{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:28:35Z","timestamp":1760243315712,"version":"build-2065373602"},"reference-count":63,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T00:00:00Z","timestamp":1661817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004383","name":"Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences","doi-asserted-by":"publisher","award":["GW2\/2015"],"award-info":[{"award-number":["GW2\/2015"]}],"id":[{"id":"10.13039\/501100004383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Although prostacyclin (PGI2) has been well described as a regulator of smooth muscle activity, limited data are available concerning its role in the myometrium of pigs. The present research aimed to examine profiles of PGI2 synthase (PTGIS) and PGI2 receptor (PTGIR) expression and 6-keto PGF1\u03b1 (a PGI2 metabolite) concentrations in the myometrium of gilts throughout the estrous cycle and during early pregnancy using qPCR, Western blot, and\/or ELISA methods. Furthermore, myometrial explants were exposed to iloprost (a stable PGI2 analog) to investigate the effect of PGI2 on the mRNA expression of factors engaged in smooth muscle contraction, nutrient transport, prostaglandin synthesis and action, and inflammatory response. PTGIS mRNA expression was greater in cyclic than in pregnant gilts on days 11\u201312 after estrus and was accompanied by greater concentrations of 6-keto PGF1\u03b1 detected in cyclic than in pregnant animals on days 11\u201320. Iloprost stimulated fatty acid transporters and contractility-related calponin 1 and caldesmon 1 mRNA expression and decreased interleukin 1\u03b2 and tumor necrosis factor transcript abundance. The obtained results indicate a physiologically relevant role of PGI2 during the estrous cycle in the porcine myometrium with its importance for regulating the expression of contractility-, nutrient transport- and inflammatory response-related factors.<\/jats:p>","DOI":"10.3390\/ani12172237","type":"journal-article","created":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T21:25:18Z","timestamp":1661894718000},"page":"2237","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prostacyclin Synthesis and Prostacyclin Receptor Expression in the Porcine Myometrium: Prostacyclin Potential to Regulate Fatty Acid Transporters, Cytokines and Contractility-Related Factors"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9852-0079","authenticated-orcid":false,"given":"Agnieszka","family":"Blitek","sequence":"first","affiliation":[{"name":"Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima 10, 10-748 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9412-3620","authenticated-orcid":false,"given":"Mateusz","family":"Luba","sequence":"additional","affiliation":[{"name":"Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima 10, 10-748 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7159-2256","authenticated-orcid":false,"given":"Magdalena","family":"Szymanska","sequence":"additional","affiliation":[{"name":"Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima 10, 10-748 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,30]]},"reference":[{"key":"ref_1","first-page":"597","article-title":"Implantation: Molecular basis of uterine dialogue","volume":"45","author":"Paria","year":"2001","journal-title":"Int. J. Dev. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/2049-1891-3-23","article-title":"Uterine biology of pigs and sheep","volume":"3","author":"Bazer","year":"2012","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1002\/mrd.22835","article-title":"Embryo-maternal dialogue during pregnancy establishment and implantation in the pig","volume":"84","author":"Waclawik","year":"2017","journal-title":"Mol. Reprod. Dev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/BF00570923","article-title":"Uterine motility of the sow during the oestrous cycle and early pregnancy","volume":"11","author":"Scheerboom","year":"1987","journal-title":"Vet. Res. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S1642-431X(12)60013-8","article-title":"Endometrial and myometrial secretion of androgens and estrone during early pregnancy and luteolysis in pigs","volume":"8","author":"Franczak","year":"2008","journal-title":"Reprod. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s13028-016-0201-z","article-title":"Comparison of the porcine uterine smooth muscle contractility on days 12\u201314 of the estrous cycle and pregnancy","volume":"58","author":"Markiewicz","year":"2016","journal-title":"Acta Vet. Scand."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.2174\/1381612043383926","article-title":"Regulation of myometrial smooth muscle functions","volume":"10","author":"Hertelendy","year":"2004","journal-title":"Curr. Pharm. Des."