{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T01:44:14Z","timestamp":1792374254989,"version":"4.4.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T00:00:00Z","timestamp":1684368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1F1A1060694 2022M3A9J3073020, 2022K2A9A1A06088842"],"award-info":[{"award-number":["2021R1F1A1060694 2022M3A9J3073020, 2022K2A9A1A06088842"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Anoctamin 1 (ANO1), a drug target for various cancers, including prostate and oral cancers, is an intracellular calcium-activated chloride ion channel that plays various physiopathological roles, especially in the induction of cancer growth and metastasis. In this study, we tested a novel compound isolated from <jats:italic>Schisandra sphenanthera<\/jats:italic>, known as schisandrathera D, for its inhibitory effect on ANO1. Schisandrathera D dose-dependently suppressed the ANO1 activation-mediated decrease in fluorescence of yellow fluorescent protein; however, it did not affect the adenosine triphosphate-induced increase in the intracellular calcium concentration or forskolin-induced cystic fibrosis transmembrane conductance regulator activity. Specifically, schisandrathera D gradually decreased the levels of ANO1 protein and significantly reduced the cell viability in ANO1-expressing cells when compared to those in ANO1-knockout cells. These effects could be attributed to the fact that schisandrathera D displayed better binding capacity to ANO1 protein than the previously known ANO1 inhibitor, Ani9. Finally, schisandrathera D increased the levels of caspase-3 and cleaved poly (ADP-ribose) polymerase 1, thereby indicating that its anticancer effect is mediated through apoptosis. Thus, this study highlights that schisandrathera D, which reduces ANO1 protein levels, has apoptosis-mediated anticancer effects in prostate and oral cancers, and thus, can be further developed into an anticancer agent.<\/jats:p>","DOI":"10.3389\/fphar.2023.1163970","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T05:35:51Z","timestamp":1684388151000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["ANO1-downregulation induced by schisandrathera D: a novel therapeutic target for the treatment of prostate and oral cancers"],"prefix":"10.3389","volume":"14","author":[{"given":"SeonJu","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Xuan","family":"Nhiem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Baek","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minuk","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongguk","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye In","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Hyeon","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oh-Bin","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Hyeog","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chul Soon","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song-Rae","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uk Yeol","family":"Moon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boksik","family":"Cha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Kyu","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungwoo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan","family":"Namkung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joohan","family":"Woo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohan","family":"Seo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1007\/164_2022_592","article-title":"Function and regulation of the calcium-activated chloride channel anoctamin 1 (TMEM16A)","volume":"2022","author":"Arreola","year":"2022","journal-title":"Handb. Exp. Pharmacol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1038\/sj.bjc.6605823","article-title":"ANO1 amplification and expression in HNSCC with a high propensity for future distant metastasis and its functions in HNSCC cell lines","volume":"103","author":"Ayoub","year":"2010","journal-title":"Br. J. Cancer."},{"key":"B3","doi-asserted-by":"publisher","first-page":"E1026","DOI":"10.1073\/pnas.1217072110","article-title":"Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling","volume":"110","author":"Britschgi","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B4","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1093\/pcmedi\/pbab003","article-title":"Neuroendocrine cells of the prostate: Histology, biological functions, and molecular mechanisms","volume":"4","author":"Butler","year":"2021","journal-title":"Precis. Clin. