{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:20:53Z","timestamp":1790709653825,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Guangdong Province","award":["2019A1515010954"],"award-info":[{"award-number":["2019A1515010954"]}]},{"name":"Natural Science Foundation of Guangdong Province","award":["2021A1515012089"],"award-info":[{"award-number":["2021A1515012089"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myometrium plays critical roles in multiple processes such as embryo spacing through peristalsis during mouse implantation, indicating vital roles of smooth muscle in the successful establishment and quality of implantation. Actin, a key element of cytoskeleton structure, plays an important role in the movement and contraction of smooth muscle cells (SMCs). However, the function of peri-implantation uterine smooth muscle and the regulation mechanism of muscle tension are still unclear. This study focused on the molecular mechanism of actin assembly regulation on implantation in smooth muscle. Phalloidin is a highly selective bicyclic peptide used for staining actin filaments (also known as F-actin). Phalloidin staining showed that F-actin gradually weakened in the CD-1 mouse myometrium from day 1 to day 4 of early pregnancy. More than 3 mice were studied for each group. Jasplakinolide (Jasp) used to inhibit F-actin depolymerization promotes F-actin polymerization in SMCs during implantation window and consequently compromises embryo implantation quality. Transcriptome analysis following Jasp treatment in mouse uterine SMCs reveals significant molecular changes associated with actin assembly. Tagln is involved in the regulation of the cell cytoskeleton and promotes the polymerization of G-actin to F-actin. Our results show that Tagln expression is gradually reduced in mouse uterine myometrium from day 1 to 4 of pregnancy. Furthermore, progesterone inhibits the expression of Tagln through the progesterone receptor. Using siRNA to knock down Tagln in day 3 SMCs, we found that phalloidin staining is decreased, which confirms the critical role of Tagln in F-actin polymerization. In conclusion, our data suggested that decreases in actin assembly in uterine smooth muscle during early pregnancy is critical to optimal embryo implantation. Tagln, a key molecule involved in actin assembly, regulates embryo implantation by controlling F-actin aggregation before implantation, suggesting moderate uterine contractility is conducive to embryo implantation. This study provides new insights into how the mouse uterus increases its flexibility to accommodate implanting embryos in the early stage of pregnancy.<\/jats:p>","DOI":"10.3390\/ijms232012494","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:58:51Z","timestamp":1666141131000},"page":"12494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Molecular Mechanism of Mouse Uterine Smooth Muscle Regulation on Embryo Implantation"],"prefix":"10.3390","volume":"23","author":[{"given":"Rui","family":"Cao","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6987-9947","authenticated-orcid":false,"given":"Zhen-Shan","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sui-Li","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Jin","family":"Liang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Miao","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song-Qi","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Hong","family":"Long","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Tong","family":"Yao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Jiang","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Huan","family":"Liang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nrg1808","article-title":"Roadmap to embryo implantation: Clues from mouse models","volume":"7","author":"Wang","year":"2006","journal-title":"Nat. Rev. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Yang, Y., He, J.-P., and Liu, J.-L. (2021). Cell\u2013Cell Communication at the Embryo Implantation Site of Mouse Uterus Revealed by Single-Cell Analysis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105177"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.celrep.2018.03.034","article-title":"ADAMTS9-Regulated Pericellular Matrix Dynamics Governs Focal Adhesion-Dependent Smooth Muscle Differentiation","volume":"23","author":"Mead","year":"2018","journal-title":"Cell Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1146\/annurev-physiol-012110-142315","article-title":"Epigenetic Control of Smooth Muscle Cell Differentiation and Phenotypic Switching in Vascular Development and Disease","volume":"74","author":"Alexander","year":"2012","journal-title":"Annu. Rev. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/s13046-021-01977-9","article-title":"A novel lncRNA ARST represses glioma progression by inhibiting ALDOA-mediated actin cytoskeleton integrity","volume":"40","author":"Sun","year":"2021","journal-title":"J. Exp. Clin. Canc. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1182\/blood-2004-11-4377","article-title":"Regulation of LIM-kinase 1 and cofilin in thrombin-stimulated platelets","volume":"107","author":"Pandey","year":"2006","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1002\/elps.1150180709","article-title":"Two-dimensional gel electrophoresis of actin-binding proteins isolated by affinity chromatography from human skeletal muscle","volume":"18","author":"Coumans","year":"1997","journal-title":"Electrophoresis"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1126\/science.289.5485.1751","article-title":"Subgroup of Reproductive Functions of Progesterone Mediated by Progesterone Receptor-B Isoform","volume":"289","author":"Mullinax","year":"2000","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"113392","DOI":"10.1016\/j.expneurol.2020.113392","article-title":"F-actin polymerization contributes to pericyte contractility in retinal capillaries","volume":"332","author":"Kureli","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5667","DOI":"10.1096\/fj.201802158RRR","article-title":"Transgelin 2 is required for embryo implantation by promoting actin polymerization","volume":"33","author":"Liang","year":"2019","journal-title":"FASEB J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1002\/aja.1000980305","article-title":"Rabbit blastocyst distribution","volume":"98","year":"1956","journal-title":"Am. J. Anat."