{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T11:18:27Z","timestamp":1784114307329,"version":"3.55.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T00:00:00Z","timestamp":1548720000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T00:00:00Z","timestamp":1548720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000062","name":"U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK102043"],"award-info":[{"award-number":["DK102043"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK102043"],"award-info":[{"award-number":["DK102043"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000070","name":"U.S. Department of Health &amp; Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["EB021483"],"award-info":[{"award-number":["EB021483"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000070","name":"U.S. Department of Health &amp; Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["EB021483"],"award-info":[{"award-number":["EB021483"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Melamine, which induces proximal tubular (PT) cell damage has a greater nephrotoxic effect when combined with cyanuric and uric acids; however, it is unknown whether such effect can stimulate calcium phosphate (CaP)\/calcium oxalate (CaOx) stone formation. Here, we show that melamine acts as an inducer of CaP, CaOx and CaP\u2009+\u2009CaOx (mixed) crystal formations in a time and concentration-dependent manner by stabilizing those crystals and further co-aggregating with melamine. To explore the physiological relevance of such melamine-augmented calcium crystal formation, we used 2-dimensional (2D) and 3D microfluidic (MF) device, embedded with PT cells, which also resembled the effect of melamine-stimulated CaP, CaOx and mixed crystal formation. Significantly, addition of preformed CaP and\/or CaOx crystal in the presence of melamine, further potentiated those crystal formations in 3D MFs, which helped the growth and aggregation of mixed crystals. Our data show that the mechanism of such predisposition of stone formation could be largely due to co-crystallization between melamine and CaP\/CaOx and pronounced effect on induction of stone-forming pathway activation in 3D MF. Taken together, melamine-induced CaP and\/or CaOx crystal formation <jats:italic>ex-vivo<\/jats:italic> will help us in understanding the larger role of melamine as an environmental toxicant in producing the pathology in similar cellular microenvironments.<\/jats:p>","DOI":"10.1038\/s41598-018-37191-5","type":"journal-article","created":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T11:03:17Z","timestamp":1548759797000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Melamine promotes calcium crystal formation in three-dimensional microfluidic device"],"prefix":"10.1038","volume":"9","author":[{"given":"Farai","family":"Gombedza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sade","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenia","family":"Awuah Boadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Nie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2364-8945","authenticated-orcid":false,"given":"Bidhan C.","family":"Bandyopadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,1,29]]},"reference":[{"key":"37191_CR1","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1097\/01.ju.0000152082.14384.d7","volume":"173","author":"MS Pearle","year":"2005","unstructured":"Pearle, M. S., Calhoun, E. A. & Curhan, G. C. Urologic Diseases in America Project: Urolithiasis. J. Urol. 173, 848\u2013857 (2005).","journal-title":"J. Urol."},{"key":"37191_CR2","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1007\/s00467-009-1116-y","volume":"25","author":"AP Evan","year":"2010","unstructured":"Evan, A. P. Physiopathology and etiology of stone formation in the kidney and the urinary tract. Pediatr. Nephrol. Berl. Ger. 25, 831\u2013841 (2010).","journal-title":"Pediatr. Nephrol. Berl. Ger."