{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:10:03Z","timestamp":1789017003753,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Beijing Life Science Academy Scientific Research Program","award":["2024100CC0090"],"award-info":[{"award-number":["2024100CC0090"]}]},{"name":"Beijing Life Science Academy Scientific Research Program","award":["2024100CB0200"],"award-info":[{"award-number":["2024100CB0200"]}]},{"name":"Beijing Life Science Academy Scientific Research Program","award":["2023100CB0060"],"award-info":[{"award-number":["2023100CB0060"]}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2022YFC3400700"],"award-info":[{"award-number":["2022YFC3400700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["22125401"],"award-info":[{"award-number":["22125401"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["22527807"],"award-info":[{"award-number":["22527807"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["22125401"],"award-info":[{"award-number":["22125401"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["22527807"],"award-info":[{"award-number":["22527807"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: Traditional bulk tissue analyses obscure the precise spatial compartmentalization of nicotine and its molecular effects within individual anatomical regions. This study aimed to develop and apply a high-resolution spatial multi-omics framework to characterize the localized disposition and functional responses induced by an acute nicotine challenge. Methods: We established a spatial multi-omics framework integrating matrix-assisted laser desorption\/ionization time-of-flight mass spectrometry imaging (MALDI-TOF MSI), air-flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI), laser microdissection (LMD)-based microscale data-independent acquisition (microDIA) proteomics, and targeted LC-MS\/MS. This platform was used to analyze the kidney and five brain regions in rats subjected to an acute nicotine challenge following an adaptation regimen. Results: Spatial mapping revealed distinct peripheral and central distribution patterns: nicotine, cotinine, and nornicotine accumulated predominantly in the renal cortex and medulla, whereas their distribution in the brain is region-dependent, with a prominent 3-hydroxycotinine signal in the olfactory bulb. Avoiding tissue homogenization enabled these spatial distributions to be linked to localized functional responses. The striatal dopamine\/DOPAC axis showed the strongest acute neurochemical response, consistent with increased dopamine turnover. Spatial metabolomics further demonstrated robust, region-specific metabolic reprogramming, with the hippocampus showing the greatest metabolic variance. LMD-resolved proteomics identified protein-level changes, particularly in the olfactory bulb and thalamus. Cross-omics revealed coordinated alterations in purine, pyrimidine, glycerophospholipid, and alanine\/aspartate\/glutamate metabolism, with the thalamus showing the greatest extensive metabolite\u2013protein concordance. Conclusions: These findings characterize acute nicotine exposure as a spatially compartmentalized process involving renal handling, region-specific brain distribution, and localized molecular response programs.<\/jats:p>","DOI":"10.3390\/metabo16090657","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:51:48Z","timestamp":1788871908000},"page":"657","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatially Resolved Multi-Omics Reveals Brain\u2013Kidney Compartmentalization and Region-Specific Molecular Reprogramming After Acute Nicotine Exposure"],"prefix":"10.3390","volume":"16","author":[{"given":"Qian","family":"Li","sequence":"first","affiliation":[{"name":"Beijing Life Science Academy, Beijing 102299, China"},{"name":"Key Laboratory of Tobacco Biological Effects, China National Tobacco Quality Supervision & Test Center, Zhengzhou 450001, China"},{"name":"College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0664-9804","authenticated-orcid":false,"given":"Lutao","family":"Xu","sequence":"additional","affiliation":[{"name":"Beijing Life Science Academy, Beijing 102299, China"},{"name":"Key Laboratory of Tobacco Biological Effects, China National Tobacco Quality Supervision & Test Center, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Beijing Life Science Academy, Beijing 102299, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoge","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Life Science Academy, Beijing 102299, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1542-0297","authenticated-orcid":false,"given":"Yu","family":"Bai","sequence":"additional","affiliation":[{"name":"Beijing Life Science Academy, Beijing 102299, China"},{"name":"College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Chen","sequence":"additional","affiliation":[{"name":"Beijing Life Science Academy, Beijing 102299, China"},{"name":"Key Laboratory of Tobacco Biological Effects, China National Tobacco Quality Supervision & Test Center, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Hou","sequence":"additional","affiliation":[{"name":"Beijing Life Science Academy, Beijing 102299, China"},{"name":"Key Laboratory of Tobacco Biological Effects, China National Tobacco Quality Supervision & Test Center, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1056\/NEJMra0809890","article-title":"Nicotine addiction","volume":"362","author":"Benowitz","year":"2010","journal-title":"N. 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