{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T16:35:17Z","timestamp":1793205317107,"version":"4.5.0"},"reference-count":52,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Septic cardiomyopathy (SCM) is a significant contributor to mortality among septic patients, but effective therapeutic strategies are still lacking. Deubiquitinating enzymes (DUBs) such as \u2026\u2026. function as crucial regulators of protein ubiquitination and may play a fundamental role in the pathogenesis of heart diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      In two models of SCM induced by lipopolysaccharide (LPS) or caecal ligation and puncture (CLP) in C57BL\/6J mice, the differential expression of DUB genes was identified by transcriptome sequencing. Sepsis models were established through LPS injection or CLP surgery in both cardiomyocyte\u2010specific YOD1 knockout (YOD1CKO) mice and littermate wild\u2010type (Yod1\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      ) mice. Potential substrates of YOD1 were identified by co\u2010immunoprecipitation coupled with liquid chromatography\u2013tandem mass spectrometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Expression of DUB YOD1 was up\u2010regulated in cardiac tissues of LPS\/CLP\u2010induced septic mice. Cardiomyocyte\u2010derived YOD1 deficiency alleviated SCM and protected cardiac function in LPS\/CLP\u2010challenged mice. Mechanistically, YOD1 interacted with the inflammasome NLRP3 and then deubiquitinated the K48 ubiquitin chain on the NLRP3 protein by its active site H262, thereby blocking degradation of NLRP3 in cardiomyocytes. Consequently, NLRP3 activation and NLRP3\u2010driven pyroptosis were increased in both cardiomyocytes and septic mouse hearts. Inhibition of NLRP3 counteracted the protective effects of YOD1 knockout in SCM mice. Furthermore, pharmacological inhibition of YOD1 improved myocardial injury elicited by CLP in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Cardiomyocyte YOD1 mediated SCM by deubiquitinating NLRP3 and promoting NLRP3\u2010driven pyroptosis. Our results have revealed a new YOD1\u2013NLRP3 axis in cardiomyocytes and identified YOD1 as a novel therapeutic target for treating SCM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70419","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:00:55Z","timestamp":1774933255000},"page":"3558-3577","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The deubiquitinase YOD1 in cardiomyocytes mediates septic cardiomyopathy by deubiquitinating and thus stabilizing the NLRP3 inflammasome"],"prefix":"10.1111","volume":"183","author":[{"given":"Zhaozheng","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Cardiology and the Key Laboratory of Cardiovascular Disease of Wenzhou The First Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Chemical Biology Research Center, School of Pharmaceutical Sciences Wenzhou Medical 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