{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T10:45:02Z","timestamp":1776163502359,"version":"3.50.1"},"reference-count":51,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T00:00:00Z","timestamp":1662595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Research and Development Program of Shaanxi","award":["2020NY-109"],"award-info":[{"award-number":["2020NY-109"]}]},{"name":"Key Research and Development Program of Shaanxi","award":["20JY009"],"award-info":[{"award-number":["20JY009"]}]},{"name":"Key Research and Development Program of Shaanxi","award":["18YSZX004"],"award-info":[{"award-number":["18YSZX004"]}]},{"name":"Key Research and Development Program of Shaanxi","award":["2022TD-56"],"award-info":[{"award-number":["2022TD-56"]}]},{"name":"Educational Commission of Shaanxi Province","award":["2020NY-109"],"award-info":[{"award-number":["2020NY-109"]}]},{"name":"Educational Commission of Shaanxi Province","award":["20JY009"],"award-info":[{"award-number":["20JY009"]}]},{"name":"Educational Commission of Shaanxi Province","award":["18YSZX004"],"award-info":[{"award-number":["18YSZX004"]}]},{"name":"Educational Commission of Shaanxi Province","award":["2022TD-56"],"award-info":[{"award-number":["2022TD-56"]}]},{"name":"Specialized Scientific Research Fund Projects of Academician Shengyong Zhang","award":["2020NY-109"],"award-info":[{"award-number":["2020NY-109"]}]},{"name":"Specialized Scientific Research Fund Projects of Academician Shengyong Zhang","award":["20JY009"],"award-info":[{"award-number":["20JY009"]}]},{"name":"Specialized Scientific Research Fund Projects of Academician Shengyong Zhang","award":["18YSZX004"],"award-info":[{"award-number":["18YSZX004"]}]},{"name":"Specialized Scientific Research Fund Projects of Academician Shengyong Zhang","award":["2022TD-56"],"award-info":[{"award-number":["2022TD-56"]}]},{"name":"Shaanxi Science and Technology Innovation Team","award":["2020NY-109"],"award-info":[{"award-number":["2020NY-109"]}]},{"name":"Shaanxi Science and Technology Innovation Team","award":["20JY009"],"award-info":[{"award-number":["20JY009"]}]},{"name":"Shaanxi Science and Technology Innovation Team","award":["18YSZX004"],"award-info":[{"award-number":["18YSZX004"]}]},{"name":"Shaanxi Science and Technology Innovation Team","award":["2022TD-56"],"award-info":[{"award-number":["2022TD-56"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alcohol is an essential element in human culture. However, alcoholism has contributed to numerous health issues, including alcoholic fatty liver and sudden death. We found that the alkaloid lotusine possessed hepato- and neuroprotection against alcohol injuries. Lotusine showed comparable protective effects to puerarin, a widely recognized antagonist against alcohol damage. To better understand the metabolic response to alcohol injury and antagonist molecules, we applied sensitive zebrafish and LC-ESI-MS to collect metabolites related to alcohol, puerarin and lotusine exposure. LC-MS identified 119 metabolites with important physiological roles. Differential metabolomic analysis showed that alcohol caused abnormal expression of 82 metabolites (60 up-regulated and 22 down-regulated). These differential metabolites involved 18 metabolic pathways and modules, including apoptosis, necroptosis, nucleotide and fatty acid metabolism. Puerarin reversed seven metabolite variations induced by alcohol, which were related to necroptosis and sphingolipid metabolism. Lotusine was found to repair five metabolites disorders invoked by alcohol, mainly through nucleotide metabolism and glutathione metabolism. In phenotypic bioassay, lotusine showed similar activities to puerarin in alleviating behavioral abnormalities, neuroapoptosis and hepatic lipid accumulation induced by alcohol exposure. Our findings provided a new antagonist, lotusine, for alcohol-induced damage and explored the roles in repairing abnormal metabolism.<\/jats:p>","DOI":"10.3390\/ijms231810385","type":"journal-article","created":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T07:05:56Z","timestamp":1662620756000},"page":"10385","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Insight into Lotusine and Puerarin in Repairing Alcohol-Induced Metabolic Disorder Based on UPLC-MS\/MS"],"prefix":"10.3390","volume":"23","author":[{"given":"Jiayang","family":"Xu","sequence":"first","affiliation":[{"name":"Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Xianyang 712100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Xianyang 712100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Yan","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Xianyang 712100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhichao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Xianyang 