{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:56:56Z","timestamp":1791601016917,"version":"4.3.4"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Acute lung injury (ALI) is a severe inflammatory condition often triggered by infections. Glycolysis and macrophage polarization play critical roles in ALI pathogenesis. This study investigates the effects of Daucosterol on lipopolysaccharide (LPS)\u2010stimulated lung injury and its potential mechanisms. In this research, BEAS\u20102B lung epithelial cells and MH\u2010S alveolar macrophages were exposed to LPS and various concentrations of Daucosterol. Cell viability was assessed using CCK\u20108 assay. Glycolytic activity was evaluated by detecting ATP production, lactate level, and extracellular acidification rate. Macrophage polarization was assessed using flow cytometry. Tumor necrosis factor (TNF)\u2010\u03b1 and interleukin (IL)\u20106 levels were detected by enzyme\u2010linked immunosorbent assay. Gene expression was evaluated by reverse transcription\u2010quantitative polymerase chain reaction and western blotting. A cecal ligation and puncture (CLP)\u2010induced ALI mouse model was used to validate the protective effect of Daucosterol in\u00a0vivo. Results showed that Daucosterol prevented the reduction in cell viability in LPS\u2010stimulated BEAS\u20102B cells. In MH\u2010S macrophages, Daucosterol inhibited LPS\u2010induced glycolysis and M1 polarization while promoting M2 polarization. Mechanistically, Daucosterol reversed the LPS\u2010induced upregulation of PFKFB3. Overexpression of PFKFB3 counteracted the inhibitory effects of Daucosterol on glycolysis and M1 polarization. In\u00a0vivo, Daucosterol significantly alleviated CLP\u2010induced ALI by improving lung histopathology, reducing pulmonary edema, enhancing oxygenation, inhibiting myeloperoxidase and caspase\u20103 activity, and decreasing TNF\u2010\u03b1 and IL\u20106 levels in bronchoalveolar lavage fluid. In conclusion, Daucosterol targets PFKFB3 to mitigate sepsis\u2010induced ALI by inhibiting glycolysis and M1 macrophage polarization, offering a potential therapeutic strategy for ALI.<\/jats:p>","DOI":"10.1111\/cbdd.70243","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T06:01:07Z","timestamp":1768802467000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Daucosterol Targets\n                    <scp>PFKFB3<\/scp>\n                    to Mitigates Sepsis\u2010Induced Acute Lung Injury by Inhibiting Glycolysis and\n                    <scp>M1<\/scp>\n                    Macrophage Polarization"],"prefix":"10.1111","volume":"107","author":[{"given":"Lulu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Intensive Care Unit The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an Second People's Hospital  Huai'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingmin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Emergency Huai'an Hospital Affiliated to Yangzhou University, the Fifth People's Hospital of Huai'an  Huai'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanfu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an Second People's Hospital  Huai'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an Second People's Hospital  Huai'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an Second People's Hospital  Huai'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1277-6156","authenticated-orcid":false,"given":"Xianjin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an Second People's Hospital  Huai'an 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