{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T05:21:18Z","timestamp":1737091278054,"version":"3.33.0"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Program Management Unit for Human Resources & Institutional Development, Research and Innovation","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"National Research Council of Thailand (NRCT)\u2013Mahidol University"},{"name":"Thailand Science Research and Innovation (TSRI)\u2013Mahidol University [Fundamental Fund: fiscal year 2024 by National Science Research and Innovation Fund (NSRF)]"},{"name":"TSRI\u2013Burapha University (Fundamental Fund fiscal year 2024 by NSRF]"},{"name":"The CIF\/CNI Grant, Faculty of Science, Mahidol University"},{"name":"Thailand Research Fund (TRF)\/TSRI through International Research Network Program","award":["IRN60W0001"],"award-info":[{"award-number":["IRN60W0001"]}]},{"name":"Thailand Research Fund (TRF)\/TSRI through International Research Network Program","award":["IRN60W0001"],"award-info":[{"award-number":["IRN60W0001"]}]},{"name":"Thailand Research Fund (TRF)\/TSRI through International Research Network Program","award":["IRN60W0001"],"award-info":[{"award-number":["IRN60W0001"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Although long-term high dietary sodium consumption often aggravates hypertension and bone loss, sodium in the intestinal lumen has been known to promote absorption of nutrients and other ions, e.g., glucose and calcium. However, whether high-salt diet (HSD) altered mucosal morphology, villous cell turnover and calcium transporter expression remained elusive. Herein, rats were treated with HSD containing 8% wt\/wt NaCl for up to 5 months. HSD rats exhibited a marked increase in sodium intake with high fecal and urinary sodium excretion, as compared to the control group treated with normal diet. Intestinal histomorphometry revealed increasing of crypt depth and villous height in 3- and 4-month HSD groups, respectively, consistent with larger mucosal-to-serosal amplification ratio that reflected an increased surface area for nutrient absorption. The signals of Ki-67-positive cells was enhanced in the crypts as visualized by multiphoton fluorescence microscopy, whereas the TUNEL-positive cells were decreased in the villi of HSD, suggesting greater crypt cell proliferation and a reduction of villous cell apoptosis. Confocal microscopy showed higher expression of TRPV6 protein in the villous tip of HSD, while PMCA<jats:sub>1<\/jats:sub> expression was increased in villous tip and crypt areas. The percentage of cells with highly expressed uroguanylin\u2014an endogenous intestinal natriuretic peptide\u2014was significantly higher in HSD group. In conclusion, HSD profoundly changed the intestinal morphology and turnover of epithelial cell, increased the expression of calcium transporters and uroguanylin. Our findings reflect pathophysiological adaptations in the intestine, which might be another target organ for drug discovery against HSD-induced osteopathy in the future.<\/jats:p>","DOI":"10.1371\/journal.pone.0317415","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T18:31:27Z","timestamp":1737052287000},"page":"e0317415","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-term excessive salt consumption alters villous and crypt morphology and the protein expression of uroguanylin, TRPV6 and PMCA1b in the rat small intestine"],"prefix":"10.1371","volume":"20","author":[{"given":"Natchayaporn","family":"Thonapan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kannikar","family":"Wongdee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sirion","family":"Aksornthong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jarinthorn","family":"Teerapornpuntakit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wacharaporn","family":"Tiyasatkulkovit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5356-1942","authenticated-orcid":true,"given":"Nattapon","family":"Panupinthu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2189-6542","authenticated-orcid":true,"given":"Narattaphol","family":"Charoenphandhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"issue":"6","key":"pone.0317415.ref001","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.jacc.2019.11.055","article-title":"Salt reduction to prevent hypertension and cardiovascular disease: JACC State-of-the-Art review","volume":"75","author":"FJ He","year":"2020","journal-title":"J Am Coll Cardiol"},{"issue":"2","key":"pone.0317415.ref002","doi-asserted-by":"crossref","first-page":"143","DOI":"10.3164\/jcbn.21-153","article-title":"Increased salt intake is associated with diabetes and characteristic dietary habits: a community-based cross-sectional study in Japan","volume":"71","author":"N Itoh","year":"2022","journal-title":"J Clin Biochem Nutr"},{"key":"pone.0317415.ref003","doi-asserted-by":"crossref","first-page":"b4567","DOI":"10.1136\/bmj.b4567","article-title":"Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies","volume":"339","author":"P Strazzullo","year":"2009","journal-title":"BMJ"},{"issue":"3","key":"pone.0317415.ref004","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1007\/s12020-015-0532-y","article-title":"Association of urinary sodium\/creatinine ratio with bone mineral density in postmenopausal women: KNHANES 2008\u20132011","volume":"49","author":"SW Kim","year":"2015","journal-title":"Endocrine"},{"issue":"10","key":"pone.0317415.ref005","doi-asserted-by":"crossref","first-page":"e14034","DOI":"10.1111\/eci.14034","article-title":"Excessive salt intake reduces bone density in the general female population","volume":"53","author":"H Takase","year":"2023","journal-title":"Eur J Clin Invest"},{"issue":"1","key":"pone.0317415.ref006","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1038\/s41598-021-81413-2","article-title":"Excessive salt consumption causes systemic calcium mishandling and worsens microarchitecture and strength of long bones in rats","volume":"11","author":"W Tiyasatkulkovit","year":"2021","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0317415.ref007","doi-asserted-by":"crossref","first-page":"12293","DOI":"10.1038\/s41598-019-48797-8","article-title":"Impairment of bone microstructure and upregulation of osteoclastogenic markers in spontaneously hypertensive rats","volume":"9","author":"W Tiyasatkulkovit","year":"2019","journal-title":"Sci Rep"},{"issue":"7","key":"pone.0317415.ref008","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1203\/00006450-198107000-00002","article-title":"Intestinal maturation: effect of luminal osmolality on net mineral secretion","volume":"15","author":"FK Ghishan","year":"1981","journal-title":"Pediatr Res"},{"issue":"4","key":"pone.0317415.ref009","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1159\/000058351","article-title":"Small bowel enterocyte apoptosis and proliferation are increased in the elderly","volume":"48","author":"R Ciccocioppo","year":"2002","journal-title":"Gerontology"},{"key":"pone.0317415.ref010","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1146\/annurev-physiol-012110-142244","article-title":"Regulation of electroneutral NaCl absorption by the small intestine","volume":"73","author":"A Kato","year":"2011","journal-title":"Annu Rev Physiol"},{"issue":"3","key":"pone.0317415.ref011","first-page":"947","article-title":"Physiology of electrolyte transport in the gut: implications for disease","volume":"9","author":"MC Rao","year":"2019","journal-title":"Compr Physiol"},{"issue":"9","key":"pone.0317415.ref012","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1017\/S0007114508088041","article-title":"Increasing sodium intake from a previous low or high intake affects water, electrolyte and acid-base balance differently","volume":"101","author":"M Heer","year":"2009","journal-title":"Br J Nutr"},{"issue":"2","key":"pone.0317415.ref013","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s11906-009-0018-5","article-title":"Effect of excessive salt intake: role of plasma sodium","volume":"11","author":"S Reuter","year":"2009","journal-title":"Curr Hypertens Rep"},{"issue":"3 Pt 1","key":"pone.0317415.ref014","first-page":"G413","article-title":"Response of rat jejunum to changes in sodium and volume balance","volume":"251","author":"NR Levens","year":"1986","journal-title":"Am J Physiol"},{"key":"pone.0317415.ref015","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.3389\/fphys.2019.01334","article-title":"Expression, localization, and effect of high salt intake on electroneutral Na+\/HCO3\u2013 cotransporter NBCn2 in rat small intestine: Implication in intestinal NaCl absorption","volume":"10","author":"JL Wang","year":"2019","journal-title":"Front Physiol"},{"issue":"8","key":"pone.0317415.ref016","doi-asserted-by":"crossref","first-page":"F943","DOI":"10.1152\/ajprenal.00504.2010","article-title":"The