{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:25:04Z","timestamp":1792160704510,"version":"4.4.0"},"reference-count":94,"publisher":"Elsevier BV","issue":"9","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20240813150422030"],"award-info":[{"award-number":["JCYJ20240813150422030"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32170799"],"award-info":[{"award-number":["32170799"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371608"],"award-info":[{"award-number":["82371608"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002402","name":"Sun Yat-sen University","doi-asserted-by":"publisher","award":["ZSQYRSSFAR0003"],"award-info":[{"award-number":["ZSQYRSSFAR0003"]}],"id":[{"id":"10.13039\/501100002402","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023B1515020016"],"award-info":[{"award-number":["2023B1515020016"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cell Reports"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.celrep.2025.116207","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T12:04:20Z","timestamp":1756469060000},"page":"116207","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":21,"title":["High matrix stiffness triggers testosterone decline in aging males by disrupting stem Leydig cell pool homeostasis"],"prefix":"10.1016","volume":"44","author":[{"given":"Jiayu","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehan","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaixuan","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy Peng","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9599-0171","authenticated-orcid":false,"given":"Jiancheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.celrep.2025.116207_bib1","doi-asserted-by":"crossref","DOI":"10.1001\/jama.2019.9290","article-title":"Testosterone Deficiency","volume":"322","author":"Halpern","year":"2019","journal-title":"JAMA"},{"key":"10.1016\/j.celrep.2025.116207_bib2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.metabol.2018.03.007","article-title":"Testosterone replacement therapy: For whom, when and how?","volume":"86","author":"Tsametis","year":"2018","journal-title":"Metabolism"},{"key":"10.1016\/j.celrep.2025.116207_bib3","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/nn.3084","article-title":"The animal and human neuroendocrinology of social cognition, motivation and behavior","volume":"15","author":"McCall","year":"2012","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.celrep.2025.116207_bib4","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1210\/er.2018-00020","article-title":"Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance","volume":"39","author":"Handelsman","year":"2018","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.celrep.2025.116207_bib5","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/nrendo.2013.135","article-title":"Testicular function and bone metabolism-beyond testosterone","volume":"9","author":"Ferlin","year":"2013","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.celrep.2025.116207_bib6","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41586-018-0554-8","article-title":"Discovery of a periosteal stem cell mediating intramembranous bone formation","volume":"562","author":"Debnath","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2025.116207_bib7","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/s41580-022-00568-6","article-title":"Regulation of adult stem cell quiescence and its functions in the maintenance of tissue integrity","volume":"24","author":"de Morree","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.celrep.2025.116207_bib8","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.immuni.2024.05.023","article-title":"The tissue-resident regulatory T cell pool is shaped by transient multi-tissue migration and a conserved residency program","volume":"57","author":"Burton","year":"2024","journal-title":"Immunity"},{"key":"10.1016\/j.celrep.2025.116207_bib9","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.stem.2020.12.004","article-title":"Single-cell analysis of the developing human testis reveals somatic niche cell specification and fetal germline stem cell establishment","volume":"28","author":"Guo","year":"2021","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.celrep.2025.116207_bib10","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1210\/endo.143.5.8802","article-title":"Age-related decreases in Leydig cell testosterone production are not restored by exposure to LH in vitro","volume":"143","author":"Chen","year":"2002","journal-title":"Endocrinology"},{"key":"10.1016\/j.celrep.2025.116207_bib11","doi-asserted-by":"crossref","first-page":"4020","DOI":"10.1038\/s41467-022-31755-w","article-title":"Nestin-dependent mitochondria-ER contacts define stem Leydig cell differentiation to attenuate male reproductive ageing","volume":"13","author":"Yao","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.celrep.2025.116207_bib12","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1172\/JCI68241","article-title":"Bathing