{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T01:41:54Z","timestamp":1788572514588,"version":"build-2803163510"},"reference-count":46,"publisher":"American Diabetes Association","issue":"5","license":[{"start":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T00:00:00Z","timestamp":1645488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,5,1]]},"abstract":"<jats:p>Chronic inflammation in liver induces insulin resistance systemically and in other tissues, including the skeletal muscle (SM); however, the underlying mechanisms remain largely unknown. RNA sequencing of primary hepatocytes from wild-type mice fed long-term high-fat diet (HFD), which have severe chronic inflammation and insulin resistance revealed that the expression of hepatokine endoplasmic reticulum aminopeptidase 1 (ERAP1) was upregulated by a HFD. Increased ERAP1 levels were also observed in interferon-\u03b3\u2013treated primary hepatocytes. Furthermore, hepatic ERAP1 overexpression attenuated systemic and SM insulin sensitivity, whereas hepatic ERAP1 knockdown had the opposite effects, with corresponding changes in serum ERAP1 levels. Mechanistically, ERAP1 functions as an antagonist-like factor, which interacts with \u03b22 adrenergic receptor (ADRB2) and reduces its expression by decreasing ubiquitin-specific peptidase 33\u2013mediated deubiquitination and thereby interrupts ADRB2-stimulated insulin signaling in the SM. The findings of this study indicate ERAP1 is an inflammation-induced hepatokine that impairs SM insulin sensitivity. Its inhibition may provide a therapeutic strategy for insulin resistance\u2013related diseases, such as type 2 diabetes.<\/jats:p>","DOI":"10.2337\/db21-0857","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T15:36:22Z","timestamp":1645544182000},"page":"921-933","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":19,"title":["Hepatokine ERAP1 Disturbs Skeletal Muscle Insulin Sensitivity Via Inhibiting USP33-Mediated ADRB2 Deubiquitination"],"prefix":"10.2337","volume":"71","author":[{"given":"Yuguo","family":"Niu","sequence":"first","affiliation":[{"name":"Zhongshan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, Ministry of Education Frontiers Center for Brain Science, Fudan University, Shanghai, China"},{"name":"Chinese Academy of Sciences (CAS) Key Laboratory of Nutrition, Metabolism and Food Safety, Innovation Center for Intervention of Chronic Disease and Promotion of Health, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haizhou","family":"Jiang","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences (CAS) Key Laboratory of Nutrition, Metabolism and Food Safety, Innovation Center for Intervention of Chronic Disease and Promotion of Health, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanrui","family":"Yin","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences (CAS) Key Laboratory of Nutrition, Metabolism and Food Safety, Innovation Center for Intervention of Chronic Disease and Promotion of Health, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenfen","family":"Wang","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences (CAS) Key Laboratory of Nutrition, Metabolism and Food Safety, Innovation Center for Intervention of Chronic Disease and Promotion of Health, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronggui","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Hu","sequence":"additional","affiliation":[{"name":"Zhongshan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, Ministry of Education Frontiers Center for Brain Science, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Peng","sequence":"additional","affiliation":[{"name":"Zhongshan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, Ministry of Education Frontiers Center for Brain Science, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousheng","family":"Shu","sequence":"additional","affiliation":[{"name":"Zhongshan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, Ministry of Education Frontiers Center for Brain Science, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Li","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences (CAS) Key Laboratory of Nutrition, Metabolism and Food Safety, Innovation Center for Intervention of Chronic Disease and Promotion of Health, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanghai","family":"Chen","sequence":"additional","affiliation":[{"name":"Zhongshan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, Ministry of Education Frontiers Center for Brain Science, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6748-4546","authenticated-orcid":false,"given":"Feifan","family":"Guo","sequence":"additional","affiliation":[{"name":"Zhongshan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, Ministry of Education Frontiers Center for Brain Science, Fudan University, Shanghai, China"},{"name":"Chinese Academy of Sciences (CAS) Key Laboratory of Nutrition, Metabolism and Food Safety, Innovation Center for Intervention of Chronic Disease and Promotion of