{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T18:27:50Z","timestamp":1771612070969,"version":"3.50.1"},"reference-count":60,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T00:00:00Z","timestamp":1725926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Grants-in-Aid for Scientific Research (C)","doi-asserted-by":"publisher","award":["23K07730"],"award-info":[{"award-number":["23K07730"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Grants-in-Aid for Scientific Research (C)","doi-asserted-by":"publisher","award":["20K08624"],"award-info":[{"award-number":["20K08624"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Uehara Memorial Foundation Research Fellowship Program","award":["23K07730"],"award-info":[{"award-number":["23K07730"]}]},{"name":"Uehara Memorial Foundation Research Fellowship Program","award":["20K08624"],"award-info":[{"award-number":["20K08624"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The cytoskeleton mediates fundamental cellular processes by organizing inter-organelle interactions. Pathogenic variants of inverted formin 2 (INF2) CAAX isoform, an actin assembly factor that is predominantly expressed in the endoplasmic reticulum (ER), are linked to focal segmental glomerulosclerosis (FSGS) and Charcot\u2013Marie\u2013Tooth (CMT) neuropathy. To investigate how pathogenic INF2 variants alter ER integrity, we used high-resolution live imaging of HeLa cells. Cells expressing wild-type (WT) INF2 showed a predominant tubular ER with perinuclear clustering. Cells expressing INF2 FSGS variants that cause mild and intermediate disease induced more sheet-like ER, a pattern similar to that seen for cells expressing WT-INF2 that were treated with actin and microtubule (MT) inhibitors. Dual CMT-FSGS INF2 variants led to more severe ER dysmorphism, with a diffuse, fragmented ER and coarse INF2 aggregates. Proper organization of both F-actin and MT was needed to modulate the tubule vs. sheet conformation balance, while MT arrays regulated spatial expansion of tubular ER in the cell periphery. Pathogenic INF2 variants also induced mitochondria fragmentation and dysregulated mitochondria distribution. Such mitochondrial abnormalities were more prominent for cells expressing CMT-FSGS compared to those with FSGS variants, indicating that the severity of the dysfunction is linked to the degree of cytoskeletal disorganization. Our observations suggest that pathogenic INF2 variants disrupt ER continuity by altering interactions between the ER and the cytoskeleton that in turn impairs inter-organelle communication, especially at ER\u2013mitochondria contact sites. ER continuity defects may be a common disease mechanism involved in both peripheral neuropathy and glomerulopathy.<\/jats:p>","DOI":"10.3390\/ijms25189783","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T07:33:25Z","timestamp":1725953605000},"page":"9783","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Altered Endoplasmic Reticulum Integrity and Organelle Interactions in Living Cells Expressing INF2 Variants"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6077-4783","authenticated-orcid":false,"given":"Quynh Thuy Huong","family":"Tran","sequence":"first","affiliation":[{"name":"Second Department of Internal Medicine, Division of Nephrology, Kansai Medical University, Hirakata 573-1010, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6624-5989","authenticated-orcid":false,"given":"Naoyuki","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Institute of Biochemical Science, Kansai Medical University, Hirakata 573-1010, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroko","family":"Ueda","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Division of Nephrology, Kansai Medical University, Hirakata 573-1010, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3183-4871","authenticated-orcid":false,"given":"Yoshiyuki","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Central Research Center, Institute of Biomedical Science, Kansai Medical University, Hirakata 573-1010, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9563-5356","authenticated-orcid":false,"given":"Hiroyasu","family":"Tsukaguchi","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Division of Nephrology, Kansai Medical University, Hirakata 573-1010, Japan"},{"name":"Clinical Genetics Center, Kansai Medical University Hospital, Hirakata 573-1191, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Obara, C.J., Moore, A.S., and Lippincott-Schwartz, J. (2022). Structural diversity within the endoplasmic reticulum\u2014From the microscale to the nanoscale. Cold Spring Harb. Perspect. Biol., 15.","DOI":"10.1101\/cshperspect.a041259"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.cell.2010.11.007","article-title":"Mechanisms