{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:22:47Z","timestamp":1791177767643,"version":"4.1.0"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T00:00:00Z","timestamp":1464220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T00:00:00Z","timestamp":1464220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Diabetic retinopathy (DR) is a serious microvascular complication of diabetes and a major cause of blindness in the developing world. Early diabetic retinopathy is characterized by a loss of pericytes and vascular endothelial cells, a breakdown of the blood\u2013retinal barrier, vascular dysfunction and vascular-neuroinflammation. However, optimal treatment options and related mechanisms are still unclear. MicroRNA-126 (miR-126) plays a potential role in the pathogenesis in DR, which may regulate VEGF, Ang-1 and VCAM-1 expressions. This study investigated the therapeutic effects and mechanisms of Niaspan treatment of DR in diabetes (DM) rats. DM rats exhibits significantly decreased miR-126 and tight junction Claudin-5\/Occludin\/ZO-1 genes expression and increased Blood retinal-barrier (BRB) breakdown, retinal apoptosis and VEGF\/VEGFR, as well as VCAM-1\/CD45 expressions in the retina compared to normal control group. Niaspan treatment significantly improved clinical and histopathological outcomes; decreased the expressions of VEGF\/VEGFR, VCAM-1\/CD45, apoptosis and BRB breakdown, significantly increased tight junction proteins and Ang-1\/Tie-2 expressions, as well as increased retinal miR-126 expression compared to non-treatment diabetic rats. These data are the first to show that Niaspan treatment ameliorates DR through its repair vascular and inhibits inflammatory effects and also suggest that the miR-126 pathway may contribute to Niaspan treatment induced benefit effects.<\/jats:p>","DOI":"10.1038\/srep26909","type":"journal-article","created":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T05:27:33Z","timestamp":1464240453000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["MicroRNA-126 contributes to Niaspan treatment induced vascular restoration after diabetic retinopathy"],"prefix":"10.1038","volume":"6","author":[{"given":"Yang","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,5,26]]},"reference":[{"key":"BFsrep26909_CR1","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1136\/bjophthalmol-2011-300539","volume":"96","author":"D Pascolini","year":"2012","unstructured":"Pascolini, D. & Mariotti, S. P. Global estimates of visual impairment: 2010. The British journal of ophthalmology 96, 614\u2013618, 10.1136\/bjophthalmol-2011-300539 (2012).","journal-title":"The British journal of ophthalmology"},{"key":"BFsrep26909_CR2","doi-asserted-by":"publisher","first-page":"143","DOI":"10.2337\/diacare.21.1.143","volume":"21","author":"LP Aiello","year":"1998","unstructured":"Aiello, L. P. et al. Diabetic retinopathy. Diabetes care 21, 143\u2013156 (1998).","journal-title":"Diabetes care"},{"key":"BFsrep26909_CR3","unstructured":"Abcouwer, S. F. Angiogenic Factors and Cytokines in Diabetic Retinopathy. Journal of clinical & cellular immunology Suppl 1, 10.4172\/2155-9899 (2013)."},{"key":"BFsrep26909_CR4","doi-asserted-by":"publisher","first-page":"995","DOI":"10.2337\/db07-1618","volume":"57","author":"JM Lachin","year":"2008","unstructured":"Lachin, J. M., Genuth, S., Nathan, D. M., Zinman, B. & Rutledge, B. N. Effect of glycemic exposure on the risk of microvascular complications in the diabetes control and complications trial\u2013revisited. Diabetes 57, 995\u20131001, 10.2337\/db07-1618 (2008).","journal-title":"Diabetes"},{"key":"BFsrep26909_CR5","doi-asserted-by":"publisher","first-page":"32","DOI":"10.2174\/157339912798829188","volume":"8","author":"GP Giuliari","year":"2012","unstructured":"Giuliari, G. P. Diabetic retinopathy: current and new treatment options. Current diabetes reviews 8, 32\u201341 (2012).","journal-title":"Current diabetes reviews"},{"key":"BFsrep26909_CR6","doi-asserted-by":"publisher","first-page":"53","DOI":"10.2353\/ajpath.2007.061237","volume":"171","author":"K Nishijima","year":"2007","unstructured":"Nishijima, K. et al. Vascular endothelial growth factor-A