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1038\/nn.3111","article-title":"The calcium-activated chloride channel anoctamin 1 acts as a heat sensor in nociceptive neurons","volume":"15","author":"Cho","year":"2012","journal-title":"Nat. Neurosci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"7145","DOI":"10.3390\/ijms22137145","article-title":"Anoctamin1 induces hyperproliferation of HaCaT keratinocytes and triggers imiquimod-induced psoriasis-like skin injury in mice","volume":"22","author":"Choi","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"3270","DOI":"10.1158\/0008-5472.CAN-12-0475-T","article-title":"TMEM16A induces MAPK and contributes directly to tumorigenesis and cancer progression","volume":"72","author":"Duvvuri","year":"2012","journal-title":"Cancer Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"19723","DOI":"10.1074\/jbc.M101892200","article-title":"Novel CFTR chloride channel activators identified by screening of combinatorial libraries based on flavone and benzoquinolizinium lead compounds","volume":"276","author":"Galietta","year":"2001","journal-title":"J. Biol. Chem."},{"key":"B9","doi-asserted-by":"publisher","first-page":"102206","DOI":"10.1016\/j.coph.2022.102206","article-title":"TMEM16A (ANO1) as a therapeutic target in cystic fibrosis","volume":"64","author":"Galietta","year":"2022","journal-title":"Curr. Opin. Pharmacol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1021\/jm030644s","article-title":"Glide: A new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening","volume":"47","author":"Halgren","year":"2004","journal-title":"J. Med. Chem."},{"key":"B11","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1080\/19336950.2021.1975411","article-title":"Molecular mechanisms of activation and regulation of ANO1-Encoded Ca(2+)-activated Cl(\u2212) channels","volume":"15","author":"Hawn","year":"2021","journal-title":"Channels (Austin)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1124\/pr.111.005009","article-title":"International union of basic and clinical pharmacology. LXXXV: Calcium-activated chloride channels","volume":"64","author":"Huang","year":"2012","journal-title":"Pharmacol. Rev."},{"key":"B13","doi-asserted-by":"publisher","first-page":"4887","DOI":"10.1113\/jphysiol.2009.176198","article-title":"Expression of anoctamin 1\/TMEM16A by interstitial cells of Cajal is fundamental for slow wave activity in gastrointestinal muscles","volume":"587","author":"Hwang","year":"2009","journal-title":"J. Physiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.3390\/ijms24021186","article-title":"Inhibition of ANO1 by cis- and trans-resveratrol and their anticancer activity in human prostate cancer PC-3 cells","volume":"24","author":"Jeon","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"113373","DOI":"10.1016\/j.biopha.2022.113373","article-title":"Anticancer effect of verteporfin on non-small cell lung cancer via downregulation of ANO1","volume":"153","author":"Jeong","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"B16","doi-asserted-by":"publisher","first-page":"7856","DOI":"10.1002\/jcp.27865","article-title":"Recent advances in TMEM16A: Structure, function, and disease","volume":"234","author":"Ji","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.2174\/0929866528666211105112131","article-title":"TMEM16A protein: Calcium-binding site and its activation mechanism","volume":"28","author":"Ji","year":"2021","journal-title":"Protein Pept. Lett."},{"key":"B18","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.cbi.2015.02.022","article-title":"Hepato-protective effects of six Schisandra lignans on acetaminophen-induced liver injury are partially associated with the inhibition of CYP-mediated bioactivation","volume":"231","author":"Jiang","year":"2015","journal-title":"Chem. Biol. Interact."},{"key":"B19","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1007\/s00405-010-1361-5","article-title":"Photodynamic therapy of early stage oral cavity and oropharynx neoplasms: An outcome analysis of 170 patients","volume":"268","author":"Karakullukcu","year":"2011","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.3390\/nu10081021","article-title":"Anti-cancer natural products and their bioactive compounds inducing ER stress-mediated apoptosis: A review","volume":"10","author":"Kim","year":"2018","journal-title":"Nutrients"},{"key":"B21","doi-asserted-by":"publisher","first-page":"5180","DOI":"10.3390\/molecules25215180","article-title":"Design of anticancer 2,4-diaminopyrimidines as novel anoctamin 1 (ANO1) ion channel blockers","volume":"25","author":"Kim","year":"2020","journal-title":"Molecules"},{"key":"B22","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.nutres.2018.07.003","article-title":"Maclurin exerts anti-cancer effects on PC3 human prostate cancer cells via activation of p38 and inhibitions of JNK, FAK, AKT, and c-Myc signaling pathways","volume":"58","author":"Lee","year":"2018","journal-title":"Nutr. Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1021\/ol027524j","article-title":"Micrandilactone A: A novel triterpene from Schisandra micrantha","volume":"5","author":"Li","year":"2003","journal-title":"Org. Lett."},{"key":"B24","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1080\/10286020.2013.824428","article-title":"Four new lignans from Schisandra sphenanthera","volume":"15","author":"Li","year":"2013","journal-title":"J. Asian Nat. Prod. Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e313","DOI":"10.4317\/medoral.19076","article-title":"ANO1 as a marker of oral squamous cell carcinoma and silencing ANO1 suppresses migration of human SCC-25 cells","volume":"19","author":"Li","year":"2014","journal-title":"Med. Oral Patol. Oral Cir. Bucal."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1002\/cncr.26483","article-title":"Two stem cell markers, ATP-binding cassette, G2 subfamily (ABCG2) and BMI-1, predict the transformation of oral leukoplakia to cancer: A long-term follow-up study","volume":"118","author":"Liu","year":"","journal-title":"Cancer"},{"key":"B27","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.canlet.2012.07.015","article-title":"Inhibition of Ca(2+)-activated Cl(\u2212) channel ANO1\/TMEM16A expression suppresses tumor growth and invasiveness in human prostate carcinoma","volume":"326","author":"Liu","year":"","journal-title":"Cancer Lett."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1016\/j.apsb.2020.12.003","article-title":"The Ca(2+)-activated chloride channel ANO1\/tmem16a: An emerging therapeutic target for epithelium-originated diseases?","volume":"11","author":"Liu","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1021\/ol300099e","article-title":"Schilancitrilactones A-C: Three unique nortriterpenoids from Schisandra lancifolia","volume":"14","author":"Luo","year":"2012","journal-title":"Org. Lett."},{"key":"B30","doi-asserted-by":"publisher","first-page":"3360","DOI":"10.1080\/14786419.2019.1700247","article-title":"Chemical constituents from Schisandra sphenanthera and their cytotoxic activity","volume":"35","author":"Mai","year":"2021","journal-title":"Nat. Prod. Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1002\/pros.24064","article-title":"Inflammatory infiltration is associated with AR expression and poor prognosis in hormone na\u00efve prostate cancer","volume":"80","author":"McAllister","year":"2020","journal-title":"Prostate"},{"key":"B32","doi-asserted-by":"publisher","first-page":"4178","DOI":"10.1096\/fj.10-160648","article-title":"Inhibition of Ca2+-activated Cl\u2212 channels by gallotannins as a possible molecular basis for health benefits of red wine and green tea","volume":"24","author":"Namkung","year":"2010","journal-title":"FASEB J."},{"key":"B33","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1038\/nature24652","article-title":"Activation mechanism of the calcium-activated chloride channel TMEM16A revealed by cryo-EM","volume":"552","author":"Paulino","year":"2017","journal-title":"Nature"},{"key":"B34","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.bjp.2018.07.009","article-title":"Toona sinensis: A comprehensive review on its traditional usages, phytochemisty, pharmacology and toxicology","volume":"29","author":"Peng","year":"2019","journal-title":"Rev. Bras. Farmacogn."},{"key":"B35","doi-asserted-by":"publisher","first-page":"e43265","DOI":"10.1371\/journal.pone.0043265","article-title":"Enhanced expression of ANO1 in head and neck squamous cell carcinoma causes cell migration and correlates with poor prognosis","volume":"7","author":"Ruiz","year":"2012","journal-title":"PLOS ONE"},{"key":"B36","doi-asserted-by":"publisher","first-page":"6644","DOI":"10.1038\/s41598-020-62860-9","article-title":"Voltage-dependent protonation of the calcium pocket enable activation of the calcium-activated chloride channel Anoctamin-1 (TMEM16A)","volume":"10","author":"Segura-Covarrubias","year":"2020","journal-title":"Sci. Rep."},{"key":"B37","doi-asserted-by":"publisher","first-page":"7100","DOI":"10.3390\/ijms22137100","article-title":"Diethylstilbestrol, a novel ANO1 inhibitor, exerts an anticancer effect on non-small cell lung cancer via inhibition of ANO1","volume":"22","author":"Seo","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.ejmech.2018.10.002","article-title":"Synthesis and biological evaluation of novel Ani9 derivatives as potent and selective ANO1 inhibitors","volume":"160","author":"Seo","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"B39","doi-asserted-by":"publisher","first-page":"e0155771","DOI":"10.1371\/journal.pone.0155771","article-title":"Ani9, A novel potent small-molecule ANO1 inhibitor with negligible effect on ANO2","volume":"11","author":"Seo","year":"2016","journal-title":"PLOS