Health, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"},{"name":"Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2022,2,22]]},"reference":[{"key":"2022042018453616900_B1","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1016\/S0140-6736(17)30058-2","article-title":"Type 2 diabetes","volume":"389","author":"Chatterjee","year":"2017","journal-title":"Lancet"},{"key":"2022042018453616900_B2","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.cell.2016.10.025","article-title":"Hematopoietic-derived galectin-3 causes cellular and systemic insulin resistance","volume":"167","author":"Li","year":"2016","journal-title":"Cell"},{"key":"2022042018453616900_B3","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/j.cmet.2015.09.023","article-title":"Fetuin B is a secreted hepatocyte factor linking steatosis to impaired glucose metabolism","volume":"22","author":"Meex","year":"2015","journal-title":"Cell Metab"},{"key":"2022042018453616900_B4","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1172\/JCI23606","article-title":"FGF-21 as a novel metabolic regulator","volume":"115","author":"Kharitonenkov","year":"2005","journal-title":"J Clin Invest"},{"key":"2022042018453616900_B5","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1038\/s41467-020-15963-w","article-title":"Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity","volume":"11","author":"Seo","year":"2020","journal-title":"Nat Commun"},{"key":"2022042018453616900_B6","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1038\/s42255-019-0065-4","article-title":"Gpnmb secreted from liver promotes lipogenesis in white adipose tissue and aggravates obesity and insulin resistance","volume":"1","author":"Gong","year":"2019","journal-title":"Nat Metab"},{"key":"2022042018453616900_B7","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.cmet.2010.09.015","article-title":"A liver-derived secretory protein, selenoprotein P, causes insulin resistance","volume":"12","author":"Misu","year":"2010","journal-title":"Cell Metab"},{"key":"2022042018453616900_B8","doi-asserted-by":"crossref","first-page":"e129492","DOI":"10.1172\/jci.insight.129492","article-title":"The hepatokine Tsukushi is released in response to NAFLD and impacts cholesterol homeostasis","volume":"4","author":"Mouchiroud","year":"2019","journal-title":"JCI Insight"},{"key":"2022042018453616900_B9","doi-asserted-by":"crossref","first-page":"8338","DOI":"10.3390\/ijms13078338","article-title":"Role of endoplasmic reticulum aminopeptidases in health and disease: from infection to cancer","volume":"13","author":"Cifaldi","year":"2012","journal-title":"Int J Mol Sci"},{"key":"2022042018453616900_B10","doi-asserted-by":"crossref","first-page":"3304","DOI":"10.1038\/s41467-019-11093-0","article-title":"ERAP1 promotes Hedgehog-dependent tumorigenesis by controlling USP47-mediated degradation of \u03b2TrCP","volume":"10","author":"Bufalieri","year":"2019","journal-title":"Nat Commun"},{"key":"2022042018453616900_B11","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/nature01074","article-title":"ERAAP customizes peptides for MHC class I molecules in the endoplasmic reticulum","volume":"419","author":"Serwold","year":"2002","journal-title":"Nature"},{"key":"2022042018453616900_B12","doi-asserted-by":"crossref","first-page":"670","DOI":"10.2337\/db19-0984","article-title":"\u03b2-Cell stress shapes CTL immune recognition of preproinsulin signal peptide by posttranscriptional regulation of endoplasmic reticulum aminopeptidase 1","volume":"69","author":"Thomaidou","year":"2020","journal-title":"Diabetes"},{"key":"2022042018453616900_B13","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.humimm.2019.02.004","article-title":"ERAP1-ERAP2 haplotypes are associated with ankylosing spondylitis in Polish patients","volume":"80","author":"Wi\u015bniewski","year":"2019","journal-title":"Hum Immunol"},{"key":"2022042018453616900_B14","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.autrev.2012.04.007","article-title":"The putative role of endoplasmic reticulum aminopeptidases in autoimmunity: insights from genomic-wide association studies","volume":"12","author":"Fierabracci","year":"2012","journal-title":"Autoimmun Rev"},{"key":"2022042018453616900_B15","doi-asserted-by":"crossref","first-page":"3241","DOI":"10.1182\/blood.V99.9.3241","article-title":"A mouse orthologue of puromycin-insensitive leucyl-specific aminopeptidase is expressed in endothelial cells and plays an important role in angiogenesis","volume":"99","author":"Miyashita","year":"2002","journal-title":"Blood"},{"key":"2022042018453616900_B16","doi-asserted-by":"crossref","first-page":"3243","DOI":"10.1158\/0008-5472.CAN-17-1946","article-title":"ERAP1-dependent antigen cross-presentation determines efficacy of adoptive T-cell therapy in mice","volume":"78","author":"Schmidt","year":"2018","journal-title":"Cancer Res"},{"key":"2022042018453616900_B17","doi-asserted-by":"crossref","first-page":"21906","DOI":"10.1074\/jbc.M111.239111","article-title":"Secretion of endoplasmic reticulum aminopeptidase 1 is involved in the activation of macrophages induced by lipopolysaccharide and