{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T20:34:02Z","timestamp":1776976442581,"version":"3.51.4"},"reference-count":62,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T00:00:00Z","timestamp":1633996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["18K06939 (to R.K.)"],"award-info":[{"award-number":["18K06939 (to R.K.)"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["17K18065 and 20K16452 (to R.Y.)"],"award-info":[{"award-number":["17K18065 and 20K16452 (to R.Y.)"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Translocated in LipoSarcoma\/Fused in Sarcoma (TLS\/FUS) is a nuclear RNA binding protein whose mutations cause amyotrophic lateral sclerosis. TLS\/FUS undergoes LLPS and forms membraneless particles with other proteins and nucleic acids. Interaction with RNA alters conformation of TLS\/FUS, which affects binding with proteins, but the effect of m6A RNA modification on the TLS\/FUS\u2013RNA interaction remains elusive. Here, we investigated the binding specificity of TLS\/FUS to m6A RNA fragments by RNA pull down assay, and elucidated that both wild type and ALS-related TLS\/FUS mutants strongly bound to m6A modified RNAs. TLS\/FUS formed cytoplasmic foci by treating hyperosmotic stress, but the cells transfected with m6A-modified RNAs had a smaller number of foci. Moreover, m6A-modified RNA transfection resulted in the cells obtaining higher resistance to the stress. In summary, we propose TLS\/FUS as a novel candidate of m6A recognition protein, and m6A-modified RNA fragments diffuse cytoplasmic TLS\/FUS foci and thereby enhance cell viability.<\/jats:p>","DOI":"10.3390\/ijms222011014","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T06:38:41Z","timestamp":1634107121000},"page":"11014","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["m6A Modified Short RNA Fragments Inhibit Cytoplasmic TLS\/FUS Aggregation Induced by Hyperosmotic Stress"],"prefix":"10.3390","volume":"22","author":[{"given":"Ryoma","family":"Yoneda","sequence":"first","affiliation":[{"name":"Division of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi","family":"Ueda","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riki","family":"Kurokawa","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.brainres.2016.03.036","article-title":"Mechanisms of FUS mutations in familial amyotrophic lateral sclerosis","volume":"1647","author":"Shang","year":"2016","journal-title":"Brain Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.neurol.2020.06.010","article-title":"FUS mutation is probably the most common pathogenic gene for JALS, especially sporadic JALS","volume":"177","author":"Chen","year":"2021","journal-title":"Rev. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"105821","DOI":"10.1016\/j.biocel.2020.105821","article-title":"\u201cSTRESSED OUT\u201d: The role of FUS and TDP-43 in amyotrophic lateral sclerosis","volume":"126","author":"Aksoy","year":"2020","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10465","DOI":"10.1038\/ncomms10465","article-title":"ALS-associated mutant FUS induces selective motor neuron degeneration through toxic gain of function","volume":"7","author":"Sharma","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Pakravan, D., Michiels, E., Bratek-Skicki, A., De Decker, M., Van Lindt, J., Alsteens, D., Derclaye, S., Van Damme, P., Schymkowitz, J., and Rousseau, F. (2021). Liquid\u2013Liquid Phase Separation Enhances TDP-43 LCD Aggregation but Delays Seeded Aggregation. Biomolecules, 11.","DOI":"10.3390\/biom11040548"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1002\/pro.4108","article-title":"Electrostatic modulation of hnRNPA1 low-complexity domain liquid\u2013liquid phase separation and aggregation","volume":"30","author":"Tsoi","year":"2021","journal-title":"Protein Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1261\/rna.078827.121","article-title":"Fusion protein EWS-FLI1 is incorporated into a protein granule in cells","volume":"27","author":"Ahmed","year":"2021","journal-title":"RNA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.bpj.2021.02.008","article-title":"Real-time observation of structure and dynamics during the liquid-to-solid transition of FUS LC","volume":"120","author":"Berkeley","year":"2021","journal-title":"Biophys. