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Herein, an integrated method involving mass spectrometry (MS)-based lipidomics and matrix-assisted laser desorption\/ionization-MS imaging (MALDI-MSI) was developed for the study of nephrotoxicity in mice exposed to 10 and 100 \u03bcg bisphenol S (BPS)\/kg body weight\/day. The BPS exposure remarkable perturbed abundances of 91 potential markers that mainly involved in five metabolic pathways. We elucidated the lipids spatial heterogeneity by using morphological analysis, probabilistic latent semantic analysis, and coregistered multimodal three-dimensional (3D)-MSI. In morphological analysis, both 10 and 100 \u03bcg BPS induced significant nephrotoxicity to mice, including glomerular necrosis in renal cortex, cloudy swelling in renal medulla, and interstitial collapsing in renal pelvis. Significant differential signaling lipids such as sphingomyelin (SM) (d22:0\/20:4), ceramide (Cer) (d18:2\/24:1), and sphingosine (d18:0) related to inflammation were found to be up-regulated and colocalized in the renal cortex, medulla, and pelvis, respectively. Also, seven significant differential lipids, which are considered to be involved in membrane homeostasis and cellular function, were found to be colocalized in the renal cortex. The observed significant variations of morphology, lipid accumulation, and metabolism in the renal cortex implicated that lipids in the renal cortex were more sensitive to BPS exposure than those in the renal medulla and pelvis. Moreover, we reconstructed a 3D-MSI model of kidney and identified two heterogeneous-related substructures in the renal cortex and pelvis upon 100 \u03bcg BPS exposure. It might be used in novel specificity evaluation and early diagnosis for environmental pollutant-induced kidney diseases.<\/jats:p>","DOI":"10.1021\/acs.analchem.7b04540","type":"journal-article","created":{"date-parts":[[2018,2,12]],"date-time":"2018-02-12T05:30:50Z","timestamp":1518413450000},"page":"3196-3204","source":"Crossref","is-referenced-by-count":91,"title":["MALDI-MS Imaging Reveals Asymmetric Spatial Distribution\nof Lipid Metabolites from Bisphenol S\u2011Induced Nephrotoxicity"],"prefix":"10.1021","volume":"90","author":[{"given":"Chao","family":"Zhao","sequence":"first","affiliation":[{"name":"Hong Kong Baptist University , , ,","place":["Hong Kong SAR, P. R. China"]},{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, P. R. China, 100085"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peisi","family":"Xie","sequence":"additional","affiliation":[{"name":"Hong Kong Baptist University , , ,","place":["Hong Kong SAR, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Yong","sequence":"additional","affiliation":[{"name":"Hong Kong Baptist University , , ,","place":["Hong Kong SAR, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1843-999X","authenticated-orcid":true,"given":"Hailin","family":"Wang","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, P. R. China, 100085"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1519-7224","authenticated-orcid":true,"given":"Arthur Chi Kong","family":"Chung","sequence":"additional","affiliation":[{"name":"Hong Kong Baptist University , , ,","place":["Hong Kong SAR, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7013-5547","authenticated-orcid":true,"given":"Zongwei","family":"Cai","sequence":"additional","affiliation":[{"name":"Hong Kong Baptist University , , ,","place":["Hong Kong SAR, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2018,2,12]]},"reference":[{"key":"2026081803244846200_cit1","volume-title":"Kirk-Othmer Encyclopedia\nof Chemical Technology","author":"Clark","year":"2012"},{"key":"2026081803244846200_cit2","doi-asserted-by":"publisher","first-page":"6515","DOI":"10.1021\/es300876n","volume":"46","author":"Liao","year":"2012","journal-title":"Environ. Sci. Technol."},{"key":"2026081803244846200_cit3","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.chroma.2013.12.074","volume":"1328","author":"Yang","year":"2014","journal-title":"J. Chromatogr. 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