{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:52:16Z","timestamp":1789757536731,"version":"4.0.1"},"reference-count":84,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"23","funder":[{"DOI":"10.13039\/501100004895","name":"European Social Fund","doi-asserted-by":"publisher","award":["PON R&I 2014\u20132020, AIM 1810057"],"award-info":[{"award-number":["PON R&I 2014\u20132020, AIM 1810057"]}],"id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007706","name":"Ministero dello Sviluppo Economico","doi-asserted-by":"publisher","award":["2019, Bando PoC-MISE \u2013 Programma #NOACRONYM"],"award-info":[{"award-number":["2019, Bando PoC-MISE \u2013 Programma #NOACRONYM"]}],"id":[{"id":"10.13039\/501100007706","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009886","name":"Regione Puglia","doi-asserted-by":"publisher","award":["Tecnopolo per la Medicina di Precisione D.G.R. n. 2117 of 21.11.2018"],"award-info":[{"award-number":["Tecnopolo per la Medicina di Precisione D.G.R. n. 2117 of 21.11.2018"]}],"id":[{"id":"10.13039\/501100009886","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["Next Generation EU, in the context of the National Recovery and Resilience Plan, Investment PE8 \u2013 Project Age-It: \u201cAgeing Well in an Ageing Society\u201d"],"award-info":[{"award-number":["Next Generation EU, in the context of the National Recovery and Resilience Plan, Investment PE8 \u2013 Project Age-It: \u201cAgeing Well in an Ageing Society\u201d"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fondazione per la Ricerca Biomedica Saverio e Isabella Cianciola"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,6,5]]},"abstract":"<jats:p>Irisin is a myokine that enhances insulin secretion and \u03b2 cell viability in both rodent and human \u03b2 cells. Here, we investigated whether irisin preserves \u03b2 cell functional mass in vivo in diabetic mice and ex vivo in human pancreatic islets from subjects with type 2 diabetes (T2D). In mice made diabetic by a high-fat diet and streptozotocin, irisin administration improved glycemic homeostasis by increasing islet insulin content and glucose-stimulated insulin secretion while also markedly stimulating \u03b2 cell proliferation. In islets from T2D subjects, which typically display substantial structural and functional impairments, irisin restored insulin content and glucose-stimulated insulin secretion. Mechanistic studies in INS-1E cells showed that chronic exposure to high glucose blunted glucose-triggered cytoplasmic calcium increases, essential for insulin secretion. Under these glucotoxic conditions, while irisin was unable to activate CREB and AKT, it induced AMPK-mTORC1-S6K\u2013dependent mobilization of endoplasmic reticulum calcium stores, resulting in enhancement of insulin secretion. Overall, these findings highlight irisin\u2019s multifaceted ability to counteract \u03b2 cell failure in experimental and human T2D.<\/jats:p>","DOI":"10.1126\/sciadv.aee4804","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T17:59:36Z","timestamp":1780682376000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["The myokine irisin ameliorates the secretory dysfunction of pancreatic \u03b2 cells in experimental and human type 2 diabetes"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6587-6087","authenticated-orcid":true,"given":"Nicola","family":"Marrano","sequence":"first","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Borrelli","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9527-9048","authenticated-orcid":true,"given":"Giuseppina","family":"Biondi","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9660-8746","authenticated-orcid":true,"given":"Martina","family":"Rella","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9064-2159","authenticated-orcid":true,"given":"Rossella","family":"D\u2019Oria","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8188-9638","authenticated-orcid":true,"given":"Valentina Annamaria","family":"Genchi","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Caccioppoli","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1499-8390","authenticated-orcid":true,"given":"Valerio","family":"Galasso","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6261-3649","authenticated-orcid":true,"given":"Giovanni","family":"Galluzzi","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Roberto","sequence":"additional","affiliation":[{"name":"Transgenic Mice Facility, Biogem S.c.ar.l., Ariano Irpino, Avellino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Signorile","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8330-7889","authenticated-orcid":true,"given":"Leonardo","family":"Vincenti","sequence":"additional","affiliation":[{"name":"General Surgery Unit, National Institute of Gastroenterology \u201cSaverio de Bellis,\u201d Research Hospital, Castellana Grotte, Bari, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1787-3791","authenticated-orcid":true,"given":"Fabrizio","family":"Aquilino","sequence":"additional","affiliation":[{"name":"General Surgery Unit, National Institute of Gastroenterology \u201cSaverio de Bellis,\u201d Research Hospital, Castellana Grotte, Bari, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Nano","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, IRCCS San Raffaele Hospital, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Baruzzi","sequence":"additional","affiliation":[{"name":"Institute of Sciences of Food Production, National Research Council of Italy, (CNR-ISPA), Bari, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Moretti","sequence":"additional","affiliation":[{"name":"Institute of Sciences of Food Production, National Research Council of Italy, (CNR-ISPA), Bari, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi Giovanni","family":"Lupo","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, Section of General Surgery and Liver Transplantation, University of Bari Aldo Moro, Bari, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4907-0635","authenticated-orcid":true,"given":"Piero","family":"Marchetti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2172-2198","authenticated-orcid":true,"given":"Lorenzo","family":"Piemonti","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, IRCCS San Raffaele Hospital, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6477-9031","authenticated-orcid":true,"given":"Angelo","family":"Cignarelli","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2728-7721","authenticated-orcid":true,"given":"Sebastio","family":"Perrini","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy."