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This study develops an integrated framework combining single\u2010cell RNA sequencing (scRNA\u2010seq) and machine learning (ML) to design nanozymes with specific enzyme\u2010mimicking types for precision treatment of DMED. First, scRNA\u2010seq analysis demonstrated increased reactive oxygen species (ROS) level and downregulated expression level of glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) in the corpus cavernosum of DMED patients. Second, a nanozyme database is constructed based on the published researches. With this database, two ML models are developed to predict the enzyme\u2010mimicking types of nanozymes, which showed that iron (Fe)\u2010based nanozymes are particularly suitable for addressing reductase deficiencies in DMED. Thus, the Fe\u2010DMOF, an Fe\u2010based single atom nanozyme (SAzyme), is synthesized, simultaneously exhibiting GPx\u2010, CAT\u2010 and SOD\u2010like activities. Fe\u2010DMOF can significantly reduce the ROS accumulation and inhibit the ROS\u2010induced histone lactylation modifications, furtherly reversing the inflammatory differentiation of fibroblasts and macrophages in the diabetic corpus cavernosum. These results not only highlight the efficacy of Fe\u2010DMOF in DMED treatment, but also validate the scRNA\u2010seq + ML framework as an effective approach for data\u2010driven SAzyme design for disease\u2010specific treatment.<\/jats:p>","DOI":"10.1002\/advs.202524169","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T19:39:11Z","timestamp":1776195551000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Design of Single\u2010Atom Nanozymes for Precision Treatment of Erectile Dysfunction with Integrated Single\u2010Cell RNA Sequencing and Machine Learning"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiang","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Nanjing Medical University  Nanjing P. R. 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