{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T13:57:09Z","timestamp":1776866229825,"version":"3.51.2"},"reference-count":51,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2019,12,10]],"date-time":"2019-12-10T00:00:00Z","timestamp":1575936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81703601"],"award-info":[{"award-number":["81703601"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81872838"],"award-info":[{"award-number":["81872838"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773814"],"award-info":[{"award-number":["81773814"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013279","name":"National Key New Drug Creation and Manufacturing Program, Ministry of Science and Technology","doi-asserted-by":"publisher","award":["2017ZX09301013"],"award-info":[{"award-number":["2017ZX09301013"]}],"id":[{"id":"10.13039\/501100013279","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2018M632429"],"award-info":[{"award-number":["2018M632429"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20180079"],"award-info":[{"award-number":["BK20180079"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2632018ZD07"],"award-info":[{"award-number":["2632018ZD07"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>High-calorie diet, circadian rhythms and metabolic features are intimately linked. However, the mediator(s) between nutritional status, circadian rhythms and metabolism remain largely unknown. This article aims to clarify the key metabolic pathways bridging nutritional status and circadian rhythms based on a combination of metabolomics and molecular biological techniques. A mouse model of high-fat diet-induced obesity was established and serum samples were collected in obese and normal mice at different zeitgeber times. Gas chromatography\/mass spectrometry, multivariate\/univariate data analyses and metabolic pathway analysis were used to reveal changes in metabolism. Metabolites involved in the metabolism of purines, carbohydrates, fatty acids and amino acids were markedly perturbed in accordance with circadian related variations, among which purine catabolism showed a typical oscillation. What\u2019s more, the rhythmicity of purine catabolism dampened in the high-fat diet group. The expressions of clock genes and metabolic enzymes in the liver were measured. The mRNA expression of Xanthine oxidase (Xor) was highly correlated with the rhythmicity of Clock, Rev-erb\u03b1 and Bmal1, as well as the metabolites involved in purine catabolism. These data showed that a high-fat diet altered the circadian rhythm of metabolic pathways, especially purine catabolism. It had an obvious circadian oscillation and a high-fat diet dampened its circadian rhythmicity. It was suggested that circadian rhythmicity of purine catabolism is related to circadian oscillations of expression of Xor, Uox and corresponding clock genes.<\/jats:p>","DOI":"10.3390\/molecules24244524","type":"journal-article","created":{"date-parts":[[2019,12,10]],"date-time":"2019-12-10T10:52:41Z","timestamp":1575975161000},"page":"4524","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Purine Catabolism Shows a Dampened Circadian Rhythmicity in a High-fat Diet-Induced Mouse Model of Obesity"],"prefix":"10.3390","volume":"24","author":[{"given":"Runbin","family":"Sun","sequence":"first","affiliation":[{"name":"Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingqiu","family":"Huang","sequence":"additional","affiliation":[{"name":"Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Yang","sequence":"additional","affiliation":[{"name":"Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"He","sequence":"additional","affiliation":[{"name":"Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyi","family":"Yu","sequence":"additional","affiliation":[{"name":"Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siqi","family":"Feng","sequence":"additional","affiliation":[{"name":"Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Xie","sequence":"additional","affiliation":[{"name":"Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangji","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Ye","sequence":"additional","affiliation":[{"name":"Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiye","family":"Aa","sequence":"additional","affiliation":[{"name":"Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bernard, S., Gonze, D., \u010cajavec, B., Herzel, H., and Kramer, A. (2007). Synchronization-Induced Rhythmicity of Circadian Oscillators in the Suprachiasmatic Nucleus. PLoS Comput. Biol., 3.","DOI":"10.1371\/journal.pcbi.0030068"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1074\/jbc.M209241200","article-title":"CREB-dependent activation of Per1 is required for light-induced signaling in the Suprachiasmatic Nucleus Circadian clock","volume":"278","author":"Tischkau","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3282","DOI":"10.4161\/15384101.2014.954454","article-title":"Loss of circadian clock gene expression is associated with tumor progression in breast cancer","volume":"13","author":"Cadenas","year":"2014","journal-title":"Cell Cycle"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"870","DOI":"10.3109\/07420528.2013.782315","article-title":"Crosstalk between the circadian clock circuitry and the immune system","volume":"30","author":"Cermakian","year":"2013","journal-title":"Chronobiol. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8138","DOI":"10.1523\/JNEUROSCI.20-21-08138.2000","article-title":"The circadian clock mutation alters sleep homeostasis in the mouse","volume":"20","author":"Naylor","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1007\/s00125-010-1920-8","article-title":"An intrinsic circadian clock of the pancreas is required for normal insulin release and glucose homeostasis in mice","volume":"54","author":"Sadacca","year":"2011","journal-title":"Diabetologia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1038\/s41591-018-0271-8","article-title":"The emerging link between cancer, metabolism, and circadian rhythms","volume":"24","author":"Masri","year":"2018","journal-title":"Nat. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.metabol.2017.11.017","article-title":"Circadian regulation of glucose, lipid, and energy metabolism in humans","volume":"84","author":"Poggiogalle","year":"2018","journal-title":"Metabolism"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1126\/science.1108750","article-title":"Obesity and metabolic syndrome in circadian Clock mutant mice","volume":"308","author":"Turek","year":"2005","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.cmet.2016.03.007","article-title":"The Small Molecule Nobiletin Targets the Molecular Oscillator to Enhance Circadian Rhythms and Protect against Metabolic Syndrome","volume":"23","author":"He","year":"2016","journal-title":"Cell Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.bbrc.2015.03.070","article-title":"Suppression of atherosclerosis by synthetic REV-ERB agonist","volume":"460","author":"Sitaula","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/nature11030","article-title":"Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists","volume":"485","author":"Solt","year":"2012","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0031-9384(98)00166-8","article-title":"Glucose, but not fat, phase shifts the feeding-entrained circadian clock","volume":"65","author":"Stephan","year":"1998","journal-title":"Physiol. Behav."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1126\/science.291.5503.490","article-title":"Entrainment of the circadian clock in the liver by feeding","volume":"291","author":"Stokkan","year":"2001","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1001\/jama.2016.6458","article-title":"Trends in obesity among adults in the United States, 2005 to 2014","volume":"315","author":"Flegal","year":"2016","journal-title":"Jama"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1210\/er.2009-0014","article-title":"Metabolism and circadian rhythms\u2014implications for obesity","volume":"31","author":"Froy","year":"2010","journal-title":"Endocr. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1080\/004982599238047","article-title":"Metabonomics: Understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data","volume":"29","author":"Nicholson","year":"1999","journal-title":"Xenobiotica"},{"key":"ref_18","first-page":"787","article-title":"The human circadian metabolome","volume":"33","author":"Dallmann","year":"2000","journal-title":"Off. Sci. Tech. Inf. Tech. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2812","DOI":"10.1074\/jbc.M115.681130","article-title":"Comparative Circadian Metabolomics reveal Differential Effects of Nutritional Challenge in the Serum and Liver","volume":"291","author":"Abbondante","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.cmet.2011.01.006","article-title":"Crosstalk between components of circadian and metabolic cycles in mammals","volume":"13","author":"Asher","year":"2011","journal-title":"Cell Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1016\/j.cell.2018.08.042","article-title":"Atlas of Circadian Metabolism Reveals System-wide Coordination and Communication between Clocks","volume":"174","author":"Dyar","year":"2018","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1210\/en.2015-1376","article-title":"Daily fasting blood glucose rhythm in male mice: A role of the circadian clock in the liver","volume":"157","author":"Ando","year":"2016","journal-title":"Endocrinology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/343536a0","article-title":"Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels","volume":"343","author":"Hardin","year":"1990","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/35088576","article-title":"Time zones: A comparative genetics of circadian clocks","volume":"2","author":"Young","year":"2001","journal-title":"Nat. Rev. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s11306-010-0241-8","article-title":"Gas chromatography time-of-flight mass spectrometry based metabolomic approach to evaluating toxicity of triptolide","volume":"7","author":"Aa","year":"2011","journal-title":"Metabolomics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s10654-014-9910-7","article-title":"Metabolomics approach reveals effects of antihypertensives and lipid-lowering drugs on the human metabolism","volume":"29","author":"Altmaier","year":"2014","journal-title":"Eur. J. Epidemiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1517\/17425255.4.6.665","article-title":"Metabolomic strategies to identify tissue-specific effects of cardiovascular drugs","volume":"4","author":"Laaksonen","year":"2008","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Liu, L., Cao, B., Aa, J., Zheng, T., Jian, S., Li, M., Wang, X., Zhao, C., Xiao, W., and Yu, X. (2012). Prediction of the pharmacokinetic parameters of triptolide in rats based on endogenous molecules in pre-dose baseline serum. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043389"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1146\/annurev-med-061511-134747","article-title":"Application of metabolomics to diagnosis of insulin resistance","volume":"64","author":"Milburn","year":"2013","journal-title":"Annu. Rev. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1593\/neo.81396","article-title":"Early Stage Diagnosis of Oral Cancer Using 1 H NMR\u2013Based Metabolomics 1 2","volume":"11","author":"Tiziani","year":"2009","journal-title":"Neoplasia"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9890","DOI":"10.1073\/pnas.0900617106","article-title":"Measurement of internal body time by blood metabolomics","volume":"106","author":"Minami","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.cmet.2013.12.016","article-title":"Circadian clocks and feeding time regulate the oscillations and levels of hepatic triglycerides","volume":"19","author":"Adamovich","year":"2014","journal-title":"Cell Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/j.bbrc.2014.06.083","article-title":"Disruption of behavioral circadian rhythms induced by psychophysiological stress affects plasma free amino acid profiles without affecting peripheral clock gene expression in mice","volume":"450","author":"Oishi","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.cmet.2009.02.002","article-title":"A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance","volume":"9","author":"Newgard","year":"2009","journal-title":"Cell Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s00726-011-1088-7","article-title":"Insulin resistance and the metabolism of branched-chain amino acids in humans","volume":"43","author":"Adeva","year":"2012","journal-title":"Amino Acids"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1172\/JCI46043","article-title":"Circadian rhythms, sleep, and metabolism","volume":"121","author":"Huang","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3389\/fchem.2014.00061","article-title":"Membrane transporters for the special amino acid glutamine: Structure\/function relationships and relevance to human health","volume":"2","author":"Pochini","year":"2014","journal-title":"Front. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1006\/mgme.1999.2857","article-title":"Glutamine, as a precursor of glutathione, and oxidative stress","volume":"67","author":"Medina","year":"1999","journal-title":"Mol. Genet. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ijcard.2015.08.109","article-title":"Regulation of uric acid metabolism and excretion","volume":"213","author":"Maiuolo","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1056\/NEJM196304042681406","article-title":"Biochemistry of uric acid and its relation to gout","volume":"268","author":"Seegmiller","year":"1963","journal-title":"N. Engl. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1001\/jama.283.18.2404","article-title":"Serum Uric Acid and Cardiovascular MortalityThe NHANES I Epidemiologic Follow-up Study, 1971\u20131992","volume":"283","author":"Fang","year":"2000","journal-title":"Jama"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2526","DOI":"10.1161\/CIRCULATIONAHA.106.657627","article-title":"Serum Concentrations of Uric Acid and the Metabolic Syndrome Among US Children and Adolescents","volume":"115","author":"Ford","year":"2007","journal-title":"Circulation"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"F625","DOI":"10.1152\/ajprenal.00140.2005","article-title":"A causal role for uric acid in fructose-induced metabolic syndrome","volume":"290","author":"Nakagawa","year":"2006","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/j.amjhyper.2006.02.014","article-title":"Serum Uric Acid Is a Determinant of Metabolic Syndrome in a Population-Based Study","volume":"19","author":"Onat","year":"2006","journal-title":"Am. J. Hypertens."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.1001\/jama.283.17.2235","article-title":"Circadian relationship of serum uric acid and nitric oxide","volume":"283","author":"Kanabrocki","year":"2000","journal-title":"Jama"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/0006-8993(93)91651-8","article-title":"Day-night variations of adenosine and its metabolizing enzymes in the brain cortex of the rat\u2014possible physiological significance for the energetic homeostasis and the sleep-wake cycle","volume":"612","author":"Herna","year":"1993","journal-title":"Brain Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s00114-002-0304-4","article-title":"The flavo-enzyme xanthine oxidase is under circadian control in the marine alga Gonyaulax","volume":"89","author":"Deng","year":"2002","journal-title":"Sci. Nat."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41574-018-0142-x","article-title":"The arrival of circadian medicine","volume":"15","author":"Panda","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"8086","DOI":"10.1021\/ac051211v","article-title":"Extraction and GC\/MS analysis of the human blood plasma metabolome","volume":"77","author":"Jiye","year":"2005","journal-title":"Anal. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1038\/aps.2010.86","article-title":"Differential regulations of blood pressure and perturbed metabolism by total ginsenosides and conventional antihypertensive agents in spontaneously hypertensive rats","volume":"31","author":"Aa","year":"2010","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"W251","DOI":"10.1093\/nar\/gkv380","article-title":"MetaboAnalyst 3.0\u2014Making metabolomics more meaningful","volume":"43","author":"Xia","year":"2015","journal-title":"Nucleic Acids Res."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/24\/4524\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:41:08Z","timestamp":1760190068000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/24\/4524"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,10]]},"references-count":51,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["molecules24244524"],"URL":"https:\/\/doi.org\/10.3390\/molecules24244524","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,10]]}}}