},{"name":"Department of Medicine and Surgery, Section of Endocrinology, LUM University, Casamassima, Bari, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Laviola","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7372-2678","authenticated-orcid":true,"given":"Francesco","family":"Giorgino","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6131-7517","authenticated-orcid":true,"given":"Annalisa","family":"Natalicchio","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2020.154304"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.44.11.1249"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.2337\/dcS13-2011"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.1.102"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-019-1196-4"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2017.06.019"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389450116666150204113928"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10777"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom11020286"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.962968"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13098-022-00922-w"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2373"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms27020787"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2012.11.014"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2013.12.007"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0229152"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2012.09.002"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-2749"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072858"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2021.108788"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0042-108730"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2013.03.002"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.2337\/db17-0002"},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","first-page":"e0175498","DOI":"10.1371\/journal.pone.0175498","article-title":"Effects and underlying mechanisms of irisin on the proliferation and apoptosis of pancreatic \u03b2 cells","volume":"12","author":"Liu S.","year":"2017","unstructured":"S. Liu, F. Du, X. Li, M. Wang, R. Duan, J. Zhang, Y. Wu, Q. Zhang, Effects and underlying mechanisms of irisin on the proliferation and apoptosis of pancreatic \u03b2 cells. PLOS ONE 12, e0175498 (2017).","journal-title":"PLOS ONE"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1159\/000495395"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13098-023-01216-5"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.5603\/EP.a2023.0035"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13098-025-01852-z"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/4674215"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/iub.2907"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34095-x"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.11.004"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2024.123230"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.84153"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj20021288"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-022-05842-y"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2005-0888"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.42.7.948"},{"key":"e_1_3_2_40_2","first-page":"E133","article-title":"NIDDM is associated with loss of pancreatic beta-cell L-type Ca2+ channel activity","volume":"270","author":"Roe M.","year":"1996","unstructured":"M. Roe, J. Worley, Y. Tokuyama, L. Philipson, J. Sturis, J. Tang, I. Dukes, G. Bell, K. Polonsky, NIDDM is associated with loss of pancreatic beta-cell L-type Ca2+ channel activity. Am. J. Physiol. 270, E133\u2013E140 (1996).","journal-title":"Am. J. Physiol."},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-019-0351-4"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2018.12.007"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20070797"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.08.112"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00094.2016"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20150009"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00769"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-021-02875-y"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-020-0355-7"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-33229-w"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S214260"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1677\/JME-07-0133"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13105-019-00706-3"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0199-y"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa786"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI127021"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004954"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-016-4188-9"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2007.00838.x"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2017.161"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0042-110934"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/6106051"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.14202\/vetworld.2020.2191-2196"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.12.013"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-00623-2"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47959-1"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.5.1437"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.2337\/db22-0472"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46829-0"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389203724666230228140808"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2015.12.049"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2022.12606"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1039\/D1FO00698C"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.3212"},{"key":"e_1_3_2_75_2","first-page":"5391","article-title":"Erythropoietin improves glucose metabolism and pancreatic \u03b2-cell damage in experimental diabetic rats","volume":"12","author":"Chen L.-N.","year":"2025","unstructured":"L.-N. Chen, Q. Sun, S.-Q. Liu, H. Hu, J. Lv, W.-J. Ji, M. Wang, M.-X. Chen, J. Zhou, Erythropoietin improves glucose metabolism and pancreatic \u03b2-cell damage in experimental diabetic rats. Mol. Med. Rep. 12, 5391\u20135398 (2025).","journal-title":"Mol. Med. Rep."},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.11.024"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1890"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.260794"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-2261"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1818598116"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01101"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1063395"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-2974"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.264945"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00828-0"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aee4804","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T18:00:09Z","timestamp":1780682409000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aee4804"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,5]]},"references-count":84,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2026,6,5]]}},"alternative-id":["10.1126\/sciadv.aee4804"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aee4804","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,5]]},"assertion":[{"value":"2025-12-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaee4804"}}