is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury. The American journal of pathology 171, 53\u201367, 10.2353\/ajpath.2007.061237 (2007).","journal-title":"The American journal of pathology"},{"key":"BFsrep26909_CR7","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1586\/erc.13.17","volume":"11","author":"S Campbell","year":"2013","unstructured":"Campbell, S. & Genest, J. HDL-C: clinical equipoise and vascular endothelial function. Expert review of cardiovascular therapy 11, 343\u2013353, 10.1586\/erc.13.17 (2013).","journal-title":"Expert review of cardiovascular therapy"},{"key":"BFsrep26909_CR8","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1001\/jamaophthalmol.2014.5108","volume":"133","author":"BE Klein","year":"2015","unstructured":"Klein, B. E., Myers, C. E., Howard, K. P. & Klein, R. Serum Lipids and Proliferative Diabetic Retinopathy and Macular Edema in Persons With Long-term Type 1 Diabetes Mellitus: The Wisconsin Epidemiologic Study of Diabetic Retinopathy. JAMA ophthalmology 133, 503\u2013510, 10.1001\/jamaophthalmol.2014.5108 (2015).","journal-title":"JAMA ophthalmology"},{"key":"BFsrep26909_CR9","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1185\/030079904125004402","volume":"20","author":"MJ Chapman","year":"2004","unstructured":"Chapman, M. J., Assmann, G., Fruchart, J. C., Shepherd, J. & Sirtori, C. Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid\u2013a position paper developed by the European Consensus Panel on HDL-C. Current medical research and opinion 20, 1253\u20131268, 10.1185\/030079904125004402 (2004).","journal-title":"Current medical research and opinion"},{"key":"BFsrep26909_CR10","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1001\/jama.284.10.1263","volume":"284","author":"MB Elam","year":"2000","unstructured":"Elam, M. B. et al. Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: A randomized trial. Arterial Disease Multiple Intervention Trial. Jama 284, 1263\u20131270 (2000).","journal-title":"Jama"},{"key":"BFsrep26909_CR11","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.expneurol.2011.09.022","volume":"232","author":"X Ye","year":"2011","unstructured":"Ye, X. et al. Niaspan enhances vascular remodeling after stroke in type 1 diabetic rats. Experimental neurology 232, 299\u2013308, 10.1016\/j.expneurol.2011.09.022 (2011).","journal-title":"Experimental neurology"},{"key":"BFsrep26909_CR12","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1002\/ana.21160","volume":"62","author":"J Chen","year":"2007","unstructured":"Chen, J. et al. Niaspan increases angiogenesis and improves functional recovery after stroke. Annals of neurology 62, 49\u201358, 10.1002\/ana.21160 (2007).","journal-title":"Annals of neurology"},{"key":"BFsrep26909_CR13","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","volume":"116","author":"DP Bartel","year":"2004","unstructured":"Bartel, D. P. MicroRNAs: genomics, biogenesis, mechanism and function. Cell 116, 281\u2013297 (2004).","journal-title":"Cell"},{"key":"BFsrep26909_CR14","doi-asserted-by":"crossref","unstructured":"Fish, J. E. & Srivastava, D. MicroRNAs: opening a new vein in angiogenesis research. Science signaling 2, pe1, 10.1126\/scisignal.252pe1 (2009).","DOI":"10.1126\/scisignal.252pe1"},{"key":"BFsrep26909_CR15","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.devcel.2008.07.002","volume":"15","author":"S Wang","year":"2008","unstructured":"Wang, S. et al. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Developmental cell 15, 261\u2013271, 10.1016\/j.devcel.2008.07.002 (2008).","journal-title":"Developmental cell"},{"key":"BFsrep26909_CR16","doi-asserted-by":"publisher","first-page":"2318","DOI":"10.2337\/db12-1391","volume":"62","author":"S Lei","year":"2013","unstructured":"Lei, S. et al. Hyperglycemia-induced protein kinase C beta2 activation induces diastolic cardiac dysfunction in diabetic rats by impairing caveolin-3 expression and Akt\/eNOS signaling. Diabetes 62, 2318\u20132328, 10.2337\/db12-1391 (2013).","journal-title":"Diabetes"},{"key":"BFsrep26909_CR17","doi-asserted-by":"publisher","first-page":"1516","DOI":"10.1073\/pnas.0707493105","volume":"105","author":"TA Harris","year":"2008","unstructured":"Harris, T. A., Yamakuchi, M., Ferlito, M., Mendell, J. T. & Lowenstein, C. J. MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proceedings of the National Academy of Sciences of the United States of America 105, 1516\u20131521, 10.1073\/pnas.0707493105 (2008).