{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:33:30Z","timestamp":1791999210697,"version":"4.4.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,3,21]],"date-time":"2017-03-21T00:00:00Z","timestamp":1490054400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,3,21]],"date-time":"2017-03-21T00:00:00Z","timestamp":1490054400000},"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>\n                    <jats:italic>Fusobacterium nucleatum<\/jats:italic>\n                    plays a key role in creating the pathogenic subgingival biofilm that initiates destructive periodontitis. It is also a common resident of the human gastrointestinal tract and has been associated with inflammatory bowel disease. The aim of the present study was to investigate the effects of green and black tea extracts as well as two of their bioactive components, EGCG and theaflavins, on the growth and virulence properties of\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    . The tea extracts and components displayed various degrees of antibacterial activity that may involve damage to the bacterial cell membrane and the chelation of iron. They also prevented biofilm formation by\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    at concentrations that did not interfere with bacterial growth. In addition, the treatment of a pre-formed\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    biofilm with the green tea extract and EGCG caused a time-dependent decrease in biofilm viability. The green and black tea extracts, EGCG, and theaflavins decreased the adherence of\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    to oral epithelial cells and matrix proteins. Moreover, these tea components also attenuated\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    -mediated hemolysis and hydrogen sulfide production, two other virulence factors expressed by this bacterium. In summary, this study showed that tea polyphenols may be of interest for treating\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    -associated disorders.\n                  <\/jats:p>","DOI":"10.1038\/srep44815","type":"journal-article","created":{"date-parts":[[2017,3,21]],"date-time":"2017-03-21T12:32:13Z","timestamp":1490099533000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":112,"title":["Tea polyphenols inhibit the growth and virulence properties of Fusobacterium nucleatum"],"prefix":"10.1038","volume":"7","author":[{"given":"Amel","family":"Ben Lagha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Haas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Grenier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,21]]},"reference":[{"key":"BFsrep44815_CR1","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/j.1600-0757.2010.00350.x","volume":"55","author":"AB Berezow","year":"2011","unstructured":"Berezow, A. B. & Darveau, R. P. Microbial shift and periodontitis. Periodontol 2000 55, 36\u201347 (2011).","journal-title":"Periodontol 2000"},{"key":"BFsrep44815_CR2","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1034\/j.1600-051x.2000.027009648.x","volume":"27","author":"LA Ximenez-Fyvie","year":"2000","unstructured":"Ximenez-Fyvie, L. A., Haffajee, A. D. & Socransky, S. S. Comparison of the microbiota of supra- and subgingival plaque in health and periodontitis. J Clin Periodontol 27, 648\u2013657 (2000).","journal-title":"J Clin Periodontol"},{"key":"BFsrep44815_CR3","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.1600-0757.2006.00187.x","volume":"42","author":"PE Kolenbrander","year":"2006","unstructured":"Kolenbrander, P. E. et al. Bacterial interactions and successions during plaque development. Periodontol 2000 42, 47\u201379 (2006).","journal-title":"Periodontol 2000"},{"key":"BFsrep44815_CR4","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1111\/j.1600-051X.1998.tb02419.x","volume":"25","author":"SS Socransky","year":"1988","unstructured":"Socransky, S. S., Haffajee, A. D., Cugini, M. A., Smith, C. & Kent, R. L. Jr. Microbial complexes in subgingival plaque. J Clin Periodontol 25, 134\u2013144 (1988).","journal-title":"J Clin