{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T14:40:47Z","timestamp":1780929647478,"version":"3.54.1"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,8,12]],"date-time":"2016-08-12T00:00:00Z","timestamp":1470960000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,8,12]],"date-time":"2016-08-12T00:00:00Z","timestamp":1470960000000},"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><jats:p>Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by an excessive inflammatory response within the lungs and severely impaired gas exchange resulting from alveolar-capillary barrier disruption and pulmonary edema. The costimulatory protein B7H3 functions as both a costimulator and coinhibitor to regulate the adaptive and innate immune response, thus participating in the development of microbial sepsis and pneumococcal meningitis. However, it is unclear whether B7H3 exerts a beneficial or detrimental role during ALI. In the present study we examined the impact of B7H3 on pulmonary inflammatory response, polymorphonuclear neutrophil (PMN) influx and lung tissue damage in a murine model of lipopolysaccharide (LPS)-induced direct ALI. Treatment with B7H3 protected mice against LPS-induced ALI, with significantly attenuated pulmonary PMN infiltration, decreased lung myeloperoxidase (MPO) activity, reduced bronchoalveolar lavage fluid (BALF) protein content and ameliorated lung pathological changes. In addition, B7H3 significantly diminished LPS-stimulated PMN chemoattractant CXCL2 production by inhibiting NF-\u03baB p65 phosphorylation and substantially attenuated LPS-induced PMN chemotaxis and transendothelial migration by down-regulating CXCR2 and Mac-1 expression. These results demonstrate that B7H3 substantially ameliorates LPS-induced ALI and this protection afforded by B7H3 is predominantly associated with its inhibitory effect on pulmonary PMN migration and infiltration.<\/jats:p>","DOI":"10.1038\/srep31284","type":"journal-article","created":{"date-parts":[[2016,8,12]],"date-time":"2016-08-12T09:22:25Z","timestamp":1470993745000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["B7H3 ameliorates LPS-induced acute lung injury via attenuation of neutrophil migration and infiltration"],"prefix":"10.1038","volume":"6","author":[{"given":"Yan","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niamh M.","family":"Foley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi Ping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Paul","family":"Redmond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang Huai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,8,12]]},"reference":[{"key":"BFsrep31284_CR1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0140-6736(67)90168-7","volume":"2","author":"DG Ashbaugh","year":"1967","unstructured":"Ashbaugh, D. G., Bigelow, D. B., Petty, T. L. & Levine, B. E. Acute respiratory distress in adults. Lancet 2, 319\u2013323 (1967).","journal-title":"Lancet"},{"key":"BFsrep31284_CR2","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1172\/JCI60331","volume":"122","author":"MA Matthay","year":"2012","unstructured":"Matthay, M. A., Ware, L. B. & Zimmerman, G. A. The acute respiratory distress syndrome. J Clin Invest 122, 2731\u20132740 (2012).","journal-title":"J Clin Invest"},{"key":"BFsrep31284_CR3","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/S0140-6736(07)60604-7","volume":"369","author":"AP Wheeler","year":"2007","unstructured":"Wheeler, A. P. & Bernard, G. R. Acute lung injury and the acute respiratory distress syndrome: a clinical review. Lancet 369, 1553\u20131564 (2007).","journal-title":"Lancet"},{"key":"BFsrep31284_CR4","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1056\/NEJMoa050333","volume":"353","author":"GD Rubenfeld","year":"2005","unstructured":"Rubenfeld, G. D. et al. Incidence and outcomes of acute lung injury. N Engl J Med 353, 1685\u20131693 (2005).","journal-title":"N Engl J Med"},{"key":"BFsrep31284_CR5","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1097\/01.CCM.0000063475.65751.1D","volume":"31","author":"CH Goss","year":"2003","unstructured":"Goss, C. H., Brower, R. G., Hudson, L. D., Rubenfeld, G. D. & ARDS Network. Incidence of acute lung injury in the United States. Crit Care Med 31, 1607\u20131611 (2003).","journal-title":"Crit Care Med"},{"key":"BFsrep31284_CR6","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1378\/chest.124.5.1871","volume":"124","author":"MR Suchyta","year":"2003","unstructured":"Suchyta, M. R., Orme, J. F. & Morris, A. H. The changing face of organ failure in ARDS. Chest 124, 1871\u20131879 (2003).","journal-title":"Chest"},{"key":"BFsrep31284_CR7","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1097\/CCM.0b013e31819fefdf","volume":"37","author":"SE Erickson","year":"2009","unstructured":"Erickson, S. E., Martin, G. S., Davis, J. L., Matthay, M. A., Eisner, M. D. & N. I. H. NHLBI ARDS Network. Recent trends in acute lung injury mortality: 1996-2005. Crit Care Med 37, 1574\u20131579 (2009).","journal-title":"Crit Care Med"},{"key":"BFsrep31284_CR8","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/nri1349","volume":"4","author":"L Chen","year":"2004","unstructured":"Chen, L. Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol 4, 336\u2013347 (2004).","journal-title":"Nat Rev Immunol"},{"key":"BFsrep31284_CR9","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1146\/annurev.immunol.23.021704.115611","volume":"23","author":"RJ Greenwald","year":"2005","unstructured":"Greenwald, R. J., Freeman, G. J. & Sharpe, A. H. The B7 family revisited. Annu Rev Immunol 23, 515\u2013548 (2005).","journal-title":"Annu Rev Immunol"},{"key":"BFsrep31284_CR10","doi-asserted-by":"crossref","first-page":"6294","DOI":"10.4049\/jimmunol.168.12.6294","volume":"168","author":"M Sun","year":"2002","unstructured":"Sun, M. et al. Characterization of mouse and human B7-H3 genes. J Immunol 168, 6294\u20136297 (2002).","journal-title":"J Immunol"},{"key":"BFsrep31284_CR11","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/85339","volume":"2","author":"AI Chapoval","year":"2001","unstructured":"Chapoval, A. I. et al. B7-H3: A costimulatory molecule for T cell activation and IFN-\u03b3 production. Nat Immunol 2, 269\u2013274 (2001).","journal-title":"Nat Immunol"},{"key":"BFsrep31284_CR12","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/ni967","volume":"4","author":"WK Suh","year":"2003","unstructured":"Suh, W. K. et al. The B7 family member B7-H3 preferentially down-regulates T helper type 1-mediated immune responses. Nat Immunol 4, 899\u2013906 (2003).","journal-title":"Nat Immunol"},{"key":"BFsrep31284_CR13","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.4049\/jimmunol.173.4.2500","volume":"173","author":"DV Prasad","year":"2004","unstructured":"Prasad, D. V. et al. Murine B7-H3 is a negative regulator of T cells. J Immunol 173, 2500\u20132506 (2004).","journal-title":"J Immunol"},{"key":"BFsrep31284_CR14","doi-asserted-by":"crossref","first-page":"5445","DOI":"10.4049\/jimmunol.173.9.5445","volume":"173","author":"L Luo","year":"2004","unstructured":"Luo, L. et al. B7-H3 enhances tumor immunity in vivo by costimulating rapid clonal expansion of antigen-specific CD8+ cytolytic T cells. J Immunol 173, 5445\u20135450 (2004).","journal-title":"J Immunol"},{"key":"BFsrep31284_CR15","doi-asserted-by":"crossref","first-page":"3092","DOI":"10.1002\/1521-4141(200211)32:11<3092::AID-IMMU3092>3.0.CO;2-0","volume":"32","author":"G Ferlazzo","year":"2002","unstructured":"Ferlazzo, G., Semino, C., Meta, M., Procopio, F., Morandi, B. & Melioli, G. T lymphocytes express B7 family molecules following interaction with dendritic cells and acquire bystander costimulatory properties. Eur J Immunol 32, 3092\u20133101 (2002).","journal-title":"Eur J Immunol"},{"key":"BFsrep31284_CR16","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1111\/j.1365-2567.2007.02723.x","volume":"123","author":"G