},{"key":"37191_CR3","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1111\/j.1523-1755.2004.00803.x","volume":"66","author":"JH Parks","year":"2004","unstructured":"Parks, J. H., Worcester, E. M., Coe, F. L., Evan, A. P. & Lingeman, J. E. Clinical implications of abundant calcium phosphatein routinely analyzed kidney stones. Kidney Int. 66, 777\u2013785 (2004).","journal-title":"Kidney Int."},{"key":"37191_CR4","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1002\/ar.20580","volume":"290","author":"P Evan Andrew","year":"2007","unstructured":"Evan Andrew, P. et al. Mechanism of Formation of Human Calcium Oxalate Renal Stones on Randall\u2019s Plaque. Anat. Rec. 290, 1315\u20131323 (2007).","journal-title":"Anat. Rec."},{"key":"37191_CR5","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1056\/NEJMcp1001011","volume":"363","author":"EM Worcester","year":"2010","unstructured":"Worcester, E. M. & Coe, F. L. Clinical Practice Calcium Kidney Stones. N. Engl. J. Med. 363, 954\u2013963 (2010).","journal-title":"N. Engl. J. Med."},{"key":"37191_CR6","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1007\/s00240-009-0191-7","volume":"37","author":"H-G Tiselius","year":"2009","unstructured":"Tiselius, H.-G., Lindb\u00e4ck, B., Fornander, A.-M. & Nilsson, M.-A. Studies on the role of calcium phosphate in the process of calcium oxalate crystal formation. Urol. Res. 37, 181\u2013192 (2009).","journal-title":"Urol. Res."},{"key":"37191_CR7","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1515\/CCLM.2004.052","volume":"42","author":"PO Schwille","year":"2004","unstructured":"Schwille, P. O., Schmiedl, A. & Manoharan, M. Is calcium oxalate nucleation in postprandial urine of males with idiopathic recurrent calcium urolithiasis related to calcium phosphate nucleation and the intensity of stone formation? Studies allowing insight into a possible role of urinary free citrate and protein. Clin. Chem. Lab. Med. 42, 283\u2013293 (2004).","journal-title":"Clin. Chem. Lab. Med."},{"key":"37191_CR8","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.juro.2008.02.041","volume":"180","author":"C Escobar","year":"2008","unstructured":"Escobar, C., Byer, K. J., Khaskheli, H. & Khan, S. R. Apatite Induced Renal Epithelial Injury: Insight Into the Pathogenesis of Kidney Stones. J. Urol. 180, 379\u2013387 (2008).","journal-title":"J. Urol."},{"key":"37191_CR9","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1016\/j.juro.2011.10.125","volume":"187","author":"SR Khan","year":"2012","unstructured":"Khan, S. R., Rodriguez, D. E., Gower, L. B. & Monga, M. Association of Randall Plaque With Collagen Fibers and Membrane Vesicles. J. Urol. 187, 1094\u20131100 (2012).","journal-title":"J. Urol."},{"key":"37191_CR10","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/s00240-010-0349-3","volume":"39","author":"H-G Tiselius","year":"2011","unstructured":"Tiselius, H.-G. A hypothesis of calcium stone formation: an interpretation of stone research during the past decades. Urol. Res. 39, 231\u2013243 (2011).","journal-title":"Urol. Res."},{"key":"37191_CR11","doi-asserted-by":"publisher","first-page":"4037","DOI":"10.1039\/c2lc40801e","volume":"12","author":"Z Wei","year":"2012","unstructured":"Wei, Z., Amponsah, P. K., Al-Shatti, M., Nie, Z. & Bandyopadhyay, B. C. Engineering of polarized tubular structures in a microfluidic device to study calcium phosphate stone formation. Lab. Chip 12, 4037\u20134040 (2012).","journal-title":"Lab. Chip"},{"key":"37191_CR12","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1039\/C6LC00197A","volume":"16","author":"G Laffite","year":"2016","unstructured":"Laffite, G. et al. Calcium oxalate precipitation by diffusion using laminar microfluidics: toward a biomimetic model of pathological microcalcifications. Lab. Chip 16, 1157\u20131160 (2016).","journal-title":"Lab. Chip"},{"key":"37191_CR13","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1038\/ki.2012.320","volume":"83","author":"VO Edvardsson","year":"2013","unstructured":"Edvardsson, V. O., Indridason, O. S., Haraldsson, G., Kjartansson, O. & Palsson, R. Temporal trends in the incidence of kidney stone disease. Kidney Int. 83, 146\u2013152 (2013).","journal-title":"Kidney Int."