{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T01:06:02Z","timestamp":1789779962936,"version":"4.0.1"},"reference-count":64,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["23ZR1413200"],"award-info":[{"award-number":["23ZR1413200"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Stroke, predominantly ischemic, is a leading cause of mortality and disability worldwide. Despite advances in intervention strategies, effective treatments to mitigate neurological injury post\u2010ischemic stroke remain limited. Hydrogen sulfide (H<jats:sub>2<\/jats:sub>S), a gas signaling molecule, has been implicated in neuroprotection, but its role in stroke is controversial. S\u2010propargyl\u2010cysteine (SPRC), an H<jats:sub>2<\/jats:sub>S donor, has shown great potential in protecting against neurological injuries, but its mechanisms in ischemic stroke are not fully understood. This study investigates the neuroprotective potential of SPRC and its mechanisms, focusing on the interplay between H<jats:sub>2<\/jats:sub>S and autophagy in modulating the cerebral microenvironment post\u2010stroke.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a comprehensive single\u2010cell RNA sequencing analysis on ischemic brain tissue to elucidate the cellular heterogeneity and specific responses related to H<jats:sub>2<\/jats:sub>S synthesis and autophagy. We utilized the GEO repository dataset GSE174574, applying stringent filtering and batch effect correction using the Harmony R package. Cellular subpopulations were identified using established markers, and H<jats:sub>2<\/jats:sub>S and autophagy scores were calculated using the JASMINE package. We also measured serum H<jats:sub>2<\/jats:sub>S levels, evaluated the pharmacodynamics of SPRC in rats, and constructed a cerebral ischemia\u2013reperfusion (I\/R) injury model to assess the neuroprotective effects of SPRC. Additionally, we examined the role of SPRC in CBS and 3\u2010MST knockout mice to determine the dependency on these H<jats:sub>2<\/jats:sub>S synthetases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our findings revealed a dysregulation in the expression of H<jats:sub>2<\/jats:sub>S and autophagy\u2010related genes in central nervous system cells, particularly in neurons, following stroke. SPRC administration significantly improved neurological behavior, metabolic activity, reduced brain infarction size, and ameliorated ultrastructure changes in stroke\u2010affected rats. Interestingly, SPRC continued to provide neuroprotection even after the knockdown of CBS and 3\u2010MST, indicating a CBS\/3\u2010MST\u2010independent mechanism. Furthermore, SPRC preserved the endogenous H<jats:sub>2<\/jats:sub>S level and strongly upregulated protective autophagy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study is the first to reveal the neuroprotection of SPRC in cerebral I\/R injury in a classical enzymatic CBS\/3\u2010MST independent manner. The potential cellular and molecular mechanisms may rely on the promotion of SPRC to activated protective autophagy. Our results suggest that SPRC could be a promising therapeutic candidate for enhancing neuroprotection and modulating autophagy in ischemic stroke.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70399","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T07:24:22Z","timestamp":1753341862000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["S\u2010Propargyl\u2010Cysteine Attenuates Stroke Heterogeneity via Promoting Protective Autophagy Across Multiple Neural Cell Types: Insights From Single\u2010Cell Sequencing"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2589-2004","authenticated-orcid":false,"given":"Xiaoming","family":"Xin","sequence":"first","affiliation":[{"name":"School of Pharmacy, Shanghai University of Medicine and Health Sciences  Shanghai China"},{"name":"Department of Pediatric Surgery, Guangzhou institute of Pediatrics, Guangdong 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