{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T23:49:16Z","timestamp":1762300156029,"version":"3.41.2"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Schistosomes undergo complicated migration in final hosts during infection, associated with differential immune responses. It has been shown that CD4<jats:sup>+<\/jats:sup> T cells play critical roles in response to <jats:italic>Schistosoma<\/jats:italic> infections and accumulated documents have indicated that miRNAs tightly regulate T cell activity. However, miRNA profiles in host T cells associated with <jats:italic>Schistosoma<\/jats:italic> infection remain poorly characterized. Therefore, we undertook the study and systematically characterized T cell miRNA profiles from the livers and blood of <jats:italic>S. japonicum<\/jats:italic> infected C57BL\/6J mice at 14- and 21-days post-infection. We observed 508 and 504 miRNAs, in which 264 miRNAs were co-detected in T cells isolated from blood and livers, respectively. The comparative analysis of T cell miRNAs from uninfected and infected C57BL\/6J mice blood showed that <jats:italic>miR-486b-5p\/3p<\/jats:italic> expression was significantly downregulated and linked to various T cell immune responses and <jats:italic>miR-375-5p<\/jats:italic> was highly upregulated, associated with Wnt signaling and pluripotency, Delta notch signaling pathways, <jats:italic>etc.<\/jats:italic> Whereas hepatic T cells showed <jats:italic>miR-466b-3p<\/jats:italic>, <jats:italic>miR-486b-3p<\/jats:italic>, <jats:italic>miR-1969<\/jats:italic>, and <jats:italic>miR-375<\/jats:italic> were differentially expressed compared to the uninfected control. The different expressions of some miRNAs were further corroborated in isolated T cells from mice and <jats:italic>in vitro<\/jats:italic> cultured EL-4 cells treated with <jats:italic>S. japonicum<\/jats:italic> worm antigens by RT-qPCR and similar results were found. In addition, bioinformatics analysis combined with RT-qPCR validation of selected targets associated with the immune system and parasite-caused infectious disease showed a significant increase in the expression of <jats:italic>Ctla4<\/jats:italic>, <jats:italic>Atg5<\/jats:italic>, <jats:italic>Hgf<\/jats:italic>, <jats:italic>Vcl<\/jats:italic> and <jats:italic>Arpc4<\/jats:italic> and a decreased expression of <jats:italic>Fermt3<\/jats:italic>, <jats:italic>Pik3r1<\/jats:italic>, <jats:italic>Myd88<\/jats:italic>, <jats:italic>Nfkbie<\/jats:italic>, <jats:italic>Ppp1r12a<\/jats:italic>, <jats:italic>Ppp3r1<\/jats:italic>, <jats:italic>Nfyb<\/jats:italic>, <jats:italic>Atg12<\/jats:italic>, <jats:italic>Ube2n<\/jats:italic>, <jats:italic>Tyrobp<\/jats:italic>, <jats:italic>Cxcr4<\/jats:italic> and <jats:italic>Tollip<\/jats:italic>. Overall, these results unveil the comprehensive repertoire of T cell miRNAs during <jats:italic>S. japonicum<\/jats:italic> infection, suggesting that the circulatory (blood) and liver systems have distinct miRNAs landscapes that may be important for regulating T cell immune response. Altogether, our findings indicated a dynamic expression pattern of T cell miRNAs during the hepatic stages of <jats:italic>S. japonicum<\/jats:italic> infection.<\/jats:p>","DOI":"10.3389\/fimmu.2022.911139","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T07:37:01Z","timestamp":1662104221000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Dynamic miRNA profile of host T cells during early hepatic stages of Schistosoma japonicum infection"],"prefix":"10.3389","volume":"13","author":[{"given":"Bikash R.","family":"Giri","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuantao","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Y.","family":"Pakharukova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guofeng","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182000000743","article-title":"Migration of the schistosomula of Schistosoma mansoni from the lungs to the hepatic portal system","volume":"80","author":"Miller","year":"1980","journal-title":"Parasitology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e0007951","DOI":"10.1371\/journal.pntd.0007951","article-title":"Schistosome migration in the definitive host","volume":"14","author":"Nation","year":"2020","journal-title":"PloS Negl Trop Dis"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182007002971","article-title":"The schistosome in the mammalian host: Understanding the mechanisms of adaptation","volume":"134","author":"Kusel","year":"2007","journal-title":"Parasitology"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.624178","article-title":"Immune evasion strategies of schistosomes","volume":"11","author":"Hambrook","year":"2021","journal-title":"Front Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nri2858","article-title":"Antigen-presenting cell function in the tolerogenic liver environment","volume":"10","author":"Thomson","year":"2010","journal-title":"Nat