Periodontol"},{"key":"BFsrep44815_CR5","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1365-2958.2008.06503.x","volume":"71","author":"CW Kaplan","year":"2009","unstructured":"Kaplan, C. W., Lux, R., Haake, S. K. & Shi, W. The Fusobacterium nucleatum outer membrane protein RadD is an arginine-inhibitable adhesin required for inter-species adherence and the structured architecture of multispecies biofilm. Mol Microbiol 71, 35\u201347 (2009).","journal-title":"Mol Microbiol"},{"key":"BFsrep44815_CR6","doi-asserted-by":"crossref","first-page":"5330","DOI":"10.1128\/JB.187.15.5330-5340.2005","volume":"187","author":"YW Han","year":"2005","unstructured":"Han, Y. W. et al. Identification and characterization of a novel adhesin unique to oral fusobacteria. J Bacteriol 187, 5330\u20135340 (2005).","journal-title":"J Bacteriol"},{"key":"BFsrep44815_CR7","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1128\/IAI.02838-14","volume":"83","author":"S Coppenhagen-Glazer","year":"2015","unstructured":"Coppenhagen-Glazer, S. et al. Fap2 of Fusobacterium nucleatum is a galactose-inhibitable adhesin involved in coaggregation, cell adhesion, and preterm birth. Infect Immun 83, 1104\u20131113 (2015).","journal-title":"Infect Immun"},{"key":"BFsrep44815_CR8","first-page":"63","volume":"22","author":"E Gaetti-Jardim J\u00fanior","year":"1999","unstructured":"Gaetti-Jardim J\u00fanior, E. & Avila-Campos, M. J. Haemagglutination and haemolysis by oral Fusobacterium nucleatum . New Microbiol 22, 63\u201367 (1999).","journal-title":"New Microbiol"},{"key":"BFsrep44815_CR9","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1902\/jop.2009.090012","volume":"80","author":"A Yoshida","year":"2009","unstructured":"Yoshida, A. et al. Hydrogen sulfide production from cysteine and homocysteine by periodontal and oral bacteria. J Periodontol 80, 1845\u20131851 (2009).","journal-title":"J Periodontol"},{"key":"BFsrep44815_CR10","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/j.1574-695X.2008.00481.x","volume":"54","author":"A Saito","year":"2008","unstructured":"Saito, A. et al. Fusobacterium nucleatum enhances invasion of human gingival epithelial and aortic endothelial cells by Porphyromonas gingivalis . FEMS Immunol Med Microbiol 54, 349\u2013355 (2008).","journal-title":"FEMS Immunol Med Microbiol"},{"key":"BFsrep44815_CR11","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.mib.2014.11.013","volume":"23","author":"YW Han","year":"2015","unstructured":"Han Y. W. Fusobacterium nucleatum: a commensal-turned pathogen. Curr Opin Microbiol 23, 141\u2013147 (2015).","journal-title":"Curr Opin Microbiol"},{"key":"BFsrep44815_CR12","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1002\/ibd.21606","volume":"17","author":"J Strauss","year":"2011","unstructured":"Strauss, J. et al. Invasive potential of gut mucosa-derived Fusobacterium nucleatum positively correlates with IBD status of the host. Inflamm Bowel Dis 17, 1971\u20131978 (2011).","journal-title":"Inflamm Bowel Dis"},{"key":"BFsrep44815_CR13","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.1007\/s13277-015-4724-0","volume":"37","author":"A Bashir","year":"2016","unstructured":"Bashir, A., Miskeen, A. Y., Hazari, Y. M., Asrafuzzaman, S. & Fazili, K. M. Fusobacterium nucleatum, inflammation, and immunity: the fire within human gut. Tumour Biol 37, 2805\u20132810 (2016).","journal-title":"Tumour Biol"},{"key":"BFsrep44815_CR14","doi-asserted-by":"crossref","first-page":"294","DOI":"10.4161\/gmic.2.5.18603","volume":"2","author":"E Allen-Vercoe","year":"2011","unstructured":"Allen-Vercoe, E., Strauss, J. & Chadee, K. Fusobacterium nucleatum: an emerging gut pathogen? Gut Microbes 2, 294\u2013298 (2011).","journal-title":"Gut Microbes"},{"key":"BFsrep44815_CR15","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/S1532-3382(12)70013-1","volume":"12","author":"D Herrera","year":"2012","unstructured":"Herrera, D., Matesanz, P., Bascones-Martinez, A. & Sanz, M. Local and systemic antimicrobial therapy in periodontics. J Evid Based Dent Pract 12, 50\u201360 (2012).","journal-title":"J Evid Based Dent Pract"},{"key":"BFsrep44815_CR16","first-page":"557","volume":"45","author":"CM