the brain","volume":"123","author":"Strittmatter","year":"2013","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.celrep.2025.116207_bib13","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1152\/physrev.00037.2011","article-title":"Interstitial fluid and lymph formation and transport: physiological regulation and roles in inflammation and cancer","volume":"92","author":"Wiig","year":"2012","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.celrep.2025.116207_bib14","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/nm.4126","article-title":"Loss of fibronectin from the aged stem cell niche affects the regenerative capacity of skeletal muscle in mice","volume":"22","author":"Lukjanenko","year":"2016","journal-title":"Nat. Med."},{"key":"10.1016\/j.celrep.2025.116207_bib15","doi-asserted-by":"crossref","DOI":"10.1002\/advs.202410808","article-title":"Reconstructing the Stem Leydig Cell Niche via the Testicular Extracellular Matrix for the Treatment of Testicular Leydig Cell Dysfunction","volume":"12","author":"Chi","year":"2025","journal-title":"Adv. Sci."},{"key":"10.1016\/j.celrep.2025.116207_bib16","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/s41568-020-0260-3","article-title":"Dysregulated haematopoietic stem cell behaviour in myeloid leukaemogenesis","volume":"20","author":"Yamashita","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.celrep.2025.116207_bib17","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1146\/annurev-pathol-020117-043935","article-title":"Stem Cell Pathology","volume":"13","author":"Fu","year":"2018","journal-title":"Annu. Rev. Pathol."},{"key":"10.1016\/j.celrep.2025.116207_bib18","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.addr.2015.11.001","article-title":"Extracellular matrix structure","volume":"97","author":"Theocharis","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.celrep.2025.116207_bib19","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a004903","article-title":"Overview of the Matrisome-An Inventory of Extracellular Matrix Constituents and Functions","volume":"4","author":"Hynes","year":"2012","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"10.1016\/j.celrep.2025.116207_bib20","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1038\/nrm3896","article-title":"Mechanotransduction and extracellular matrix homeostasis","volume":"15","author":"Humphrey","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.celrep.2025.116207_bib21","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/nrm3904","article-title":"Remodelling the extracellular matrix in development and disease","volume":"15","author":"Bonnans","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.celrep.2025.116207_bib22","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.jare.2022.11.008","article-title":"Extracellular matrix in skin diseases: The road to new therapies","volume":"51","author":"Malta","year":"2023","journal-title":"J. Adv. Res."},{"key":"10.1016\/j.celrep.2025.116207_bib23","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0962-8924(02)00007-7","article-title":"Extracellular matrix in vascular morphogenesis and disease: structure versus signal","volume":"13","author":"Brooke","year":"2003","journal-title":"Trends Cell Biol."},{"key":"10.1016\/j.celrep.2025.116207_bib24","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/nrm.2017.108","article-title":"Mechanical forces direct stem cell behaviour in development and regeneration","volume":"18","author":"Vining","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.celrep.2025.116207_bib25","doi-asserted-by":"crossref","first-page":"3523","DOI":"10.1002\/j.2040-4603.2022.tb00222.x","article-title":"Extracellular Matrix Stiffness in Lung Health and Disease","volume":"12","author":"Guo","year":"2022","journal-title":"Compr. Physiol."},{"key":"10.1016\/j.celrep.2025.116207_bib26","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jare.2022.12.007","article-title":"A single-cell transcriptomic landscape of mouse testicular aging","volume":"53","author":"Zhang","year":"2023","journal-title":"J. Adv. Res."},{"key":"10.1016\/j.celrep.2025.116207_bib27","doi-asserted-by":"crossref","DOI":"10.1111\/cpr.13746","article-title":"Matrix stiffness regulates mitochondria-lysosome contacts to modulate the mitochondrial network, alleviate the senescence of MSCs","volume":"58","author":"Wang","year":"2025","journal-title":"Cell Prolif."