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1530\/jrf.0.0200407","article-title":"The position and spacing of implantation sites in the uterus of the rat during early pregnancy","volume":"20","author":"Heald","year":"1969","journal-title":"Reproduction"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1530\/jrf.0.0240423","article-title":"The timing and variation of pre-implantation events in the mouse","volume":"24","author":"Restall","year":"1971","journal-title":"Reproduction"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1095\/biolreprod12.1.1","article-title":"Some Comparative Aspects of Implantation","volume":"12","author":"Wimsatt","year":"1975","journal-title":"Biol. Reprod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1530\/jrf.0.0460363","article-title":"Distribution and development of embryos in the pig","volume":"46","author":"Anderson","year":"1976","journal-title":"Reproduction"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1016\/j.mam.2012.07.017","article-title":"Navigating the site for embryo implantation: Biomechanical and molecular regulation of intrauterine embryo distribution","volume":"34","author":"Chen","year":"2013","journal-title":"Mol. Aspects Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1006\/geno.1998.5267","article-title":"Expression and Cytogenetic Localization of the Human SM22 Gene (TAGLN)","volume":"49","author":"Forsythe","year":"1998","journal-title":"Genomics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1513\/pats.200601-008AW","article-title":"Transforming Growth Factor \u03b2: A Central Modulator of Pulmonary and Airway Inflammation and Fibrosis","volume":"3","author":"Sheppard","year":"2006","journal-title":"Proc. Am. Thorac. Soc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.biocel.2008.02.011","article-title":"Transgelin: An actin-binding protein and tumour suppressor","volume":"41","author":"Assinder","year":"2009","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.ebiom.2018.10.041","article-title":"Salvianolic acid A targeting the transgelin-actin complex to enhance vasoconstriction","volume":"37","author":"Zhong","year":"2018","journal-title":"eBioMedicine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1016\/j.ejogrb.2009.02.044","article-title":"Integration of endocrine and mechanical signals in the regulation of myometrial functions during pregnancy and labour","volume":"144","author":"Shynlova","year":"2009","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1096\/cj.01-0104hyp","article-title":"Pressure-induced actin polymerization in vascular smooth muscle as a mechanism underlying myogenic behavior","volume":"16","author":"Cipolla","year":"2002","journal-title":"FASEB J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5163","DOI":"10.1074\/jbc.275.7.5163","article-title":"Effects of Jasplakinolide on the Kinetics of Actin Polymerization","volume":"275","author":"Bubb","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.celrep.2015.03.035","article-title":"Entosis Allows Timely Elimination of the Luminal Epithelial Barrier for Embryo Implantation","volume":"11","author":"Li","year":"2015","journal-title":"Cell Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"201614946-E8088","DOI":"10.1073\/pnas.1614946113","article-title":"Planar ce ll polarity signaling in the uterus directs appropriate positioning of the crypt for embryo implantation","volume":"113","author":"Yuan","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/S0015-0282(97)80075-1","article-title":"Relation between endometrial wavelike activity and fecundability in spontaneous cycles","volume":"67","author":"Ijland","year":"1997","journal-title":"Fertil. Steril."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s12672-012-0103-0","article-title":"Glucocorticoids Regulate Gene Expression and Repress Cellular Proliferation in Human Uterine Leiomyoma Cells","volume":"3","author":"Whirledge","year":"2012","journal-title":"Horm. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1093\/humrep\/deq222","article-title":"Decreased pregnancy rate is linked to abnormal uterine peristalsis caused by intramural fibroids","volume":"25","author":"Yoshino","year":"2010","journal-title":"Hum. Reprod."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4349","DOI":"10.1074\/jbc.M110.197202","article-title":"Transient \u03b22-Adrenoceptor Activation Confers Pregnancy Loss by Disrupting Embryo Spacing at Implantation","volume":"286","author":"Chen","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1095\/biolreprod.107.060293","article-title":"Embryo Spacing and Implantation Timing Are Differentially Regulated by LPA3-Mediated Lysophosphatidic Acid Signaling in Mice1","volume":"77","author":"Hama","year":"2007","journal-title":"Biol. Reprod."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1093\/humrep\/13.7.1968","article-title":"Uterine contractions at the time of embryo transfer alter pregnancy rates after in-vitro fertilization","volume":"13","author":"Fanchin","year":"1998","journal-title":"Hum. Reprod."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"S57","DOI":"10.1016\/S1472-6483(10)60450-6","article-title":"Uterine dynamics: Impact on the human reproduction process","volume":"18","author":"Fanchin","year":"2009","journal-title":"Reprod. Biomed. Online"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1196\/annals.1389.030","article-title":"Uterine Contractility Evaluated on Cine Magnetic Resonance Imaging","volume":"1101","author":"Togashi","year":"2007","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1093\/jnci\/87.1.46","article-title":"Jasplakinolide\u2019s inhibition of the growth of prostate carcinoma cells in vitro with disruption of the actin cytoskeleton","volume":"87","author":"Senderowicz","year":"1995","journal-title":"J. Natl. Cancer. Inst."