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Macrophage pyroptosis represents a pro-inflammatory event and a potential therapeutic target. Here, we report a single-atom immunomodulator, a potassium-based single-atom catalyst (K-SAC) with K\u2013N\n                    <jats:sub>4<\/jats:sub>\n                    sites, that suppresses macrophage pyroptosis for ALI therapy through antioxidant catalysis. Constructed from biocompatible potassium, the most abundant intracellular metal in humans, K-SAC displays potent superoxide dismutase- and catalase-like activities, with the underlying mechanisms revealed by density functional theory simulations. Following preferential macrophage uptake, K-SAC scavenges reactive oxygen species, downregulates gasdermin D and its N-terminal fragment, activates endosomal sorting complexes required for transport-mediated membrane repair, and promotes membrane phospholipid remodeling, thereby effectively inhibiting macrophage pyroptosis. Notably, this catalytic membrane repair mechanism offers a versatile strategy for restoring membrane integrity. Such catalytic inhibition of pyroptosis preserves pulmonary immune homeostasis and ameliorates lipopolysaccharide- or cecal ligation and puncture-induced ALI, establishing a catalytic immunotherapeutic approach using a physiologically abundant element for therapeutic applications.\n                  <\/jats:p>","DOI":"10.1038\/s41467-026-76331-8","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T17:56:21Z","timestamp":1785866181000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A potassium-based single-atom catalyst enables acute lung injury immunotherapy in mice by inhibiting macrophage pyroptosis"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5606-894X","authenticated-orcid":false,"given":"Xiangyu","family":"Lu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmin","family":"Jian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cai","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijie","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanru","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyi","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanning","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2434-4954","authenticated-orcid":false,"given":"Ke","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3352-7162","authenticated-orcid":false,"given":"Xin","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8790-195X","authenticated-orcid":false,"given":"Jianlin","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"76331_CR1","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1001\/jama.2016.0291","volume":"315","author":"G Bellani","year":"2016","unstructured":"Bellani, G. et al. 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