{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:09:49Z","timestamp":1791230989764,"version":"4.1.0"},"reference-count":54,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,10]],"date-time":"2022-12-10T00:00:00Z","timestamp":1670630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"China Agriculture Research System of MOF and MARA","award":["CARS-42"],"award-info":[{"award-number":["CARS-42"]}]},{"name":"China Agriculture Research System of MOF and MARA","award":["JATS (2021) 326"],"award-info":[{"award-number":["JATS (2021) 326"]}]},{"DOI":"10.13039\/501100020051","name":"Jiangsu Agricultural Industry Technology System","doi-asserted-by":"publisher","award":["CARS-42"],"award-info":[{"award-number":["CARS-42"]}],"id":[{"id":"10.13039\/501100020051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020051","name":"Jiangsu Agricultural Industry Technology System","doi-asserted-by":"publisher","award":["JATS (2021) 326"],"award-info":[{"award-number":["JATS (2021) 326"]}],"id":[{"id":"10.13039\/501100020051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The imbalance in polyunsaturated fatty acid (PUFA) composition in human food is ubiquitous and closely related to obesity and cardiovascular diseases. The development of n-3 PUFA-enriched poultry products is of great significance for optimizing fatty acid composition. This study aimed to improve our understanding of the effects of dietary linseed oil on hepatic metabolism using untargeted metabolomics and 4D label-free proteome analysis. A total of 91 metabolites and 63 proteins showed differences in abundance in duck livers between the high linseed oil and control groups. Pathway analysis revealed that the biosynthesis of unsaturated fatty acids, linoleic acid, glycerophospholipid, and pyrimidine metabolisms were significantly enriched in ducks fed with linseed oil. Meanwhile, dietary linseed oil changed liver fatty acid composition, which was reflected in the increase in the abundance of downstream metabolites, such as \u03b1-linolenic acid (ALA; 18:3n-3) as a substrate, including n-3 PUFA and its related glycerophospholipids, and a decrease in downstream n-6 PUFA synthesis using linoleic acid (LA; 18:2n-6) as a substrate. Moreover, the anabolism of PUFA in duck livers showed substrate-dependent effects, and the expression of related proteins in the process of fatty acid anabolism, such as FADS2, LPIN2, and PLA2G4A, were significantly regulated by linseed oil. Collectively, our work highlights the ALA substrate dependence during n-3 PUFA synthesis in duck livers. The present study expands our knowledge of the process products of PUFA metabolism and provides some potential biomarkers for liver health.<\/jats:p>","DOI":"10.3390\/ijms232415690","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T01:42:27Z","timestamp":1670809347000},"page":"15690","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Metabolomics and Proteomics Characterizing Hepatic Reactions to Dietary Linseed Oil in Duck"],"prefix":"10.3390","volume":"23","author":[{"given":"Yang","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding and Molecular Design of Jiangsu Province, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding and Molecular Design of Jiangsu Province, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laidi","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding and Molecular Design of Jiangsu Province, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding and Molecular Design of Jiangsu Province, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingqiang","family":"Dong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding and Molecular Design of Jiangsu Province, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiu","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding and Molecular Design of Jiangsu Province, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulin","family":"Bi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding and Molecular Design of Jiangsu Province, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohong","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding and Molecular Design of Jiangsu Province, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5712-626X","authenticated-orcid":false,"given":"Guobin","family":"Chang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding and Molecular Design of Jiangsu Province, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Djuricic, I., and Calder, P.C. (2021). Beneficial outcomes of omega-6 and omega-3 polyunsaturated fatty acids on human health: An update for 2021. Nutrients, 13.","DOI":"10.3390\/nu13072421"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.lfs.2018.04.049","article-title":"Omega-3 