ONE"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e0133656","DOI":"10.1371\/journal.pone.0133656","article-title":"Inhibition of ANO1\/TMEM16A chloride channel by idebenone and its cytotoxicity to cancer cell lines","volume":"10","author":"Seo","year":"2015","journal-title":"PLOS ONE"},{"key":"B41","doi-asserted-by":"publisher","first-page":"e0174935","DOI":"10.1371\/journal.pone.0174935","article-title":"Inhibition of ANO1 by luteolin and its cytotoxicity in human prostate cancer PC-3 cells","volume":"12","author":"Seo","year":"2017","journal-title":"PLOS ONE"},{"key":"B42","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1007\/s10822-007-9133-z","article-title":"Epik: A software program for pK(a) prediction and protonation state generation for drug-like molecules","volume":"21","author":"Shelley","year":"2007","journal-title":"J. Comput. Aid. Mol. Des."},{"key":"B43","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1039\/c4np00117f","article-title":"Triterpenoids from the schisandraceae family: An update","volume":"32","author":"Shi","year":"2015","journal-title":"Nat. Prod. Rep."},{"key":"B44","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1038\/s41419-018-0735-2","article-title":"Inhibition of ANO1\/TMEM16A induces apoptosis in human prostate carcinoma cells by activating TNF-\u03b1 signaling","volume":"9","author":"Song","year":"2018","journal-title":"Cell Death Dis."},{"key":"B45","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1016\/j.biopha.2017.10.145","article-title":"An overview of neuroprotective and cognitive enhancement properties of lignans from Schisandra chinensis","volume":"97","author":"Sowndhararajan","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"B46","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1038\/s41589-019-0304-8","article-title":"Harnessing the anti-cancer natural product nimbolide for targeted protein degradation","volume":"15","author":"Spradlin","year":"2019","journal-title":"Nat. Chem. Biol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1002\/pros.21383","article-title":"PC3 is a cell line characteristic of prostatic small cell carcinoma","volume":"71","author":"Tai","year":"2011","journal-title":"Prostate"},{"key":"B49","doi-asserted-by":"publisher","first-page":"4626","DOI":"10.1021\/acs.jmedchem.7b00020","article-title":"Substituted 2-Acylaminocycloalkylthiophene-3-carboxylic acid arylamides as inhibitors of the calcium-activated chloride channel transmembrane protein 16A (TMEM16A)","volume":"60","author":"Truong","year":"2017","journal-title":"J. Med. Chem."},{"key":"B50","doi-asserted-by":"publisher","first-page":"134","DOI":"10.6026\/97320630007134","article-title":"Selection of an improved HDAC8 inhibitor through structure-based drug design","volume":"7","author":"Vijayakumar","year":"2011","journal-title":"Bioinformation"},{"key":"B51","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/s11306-020-01727-6","article-title":"Metabolic landscape of oral squamous cell carcinoma","volume":"16","author":"Vit\u00f3rio","year":"2020","journal-title":"Metabolomics"},{"key":"B52","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.jchromb.2008.02.016","article-title":"Simultaneous quantification of four active Schisandra lignans from a traditional Chinese medicine Schisandra chinensis(Wuweizi) in rat plasma using liquid chromatography\/mass spectrometry","volume":"865","author":"Wang","year":"2008","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1016\/j.apsb.2020.11.004","article-title":"Discovery of 4-arylthiophene-3-carboxylic acid as inhibitor of ANO1 and its effect as analgesic agent","volume":"11","author":"Wang","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"B54","doi-asserted-by":"publisher","first-page":"114413","DOI":"10.1016\/j.ejmech.2022.114413","article-title":"Optimization of 4-arylthiophene-3-carboxylic acid derivatives as inhibitors of ANO1: Lead optimization studies toward their analgesic efficacy for inflammatory pain","volume":"237","author":"Wang","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"B55","doi-asserted-by":"publisher","first-page":"119132","DOI":"10.1016\/j.bbamcr.2021.119132","article-title":"Cepharanthine, a novel selective ANO1 inhibitor with potential for lung adenocarcinoma therapy","volume":"1868","author":"Zhang","year":"2021","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1163970\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T05:35:55Z","timestamp":1684388155000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1163970\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,18]]},"references-count":55,"alternative-id":["10.3389\/fphar.2023.1163970"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1163970","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,18]]},"article-number":"1163970"}}