Rev Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27254","article-title":"Immune tolerance in liver disease","volume":"60","author":"Crispe","year":"2014","journal-title":"Hepatology"},{"key":"B7","article-title":"Biology of schistosoma japonicum. from cercaria penetrating into host skin to producing egg","volume":"106","author":"He","year":"1993","journal-title":"Chin Med J (Engl)"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/pim.12087","article-title":"Immunology of human schistosomiasis","volume":"36","author":"Colley","year":"2014","journal-title":"Parasit Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1128\/iai.54.3.820-826.1986","article-title":"Anti-L3T4 antibody treatment suppresses hepatic granuloma formation and abrogates antigen-induced interleukin-2 production in Schistosoma mansoni infection","volume":"54","author":"Mathew","year":"1986","journal-title":"Infect Immun"},{"key":"B10","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1086\/324668","article-title":"Clinical and immunologic evaluation of 31 patients with acute schistosomiasis mansoni","volume":"185","author":"de Jesus","year":"2002","journal-title":"J Infect Dis"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199804)28:04<1408::AID-IMMU1408>3.0.CO;2-H","article-title":"Type 1 and type 2 cytokine-producing mouse CD4+ and CD8+ T cells in acute Schistosoma mansoni infection","volume":"28","author":"Fallon","year":"1998","journal-title":"Eur J Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-012-0354-4","article-title":"Th2 responses in schistosomiasis","volume":"34","author":"Fairfax","year":"2012","journal-title":"Semin Immunopathol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2014.06.003","article-title":"Host protective roles of type 2 immunity: Parasite killing and tissue repair, flip sides of the same coin","volume":"26","author":"Allen","year":"2014","journal-title":"Semin Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.6.3920","article-title":"Severe CD4 T cell-mediated immunopathology in murine schistosomiasis is dependent on IL-12p40 and correlates with high levels of IL-17","volume":"175","author":"Rutitzky","year":"2005","journal-title":"J Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.5.3157","article-title":"The pathogenesis of schistosomiasis is controlled by cooperating IL-10-Producing innate effector and regulatory T cells","volume":"172","author":"Hesse","year":"2004","journal-title":"J Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.10.5839","article-title":"Regulatory T cell responses develop in parallel to Th responses and control the magnitude and phenotype of the Th effector populatio","volume":"176","author":"Taylor","year":"2006","journal-title":"J Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004097","article-title":"Follicular helper T cells promote liver pathology in mice during Schistosoma japonicum infection","volume":"10","author":"Chen","year":"2014","journal-title":"PloS Pathog"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-017-16783-7","article-title":"Up-regulation of interleukin-21 contributes to liver pathology of schistosomiasis by driving GC immune responses and activating HSCs in mice","volume":"7","author":"Wang","year":"2017","journal-title":"Sci Rep"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00061","article-title":"T Lymphocyte-mediated liver immunopathology of schistosomiasis","volume":"11","author":"Zheng","year":"2020","journal-title":"Front Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: Genomics, biogenesis, mechanism, and function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067037","article-title":"MicroRNA-gene expression network in murine liver during Schistosoma japonicum infection","volume":"8","author":"Cai","year":"2013","journal-title":"PloS One"},{"key":"B22","doi-asserted-by":"publisher","first-page":"3554","DOI":"10.3390\/ijms22073554","article-title":"MicroRNA interference in hepatic host-pathogen interactions","volume":"22","author":"Morishita","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevImmunol.2013006858","article-title":"MicroRNA regulation of T-lymphocyte immunity: Modulation of molecular networks responsible for T-cell activation, differentiation, and development","volume":"33","author":"Podshivalova","year":"2013","journal-title":"Critic Rev Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/med.21539","article-title":"Roles of microRNAs in T cell immunity: Implications forStrategy development against infectious diseases","volume":"39","author":"Giri","year":"2019","journal-title":"Med Res Rev"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050572","article-title":"T Cell lineage choice and differentiation in the absence of the RNase III enzyme dicer","volume":"201","author":"Cobb","year":"2005","journal-title":"J Exp Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050678","article-title":"Aberrant T cell differentiation in the absence of