Zhang","year":"2008","unstructured":"Zhang, G., Hou, J., Shi, J., Yu, G., Lu, B. & Zhang, X. Soluble CD276 (B7-H3) is released from monocytes, dendritic cells and activated T cells and is detectable in normal human serum. Immunology 123, 538\u2013546 (2008).","journal-title":"Immunology"},{"key":"BFsrep31284_CR17","doi-asserted-by":"crossref","first-page":"3677","DOI":"10.4049\/jimmunol.0904020","volume":"185","author":"G Zhang","year":"2010","unstructured":"Zhang, G. et al. B7-H3 augments the inflammatory response and is associated with human sepsis. J Immunol 185, 3677\u20133684 (2010).","journal-title":"J Immunol"},{"key":"BFsrep31284_CR18","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1007\/s12031-008-9133-z","volume":"37","author":"X Chen","year":"2009","unstructured":"Chen, X. et al. Circulating B7-H3 (CD276) elevations in cerebrospinal fluid and plasma of children with bacterial meningitis. J Mol Neurosci 37, 86\u201394 (2009).","journal-title":"J Mol Neurosci"},{"key":"BFsrep31284_CR19","doi-asserted-by":"crossref","first-page":"347","DOI":"10.4049\/jimmunol.1103715","volume":"189","author":"X Chen","year":"2012","unstructured":"Chen, X. et al. B7-H3 participates in the development of experimental pneumococcal meningitis by augmentation of the inflammatory response via a TLR2-dependent mechanism. J Immunol 189, 347\u2013355 (2012).","journal-title":"J Immunol"},{"key":"BFsrep31284_CR20","doi-asserted-by":"crossref","first-page":"S195","DOI":"10.1097\/01.CCM.0000057843.47705.E8","volume":"31","author":"E Abraham","year":"2003","unstructured":"Abraham, E. Neutrophils and acute lung injury. Crit Care Med 31, S195\u2013199 (2003).","journal-title":"Crit Care Med"},{"key":"BFsrep31284_CR21","doi-asserted-by":"crossref","first-page":"293","DOI":"10.2119\/molmed.2010.00138","volume":"17","author":"J Grommes","year":"2011","unstructured":"Grommes, J. & Soehnlein, O. Contribution of neutrophils to acute lung injury. Mol Med 17, 293\u2013307 (2011).","journal-title":"Mol Med"},{"key":"BFsrep31284_CR22","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1146\/annurev-physiol-030212-183756","volume":"75","author":"J Bhattacharya","year":"2013","unstructured":"Bhattacharya, J. & Matthay, M. A. Regulation and repair of the alveolar-capillary barrier in acute lung injury. Annu Rev Physiol 75, 593\u2013615 (2013).","journal-title":"Annu Rev Physiol"},{"key":"BFsrep31284_CR23","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.cell.2008.02.043","volume":"133","author":"Y Imai","year":"2008","unstructured":"Imai, Y. et al. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell 133, 235\u2013249 (2008).","journal-title":"Cell"},{"key":"BFsrep31284_CR24","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1164\/ajrccm.150.1.8025736","volume":"150","author":"KP Steinberg","year":"1994","unstructured":"Steinberg, K. P., Milberg, J. A., Martin, T. R., Maunder, R. J., Cockrill, B. A. & Hudson, L. D. Evolution of bronchoalveolar cell populations in the adult respiratory distress syndrome. Am J Respir Crit Care Med 150, 113\u2013122 (1994).","journal-title":"Am J Respir Crit Care Med"},{"key":"BFsrep31284_CR25","doi-asserted-by":"crossref","first-page":"L1137","DOI":"10.1152\/ajplung.2000.279.6.L1137","volume":"279","author":"E Abraham","year":"2000","unstructured":"Abraham, E., Carmody, A., Shenkar, R. & Arcaroli, J. Neutrophils as early immunologic effectors in hemorrhage- or endotoxemia-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol 279, L1137\u20131145 (2000).","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"BFsrep31284_CR26","doi-asserted-by":"crossref","first-page":"L1083","DOI":"10.1152\/ajplung.2000.279.6.L1083","volume":"279","author":"M Chignard","year":"2000","unstructured":"Chignard, M. & Balloy, V. Neutrophil recruitment and increased permeability during acute lung injury induced by lipopolysaccharide. Am J Physiol Lung Cell Mol Physiol 