{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:39:19Z","timestamp":1793036359770,"version":"4.5.0"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>With the acceleration of the aging process, the prevalence and severity of erectile dysfunction (ED) related to aging continue to rise, significantly impacting the physical and mental health of patients and their partners.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The objective of this study was to elucidate the cellular and transcriptomic heterogeneity and immune microenvironment of the aging penile corpus cavernosum in aging-related ED (ARED), while also exploring the potential pathological mechanisms driving ARED pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>In this study, we performed single-cell RNA sequencing on penile tissues from six older patients with ARED, including four older mild ED (OmED) and two older severe ED (OsED) cases, and compared with three younger healthy controls from public data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Through clustering and comparative analysis, we identified nine major cell types including immune cells. Our research revealed the heterogeneity of smooth muscle cells (SMC), endothelial cells (EC) and immune cells in penile environment, and determined the key cell subsets, such as C1_RERGL (a subcluster of SMC) and Macro_CXCL8, and molecular features involved in the pathogenesis of ARED. Furthermore, by constructing a comprehensive cellular communication network, the signals and interactions between macrophages (Macro) and other cell types were emphasized. We found that the interaction of ligand-receptor pairs such as CXCL2\/3\/8 \u2013 ACKR1 and HLA-E \u2013 KLRK1 were enhanced in the ARED group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion and conclusion<\/jats:title>\n                    <jats:p>The mild ED phase represents a critical window of cellular functional transition in penile tissue. In ARED, we observed functional dysfunction of EC and SMC, accompanied by changed expression levels of key genes. Concurrently, the pro-inflammatory Macro_CXCL8 exhibited increased proportion in the microenvironment, which may contribute to disease progression. This work not only provides a detailed description of the cellular atlas of the aging penis but also offers new insights into its role in the pathogenesis of ARED and may provide potential targets for the development of new therapies for ARED.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1671482","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T05:30:17Z","timestamp":1761715817000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Single-cell atlas of human penile corpus cavernosum reveals cellular and functional heterogeneity of aging-related erectile dysfunction"],"prefix":"10.3389","volume":"16","author":[{"given":"Bailing","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueheng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhizhong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Bo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kongrong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingtao","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"B1","article-title":"Erectile dysfunction","volume":"94","author":"Rew","year":"2016","journal-title":"Am Fam Physician"},{"key":"B2","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/s0022-5347(17)34871-1","article-title":"Impotence and its medical and psychosocial correlates: results of the massachusetts male aging study","volume":"151","author":"Feldman","year":"1994","journal-title":"J Urol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-410x.1999.00142.x","article-title":"The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences","volume":"84","author":"Ayta","year":"1999","journal-title":"BJU Int"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-4232fje","article-title":"Elevated rhoa\/rho-kinase activity in the aged rat penis: mechanism for age-associated erectile dysfunction","volume":"20","author":"Jin","year":"2006","journal-title":"FASEB J"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijir.3901158","article-title":"Psycho-biological correlates of hypoactive sexual desire in patients with erectile dysfunction","volume":"16","author":"Corona","year":"2004","journal-title":"Int J Impot Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2164\/jandrol.110.011338","article-title":"Erectile dysfunction: A harbinger or consequence: does its detection lead to a window of curability","volume":"32","author":"Miner","year":"2011","journal-title":"J Androl"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2007.02.001","article-title":"Treatment options for erectile dysfunction","volume":"36","author":"Brant","year":"2007","journal-title":"Endocrinol Metab Clin North Am"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60520-0","article-title":"Erectile dysfunction","volume":"381","author":"Shamloul","year":"2013","journal-title":"Lancet"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.pop.2019.02.006","article-title":"Erectile dysfunction","volume":"46","author":"Irwin","year":"2019","journal-title":"Prim Care"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2021.06.007","article-title":"European association of urology guidelines on sexual and reproductive health-2021 update: male sexual dysfunction","volume":"80","author":"Salonia","year":"2021","journal-title":"Eur Urol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1177\/1074248418771896","article-title":"A new perspective on the nitrate-phosphodiesterase type 5 inhibitor interaction","volume":"23","author":"Kloner","year":"2018","journal-title":"J Cardiovasc Pharmacol Ther"},{"key":"B12","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.sxmr.2015.10.011","article-title":"Aging and erectile dysfunction","volume":"4","author":"Echeverri Tirado","year":"2016","journal-title":"Sex Med Rev"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.21037\/tau.2016.11.18","article-title":"Aging related erectile dysfunction-potential mechanism to halt or delay its onset","volume":"6","author":"Ferrini","year":"2017","journal-title":"Transl Androl Urol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-6109.2011.02505.x","article-title":"Investigative