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"714","DOI":"10.3389\/fendo.2019.00714","article-title":"Multifactorial regulation of myometrial contractility during pregnancy and parturition","volume":"10","author":"Mendelson","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1262\/jrd.20148","article-title":"Local and systemic effects of the embryos on the uterine tissues during early pregnancy in pigs","volume":"55","author":"Franczak","year":"2009","journal-title":"J. Reprod. Dev."},{"key":"ref_10","unstructured":"Garfield, R.E., and Tabb, T.N. (1994). The roles and regulation of prostaglandins within the uterus. Control of Uterine Contractility, CRC Press. [1st ed.]."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/j.1439-0531.2007.00859.x","article-title":"The role of the endometrium in endocrine regulation of the animal oestrous cycle","volume":"43","author":"Krzymowski","year":"2008","journal-title":"Reprod. Domest. Anim."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"33157","DOI":"10.1074\/jbc.271.52.33157","article-title":"Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2","volume":"271","author":"Smith","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.plefa.2003.04.002","article-title":"Prostaglandin synthases: Recent developments and a novel hypothesis","volume":"70","author":"Helliwell","year":"2004","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.bbrc.2005.08.021","article-title":"Cellular and molecular biology of prostacyclin synthase","volume":"338","author":"Wu","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/978-1-4615-5325-0_27","article-title":"Molecular cloning of prostacyclin synthase from bovine endothelial cells","volume":"400A","author":"Tanabe","year":"1997","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1006\/excr.2001.5198","article-title":"Colocalization prostacyclin (PGI2) synthase\u2014caveolin-1 in endothelial cells and new roles for PGI2 in angiogenesis","volume":"266","author":"Spisni","year":"2001","journal-title":"Exp. Cell Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1152\/physrev.1999.79.4.1193","article-title":"Prostanoid receptors: Structures, properties, and functions","volume":"79","author":"Narumiya","year":"1999","journal-title":"Physiol. Rev."},{"key":"ref_18","first-page":"625","article-title":"Multiple signaling options for prostacyclin","volume":"24","author":"Wise","year":"2003","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/sj.bjp.0702383","article-title":"Effects of the adenylyl cyclase inhibitor SQ22536 on iloprost-induced vasorelaxation and cyclic AMP elevation in isolated guinea-pig aorta","volume":"126","author":"Turcato","year":"1999","journal-title":"Br. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/41780","article-title":"Altered pain perception and inflammatory response in mice lacking prostacyclin receptor","volume":"388","author":"Murata","year":"1997","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1530\/REP-09-0081","article-title":"Quantitative characterization of prostaglandins in the uterus of early pregnant cattle","volume":"138","author":"Ulbrich","year":"2009","journal-title":"Reproduction"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1530\/rep.1.00799","article-title":"Developmental regulation of prostacyclin synthase and prostacyclin receptors in the ovine uterus and conceptus during the peri-implantation period","volume":"131","author":"Cammas","year":"2006","journal-title":"Reproduction"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1016\/j.theriogenology.2012.07.028","article-title":"Regulation of prostacyclin synthase expression and prostacyclin content in the pig endometrium","volume":"78","author":"Morawska","year":"2012","journal-title":"Theriogenology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.theriogenology.2015.05.034","article-title":"Prostacyclin receptor (PTGIR) in the porcine endometrium: Regulation of expression and role in luminal epithelial and stromal cells","volume":"84","author":"Blitek","year":"2015","journal-title":"Theriogenology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1093\/biolre\/ioy178","article-title":"Prostacyclin synthesis and prostacyclin receptor expression in the porcine corpus luteum: Evidence for a luteotropic role in vitro","volume":"100","author":"Szymanska","year":"2019","journal-title":"Biol. Reprod."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.theriogenology.2014.05.014","article-title":"Expression profile and role of prostacyclin receptor (PTGIR) in peri-implantation porcine conceptuses","volume":"82","author":"Szymanska","year":"2014","journal-title":"Theriogenology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0014-2999(02)01489-9","article-title":"In vitro pharmacological characterization of the prostanoid receptor population in the non-pregnant porcine myometrium","volume":"442","author":"Cao","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.theriogenology.2012.10.020","article-title":"Synthesis of prostacyclin and its effect on the contractile activity of the inflamed porcine uterus","volume":"79","author":"Jana","year":"2013","journal-title":"Theriogenology"},{"key":"ref_29","first-page":"1953","article-title":"Gross ovarian changes during estrous cycle of swine","volume":"29","author":"Akins","year":"1968","journal-title":"Am. J. Vet. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/ar.1091900112","article-title":"Growth, protein content and distribution of early pig embryos","volume":"190","author":"Anderson","year":"1978","journal-title":"Anat. Rec."},{"key":"ref_31","unstructured":"Rodriguez-Martinez, H., Vallet, J.L., and Ziecik, A.J. (2009). Development of the pig placenta. Control of Pig Reproduction VIII, Nottingham University Press."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1089\/cmb.2005.12.1047","article-title":"Comprehensive algorithm for quantitative real-time polymerase chain reaction","volume":"12","author":"Zhao","year":"2005","journal-title":"J. Comput. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.anireprosci.2016.09.005","article-title":"Endometrial and conceptus response to exogenous progesterone treatment in early pregnant gilts following hormonally-induced estrus","volume":"174","author":"Szymanska","year":"2016","journal-title":"Anim. Reprod. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5245","DOI":"10.1158\/0008-5472.CAN-04-0496","article-title":"Normalization of real-time quantitative reverse transcription-PCR data: A model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets","volume":"64","author":"Andersen","year":"2004","journal-title":"Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/S0002-9378(99)70282-6","article-title":"Changes in prostacyclin synthase in pregnant sheep myometrium, endometrium, and placenta at spontaneous term. labor and regulation by estradiol and progesterone","volume":"180","author":"Wu","year":"1999","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/0090-6980(84)90019-4","article-title":"Increase in concentrations of prostaglandin endoperoxide synthase and prostacyclin synthase in human myometrium in late pregnancy","volume":"28","author":"Moonen","year":"1984","journal-title":"Prostaglandins"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5274","DOI":"10.1210\/jc.2002-020521","article-title":"Expression of prostaglandin I(2) synthase, but not prostaglandin E synthase, changes in myometrium of women at term pregnancy","volume":"87","author":"Giannoulias","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/0090-6980(79)90082-0","article-title":"Prostacyclin (PGI2) in pregnant human uterus","volume":"17","author":"Omini","year":"1979","journal-title":"Prostaglandins"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/0090-6980(88)90125-6","article-title":"The significance of prostacyclin produced by pregnant rat myometrium: The relationship between myometrial prostacyclin producing activity and passive stretch of myometrium by growing conceptus","volume":"35","author":"Kawano","year":"1988","journal-title":"Prostaglandins"},{"key":"ref_41","first-page":"3966","article-title":"Prostacyclin primes pregnant human myometrium for an enhanced contractile response in parturition","volume":"118","author":"Fetalvero","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1530\/rep.1.00038","article-title":"Temporal expression and signalling of prostacyclin receptor in the human endometrium across the menstrual cycle","volume":"127","author":"Battersby","year":"2004","journal-title":"Reproduction"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0952-3278(03)00113-3","article-title":"Expression of prostanoid receptors in human lower segment pregnant myometrium","volume":"69","author":"Leonhardt","year":"2003","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/0952-3278(89)90151-8","article-title":"The presence of prostacyclin binding sites in nonpregnant bovine uterine tissue","volume":"38","author":"Chegini","year":"1989","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.prostaglandins.2016.02.002","article-title":"Expression of the energy substrate transporters in the uterine fibroids","volume":"123","author":"Knapp","year":"2016","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1111\/j.1439-0531.2009.01468.x","article-title":"Changes of connexin43 expression in non-pregnant porcine myometrium correlate with progesterone concentration during oestrous cycle","volume":"45","author":"Karasinski","year":"2010","journal-title":"Reprod. Domest. Anim."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/BF03194644","article-title":"Relative transcript abundance of oxytocin receptor gene in porcine uterus during luteolysis and early pregnancy","volume":"47","author":"Oponowicz","year":"2006","journal-title":"J. Appl. Genet."