279, L1083\u20131090 (2000).","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"BFsrep31284_CR27","doi-asserted-by":"crossref","first-page":"R7","DOI":"10.1152\/ajpregu.00738.2001","volume":"283","author":"TS Olson","year":"2002","unstructured":"Olson, T. S. & Ley, K. Chemokines and chemokine receptors in leukocyte trafficking. Am J Physiol Regul Integr Comp Physiol 283, R7\u201328 (2002).","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"BFsrep31284_CR28","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1164\/rccm.200601-103OC","volume":"175","author":"F Rios-Santos","year":"2007","unstructured":"Rios-Santos, F. et al. Down-regulation of CXCR2 on neutrophils in severe sepsis is mediated by inducible nitric oxide synthase-derived nitric oxide. Am J Respir Crit Care Med 175, 490\u2013497 (2007).","journal-title":"Am J Respir Crit Care Med"},{"key":"BFsrep31284_CR29","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.intimp.2013.06.034","volume":"17","author":"K Futosi","year":"2013","unstructured":"Futosi, K., Fodor, S. & Mocsai, A. Neutrophil cell surface receptors and their intracellular signal transduction pathways. Int Immunophamacol 17, 638\u2013650 (2013).","journal-title":"Int Immunophamacol"},{"key":"BFsrep31284_CR30","first-page":"490","volume":"132","author":"PE Parsons","year":"1985","unstructured":"Parsons, P. E., Fowler, A. A., Hyers, T. M. & Henson, P. M. Chemotactic activity in bronchoalveolar lavage fluid from patients with adult respiratory distress syndrome. Am Rev Respir Dis 132, 490\u2013493 (1985).","journal-title":"Am Rev Respir Dis"},{"key":"BFsrep31284_CR31","first-page":"465","volume":"14","author":"M Peri","year":"2008","unstructured":"Peri, M., Lomas-Neira, J., Chung, C. S. & Ayala, A. Epithelial cell apoptosis and neutrophil recruitment in acute lung injury \u2013 a unifying hypothesis? What we have learned from small interfering RNAs. Mol Med 14, 465\u2013475 (2008).","journal-title":"Mol Med"},{"key":"BFsrep31284_CR32","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1146\/annurev.immunol.23.021704.115611","volume":"23","author":"RJ Greenwald","year":"2005","unstructured":"Greenwald, R. J., Freeman, G. J. & Sharpe, A. H. The B7 family revisited. Annu Rev Immunol 23, 515\u2013548 (2005).","journal-title":"Annu Rev Immunol"},{"key":"BFsrep31284_CR33","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1007\/s00262-012-1278-5","volume":"61","author":"TW Sun","year":"2012","unstructured":"Sun, T. W. et al. B7-H3 is expressed in human hepatocellular carcinoma and is associated with tumor aggressiveness and postoperative recurrence. Cancer Immunol Immunother 61, 2171\u20132182 (2012).","journal-title":"Cancer Immunol Immunother"},{"key":"BFsrep31284_CR34","doi-asserted-by":"crossref","first-page":"2764","DOI":"10.1002\/ijc.28474","volume":"134","author":"L Wang","year":"2014","unstructured":"Wang, L., Kang, F. B. & Shan, B. E. B7-H3-mediated tumor immunology: friend or foe? Int J Cancer 134, 2764\u20132771 (2014).","journal-title":"Int J Cancer"},{"key":"BFsrep31284_CR35","doi-asserted-by":"crossref","first-page":"5445","DOI":"10.4049\/jimmunol.173.9.5445","volume":"173","author":"L Luo","year":"2004","unstructured":"Luo, L. et al. B7-H3 enhances tumor immunity in vivo by costimulating rapid clonal expansion of antigen-specific CD8+ cytolytic T cells. J Immunol 173, 5445\u20135450 (2004).","journal-title":"J Immunol"},{"key":"BFsrep31284_CR36","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0022-1759(96)00236-0","volume":"202","author":"RJ Szarka","year":"1997","unstructured":"Szarka, R. J., Wang, N., Gordon, L., Nation, P. N. & Smith, R. H. A murine model of pulmonary damage induced by lipopolysaccharide via intranasal instillation. J Immunol Methods 202, 49\u201357 (1997).","journal-title":"J Immunol Methods"},{"key":"BFsrep31284_CR37","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1164\/rccm.200608-1246OC","volume":"176","author":"GM