{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T06:02:19Z","timestamp":1784959339460,"version":"3.55.0"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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":["U24A20814"],"award-info":[{"award-number":["U24A20814"]}],"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":["82570321"],"award-info":[{"award-number":["82570321"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LMS25H020006"],"award-info":[{"award-number":["LMS25H020006"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Septic cardiomyopathy (SCM) is the leading cause of mortality among patients diagnosed with sepsis. Nevertheless, the precise mechanisms underlying its pathogenesis remain poorly understood. Deubiquitinating enzymes (DUBs) play a vital role in various cardiovascular diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study investigated deubiquitinating enzymes in septic myocardial injury via public RNA\u2010Seq. Pyroptosis was modelled in primary neonatal rat cardiomyocytes using lipopolysaccharide (LPS) and nigericin, with levels assessed by IL\u20111\u03b2 ELISA, Western blot, PI staining, CCK\u20118 and LDH assays. Potential substrates of OTUD5 were screened by Co\u2011immunoprecipitation. Cardiomyocyte\u2011specific OTUD5\u2011knockout mice generated by CRISPR\/Cas9 were subjected to LPS\u2011 or Caecal ligation and puncture (CLP)\u2011induced sepsis models for cardiac function and pyroptosis evaluation. AAV9\u2011mediated cardiomyocyte\u2011specific OTUD5 overexpression in NLRP3\u2011knockout mice was used to validate OTUD5\u2011NLRP3 functional interaction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>This study identifies the deubiquitinating enzyme OTUD5 as being significantly upregulated in myocardial tissue subjected to sepsis induced by LPS and CLP. Cardiomyocyte\u2010specific knockout of OTUD5 leads to exacerbated septic myocardial injury and pyroptosis. Mechanistically, OTUD5 directly interacted with NLRP3, with its C224 site facilitating deubiquitination to inhibit NLRP3 activation. Notably, the protective effects associated with OTUD5 overexpression were lost in NLRP3 knockout mice, underscoring its dependence on NLRP3 for function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study has confirmed that OTUD5 inhibits pyroptosis by suppressing the activity of NLRP3, thereby ameliorating septic cardiomyopathy. OTUD5 is worthy of further exploration as a potential therapeutic target for septic cardiomyopathy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>The expression levels of the deubiquitinating enzyme OTUD5 are elevated in tissues affected by sepsis\u2010induced cardiomyopathy.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Cardiomyocyte\u2010specific OTUD5 is a protective factor against myocardial pyroptosis and cardiac dysfunction induced by LPS and CLP.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>OTUD5 interacts with NLRP3, and its C224 site promotes deubiquitination while inhibiting the activation of NLRP3.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70743","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T03:29:41Z","timestamp":1783913381000},"source":"Crossref","is-referenced-by-count":0,"title":["Cardiomyocyte\u2010enriched OTUD5 alleviates septic cardiomyopathy by promoting NLRP3 deubiquitination and inhibiting NLRP3 inflammasome activation"],"prefix":"10.1002","volume":"16","author":[{"given":"Yucheng","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Geriatric Medicine First Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Chemical Biology Research Center School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou Zhejiang 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