{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:22:42Z","timestamp":1790137362969,"version":"4.0.1"},"reference-count":49,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"863","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82300799"],"award-info":[{"award-number":["82300799"]}],"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":["82274024"],"award-info":[{"award-number":["82274024"]}],"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":["82373950"],"award-info":[{"award-number":["82373950"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Beijing Natural Science Foundation","award":["7254415"],"award-info":[{"award-number":["7254415"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,8,19]]},"abstract":"<jats:p>\n                    Platelet dysfunction drives bleeding complications in patients with advanced chronic kidney disease (CKD), worsening clinical outcomes. However, the underlying mechanisms remain unclear, limiting treatment options. In this study, we identified the expression of urea transporter B (SLC14A1\/UT-B) in human and mouse platelets. By analyzing a clinical cohort of patients with CKD, we demonstrated that single-nucleotide polymorphisms in\n                    <jats:italic toggle=\"yes\">SLC14A1<\/jats:italic>\n                    were associated with bleeding events in CKD. Using a 5\/6 nephrectomy (5\/6 Nx) mouse model and blood samples from patients with advanced CKD, we found that SLC14A1\/UT-B\u2013mediated urea influx underlies platelet dysfunction in advanced CKD given that both genetic knockout of\n                    <jats:italic toggle=\"yes\">Slc14a1<\/jats:italic>\n                    or pharmacological inhibition of UT-B reversed mouse and human platelet dysfunction induced by urea or advanced CKD plasma. SLC14A1\/UT-B\u2013mediated urea influx induced protein carbamylation, which drove platelet dysfunction. By characterizing the carbamylation profiles of proteins in human and mouse platelets, we demonstrated that carbamylation disrupted cytoskeletal rearrangement, degranulation, and inside-out integrin \u03b1IIb\u03b23 signaling transduction during platelet activation, leading to impaired platelet aggregation, secretion, and spreading in advanced CKD. Furthermore, treatment of 5\/6 Nx mice with the UT-B inhibitor PU-48 effectively preserved platelet function and improved hemostatic ability. These findings suggest that SLC14A1\/UT-B promoted urea uptake in platelets and mediated bleeding in advanced CKD, highlighting its potential as a therapeutic target for managing bleeding complications in patients with advanced CKD.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.aed4678","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:59:03Z","timestamp":1787162343000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Urea transporter B\u2013mediated urea uptake\u2013induced protein carbamylation in platelets underlies bleeding in chronic kidney disease"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4085-4302","authenticated-orcid":true,"given":"Zhiwei","family":"Qiu","sequence":"first","affiliation":[{"name":"Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100191, China."},{"name":"Beijing Key Laboratory of Clinical Pharmacology and Translation of Innovative Drugs, Beijing 100034, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1847-9323","authenticated-orcid":true,"given":"Fei","family":"Xiong","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100191, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2060-5552","authenticated-orcid":true,"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100191, China."},{"name":"Beijing Key Laboratory of Clinical Pharmacology and Translation of Innovative Drugs, Beijing 100034, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100191, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Gao","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100034, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4793-6872","authenticated-orcid":true,"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100034, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100191, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100191, China."},{"name":"Beijing Key Laboratory of Clinical Pharmacology and Translation of Innovative Drugs, Beijing 100034, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruofei","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100191, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linyu","family":"Cao","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100191, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100191, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangying","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Basic Innovation Research, Beijing Hospital, National Center for Gerontology; National Clinical Research Center for Gerontology; Key Laboratory of Geriatrics of NHC; Beijing Key Laboratory of Aging Mechanism and Intervention Research on Aging-Related Diseases; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China."},{"name":"Department of Cardiology, Beijing Hospital, National Center for Gerontology; National Clinical Research Center for Gerontology; Key Laboratory of Geriatrics of NHC; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianze","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Beihua University, Jilin 132013, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Beihua University, Jilin 132013, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7298-3307","authenticated-orcid":true,"given":"Jie","family":"Dong","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100034, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7966-2095","authenticated-orcid":true,"given":"Baoxue","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4186-1005","authenticated-orcid":true,"given":"Yimin","family":"Cui","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100191, China."},{"name":"Beijing Key Laboratory of Clinical Pharmacology and Translation of Innovative Drugs, Beijing 100034, China."},{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8245-2611","authenticated-orcid":true,"given":"Qian","family":"Xiang","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100191, China."},{"name":"Beijing Key Laboratory of Clinical Pharmacology and Translation of Innovative Drugs, Beijing 100034, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.2299"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.0000000000000199"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2022010013"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(70)80026-2"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1970.00310110093013"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1055\/a-2373-3792"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.0000000000000106"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.inorgchem.5c01041"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-96-6898-4_6"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1263"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1104"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-017-9343-8_4"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tmrv.2016.10.003"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tracli.2022.03.001"},{"key":"e_1_3_2_16_2","first-page":"101703","article-title":"Computational exploration of SLC14A1 genetic variants through structure modeling, protein-ligand docking, and molecular dynamics simulation","volume":"38","author":"Sultana T.","year":"2024","unstructured":"T. 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