{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:48:31Z","timestamp":1791557311802,"version":"4.3.4"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T00:00:00Z","timestamp":1653609600000},"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><jats:italic>Cryptococcus neoformans<\/jats:italic>infection in the central nervous system is a severe infectious disease with poor outcomes and high mortality. It has been estimated that there are 220,000 new cases each year. Over 90% of<jats:italic>C. neoformans<\/jats:italic>meningitis cases were diagnosed in AIDS patients with CD4<jats:sup>+<\/jats:sup>T cell count &amp;lt;100 cells\/\u03bcl; however, the mechanism of cryptococcal meningitis in patients with normal immune functions remains unclear. IL-17 is a pro-inflammatory cytokine and plays an important role in anti-fungal immunity. Here we report that significantly high levels of IL-17 were predominantly detected in the cerebrospinal fluid of patients with either AIDS- or non-AIDS-associated<jats:italic>C. neoformans<\/jats:italic>meningitis but not in patients with tuberculous meningitis or non-neurosyphilis. Antifungal therapy minimized the IL-17 level in the cerebrospinal fluid. An<jats:italic>in vitro<\/jats:italic>mechanistic study showed that<jats:italic>C. neoformans<\/jats:italic>stimulation of healthy peripheral blood mononuclear cells prompted IL-17 production, and CD4<jats:sup>+<\/jats:sup>T cells were the predominant IL-17-producing cells. IL-17 production by<jats:italic>C. neoformans<\/jats:italic>stimulation was STAT3 signaling dependent. Inhibition of STAT3 phosphorylation attenuated the<jats:italic>C. neoformans<\/jats:italic>-mediated IL-17 expression. Our data highlighted the significance of CD4<jats:sup>+<\/jats:sup>T cells in antifungal immunity and suggested IL-17 as a diagnostic biomarker of<jats:italic>C. neoformans<\/jats:italic>infection and STAT3 as a checkpoint for antifungal targeted therapies.<\/jats:p>","DOI":"10.3389\/fimmu.2022.872286","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T06:27:40Z","timestamp":1654064860000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Cryptococcus neoformans Infection Induces IL-17 Production by Promoting STAT3 Phosphorylation in CD4+ T Cells"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiaoman","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinru","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bintao","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoliang","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongling","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tie Fu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Ling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/17.5.837","article-title":"Cryptococcal Meningitis and AIDS","volume":"17","author":"Powderly","year":"1993","journal-title":"Clin Infect Diseases: An Off Publ Infect Dis Soc America"},{"key":"B2","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1093\/ije\/27.4.698","article-title":"Causes of Death in a Rural, Population-Based Human Immunodeficiency Virus Type 1 (HIV-1) Natural History Cohort in Uganda","volume":"27","author":"Okongo","year":"1998","journal-title":"Int J Epidemiol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/s1473-3099(17)30243-8","article-title":"Global Burden of Disease of HIV-Associated Cryptococcal Meningitis: An Updated Analysis","volume":"17","author":"Rajasingham","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.8.5367","article-title":"IL-13 Induces Disease-Promoting Type 2 Cytokines, Alternatively Activated Macrophages and Allergic Inflammation During Pulmonary Infection of Mice With Cryptococcus Neoformans","volume":"179","author":"M\u00fcller","year":"2007","journal-title":"J Immunol (Baltimore Md.: 1950)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00274-06","article-title":"Protection Against Cryptococcosis by Using a Murine Gamma Interferon-Producing Cryptococcus Neoformans Strain","volume":"75","author":"Wormley","year":"2007","journal-title":"Infection Immun"},{"key":"B6","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1097\/qad.0000000000000904","article-title":"Interleukin-17 Mediated Differences in the Pathogenesis of HIV-1-Associated Tuberculous and Cryptococcal Meningitis","volume":"30","author":"Marais","year":"2016","journal-title":"AIDS (Lond Engl)"},{"key":"B7","doi-asserted-by":"crossref","first-page":"494","DOI":"10.4049\/jimmunol.162.1.494","article-title":"IL-17 is Produced by Nickel-Specific T Lymphocytes and Regulates ICAM-1 Expression and Chemokine Production in Human Keratinocytes: Synergistic or Antagonist Effects With IFN-Gamma and TNF-Alpha","volume":"162","author":"Albanesi","year":"1999","journal-title":"J Immunol (Baltimore Md.: 