interferon-gamma","volume":"286","author":"Goto","year":"2011","journal-title":"J Biol Chem"},{"key":"2022042018453616900_B18","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1172\/JCI88880","article-title":"Skeletal muscle inflammation and insulin resistance in obesity","volume":"127","author":"Wu","year":"2017","journal-title":"J Clin Invest"},{"key":"2022042018453616900_B19","doi-asserted-by":"crossref","first-page":"ra33","DOI":"10.1126\/scisignal.2000444","article-title":"Oxygen-regulated \u03b2(2)-adrenergic receptor hydroxylation by EGLN3 and ubiquitylation by pVHL","volume":"2","author":"Xie","year":"2009","journal-title":"Sci Signal"},{"key":"2022042018453616900_B20","doi-asserted-by":"crossref","first-page":"640","DOI":"10.2337\/db16-0954","article-title":"Deletion of ATF4 in AgRP neurons promotes fat loss mainly via increasing energy expenditure","volume":"66","author":"Deng","year":"2017","journal-title":"Diabetes"},{"key":"2022042018453616900_B21","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.cmet.2009.09.013","article-title":"Hypothalamic orexin stimulates feeding-associated glucose utilization in skeletal muscle via sympathetic nervous system","volume":"10","author":"Shiuchi","year":"2009","journal-title":"Cell Metab"},{"key":"2022042018453616900_B22","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/j.1476-5381.2010.00677.x","article-title":"\u03b2-adrenoceptor stimulation potentiates insulin-stimulated PKB phosphorylation in rat cardiomyocytes via cAMP and PKA","volume":"160","author":"Stuenaes","year":"2010","journal-title":"Br J Pharmacol"},{"key":"2022042018453616900_B23","doi-asserted-by":"crossref","first-page":"6622","DOI":"10.1096\/fj.201802351R","article-title":"M1 muscarinic receptors regulate the phosphorylation of AMPA receptor subunit GluA1 via a signaling pathway linking cAMP-PKA and PI3K-Akt","volume":"33","author":"Zhao","year":"2019","journal-title":"FASEB J"},{"key":"2022042018453616900_B24","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1016\/j.cellsig.2005.03.011","article-title":"Adrenaline potentiates insulin-stimulated PKB activation via cAMP and Epac: implications for cross talk between insulin and adrenaline","volume":"17","author":"Brennesvik","year":"2005","journal-title":"Cell Signal"},{"key":"2022042018453616900_B25","doi-asserted-by":"crossref","first-page":"146","DOI":"10.3390\/cells10010146","article-title":"\u03b22-Adrenergic signaling modulates mitochondrial function and morphology in skeletal muscle in response to aerobic exercise","volume":"10","author":"Azevedo Voltarelli","year":"2021","journal-title":"Cells"},{"key":"2022042018453616900_B26","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1093\/oxfordjournals.jbchem.a022371","article-title":"Molecular cloning of adipocyte-derived leucine aminopeptidase highly related to placental leucine aminopeptidase\/oxytocinase","volume":"125","author":"Hattori","year":"1999","journal-title":"J Biochem"},{"key":"2022042018453616900_B27","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/sj.bjp.0706059","article-title":"2-Furoyl-LIGRL-NH2, a potent agonist for proteinase-activated receptor-2, as a gastric mucosal cytoprotective agent in mice","volume":"144","author":"Kawabata","year":"2005","journal-title":"Br J Pharmacol"},{"key":"2022042018453616900_B28","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.2337\/db15-1565","article-title":"A novel function of hepatic FOG2 in insulin sensitivity and lipid metabolism through PPAR\u03b1","volume":"65","author":"Guo","year":"2016","journal-title":"Diabetes"},{"key":"2022042018453616900_B29","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.cmet.2007.08.014","article-title":"SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B","volume":"6","author":"Sun","year":"2007","journal-title":"Cell Metab"},{"key":"2022042018453616900_B30","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/s41419-017-0239-5","article-title":"Downregulation of \u03b21,4-galactosyltransferase 5 improves insulin resistance by promoting adipocyte commitment and reducing inflammation","volume":"9","author":"Li","year":"2018","journal-title":"Cell Death Dis"},{"key":"2022042018453616900_B31","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1210\/me.2005-0171","article-title":"A novel partial agonist of peroxisome proliferator-activated receptor-gamma (PPAR\u03b3) recruits PPAR\u03b3-coactivator-1\u03b1, prevents triglyceride accumulation, and potentiates insulin signaling in vitro","volume":"20","author":"Burgermeister","year":"2006","journal-title":"Mol Endocrinol"},{"key":"2022042018453616900_B32","doi-asserted-by":"crossref","first-page":"3103","DOI":"10.2337\/db13-0182","article-title":"PRLR regulates hepatic insulin sensitivity in mice via STAT5","volume":"62","author":"Yu","year":"2013","journal-title":"Diabetes"},{"key":"2022042018453616900_B33","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.abb.2014.12.009","article-title":"Palmitate induces insulin resistance in human HepG2 hepatocytes by enhancing ubiquitination and proteasomal degradation of key insulin signaling