epithelial sodium\/proton exchanger, NHE3, is necessary for renal and intestinal calcium (re)absorption","volume":"302","author":"W Pan","year":"2012","journal-title":"Am J Physiol Renal Physiol"},{"issue":"8","key":"pone.0317415.ref017","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1172\/JCI20057","article-title":"A novel role for uroguanylin in the regulation of sodium balance","volume":"112","author":"LR Forte","year":"2003","journal-title":"J Clin Invest"},{"issue":"2","key":"pone.0317415.ref018","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/S0272-6386(96)90318-2","article-title":"Salt and water homeostasis: uroguanylin is a circulating peptide hormone with natriuretic activity","volume":"28","author":"LR Forte","year":"1996","journal-title":"Am J Kidney Dis"},{"issue":"3","key":"pone.0317415.ref019","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1681\/ASN.2005080818","article-title":"Cellular effects of guanylin and uroguanylin","volume":"17","author":"A Sindic","year":"2006","journal-title":"J Am Soc Nephrol"},{"issue":"12","key":"pone.0317415.ref020","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/s41575-022-00675-x","article-title":"The role of goblet cells and mucus in intestinal homeostasis","volume":"19","author":"JK Gustafsson","year":"2022","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"2","key":"pone.0317415.ref021","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1210\/jcem-55-2-369","article-title":"The role of dietary sodium on renal excretion and intestinal absorption of calcium and on vitamin D metabolism","volume":"55","author":"NA Breslau","year":"1982","journal-title":"J Clin Endocrinol Metab"},{"issue":"8","key":"pone.0317415.ref022","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1097\/00004872-199308000-00003","article-title":"The kidney and essential hypertension: a link to osteoporosis?","volume":"11","author":"GA MacGregor","year":"1993","journal-title":"J Hypertens"},{"issue":"6","key":"pone.0317415.ref023","doi-asserted-by":"crossref","first-page":"G1193","DOI":"10.1152\/ajpgi.00237.2009","article-title":"Human duodenum responses to vitamin D metabolites of TRPV6 and other genes involved in calcium absorption","volume":"297","author":"S Balesaria","year":"2009","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"23","key":"pone.0317415.ref024","doi-asserted-by":"crossref","first-page":"7142","DOI":"10.3748\/wjg.v21.i23.7142","article-title":"Molecular aspects of intestinal calcium absorption","volume":"21","author":"G Diaz de Barboza","year":"2015","journal-title":"World J Gastroenterol"},{"issue":"4","key":"pone.0317415.ref025","doi-asserted-by":"crossref","first-page":"181","DOI":"10.3109\/10408363.2010.536429","article-title":"Molecular mechanisms for regulation of intestinal calcium absorption by vitamin D and other factors","volume":"47","author":"JC Fleet","year":"2010","journal-title":"Crit Rev Clin Lab Sci"},{"key":"pone.0317415.ref026","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/bs.vh.2014.12.010","article-title":"Vitamin D-enhanced duodenal calcium transport","volume":"98","author":"K Wongdee","year":"2015","journal-title":"Vitam Horm"},{"issue":"24","key":"pone.0317415.ref027","doi-asserted-by":"crossref","first-page":"3344","DOI":"10.3748\/wjg.v26.i24.3344","article-title":"Intestinal Ca2+ absorption revisited: A molecular and clinical approach","volume":"26","author":"VA Areco","year":"2020","journal-title":"World J Gastroenterol"},{"key":"pone.0317415.ref028","doi-asserted-by":"crossref","first-page":"30301","DOI":"10.1038\/srep30301","article-title":"Oral CoQ10 attenuates high salt-induced hypertension by restoring neurotransmitters and cytokines in the hypothalamic paraventricular nucleus","volume":"6","author":"HL Gao","year":"2016","journal-title":"Sci Rep"},{"issue":"11","key":"pone.0317415.ref029","doi-asserted-by":"crossref","first-page":"E1010","DOI":"10.1152\/ajpendo.00049.2015","article-title":"Positive long-term outcomes from presuckling calcium supplementation in lactating rats and the offspring","volume":"308","author":"P Suntornsaratoon","year":"2015","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"pone.0317415.ref030","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.abb.2015.11.038","article-title":"Intestinal mucosal changes and upregulated calcium transporter