},{"key":"ref_48","first-page":"151","article-title":"In vitro contractile activity of porcine myometrium during luteolysis and early pregnancy: Effect of oxytocin and progesterone","volume":"5","author":"Kurowicka","year":"2005","journal-title":"Reprod. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3981","DOI":"10.1210\/jcem.86.8.7727","article-title":"Reorganization of myofilament proteins and decreased cGMP-dependent protein kinase in the human uterus during pregnancy","volume":"86","author":"Cornwell","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"12115","DOI":"10.1016\/S0021-9258(18)98864-2","article-title":"Caldesmon, a novel regulatory protein in smooth muscle and nonmuscle actomyosin systems","volume":"266","author":"Sobue","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/j.1365-201X.1998.tb10697.x","article-title":"Regulation of smooth muscle actin-myosin interaction and force by calponin","volume":"164","author":"Winder","year":"1998","journal-title":"Acta Physiol. Scand."},{"key":"ref_52","first-page":"3829","article-title":"Possible dual roles for prostacyclin in human pregnancy and labor","volume":"118","author":"Taggart","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s12958-022-00914-5","article-title":"Integrative metabolomics profiling reveals aberrations in myometrium associated with adenomyosis: A pilot study","volume":"20","author":"Song","year":"2022","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1159\/000512460","article-title":"Maternal myometrium metabolomics profiles in labor: Preliminary results","volume":"86","author":"Qian","year":"2021","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1262\/jrd.2011-019","article-title":"Select nutrients in the uterine lumen of sheep and pigs affect conceptus development","volume":"58","author":"Bazer","year":"2012","journal-title":"J. Reprod. Dev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.theriogenology.2019.01.002","article-title":"Regulation of expression and role of peroxisome proliferator-activated receptors (PPARs) in luminal epithelial and stromal cells of the porcine endometrium","volume":"127","author":"Blitek","year":"2019","journal-title":"Theriogenology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S1098-8823(03)00050-9","article-title":"Cyclooxygenase enzymes and prostaglandins in reproductive tract physiology and pathology","volume":"71","author":"Sales","year":"2003","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.prostaglandins.2004.11.002","article-title":"Uterine region-dependent differences in responsiveness to prostaglandins in the non-pregnant porcine myometrium","volume":"75","author":"Cao","year":"2005","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.theriogenology.2006.03.001","article-title":"Expression of enzymes of cyclooxygenase pathway and secretion of prostaglandin E2 and F2alpha by porcine myometrium during luteolysis and early pregnancy","volume":"66","author":"Franczak","year":"2006","journal-title":"Theriogenology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"702","DOI":"10.4049\/jimmunol.178.2.702","article-title":"Prostaglandin I2 analogs inhibit proinflammatory cytokine production and T cell stimulatory function of dendritic cells","volume":"178","author":"Zhou","year":"2007","journal-title":"J. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6981","DOI":"10.4049\/jimmunol.0901045","article-title":"Prostacyclin inhibits IFN-gamma-stimulated cytokine expression by reduced recruitment of CBP\/p300 to STAT1 in a SOCS-1-independent manner","volume":"183","author":"Strassheim","year":"2009","journal-title":"J. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1111\/j.1365-2222.2010.03558.x","article-title":"Iloprost has potent anti-inflammatory properties on human monocyte-derived dendritic cells","volume":"40","author":"Blumnethal","year":"2010","journal-title":"Clin. Exp. Allergy"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"R101","DOI":"10.1530\/JOE-16-0157","article-title":"Myometrial cytokines and their role in the onset of labour","volume":"231","author":"Sivarajasingam","year":"2016","journal-title":"J. Endocrinol."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/12\/17\/2237\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:20:12Z","timestamp":1760142012000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/12\/17\/2237"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,30]]},"references-count":63,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ani12172237"],"URL":"https:\/\/doi.org\/10.3390\/ani12172237","relation":{},"ISSN":["2076-2615"],"issn-type":[{"type":"electronic","value":"2076-2615"}],"subject":[],"published":{"date-parts":[[2022,8,30]]}}}