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7115","DOI":"10.1074\/jbc.TM118.001192","article-title":"The molecular language of membraneless organelles","volume":"294","author":"Gomes","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.cell.2018.12.035","article-title":"Considerations and Challenges in Studying Liquid-Liquid Phase Separation and Biomolecular Condensates","volume":"176","author":"Alberti","year":"2019","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/s41583-020-00407-7","article-title":"The functional organization of axonal mRNA transport and translation","volume":"22","author":"Costa","year":"2021","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"118984","DOI":"10.1016\/j.bbamcr.2021.118984","article-title":"Combating deleterious phase transitions in neurodegenerative disease","volume":"1868","author":"Darling","year":"2021","journal-title":"Biochim. Biophys. Acta BBA Mol. Cell Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.brainres.2018.04.036","article-title":"The physiological and pathological biophysics of phase separation and gelation of RNA binding proteins in amyotrophic lateral sclerosis and fronto-temporal lobar degeneration","volume":"1693","author":"Lin","year":"2018","journal-title":"Brain Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.celrep.2018.06.070","article-title":"Molecular Dissection of FUS Points at Synergistic Effect of Low-Complexity Domains in Toxicity","volume":"24","author":"Bogaert","year":"2018","journal-title":"Cell Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1002\/pro.4101","article-title":"Liquid\u2013liquid phase separation of Tau by self and complex coacervation","volume":"30","author":"Najafi","year":"2021","journal-title":"Protein Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"31882","DOI":"10.1073\/pnas.2012460117","article-title":"Regulatory mechanisms of tau protein fibrillation under the conditions of liquid\u2013liquid phase separation","volume":"117","author":"Boyko","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.semcdb.2019.05.023","article-title":"Cytoplasmic functions of TDP-43 and FUS and their role in ALS","volume":"99","author":"Birsa","year":"2020","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1002\/humu.22319","article-title":"TARDBP and FUS Mutations Associated with Amyotrophic Lateral Sclerosis: Summary and Update","volume":"34","author":"Lattante","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.cell.2018.03.056","article-title":"FUS Phase Separation Is Modulated by a Molecular Chaperone and Methylation of Arginine Cation-\u03c0 Interactions","volume":"173","author":"Qamar","year":"2018","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2951","DOI":"10.15252\/embj.201696394","article-title":"Phosphorylation of the FUS low-complexity domain disrupts phase separation, aggregation, and toxicity","volume":"36","author":"Monahan","year":"2017","journal-title":"EMBO J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9523","DOI":"10.1038\/s41598-021-89075-w","article-title":"Non-coding RNA suppresses FUS aggregation caused by mechanistic shear stress on pipetting in a sequence-dependent manner","volume":"11","author":"Hamad","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2018.03.003","article-title":"Nuclear Import Receptor Inhibits Phase Separation of FUS through Binding to Multiple Sites","volume":"173","author":"Yoshizawa","year":"2018","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41594-020-0399-3","article-title":"Hsp27 chaperones FUS phase separation under the modulation of stress-induced phosphorylation","volume":"27","author":"Liu","year":"2020","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1126\/science.aar7366","article-title":"RNA buffers the phase separation behavior of prion-like RNA binding proteins","volume":"360","author":"Maharana","year":"2018","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Levone, B.R., Lenzken, S.C., Antonaci, M., Maiser, A., Rapp, A., Conte, F., Reber, S., Mechtersheimer, J., Ronchi, A.E., and M\u00fchlemann, O. (2021). FUS-dependent liquid\u2013liquid phase separation is important for DNA repair initiation. J. Cell Biol., 220.","DOI":"10.1083\/jcb.202008030"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/jnc.14481","article-title":"The m6A-epitranscriptomic signature in neurobiology: From neurodevelopment to brain plasticity","volume":"147","author":"Widagdo","year":"2018","journal-title":"J. Neurochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1007\/s13238-019-00660-2","article-title":"Binding to m6A RNA promotes YTHDF2-mediated phase