},{"key":"10.1016\/j.celrep.2025.116207_bib28","doi-asserted-by":"crossref","DOI":"10.1186\/s13045-019-0795-5","article-title":"Higher matrix stiffness as an independent initiator triggers epithelial-mesenchymal transition and facilitates HCC metastasis","volume":"12","author":"Dong","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"10.1016\/j.celrep.2025.116207_bib29","doi-asserted-by":"crossref","first-page":"C1","DOI":"10.1152\/ajpcell.00559.2003","article-title":"Cell mechanics and mechanotransduction: pathways, probes, and physiology","volume":"287","author":"Huang","year":"2004","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"10.1016\/j.celrep.2025.116207_bib30","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1126\/science.1193270","article-title":"Piezo1 and Piezo2 Are Essential Components of Distinct Mechanically Activated Cation Channels","volume":"330","author":"Coste","year":"2010","journal-title":"Science"},{"key":"10.1016\/j.celrep.2025.116207_bib31","article-title":"TRP (transient receptor potential) ion channel family: structures, biological functions and therapeutic interventions for diseases","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.celrep.2025.116207_bib32","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.pbi.2017.06.009","article-title":"Regulation of calcium and magnesium homeostasis in plants: from transporters to signaling network","volume":"39","author":"Tang","year":"2017","journal-title":"Curr. Opin. Plant Biol."},{"key":"10.1016\/j.celrep.2025.116207_bib33","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.tcb.2022.07.004","article-title":"Calcium homeostasis and cancer: insights from endoplasmic reticulum-centered organelle communications","volume":"33","author":"Zheng","year":"2023","journal-title":"Trends Cell Biol."},{"key":"10.1016\/j.celrep.2025.116207_bib34","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/j.cell.2012.11.034","article-title":"Force fluctuations within focal adhesions mediate ECM-rigidity sensing to guide directed cell migration","volume":"151","author":"Plotnikov","year":"2012","journal-title":"Cell"},{"key":"10.1016\/j.celrep.2025.116207_bib35","doi-asserted-by":"crossref","DOI":"10.1002\/advs.202405705","article-title":"Piezo1 Regulates Stiffness-Dependent DRG Axon Regeneration via Modifying Cytoskeletal Dynamics","volume":"11","author":"Lei","year":"2024","journal-title":"Adv. Sci."},{"key":"10.1016\/j.celrep.2025.116207_bib36","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2022.110342","article-title":"Tethering Piezo channels to the actin cytoskeleton for mechanogating via the cadherin-\u03b2-catenin mechanotransduction complex","volume":"38","author":"Wang","year":"2022","journal-title":"Cell Rep."},{"key":"10.1016\/j.celrep.2025.116207_bib37","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2006786118","article-title":"Mad dephosphorylation at the nuclear pore is essential for asymmetric stem cell division","volume":"118","author":"Sardi","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.celrep.2025.116207_bib38","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-32572-2","article-title":"Enantiomeric A\u03b2 peptides inhibit the fluid shear stress response of PIEZO1","volume":"8","author":"Maneshi","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.celrep.2025.116207_bib39","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/s41580-018-0052-8","article-title":"The machineries, regulation and cellular functions of mitochondrial calcium","volume":"19","author":"Giorgi","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.celrep.2025.116207_bib40","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.1016\/j.ymthe.2023.07.008","article-title":"Targeting RNA oxidation by ISG20-mediated degradation is a potential therapeutic strategy for acute kidney injury","volume":"31","author":"Jia","year":"2023","journal-title":"Mol. Ther."},{"key":"10.1016\/j.celrep.2025.116207_bib41","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1146\/annurev.arplant.55.031903.141701","article-title":"Reactive oxygen species: metabolism, oxidative stress, and signal transduction","volume":"55","author":"Apel","year":"2004","journal-title":"Annu. Rev. Plant Biol."},{"key":"10.1016\/j.celrep.2025.116207_bib42","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1095\/biolreprod63.6.1825","article-title":"Desert hedgehog (Dhh) gene is required in the mouse testis for formation of adult-type Leydig cells and normal development of peritubular cells and seminiferous tubules","volume":"63","author":"Clark","year":"2000","journal-title":"Biol. Reprod."},{"key":"10.1016\/j.celrep.2025.116207_bib43","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.celrep.2015.06.054","article-title":"AMP-Activated Protein Kinase Directly Phosphorylates and Destabilizes Hedgehog Pathway Transcription Factor GLI1 in Medulloblastoma","volume":"12","author":"Li","year":"2015","journal-title":"Cell Rep."},{"key":"10.1016\/j.celrep.2025.116207_bib44","doi-asserted-by":"crossref","first-page":"9538","DOI":"10.18632\/oncotarget.7070","article-title":"The energy sensor AMPK regulates Hedgehog signaling in human cells through a unique Gli1 metabolic checkpoint","volume":"7","author":"Di Magno","year":"2016","journal-title":"Oncotarget"},{"key":"10.1016\/j.celrep.2025.116207_bib45","doi-asserted-by":"crossref","first-page":"49869","DOI":"10.18632\/oncotarget.17769","article-title":"Dual degradation signals destruct GLI1: AMPK inhibits GLI1 through \u03b2-TrCP-mediated proteasome degradation","volume":"8","author":"Zhang","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.celrep.2025.116207_bib46","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.stem.2023.05.012","article-title":"Organoid cultures for cancer modeling","volume":"30","author":"Yan","year":"2023","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.celrep.2025.116207_bib47","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1038\/cr.2014.149","article-title":"Characterization of Nestin-positive stem Leydig cells as a potential source for the treatment of testicular Leydig cell dysfunction","volume":"24","author":"Jiang","year":"2014","journal-title":"Cell Res."