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/sj.bjc.6604802","article-title":"Reversibility of apoptosis in cancer cells","volume":"100","author":"Tang","year":"2009","journal-title":"Br. J. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5955","DOI":"10.1038\/s41598-021-85335-x","article-title":"NG2\/CSPG4, CD146\/MCAM and VAP1\/AOC3 are regulated by myocardin-related transcription factors in smooth muscle cells","volume":"11","author":"Rippe","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1152\/physrev.00041.2003","article-title":"Molecular Regulation of Vascular Smooth Muscle Cell Differentiation in Development and Disease","volume":"84","author":"Owens","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"665919","DOI":"10.3389\/fcell.2021.665919","article-title":"Feedback-Driven Mechanisms Between Phosphorylated Caveolin-1 and Contractile Actin Assemblies Instruct Persistent Cell Migration","volume":"9","author":"Shi","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/0092-8674(92)90143-Z","article-title":"Caveolin, a protein component of caveolae membrane coats","volume":"68","author":"Rothberg","year":"1992","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"C1513","DOI":"10.1152\/ajpcell.1997.272.5.C1513","article-title":"Phenotypic characterization of an intestinal subepithelial myofibroblast cell line","volume":"272","author":"Valentich","year":"1997","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1242\/jcs.080804","article-title":"Phosphorylated filamin A regulates actin-linked caveolae dynamics","volume":"124","author":"Muriel","year":"2011","journal-title":"J. Cell Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7293","DOI":"10.1074\/jbc.M108986200","article-title":"Contribution of the Helix-Loop-Helix Factor Id2 to Regulation of Vascular Smooth Muscle Cell Proliferation","volume":"277","author":"Matsumura","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1530\/REP-06-0068","article-title":"Secreted phosphoprotein 1 (osteopontin) is expressed by stromal macrophages in cyclic and pregnant endometrium of mice, but is induced by estrogen in luminal epithelium during conceptus attachment for implantation","volume":"132","author":"White","year":"2006","journal-title":"Reproduction"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1095\/biolreprod.102.013573","article-title":"Osteopontin Is Synthesized by Uterine Glands and a 45-kDa Cleavage Fragment Is Localized at the Uterine-Placental Interface Throughout Ovine Pregnancy1","volume":"69","author":"Johnson","year":"2003","journal-title":"Biol. Reprod."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1111\/j.1582-4934.2012.01567.x","article-title":"Interactions between inflammatory signals and the progesterone receptor in regulating gene expression in pregnant human uterine myocytes","volume":"16","author":"Lee","year":"2012","journal-title":"J. Cell Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1530\/JOE-11-0358","article-title":"Estrogen receptor (ER) expression and function in the pregnant human myometrium: Estradiol via ER\u03b1 activates ERK1\/2 signaling in term myometrium","volume":"212","author":"Welsh","year":"2012","journal-title":"J. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.ebiom.2018.11.038","article-title":"Estrogen receptor alpha isoform ERdelta7 in myometrium modulates uterine quiescence during pregnancy","volume":"39","author":"Anamthathmakula","year":"2018","journal-title":"eBioMedicine"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1093\/molehr\/gaz028","article-title":"Interplay of transcriptional signaling by progesterone, cyclic AMP, and inflammation in myometrial cells: Implications for the control of human parturition","volume":"25","author":"Stanfield","year":"2019","journal-title":"Mol. Hum. Reprod."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1038\/nm.3012","article-title":"Mechanisms of implantation: Strategies for successful pregnancy","volume":"18","author":"Cha","year":"2012","journal-title":"Nat. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.bbrc.2020.05.220","article-title":"Smooth muscle 22\u03b1 deficiency impairs oxytocin-induced uterine contractility in mice at full-term pregnancy","volume":"529","author":"Gao","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1128\/MCB.2001.21.4.1336-1344.2001","article-title":"Analysis of SM22\u03b1-Deficient Mice Reveals Unanticipated Insights into Smooth Muscle Cell Differentiation and Function","volume":"21","author":"Zhang","year":"2001","journal-title":"Mol. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0014-5793(04)00220-0","article-title":"Ablation of SM22\u03b1 decreases contractility and actin contents of mouse vascular smooth muscle","volume":"562","author":"Zeidan","year":"2004","journal-title":"FEBS Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e2321","DOI":"10.1038\/cddis.2016.196","article-title":"Transgelin is a TGF\u03b2-inducible gene that regulates osteoblastic and adipogenic differentiation of human skeletal stem cells through actin cytoskeleston organization","volume":"7","author":"Elsafadi","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_54","first-page":"E1","article-title":"Early growth response protein-1 mediates lipotoxicity-associated placental inflammation: Role in maternal obesity","volume":"305","author":"Saben","year":"2013","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/20\/12494\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:56:46Z","timestamp":1760144206000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/20\/12494"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,18]]},"references-count":55,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms232012494"],"URL":"https:\/\/doi.org\/10.3390\/ijms232012494","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,18]]}}}