separation","volume":"11","author":"Wang","year":"2020","journal-title":"Protein Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1038\/s41598-020-59496-0","article-title":"RNA sequence and length contribute to RNA-induced conformational change of TLS\/FUS","volume":"10","author":"Hamad","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13578-016-0068-8","article-title":"The binding specificity of Translocated in LipoSarcoma\/FUsed in Sarcoma with lncRNA transcribed from the promoter region of cyclin D1","volume":"6","author":"Yoneda","year":"2016","journal-title":"Cell Biosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5626","DOI":"10.1074\/jbc.RA119.011556","article-title":"Long noncoding RNA pncRNA-D reduces cyclin D1 gene expression and arrests cell cycle through RNA m6A modification","volume":"295","author":"Yoneda","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4572","DOI":"10.1038\/s41598-019-41040-4","article-title":"Increased FUS levels in astrocytes leads to astrocyte and microglia activation and neuronal death","volume":"9","author":"Onori","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1002\/jcp.24395","article-title":"FUS\/TLS assembles into stress granules and is a prosurvival factor during hyperosmolar stress","volume":"228","author":"Sama","year":"2013","journal-title":"J. Cell. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1750-1326-8-30","article-title":"Amyotrophic lateral sclerosis-linked FUS\/TLS alters stress granule assembly and dynamics","volume":"8","author":"Baron","year":"2013","journal-title":"Mol. Neurodegener."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.bbrc.2014.08.115","article-title":"Aggregation of ALS-linked FUS mutant sequesters RNA binding proteins and impairs RNA granules formation","volume":"452","author":"Takanashi","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"13416","DOI":"10.1038\/srep13416","article-title":"Distinct partitioning of ALS associated TDP-43, FUS and SOD1 mutants into cellular inclusions","volume":"5","author":"Farrawell","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"35195","DOI":"10.1038\/srep35195","article-title":"FUS interacts with nuclear matrix-associated protein SAFB1 as well as Matrin3 to regulate splicing and ligand-mediated transcription","volume":"6","author":"Yamaguchi","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1038\/emboj.2010.143","article-title":"ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import","volume":"29","author":"Dormann","year":"2010","journal-title":"EMBO J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1038\/nsmb.2163","article-title":"RNA targets of wild-type and mutant FET family proteins","volume":"18","author":"Hoell","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7713","DOI":"10.1093\/nar\/gkab582","article-title":"The phase separation-dependent FUS interactome reveals nuclear and cytoplasmic function of liquid\u2013liquid phase separation","volume":"49","author":"Reber","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1038\/cr.2014.152","article-title":"Crystal structure of the YTH domain of YTHDF2 reveals mechanism for recognition of N6-methyladenosine","volume":"24","author":"Zhu","year":"2014","journal-title":"Cell Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41419-021-03625-8","article-title":"Linking the YTH domain to cancer: The importance of YTH family proteins in epigenetics","volume":"12","author":"Shi","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Hazra, D., Chapat, C., and Graille, M. (2019). m6A mRNA Destiny: Chained to the rhYTHm by the YTH-Containing Proteins. Genes, 10.","DOI":"10.3390\/genes10010049"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1038\/s41422-019-0210-3","article-title":"Multivalent m6A motifs promote phase separation of YTHDF proteins","volume":"29","author":"Gao","year":"2019","journal-title":"Cell Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1111\/jcmm.14847","article-title":"m 6 A facilitates YTHDF-independent phase separation","volume":"24","author":"Liu","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"9134","DOI":"10.1039\/D0CC03776A","article-title":"Direct visualization of the conformational change of FUS\/TLS upon binding to promoter-associated non-coding RNA","volume":"56","author":"Hamad","year":"2020","journal-title":"Chem. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1038\/nn.3688","article-title":"Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis","volume":"17","author":"Johnson","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2005.e1","DOI":"10.1016\/j.neurobiolaging.2015.02.008","article-title":"Mutational analysis of MATR3 in Taiwanese patients with amyotrophic lateral sclerosis","volume":"36","author":"Lin","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.ajpath.2017.10.007","article-title":"Matrin 3 Is a Component of Neuronal Cytoplasmic Inclusions of Motor Neurons in Sporadic Amyotrophic Lateral Sclerosis","volume":"188","author":"Tada","year":"2018","journal-title":"Am. J. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/srep00603","article-title":"Widespread binding of FUS along nascent RNA regulates alternative splicing in the brain","volume":"2","author":"Rogelj","year":"2012","journal-title":"Sci. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1126\/science.1154584","article-title":"TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis","volume":"319","author":"Sreedharan","year":"2008","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/j.bbapap.2007.07.015","article-title":"The nuclear PP1 interacting protein ZAP3 (ZAP) is a putative nucleoside kinase that complexes with SAM68, CIA, NF110\/45, and HNRNP-G","volume":"1774","author":"Chaulk","year":"2007","journal-title":"Biochim. Biophys. Acta BBA Proteins Proteom."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1091\/mbc.e14-05-1007","article-title":"FUS is sequestered in nuclear aggregates in ALS patient fibroblasts","volume":"25","author":"Schwartz","year":"2014","journal-title":"Mol. Biol. Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"263","DOI":"10.3389\/fnmol.2017.00263","article-title":"Autophagy Dysregulation in ALS: When Protein Aggregates Get Out of Hand","volume":"10","author":"Ramesh","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Kroschwald, S., Maharana, S., and Simon, A. (2017). Hexanediol: A chemical probe to investigate the material properties of membrane-less compartments. Matters, 3.","DOI":"10.19185\/matters.201702000010"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"89","DOI":"10.11648\/j.bs.20200604.13","article-title":"Potential Inhibitor Against Phase Separation, 1,6-hexanediol Specifically Binds to Beta Actin in Nuclear Extract of Human Cell Line","volume":"6","author":"Ueda","year":"2020","journal-title":"Biomed. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"100260","DOI":"10.1016\/j.jbc.2021.100260","article-title":"1,6-Hexanediol, commonly used to dissolve liquid\u2013liquid phase separated condensates, directly impairs kinase and phosphatase activities","volume":"296","author":"Kaltheuner","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e202001005","DOI":"10.26508\/lsa.202001005","article-title":"1,6-hexanediol rapidly immobilizes and condenses chromatin in living human cells","volume":"4","author":"Itoh","year":"2021","journal-title":"Life Sci. Alliance"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.addr.2015.05.012","article-title":"Basic biology and therapeutic implications of lncRNA","volume":"87","author":"Khorkova","year":"2015","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1080\/17460441.2018.1501024","article-title":"Developments in lncRNA drug discovery: Where are we heading?","volume":"13","author":"Blokhin","year":"2018","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1002\/hep.28393","article-title":"Systemic genome screening identifies the outcome associated focal loss of long noncoding RNA PRAL in hepatocellular carcinoma","volume":"63","author":"Zhou","year":"2016","journal-title":"Hepatology"},{"key":"ref_61","first-page":"707","article-title":"Oligonucleotide therapeutics in neurodegenerative diseases","volume":"15","author":"Scoles","year":"2018","journal-title":"RNA Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"10937","DOI":"10.1074\/jbc.RA117.000598","article-title":"Arginine methylation of translocated in liposarcoma (TLS) inhibits its binding to long noncoding RNA, abrogating TLS-mediated repression of CBP\/p300 activity","volume":"293","author":"Cui","year":"2018","journal-title":"J. Biol. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/20\/11014\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:12:18Z","timestamp":1760166738000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/20\/11014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,12]]},"references-count":62,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["ijms222011014"],"URL":"https:\/\/doi.org\/10.3390\/ijms222011014","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,12]]}}}