models in erectile dysfunction: A state-of-the-art review of current animal models","volume":"8","author":"Chung","year":"2011","journal-title":"J Sex Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114760","article-title":"Molecular and spatial signatures of human and rat corpus cavernosum physiopathological processes at single-cell resolution","volume":"43","author":"Yin","year":"2024","journal-title":"Cell Rep"},{"key":"B16","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell"},{"key":"B17","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.cels.2019.03.003","article-title":"Doubletfinder: doublet detection in single-cell rna sequencing data using artificial nearest neighbors","volume":"8","author":"McGinnis","year":"2019","journal-title":"Cell Syst"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-024-01020-z","article-title":"Using clusterprofiler to characterize multiomics data","volume":"19","author":"Xu","year":"2024","journal-title":"Nat Protoc"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr260","article-title":"Molecular signatures database (Msigdb) 3.0","volume":"27","author":"Liberzon","year":"2011","journal-title":"Bioinformatics"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7","article-title":"Gsva: gene set variation analysis for microarray and rna-seq data","volume":"14","author":"Hanzelmann","year":"2013","journal-title":"BMC Bioinf"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-020-0336-2","article-title":"A scalable scenic workflow for Single-cell gene regulatory network analysis","volume":"15","author":"Van de Sande","year":"2020","journal-title":"Nat Protoc"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res"},{"key":"B23","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1038\/s41596-024-01045-4","article-title":"Cellchat for systematic analysis of cell-cell communication from single-cell transcriptomics","volume":"20","author":"Jin","year":"2025","journal-title":"Nat Protoc"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1016\/j.ccell.2022.10.008","article-title":"High-resolution single-cell atlas reveals diversity and plasticity of tissue-resident neutrophils in non-small cell lung cancer","volume":"40","author":"Salcher","year":"2022","journal-title":"Cancer Cell"},{"key":"B25","doi-asserted-by":"publisher","first-page":"4827","DOI":"10.1038\/s41467-022-32552-1","article-title":"A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues","volume":"13","author":"Saul","year":"2022","journal-title":"Nat Commun"},{"key":"B26","doi-asserted-by":"publisher","first-page":"4302","DOI":"10.1038\/s41467-022-31950-9","article-title":"Single-cell transcriptome atlas of the human corpus cavernosum","volume":"13","author":"Zhao","year":"2022","journal-title":"Nat Commun"},{"key":"B27","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1093\/procel\/pwad039","article-title":"A single-nucleus transcriptomic atlas of primate liver aging uncovers the pro-senescence role of srebp2 in hepatocytes","volume":"15","author":"Yang","year":"2024","journal-title":"Protein Cell"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.220004","article-title":"Notch signalling in healthy and diseased vasculature","volume":"12","author":"Del Gaudio","year":"2022","journal-title":"Open Biol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/srep10891","article-title":"The pericyte as a cellular regulator of penile erection and a novel therapeutic target for erectile dysfunction","volume":"5","author":"Yin","year":"2015","journal-title":"Sci Rep"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz849","article-title":"Matrisomedb: the ecm-protein knowledge database","volume":"48","author":"Shao","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsxm.2016.01.016","article-title":"Pharmacotherapy for erectile dysfunction: recommendations from the fourth international consultation for sexual medicine (Icsm 2015)","volume":"13","author":"Hatzimouratidis","year":"2016","journal-title":"J Sex Med"},{"key":"B32","doi-asserted-by":"publisher","first-page":"802","DOI":"10.3390\/brainsci13050802","article-title":"Erectile dysfunction: treatments, advances and new therapeutic strategies","volume":"13","author":"Argiolas","year":"2023","journal-title":"Brain Sci"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2003.t01-1-12045.x","article-title":"Acrokeratosis verruciformis of hopf is caused by mutation in atp2a2: evidence that it is allelic to darier\u2019s disease","volume":"120","author":"Dhitavat","year":"2003","journal-title":"J Invest Dermatol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"16003","DOI":"10.1038\/nrdp.2016.3","article-title":"Erectile dysfunction","volume":"2","author":"Yafi","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn325","article-title":"Phosphoinositide 3-kinase signalling in the vascular system","volume":"82","author":"Morello","year":"2009","journal-title":"Cardiovasc Res"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)80595-4","article-title":"Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor","volume":"96","author":"Brunet","year":"1999","journal-title":"Cell"},{"key":"B37","article-title":"Egr-1 mediates transcriptional activation of igf-ii gene in response to hypoxia","volume":"59","author":"Bae","year":"1999","journal-title":"Cancer Res"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65312-6","article-title":"Pathways of egr-1-mediated gene transcription in vascular biology","volume":"154","author":"Silverman","year":"1999","journal-title":"Am J Pathol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"2248","DOI":"10.3390\/jcm10112248","article-title":"Circulating ptgs2, jag1, gucy2c and pgf mrna in peripheral blood and serum as potential biomarkers for patients with metastatic colon cancer","volume":"10","author":"Jimenez-Luna","year":"2021","journal-title":"J Clin Med"},{"key":"B40","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s12915-017-0381-7","article-title":"Differential darc\/ackr1 expression distinguishes venular from non-venular endothelial cells in murine tissues","volume":"15","author":"Thiriot","year":"2017","journal-title":"BMC Biol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.110.215871","article-title":"Differential