{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T22:49:26Z","timestamp":1783032566540,"version":"3.54.6"},"reference-count":60,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["1R03 CA208573"],"award-info":[{"award-number":["1R03 CA208573"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Ovarian cancer is the most lethal gynecological malignancy in women. Metformin intake is associated with a reduced incidence of ovarian cancer and increased overall survival rate. We determined the effect of metformin on sphere formation, extracellular matrix invasion, and transcriptome profile of ovarian cancer cells (COVCAR) isolated from ascites of chickens that naturally developed ovarian cancer. We found that metformin treatment significantly decreased sphere formation and invasiveness of COVCAR cells. RNA-Seq data analysis revealed 0, 4, 365 differentially expressed genes in cells treated with 0.5, 1, 2 mM metformin, respectively compared to controls. Transcriptomic and ingenuity pathway analysis (IPA) revealed significant downregulation of MMP7, AICDA, GDPD2, APOC3, APOA1 and predicted inhibition of upstream regulators NFKB, STAT3, TP53 that are involved in epithelial\u2013mesenchymal transition, DNA repair, and lipid metabolism. The analysis revealed significant upregulation of RASD2, IHH, CRABP-1 and predicted activation of upstream regulators VEGF and E2F1 that are associated with angiogenesis and cell cycle. Causal network analysis revealed novel pathways suggesting predicted inhibition of ovarian cancer through master regulator ASCL1 and dataset genes DCX, SEMA6B, HEY2, and KCNIP2. In summary, advanced pathway analysis in IPA revealed novel target genes, upstream regulators, and pathways affected by metformin treatment of COVCAR cells.<\/jats:p>","DOI":"10.3390\/genes13010030","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T10:16:18Z","timestamp":1640254578000},"page":"30","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Metformin Affects the Transcriptomic Profile of Chicken Ovarian Cancer Cells"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5567-4713","authenticated-orcid":false,"given":"Lalitha","family":"Gopalan","sequence":"first","affiliation":[{"name":"Department of Animal Science, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aswathy","family":"Sebastian","sequence":"additional","affiliation":[{"name":"The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig A.","family":"Praul","sequence":"additional","affiliation":[{"name":"The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istvan","family":"Albert","sequence":"additional","affiliation":[{"name":"The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA"},{"name":"Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh","family":"Ramachandran","sequence":"additional","affiliation":[{"name":"Department of Animal Science, The Pennsylvania State University, University Park, PA 16802, USA"},{"name":"Center for Reproductive Biology and Health, Department of Animal Science, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.ygyno.2017.05.006","article-title":"A SEER-Medicare analysis of the impact of metformin on overall survival in ovarian cancer","volume":"146","author":"Garcia","year":"2017","journal-title":"Gynecol. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1007\/s00125-017-4318-z","article-title":"Metformin: Historical Overview","volume":"60","author":"Bailey","year":"2017","journal-title":"Diabetologia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"207","DOI":"10.3322\/caac.20078","article-title":"Diabetes and Cancer: A Consensus Report","volume":"60","author":"Giovannucci","year":"2010","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/s41598-018-37247-6","article-title":"Metformin prevents cell tumorigenesis through autophagy-related cell death","volume":"9","author":"Baldelli","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e7605","DOI":"10.1097\/MD.0000000000007605","article-title":"Continuous use of metformin can improve survival in type 2 diabetic patients with ovarian cancer","volume":"96","author":"Wang","year":"2017","journal-title":"Medicine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.ygyno.2011.06.038","article-title":"Use of metformin and the risk of ovarian cancer: A case\u2013control analysis","volume":"123","author":"Bodmer","year":"2011","journal-title":"Gynecol. Oncol."