},{"key":"10.1016\/j.celrep.2025.116207_bib48","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1002\/jcp.24683","article-title":"3D cell culture systems: advantages and applications","volume":"230","author":"Ravi","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"10.1016\/j.celrep.2025.116207_bib49","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1038\/nprot.2012.127","article-title":"Stiffness-controlled three-dimensional extracellular matrices for high-resolution imaging of cell behavior","volume":"7","author":"Fischer","year":"2012","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.celrep.2025.116207_bib50","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/s41571-021-00588-9","article-title":"Harnessing cytokines and chemokines for cancer therapy","volume":"19","author":"Propper","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.celrep.2025.116207_bib51","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1056\/NEJM197205182862006","article-title":"Acetylcholine--current status in physiology, pharmacology and medicine","volume":"286","author":"Koelle","year":"1972","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.celrep.2025.116207_bib52","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/nrcardio.2016.174","article-title":"Thyroid hormones and cardiovascular disease","volume":"14","author":"Jabbar","year":"2017","journal-title":"Nat. Rev. Cardiol."},{"key":"10.1016\/j.celrep.2025.116207_bib53","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/nature10408","article-title":"A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable","volume":"478","author":"Tian","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2025.116207_bib54","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.tcb.2021.10.002","article-title":"Mechanical communication in fibrosis progression","volume":"32","author":"Long","year":"2022","journal-title":"Trends Cell Biol."},{"key":"10.1016\/j.celrep.2025.116207_bib55","doi-asserted-by":"crossref","first-page":"282","DOI":"10.20892\/j.issn.2095-3941.2019.0437","article-title":"Role of the mechanical microenvironment in cancer development and progression","volume":"17","author":"Liu","year":"2020","journal-title":"Cancer Biol. Med."},{"key":"10.1016\/j.celrep.2025.116207_bib56","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2304288120","article-title":"Defined extracellular matrix compositions support stiffness-insensitive cell spreading and adhesion signaling","volume":"120","author":"Conway","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.celrep.2025.116207_bib57","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.actbio.2021.07.009","article-title":"Heterogeneous microenvironmental stiffness regulates pro-metastatic functions of breast cancer cells","volume":"131","author":"Liu","year":"2021","journal-title":"Acta Biomater."},{"key":"10.1016\/j.celrep.2025.116207_bib58","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2023.106275","article-title":"Matrix stiffness induces epithelial-to-mesenchymal transition via Piezo1-regulated calcium flux in prostate cancer cells","volume":"26","author":"Lopez-Cavestany","year":"2023","journal-title":"iScience"},{"key":"10.1016\/j.celrep.2025.116207_bib59","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1002\/jcp.31074","article-title":"Matrix stiffness regulates neovascular homeostasis through autophagy in nude mice","volume":"238","author":"Wang","year":"2023","journal-title":"J. Cell. Physiol."},{"key":"10.1016\/j.celrep.2025.116207_bib60","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.cell.2006.06.044","article-title":"Matrix elasticity directs stem cell lineage specification","volume":"126","author":"Engler","year":"2006","journal-title":"Cell"},{"key":"10.1016\/j.celrep.2025.116207_bib61","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/nmat2732","article-title":"Harnessing traction-mediated manipulation of the cell\/matrix interface to control stem-cell fate","volume":"9","author":"Huebsch","year":"2010","journal-title":"Nat. Mater."