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Despite extensive research on ischemic stroke (IS), current therapies remain constrained by single\u2010target limitations, and a unified therapeutic strategy that concurrently mitigates reactive oxygen species (ROS) overload and restores mitochondrial function remains elusive. Herein, we report a single\u2010atom FeCo N\/C nanozyme that uniquely integrates dual enzyme\u2010mimicking activities\u2014catalase (CAT) and NADH oxidase\u2014enabling simultaneous H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    scavenging and NAD\n                    <jats:sup>+<\/jats:sup>\n                    regeneration. The nanozyme exhibits a Michaelis\u2013Menten constant (K\n                    <jats:sub>m<\/jats:sub>\n                    ) of 4.64 m\n                    <jats:sc>m<\/jats:sc>\n                    for H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    decomposition, reflecting an 11.2\u2010fold higher substrate affinity than natural catalase, and a K\n                    <jats:sub>m<\/jats:sub>\n                    of 51.4 \u00b5\n                    <jats:sc>m<\/jats:sc>\n                    for NADH oxidation\u2014significantly outperforming natural NADH oxidase. Density functional theory reveals that the FeCoN\n                    <jats:sub>6<\/jats:sub>\n                    active site enables synergistic Fe\u2500Co interactions, lowering energy barriers for O\n                    <jats:sub>2<\/jats:sub>\n                    evolution. In HT22 neurons under oxygen\u2010glucose deprivation\/reoxygenation, FeCo N\/C reduces ROS, restores NAD\n                    <jats:sup>+<\/jats:sup>\n                    \/NADH homeostasis, and boosts ATP synthesis, effectively suppressing apoptosis. In a murine middle cerebral artery occlusion\/reperfusion model, a single intracerebroventricular dose (0.5 \u00b5L, 5\u00a0mg mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) reduces infarct volume from 58.0% to 32.9% and significantly improves neurological function. This work establishes a multitarget nanotherapeutic paradigm that bridges redox regulation and bioenergetic recovery, offering a clinically translatable strategy for ischemia\u2010reperfusion injury.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202505735","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T05:21:32Z","timestamp":1765776092000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Single\u2010Atom FeCo\u2010N\n                    <sub>6<\/sub>\n                    Nanozyme with Dual Enzyme\u2010Mimicking Activity Reverses Redox Imbalance and Bioenergetic Collapse in Ischemic Stroke"],"prefix":"10.1002","volume":"15","author":[{"given":"Mengying","family":"Li","sequence":"first","affiliation":[{"name":"Department of Chemistry Capital Normal University  Beijing 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1501-5005","authenticated-orcid":false,"given":"Yuqing","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Chemistry Capital Normal University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012781"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40779-023-00463-x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.0048"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201013848\u20101"},{"key":"e_1_2_9_6_1","first-page":"1","article-title":"Neuronal Iniuries in Cerebral Infarction and Ischemicstroke: From Mechanisms To Treatment (Review)","volume":"49","author":"Zhao 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