},{"key":"37191_CR14","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/nrneph.2011.24","volume":"7","author":"RP Dalal","year":"2011","unstructured":"Dalal, R. P. & Goldfarb, D. S. Melamine-related kidney stones and renal toxicity. Nat. Rev. Nephrol. 7, 267\u2013274 (2011).","journal-title":"Nat. Rev. Nephrol."},{"key":"37191_CR15","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1681\/ASN.2008101065","volume":"20","author":"AK Hau","year":"2009","unstructured":"Hau, A. K., Kwan, T. H. & Li, P. K. Melamine Toxicity and the Kidney. J. Am. Soc. Nephrol. 20, 245\u2013250 (2009).","journal-title":"J. Am. Soc. Nephrol."},{"key":"37191_CR16","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1016\/j.tiv.2013.04.011","volume":"27","author":"F-C Kuo","year":"2013","unstructured":"Kuo, F.-C., Tseng, Y.-T., Wu, S.-R., Wu, M.-T. & Lo, Y.-C. Melamine activates NF\u03baB\/COX-2\/PGE2 pathway and increases NADPH oxidase\u2013dependent ROS production in macrophages and human embryonic kidney cells. Toxicol. In Vitro 27, 1603\u20131611 (2013).","journal-title":"Toxicol. In Vitro"},{"key":"37191_CR17","first-page":"383","volume":"36","author":"G Chengzhi","year":"2013","unstructured":"Chengzhi, G., Hui, Y. & Zuping, H. Melamine causes apoptosis of rat kidney epithelial cell line (NRK\u201052e cells) via excessive intracellular ROS (reactive oxygen species) and the activation of p38 MAPK pathway. Cell Biol. Int. 36, 383\u2013389 (2013).","journal-title":"Cell Biol. Int."},{"key":"37191_CR18","doi-asserted-by":"publisher","first-page":"C27","DOI":"10.1152\/ajpcell.00225.2016","volume":"313","author":"AJ Yiu","year":"2017","unstructured":"Yiu, A. J., Ibeh, C.-L., Roy, S. K. & Bandyopadhyay, B. C. Melamine induces Ca2+\u2212sensing receptor activation and elicits apoptosis in proximal tubular cells. Am. J. Physiol.-Cell Physiol. 313, C27\u2013C41 (2017).","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"37191_CR19","first-page":"1158","volume":"13","author":"G Wiegele","year":"1998","unstructured":"Wiegele, G., Brandis, M. & Zimmerhackl, L. B. Apoptosis and necrosis during ischaemia in renal tubular cells (LLC-PK1 and MDCK). Nephrol. Dial. Transplant. Off. Publ. Eur. Dial. Transpl. Assoc. - Eur. Ren. Assoc. 13, 1158\u20131167 (1998).","journal-title":"Nephrol. Dial. Transplant. Off. Publ. Eur. Dial. Transpl. Assoc. - Eur. Ren. Assoc."},{"key":"37191_CR20","doi-asserted-by":"publisher","first-page":"12908","DOI":"10.1074\/jbc.M410013200","volume":"280","author":"BC Bandyopadhyay","year":"2005","unstructured":"Bandyopadhyay, B. C. et al. Apical Localization of a Functional TRPC3\/TRPC6-Ca2+\u2212Signaling Complex in Polarized Epithelial Cells ROLE IN APICAL Ca2+ INFLUX. J. Biol. Chem. 280, 12908\u201312916 (2005).","journal-title":"J. Biol. Chem."},{"key":"37191_CR21","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1038\/ki.2011.174","volume":"80","author":"FJ Garc\u00eda L\u00f3pez","year":"2011","unstructured":"Garc\u00eda L\u00f3pez, F. J. & Quereda, C. Melamine toxicity: one more culprit in calcium kidney lithiasis. Kidney Int. 80, 694\u2013696 (2011).","journal-title":"Kidney Int."},{"key":"37191_CR22","first-page":"F604","volume":"270","author":"JR Asplin","year":"1996","unstructured":"Asplin, J. R., Mandel, N. S. & Coe, F. L. Evidence of calcium phosphate supersaturation in the loop of Henle. Am. J. Physiol. 270, F604\u2013613 (1996).","journal-title":"Am. J. Physiol."},{"key":"37191_CR23","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1007\/s00240-013-0602-7","volume":"41","author":"H-G Tiselius","year":"2013","unstructured":"Tiselius, H.-G. The role of calcium phosphate in the development of Randall\u2019s plaques. Urolithiasis 41, 369\u2013377 (2013).","journal-title":"Urolithiasis"},{"key":"37191_CR24","doi-asserted-by":"publisher","first-page":"e61","DOI":"10.1159\/000080258","volume":"98","author":"JA Jonassen","year":"2004","unstructured":"Jonassen, J. A., Cao, L.