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"BFsrep26909_CR18","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.devcel.2008.07.008","volume":"15","author":"JE Fish","year":"2008","unstructured":"Fish, J. E. et al. miR-126 regulates angiogenic signaling and vascular integrity. Developmental cell 15, 272\u2013284, 10.1016\/j.devcel.2008.07.008 (2008).","journal-title":"Developmental cell"},{"key":"BFsrep26909_CR19","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1038\/sj.gt.3302230","volume":"11","author":"H Nambu","year":"2004","unstructured":"Nambu, H. et al. Angiopoietin 1 inhibits ocular neovascularization and breakdown of the blood-retinal barrier. Gene therapy 11, 865\u2013873, 10.1038\/sj.gt.3302230 (2004).","journal-title":"Gene therapy"},{"key":"BFsrep26909_CR20","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1002\/emmm.201200224","volume":"4","author":"C Besler","year":"2012","unstructured":"Besler, C., Luscher, T. F. & Landmesser, U. Molecular mechanisms of vascular effects of High-density lipoprotein: alterations in cardiovascular disease. EMBO molecular medicine 4, 251\u2013268, 10.1002\/emmm.201200224 (2012).","journal-title":"EMBO molecular medicine"},{"key":"BFsrep26909_CR21","unstructured":"Yu, J. Y. & Lyons, T. J. Modified Lipoproteins in Diabetic Retinopathy: A Local Action in the Retina. Journal of clinical & experimental ophthalmology 4, 10.4172\/2155-9570.1000314 (2013)."},{"key":"BFsrep26909_CR22","doi-asserted-by":"publisher","first-page":"191382","DOI":"10.1155\/2015\/191382","volume":"2015","author":"R Crosby-Nwaobi","year":"2015","unstructured":"Crosby-Nwaobi, R. et al. Cross Talk between Lipid Metabolism and Inflammatory Markers in Patients with Diabetic Retinopathy. Journal of diabetes research 2015, 191382, 10.1155\/2015\/191382 (2015).","journal-title":"Journal of diabetes research"},{"key":"BFsrep26909_CR23","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/BF00283746","volume":"22","author":"TL Dornan","year":"1982","unstructured":"Dornan, T. L., Carter, R. D., Bron, A. J., Turner, R. C. & Mann, J. I. Low density lipoprotein cholesterol: an association with the severity of diabetic retinopathy. Diabetologia 22, 167\u2013170 (1982).","journal-title":"Diabetologia"},{"key":"BFsrep26909_CR24","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1172\/jci2425","volume":"102","author":"AJ Barber","year":"1998","unstructured":"Barber, A. J. et al. Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. The Journal of clinical investigation 102, 783\u2013791, 10.1172\/jci2425 (1998).","journal-title":"The Journal of clinical investigation"},{"key":"BFsrep26909_CR25","first-page":"1418","volume":"15","author":"AM Joussen","year":"2009","unstructured":"Joussen, A. M. et al. TNF-alpha mediated apoptosis plays an important role in the development of early diabetic retinopathy and long-term histopathological alterations. Molecular vision 15, 1418\u20131428 (2009).","journal-title":"Molecular vision"},{"key":"BFsrep26909_CR26","doi-asserted-by":"publisher","first-page":"96","DOI":"10.4103\/0975-3583.83035","volume":"2","author":"W Zhang","year":"2011","unstructured":"Zhang, W., Liu, H., Al-Shabrawey, M., Caldwell, R. W. & Caldwell, R. B. Inflammation and diabetic retinal microvascular complications. Journal of cardiovascular disease research 2, 96\u2013103, 10.4103\/0975-3583.83035 (2011).","journal-title":"Journal of cardiovascular disease research"},{"key":"BFsrep26909_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.survophthal.2008.10.001","volume":"54","author":"N Bhagat","year":"2009","unstructured":"Bhagat, N., Grigorian, R. A., Tutela, A. & Zarbin, M. A. Diabetic macular edema: pathogenesis and treatment. Survey of ophthalmology 54, 1\u201332, 10.1016\/j.survophthal.2008.10.001 (2009).","journal-title":"Survey of ophthalmology"},{"key":"BFsrep26909_CR28","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1001\/archopht.1996.01100130062010","volume":"114","author":"AP