{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T18:13:58Z","timestamp":1788113638566,"version":"build-2803163510"},"reference-count":33,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":153,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"The National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82330079"],"award-info":[{"award-number":["82330079"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Chongqing Municipal Health Commission Project","award":["2025CCXM001"],"award-info":[{"award-number":["2025CCXM001"]}]},{"name":"Science and Technology Research Program of Chongqing Municipal Education Commission","award":["KJZD-K202512803"],"award-info":[{"award-number":["KJZD-K202512803"]}]},{"name":"Science Foundation of State Key Laboratory of Trauma and Chemical Poisoning","award":["2024\u00a0K003"],"award-info":[{"award-number":["2024\u00a0K003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sepsis-related myocardial dysfunction significantly increases the mortality risk of sepsis. However, its underlying mechanism remains incompletely understood, and effective therapeutic strategies are still lacking. Transcriptomic profiling from septic patients showed endoplasmic reticulum stress (ERS) were the main pathways participating in the occurrence of sepsis myocardial dysfunction. Therefore, this study aimed to explore the protective effect of 4-phenylbutyric acid (4-PBA) on sepsis-induced myocardial injury and specify its molecular regulatory mechanism, to provide experimental basis for clinical intervention of septic myocardial dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In vivo and in vitro models of sepsis were used, and 4-PBA (5\u00a0mg\/kg) was administered for intervention. Mitochondria-associated ER-membrane (MAM) formation, mitochondrial dynamics, mitochondrial function, glycolytic metabolism, and protein lactylation were systematically examined. Molecular docking and site-directed mutation were applied to verify the direct binding and catalytic sites of 4-PBA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>4-PBA significantly alleviated sepsis-induced myocardial dysfunction (SIMD). The mechanism was closely related to 4-PBA inhibiting MAM formation and improving the mitochondrial dynamic balance and mitochondrial function. 4-PBA inhibited MAM formation mainly via decreasing the lactate production and lactylation of Arpc1b-K308 by inhibiting the glycolysis limiting enzyme HK2, and 4-PBA inhibited HK2 activity by binding K621 and K624 catalytic sites.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The results indicate that 4-PBA protects cardiac function following sepsis by recovering mitochondrial dynamics balance. This finding provides a novel therapeutic strategy and potential target for SIMD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/burnst\/tkag039","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T11:20:18Z","timestamp":1780312818000},"source":"Crossref","is-referenced-by-count":0,"title":["4-phenylbutyric acid alleviated sepsis-induced myocardial dysfunction by inhibition of MAM formation to improve mitochondrial dynamic balance in myocardial cells"],"prefix":"10.1093","volume":"14","author":[{"given":"Yue","family":"Wu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Department of Shock and Transfusion, Daping Hospital, Army Medical University , No. 10 Changjiang Branch Road, Yuzhong District, Chongqing 400042 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijin","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Gynecologic 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,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyong","family":"Zou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Department of Shock and Transfusion, Daping Hospital, Army Medical University , No. 10 Changjiang Branch Road, Yuzhong District, Chongqing 400042 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4421-9708","authenticated-orcid":false,"given":"Xiaodan","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Department of Shock and Transfusion, Daping Hospital, Army Medical University , No. 10 Changjiang Branch Road, Yuzhong District, Chongqing 400042 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical 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