{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T23:07:19Z","timestamp":1791068839895,"version":"4.1.0"},"reference-count":65,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T00:00:00Z","timestamp":1632960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State assignment","award":["AAAA-A18-118012290142-9"],"award-info":[{"award-number":["AAAA-A18-118012290142-9"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Serum albumin possesses esterase and pseudo-esterase activities towards a number of endogenous and exogenous substrates, but the mechanism of interaction of various esters and other compounds with albumin is still unclear. In the present study, proton nuclear magnetic resonance (1H NMR) has been applied to the study of true esterase activity of albumin, using the example of bovine serum albumin (BSA) and p-nitrophenyl acetate (NPA). The site of BSA esterase activity was then determined using molecular modelling methods. According to the data obtained, the accumulation of acetate in the presence of BSA in the reaction mixture is much more intense as compared with the spontaneous hydrolysis of NPA, which indicates true esterase activity of albumin towards NPA. Similar results were obtained for p-nitophenyl propionate (NPP) as substrate. The rate of acetate and propionate release confirms the assumption that there is a site of true esterase activity in the albumin molecule, which is different from the site of the pseudo-esterase activity Sudlow II. The results of molecular modelling of BSA and NPA interaction make it possible to postulate that Sudlow site I is the site of true esterase activity of albumin.<\/jats:p>","DOI":"10.3390\/ijms221910593","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T10:22:42Z","timestamp":1632997362000},"page":"10593","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Esterase Activity of Serum Albumin Studied by 1H NMR Spectroscopy and Molecular Modelling"],"prefix":"10.3390","volume":"22","author":[{"given":"Daria A.","family":"Belinskaia","sequence":"first","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, pr. Torez 44, 194223 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina A.","family":"Voronina","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, pr. Torez 44, 194223 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4861-5974","authenticated-orcid":false,"given":"Mikhail A.","family":"Vovk","sequence":"additional","affiliation":[{"name":"Centre for Magnetic Resonance, St. Petersburg State University, Universitetskij pr., 26, Peterhof, 198504 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir I.","family":"Shmurak","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, pr. Torez 44, 194223 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia A.","family":"Batalova","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, pr. Torez 44, 194223 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard O.","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Leicester School of Allied Health Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolay V.","family":"Goncharov","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, pr. 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Graph."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1134\/S1068162015020041","article-title":"On the enzymatic activity of albumin","volume":"41","author":"Goncharov","year":"2015","journal-title":"Russ. J. Bioorg. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"22582","DOI":"10.1074\/jbc.M802555200","article-title":"Pseudo-esterase activity of human albumin: Slow turnover on tyrosine 411 and stable acetylation of 82 residues including 59 lysines","volume":"283","author":"Lockridge","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1134\/S1068162020030036","article-title":"Theoretical and practical aspects of albumin esterase ctivity","volume":"46","author":"Belinskaia","year":"2020","journal-title":"Russ. J. Bioorg. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/0006-3002(59)90184-2","article-title":"Reaction of plasma albumin with I-naphthyl N-methylcarbamate and certain other esters","volume":"36","author":"Casida","year":"1959","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1016\/S0021-9258(19)45642-1","article-title":"The esterase activity of bovine mercaptalbumin. The reaction of the protein with p-nitrophenyl acetate","volume":"247","author":"Tildon","year":"1972","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zaidi, N., Ajmal, M.R., Rabbani, G., Ahmad, E., and Khan, R.H. (2013). A comprehensive insight into binding of hippuric acid to human serum albumin: A study to uncover its impaired elimination through hemodialysis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071422"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0378-4274(01)00543-4","article-title":"Enzymes involved in the detoxification of organophosphorus, carbamate and pyrethroid insecticides through hydrolysis","volume":"128","author":"Sogorb","year":"2002","journal-title":"Toxicol. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1021\/tx800075x","article-title":"Serum albumin is as efficient as paraxonase in the detoxication of paraoxon at toxicologically relevant concentrations","volume":"21","author":"Sogorb","year":"2008","journal-title":"Chem. Res. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.cbi.2010.03.001","article-title":"Serum albumins and detoxication of anti-cholinesterase agents","volume":"187","author":"Sogorb","year":"2010","journal-title":"Chem. Biol. Interact."},{"key":"ref_13","first-page":"13","article-title":"Investigation of soman binding with albumin by a molecular modeling method","volume":"116","author":"Belinskaya","year":"2012","journal-title":"Toksikol. Vestnik Toxicol. Bull."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1134\/S1068162014050033","article-title":"Serum albumin: Search for new sites of interaction with organophosphorus compounds by the example of soman","volume":"40","author":"Belinskaia","year":"2014","journal-title":"Russ. J. Bioorg. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1134\/S0022093017040032","article-title":"Comparative analysis of esterase and paraoxonase activities of different serum albumin species","volume":"53","author":"Goncharov","year":"2017","journal-title":"J. Evol. Biochem. Physiol."},{"key":"ref_16","unstructured":"Schanda, P. (2007). Development and Application of Fast NMR Methods for the Study of Protein Structure and Dynamics. Biol. Phys., Available online: https:\/\/tel.archives-ouvertes.fr\/tel-00181457\/document."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.sbi.2019.06.005","article-title":"Emerging solution NMR methods to illuminate the structural and dynamic properties of proteins","volume":"58","author":"Arthanari","year":"2019","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5558","DOI":"10.1021\/jo100837a","article-title":"Design, validation, and implementation of a rapid-injection NMR system","volume":"75","author":"Denmark","year":"2010","journal-title":"J. Org. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5395","DOI":"10.1021\/acs.analchem.9b00660","article-title":"Combined in-cell NMR and simulation approach to probe redox-dependent pathway control","volume":"91","author":"Jensen","year":"2019","journal-title":"Anal. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5846","DOI":"10.1039\/D0AY01736A","article-title":"Kinetic analysis of an enzymatic hydrolysis of p-nitrophenyl acetate with carboxylesterase by pressure-assisted capillary electrophoresis\/dynamic frontal analysis","volume":"12","author":"Mine","year":"2020","journal-title":"Anal. Methods"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/B978-0-08-046884-6.00414-0","article-title":"Esterases","volume":"Volume 4","author":"Lockridge","year":"2010","journal-title":"Comprehensive Toxicology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s10517-011-1457-y","article-title":"Comparative analysis of esterase activities of human, mouse, and rat blood","volume":"152","author":"Rudakova","year":"2011","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jmb.2005.07.075","article-title":"Structural basis of the drug-binding specificity of human serum albumin","volume":"353","author":"Ghuman","year":"2005","journal-title":"J. Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.jmb.2008.06.016","article-title":"Crystallographic analysis of human serum albumin complexed with 4Z,15E-bilirubin-IXalpha","volume":"381","author":"Zunszain","year":"2008","journal-title":"J. Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1006\/jmbi.2000.5208","article-title":"Crystal structures of human serum albumin complexed with monounsaturated and polyunsaturated fatty acids","volume":"314","author":"Petitpas","year":"2001","journal-title":"J. Mol. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Goncharov, N.V., Belinskaia, D.A., Shmurak, V.I., Terpilowski, M.A., Jenkins, R.O., and Avdonin, P.V. (2017). Serum albumin binding and esterase cctivity: Mechanistic interactions with organophosphates. Molecules, 22.","DOI":"10.3390\/molecules22071201"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1134\/S1068162019060086","article-title":"Effect of Cys34 oxidation state of albumin on its interaction with paraoxon according to molecular modeling data","volume":"45","author":"Belinskaia","year":"2019","journal-title":"Russ. J. Bioorg. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1023\/B:PHAM.0000016241.84630.06","article-title":"Esterase-like activity of serum albumin: Characterization of its structural chemistry using p-nitrophenyl esters as substrates","volume":"21","author":"Sakurai","year":"2004","journal-title":"Pharm. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1021\/tx300096a","article-title":"Cys34 adducts of reactive oxygen species in human serum albumin","volume":"25","author":"Grigoryan","year":"2012","journal-title":"Chem. Res. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/sj.bjp.0707251","article-title":"Physiological and pathological changes in the redox state of human serum albumin critically influence its binding properties","volume":"151","author":"Oettl","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Nagumo, K., Tanaka, M., Chuang, V.T., Setoyama, H., Watanabe, H., Yamada, N., Kubota, K., Tanaka, M., Matsushita, K., and Yoshida, A. (2014). Cys34-cysteinylated human serum albumin is a sensitive plasma marker in oxidative stress-related chronic diseases. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085216"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"320","DOI":"10.5414\/CN108040","article-title":"Close Relationship between redox Ssate of human serum albumin and serum cysteine levels in non-diabetic CKD patients with various degrees of renal function","volume":"82","author":"Suzuki","year":"2014","journal-title":"Clin. Nephrol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.3892\/etm.2017.4268","article-title":"Oxidation of human serum albumin exhibits inter-individual variability after an ultra-marathon mountain race","volume":"13","author":"Spanidis","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1097\/01.CCM.0000169876.14858.91","article-title":"Heterogeneity and oxidation status of commercial human albumin preparations in clinical use","volume":"33","author":"Rael","year":"2005","journal-title":"Crit. Care Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1248\/bpb.b15-00843","article-title":"Quantitation of oxidative modifications of commercial human albumin for clinical use","volume":"39","author":"Takahashi","year":"2016","journal-title":"Biol. Pharm. Bull."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/ams2.259","article-title":"Comparison of quality of human serum albumin preparations in two pharmaceutical products","volume":"4","author":"Nakae","year":"2017","journal-title":"Acute Med. Surg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1021\/ac9802630","article-title":"Quantitative determination of biological sulfhydryl groups by postcolumn derivatization and elucidation of microheterogeneity of serum albumins","volume":"70","author":"Yasuhara","year":"1998","journal-title":"Anal. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1023\/A:1011029226072","article-title":"Effect of oxidative stress on the structure and function of human serum albumin","volume":"18","author":"Anraku","year":"2001","journal-title":"Pharm. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1248\/bpb.b20-00205","article-title":"Effects of oxidation of human serum albumin on the binding of aripiprazole","volume":"43","author":"Sakurama","year":"2020","journal-title":"Biol. Pharm. Bull."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"E653","DOI":"10.1073\/pnas.1221050110","article-title":"Intrinsic evolutionary constraints on protease structure, enzyme acylation, and the identity of the catalytic triad","volume":"110","author":"Buller","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","unstructured":"Stryer, L., Berg, J.M., and Tymoczko, J.L. (2006). Biochemistry, W.H.Freeman & Co. [6th ed.]."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10572","DOI":"10.1021\/ja020243m","article-title":"Role of the catalytic triad and oxyanion hole in acetylcholinesterase catalysis: An ab initio QM\/MM study","volume":"124","author":"Zhang","year":"2002","journal-title":"J. Am. Chem. Soc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/BF01047105","article-title":"Acetylcholinesterase kinetics","volume":"8","author":"Hofer","year":"1981","journal-title":"Biophys. Struct. Mech."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1110\/ps.035436.108","article-title":"Unconventional serine proteases: Variations on the catalytic Ser\/His\/Asp triad configuration","volume":"17","author":"Ekici","year":"2008","journal-title":"Protein Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.bcp.2009.10.007","article-title":"Reaction of human albumin with aspirin in vitro: Mass spectrometric identification of acetylated lysines 199, 402, 519, and 545","volume":"79","author":"Liyasova","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11886","DOI":"10.1021\/jp506629y","article-title":"Elucidating the origin of the esterase activity of human serum albumin using QM\/MM calculations","volume":"118","author":"Phuangsawai","year":"2014","journal-title":"J. Phys. Chem. B"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/0161-5890(91)90093-Y","article-title":"Acetylsalicylate-human serum albumin interaction as studied by NMR spectroscopy--antigenicity-producing mechanism of acetylsalicylic acid","volume":"28","author":"Honma","year":"1991","journal-title":"Mol. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.pestbp.2019.10.004","article-title":"In vitro interaction of organophosphate metabolites with bovine serum albumin: A comparative 1H NMR, fluorescence and molecular docking analysis","volume":"163","author":"Dahiya","year":"2020","journal-title":"Pestic. Biochem. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1080\/07391102.2020.1745280","article-title":"Analyzing organophosphate pesticide-serum albumin binding interaction: A combined STD NMR and molecular docking study","volume":"39","author":"Dahiya","year":"2021","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.toxlet.2003.10.014","article-title":"Methyl parathion interaction with human and bovine serum albumin","volume":"147","author":"Silva","year":"2004","journal-title":"Toxicol. Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"126698","DOI":"10.1016\/j.chemosphere.2020.126698","article-title":"Mechanism of interactions between organophosphorus insecticides and human serum albumin: Solid-phase microextraction, thermodynamics and computational approach","volume":"253","author":"Zhao","year":"2020","journal-title":"Chemosphere"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Lyagin, I., and Efremenko, E. (2021). Enzymes, Reacting with Organophosphorus Compounds as Detoxifiers: Diversity and Functions. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041761"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1042\/bj2400933","article-title":"Nomenclature of esterases","volume":"240","author":"Pen","year":"1986","journal-title":"Biochem. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.2174\/1381612821666150302113906","article-title":"Structure and enzymatic activities of human serum albumin","volume":"21","author":"Wang","year":"2015","journal-title":"Curr. Pharm. Des."},{"key":"ref_55","unstructured":"(2021, September 22). 4-Nitrophenol. Available online: http:\/\/www.biosite.dk\/leksikon\/4-nitrophenol.htm."},{"key":"ref_56","first-page":"1010","article-title":"HyperChem: A software package for computational chemistry and molecular modeling","volume":"14","author":"Froimowitz","year":"1993","journal-title":"Biotechniques"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/prot.22879","article-title":"Automated minimization of steric clashes in protein structures","volume":"79","author":"Ramachandran","year":"2011","journal-title":"Proteins"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1\u20132","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Lyskov, S., Chou, F.C., Conch\u00fair, S.\u00d3., Der, B.S., Drew, K., Kuroda, D., Xu, J., Weitzner, B.D., Renfrew, P.D., and Sripakdeevong, P. (2013). Serverification of molecular modeling applications: The Rosetta Online Server that Includes Everyone (ROSIE). PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063906"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/978-94-015-7658-1_21","article-title":"Interaction models for water in relation to protein hydration","volume":"Volume 14","author":"Pullman","year":"1981","journal-title":"Intermolecular Forces. The Jerusalem Symposia on Quantum Chemistry and Biochemistry"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"074101","DOI":"10.1063\/1.3073889","article-title":"Isothermal-isobaric molecular dynamics using stochastic velocity rescaling","volume":"130","author":"Bussi","year":"2009","journal-title":"J. Chem. Phys."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.1063\/1.448118","article-title":"Molecular dynamics with coupling to an external bath","volume":"81","author":"Berendsen","year":"1984","journal-title":"J. Chem. Phys."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle mesh Ewald: An N\u22c5log(N) method for Ewald sums in large systems","volume":"3","author":"Darden","year":"1993","journal-title":"J. Chem. Phys."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1002\/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H","article-title":"LINCS: A linear constraint solver for molecular simulations","volume":"18","author":"Hess","year":"1997","journal-title":"J. Comp. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/19\/10593\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:07:50Z","timestamp":1760166470000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/19\/10593"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,30]]},"references-count":65,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["ijms221910593"],"URL":"https:\/\/doi.org\/10.3390\/ijms221910593","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,30]]}}}