{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T01:33:31Z","timestamp":1789263211193,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"43","license":[{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270803"],"award-info":[{"award-number":["82270803"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070726"],"award-info":[{"award-number":["82070726"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["2024AFA019"],"award-info":[{"award-number":["2024AFA019"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Nephrolithiasis is increasingly prevalent worldwide. Although metabolic dysregulation has emerged as an important feature of the disease, the specific metabolic programs within tubular epithelial cells that drive stone formation remain poorly understood. Here, we use single\u2010cell transcriptomics to profile mouse models of nephrolithiasis and identify a marked suppression of gluconeogenesis in renal proximal tubular epithelial cells, driven by downregulation of the rate\u2010limiting enzyme glucose\u20106\u2010phosphatase (G6PC) and associated with lactate accumulation. We further show that loss of G6PC or lactate accumulation is sufficient to activate TGF\u2010\u03b2\/SMAD3 signaling, driving epithelial\u2013mesenchymal transition (EMT) and a profibrotic epithelial program associated with enhanced crystal deposition. Mechanistically, lactate induces lactylation of the transcription factor SNAIL1 at lysine 206, facilitating its nuclear localization and transcriptional activation of TGF\u2010\u03b2. Together, these findings establish a G6PC\u2010lactate\u2010SNAIL1 axis linking metabolic dysregulation to epithelial remodeling during nephrolithiasis.<\/jats:p>","DOI":"10.1002\/advs.75585","type":"journal-article","created":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T17:36:56Z","timestamp":1778434616000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["G6PC Downregulation Promotes Renal Calcium Oxalate Stone Formation via Lactate\u2010Induced SNAIL1 K206 Lactylation and Epithelial\u2010Mesenchymal Transition"],"prefix":"10.1002","volume":"13","author":[{"given":"Kai","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Urology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"},{"name":"Department of Urology The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan Shandong China"},{"name":"Shandong Medicine and Health Key Laboratory of Organ Transplantation and Nephrosis Shandong Institute of Nephrology  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixin","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Urology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"},{"name":"Tumor Precision Diagnosis and Treatment Technology and Translational Medicine Hubei Engineering Research Center Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Duan","sequence":"additional","affiliation":[{"name":"Tumor Precision Diagnosis and Treatment Technology and Translational Medicine Hubei Engineering Research Center Zhongnan Hospital of Wuhan University  Wuhan Hubei China"},{"name":"Department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangjun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology the First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huahui","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Urology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"},{"name":"Tumor Precision Diagnosis and Treatment Technology and Translational Medicine Hubei Engineering Research Center Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyang","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Shenzhen University Shenzhen Second People's Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongmin","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Urology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"},{"name":"Tumor Precision Diagnosis and Treatment Technology and Translational Medicine Hubei Engineering Research Center Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"},{"name":"Tumor Precision Diagnosis and Treatment Technology and Translational Medicine Hubei Engineering Research Center Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youmiao","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Urology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"},{"name":"Tumor Precision Diagnosis and Treatment Technology and Translational Medicine Hubei Engineering Research Center Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhen","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Urology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"},{"name":"Tumor Precision Diagnosis and Treatment Technology and Translational Medicine Hubei Engineering Research Center Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology Jiangnan University Medical Center  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengcheng","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Science Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Urology Jiangnan University Medical Center  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7425-8751","authenticated-orcid":false,"given":"Ninghan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Urology Jiangnan University Medical Center  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9730-7276","authenticated-orcid":false,"given":"Hua","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Urology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"},{"name":"Tumor Precision Diagnosis and Treatment Technology and Translational Medicine Hubei Engineering Research Center Zhongnan Hospital of Wuhan University  Wuhan Hubei China"},{"name":"Taikang Center for Life and Medical Sciences Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.8"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2014.05.117"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2012.11.004"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/js9.0000000000003417"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581\u2010019\u20100216\u20106"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1681\/asn.2021050680"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106524"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581\u2010024\u201000836\u2010y"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2023.08.006"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202413937"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101678\u20101"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.09.033"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1039\/c4tb01626b"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2024.112609"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201038975\u20108"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40164\u2010022\u201000320\u2010y"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/15680096113136660102"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adc9465"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/8836355"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476\u20105381.2011.01242.x"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1681\/asn.0000000000000421"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijsu.2016.11.023"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/7277966"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103246"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202507068"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2025.1636185"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70421"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2025.1644886"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010025\u201001554\u2010z"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.156324"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202307216"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010024\u201005427\u20105"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8060757"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.724200"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40170\u2010024\u201000362\u20102"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3724\/abbs.2023074"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202408945"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.137668"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.75585","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.75585","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.75585","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T16:01:29Z","timestamp":1785772889000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.75585"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,10]]},"references-count":38,"journal-issue":{"issue":"43","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/advs.75585"],"URL":"https:\/\/doi.org\/10.1002\/advs.75585","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,10]]},"assertion":[{"value":"2026-03-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e75585"}}