Ardila","year":"2010","unstructured":"Ardila, C. M., Granada, M. I. & Guzman, I. C. Antibiotic resistance of subgingival species in chronic periodontitis patients. J Periodontal Res 45, 557\u2013563 (2010).","journal-title":"J Periodontal Res"},{"key":"BFsrep44815_CR17","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.ijantimicag.2007.07.022","volume":"30","author":"A Mosca","year":"2007","unstructured":"Mosca, A., Miraglioatta, L., Iodice, M. A., Abbinante, A. & Miragliotta G. Antimicrobial profiles of Prevotella spp. and Fusobacterium nucleatum isolated from periodontal infections in a selected area of southern Italy. Int J Antimicrob Agents 30, 521\u2013524 (2007).","journal-title":"Int J Antimicrob Agents"},{"key":"BFsrep44815_CR18","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1111\/j.1600-051X.2005.00782.x","volume":"32","author":"AJ van Winkelhoff","year":"2005","unstructured":"van Winkelhoff, A. J., Herrera, D., Oteo, A. & Sanz, M. Antimicrobial profiles of periodontal pathogens isolated from periodontitis patients in The Netherlands and Spain. J Clin Periodontol 32, 893\u2013898 (2005).","journal-title":"J Clin Periodontol"},{"key":"BFsrep44815_CR19","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1080\/10408398.2011.623198","volume":"54","author":"MS Butt","year":"2014","unstructured":"Butt, M. S. et al. Black tea polyphenols: a mechanistic treatise. Crit Rev Food Sci Nutr 54, 1002\u20131011 (2014).","journal-title":"Crit Rev Food Sci Nutr"},{"key":"BFsrep44815_CR20","first-page":"79","volume":"25","author":"C Cabrera","year":"2006","unstructured":"Cabrera, C., Artacho, R. & Gimenez, R. Beneficial effects of green tea \u2013 a review. J Am Acad Nutr 25, 79\u201399 (2006).","journal-title":"J Am Acad Nutr"},{"key":"BFsrep44815_CR21","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s10787-015-0236-1","volume":"23","author":"M Afzal","year":"2015","unstructured":"Afzal, M., Safer, A. M. & Menon, M. Green tea polyphenols and their potential role in health and disease. Inflammopharmacology 23, 151\u2013161 (2015).","journal-title":"Inflammopharmacology"},{"key":"BFsrep44815_CR22","doi-asserted-by":"crossref","first-page":"434","DOI":"10.3389\/fmicb.2014.00434","volume":"5","author":"WC Reygaert","year":"2014","unstructured":"Reygaert, W. C. The antimicrobial possibilities of green tea. Front Microbiol 5, 434 (2014).","journal-title":"Front Microbiol"},{"key":"BFsrep44815_CR23","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.foodres.2013.01.032","volume":"53","author":"S Bansal","year":"2013","unstructured":"Bansal, S. et al. Tea: A native source of antimicrobial agents. Food Res Int 53, 568\u2013584 (2013).","journal-title":"Food Res Int"},{"key":"BFsrep44815_CR24","doi-asserted-by":"crossref","first-page":"34520","DOI":"10.1038\/srep34520","volume":"6","author":"A Ben Lagha","year":"2016","unstructured":"Ben Lagha, A. & Grenier, D. 2016. Tea polyphenols inhibit the activation of NF-\u03baB and the secretion of cytokines and matrix metalloproteinases by macrophages stimulated with Fusobacterium nucleatum . Sci Rep 6, 34520 (2016).","journal-title":"Sci Rep"},{"key":"BFsrep44815_CR25","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1038\/nrmicro1046","volume":"2","author":"UE Schaible","year":"2004","unstructured":"Schaible, U. E. & Kaufmann S. H. E. Iron and Microbial infection. Nature Rev Microbiol 2, 946\u2013953 (2004).","journal-title":"Nature Rev Microbiol"},{"key":"BFsrep44815_CR26","doi-asserted-by":"crossref","first-page":"e0143158","DOI":"10.1371\/journal.pone.0143158","volume":"10","author":"TB Bedran","year":"2015","unstructured":"Bedran, T. B., Morin, M. P., Spolidorio, D. P. & Grenier, D. Black tea extract and its theaflavin derivatives inhibit the growth of periodontopathogens and modulate interleukin-8 and \u03b2-defensin secretion in oral epithelial cells. PLoS One 10, e0143158 (2015).","journal-title":"PLoS One"},{"key":"BFsrep44815_CR27","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1111\/jre.12142","volume":"49","author":"T Bedran","year":"2014","unstructured":"Bedran, T., Feghali, K., Zhao, L., Spolidorio, D. & Grenier, D. Green tea extract and its major