},{"key":"ref_7","first-page":"e133247","article-title":"Phase II clinical trial of metformin as a cancer stem cell-targeting agent in ovarian cancer","volume":"5","author":"Brown","year":"2020","journal-title":"JCI Insight"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1097\/AOG.0b013e3182393ab3","article-title":"Relationship of Type II Diabetes and Metformin Use to Ovarian Cancer Progression, Survival, and Chemosensitivity","volume":"119","author":"Romero","year":"2012","journal-title":"Obstet. Gynecol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1136\/ijgc-2018-000060","article-title":"Association of metformin use with ovarian cancer incidence and prognosis: A systematic review and meta-analysis","volume":"29","author":"Shi","year":"2019","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1002\/dmrr.2649","article-title":"Metformin reduces ovarian cancer risk in Taiwanese women with type 2 diabetes mellitus","volume":"31","author":"Tseng","year":"2015","journal-title":"Diabetes\/Metab. Res. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1177\/1933719113488441","article-title":"Metformin, at concentrations corresponding to the treatment of diabetes, potentiates the cytotoxic effects of carboplatin in cultures of ovarian cancer cells","volume":"20","author":"Erices","year":"2013","journal-title":"Reprod. Sci."},{"key":"ref_12","first-page":"2404","article-title":"Metformin improves the sensitivity of ovarian cancer cells to chemotherapeutic agents","volume":"18","author":"Yang","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.ygyno.2012.07.115","article-title":"Metformin targets ovarian cancer stem cells in vitro and in vivo","volume":"127","author":"Shank","year":"2012","journal-title":"Gynecol. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1593\/neo.11148","article-title":"Metformin suppresses ovarian cancer growth and metastasis with enhancement of cisplatin cytotoxicity in Vivo","volume":"13","author":"Rattan","year":"2011","journal-title":"Neoplasia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/1477-7827-1-67","article-title":"Animal models of ovarian cancer","volume":"1","author":"Vanderhyden","year":"2003","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Mendes, N., Dias Carvalho, P., Martins, F., Mendon\u00e7a, S., Malheiro, A.R., Ribeiro, A., Carvalho, J., and Velho, S. (2020). Animal Models to Study Cancer and Its Microenvironment. Advances in Experimental Medicine and Biology, Springer.","DOI":"10.1007\/978-3-030-34025-4_20"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/bjc.1951.7","article-title":"Some Unusual Gonadal Tumours of the Fowl","volume":"5","author":"Campbell","year":"1951","journal-title":"Br. J. Cancer"},{"key":"ref_18","unstructured":"Fredrickson, T.N. (2021, October 01). Ovarian Tumors of the Hen, Available online: https:\/\/ehp.niehs.nih.gov\/doi\/abs\/10.1289\/ehp.877335."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1006\/gyno.2002.6806","article-title":"A Pilot Study of Ovarian Cancer Chemoprevention Using Medroxyprogesterone Acetate in an Avian Model of Spontaneous Ovarian Carcinogenesis","volume":"87","author":"Barnes","year":"2002","journal-title":"Gynecol. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.ygyno.2009.02.011","article-title":"E-cadherin expression in ovarian cancer in the laying hen, Gallus domesticus, compared to human ovarian cancer","volume":"113","author":"Ansenberger","year":"2009","journal-title":"Gynecol. Oncol."},{"key":"ref_21","unstructured":"Baker, H., and Fathalla, M.F. (1969). Veterinary Pathology, Campbell. Technical Report."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1158\/1940-6207.CAPR-08-0065","article-title":"Ovarian Adenocarcinomas in the Laying Hen and Women Share Similar Alterations in p53, ras, and HER-2\/neu","volume":"2","author":"Hakim","year":"2009","journal-title":"Cancer Prev. Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Tiwari, A., Hadley, J.A., Hendricks, G.L., Elkin, R.G., Cooper, T., and Ramachandran, R. (2013). Characterization of Ascites-Derived Ovarian Tumor Cells from Spontaneously Occurring Ovarian Tumors of the Chicken: Evidence for E-Cadherin Upregulation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0057582"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1016\/j.psj.2019.11.052","article-title":"Characterization of ascites-derived aldehyde dehydrogenase\u2013positive ovarian cancer stem cells isolated from Leghorn chickens","volume":"99","author":"Tiwari","year":"2020","journal-title":"Poult. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/nature10166","article-title":"Integrated genomic analyses of ovarian carcinoma","volume":"474","author":"Bell","year":"2011","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1309\/AJCPD8NBSHXRXQL7","article-title":"APOA1 mRNA expression in ovarian serous carcinoma effusions is a marker of longer survival","volume":"142","author":"Stavnes","year":"2014","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1038\/onc.2011.347","article-title":"Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation","volume":"31","author":"Wang","year":"2012","journal-title":"Oncogene"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5666","DOI":"10.1126\/science.1094637","article-title":"Stress-dependent regulation of FOXO transcription factors by the sirt1 deacetylase","volume":"303","author":"Brunet","year":"2004","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.mehy.2006.01.050","article-title":"SIRT1: Tumor promoter or tumor suppressor?","volume":"67","author":"Lim","year":"2006","journal-title":"Med. Hypotheses"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1111\/j.1474-9726.2007.00304.x","article-title":"SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction","volume":"6","author":"Wang","year":"2007","journal-title":"Aging Cell"},{"key":"ref_31","first-page":"7557","article-title":"Metformin in combination with cisplatin inhibits cell viability and induces apoptosis of human ovarian cancer cells by inactivating ERK 1\/2","volume":"14","author":"Dang","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2835","DOI":"10.7314\/APJCP.2014.15.6.2835","article-title":"Up-regulating of RASD1 and Apoptosis of DU-145 Human Prostate Cancer Cells Induced by Formononetin in Vitro","volume":"15","author":"Liu","year":"2014","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1055\/s-0033-1341510","article-title":"Calycosin Induces Apoptosis by Upregulation of RASD1 in Human Breast Cancer Cells MCF-7","volume":"45","author":"Tian","year":"2013","journal-title":"Horm. Metab. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1038\/sj.cdd.4401140","article-title":"GITR interacts with the pro-apoptotic protein Siva and induces apoptosis","volume":"9","author":"Spinicelli","year":"2002","journal-title":"Cell Death Differ."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2827","DOI":"10.4049\/jimmunol.1801338","article-title":"UBASH3A Regulates the Synthesis and Dynamics of TCR\u2013CD3 Complexes","volume":"203","author":"Ge","year":"2019","journal-title":"J. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"30920","DOI":"10.1074\/jbc.M706870200","article-title":"T-cell Ubiquitin Ligand Affects Cell Death through a Functional Interaction with Apoptosis-inducing Factor, a Key Factor of Caspase-independent Apoptosis","volume":"282","author":"Collingwood","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41580-020-0237-9","article-title":"Guidelines and definitions for research on epithelial\u2013mesenchymal transition","volume":"21","author":"Yang","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1159\/000147748","article-title":"An Overview of Epithelio-Mesenchymal Transformation","volume":"154","author":"Hay","year":"1995","journal-title":"Cells Tissues Organs"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4227","DOI":"10.1038\/s41388-020-1288-2","article-title":"Single-cell EMT-related transcriptional analysis revealed intra-cluster heterogeneity of tumor cell clusters in epithelial ovarian cancer ascites","volume":"39","author":"Kan","year":"2020","journal-title":"Oncogene"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1158\/1535-7163.MCT-17-0927","article-title":"Metformin Suppresses Tumor Progression by Inactivating Stromal Fibroblasts in Ovarian Cancer","volume":"17","author":"Xu","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1186\/s12885-019-5945-1","article-title":"Metformin reverses mesenchymal phenotype of primary breast cancer cells through STAT3\/NF-\u03baB pathways","volume":"19","year":"2019","journal-title":"BMC Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s10549-008-9916-5","article-title":"Therapeutic metformin\/AMPK activation promotes the angiogenic phenotype in the ER\u03b1 negative MDA-MB-435 breast cancer model","volume":"113","author":"Phoenix","year":"2009","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1158\/2159-8290.CD-11-0280","article-title":"Metformin Accelerates the Growth of BRAF V600E -Driven Melanoma by Upregulating VEGF-A","volume":"2","author":"Martin","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1016\/j.ajpath.2014.05.006","article-title":"Angiopoietins promote ovarian cancer progression by establishing a procancer microenvironment","volume":"184","author":"Brunckhorst","year":"2014","journal-title":"Am. J. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e957508","DOI":"10.4161\/21688362.2014.957508","article-title":"The angiopoietin-Tie2 signaling axis in the vascular leakage of systemic inflammation","volume":"3","author":"Milam","year":"2015","journal-title":"Tissue Barriers"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7692","DOI":"10.1038\/sj.onc.1210573","article-title":"Apelin is a potent activator of tumour neoangiogenesis","volume":"26","author":"Sorli","year":"2007","journal-title":"Oncogene"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.ydbio.2007.03.004","article-title":"Paracrine and autocrine mechanisms of apelin signaling govern embryonic and tumor angiogenesis","volume":"305","author":"Kretz","year":"2007","journal-title":"Dev. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1158\/1541-7786.MCR-18-0989","article-title":"Multifunctional APJ Pathway Promotes Ovarian Cancer Progression and Metastasis","volume":"17","author":"Neelakantan","year":"2019","journal-title":"Mol. Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/s41388-020-01562-y","article-title":"FOXO3a-driven miRNA signatures suppresses VEGF-A\/NRP1 signaling and breast cancer metastasis","volume":"40","author":"Song","year":"2021","journal-title":"Oncogene"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"C4","DOI":"10.1152\/ajpcell.00296.2011","article-title":"A novel inverse relationship between metformin-triggered AMPK-SIRT1 signaling and p53 protein abundance in high glucose-exposed HepG2 cells","volume":"303","author":"Nelson","year":"2012","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1158\/1535-7163.MCT-12-1226-T","article-title":"Metformin Blocks Melanoma Invasion and Metastasis Development in AMPK\/p53-Dependent Manner","volume":"12","author":"Cerezo","year":"2013","journal-title":"Mol. Cancer Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.molcel.2005.03.027","article-title":"AMP-activated protein kinase induces a p53-dependent metabolic checkpoint","volume":"18","author":"Jones","year":"2005","journal-title":"Mol. Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5308","DOI":"10.1128\/MCB.22.15.5308-5318.2002","article-title":"E2F1 Induces Phosphorylation of p53 That Is Coincident with p53 Accumulation and Apoptosis","volume":"22","author":"Rogoff","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4931","DOI":"10.1158\/0008-5472.CAN-10-0501","article-title":"Regulation of vascular endothelial growth factor receptors by Rb and E2F1: Role of acetylation","volume":"70","author":"Pillai","year":"2010","journal-title":"Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/nrc2696","article-title":"Emerging roles of E2Fs in cancer: An exit from cell cycle control","volume":"9","author":"Chen","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2823","DOI":"10.1007\/s13277-015-4770-7","article-title":"E2F1: A promising regulator in ovarian carcinoma","volume":"37","author":"Zhan","year":"2016","journal-title":"Tumor Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1128\/MCB.02147-06","article-title":"E2f1, E2f2, and E2f3 Control E2F Target Expression and Cellular Proliferation via a p53-Dependent Negative Feedback Loop","volume":"27","author":"Timmers","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4295","DOI":"10.1038\/onc.2009.282","article-title":"Pro-proliferative FoxM1 is a target of p53-mediated repression","volume":"28","author":"Barsotti","year":"2009","journal-title":"Oncogene"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Xia, Y., Chang, T., Wang, Y., Liu, Y., Li, W., Li, M., and Fan, H.Y. (2014). YAP promotes ovarian cancer cell tumorigenesis and is indicative of a poor prognosis for ovarian cancer patients. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091770"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1186\/s13046-019-1346-1","article-title":"Metformin targets a YAP1-TEAD4 complex via AMPK\u03b1 to regulate CCNE1\/2 in bladder cancer cells","volume":"38","author":"Wu","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/1\/30\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:51:50Z","timestamp":1760169110000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/1\/30"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,23]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["genes13010030"],"URL":"https:\/\/doi.org\/10.3390\/genes13010030","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,23]]}}}