Adamis","year":"1996","unstructured":"Adamis, A. P. et al. Inhibition of vascular endothelial growth factor prevents retinal ischemia-associated iris neovascularization in a nonhuman primate. Archives of ophthalmology (Chicago, Ill: 1960) 114, 66\u201371 (1996).","journal-title":"Archives of ophthalmology (Chicago, Ill: 1960)"},{"key":"BFsrep26909_CR29","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1196\/annals.1420.016","volume":"1123","author":"E Vandenbroucke","year":"2008","unstructured":"Vandenbroucke, E., Mehta, D., Minshall, R. & Malik, A. B. Regulation of endothelial junctional permeability. Annals of the New York Academy of Sciences 1123, 134\u2013145, 10.1196\/annals.1420.016 (2008).","journal-title":"Annals of the New York Academy of Sciences"},{"key":"BFsrep26909_CR30","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s10456-007-9067-z","volume":"10","author":"KK Erickson","year":"2007","unstructured":"Erickson, K. K., Sundstrom, J. M. & Antonetti, D. A. Vascular permeability in ocular disease and the role of tight junctions. Angiogenesis 10, 103\u2013117, 10.1007\/s10456-007-9067-z (2007).","journal-title":"Angiogenesis"},{"key":"BFsrep26909_CR31","doi-asserted-by":"publisher","first-page":"E1661","DOI":"10.1210\/jc.2013-3868","volume":"99","author":"J Osipova","year":"2014","unstructured":"Osipova, J. et al. Diabetes-associated microRNAs in pediatric patients with type 1 diabetes mellitus: a cross-sectional cohort study. The Journal of clinical endocrinology and metabolism 99, E1661\u20131665, 10.1210\/jc.2013-3868 (2014).","journal-title":"The Journal of clinical endocrinology and metabolism"},{"key":"BFsrep26909_CR32","doi-asserted-by":"publisher","first-page":"17","DOI":"10.7150\/ijms.7329","volume":"11","author":"P Ye","year":"2014","unstructured":"Ye, P., Liu, J., He, F., Xu, W. & Yao, K. Hypoxia-induced deregulation of miR-126 and its regulative effect on VEGF and MMP-9 expression. International journal of medical sciences 11, 17\u201323, 10.7150\/ijms.7329 (2014).","journal-title":"International journal of medical sciences"},{"key":"BFsrep26909_CR33","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.yjmcc.2012.04.003","volume":"53","author":"S Meng","year":"2012","unstructured":"Meng, S. et al. Downregulation of microRNA-126 in endothelial progenitor cells from diabetes patients, impairs their functional properties, via target gene Spred-1. Journal of molecular and cellular cardiology 53, 64\u201372, 10.1016\/j.yjmcc.2012.04.003 (2012).","journal-title":"Journal of molecular and cellular cardiology"},{"key":"BFsrep26909_CR34","doi-asserted-by":"publisher","first-page":"341","DOI":"10.2174\/15701611113119990017","volume":"13","author":"C van Solingen","year":"2015","unstructured":"van Solingen, C., Bijkerk, R., de Boer, H. C., Rabelink, T. J. & van Zonneveld, A. J. The Role of microRNA-126 in Vascular Homeostasis. Current vascular pharmacology 13, 341\u2013351 (2015).","journal-title":"Current vascular pharmacology"},{"key":"BFsrep26909_CR35","doi-asserted-by":"publisher","first-page":"4402","DOI":"10.1167\/iovs.10-6879","volume":"52","author":"B Kovacs","year":"2011","unstructured":"Kovacs, B., Lumayag, S., Cowan, C. & Xu, S. MicroRNAs in early diabetic retinopathy in streptozotocin-induced diabetic rats. Investigative ophthalmology & visual science 52, 4402\u20134409, 10.1167\/iovs.10-6879 (2011).","journal-title":"Investigative ophthalmology & visual science"},{"key":"BFsrep26909_CR36","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.bbrc.2015.08.121","volume":"466","author":"J Wu","year":"2015","unstructured":"Wu, J. et al. Protective effects of methane-rich saline on diabetic retinopathy via anti-inflammation in a streptozotocin-induced diabetic rat model. Biochemical and biophysical research communications 466, 155\u2013161, 10.1016\/j.bbrc.2015.08.121 (2015).","journal-title":"Biochemical and biophysical research communications"},{"key":"BFsrep26909_CR37","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1093\/cvr\/cvq001","volume":"86","author":"O Barreiro","year":"2010","unstructured":"Barreiro, O., Martin, P., Gonzalez-Amaro, R. & Sanchez-Madrid, F. Molecular cues guiding inflammatory responses. Cardiovascular