712100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wei","sequence":"additional","affiliation":[{"name":"College of Biology Pharmacy & Food Engineering, Shangluo University, Shangluo 726000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luqi","family":"Li","sequence":"additional","affiliation":[{"name":"Life Science Research Core Services, Northwest A&F University, Yangling, Xianyang 712100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7904-2347","authenticated-orcid":false,"given":"Qiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Xianyang 712100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,8]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2021). Regional Office for South-East Asia Preventing Violence against Children 2020: Report for the WHO South-East Asia Region, World Health Organization. Regional Office for South-East Asia."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.livres.2018.11.002","article-title":"Alcoholic liver disease: A current molecular and clinical perspective","volume":"2","author":"Ohashi","year":"2018","journal-title":"Liver Res."},{"key":"ref_3","first-page":"155","article-title":"Chronic diseases and conditions related to alcohol use","volume":"35","author":"Shield","year":"2013","journal-title":"Alcohol Res. Curr. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.freeradbiomed.2022.03.027","article-title":"Loss of ERdj5 exacerbates oxidative stress in mice with alcoholic liver disease via suppressing Nrf2","volume":"184","author":"Hong","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Hyun, J., Han, J., Lee, C., Yoon, M., and Jung, Y. (2021). Pathophysiological aspects of alcohol metabolism in the liver. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115717"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lin, T.-A., Ke, B.-J., Cheng, S.-C., and Lee, C.-L. (2021). Red quinoa bran extract prevented alcoholic fatty liver disease via increasing antioxidative system and repressing fatty acid synthesis factors in mice fed alcohol liquid diet. Molecules, 26.","DOI":"10.3390\/molecules26226973"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.jep.2018.06.008","article-title":"Phenolic acid and flavonoid-rich fraction of Sasa quelpaertensis Nakai leaves prevent alcohol induced fatty liver through AMPK activation","volume":"224","author":"Herath","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1007\/s00204-019-02447-0","article-title":"The LRP6 functional mutation Rs2302685 contributes to individual susceptibility to alcoholic liver injury related to the Wnt\/\u03b2-catenin-TCF1-CYP2E1 signaling pathway","volume":"93","author":"Xu","year":"2019","journal-title":"Arch. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"iii16","DOI":"10.1136\/jnnp.2004.045708","article-title":"Alcohol and the nervous system","volume":"75","author":"McIntosh","year":"2004","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2174\/1874467213666200512114943","article-title":"Alcoholic neuropathy: Involvement of multifaceted signalling mechanisms","volume":"14","author":"Behl","year":"2021","journal-title":"Curr. Mol. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1007\/s00415-018-9123-1","article-title":"Alcohol-related peripheral neuropathy: A systematic review and meta-analysis","volume":"266","author":"Julian","year":"2019","journal-title":"J. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1007\/s12640-022-00477-8","article-title":"Exploring the therapeutic potential of targeting purinergic and orexinergic receptors in alcoholic neuropathy","volume":"40","author":"Madaan","year":"2022","journal-title":"Neurotox. Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Chen, Y.-C., Yang, L.-F., Lai, C.-L., and Yin, S.-J. (2021). Acetaldehyde enhances alcohol sensitivity and protects against alcoholism: Evidence from alcohol metabolism in subjects with variant ALDH2*2 gene allele. Biomolecules, 11.","DOI":"10.3390\/biom11081183"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e13245","DOI":"10.1111\/cpr.13245","article-title":"Altered gut microbiota and metabolites profile are associated with reduced bone metabolism in ethanol-induced osteoporosis","volume":"55","author":"Liu","year":"2022","journal-title":"Cell Prolif."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Irwin, C., van Reenen, M., Mason, S., Mienie, L.J., Wevers, R.A., Westerhuis, J.A., and Reinecke, C.J. (2018). The 1H-NMR-based metabolite profile of acute alcohol consumption: A metabolomics intervention study. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0196850"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1016\/j.biotechadv.2015.08.001","article-title":"Discovery and resupply of pharmacologically active plant-derived natural products: A review","volume":"33","author":"Atanasov","year":"2015","journal-title":"Biotechnol. Adv."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1111\/j.1530-0277.1996.tb01668.x","article-title":"Isoflavonoid compounds extracted from pueraria lobata suppress alcohol preference in a pharmacogenetic Rat model of alcoholism","volume":"20","author":"Lin","year":"1996","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"111121","DOI":"10.1016\/j.biopha.2020.111121","article-title":"Puerariae Lobatae radix flavonoids and puerarin alleviate alcoholic liver injury in zebrafish by regulating alcohol and lipid metabolism","volume":"134","author":"Liu","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.bbrc.2011.09.077","article-title":"Restoration of autophagy by puerarin in ethanol-treated hepatocytes via the activation of AMP-activated protein kinase","volume":"414","author":"Noh","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1590\/1414-431x20144250","article-title":"Puerarin protects against damage to spatial learning and memory ability in mice with chronic alcohol poisoning","volume":"48","author":"Cui","year":"2015","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"891","DOI":"10.3389\/fpls.2016.00891","article-title":"Current Advances in the Metabolomics Study on Lotus Seeds","volume":"7","author":"Zhu","year":"2016","journal-title":"Front. Plant Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s11626-020-00466-1","article-title":"Lotusine, an alkaloid from Nelumbo nucifera (Gaertn.), attenuates doxorubicin-induced toxicity in embryonically derived H9c2 cells","volume":"56","author":"Harishkumar","year":"2020","journal-title":"Vitro Cell. Dev. Biol.-Anim."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ryu, T.-K., Roh, E., Shin, H.-S., and Kim, J.-E. (2022). Inhibitory effect of lotusine on solar UV-induced matrix metalloproteinase-1 expression. Plants, 11.","DOI":"10.3390\/plants11060773"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"113538","DOI":"10.1016\/j.jep.2020.113538","article-title":"Developmental toxicity of clerodendrum cyrtophyllum turcz ethanol extract in zebrafish embryo","volume":"267","author":"Nguyen","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/s41573-021-00210-8","article-title":"Zebrafish disease models in drug discovery: From preclinical modelling to clinical trials","volume":"20","author":"Patton","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"114638","DOI":"10.1016\/j.jep.2021.114638","article-title":"Progress in using zebrafish as a toxicological model for traditional chinese medicine","volume":"282","author":"Zhang","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"113842","DOI":"10.1016\/j.ecoenv.2022.113842","article-title":"Zebrafish (Danio rerio) as a model organism for screening nephrotoxic chemicals and related mechanisms","volume":"242","author":"Lim","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"113870","DOI":"10.1016\/j.ecoenv.2022.113870","article-title":"Isoprocarb causes neurotoxicity of zebrafish embryos through oxidative stress-induced apoptosis","volume":"242","author":"Wang","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/nrd4627","article-title":"Zebrafish as tools for drug discovery","volume":"14","author":"MacRae","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_30","first-page":"e21785","article-title":"Recent advances in LC-MS-based metabolomics for clinical biomarker discovery","volume":"41","author":"Chen","year":"2022","journal-title":"Mass Spectrom. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/mas.21611","article-title":"Functional metabolomics decipher biochemical functions and associated mechanisms underlie small-molecule metabolism","volume":"39","author":"Hu","year":"2020","journal-title":"Mass Spectrom. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Picart-Armada, S., Fern\u00e1ndez-Albert, F., Vinaixa, M., Rodr\u00edguez, M.A., Aivio, S., Stracker, T.H., Yanes, O., and Perera-Lluna, A. (2017). Null diffusion-based enrichment for metabolomics data. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0189012"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3892\/ijmm.2021.4922","article-title":"The potential role of necroptosis in clinical diseases (review)","volume":"47","author":"Dai","year":"2021","journal-title":"Int. J. Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1111\/j.1476-5381.2010.01108.x","article-title":"Semaphorin 3A inhibits growth of adult sympathetic and parasympathetic neurones via distinct cyclic nucleotide signalling pathways","volume":"162","author":"Nangle","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.1158\/0008-5472.CAN-18-3776","article-title":"Transketolase deficiency protects the liver from DNA damage by increasing levels of ribose 5-phosphate and nucleotides","volume":"79","author":"Li","year":"2019","journal-title":"Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"171","DOI":"10.17219\/acem\/81520","article-title":"Effects of puerarin on spatial Learning and memory function in mice with acute alcohol consumption: An evaluation based upon firing rate and oxygen saturation analysis","volume":"28","author":"Li","year":"2019","journal-title":"Adv. Clin. Exp. Med. Off. Organ Wroc. Med. Univ."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.drugalcdep.2012.04.012","article-title":"The isoflavone puerarin reduces alcohol intake in heavy drinkers: A pilot study","volume":"126","author":"Penetar","year":"2012","journal-title":"Drug Alcohol Depend."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e13193","DOI":"10.1111\/cpr.13193","article-title":"Roles of necroptosis in alcoholic liver disease and hepatic pathogenesis","volume":"55","author":"Zhou","year":"2022","journal-title":"Cell Prolif."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1002\/hep.26200","article-title":"Absence of receptor interacting protein kinase 3 prevents ethanol-induced liver injury","volume":"57","author":"Roychowdhury","year":"2013","journal-title":"Hepatology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.biochi.2018.07.021","article-title":"Sphingolipid metabolism in non-alcoholic fatty liver diseases","volume":"159","author":"Polizzi","year":"2019","journal-title":"Biochimie"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.2174\/1570159X16666180416152243","article-title":"Necroptosis signaling pathways in stroke: From mechanisms to therapies","volume":"16","author":"Yi","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e2016969118","DOI":"10.1073\/pnas.2016969118","article-title":"Sphingolipid metabolism governs purkinje cell patterned degeneration in Atxn1[82Q]\/+ mice","volume":"118","author":"Blot","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1111\/j.1530-0277.2006.00147.x","article-title":"Abnormal transsulfuration and glutathione metabolism in the micropig model of alcoholic liver disease","volume":"30","author":"Villanueva","year":"2006","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1254\/jphs.08R01CR","article-title":"Regulation of neuronal glutathione synthesis","volume":"108","author":"Aoyama","year":"2008","journal-title":"J. Pharmacol. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nmeth.3393","article-title":"MS-DIAL: Data-independent MS\/MS deconvolution for comprehensive metabolome analysis","volume":"12","author":"Tsugawa","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"D622","DOI":"10.1093\/nar\/gkab1062","article-title":"HMDB 5.0: The human metabolome database for 2022","volume":"50","author":"Wishart","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"11692","DOI":"10.1021\/acs.analchem.1c01465","article-title":"CFM-ID 4.0: More accurate ESI-MS\/MS spectral prediction and compound identification","volume":"93","author":"Wang","year":"2021","journal-title":"Anal. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Djoumbou-Feunang, Y., Pon, A., Karu, N., Zheng, J., Li, C., Arndt, D., Gautam, M., Allen, F., and Wishart, D.S. (2019). CFM-ID 3.0: Significantly improved ESI-MS\/MS prediction and compound identification. Metabolites, 9.","DOI":"10.3390\/metabo9040072"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Rohart, F., Gautier, B., Singh, A., and Cao, K.-A.L. (2017). MixOmics: An R package for \u2032omics feature selection and multiple data integration. PLoS Comput. Biol., 13.","DOI":"10.1101\/108597"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Picart-Armada, S., Fern\u00e1ndez-Albert, F., Vinaixa, M., Yanes, O., and Perera-Lluna, A. (2018). FELLA: An R package to enrich metabolomics data. BMC Bioinform., 19.","DOI":"10.1186\/s12859-018-2487-5"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"132933","DOI":"10.1016\/j.foodchem.2022.132933","article-title":"Metabolomic navigated citrus waste repurposing to restore amino acids disorder in neural lesion","volume":"387","author":"Zhang","year":"2022","journal-title":"Food Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10385\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:27:29Z","timestamp":1760142449000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10385"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,8]]},"references-count":51,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ijms231810385"],"URL":"https:\/\/doi.org\/10.3390\/ijms231810385","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,8]]}}}