constituent epigallocatechin-3-gallate induce epithelial \u03b2-defensin secretion and prevent \u03b2-defensin degradation by Porphyromonas gingivalis . J Periodontal Res 49, 615\u2013623 (2014).","journal-title":"J Periodontal Res"},{"key":"BFsrep44815_CR28","first-page":"4","volume":"2012","author":"UK Gursoy","year":"2012","unstructured":"Gursoy, U. K. & Kononen, E. Understanding the roles of gingival beta-defensins. J Oral Microbiol 2012, 4 (2012).","journal-title":"J Oral Microbiol"},{"key":"BFsrep44815_CR29","doi-asserted-by":"crossref","first-page":"2914","DOI":"10.1128\/AAC.49.7.2914-2920.2005","volume":"49","author":"Navarro-Martinez","year":"2005","unstructured":"Navarro-Martinez et al. Antifolate activity of epigallocatechin against Stenotrophomonas maltophila . Antimicrob Agents Chemother 49, 2914\u20132920 (2005).","journal-title":"Antimicrob Agents Chemother"},{"key":"BFsrep44815_CR30","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.archoralbio.2016.01.014","volume":"65","author":"J Fournier-Larente","year":"2016","unstructured":"Fournier-Larente, J., Morin, M. P. & Grenier, D. Green tea catechins potentiate the effect of antibiotics and modulate adherence and gene expression in Porphyromonas gingivalis . Arch Oral Biol 65, 35\u201343 (2016).","journal-title":"Arch Oral Biol"},{"key":"BFsrep44815_CR31","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1111\/jam.12458","volume":"116","author":"Y Asahi","year":"2014","unstructured":"Asahi, Y. et al. Effects of the tea catechin epigallocatechin gallate on Porphyromonas gingivalis biofilms. J Appl Microbiol 116, 1164\u20131171 (2014).","journal-title":"J Appl Microbiol"},{"key":"BFsrep44815_CR32","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1128\/CMR.9.1.55","volume":"9","author":"AI Bolstad","year":"1996","unstructured":"Bolstad, A. I., Jensen, H. B. & Bakken, V. Taxonomy, biology, and periodontal aspects of Fusobacterium nucleatum . Clin Microbiol Rev 9, 55\u201371 (1996).","journal-title":"Clin Microbiol Rev"},{"key":"BFsrep44815_CR33","doi-asserted-by":"crossref","first-page":"2721","DOI":"10.1128\/iai.55.11.2721-2726.1987","volume":"55","author":"JR Winkler","year":"1987","unstructured":"Winkler, J. R., John, S. R., Kramer, R. H., Hoover, C. I. & Murray, P. A. Attachment of oral bacteria to a basement-membrane-like matrix and to purified matrix proteins. Infect Immun 55, 2721\u20132726 (1987).","journal-title":"Infect Immun"},{"key":"BFsrep44815_CR34","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/0003-9969(83)90109-7","volume":"28","author":"WA Falkler","year":"1983","unstructured":"Falkler, W. A., Clayman, E. B. & Shaefer, D. F. Haemolysis of human erythrocytes by the Fusobacterium nucleatum associated with periodontal disease. Arch Oral Biol 28, 735\u2013739 (1983).","journal-title":"Arch Oral Biol"},{"key":"BFsrep44815_CR35","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S0006-2952(97)00155-X","volume":"54","author":"LN Grinberg","year":"1997","unstructured":"Grinberg, L. N. et al. Protective effects of tea polyphenols against oxidative damage to red blood cells. Biochem Pharmacol 54, 973\u2013978 (1997).","journal-title":"Biochem Pharmacol"},{"key":"BFsrep44815_CR36","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.bbrc.2009.11.113","volume":"391","author":"W Chen","year":"2010","unstructured":"Chen, W. et al. Bacteria-derived hydrogen sulfide promotes IL-8 production from epithelial cells. Biochem Biophys Res Commun 391, 645\u2013650 (2010).","journal-title":"Biochem Biophys Res Commun"},{"key":"BFsrep44815_CR37","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/0003-9969(94)00165-8","volume":"40","author":"LG Ratkay","year":"1995","unstructured":"Ratkay, L. G., Waterfield, J. D. & Tonzetich, J. Stimulation of enzyme and cytokine production by methyl mercaptan in human gingival fibroblast and monocyte cell cultures. Arch Oral Biol 40, 337\u2013444 (1995).","journal-title":"Arch Oral Biol"},{"key":"BFsrep44815_CR38","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1111\/j.1600-0765.2007.00999.x","volume":"43","author":"H Takeuchi","year":"2008","unstructured":"Takeuchi, H., Setoguchi, T., Machigashira, M., Kanbara, K. & Izumi, Y. Hydrogen