1950)"},{"key":"B8","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.162.1.577","article-title":"Evidence for a Role of IL-17 in Organ Allograft Rejection: IL-17 Promotes the Functional Differentiation of Dendritic Cell Progenitors","volume":"162","author":"Antonysamy","year":"1999","journal-title":"J Immunol (Baltimore Md.: 1950)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.11.6107","article-title":"Microbial Lipopeptides Induce the Production of IL-17 in Th Cells","volume":"165","author":"Infante-Duarte","year":"2000","journal-title":"J Immunol (Baltimore Md.: 1950)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500909","article-title":"IL-17-Mediated Immunity to the Opportunistic Fungal Pathogen Candida Albicans","volume":"195","author":"Conti","year":"2015","journal-title":"J Immunol (Baltimore Md.: 1950)"},{"key":"B11","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.semcdb.2018.01.008","article-title":"Organ-Specific Mechanisms Linking Innate and Adaptive Antifungal Immunity","volume":"89","author":"Drummond","year":"2019","journal-title":"Semin Cell Dev Biol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.4A1015-483R","article-title":"JAK\/STAT Regulation of Aspergillus Fumigatus Corneal Infections and IL-6\/23-Stimulated Neutrophil, IL-17, Elastase, and MMP9 Activity","volume":"100","author":"Taylor","year":"2016","journal-title":"J leukocyte Biol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2010.00951.x","article-title":"Peripheral CD4+ T-Cell Differentiation Regulated by Networks of Cytokines and Transcription Factors","volume":"238","author":"Zhu","year":"2010","journal-title":"Immunol Rev"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.17797","article-title":"An Herbal Formula Attenuates Collagen-Induced Arthritis via Inhibition of JAK2-STAT3 Signaling and Regulation of Th17 Cells in Mice","volume":"8","author":"Wu","year":"2017","journal-title":"Oncotarget"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/nature06764","article-title":"Impaired T(H)17 Cell Differentiation in Subjects With Autosomal Dominant Hyper-IgE Syndrome","volume":"452","author":"Milner","year":"2008","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.02.013","article-title":"Prostaglandin E2 Suppresses Antifungal Immunity by Inhibiting Interferon Regulatory Factor 4 Function and Interleukin-17 Expression in T Cells","volume":"36","author":"Valdez","year":"2012","journal-title":"Immunity"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nrm909","article-title":"Stats: Transcriptional Control and Biological Impact","volume":"3","author":"Levy","year":"2002","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/0092-8674(94)90235-6","article-title":"Molecular Cloning of APRF, a Novel IFN-Stimulated Gene Factor 3 P91-Related Transcription Factor Involved in the Gp130-Mediated Signaling Pathway","volume":"77","author":"Akira","year":"1994","journal-title":"Cell"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.21.19.6615-6625.2001","article-title":"Tissue-Specific Autoregulation of the Stat3 Gene and its Role in Interleukin-6-Induced Survival Signals in T Cells","volume":"21","author":"Narimatsu","year":"2001","journal-title":"Mol Cell Biol"},{"key":"B20","doi-asserted-by":"crossref","DOI":"10.1158\/0008-5472.939.65.3","article-title":"Novel Roles of Unphosphorylated STAT3 in Oncogenesis and Transcriptional Regulation","volume":"65","author":"Yang","year":"2005","journal-title":"Cancer Res"},{"key":"B21","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1086\/649858","article-title":"Clinical Practice Guidelines for the Management of Cryptococcal Disease: 2010 Update by the Infectious Diseases Society of America","volume":"50","author":"Perfect","year":"2010","journal-title":"Clin Infect diseases: an Off Publ Infect Dis Soc Am"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ011","article-title":"Adult Bacterial Meningitis: Earlier Treatment and Improved Outcome Following Guideline Revision Promoting Prompt Lumbar Puncture","volume":"60","author":"Glim\u00e5ker","year":"2015","journal-title":"Clin Infect Diseases: An Off Publ Infect Dis Soc Am"},{"key":"B23","article-title":"Clinical Presentations and Outcomes of Penicillium Marneffei Infections: A Series From 1994 to 2004","volume":"14","author":"Wu","year":"2008","journal-title":"Hong Kong Med J = Xianggang yi xue za zhi"},{"key":"B24","first-page":"798","article-title":"Pathology of Penicillium Marneffei. An Emerging Acquired Immunodeficiency Syndrome-Related Pathogen","volume":"121","author":"Cooper","year":"1997","journal-title":"Arch Pathol Lab Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-017-0601-0","article-title":"Epidemiology of Fungal Infections in China","volume":"12","author":"Chen","year":"2018","journal-title":"Front Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/s11046-011-9471-1","article-title":"Cryptococcosis