determining the morphology of the peripheral ER","volume":"143","author":"Shibata","year":"2010","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/s41586-021-04204-9","article-title":"ER proteins decipher the tubulin code to regulate organelle distribution","volume":"601","author":"Zheng","year":"2021","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"eaan5835","DOI":"10.1126\/science.aan5835","article-title":"Here, there, and everywhere: The importance of ER membrane contact sites","volume":"361","author":"Wu","year":"2018","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.yexcr.2015.04.009","article-title":"ER sheet\u2013tubule balance is regulated by an array of actin filaments and microtubules","volume":"337","author":"Joensuu","year":"2015","journal-title":"Exp. Cell Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"aaf3928","DOI":"10.1126\/science.aaf3928","article-title":"Increased spatiotemporal resolution reveals highly dynamic dense tubular matrices in the peripheral ER","volume":"354","author":"Obara","year":"2016","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1016\/j.cell.2018.09.057","article-title":"Visualizing intracellular organelle and cytoskeletal interactions at nanoscale resolution on millisecond timescales","volume":"175","author":"Guo","year":"2018","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/nature22369","article-title":"Applying systems-level spectral imaging and analysis to reveal the organelle interactome","volume":"546","author":"Valm","year":"2017","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41586-021-03977-3","article-title":"Whole-cell organelle segmentation in volume electron microscopy","volume":"599","author":"Heinrich","year":"2021","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/nrn2946","article-title":"Hereditary spastic paraplegias: Membrane traffic and the motor pathway","volume":"12","author":"Blackstone","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1146\/annurev-neuro-062111-150400","article-title":"Cellular pathways of hereditary spastic paraplegia","volume":"35","author":"Blackstone","year":"2012","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Koppers, M., \u00d6zkan, N., and Far\u00edas, G.G. (2020). Complex interactions between membrane-bound organelles, biomolecular condensates and the cytoskeleton. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.618733"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1083\/jcb.103.4.1557","article-title":"Microtubules and the endoplasmic reticulum are highly interdependent structures","volume":"103","author":"Terasaki","year":"1986","journal-title":"J. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e08828","DOI":"10.7554\/eLife.08828","article-title":"A mitochondria-anchored isoform of the actin-nucleating spire protein regulates mitochondrial division","volume":"4","author":"Manor","year":"2015","journal-title":"eLife"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3427","DOI":"10.1242\/jcs.206433","article-title":"Actin assembly mechanisms at a glance","volume":"130","author":"Rottner","year":"2017","journal-title":"J. Cell Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0962-8924(03)00153-3","article-title":"The formins: Active scaffolds that remodel the cytoskeleton","volume":"13","author":"Wallar","year":"2003","journal-title":"Trends Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1038\/ncb1007-1110","article-title":"The many faces of actin: Matching assembly factors with cellular structures","volume":"9","author":"Chhabra","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1002\/cm.21409","article-title":"Inverted formins: A subfamily of atypical formins","volume":"74","author":"Hegsted","year":"2017","journal-title":"Cytoskeleton"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4581","DOI":"10.1007\/s00018-020-03550-7","article-title":"The formin INF2 in disease: Progress from 10 years of research","volume":"77","author":"Alonso","year":"2020","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.molcel.2005.04.002","article-title":"Structural basis of Rho GTPase-mediated activation of the formin mDia1","volume":"18","author":"Otomo","year":"2005","journal-title":"Mol. Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/ng.505","article-title":"Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis","volume":"42","author":"Brown","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1056\/NEJMra1106556","article-title":"Focal segmental glomerulosclerosis","volume":"365","author":"Kaskel","year":"2011","journal-title":"NEJM"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1056\/NEJMoa1109122","article-title":"INF2 mutations in Charcot\u2013Marie\u2013Tooth disease with glomerulopathy","volume":"365","author":"Boyer","year":"2011","journal-title":"NEJM"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/j.devcel.2010.04.001","article-title":"The formin INF2 regulates basolateral-to-apical transcytosis and lumen formation in association with Cdc42 and MAL2","volume":"18","author":"Madrid","year":"2010","journal-title":"Dev. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1681\/ASN.2019111174","article-title":"A deregulated stress response underlies distinct INF2-associated disease profiles","volume":"31","author":"Bayraktar","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1126\/science.1228360","article-title":"An actin-dependent step in mitochondrial fission mediated by the ER-associated formin INF2","volume":"339","author":"Korobova","year":"2013","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ueda, H., Tran, Q.T.H., Tran, L.N.T., Higasa, K., Ikeda, Y., Kondo, N., Hashiyada, M., Sato, C., Sato, Y., and Ashida, A. (2023). Characterization of cytoskeletal and structural effects of INF2 variants causing glomerulopathy and neuropathy. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-38588-7"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4822","DOI":"10.1091\/mbc.e11-05-0457","article-title":"Splice variant\u2013specific cellular function of the formin INF2 in maintenance of Golgi architecture","volume":"22","author":"Ramabhadran","year":"2011","journal-title":"Mol. Biol. Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"26754","DOI":"10.1074\/jbc.M604666200","article-title":"INF2 is a WASP homology 2 motif-containing formin that severs actin filaments and accelerates both polymerization and depolymerization","volume":"281","author":"Chhabra","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1681\/ASN.2019050443","article-title":"FSGS-Causing INF2 mutation impairs cleaved INF2 N-fragment functions in podocytes","volume":"31","author":"Subramanian","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1242\/jcs.040691","article-title":"INF2 is an endoplasmic reticulum-associated formin protein","volume":"122","author":"Chhabra","year":"2009","journal-title":"J. Cell Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1083\/jcb.201709111","article-title":"INF2-mediated actin polymerization at the ER stimulates mitochondrial calcium uptake, inner membrane constriction, and division","volume":"217","author":"Chakrabarti","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1681\/ASN.2012080834","article-title":"Inverted formin 2 regulates actin dynamics by antagonizing rho\/diaphanous-related formin signaling","volume":"24","author":"Sun","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e2104309119","DOI":"10.1073\/pnas.2104309119","article-title":"A role for endoplasmic reticulum dynamics in the cellular distribution of microtubules","volume":"119","author":"Tikhomirova","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Nieto-Garai, J.A., Olazar-Intxausti, J., Anso, I., Lorizate, M., Terrones, O., and Contreras, F.-X. (2022). Super-Resolution Microscopy to Study Interorganelle Contact Sites. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232315354"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4575","DOI":"10.1091\/mbc.e11-07-0616","article-title":"Differential interactions of the formins INF2, mDia1, and mDia2 with microtubules","volume":"22","author":"Gaillard","year":"2011","journal-title":"Mol. Biol. Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"34234","DOI":"10.1074\/jbc.M112.365122","article-title":"Mutations to the formin homology 2 domain of inf2 protein have unexpected effects on actin polymerization and severing","volume":"287","author":"Ramabhadran","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/cm.21623","article-title":"Interplay between endoplasmic reticulum membrane contacts and actomyosin cytoskeleton","volume":"77","author":"Zhang","year":"2020","journal-title":"Cytoskeleton"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/s41556-019-0313-6","article-title":"Ultrastructure and dynamics of the actin\u2212myosin II cytoskeleton during mitochondrial fission","volume":"21","author":"Yang","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1091\/mbc.E19-09-0491","article-title":"New twists in actin\u2014Microtubule interactions","volume":"32","author":"Pimm","year":"2021","journal-title":"Mol. Biol. Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/35050598","article-title":"Coordination of microtubules and the actin cytoskeleton by the Rho effector mDia1","volume":"3","author":"Ishizaki","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1083\/jcb.200911024","article-title":"ER sliding dynamics and ER-mitochondrial contacts occur on acetylated microtubules","volume":"190","author":"Friedman","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3181","DOI":"10.1007\/s00018-018-2855-3","article-title":"Coordination of microtubule acetylation and the actin cytoskeleton by formins","volume":"75","author":"Alonso","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1091\/mbc.e15-07-0489","article-title":"An mDia1-INF2 formin activation cascade facilitated by IQGAP1 regulates stable microtubules in migrating cells","volume":"27","author":"Bartolini","year":"2016","journal-title":"Mol. Biol. Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41580-019-0180-9","article-title":"The functional universe of membrane contact sites","volume":"21","author":"Prinz","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/s41580-023-00613-y","article-title":"The multiple links between actin and mitochondria","volume":"24","author":"Fung","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/s41586-021-03214-x","article-title":"Function and regulation of the divisome for mitochondrial fission","volume":"590","author":"Kraus","year":"2021","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/978-90-481-2813-6_9","article-title":"The role of mitochondrial network dynamics in the pathogenesis of Charcot-Marie-Tooth disease","volume":"652","author":"Palau","year":"2009","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1146\/annurev-genet-110410-132529","article-title":"Fusion and fission: Interlinked processes critical for mitochondrial health","volume":"46","author":"Chan","year":"2012","journal-title":"Annu. Rev. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1681\/ASN.2019121292","article-title":"New paradigm for cytoskeletal organization in podocytes: Proteolytic fragments of INF2 formin function independently of INF2 actin regulatory activity","volume":"31","author":"Krendel","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Salzer, J.L. (2015). Schwann cell myelination. Cold Spring Harb. Perspect Biol., 7.","DOI":"10.1101\/cshperspect.a020529"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1038\/s41556-019-0307-4","article-title":"A complex containing lysine-acetylated actin inhibits the formin INF2","volume":"21","author":"Fung","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"26847","DOI":"10.1074\/jbc.M113.472415","article-title":"Actin monomers activate inverted formin 2 by competing with its autoinhibitory interaction","volume":"288","author":"Ramabhadran","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.ajhg.2020.11.008","article-title":"DAAM2 variants cause nephrotic syndrome via actin dysregulation","volume":"107","author":"Schneider","year":"2020","journal-title":"Am. J. Hum. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S0955-0674(99)00058-7","article-title":"Functional cooperation between the microtubule and actin cytoskeletons","volume":"12","author":"Goode","year":"2000","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1681\/ASN.V133630","article-title":"A conditionally immortalized human podocyte cell line demonstrating nephrin and podocin expression","volume":"13","author":"Saleem","year":"2002","journal-title":"JASN"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1083\/jcb.105.4.1473","article-title":"Effects of cytochalasin and phalloidin on actin","volume":"105","author":"Cooper","year":"1987","journal-title":"J. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.leukres.2005.08.009","article-title":"Nocodazole, a microtubule de-polymerising agent, induces apoptosis of chronic lymphocytic leukaemia cells associated with changes in Bcl-2 phosphorylation and expression","volume":"30","author":"Beswick","year":"2006","journal-title":"Leuk. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/s41586-024-07637-0","article-title":"Mechanisms of actin filament severing and elongation by formins","volume":"632","author":"Palmer","year":"2024","journal-title":"Nature"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"eadn9560","DOI":"10.1126\/science.adn9560","article-title":"Molecular mechanism of actin filament elongation by formins","volume":"384","author":"Oosterheert","year":"2024","journal-title":"Science"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/18\/9783\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:52:56Z","timestamp":1760111576000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/18\/9783"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,10]]},"references-count":60,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ijms25189783"],"URL":"https:\/\/doi.org\/10.3390\/ijms25189783","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,10]]}}}