-C., Honeyman, T. & Scheid, C. R. Intracellular Events in the Initiation of Calcium Oxalate Stones. Nephron Exp. Nephrol. 98, e61\u2013e64 (2004).","journal-title":"Nephron Exp. Nephrol."},{"key":"37191_CR25","doi-asserted-by":"publisher","first-page":"71","DOI":"10.4103\/0974-7796.82171","volume":"3","author":"X Lu","year":"2011","unstructured":"Lu, X. et al. Gender and urinary pH affect melamine-associated kidney stone formation risk. Urol. Ann. 3, 71\u201374 (2011).","journal-title":"Urol. Ann."},{"key":"37191_CR26","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1002\/art.1780260211","volume":"26","author":"H Paul","year":"1983","unstructured":"Paul, H., Reginato, A. J. & Schumacher, H. R. Alizarin red S staining as a screening test to detect calcium compounds in synovial fluid. Arthritis Rheum. 26, 191\u2013200 (1983).","journal-title":"Arthritis Rheum."},{"key":"37191_CR27","first-page":"186","volume":"109","author":"AD Proia","year":"1985","unstructured":"Proia, A. D. & Brinn, N. T. Identification of calcium oxalate crystals using alizarin red S stain. Arch. Pathol. Lab. Med. 109, 186\u2013189 (1985).","journal-title":"Arch. Pathol. Lab. Med."},{"key":"37191_CR28","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.archoralbio.2017.05.001","volume":"82","author":"I Lau","year":"2017","unstructured":"Lau, I. et al. Microcalcifications in stone-obstructed human submandibular gland are associated with apoptosis and cell proliferation. Arch. Oral Biol. 82, 99\u2013108 (2017).","journal-title":"Arch. Oral Biol."},{"key":"37191_CR29","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.ab.2004.02.002","volume":"329","author":"CA Gregory","year":"2004","unstructured":"Gregory, C. A., Gunn, W. G., Peister, A. & Prockop, D. J. An Alizarin red-based assay of mineralization by adherent cells in culture: comparison with cetylpyridinium chloride extraction. Anal. Biochem. 329, 77\u201384 (2004).","journal-title":"Anal. Biochem."},{"key":"37191_CR30","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1354\/vp.45-3-417","volume":"45","author":"ME Thompson","year":"2008","unstructured":"Thompson, M. E. et al. Characterization of melamine-containing and calcium oxalate crystals in three dogs with suspected pet food-induced nephrotoxicosis. Vet. Pathol. 45, 417\u2013426 (2008).","journal-title":"Vet. Pathol."},{"key":"37191_CR31","doi-asserted-by":"publisher","first-page":"4628","DOI":"10.1021\/cr0782574","volume":"108","author":"L Wang","year":"2008","unstructured":"Wang, L. & Nancollas, G. H. Calcium Orthophosphates: Crystallization and Dissolution. Chem. Rev. 108, 4628\u20134669 (2008).","journal-title":"Chem. Rev."},{"key":"37191_CR32","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1351\/pac200779050825","volume":"79","author":"PG Koutsoukos","year":"2007","unstructured":"Koutsoukos, P. G., Kofina, A. N. & Kanellopoulou, D. G. Solubility of salts in water: Key issue for crystal growth and dissolution processes. Pure Appl. Chem. 79, 825\u2013850 (2007).","journal-title":"Pure Appl. Chem."},{"key":"37191_CR33","doi-asserted-by":"publisher","first-page":"F476","DOI":"10.1152\/ajprenal.00363.2006","volume":"293","author":"S Terryn","year":"2007","unstructured":"Terryn, S. et al. A primary culture of mouse proximal tubular cells, established on collagen-coated membranes. Am. J. Physiol. Renal Physiol. 293, F476\u2013485 (2007).","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"37191_CR34","doi-asserted-by":"publisher","first-page":"5463","DOI":"10.1039\/C6CE00697C","volume":"18","author":"X-Y Sun","year":"2016","unstructured":"Sun, X.-Y., Ouyang, J.-M. & Xu, M. Synthesis, characterization, and cytotoxicity assay of calcium oxalate dihydrate crystals in various shapes. CrystEngComm 18, 5463\u20135473 (2016).","journal-title":"CrystEngComm"},{"key":"37191_CR35","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1189\/jlb.0610381","volume":"89","author":"BC Bandyopadhyay","year":"2011","unstructured":"Bandyopadhyay, B. C., Pingle, S. C. & Ahern, G. P. Store-operated Ca2+ signaling in dendritic cells occurs independently of STIM1. J. Leukoc. Biol. 89, 57\u201362 (2011).","journal-title":"J. Leukoc. Biol."