in China (1985-2010): Review of Cases From Chinese Database","volume":"173","author":"Yuchong","year":"2012","journal-title":"Mycopathologia"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838535","article-title":"Induction, Function and Regulation of IL-17-Producing T Cells","volume":"38","author":"Mills","year":"2008","journal-title":"Eur J Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00929-09","article-title":"Precarious Balance: Th17 Cells in Host Defense","volume":"78","author":"Peck","year":"2010","journal-title":"Infection Immun"},{"key":"B29","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.144.4.1472","article-title":"Depletion of CD4+ (L3T4+) Lymphocytes In Vivo Impairs Murine Host Defense to Cryptococcus Neoformans","volume":"144","author":"Mody","year":"1990","journal-title":"J Immunol (Baltimore Md.: 1950)"},{"key":"B30","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.152.5.2344","article-title":"CD4+ T Cell-Dependent Acquired State of Immunity That Protects the Brain Against Cryptococcus Neoformans","volume":"152","author":"Hill","year":"1994","journal-title":"J Immunol (Baltimore Md.: 1950)"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1128\/iai.68.2.456-462.2000","article-title":"Requirement for CD4(+) T Lymphocytes in Host Resistance Against Cryptococcus Neoformans in the Central Nervous System of Immunized Mice","volume":"68","author":"Buchanan","year":"2000","journal-title":"Infection Immun"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3282a4a64d","article-title":"HIV-Associated Cryptococcal Meningitis","volume":"21","author":"Jarvis","year":"2007","journal-title":"AIDS (Lond Engl)"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy602","article-title":"HIV-Associated Cryptococcal Meningitis Occurring at Relatively Higher CD4 Counts","volume":"219","author":"Tugume","year":"2019","journal-title":"J Infect Dis"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2012.00291","article-title":"Vaccine and Immunotherapeutic Approaches for the Prevention of Cryptococcosis: Lessons Learned From Animal Models","volume":"3","author":"Hole","year":"2012","journal-title":"Front Microbiol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830220617","article-title":"Cytokine Enhancement of Complement-Dependent Phagocytosis by Macrophages: Synergy of Tumor Necrosis Factor-Alpha and Granulocyte-Macrophage Colony-Stimulating Factor for Phagocytosis of Cryptococcus Neoformans","volume":"22","author":"Collins","year":"1992","journal-title":"Eur J Immunol"},{"key":"B36","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.142.9.3219","article-title":"Fungicidal Activity of IFN-Gamma-Activated Macrophages. Extracellular Killing of Cryptococcus Neoformans","volume":"142","author":"Flesch","year":"1989","journal-title":"J Immunol (Baltimore Md.: 1950)"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.7.3419","article-title":"Antibody Efficacy in Murine Pulmonary Cryptococcus Neoformans Infection: A Role for Nitric Oxide","volume":"168","author":"Rivera","year":"2002","journal-title":"J Immunol (Baltimore Md.: 1950)"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e6854","DOI":"10.1371\/journal.pone.0006854","article-title":"Insights Into the Mechanisms of Protective Immunity Against Cryptococcus Neoformans Infection Using a Mouse Model of Pulmonary Cryptococcosis","volume":"4","author":"Wozniak","year":"2009","journal-title":"PLoS One"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmii.2018.08.019","article-title":"Cytokine Profiles in Cerebrospinal Fluid of Patients With Meningitis at a Tertiary General Hospital in China","volume":"53","author":"Liu","year":"2020","journal-title":"J Microbiology Immunology Infection = Wei mian yu gan ran za zhi"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.070004","article-title":"Molecular Interactions Between T Cells and Fibroblast-Like Synoviocytes: Role of Membrane Tumor Necrosis Factor-Alpha on Cytokine-Activated T Cells","volume":"171","author":"Tran","year":"2007","journal-title":"Am J Pathol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1002\/art.20106","article-title":"Effector Function of Type II Collagen-Stimulated T Cells From Rheumatoid Arthritis Patients: Cross-Talk Between T Cells and Synovial Fibroblasts","volume":"50","author":"Cho","year":"2004","journal-title":"Arthritis Rheumatism"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.2.1463","article-title":"IL-15 and the Initiation of Cell Contact-Dependent Synovial Fibroblast-T Lymphocyte Cross-Talk in Rheumatoid Arthritis: Effect of Methotrexate","volume":"173","author":"Miranda-Car\u00fas","year":"2004","journal-title":"J Immunol (Baltimore Md.: 