and FGF-23 expression during lactation: Contribution of lactogenic hormone prolactin","volume":"590","author":"K Wongdee","year":"2016","journal-title":"Arch Biochem Biophys"},{"issue":"6279","key":"pone.0317415.ref031","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1126\/science.aaf1648","article-title":"Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut","volume":"351","author":"MR Howitt","year":"2016","journal-title":"Science"},{"issue":"3","key":"pone.0317415.ref032","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s102380200018","article-title":"A simple new method to calculate small intestine absorptive surface in the rat","volume":"2","author":"K Kisielinski","year":"2002","journal-title":"Clin Exp Med"},{"issue":"1","key":"pone.0317415.ref033","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.scr.2014.12.002","article-title":"Cryosectioning the intestinal crypt-villus axis: an ex vivo method to study the dynamics of epigenetic modifications from stem cells to differentiated cells","volume":"14","author":"A Vincent","year":"2015","journal-title":"Stem Cell Res"},{"issue":"6","key":"pone.0317415.ref034","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1023\/A:1012154506858","article-title":"Influence of morphometric factors on quantitation of paracellular permeability of intestinal epithelia in vitro","volume":"14","author":"A Collett","year":"1997","journal-title":"Pharm Res"},{"issue":"3","key":"pone.0317415.ref035","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9","article-title":"The Ki-67 protein: from the known and the unknown","volume":"182","author":"T Scholzen","year":"2000","journal-title":"J Cell Physiol"},{"key":"pone.0317415.ref036","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.3389\/fimmu.2020.02054","article-title":"Mucins in intestinal mucosal defense and inflammation: Learning from clinical and experimental studies","volume":"11","author":"JA Grondin","year":"2020","journal-title":"Front Immunol"},{"issue":"9","key":"pone.0317415.ref037","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1359\/jbmr.080408","article-title":"Sodium and bone health: impact of moderately high and low salt intakes on calcium metabolism in postmenopausal women","volume":"23","author":"B Teucher","year":"2008","journal-title":"J Bone Miner Res"},{"issue":"1","key":"pone.0317415.ref038","article-title":"Analysis of 1,25-dihydroxyvitamin D3 genomic action reveals calcium-regulating and calcium-independent effects in mouse intestine and human enteroids","volume":"41","author":"S Li","year":"2021","journal-title":"Mol Cell Biol"},{"issue":"1","key":"pone.0317415.ref039","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1152\/physrev.00015.2012","article-title":"Gastric acid, calcium absorption, and their impact on bone health","volume":"93","author":"S Kopic","year":"2013","journal-title":"Physiol Rev"},{"issue":"Suppl 1","key":"pone.0317415.ref040","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.2215\/CJN.05910809","article-title":"Calcium metabolism in health and disease","volume":"5","author":"M. Peacock","year":"2010","journal-title":"Clin J Am Soc Nephrol"},{"issue":"3","key":"pone.0317415.ref041","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1002\/cphy.c200014","article-title":"Intestinal calcium absorption","volume":"11","author":"K Wongdee","year":"2021","journal-title":"Compr Physiol"},{"issue":"2","key":"pone.0317415.ref042","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.bpg.2016.02.007","article-title":"Physiology of intestinal absorption and secretion","volume":"30","author":"PR Kiela","year":"2016","journal-title":"Best Pract Res Clin Gastroenterol"},{"issue":"4","key":"pone.0317415.ref043","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s12576-017-0530-3","article-title":"An approach to the research on ion and water properties in the interphase between the plasma membrane and bulk extracellular solution","volume":"67","author":"H Hibino","year":"2017","journal-title":"J Physiol Sci"},{"issue":"5","key":"pone.0317415.ref044","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1203\/00006450-199605000-00022","article-title":"Effect of resistant and digestible starch on intestinal absorption of calcium, iron, and zinc in infant pigs","volume":"39","author":"MB Morais","year":"1996","journal-title":"Pediatr