{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:33:24Z","timestamp":1786120404780,"version":"build-2736575974"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To evaluate the clinical prognostic value of the core circadian transcription factor brain and muscle ARNT-like 1 (BMAL1) in sepsis-induced acute lung injury (SI-ALI) and explore its mechanistic role in orchestrating organellar homeostasis and macrophage resilience.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>Prospective clinical cohort study and randomized blinded preclinical laboratory investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting:<\/jats:title>\n                    <jats:p>ICU and research laboratory of Renmin Hospital of Wuhan University.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Subjects:<\/jats:title>\n                    <jats:p>Thirty patients with SI-ALI and 12 healthy controls; adult male C57BL\/6 mice and mouse alveolar macrophage cell line (MH-S) alveolar macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions:<\/jats:title>\n                    <jats:p>Clinical monitoring of BMAL1, clock circadian regulator (CLOCK) genes, and hormones. Murine cecal ligation and puncture models, lipopolysaccharide treated MH-S cell treated with nobiletin, small interfering RNA-mediated knockdown of BMAL1, and pharmacological modulators of endoplasmic reticulum (ER)-phagy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results:<\/jats:title>\n                    <jats:p>Patients with SI-ALI exhibited profound circadian arrhythmia with significantly reduced expression of BMAL1 and CLOCK. BMAL1 levels were significantly lower in nonsurvivors and served as a robust predictor of 28-day mortality (area under the curve = 0.8177), showing a significant negative correlation with Sequential Organ Failure Assessment scores. In preclinical models, pharmacological activation of BMAL1 via nobiletin significantly mitigated lung histopathological damage, improved 5-day survival, and enhanced macrophage phagocytic and bactericidal activity. Mechanistically, BMAL1 deficiency impaired family with sequence similarity 134, member B-mediated ER-phagy, leading to inositol-requiring enzyme 1 increased and NADH:ubiquinone oxidoreductase core subunit V1, ATP synthase F1 subunit alpha, and seahorse-derived respiration\/adenosine triphosphate production decreased. Nobiletin rescued these organellar defects in a BMAL1-dependent manner.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>BMAL1 is a master regulator of cellular homeostasis in SI-ALI. It protects against lung injury by orchestrating a coordinated response between ER-phagy and mitochondrial metabolism. BMAL1 represents a clinically valuable prognostic biomarker and a potential therapeutic target for SI-ALI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1097\/ccm.0000000000007182","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T14:00:30Z","timestamp":1780322430000},"page":"2135-2146","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Brain and Muscle ARNT-Like 1 Ameliorates Sepsis-Induced Acute Lung Injury by Orchestrating Endoplasmic Reticulum-Phagy and Mitochondrial Metabolism"],"prefix":"10.1097","volume":"54","author":[{"given":"Jingqi","family":"Li","sequence":"first","affiliation":[{"name":"All authors: Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiping","family":"Liu","sequence":"additional","affiliation":[{"name":"All authors: Department of Critical 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