},{"key":"37191_CR36","doi-asserted-by":"publisher","first-page":"F1109","DOI":"10.1152\/ajprenal.00620.2007","volume":"294","author":"SR Khan","year":"2008","unstructured":"Khan, S. R. & Glenton, P. A. Calcium oxalate crystal deposition in kidneys of hypercalciuric mice with disrupted type IIa sodium-phosphate cotransporter. Am. J. Physiol. Renal Physiol. 294, F1109\u20131115 (2008).","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"37191_CR37","doi-asserted-by":"publisher","first-page":"16008","DOI":"10.1038\/nrdp.2016.8","volume":"2","author":"SR Khan","year":"2016","unstructured":"Khan, S. R. et al. Kidney stones. Nat. Rev. Dis. Primer 2, 16008 (2016).","journal-title":"Nat. Rev. Dis. Primer"},{"key":"37191_CR38","first-page":"172ra22","volume":"5","author":"X Zheng","year":"2013","unstructured":"Zheng, X. et al. Melamine-induced renal toxicity is mediated by the gut microbiota. Sci. Transl. Med. 5, 172ra22 (2013).","journal-title":"Sci. Transl. Med."},{"key":"37191_CR39","doi-asserted-by":"publisher","first-page":"2009","DOI":"10.1007\/s00216-012-5971-1","volume":"403","author":"NN Yazgan","year":"2012","unstructured":"Yazgan, N. N., Boyac\u0131, \u0130. H., Topcu, A. & Tamer, U. Detection of melamine in milk by surface-enhanced Raman spectroscopy coupled with magnetic and Raman-labeled nanoparticles. Anal. Bioanal. Chem. 403, 2009\u20132017 (2012).","journal-title":"Anal. Bioanal. Chem."},{"key":"37191_CR40","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.saa.2012.09.004","volume":"99","author":"R Selvaraju","year":"2012","unstructured":"Selvaraju, R., Raja, A. & Thiruppathi, G. FT-Raman spectral analysis of human urinary stones. Spectrochim. Acta. A. Mol. Biomol. Spectrosc. 99, 205\u2013210 (2012).","journal-title":"Spectrochim. Acta. A. Mol. Biomol. Spectrosc."},{"key":"37191_CR41","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.semnephrol.2009.03.008","volume":"29","author":"JM Sands","year":"2009","unstructured":"Sands, J. M. & Layton, H. E. The Physiology of Urinary Concentration: an Update. Semin. Nephrol. 29, 178\u2013195 (2009).","journal-title":"Semin. Nephrol."},{"key":"37191_CR42","doi-asserted-by":"publisher","first-page":"3459","DOI":"10.1016\/j.biomaterials.2010.01.082","volume":"31","author":"LK Fiddes","year":"2010","unstructured":"Fiddes, L. K. et al. A circular cross-section PDMS microfluidics system for replication of cardiovascular flow conditions. Biomaterials 31, 3459\u20133464 (2010).","journal-title":"Biomaterials"},{"key":"37191_CR43","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1159\/000313944","volume":"169","author":"N Nakhoul","year":"2011","unstructured":"Nakhoul, N. & Batuman, V. Role of proximal tubules in the pathogenesis of kidney disease. Contrib. Nephrol. 169, 37\u201350 (2011).","journal-title":"Contrib. Nephrol."},{"key":"37191_CR44","doi-asserted-by":"crossref","unstructured":"Nakamura, M. et al. Roles of Renal Proximal Tubule Transport in Acid\/Base Balance and Blood PressureRegulation. BioMed Res. Int. 2014 (2014).","DOI":"10.1155\/2014\/504808"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-37191-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-37191-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-37191-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T05:22:25Z","timestamp":1671254545000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-37191-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,29]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["37191"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-37191-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,29]]},"assertion":[{"value":"4 June 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 January 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"875"}}