research 86, 174\u2013182, 10.1093\/cvr\/cvq001 (2010).","journal-title":"Cardiovascular research"},{"key":"BFsrep26909_CR38","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/s0002-9440(10)63952-1","volume":"158","author":"AM Joussen","year":"2001","unstructured":"Joussen, A. M. et al. Leukocyte-mediated endothelial cell injury and death in the diabetic retina. The American journal of pathology 158, 147\u2013152,10.1016\/s0002-9440(10)63952-1 (2001).","journal-title":"The American journal of pathology"},{"key":"BFsrep26909_CR39","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1136\/bjo.78.5.370","volume":"78","author":"S Tang","year":"1994","unstructured":"Tang, S., Le-Ruppert, K. C. & Gabel, V. P. Expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on proliferating vascular endothelial cells in diabetic epiretinal membranes. The British journal of ophthalmology 78, 370\u2013376 (1994).","journal-title":"The British journal of ophthalmology"},{"key":"BFsrep26909_CR40","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1016\/j.bbamcr.2012.07.011","volume":"1823","author":"R Sessa","year":"2012","unstructured":"Sessa, R. et al. The miR-126 regulates angiopoietin-1 signaling and vessel maturation by targeting p85beta. Biochimica et biophysica acta 1823, 1925\u20131935, 10.1016\/j.bbamcr.2012.07.011 (2012).","journal-title":"Biochimica et biophysica acta"},{"key":"BFsrep26909_CR41","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1161\/atvbaha.107.161539","volume":"29","author":"SW Jin","year":"2009","unstructured":"Jin, S. W. & Patterson, C. The opening act: vasculogenesis and the origins of circulation. Arteriosclerosis, thrombosis and vascular biology 29, 623\u2013629, 10.1161\/atvbaha.107.161539 (2009).","journal-title":"Arteriosclerosis, thrombosis and vascular biology"},{"key":"BFsrep26909_CR42","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1016\/s0002-9440(10)61115-7","volume":"160","author":"AM Joussen","year":"2002","unstructured":"Joussen, A. M. et al. Suppression of diabetic retinopathy with angiopoietin-1. The American journal of pathology 160, 1683\u20131693, 10.1016\/s0002-9440(10)61115-7 (2002).","journal-title":"The American journal of pathology"},{"key":"BFsrep26909_CR43","first-page":"213","volume":"79","author":"A Papapetropoulos","year":"1999","unstructured":"Papapetropoulos, A. et al. Direct actions of angiopoietin-1 on human endothelium: evidence for network stabilization, cell survival and interaction with other angiogenic growth factors. Laboratory investigation; a journal of technical methods and pathology 79, 213\u2013223 (1999).","journal-title":"Laboratory investigation; a journal of technical methods and pathology"},{"key":"BFsrep26909_CR44","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1016\/S0092-8674(00)81813-9","volume":"87","author":"C Suri","year":"1996","unstructured":"Suri, C. et al. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 87, 1171\u20131180 (1996).","journal-title":"Cell"},{"key":"BFsrep26909_CR45","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1167\/iovs.07-1206","volume":"49","author":"J Cai","year":"2008","unstructured":"Cai, J., Kehoe, O., Smith, G. M., Hykin, P. & Boulton, M. E. The angiopoietin\/Tie-2 system regulates pericyte survival and recruitment in diabetic retinopathy. Investigative ophthalmology & visual science 49, 2163\u20132171, 10.1167\/iovs.07-1206 (2008).","journal-title":"Investigative ophthalmology & visual science"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep26909","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep26909.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep26909.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T11:17:14Z","timestamp":1672831034000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep26909"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,26]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,7,18]]}},"alternative-id":["BFsrep26909"],"URL":"https:\/\/doi.org\/10.1038\/srep26909","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,26]]},"assertion":[{"value":"18 February 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 May 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"26909"}}