},{"key":"10.1016\/j.celrep.2025.116207_bib62","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.biomaterials.2018.01.014","article-title":"Simultaneous inhibition of hedgehog signaling and tumor proliferation remodels stroma and enhances pancreatic cancer therapy","volume":"159","author":"Zhao","year":"2018","journal-title":"Biomaterials"},{"key":"10.1016\/j.celrep.2025.116207_bib63","doi-asserted-by":"crossref","DOI":"10.1186\/s12951-024-02871-0","article-title":"Losartan-based nanocomposite hydrogel overcomes chemo-immunotherapy resistance by remodeling tumor mechanical microenvironment","volume":"22","author":"Hou","year":"2024","journal-title":"J. Nanobiotechnology"},{"key":"10.1016\/j.celrep.2025.116207_bib64","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1021\/acs.molpharmaceut.8b00319","article-title":"Digesting a Path Forward: The Utility of Collagenase Tumor Treatment for Improved Drug Delivery","volume":"15","author":"Dolor","year":"2018","journal-title":"Mol. Pharm."},{"key":"10.1016\/j.celrep.2025.116207_bib65","doi-asserted-by":"crossref","DOI":"10.1186\/s13045-022-01252-0","article-title":"Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy","volume":"15","author":"Jiang","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"10.1016\/j.celrep.2025.116207_bib66","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1152\/physrev.00053.2021","article-title":"Vascular mechanotransduction","volume":"103","author":"Davis","year":"2023","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.celrep.2025.116207_bib67","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/s41580-022-00472-z","article-title":"Interplay between mechanics and signalling in regulating cell fate","volume":"23","author":"De Belly","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.celrep.2025.116207_bib68","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1161\/CIRCRESAHA.123.322798","article-title":"PIEZO Ion Channels in Cardiovascular Functions and Diseases","volume":"134","author":"Coste","year":"2024","journal-title":"Circ. Res."},{"key":"10.1016\/j.celrep.2025.116207_bib69","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1038\/s41580-024-00773-5","article-title":"Mechanisms of mechanotransduction and physiological roles of PIEZO channels","volume":"25","author":"Xiao","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.celrep.2025.116207_bib70","article-title":"Piezo1 Channels as Force Sensors in Mechanical Force-Related Chronic Inflammation","volume":"13","author":"Liu","year":"2022","journal-title":"Front. Immunol."},{"key":"10.1016\/j.celrep.2025.116207_bib71","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.neuron.2018.09.046","article-title":"A Feedforward Mechanism Mediated by Mechanosensitive Ion Channel PIEZO1 and Tissue Mechanics Promotes Glioma Aggression","volume":"100","author":"Chen","year":"2018","journal-title":"Neuron"},{"key":"10.1016\/j.celrep.2025.116207_bib72","doi-asserted-by":"crossref","first-page":"C92","DOI":"10.1152\/ajpcell.00346.2018","article-title":"Piezo1 mediates angiogenesis through activation of MT1-MMP signaling","volume":"316","author":"Kang","year":"2019","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"10.1016\/j.celrep.2025.116207_bib73","article-title":"The mechanosensitive Piezo1 channel mediates heart mechano-chemo transduction","volume":"12","author":"Jiang","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.celrep.2025.116207_bib74","doi-asserted-by":"crossref","DOI":"10.1038\/s41419-024-06466-3","article-title":"Mechanical stiffness promotes skin fibrosis via Piezo1-Wnt2\/Wnt11-CCL24 positive feedback loop","volume":"15","author":"He","year":"2024","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.celrep.2025.116207_bib75","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.cell.2012.02.035","article-title":"Mitochondria: in sickness and in health","volume":"148","author":"Nunnari","year":"2012","journal-title":"Cell"},{"key":"10.1016\/j.celrep.2025.116207_bib76","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.tcb.2023.03.009","article-title":"Mitochondria in cancer stem cells: Achilles heel or hard armor","volume":"33","author":"Zheng","year":"2023","journal-title":"Trends Cell Biol."},{"key":"10.1016\/j.celrep.2025.116207_bib77","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/cdd.2012.81","article-title":"The pathways of mitophagy for quality control and clearance of mitochondria","volume":"20","author":"Ashrafi","year":"2013","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.celrep.2025.116207_bib78","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/s41568-021-00435-0","article-title":"The role of ROS in tumour development and progression","volume":"22","author":"Cheung","year":"2022","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.celrep.2025.116207_bib79","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/nrm2256","article-title":"ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis","volume":"8","author":"D'Autr\u00e9aux","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.celrep.2025.116207_bib80","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1152\/physrev.00026.2013","article-title":"Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release","volume":"94","author":"Zorov","year":"2014","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.celrep.2025.116207_bib81","doi-asserted-by":"crossref","DOI":"10.1095\/biolreprod.112.107052","article-title":"Aging and luteinizing hormone effects on reactive oxygen species production and DNA damage in rat Leydig cells","volume":"88","author":"Beattie","year":"2013","journal-title":"Biol. Reprod."