dicer","volume":"202","author":"Muljo","year":"2005","journal-title":"J Exp Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1953310","article-title":"Canonical and alternate functions of the microrna biogenesis machinery","volume":"24","author":"Chong","year":"2010","journal-title":"Gene Dev"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2010.49","article-title":"Loss of microRNAs in thymus perturbs invariant NKT cell development and function","volume":"7","author":"Seo","year":"2010","journal-title":"Cell Mol Immunol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-018-05196-3","article-title":"Differential cell-intrinsic regulations of germinal center b and T cells by miR-146a and miR-146b","volume":"9","author":"Cho","year":"2018","journal-title":"Nat Commun"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2020.05.003","article-title":"miR-155 indicates the fate of CD4+ T cells","volume":"224","author":"Chen","year":"2020","journal-title":"Immunol Lett"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103175","article-title":"Dynamic microRNA gene transcription and processing during T cell development","volume":"188","author":"Kirigin","year":"2012","journal-title":"J Immunol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"R25","DOI":"10.1186\/gb-2009-10-3-r25","article-title":"Ultrafast and memory-efficient alignment of short DNA sequences to the human genome","volume":"10","author":"Langmead","year":"2009","journal-title":"Genome Biol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt509","article-title":"Infernal 1.1: 100-fold faster RNA homology searches","volume":"29","author":"Nawrocki","year":"2013","journal-title":"Bioinformatics"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1394","article-title":"Discovering microRNAs from deep sequencing data using miRDeep","volume":"26","author":"Friedl\u00e4nder","year":"2008","journal-title":"Nat Biotechnol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1778","article-title":"Counting absolute numbers of molecules using unique molecular identifiers","volume":"9","author":"Kivioja","year":"2011","journal-title":"Nat Methods"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp612","article-title":"DEGseq: an r package for identifying differentially expressed genes from RNA-seq data","volume":"26","author":"Wang","year":"2010","journal-title":"Bioinformatics"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl243","article-title":"RNAhybrid: microRNA target prediction easy, fast and flexible","volume":"34","author":"Kr\u00fcger","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"B38","doi-asserted-by":"publisher","first-page":"R1","DOI":"10.1186\/gb-2003-5-1-r1","article-title":"MicroRNA targets in Drosophila","volume":"5","author":"Enright","year":"2003","journal-title":"Genome Biol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"e05005","DOI":"10.7554\/eLife.05005","article-title":"Predicting effective microRNA target sites in mammalian mRNAs","volume":"4","author":"Agarwal","year":"2015","journal-title":"Elife"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/75556","article-title":"Gene ontology: Tool for the unification of biology. the gene ontology consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat Genet"},{"key":"B41","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"B42","article-title":"The bonferonni and \u0160id\u00e1k corrections for multiple comparisons","volume":"3","author":"Abdi","year":"2007","journal-title":"Encyclopedia measurement Stat"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative CT method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat Protoc"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab297","article-title":"miRTargetLink 2.0\u2013interactive miRNA target gene and target pathway networks","volume":"49","author":"Kern","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"B45","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1111\/imr.12061","article-title":"Micro RNA regulation of T-cell differentiation and function","volume":"253","author":"Jeker","year":"2013","journal-title":"Immunol Rev"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201947882","article-title":"Schistosomal extracellular vesicle-enclosed mirRNAs modulate host T helper cell differentiation","volume":"21","author":"Meningher","year":"2020","journal-title":"EMBO Rep"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02737","article-title":"CTLA-4 and PD-1 control of T-cell motility and migration: Implications for tumor immunotherapy","volume":"9","author":"Brunner-Weinzierl","year":"2018","journal-title":"Front Immunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1126\/science.1131078","article-title":"Reversal of the TCR stop signal by CTLA-4","volume":"313","author":"Schneider","year":"2006","journal-title":"Science"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02334","article-title":"Exploring the role of autophagy-related gene 5 (ATG5) yields important