molecules","volume":"566","author":"Ishii","year":"2015","journal-title":"Arch Biochem Biophys"},{"key":"2022042018453616900_B34","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1002\/jcp.25650","article-title":"The natural cAMP elevating compound forskolin in cancer therapy: is it time?","volume":"232","author":"Sapio","year":"2017","journal-title":"J Cell Physiol"},{"key":"2022042018453616900_B35","doi-asserted-by":"crossref","first-page":"2788","DOI":"10.3390\/nu11112788","article-title":"PipeNig\u00ae-FL, a fluid extract of black pepper (Piper nigrum L.) with a high standardized content of trans-\u03b2-caryophyllene, reduces lipid accumulation in 3T3-L1 preadipocytes and improves glucose uptake in C2C12 myotubes","volume":"11","author":"Geddo","year":"2019","journal-title":"Nutrients"},{"key":"2022042018453616900_B36","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1158\/0008-5472.CAN-17-1805","article-title":"The E3 ligase RING1 targets p53 for degradation and promotes cancer cell proliferation and survival","volume":"78","author":"Shen","year":"2018","journal-title":"Cancer Res"},{"key":"2022042018453616900_B37","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1016\/j.cmet.2014.11.002","article-title":"Cell-type-resolved quantitative proteomics of murine liver","volume":"20","author":"Azimifar","year":"2014","journal-title":"Cell Metab"},{"key":"2022042018453616900_B38","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1038\/s41591-019-0610-4","article-title":"Adipsin preserves beta cells in diabetic mice and associates with protection from type 2 diabetes in humans","volume":"25","author":"G\u00f3mez-Banoy","year":"2019","journal-title":"Nat Med"},{"key":"2022042018453616900_B39","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1161\/CIRCULATIONAHA.115.019860","article-title":"\u03b2-Adrenergic receptors cooperate with transcription factors: the \u201cSTAT\u201d of their union","volume":"133","author":"Balligand","year":"2016","journal-title":"Circulation"},{"key":"2022042018453616900_B40","doi-asserted-by":"crossref","first-page":"22166","DOI":"10.1074\/jbc.M709668200","article-title":"Nedd4 mediates agonist-dependent ubiquitination, lysosomal targeting, and degradation of the beta2-adrenergic receptor","volume":"283","author":"Shenoy","year":"2008","journal-title":"J Biol Chem"},{"key":"2022042018453616900_B41","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1038\/emboj.2009.128","article-title":"The deubiquitinases USP33 and USP20 coordinate beta2 adrenergic receptor recycling and resensitization","volume":"28","author":"Berthouze","year":"2009","journal-title":"EMBO J"},{"key":"2022042018453616900_B42","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.4049\/jimmunol.1900475","article-title":"Frequent loss of IRF2 in cancers leads to immune evasion through decreased MHC class I antigen presentation and increased PD-L1 expression","volume":"203","author":"Kriegsman","year":"2019","journal-title":"J Immunol"},{"key":"2022042018453616900_B43","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.2337\/db11-0194","article-title":"Inflammation is necessary for long-term but not short-term high-fat diet-induced insulin resistance","volume":"60","author":"Lee","year":"2011","journal-title":"Diabetes"},{"key":"2022042018453616900_B44","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/j.molcel.2015.04.008","article-title":"ERp44 exerts redox-dependent control of blood pressure at the ER","volume":"58","author":"Hisatsune","year":"2015","journal-title":"Mol Cell"},{"key":"2022042018453616900_B45","doi-asserted-by":"crossref","first-page":"12464","DOI":"10.1038\/s41598-018-30159-5","article-title":"ERAP1 deficient mice have reduced type 1 regulatory T cells and develop skeletal and intestinal features of ankylosing spondylitis","volume":"8","author":"Pepelyayeva","year":"2018","journal-title":"Sci Rep"},{"key":"2022042018453616900_B46","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.exger.2016.03.005","article-title":"\u03b22-Adrenergic receptor ablation modulates hepatic lipid accumulation and glucose tolerance in aging mice","volume":"78","author":"Shi","year":"2016","journal-title":"Exp Gerontol"}],"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/71\/5\/921\/673161\/db210857.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/71\/5\/921\/673161\/db210857.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T12:44:02Z","timestamp":1667393042000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/71\/5\/921\/144599\/Hepatokine-ERAP1-Disturbs-Skeletal-Muscle-Insulin"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,22]]},"references-count":46,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,2,22]]},"published-print":{"date-parts":[[2022,5,1]]}},"URL":"https:\/\/doi.org\/10.2337\/db21-0857","relation":{"has-preprint":[{"id-type":"doi","id":"10.2337\/figshare.19184258.v1","asserted-by":"object"},{"id-type":"doi","id":"10.2337\/figshare.19184258","asserted-by":"object"}]},"ISSN":["0012-1797"],"issn-type":[{"value":"0012-1797","type":"print"}],"subject":[],"published":{"date-parts":[[2022,2,22]]}}}