and omega-6 polyunsaturated fatty acids: Dietary sources, metabolism, and significance\u2014A review","volume":"203","author":"Saini","year":"2018","journal-title":"Life Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1194\/jlr.R120000800","article-title":"Roles of polyunsaturated fatty acids, from mediators to membranes","volume":"61","author":"Harayama","year":"2020","journal-title":"J. Lipid Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.plipres.2009.12.002","article-title":"The key roles of elongases and desaturases in mammalian fatty acid metabolism: Insights from transgenic mice","volume":"49","author":"Guillou","year":"2010","journal-title":"Prog. Lipid Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1017\/S0029665117001112","article-title":"Can we improve the nutritional quality of meat?","volume":"76","author":"Scollan","year":"2017","journal-title":"Proc. Nutr. Soc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1016\/j.cell.2022.04.002","article-title":"Nutrition, longevity and disease: From molecular mechanisms to interventions","volume":"185","author":"Longo","year":"2022","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"805s","DOI":"10.1093\/jn\/127.5.805S","article-title":"Lipoprotein metabolism and fattening in poultry","volume":"127","author":"Hermier","year":"1997","journal-title":"J. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zaefarian, F., Abdollahi, M.R., Cowieson, A., and Ravindran, V. (2019). Avian liver: The forgotten organ. Animals, 9.","DOI":"10.3390\/ani9020063"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1080\/00071668.2020.1812527","article-title":"Research progress into the physiological changes in metabolic pathways in waterfowl with hepatic steatosis","volume":"62","author":"Wei","year":"2021","journal-title":"Br. Poult. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1097\/FJC.0b013e3181af04e5","article-title":"Flaxseed and cardiovascular health","volume":"54","author":"Prasad","year":"2009","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Shahid, M.S., Wu, Y., Xiao, Z., Raza, T., Dong, X., and Yuan, J. (2019). Duration of the flaxseed diet promotes deposition of n-3 fatty acids in the meat and skin of Peking ducks. Food Nutr. Res., 63.","DOI":"10.29219\/fnr.v63.3590"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1017\/S1751731115001287","article-title":"Effect of flaxseed on the fatty acid profile of egg yolk and antioxidant status of their neonatal offspring in Huoyan geese","volume":"9","author":"Chen","year":"2015","journal-title":"Animal"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.aninu.2017.08.001","article-title":"Effect of dietary incorporation of n-3 polyunsaturated fatty acids rich oil sources on fatty acid profile, keeping quality and sensory attributes of broiler chicken meat","volume":"3","author":"Kalakuntla","year":"2017","journal-title":"Anim. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1030712","DOI":"10.3389\/fnut.2022.1030712","article-title":"Dietary linseed oil affects the polyunsaturated fatty acid and transcriptome profiles in the livers and breast muscles of ducks","volume":"9","author":"Wang","year":"2022","journal-title":"Front. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1017\/S0043933911000481","article-title":"Lipoprotein metabolism in poultry","volume":"67","author":"Alvarenga","year":"2011","journal-title":"World\u2019s Poult. Sci. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1146\/annurev-physiol-021317-121550","article-title":"SR-B1: A unique multifunctional receptor for cholesterol Influx and efflux","volume":"80","author":"Shen","year":"2018","journal-title":"Annu. Rev. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gracia-Rubio, I.M.C., Civeira, F., and Cenarro, A. (2021). SR-B1, a Key Receptor Involved in the Progression of Cardiovascular Disease: A Perspective from Mice and Human Genetic Studies. Biomedicines, 9.","DOI":"10.3390\/biomedicines9060612"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1007\/s10695-019-00636-3","article-title":"Linseed oil can decrease liver fat deposition and improve antioxidant ability of juvenile largemouth bass, Micropterus salmoides","volume":"45","author":"Shi","year":"2019","journal-title":"Fish Physiol. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.numecd.2005.12.010","article-title":"Decrease in blood triglycerides associated with the consumption of eggs of hens fed with food supplemented with fish oil","volume":"17","author":"Bovet","year":"2007","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1159\/000100818","article-title":"Effect of dietary alpha-linolenic fatty acid derived from chia when fed as ground seed, whole seed and oil on lipid content and fatty acid composition of rat plasma","volume":"51","author":"Ayerza","year":"2007","journal-title":"Ann. Nutr. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1093\/jn\/134.11.2991","article-title":"Dietary alpha-linolenic acid reduces inflammatory and lipid cardiovascular risk factors in hypercholesterolemic men and women","volume":"134","author":"Zhao","year":"2004","journal-title":"J. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"9995","DOI":"10.1021\/acs.jafc.7b02918","article-title":"Effects of Dietary n-6:n-3 PUFA Ratios on Lipid Levels and Fatty Acid Profile of Cherry Valley Ducks at 15\u201342 Days of Age","volume":"65","author":"Li","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"R1234","DOI":"10.1152\/ajpregu.00346.2016","article-title":"Dietary \u03b1-linolenic acid supplementation alters skeletal muscle plasma membrane lipid composition, sarcolemmal FAT\/CD36 abundance, and palmitate transport rates","volume":"311","author":"Chorner","year":"2016","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1093\/ps\/81.10.1555","article-title":"Dietary linseed oil produces lower abdominal fat deposition but higher de novo fatty acid synthesis in broiler chickens","volume":"81","author":"Crespo","year":"2002","journal-title":"Poult. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.theriogenology.2019.03.016","article-title":"Dietary supplementation with linseed oil improves semen quality, reproductive hormone, gene and protein expression related to testosterone synthesis in aging layer breeder roosters","volume":"131","author":"Qi","year":"2019","journal-title":"Theriogenology"},{"key":"ref_26","first-page":"474","article-title":"Effect of dietary omega6\/omega3 on growth performance, carcass traits, meat quality and fatty acid profiles of Beijing-you chicken","volume":"94","author":"Qi","year":"2010","journal-title":"J. Anim. Physiol. Anim. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/0005-2760(92)90202-7","article-title":"Plasma clearance of model lipoproteins containing saturated and polyunsaturated monoacylglycerols injected intravenously in the rat","volume":"1127","author":"Mortimer","year":"1992","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1172\/JCI113806","article-title":"Dietary polyunsaturated fats of the W-6 and W-3 series reduce postprandial lipoprotein levels. Chronic and acute effects of fat saturation on postprandial lipoprotein metabolism","volume":"82","author":"Weintraub","year":"1988","journal-title":"J. Clin. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jnutbio.2016.03.014","article-title":"Intake of a Western diet containing cod instead of pork alters fatty acid composition in tissue phospholipids and attenuates obesity and hepatic lipid accumulation in mice","volume":"33","author":"Liisberg","year":"2016","journal-title":"J. Nutr. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"361895","DOI":"10.1155\/2013\/361895","article-title":"Fatty Acid modulation of the endocannabinoid system and the effect on food intake and metabolism","volume":"2013","author":"Naughton","year":"2013","journal-title":"Int. J. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/S1734-1140(11)70576-X","article-title":"Activity of essential phospholipids (EPL) from soybean in liver diseases","volume":"63","author":"Gundermann","year":"2011","journal-title":"Pharmacol. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1017\/S1464793104006578","article-title":"Dietary fats and membrane function: Implications for metabolism and disease","volume":"80","author":"Hulbert","year":"2005","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s00232-005-0789-9","article-title":"Membrane effects of the n-3 fish oil fatty acids, which prevent fatal ventricular arrhythmias","volume":"206","author":"Leaf","year":"2005","journal-title":"J. Membr. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1042\/bj3450061","article-title":"Characterization of plasma unsaturated lysophosphatidylcholines in human and rat","volume":"345","author":"Croset","year":"2000","journal-title":"Biochem. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1093\/gerona\/gly100","article-title":"Targeted metabolomics shows low plasma lysophosphatidylcholine 18:2 predicts greater decline of gait speed in older adults: The baltimore longitudinal study of aging","volume":"74","author":"Moaddel","year":"2019","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.pharmthera.2009.06.008","article-title":"Lipids as targets for novel anti-inflammatory therapies","volume":"124","author":"Huwiler","year":"2009","journal-title":"Pharmacol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.jnutbio.2009.12.004","article-title":"Mechanisms underlying the cardioprotective effects of omega-3 polyunsaturated fatty acids","volume":"21","author":"Adkins","year":"2010","journal-title":"J. Nutr. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1111\/j.1471-4159.2006.04371.x","article-title":"Modulation of inflammation in brain: A matter of fat","volume":"101","author":"Farooqui","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Balogun, K.A., Albert, C.J., Ford, D.A., Brown, R.J., and Cheema, S.K. (2013). Dietary omega-3 polyunsaturated fatty acids alter the fatty acid composition of hepatic and plasma bioactive lipids in C57BL\/6 mice: A lipidomic approach. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082399"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/0952-3278(90)90073-T","article-title":"N-6 and N-3 PUFA in liver lipids, thromboxane formation and blood pressure from SHR during diets supplemented with evening primrose, sunflowerseed or fish oil","volume":"39","author":"Singer","year":"1990","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"S159","DOI":"10.3177\/jnsv.61.S159","article-title":"Functional Lipids in Metabolic Syndrome","volume":"61","author":"Nagao","year":"2015","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.plipres.2007.12.004","article-title":"The opposing effects of n-3 and n-6 fatty acids","volume":"47","author":"Schmitz","year":"2008","journal-title":"Prog. Lipid Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1111\/j.1476-5381.2009.00290.x","article-title":"Resolvins and protectins: Mediating solutions to inflammation","volume":"158","author":"Kohli","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1007\/s11033-008-9385-2","article-title":"Molecular characterization, chromosomal localization and association analysis with back-fat thickness of porcine LPIN2 and LPIN3","volume":"36","author":"He","year":"2009","journal-title":"Mol. Biol. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"113842","DOI":"10.1016\/j.ygcen.2021.113842","article-title":"Nuclear progesterone receptor regulates ptger4b and PLA2G4A expression in zebrafish (Danio rerio) ovulation","volume":"311","author":"Baker","year":"2021","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Lee, J.H., Jeon, J.H., and Lee, M.J. (2020). Docosahexaenoic Acid, a Potential Treatment for Sarcopenia, Modulates the Ubiquitin-Proteasome and the Autophagy-Lysosome Systems. Nutrients, 12.","DOI":"10.3390\/nu12092597"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6977","DOI":"10.3390\/md13116977","article-title":"Omega-3 fatty acids and skeletal muscle health","volume":"13","author":"Jeromson","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1002\/jcsm.12486","article-title":"Myopalladin promotes muscle growth through modulation of the serum response factor pathway","volume":"11","author":"Filomena","year":"2020","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e26439","DOI":"10.7554\/eLife.26439","article-title":"KLHL41 stabilizes skeletal muscle sarcomeres by nonproteolytic ubiquitination","volume":"6","author":"Cenik","year":"2017","journal-title":"eLife"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e2100230118","DOI":"10.1073\/pnas.2100230118","article-title":"MYO1F regulates antifungal immunity by regulating acetylation of microtubules","volume":"118","author":"Sun","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1101\/gad.217240.113","article-title":"The methyltransferase SMYD3 mediates the recruitment of transcriptional cofactors at the myostatin and c-Met genes and regulates skeletal muscle atrophy","volume":"27","author":"Proserpio","year":"2013","journal-title":"Genes Dev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/s41419-021-04009-8","article-title":"SMYD3 promotes hepatocellular carcinoma progression by methylating S1PR1 promoters","volume":"12","author":"Zhang","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nmeth.1322","article-title":"Universal sample preparation method for proteome analysis","volume":"6","author":"Zougman","year":"2009","journal-title":"Nat. Methods"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15690\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:37:58Z","timestamp":1760146678000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15690"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,10]]},"references-count":54,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232415690"],"URL":"https:\/\/doi.org\/10.3390\/ijms232415690","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,10]]}}}