{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T06:29:56Z","timestamp":1781850596169,"version":"3.54.5"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T00:00:00Z","timestamp":1672358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002848","name":"the Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["1180613"],"award-info":[{"award-number":["1180613"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"the Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["11181000"],"award-info":[{"award-number":["11181000"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"the Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["1210644"],"award-info":[{"award-number":["1210644"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"the Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["1220325"],"award-info":[{"award-number":["1220325"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"the Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["15130011"],"award-info":[{"award-number":["15130011"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"the Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["21191341"],"award-info":[{"award-number":["21191341"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"the Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["EQM140131"],"award-info":[{"award-number":["EQM140131"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cardiomyopathy is commonly observed in patients with autosomal dominant polycystic kidney disease (ADPKD), even when they have normal renal function and arterial pressure. The role of cardiomyocyte polycystin-1 (PC1) in cardiovascular pathophysiology remains unknown. PC1 is a potential regulator of BIN1 that maintains T-tubule structure, and alterations in BIN1 expression induce cardiac pathologies. We used a cardiomyocyte-specific PC1-silenced (PC1-KO) mouse model to explore the relevance of cardiomyocyte PC1 in the development of heart failure (HF), considering reduced BIN1 expression induced T-tubule remodeling as a potential mechanism. PC1-KO mice exhibited an impairment of cardiac function, as measured by echocardiography, but no signs of HF until 7\u20139 months of age. Of the PC1-KO mice, 43% died suddenly at 7 months of age, and 100% died after 9 months with dilated cardiomyopathy. Total BIN1 mRNA, protein levels, and its localization in plasma membrane-enriched fractions decreased in PC1-KO mice. Moreover, the BIN1 + 13 isoform decreased while the BIN1 + 13 + 17 isoform was overexpressed in mice without signs of HF. However, BIN1 + 13 + 17 overexpression was not observed in mice with HF. T-tubule remodeling and BIN1 score measured in plasma samples were associated with decreased PC1-BIN1 expression and HF development. Our results show that decreased PC1 expression in cardiomyocytes induces dilated cardiomyopathy associated with diminished BIN1 expression and T-tubule remodeling. In conclusion, positive modulation of BIN1 expression by PC1 suggests a novel pathway that may be relevant to understanding the pathophysiological mechanisms leading to cardiomyopathy in ADPKD patients.<\/jats:p>","DOI":"10.3390\/ijms24010667","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T04:07:09Z","timestamp":1672632429000},"page":"667","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Polycystin-1 Is a Crucial Regulator of BIN1 Expression and T-Tubule Remodeling Associated with the Development of Dilated Cardiomyopathy"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7807-2050","authenticated-orcid":false,"given":"Magda C.","family":"D\u00edaz-Vesga","sequence":"first","affiliation":[{"name":"Programa de Fisiolog\u00eda y Biof\u00edsica, ICBM, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"},{"name":"Advanced Center for Chronic Diseases, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"},{"name":"Departamento de Ciencias B\u00e1sicas de la Salud, Facultad de Ciencias de la Salud, Pontificia Universidad Javeriana Cali, Cali 760031, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal","family":"Flores-Vergara","sequence":"additional","affiliation":[{"name":"Programa de Fisiolog\u00eda y Biof\u00edsica, ICBM, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"},{"name":"Advanced Center for Chronic Diseases, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"},{"name":"Advanced Center for Chronic Diseases, Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Universidad de Chile, Santiago 8380492, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0517-5697","authenticated-orcid":false,"given":"Jaime A.","family":"Riquelme","sequence":"additional","affiliation":[{"name":"Advanced Center for Chronic Diseases, Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Universidad de Chile, Santiago 8380492, Chile"},{"name":"Departamento de Qu\u00edmica Farmacol\u00f3gica y Toxicol\u00f3gica, Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Universidad de Chile, Santiago 8380492, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Llancaqueo","sequence":"additional","affiliation":[{"name":"Departamento Cardiovascular, Hospital Cl\u00ednico Universidad de Chile, Santiago 8380456, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Programa de Fisiopatolog\u00eda, ICBM, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"},{"name":"Centro de Estudios en Ejercicio, Metabolismo y C\u00e1ncer (CEMC), ICBM, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4015-7438","authenticated-orcid":false,"given":"Cecilia","family":"Vergara","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda, Facultad de Ciencias, Universidad de Chile, Santiago 7750000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Michea","sequence":"additional","affiliation":[{"name":"Programa de Fisiolog\u00eda y Biof\u00edsica, ICBM, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"},{"name":"Division of Nephrology, Department of Medicine, Hospital Cl\u00ednico Universidad