Mutlu","year":"2007","unstructured":"Mutlu, G. M. et al. Electroporation-mediated genetrasfer of the Na+, K+-ATPase rescues endotoxim-induced lung injury. Am J Respir Crit Care Med 176, 582\u2013590 (2007).","journal-title":"Am J Respir Crit Care Med"},{"key":"BFsrep31284_CR38","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1164\/rccm.200804-625OC","volume":"17","author":"T Cui","year":"2010","unstructured":"Cui, T. et al. Milk fat globule epidermal growth factor 8 attenuates acute lung injury in mice after intestinal ischemia and reperfusion. Am J Respir Crit Care Med 17, 238\u2013246 (2010).","journal-title":"Am J Respir Crit Care Med"},{"key":"BFsrep31284_CR39","doi-asserted-by":"crossref","first-page":"8735","DOI":"10.4049\/jimmunol.181.12.8735","volume":"181","author":"Z Wang","year":"2008","unstructured":"Wang, Z., Rui, T., Yang, M., Valiyeva, F. & Kvietys, P. R. Alveolar macrophages from septic mice promote polymorphonuclear leukocyte transendothelial migration via an endothelial cell Src kinase\/NADPH oxidase pathway. J Immunol 181, 8735\u20138744 (2008).","journal-title":"J Immunol"},{"key":"BFsrep31284_CR40","doi-asserted-by":"crossref","first-page":"L1164","DOI":"10.1152\/ajplung.00248.2005","volume":"290","author":"KS Farley","year":"2006","unstructured":"Farley, K. S. et al. Effects of macrophage inducible nitric oxide synthase in murine septic lung injury. Am J Physiol Lung Cell Mol Physiol 290, L1164\u20131172 (2006).","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"BFsrep31284_CR41","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1189\/jlb.0207126","volume":"82","author":"MA Magalhaes","year":"2007","unstructured":"Magalhaes, M. A., Zhu, F., Sarantis, H., Gray-Owen, S. D., Ellen, R. P. & Glogauer, M. Expression and translocation of fluorescent-tagged p21-activated kinase-binding domain and PH domain of protein kinase B during murines neutrophil chemotaxis. J Leukoc Biol 82, 559\u2013566 (2007).","journal-title":"J Leukoc Biol"},{"key":"BFsrep31284_CR42","doi-asserted-by":"crossref","first-page":"4293","DOI":"10.4049\/jimmunol.1003872","volume":"187","author":"JM Buckley","year":"2011","unstructured":"Buckley, J. M. et al. Increased susceptibility of ST2-deficient mice to polymicrobial sepsis is associated with an impaired bactericidal function. J Immunol 187, 4293\u20134299 (2011).","journal-title":"J Immunol"},{"key":"BFsrep31284_CR43","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1002\/eji.201243077","volume":"43","author":"Q Zhang","year":"2013","unstructured":"Zhang, Q. et al. Inefficient antimicrobial functions of innate phagocytes render infant mice more susceptible to bacterial infection. Eur J Immunol 43, 1322\u20131332 (2013).","journal-title":"Eur J Immunol"},{"key":"BFsrep31284_CR44","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1189\/jlb.0608382","volume":"85","author":"BM Maher","year":"2009","unstructured":"Maher, B. M., Dhonnchu, T. N., Burke, J. P., Soo, A., Wood, A. E. & Watson, R. W. Statins alter neutrophil migration by modulating cellular Rho activity \u2013 a potential mechanism for stain-mediated pleotropic effects? J Leukoc Biol 85, 186\u2013193 (2009).","journal-title":"J Leukoc Biol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep31284","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep31284.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep31284.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T20:32:19Z","timestamp":1672864339000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep31284"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,12]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,11,14]]}},"alternative-id":["BFsrep31284"],"URL":"https:\/\/doi.org\/10.1038\/srep31284","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,12]]},"assertion":[{"value":"8 March 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 August 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":"31284"}}