sulfide inhibits cell proliferation and induces cell cycle arrest via an elevated p21Cip1 level in Ca9-22 cells. J Periodontal Res 43, 90\u201395 (2008).","journal-title":"J Periodontal Res"},{"key":"BFsrep44815_CR39","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3177\/jnsv.54.89","volume":"54","author":"P Lodhia","year":"2008","unstructured":"Lodhia, P. et al. Effect of green tea on volatile sulfur compounds in mouth air. J Nutr Sci Vitaminol 54, 89\u201394 (2008).","journal-title":"J Nutr Sci Vitaminol"},{"key":"BFsrep44815_CR40","doi-asserted-by":"crossref","first-page":"975148","DOI":"10.5402\/2013\/975148","volume":"2013","author":"S Rassameemasmaung","year":"2013","unstructured":"Rassameemasmaung, S., Phusudsawang, P. & Sangalungkarn, V. Effect of green tea mouthwash on oral malodor. ISRN Prev Med 2013, 975148 (2013).","journal-title":"ISRN Prev Med"},{"key":"BFsrep44815_CR41","doi-asserted-by":"crossref","first-page":"e0131758","DOI":"10.1371\/journal.pone.0131758","volume":"10","author":"D Grenier","year":"2015","unstructured":"Grenier, D., Chen, H., Ben Lagha, A., Fournier-Larente, J. & Morin, M. P. Dual action of myricetin on Porphyromonas gingivalis and the inflammatory response of host cells: A promising therapeutic molecule for periodontal diseases. PLoS One 10, e0131758 (2015).","journal-title":"PLoS One"},{"key":"BFsrep44815_CR42","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12906-015-0557-z","volume":"15","author":"MP Morin","year":"2015","unstructured":"Morin, M. P. et al. Green tea extract and its major constituent epigallocatechin-3-gallate inhibit growth and halitosis-related properties of Solobacterium moorei . BMC Complement Altern Med 15, 48 (2015).","journal-title":"BMC Complement Altern Med"},{"key":"BFsrep44815_CR43","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0003-2697(87)90612-9","volume":"160","author":"B Schwyn","year":"1987","unstructured":"Schwyn, B. & Neilands, J. B. Universal chemical assay for the detection and determination of siderophores. Anal Biochem 160, 47\u201356 (1987).","journal-title":"Anal Biochem"},{"key":"BFsrep44815_CR44","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1021\/bi00784a033","volume":"10","author":"T Emery","year":"1971","unstructured":"Emery, T. Role of ferrichrome as a ferric ionophore in Ustilago sphaerogena . Biochemistry 10, 1483\u20131488 (1971).","journal-title":"Biochemistry"},{"key":"BFsrep44815_CR45","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/1472-6882-12-80","volume":"12","author":"A Marquis","year":"2012","unstructured":"Marquis, A., Genovese, S., Epifano, F. & Grenier, D. The plant coumarins auraptene and lacinartin as potential multifunctional therapeutic agents for treating periodontal disease. BMC Complement Altern Med 12, 80 (2012).","journal-title":"BMC Complement Altern Med"},{"key":"BFsrep44815_CR46","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1067\/moe.2000.107360","volume":"90","author":"EP Gilchrist","year":"2000","unstructured":"Gilchrist, E. P., Moyer, M. P., Shillitoe, E. J., Clare, N. & Murrah, V. A. Establishment of a human polyclonal oral epithelial cell line. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 90, 340\u2013347 (2000).","journal-title":"Oral Surg Oral Med Oral Pathol Oral Radiol Endod"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep44815.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep44815","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep44815.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T18:48:12Z","timestamp":1671821292000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep44815"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,21]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,4,12]]}},"alternative-id":["BFsrep44815"],"URL":"https:\/\/doi.org\/10.1038\/srep44815","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,21]]},"assertion":[{"value":"3 November 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 February 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 March 2017","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":"44815"}}