Res"},{"key":"pone.0317415.ref045","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1113\/jphysiol.1984.sp015034","article-title":"The influence of mucus on the diffusion of chloride ions across the oesophagus of the minnow (Phoxinus phoxinus L.)","volume":"346","author":"KL Shephard","year":"1984","journal-title":"J Physiol"},{"issue":"1\u20132","key":"pone.0317415.ref046","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s11010-013-1885-2","article-title":"Antioxidant and antiapoptotic properties of melatonin restore intestinal calcium absorption altered by menadione","volume":"387","author":"A Carpentieri","year":"2014","journal-title":"Mol Cell Biochem"},{"issue":"5","key":"pone.0317415.ref047","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1007\/s12576-019-00688-3","article-title":"Factors inhibiting intestinal calcium absorption: hormones and luminal factors that prevent excessive calcium uptake","volume":"69","author":"K Wongdee","year":"2019","journal-title":"J Physiol Sci"},{"issue":"3","key":"pone.0317415.ref048","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1152\/physrev.00028.2016","article-title":"The plasma membrane calcium ATPases and their role as major new players in human disease","volume":"97","author":"N Stafford","year":"2017","journal-title":"Physiol Rev"},{"issue":"11","key":"pone.0317415.ref049","doi-asserted-by":"crossref","DOI":"10.3390\/ijms24119642","article-title":"The natriuretic peptide system: A single entity, pleiotropic effects","volume":"24","author":"V Della Corte","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"8","key":"pone.0317415.ref050","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1172\/JCI200318743","article-title":"Uroguanylin knockout mice have increased blood pressure and impaired natriuretic response to enteral NaCl load","volume":"112","author":"JN Lorenz","year":"2003","journal-title":"J Clin Invest"},{"issue":"2","key":"pone.0317415.ref051","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1152\/physrev.00056.2003","article-title":"Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases","volume":"85","author":"P Meneton","year":"2005","journal-title":"Physiol Rev"},{"key":"pone.0317415.ref052","doi-asserted-by":"crossref","first-page":"3171","DOI":"10.2147\/JIR.S318327","article-title":"Role of goblet cells in intestinal barrier and mucosal immunity","volume":"14","author":"S Yang","year":"2021","journal-title":"J Inflamm Res"},{"issue":"4526","key":"pone.0317415.ref053","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1126\/science.7302593","article-title":"Intestinal diffusion barrier: unstirred water layer or membrane surface mucous coat?","volume":"214","author":"KW Smithson","year":"1981","journal-title":"Science"},{"issue":"8","key":"pone.0317415.ref054","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.molmed.2015.06.003","article-title":"Three cheers for the goblet cell: maintaining homeostasis in mucosal epithelia","volume":"21","author":"HA McCauley","year":"2015","journal-title":"Trends Mol Med"},{"key":"pone.0317415.ref055","doi-asserted-by":"crossref","first-page":"718710","DOI":"10.3389\/fnut.2022.718710","article-title":"The influence of nutrition on intestinal permeability and the microbiome in health and disease","volume":"9","author":"O Inczefi","year":"2022","journal-title":"Front Nutr"},{"issue":"2","key":"pone.0317415.ref056","doi-asserted-by":"crossref","first-page":"C317","DOI":"10.1152\/ajpcell.00330.2023","article-title":"Enhancement of intestinal calcium transport by short-chain fatty acids: roles of Na+\/H+ exchanger 3 and transient receptor potential vanilloid subfamily 6","volume":"326","author":"N Thammayon","year":"2024","journal-title":"Am J Physiol Cell Physiol"},{"issue":"9","key":"pone.0317415.ref057","article-title":"High-salt diet and intestinal microbiota: influence on cardiovascular disease and inflammatory bowel disease","volume":"13","author":"X Wang","year":"2024","journal-title":"Biology (Basel)"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0317415","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T18:32:00Z","timestamp":1737052320000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0317415"}},"subtitle":[],"editor":[{"given":"Birendra","family":"Mishra","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,1,16]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0317415","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,16]]}}}