insights into autophagy in Autoimmune\/Autoinflammatory diseases","volume":"9","author":"Ye","year":"2018","journal-title":"Front Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.15.7144","article-title":"Hepatocyte growth factor and macrophage inflammatory protein 1 beta: Structurally distinct cytokines that induce rapid cytoskeletal changes and subset-preferential migration in T cells","volume":"91","author":"Adams","year":"1994","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10358","article-title":"HGF\/SF-met signaling in the control of branching morphogenesis and invasion","volume":"88","author":"Zhang","year":"2003","journal-title":"J Cell Biochem"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.6181","article-title":"The interaction of Arp2\/3 complex with actin: Nucleation, high affinity pointed end capping, and formation of branching networks of filaments","volume":"95","author":"Mullins","year":"1998","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B53","doi-asserted-by":"publisher","first-page":"8952","DOI":"10.1038\/s41598-017-08357-4","article-title":"Arp2\/3 complex controls T cell homeostasis by maintaining surface TCR levels Via regulating TCR+ endosome trafficking","volume":"7","author":"Zhang","year":"2017","journal-title":"Sci Rep"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.04.040","article-title":"A mammalian microRNA expression atlas based on small RNA library sequencing","volume":"129","author":"Landgraf","year":"2007","journal-title":"Cell"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.05.009","article-title":"Regulation of microRNA expression and abundance during lymphopoiesis","volume":"32","author":"Kuchen","year":"2010","journal-title":"Immunity"},{"key":"B56","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1038\/ni.2057","article-title":"Distinct microRNA signatures in human lymphocyte subsets and enforcement of the naive state in CD4+ T cells by the microRNA miR-125b","volume":"12","author":"Rossi","year":"2011","journal-title":"Nat Immunol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"dev190520","DOI":"10.1242\/dev.190520","article-title":"MicroRNA profiling of mouse cortical progenitors and neurons reveals mir-486-5p as a regulator of neurogenesis","volume":"147","author":"Dori","year":"2020","journal-title":"Development"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-13-240","article-title":"Pim-1 kinase is a target of miR-486-5p and eukaryotic translation initiation factor 4E, and plays a critical role in lung cancer","volume":"13","author":"Pang","year":"2014","journal-title":"Mol Cancer"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1007\/s13402-014-0176-6","article-title":"Differential expression of miR-139, miR-486 and miR-21 in breast cancer patients sub-classified according to lymph node status","volume":"37","author":"Rask","year":"2014","journal-title":"Cell Oncol (Dordr)"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2020.11289","article-title":"Downregulation of miR\u2212486\u22125p alleviates LPS\u2212Induced inflammatory injury, oxidative stress and apoptosis in chondrogenic cell ATDC5 by targeting NRF1","volume":"22","author":"Chang","year":"2020","journal-title":"Mol Med Rep"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.781815","article-title":"miR-223: An immune regulator in infectious disorders","volume":"12","author":"Yuan","year":"2021","journal-title":"Front Immunol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1089\/gtmb.2015.0090","article-title":"MicroRNA-223 is upregulated in active tuberculosis patients and inhibits apoptosis of macrophages by targeting FOXO3","volume":"19","author":"Xi","year":"2015","journal-title":"Genet Test Mol Biomarkers"},{"key":"B63","doi-asserted-by":"publisher","first-page":"17691","DOI":"10.1038\/s41598-020-74965-2","article-title":"The protective role of mir-223 in sepsis-induced mortality","volume":"10","author":"Liu","year":"2020","journal-title":"Sci Rep"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.41159","article-title":"MicroRNA-122 supports robust innate immunity in hepatocytes by targeting the RTKs\/STAT3 signaling pathway","volume":"8","author":"Xu","year":"2019","journal-title":"Elife"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201011099","article-title":"miR669a and miR669q prevent skeletal muscle differentiation in postnatal cardiac progenitors","volume":"193","author":"Crippa","year":"2011","journal-title":"J Cell Biol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.911139\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T07:37:14Z","timestamp":1662104234000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.911139\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,2]]},"references-count":65,"alternative-id":["10.3389\/fimmu.2022.911139"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.911139","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2022,9,2]]},"article-number":"911139"}}