of HSC70 and pharmacological blockade of lysosomal degradation prevented USP9X degradation following inflammatory stimulation. Furthermore, a cell\u2010penetrating peptide mimicking the KFERQ sequence of USP9X that blocked its interaction with HSC70 and the subsequent CMA\u2010mediated degradation, thereby promoting inflammation resolution and cardiac repair post\u2010MI. Collectively, these findings establish the USP9X\u2013TRAFD1 axis and its CMA\u2010mediated degradation as critical checkpoints in post\u2010MI inflammation, highlighting USP9X stabilization as a therapeutic strategy for ischemic heart disease.<\/jats:p>","DOI":"10.1002\/advs.202518950","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T20:10:03Z","timestamp":1769631003000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Chaperone\u2010Mediated Autophagic Degradation of USP9X in Macrophages Exacerbates Postmyocardial Infarction Inflammation and Cardiac Dysfunction"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4378-6683","authenticated-orcid":false,"given":"Biqing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiology The Second Affiliated Hospital Zhejiang University School of Medicine Zhejiang University  Hangzhou China"},{"name":"State Key Laboratory of Transvascular Implantation Devices Heart Regeneration and Repair Key Laboratory of Zhejiang province Transvascular Implant Instrument Research Institute Binjiang Institute of Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangheng","family":"Cai","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Qingdao University  Qingdao Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqi","family":"Li","sequence":"additional","affiliation":[{"name":"Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Liu","sequence":"additional","affiliation":[{"name":"Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhui","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Second Affiliated Hospital Zhejiang University School of Medicine Zhejiang University  Hangzhou China"},{"name":"State Key Laboratory of Transvascular Implantation Devices Heart Regeneration and Repair Key Laboratory of Zhejiang province Transvascular Implant Instrument Research Institute Binjiang Institute of Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Second Affiliated Hospital Zhejiang University School of Medicine Zhejiang University  Hangzhou China"},{"name":"State Key Laboratory of Transvascular Implantation Devices Heart Regeneration and Repair Key Laboratory of Zhejiang province Transvascular Implant Instrument Research Institute Binjiang Institute of Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5992-9904","authenticated-orcid":false,"given":"Ding","family":"Ai","sequence":"additional","affiliation":[{"name":"The Province and Ministry Co\u2010sponsored Collaborative Innovation Center for Medical Epigenetics State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) Tianjin Institute of Cardiology The Second Hospital of Tianjin Medical University Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6699-8470","authenticated-orcid":false,"given":"Xinyang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Second Affiliated Hospital Zhejiang University School of Medicine Zhejiang University  Hangzhou China"},{"name":"State Key Laboratory of Transvascular Implantation Devices Heart Regeneration and Repair Key Laboratory of Zhejiang province Transvascular Implant Instrument Research Institute Binjiang Institute of Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/cir.0000000000000757"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735\u20101097(24)03328\u2010X"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacasi.2024.01.013"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.121.021682"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht090"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.11.024"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.01.073"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569\u2010022\u201000823\u20105"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401\u2010023\u201001222\u20103"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac223"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0735\u20101097(02)02564\u20100"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2022.2062535"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.4274\/balkanmedj.galenos.2023.2022\u201012\u201015"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2022.07.022"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.97767"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201052739\u2010y"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.111.243196"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1182364"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010015\u20101851\u20100"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2101592118"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107471"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2025.01.009"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci154217"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010024\u201000729\u20109"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010022\u201000966\u20104"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010018\u20100001\u20106"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2013.153"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2121133119"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2096397"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202319232"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010024\u201002004\u2010x"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2021.05.003"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.121.057549"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.124.323658"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.140"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1003893107"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.108.769331"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.03.002"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2017.224"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395\u2010017\u20100609\u20102"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M508221200"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M806923200"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010019\u20100323\u20103"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1815027116"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2012.58"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.07.001"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1582973"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2016.01.006"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010022\u201001068\u2010y"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202306535"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.12.002"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2016.1268302"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000301"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421\u2010023\u201000573\u20109"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12950\u2010021\u201000271\u2010x"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28809"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.05.027"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010024\u201007237\u2010w"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7823"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.116.303577"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395\u2010018\u20100686\u2010x"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210\u2010024\u201003313\u20102"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20140860"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2025.02.014"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2024.189099"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA117.000392"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388\u2010018\u20100134\u20102"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.08.010"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2012.10.010"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2017.11.001"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.831168"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.123.064121"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395\u2010023\u201001028\u20108"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.121.318908"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.100097"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2024.06.001"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112346"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202301852"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1659610"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcibr1512011"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im1401s83"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.8.4272"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202518950","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202518950","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202518950","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T10:18:59Z","timestamp":1775125139000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202518950"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":82,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/advs.202518950"],"URL":"https:\/\/doi.org\/10.1002\/advs.202518950","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,28]]},"assertion":[{"value":"2025-09-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e18950"}}