de Chile, Santiago 8380456, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6874-6621","authenticated-orcid":false,"given":"Paulina","family":"Donoso","sequence":"additional","affiliation":[{"name":"Programa de Fisiolog\u00eda y Biof\u00edsica, ICBM, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8755-1590","authenticated-orcid":false,"given":"Andrew F. G.","family":"Quest","sequence":"additional","affiliation":[{"name":"Advanced Center for Chronic Diseases, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"},{"name":"Centro de Estudios en Ejercicio, Metabolismo y C\u00e1ncer (CEMC), ICBM, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"},{"name":"Laboratorio de Comunicaciones Celulares, Programa de Biolog\u00eda Celular y Molecular, ICBM, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivonne","family":"Olmedo","sequence":"additional","affiliation":[{"name":"Programa de Fisiopatolog\u00eda, ICBM, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4690-2803","authenticated-orcid":false,"given":"Zully","family":"Pedrozo","sequence":"additional","affiliation":[{"name":"Programa de Fisiolog\u00eda y Biof\u00edsica, ICBM, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"},{"name":"Advanced Center for Chronic Diseases, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"},{"name":"Centro de Estudios en Ejercicio, Metabolismo y C\u00e1ncer (CEMC), ICBM, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/S0140-6736(18)32782-X","article-title":"Autosomal dominant polycystic kidney disease","volume":"393","author":"Alam","year":"2019","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1016\/j.bbrc.2004.08.044","article-title":"Polycystins, calcium signaling, and human diseases","volume":"322","author":"Delmas","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1083\/jcb.201006173","article-title":"The cell biology of polycystic kidney disease","volume":"191","author":"Chapin","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e149","DOI":"10.1159\/000093216","article-title":"The Pathogenesis of Autosomal Dominant Polycystic Kidney Disease","volume":"103","author":"Sutters","year":"2006","journal-title":"Nephron-Exp. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nrneph.2009.13","article-title":"Cardiovascular abnormalities in autosomal-dominant polycystic kidney disease","volume":"5","author":"Ecder","year":"2009","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.ekir.2017.05.014","article-title":"Autosomal Dominant Polycystic Kidney Patients May Be Predisposed to Various Cardiomyopathies","volume":"2","author":"Chebib","year":"2017","journal-title":"Kidney Int. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1536\/ihj.20-155","article-title":"Sudden Unexpected Death of Infantile Dilated Cardiomyopathy with JPH2 and PKD1 Gene Variants","volume":"61","author":"Miura","year":"2020","journal-title":"Int. Heart J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"42","DOI":"10.4038\/jccp.v46i1-2.7750","article-title":"Adult polycystic kidney disease and idiopathic dilated cardiomyopathy: A rare genetic asso-ciation","volume":"46","author":"Mariathasan","year":"2016","journal-title":"J. Ceylon Coll. Physicians"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12451","DOI":"10.1002\/jcp.28094","article-title":"Autosomal dominant polycystic kidney disease: Disrupted pathways and potential therapeutic interventions","volume":"234","author":"Malekshahabi","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1161\/CIRCULATIONAHA.114.013537","article-title":"Polycystin-1 Is a Cardiomyocyte Mechanosensor That Governs L-Type Ca2+ Channel Protein Stability","volume":"131","author":"Pedrozo","year":"2015","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1161\/CIRCULATIONAHA.118.034731","article-title":"Polycystin-1 Assembles With Kv Channels to Govern Cardiomyocyte Repolarization and Contractility","volume":"140","author":"Altamirano","year":"2019","journal-title":"Circulation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1038\/nm.3543","article-title":"Cardiac BIN1 folds T-tubule membrane, controlling ion flux and limiting arrhythmia","volume":"20","author":"Hong","year":"2014","journal-title":"Nat. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1016\/j.bbamcr.2015.11.004","article-title":"BIN1 regulates dynamic t-tubule membrane","volume":"1863","author":"Fu","year":"2016","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s11427-016-0249-x","article-title":"Cardiac BIN1 (cBIN1) is a regulator of cardiac contractile function and an emerging biomarker of heart muscle health","volume":"60","author":"Zhou","year":"2017","journal-title":"Sci. China Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1146\/annurev-physiol-061121-040148","article-title":"Cardiac Transverse Tubules in Physiology and Heart Failure","volume":"84","author":"Louch","year":"2022","journal-title":"Annu. Rev. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.cell.2009.04.010","article-title":"The BAR Domain Superfamily: Membrane-Molding Macromolecules","volume":"137","author":"Frost","year":"2009","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.hrthm.2011.11.055","article-title":"BIN1 is reduced and Cav1.2 trafficking is impaired in human failing cardiomyocytes","volume":"9","author":"Hong","year":"2012","journal-title":"Heart Rhythm"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1002\/jcb.25198","article-title":"Cardiac-Specific Disruption of Bin1 in Mice Enables a Model of Stress- and Age-Associated Dilated Cardio-myopathy","volume":"116","author":"Mulgrew","year":"2015","journal-title":"J. Cell. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1161\/CIRCRESAHA.116.303448","article-title":"Dependence of Cardiac Transverse Tubules on the BAR Domain Protein Amphiphysin II (BIN-1)","volume":"115","author":"Caldwell","year":"2014","journal-title":"Circ. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1161\/CIRCRESAHA.109.212324","article-title":"T-Tubule Remodeling During Transition From Hypertrophy to Heart Failure","volume":"107","author":"Wei","year":"2010","journal-title":"Circ. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Li, J., Richmond, B., and Hong, T. (2021). Cardiac T-Tubule cBIN1-Microdomain, a Diagnostic Marker and Therapeutic Target of Heart Failure. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052299"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1001\/jamacardio.2018.3539","article-title":"Association of a Novel Diagnostic Biomarker, the Plasma Cardiac Bridging Integrator 1 Score, With Heart Failure With Preserved Ejection Fraction and Cardiovascular Hospitalization","volume":"3","author":"Nikolova","year":"2018","journal-title":"JAMA Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.hrthm.2012.01.024","article-title":"Plasma BIN1 correlates with heart failure and predicts arrhythmia in patients with arrhythmogenic right ventricular cardiomyopathy","volume":"9","author":"Hong","year":"2012","journal-title":"Heart Rhythm"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1053\/ajkd.2001.27720","article-title":"Survival after end-stage renal disease in autosomal dominant polycystic kidney disease: Contribution of extrarenal complications to mortality","volume":"38","author":"Perrone","year":"2001","journal-title":"Am. J. Kidney Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.ebiom.2019.01.011","article-title":"Primary cardiac manifestation of autosomal dominant polycystic kidney disease revealed by patient induced pluripotent stem cell-derived cardiomyocytes","volume":"40","author":"Lee","year":"2019","journal-title":"Ebiomedicine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.ekir.2019.12.007","article-title":"Polycystins, ADPKD, and Cardiovascular Disease","volume":"5","author":"Kuo","year":"2020","journal-title":"Kidney Int. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.lfs.2015.10.025","article-title":"Men and mice: Relating their ages","volume":"152","author":"Dutta","year":"2016","journal-title":"Life Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1046\/j.1523-1755.2003.00264.x","article-title":"The role of parental hypertension in the frequency and age of diagnosis of hypertension in offspring with autosomal-dominant polycystic kidney disease","volume":"64","author":"Schrier","year":"2003","journal-title":"Kidney Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6854","DOI":"10.1073\/pnas.0809777106","article-title":"Loss of T-tubules and other changes to surface topography in ventricular myocytes from failing human and rat heart","volume":"106","author":"Lyon","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"H1658","DOI":"10.1152\/ajpheart.00946.2020","article-title":"Role of t-tubule remodeling on mechanisms of abnormal calcium release during heart failure development in canine ventricle","volume":"320","author":"Yamakawa","year":"2021","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1113\/JP277273","article-title":"Cardiomyocyte substructure reverts to an immature phenotype during heart failure","volume":"597","author":"Lipsett","year":"2019","journal-title":"J. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1093\/cvr\/cvw111","article-title":"Elevated ventricular wall stress disrupts cardiomyocyte t-tubule structure and calcium homeostasis","volume":"112","author":"Frisk","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"ref_33","first-page":"1","article-title":"The Physiology and Pathophysiology of T-Tubules in the Heart","volume":"12","author":"Setterberg","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1152\/physrev.00037.2015","article-title":"Cardiac T-Tubule Microanatomy and Function","volume":"97","author":"Hong","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.jacbts.2020.03.006","article-title":"In Mice Subjected to Chronic Stress, Exogenous cBIN1 Preserves Calcium-Handling Machinery and Cardiac Function","volume":"5","author":"Liu","year":"2020","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1093\/cvr\/cvab195","article-title":"Human BIN1 isoforms grow, maintain, and regenerate excitation\u2013contraction couplons in adult rat and human stem cell-derived cardiomyocytes","volume":"118","author":"Guo","year":"2022","journal-title":"Cardiovasc. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"708","DOI":"10.3389\/fphys.2020.00708","article-title":"Exogenous Cardiac Bridging Integrator 1 Benefits Mouse Hearts With Pre-existing Pressure Overload-Induced Heart Failure","volume":"11","author":"Li","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"ra19","DOI":"10.1126\/scisignal.2001556","article-title":"c-MYC Suppresses BIN1 to Release Poly(ADP-Ribose) Polymerase 1: A Mechanism by Which Cancer Cells Acquire Cisplatin Resistance","volume":"4","author":"Pyndiah","year":"2011","journal-title":"Sci. Signal."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"29001","DOI":"10.1073\/pnas.2009334117","article-title":"TAZ\/Wnt-\u03b2-catenin\/c-MYC axis regulates cystogenesis in polycystic kidney disease","volume":"117","author":"Lee","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.bbamcr.2017.11.001","article-title":"Mechanical stretch increases L-type calcium channel stability in cardiomyocytes through a polycys-tin-1\/AKT-dependent mechanism","volume":"1865","author":"Olmedo","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Cell. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/1\/667\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:56:36Z","timestamp":1760147796000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/1\/667"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,30]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["ijms24010667"],"URL":"https:\/\/doi.org\/10.3390\/ijms24010667","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,30]]}}}