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Despite its severity, no effective drugs currently exist for sepsis treatment. This study explores whether pathogen\u2010derived carbon dots can mitigate their inherent toxicity while leveraging their structural similarity to pathogens to competitively bind pattern recognition receptors, thereby inhibiting sepsis. Based on this concept, <jats:italic>E. coli<\/jats:italic> wall\u2010derived carbon dots (E\u2010CDs) are synthesized and shown to reduce inflammatory cytokine production, protect organ function, and improve survival in septic mice. Mechanistic studies reveal that E\u2010CDs competitively bind to lipopolysaccharide\u2010binding protein with lipopolysaccharide, promoting toll\u2010like receptor 4 degradation via the lysosomal pathway and inhibiting nuclear factor kappa\u2010B (NF\u2010\u03baB) activation. Additionally, E\u2010CDs exhibit antioxidant properties, reducing oxidative stress and mitochondrial DNA release, thereby suppressing overactivation of the stimulator of interferon genes pathway. In septic cynomolgus monkeys and patient\u2010derived peripheral blood mononuclear cells, E\u2010CDs alleviate inflammation and oxidative stress. Overall, this study demonstrates that E\u2010CDs can suppress the cytokine storm in sepsis by co\u2010silencing innate immune pathways, suggesting that converting pathogens into carbon dots offers a novel therapeutic strategy.<\/jats:p>","DOI":"10.1002\/adma.202414237","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T01:48:41Z","timestamp":1736300921000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Suppression of Sepsis Cytokine Storm by <i>Escherichia Coli<\/i> Cell Wall\u2010Derived Carbon Dots"],"prefix":"10.1002","volume":"37","author":[{"given":"Yinan","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy Nankai University  Tianjin 300350 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy Nankai University  Tianjin 300350 China"},{"name":"Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs Tianjin International Joint Academy of Biomedicine  Tianjin 300457 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Qiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy Nankai University  Tianjin 300350 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy Nankai University  Tianjin 300350 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy Nankai University  Tianjin 300350 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caihong","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy Nankai University  Tianjin 300350 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy Nankai University  Tianjin 300350 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy Nankai University  Tianjin 300350 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Tianjin Fourth Central Hospital  Tianjin 300142 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqing","family":"Gao","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases Tianjin Third Central Hospital  Tianjin 300170 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy Nankai University  Tianjin 300350 China"},{"name":"Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs Tianjin International Joint Academy of Biomedicine  Tianjin 300457 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8962-2193","authenticated-orcid":false,"given":"Tao","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy Nankai University  Tianjin 300350 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32989-7"},{"key":"e_1_2_9_2_1","first-page":"20","author":"Huang M.","year":"2019","journal-title":"Int. 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