},{"key":"10.1016\/j.celrep.2025.116207_bib82","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.mce.2015.03.013","article-title":"Knockout of the transcription factor Nrf2: Effects on testosterone production by aging mouse Leydig cells","volume":"409","author":"Chen","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"10.1016\/j.celrep.2025.116207_bib83","doi-asserted-by":"crossref","first-page":"4461","DOI":"10.7150\/thno.35219","article-title":"Vitamin C kills thyroid cancer cells through ROS-dependent inhibition of MAPK\/ERK and PI3K\/AKT pathways via distinct mechanisms","volume":"9","author":"Su","year":"2019","journal-title":"Theranostics"},{"key":"10.1016\/j.celrep.2025.116207_bib84","doi-asserted-by":"crossref","DOI":"10.1016\/j.chemosphere.2023.139593","article-title":"The impaired swim bladder via ROS-mediated inhibition of the Wnt\/Hedgehog pathway in zebrafish embryos exposed to eight toxic chemicals and binary chemical mixtures","volume":"338","author":"Gao","year":"2023","journal-title":"Chemosphere"},{"key":"10.1016\/j.celrep.2025.116207_bib85","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.stem.2021.02.011","article-title":"Mitochondria as Signaling Organelles Control Mammalian Stem Cell Fate","volume":"28","author":"Chakrabarty","year":"2021","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.celrep.2025.116207_bib86","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1016\/j.stem.2022.07.010","article-title":"The mitochondrial protein OPA1 regulates the quiescent state of adult muscle stem cells","volume":"29","author":"Baker","year":"2022","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.celrep.2025.116207_bib87","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/s41418-018-0062-2","article-title":"The tango of ROS and p53 in tissue stem cells","volume":"25","author":"Chen","year":"2018","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.celrep.2025.116207_bib88","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.cmet.2019.05.007","article-title":"Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids","volume":"30","author":"Ouchi","year":"2019","journal-title":"Cell Metab."},{"key":"10.1016\/j.celrep.2025.116207_bib89","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1016\/j.cell.2018.11.013","article-title":"Long-Term Expansion of Functional Mouse and Human Hepatocytes as 3D Organoids","volume":"175","author":"Hu","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.celrep.2025.116207_bib90","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1136\/gutjnl-2019-319256","article-title":"Liver organoids: from basic research to therapeutic applications","volume":"68","author":"Prior","year":"2019","journal-title":"Gut"},{"key":"10.1016\/j.celrep.2025.116207_bib91","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1161\/CIRCRESAHA.122.321768","article-title":"Blood Vessel Organoids for Development and Disease","volume":"132","author":"Salewskij","year":"2023","journal-title":"Circ. Res."},{"key":"10.1016\/j.celrep.2025.116207_bib92","article-title":"Preparation of hydrogel substrates with tunable mechanical properties","volume":"Chapter 10","author":"Tse","year":"2010","journal-title":"Curr. Protoc. Cell Biol."},{"key":"10.1016\/j.celrep.2025.116207_bib93","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nprot.2017.140","article-title":"Use of a three-layer gradient system of cells for rat testicular organoid generation","volume":"13","author":"Alves-Lopes","year":"2018","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.celrep.2025.116207_bib94","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1073\/pnas.0507692103","article-title":"In search of rat stem Leydig cells: identification, isolation, and lineage-specific development","volume":"103","author":"Ge","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Cell Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211124725009787?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211124725009787?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:23:48Z","timestamp":1790137428000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2211124725009787"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":94,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["S2211124725009787"],"URL":"https:\/\/doi.org\/10.1016\/j.celrep.2025.116207","relation":{},"ISSN":["2211-1247"],"issn-type":[{"value":"2211-1247","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"High matrix stiffness triggers testosterone decline in aging males by disrupting stem Leydig cell pool homeostasis","name":"articletitle","label":"Article Title"},{"value":"Cell Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.celrep.2025.116207","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"116207"}}