{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:01:32Z","timestamp":1788454892985,"version":"build-2803163510"},"reference-count":61,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Special Program for Scientific and Technological Basic Resources Investigation of the Ministry of Science and Technology of China","award":["2023FY100405"],"award-info":[{"award-number":["2023FY100405"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The development and replacement of hair play a significant role in the life history of animals. In recent years, retinoic-acid-related orphan receptor alpha (Ror\u03b1) has been found to participate in the regulation of hair follicle development, yet the underlying mechanisms remain incompletely understood. This study aims to analyze the regulatory role of Ror\u03b1 on the cytoskeleton of hair follicle stem cells (HFSCs). We treated HFSCs with a RORA agonist and subsequently analyzed differential gene expression using qPCR, Western blotting, and immunofluorescence, finding that agonist-induced activation of RORA suppressed the expression levels of cytoskeleton-related genes. Additionally, F-actin staining with phalloidin, followed by migration assays and wound healing tests for cell migration detection, revealed that this process affected the cytoskeletal state of HFSCs and inhibited their migration and adhesion capabilities. We further conducted interaction analyses using CUT&amp;RUN combined with ddPCR and EMSA, demonstrating that RORA can bind to the promoter regions of the Actg1 gene and regulate their transcription. This study contributes to a comprehensive understanding of the regulatory processes involved in hair follicle development and may provide broader insights into the treatment of diseases such as alopecia.<\/jats:p>","DOI":"10.3390\/biom15060863","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T06:19:28Z","timestamp":1749795568000},"page":"863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Retinoic-Acid-Related Orphan Receptor Alpha Is Involved in the Regulation of the Cytoskeleton of Hair Follicle Stem Cells"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1615-7382","authenticated-orcid":false,"given":"Yu","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7368-0057","authenticated-orcid":false,"given":"Xuefei","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, China"},{"name":"National Forestry and Grassland Administration Research Center of Engineering Technology for Wildlife Conservation and Utilization, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqi","family":"Li","sequence":"additional","affiliation":[{"name":"College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9686-3342","authenticated-orcid":false,"given":"Suying","family":"Bai","sequence":"additional","affiliation":[{"name":"College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, China"},{"name":"Detecting Center of Wildlife, State Forestry and Grassland Administration, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, China"},{"name":"Detecting Center of Wildlife, State Forestry and Grassland Administration, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/S0733-8635(05)70216-3","article-title":"The biology of hair care","volume":"18","author":"Draelos","year":"2000","journal-title":"Dermatol. Clin."},{"key":"ref_2","first-page":"S12","article-title":"The Biology, Structure, and Function of Eyebrow Hair","volume":"13","author":"Nguyen","year":"2014","journal-title":"J. Drugs Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/s41580-023-00662-3","article-title":"Local and systemic mechanisms that control the hair follicle stem cell niche","volume":"25","author":"Zhang","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Lin, X., Zhu, L., and He, J. (2022). Morphogenesis, Growth Cycle and Molecular Regulation of Hair Follicles. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.899095"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.semcdb.2007.01.005","article-title":"Determination of hair structure and shape","volume":"18","author":"Schlake","year":"2007","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_6","first-page":"31","article-title":"Histochemistry of the human hair follicle","volume":"78","author":"Wollina","year":"1997","journal-title":"EXS"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/jez.b.33","article-title":"Molecular biology of hair morphogenesis: Development and cycling","volume":"298B","author":"Botchkarev","year":"2003","journal-title":"J. Exp. Zool. B Mol. Dev. Evol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/sj.jid.5701180","article-title":"Complex hair cycle domain patterns and regenerative hair waves in living rodents","volume":"128","author":"Plikus","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1046\/j.1365-2133.2000.03408.x","article-title":"Thyroid hormone receptor beta1 is expressed in the human hair follicle","volume":"142","author":"Billoni","year":"2000","journal-title":"Br. J. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Grymowicz, M., Rudnicka, E., Podfigurna, A., Napierala, P., Smolarczyk, R., Smolarczyk, K., and Meczekalski, B. (2020). Hormonal Effects on Hair Follicles. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155342"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1096\/fj.201700260RR","article-title":"Androgens trigger different growth responses in genetically identical human hair follicles in organ culture that reflect their epigenetic diversity in life","volume":"32","author":"Miranda","year":"2018","journal-title":"FASEB J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/j.1365-3164.2008.00652.x","article-title":"Spaying-induced coat changes: The role of gonadotropins, GnRH and GnRH treatment on the hair cycle of female dogs","volume":"19","author":"Reichler","year":"2008","journal-title":"Vet. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1111\/1523-1747.ep12294690","article-title":"Control of hair growth with parathyroid hormone (7-34)","volume":"108","author":"Schilli","year":"1997","journal-title":"J. Investig. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1530\/jrf.0.1160025","article-title":"Effects of maintaining solstice light and temperature on reproductive activity, coat growth, plasma prolactin and melatonin in goats","volume":"116","author":"Gebbie","year":"1999","journal-title":"J. Reprod. Fertil."},{"key":"ref_15","first-page":"365","article-title":"Seasonal Gene Expression Profile Responsible for Hair Follicle Development in Angora Goats","volume":"29","author":"Kul","year":"2023","journal-title":"Kafkas Univ. Vet. Fak. Derg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1111\/1346-8138.13897","article-title":"Aging in hair follicle stem cells and niche microenvironment","volume":"44","author":"Ji","year":"2017","journal-title":"J. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"784","DOI":"10.47102\/annals-acadmedsg.STlee","article-title":"A review: The location, molecular characterisation and multipotency of hair follicle epidermal stem cells","volume":"33","author":"Ma","year":"2004","journal-title":"Ann. Acad. Med. Sing."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"232","DOI":"10.4161\/cc.5.3.2397","article-title":"The pluripotency of hair follicle stem cells","volume":"5","author":"Hoffman","year":"2006","journal-title":"Cell Cycle"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"181","DOI":"10.5604\/17322693.991445","article-title":"Hair follicle as a novel source of stem cells","volume":"66","author":"Joachimiak","year":"2012","journal-title":"Postepy Hig. Med. Dosw."},{"key":"ref_20","first-page":"197","article-title":"Melatonin: A chemical photoperiodic signal with clinical significance in humans","volume":"111","author":"Pang","year":"1998","journal-title":"Chin. Med. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-079X.2007.00512.x","article-title":"Melatonin and the hair follicle","volume":"44","author":"Fischer","year":"2008","journal-title":"J. Pineal Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/s00114-018-1585-6","article-title":"Long noncoding RNA and gene expression analysis of melatonin-exposed Liaoning cashmere goat fibroblasts indicating cashmere growth","volume":"105","author":"Jin","year":"2018","journal-title":"Sci. Nat."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rong, Y., Ma, R., Zhang, Y., and Guo, Z. (2024). Melatonin\u2019s effect on hair follicles in a goat (Capra hircus) animal model. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1361100"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e12569","DOI":"10.1111\/jpi.12569","article-title":"Melatonin promotes secondary hair follicle development of early postnatal cashmere goat and improves cashmere quantity and quality by enhancing antioxidant capacity and suppressing apoptosis","volume":"67","author":"Yang","year":"2019","journal-title":"J. Pineal Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1111\/j.1365-2133.2004.05685.x","article-title":"Melatonin increases anagen hair rate in women with androgenetic alopecia or diffuse alopecia: Results of a pilot randomized controlled trial","volume":"150","author":"Fischer","year":"2004","journal-title":"Br. J. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"236","DOI":"10.4103\/0974-7753.111199","article-title":"Topical melatonin for treatment of androgenetic alopecia","volume":"4","author":"Fischer","year":"2012","journal-title":"Int. J. Trichol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Nematisouldaragh, D., Kirshenbaum, E., Uzonna, M., Kirshenbaum, L., and Rabinovich-Nikitin, I. (2024). The Role of Retinoic-Acid-Related Orphan Receptor (RORs) in Cellular Homeostasis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252111340"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ma, H., Kang, J., Fan, W., He, H., and Huang, F. (2021). ROR: Nuclear Receptor for Melatonin or Not?. Molecules, 26.","DOI":"10.3390\/molecules26092693"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lu, Z., Wu, J., Wu, J., Zhang, T., Liu, J., Mu, Q., Wu, Z., Zhang, Y., Su, R., and Liu, Z. (2023). Melatonin regulates the periodic growth of secondary hair follicles through the nuclear receptor ROR\u03b1. Front. Vet. Sci., 10.","DOI":"10.3389\/fvets.2023.1203302"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhao, X., Li, S., Xu, Y., Bai, S., and Zhang, W. (2024). Retinoic Acid-Related Orphan Receptor Alpha May Regulate the State of Hair Follicle Stem Cells by Upregulating the Expression of BNIP3. Animals, 14.","DOI":"10.3390\/ani14233477"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1007\/s11033-022-08025-5","article-title":"Roles of the cytoskeleton in human diseases","volume":"50","author":"Li","year":"2023","journal-title":"Mol. Biol. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.tibs.2019.11.003","article-title":"The Cytoskeleton as Regulator of Cell Signaling Pathways","volume":"45","author":"Moujaber","year":"2020","journal-title":"Trends Biochem. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1016\/j.lfs.2005.05.017","article-title":"Role of the isoprenoid pathway in ras transforming activity, cytoskeleton organization, cell proliferation and apoptosis","volume":"77","author":"Bifulco","year":"2005","journal-title":"Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0304-3835(97)00268-1","article-title":"The role of the cytoskeleton in migration and proliferation of a cultured human gastric cancer cell line using a new metastasis model","volume":"119","author":"Iwazaki","year":"1997","journal-title":"Cancer Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.bbrc.2006.07.046","article-title":"A cytoskeleton-associated protein, TMAP\/CKAP2, is involved in the proliferation of human foreskin fibroblasts","volume":"348","author":"Jeon","year":"2006","journal-title":"Biochem. Bioph. Res. Co."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1089\/dna.2019.5087","article-title":"Regulation of Hippo Signaling by Mechanical Signals and the Cytoskeleton","volume":"39","author":"Zhang","year":"2020","journal-title":"DNA Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/s43587-021-00103-w","article-title":"Escape of hair follicle stem cells causes stem cell exhaustion during aging","volume":"1","author":"Zhang","year":"2021","journal-title":"Nat. Aging"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0092-8674(01)00208-2","article-title":"Morphogenesis and renewal of hair follicles from adult multipotent stem cells","volume":"104","author":"Oshima","year":"2001","journal-title":"Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/0092-8674(94)90383-2","article-title":"Location of stem cells of human hair follicles by clonal analysis","volume":"76","author":"Rochat","year":"1994","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.cell.2020.06.031","article-title":"Cell Types Promoting Goosebumps Form a Niche to Regulate Hair Follicle Stem Cells","volume":"182","author":"Shwartz","year":"2020","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ab.2003.08.029","article-title":"Identification of natural ligands of retinoic acid receptor-related orphan receptor \u03b1 ligand-binding domain expressed in Sf9 cells: A mass spectrometry approach","volume":"323","author":"Bitsch","year":"2003","journal-title":"Anal. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1039\/c3md00005b","article-title":"Synthetic modulators of the retinoic acid receptor-related orphan receptors","volume":"4","author":"Kamenecka","year":"2013","journal-title":"MedChemComm"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nrd4100","article-title":"REV-ERB and ROR nuclear receptors as drug targets","volume":"13","author":"Kojetin","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.tem.2012.05.012","article-title":"Action of RORs and their ligands in (patho)physiology","volume":"23","author":"Solt","year":"2012","journal-title":"Trends. Endocrin. Met."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Acevedo, N., Saaf, A., Soderhall, C., Melen, E., Mandelin, J., Pietras, C.O., Ezer, S., Karisola, P., Vendelin, J., and Gennas, G.B.A. (2013). Interaction between retinoid acid receptor-related orphan receptor alpha (RORA) and neuropeptide S receptor 1 (NPSR1) in asthma. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060111"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/s41531-023-00563-4","article-title":"Neuroprotective role for RORA in Parkinson\u2019s disease revealed by analysis of post-mortem brain and a dopaminergic cell line","volume":"9","author":"Hurley","year":"2023","journal-title":"NPJ Park. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1023\/B:BEGE.0000017875.78571.a6","article-title":"Spatial memory of heterozygous staggerer (Rora+\/Rorasg) versus normal (Rora+\/Rora+) mice during aging","volume":"34","author":"Caston","year":"2004","journal-title":"Behav. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1002\/(SICI)1096-9861(19990823)411:2<267::AID-CNE7>3.0.CO;2-4","article-title":"Cerebellar Purkinje cell loss during life span of the heterozygous staggerer mouse (Rora(+)\/Rora(sg)) is gender-related","volume":"411","author":"Doulazmi","year":"1999","journal-title":"J. Comp. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"380","DOI":"10.4238\/2015.January.23.11","article-title":"Expression of the ROR\u03b1 gene in Inner Mongolian cashmere goat hair follicles","volume":"14","author":"Zhao","year":"2015","journal-title":"Genet. Mol. Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhao, X., Li, S., Xu, Y., Bai, S., and Zhang, W. (2025). Melatonin-Mediated Circadian Rhythm Signaling Exhibits Bidirectional Regulatory Effects on the State of Hair Follicle Stem Cells. Biomolecules, 15.","DOI":"10.3390\/biom15020226"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhao, X., Li, S., Bai, S., and Zhang, W. (2025). The Retinoic-Acid-Related Orphan Receptor Alpha May Be Highly Involved in the Regulation of Seasonal Hair Molting. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26041579"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3497","DOI":"10.1111\/j.1582-4934.2008.00684.x","article-title":"Control of chondrocyte gene expression by actin dynamics: A novel role of cholesterol\/Ror-\u03b1 signalling in endochondral bone growth","volume":"13","author":"Woods","year":"2009","journal-title":"J. Cell Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Sun, M., and Zaman, M.H. (2017). Modeling, signaling and cytoskeleton dynamics: Integrated modeling-experimental frameworks in cell migration. Wires. Syst. Biol. Med., 9.","DOI":"10.1002\/wsbm.1365"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S1357-2725(02)00071-7","article-title":"Actin, microtubules and focal adhesion dynamics during cell migration","volume":"35","author":"Imhof","year":"2003","journal-title":"Int. J. Biochem. Cell B"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/0092-8674(82)90048-4","article-title":"Treadmilling of tubulin and actin","volume":"28","author":"Cleveland","year":"1982","journal-title":"Cell"},{"key":"ref_56","first-page":"284","article-title":"Treadmilling or fragmentation? A proposed repair mechanism for actin filaments","volume":"35","author":"Grazi","year":"1986","journal-title":"Ital. J. Biochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1002\/(SICI)1521-1878(199810)20:10<830::AID-BIES8>3.0.CO;2-N","article-title":"Microtubule treadmilling: What goes around comes around","volume":"20","author":"Margolis","year":"1998","journal-title":"BioEssays"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"R369","DOI":"10.1016\/S0960-9822(06)00177-1","article-title":"Microtubule dynamics: Treadmilling comes around again","volume":"7","author":"Salmon","year":"1997","journal-title":"Curr. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"323","DOI":"10.3233\/CBM-190361","article-title":"MiR-652 serves as a prognostic biomarker in gastric cancer and promotes tumor proliferation, migration, and invasion via targeting RORA","volume":"26","author":"Li","year":"2019","journal-title":"Cancer Biomark."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1158\/1541-7786.MCR-18-0267","article-title":"miR-652 Promotes Tumor Proliferation and Metastasis by Targeting RORA in Endometrial Cancer","volume":"16","author":"Sun","year":"2018","journal-title":"Mol. Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Zhao, J., Jiang, Y., Chen, L., Ma, Y., Zhang, H., Zhou, J., Li, H., and Jing, Z. (2021). The EIF4A3\/CASC2\/RORA Feedback Loop Regulates the Aggressive Phenotype in Glioblastomas. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.699933"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/6\/863\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:51:21Z","timestamp":1760032281000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/6\/863"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,13]]},"references-count":61,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["biom15060863"],"URL":"https:\/\/doi.org\/10.3390\/biom15060863","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,13]]}}}