1950)"},{"key":"B43","doi-asserted-by":"publisher","first-page":"rs10","DOI":"10.1126\/scisignal.2003203","article-title":"Elucidating Human Phosphatase-Substrate Networks","volume":"6","author":"Li","year":"2013","journal-title":"Sci Signaling"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/nrc780","article-title":"NF-kappaB in Cancer: From Innocent Bystander to Major Culprit","volume":"2","author":"Karin","year":"2002","journal-title":"Nat Rev Cancer"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090207","article-title":"IL-17 can Promote Tumor Growth Through an IL-6-Stat3 Signaling Pathway","volume":"206","author":"Wang","year":"2009","journal-title":"J Exp Med"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C600321200","article-title":"STAT3 Regulates Cytokine-Mediated Generation of Inflammatory Helper T Cells","volume":"282","author":"Yang","year":"2007","journal-title":"J Biol Chem"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.8.4901","article-title":"Stat3 and Stat4 Direct Development of IL-17-Secreting Th Cells","volume":"178","author":"Mathur","year":"2007","journal-title":"J Immunol (Baltimore Md.: 1950)"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2005.03.010","article-title":"Multiple Reasons for an Inefficient STAT1 Response Upon IL-6-Type Cytokine Stimulation","volume":"17","author":"Haan","year":"2005","journal-title":"Cell signalling"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203525","article-title":"Complex Roles of Stat1 in Regulating Gene Expression","volume":"19","author":"Ramana","year":"2000","journal-title":"Oncogene"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.5.1274-1282.1996","article-title":"Molecular Analysis of Genetic Differences Between Mycobacterium Bovis BCG and Virulent M. bovis","volume":"178","author":"Mahairas","year":"1996","journal-title":"J Bacteriology"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00239","article-title":"The Impact of Genome Region of Difference 4 (RD4) on Mycobacterial Virulence and BCG Efficacy","volume":"7","author":"Ru","year":"2017","journal-title":"Front Cell Infection Microbiol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2004.09.007","article-title":"ESAT-6 Proteins: Protective Antigens and Virulence Factors","volume":"12","author":"Brodin","year":"2004","journal-title":"Trends Microbiol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-144-11-3195","article-title":"A Mycobacterium Tuberculosis Operon Encoding ESAT-6 and a Novel Low-Molecular-Mass Culture Filtrate Protein (CFP-10)","volume":"144","author":"Berthet","year":"1998","journal-title":"Microbiol (Reading England)"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.40.7.2339-2345.2002","article-title":"Rapid and Simple Approach for Identification of Mycobacterium Tuberculosis Complex Isolates by PCR-Based Genomic Deletion Analysis","volume":"40","author":"Parsons","year":"2002","journal-title":"J Clin Microbiol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2008.05.002","article-title":"Role of M. Tuberculosis RD-1 Region Encoded Secretory Proteins in Protective Response and Virulence","volume":"88","author":"Ganguly","year":"2008","journal-title":"Tuberculosis (Edinburgh Scotland)"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2016.07.005","article-title":"Lung Damage Induced by Hyperglycemia in Diabetic Rats: The Role of Signal Transducer and Activator of Transcription 3 (STAT3)","volume":"30","author":"Wang","year":"2016","journal-title":"J Diabetes Its Complications"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.2174\/138161281939131127115940","article-title":"The STAT3 Inhibitor Stattic Impairs Cardiomyocyte Mitochondrial Function Through Increased Reactive Oxygen Species Formation","volume":"19","author":"Boengler","year":"2013","journal-title":"Curr Pharm Design"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1530\/jme-20-0321","article-title":"Neuritin Inhibits Astrogliosis to Ameliorate Diabetic Cognitive Dysfunction","volume":"66","author":"Zhang","year":"2021","journal-title":"J Mol Endocrinol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.7.4313","article-title":"Cutting Edge: An In Vivo Requirement for STAT3 Signaling in TH17 Development and TH17-Dependent Autoimmunity","volume":"179","author":"Harris","year":"2007","journal-title":"J Immunol (Baltimore Md.: 1950)"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.872286\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T22:18:05Z","timestamp":1675721885000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.872286\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,27]]},"references-count":59,"alternative-id":["10.3389\/fimmu.2022.872286"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.872286","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,27]]},"article-number":"872286"}}