endothelial transcriptomics identifies semaphorin 3g as a vascular class 3 semaphorin","volume":"31","author":"Kutschera","year":"2011","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.23869","article-title":"Decorin is a pivotal effector in the extracellular matrix and tumour microenvironment","volume":"9","author":"Zhang","year":"2018","journal-title":"Oncotarget"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1914143116","article-title":"Single-cell transcriptomics of the human retinal pigment epithelium and choroid in health and macular degeneration","volume":"116","author":"Voigt","year":"2019","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B44","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1161\/ATVBAHA.109.196725","article-title":"Fibulin-2 and fibulin-5 cooperatively function to form the internal elastic lamina and protect from vascular injury","volume":"30","author":"Chapman","year":"2010","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abf4335","article-title":"Foxc2 controls adult lymphatic endothelial specialization, function, and gut lymphatic barrier preventing multiorgan failure","volume":"7","author":"Gonzalez-Loyola","year":"2021","journal-title":". Sci Adv"},{"key":"B46","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s13059-020-1949-z","article-title":"Robustness and applicability of transcription factor and pathway analysis tools on single-cell rna-seq data","volume":"21","author":"Holland","year":"2020","journal-title":"Genome Biol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/7805115","article-title":"Txnip: A double-edged sword in disease and therapeutic outlook","volume":"2022","author":"Pan","year":"2022","journal-title":"Oxid Med Cell Longev"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-0316","article-title":"Spatiotemporal immune landscape of colorectal cancer liver metastasis at single-cell level","volume":"12","author":"Wu","year":"2022","journal-title":"Cancer Discov"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.21.8612","article-title":"The metabolism of L-arginine and its significance for the biosynthesis of endothelium-derived relaxing factor: cultured endothelial cells recycle L-citrulline to L-arginine","volume":"87","author":"Hecker","year":"1990","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2021.02.041","article-title":"Mitochondrial redox and tca cycle metabolite signaling in the heart","volume":"166","author":"Vujic","year":"2021","journal-title":"Free Radic Biol Med"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.18.6964","article-title":"Primary structure, synthesis, and biological activity of rat endothelin, an endothelium-derived vasoconstrictor peptide","volume":"85","author":"Yanagisawa","year":"1988","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/ni944","article-title":"Btla is a lymphocyte inhibitory receptor with similarities to ctla-4 and pd-1","volume":"4","author":"Watanabe","year":"2003","journal-title":"Nat Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01210-5","article-title":"Autoreactive cd8(+) T cells are restrained by an exhaustion-like program that is maintained by lag3","volume":"23","author":"Grebinoski","year":"2022","journal-title":"Nat Immunol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/imm.12888","article-title":"Human dendritic cell subsets: an update","volume":"154","author":"Collin","year":"2018","journal-title":"Immunology"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1126\/science.abe6474","article-title":"Pan-cancer single-cell landscape of tumor-infiltrating T cells","volume":"374","author":"Zheng","year":"2021","journal-title":"Science"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/1650456","article-title":"Intermittent hypoxia enhances thp-1 monocyte adhesion and chemotaxis and promotes M1 macrophage polarization via rage","volume":"2018","author":"Zhou","year":"2018","journal-title":"BioMed Res Int"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.02.009","article-title":"Interferon gamma induces reversible metabolic reprogramming of M1 macrophages to sustain cell viability and pro-inflammatory activity","volume":"30","author":"Wang","year":"2018","journal-title":"EBioMedicine"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00614","article-title":"Molecular mechanisms that influence the macrophage M1-M2 polarization balance","volume":"5","author":"Wang","year":"2014","journal-title":"Front Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.104","article-title":"Nf-kappab signaling in inflammation and cancer","volume":"2","author":"Zhang","year":"2021","journal-title":"MedComm (2020)"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.050186","article-title":"Transcription factor maff (Maf basic leucine zipper transcription factor F) regulates an atherosclerosis relevant network connecting inflammation and cholesterol metabolism","volume":"143","author":"von Scheidt","year":"2021","journal-title":"Circulation"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14493","article-title":"Zinc finger protein 91 positively regulates the production of il-1beta in macrophages by activation of mapks and non-canonical caspase-8 inflammasome","volume":"175","author":"Mi","year":"2018","journal-title":"Br J Pharmacol"},{"key":"B62","doi-asserted-by":"publisher","first-page":"2387","DOI":"10.1038\/s41467-019-10335-5","article-title":"Senescent cells evade immune clearance via hla-E-mediated nk and cd8(+) T cell inhibition","volume":"10","author":"Pereira","year":"2019","journal-title":"Nat Commun"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/35869","article-title":"Hla-E binds to natural killer cell receptors cd94\/nkg2a","volume":"391","author":"Braud","year":"1998","journal-title":"Nature"},{"key":"B64","doi-asserted-by":"publisher","first-page":"e13783","DOI":"10.1111\/acel.13783","article-title":"Age-associated adipose tissue inflammation promotes monocyte chemotaxis and enhances atherosclerosis","volume":"22","author":"Song","year":"2023","journal-title":"Aging Cell"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.12.8670","article-title":"Chemokine receptor ccr1 regulates inflammatory cell infiltration after renal ischemia-reperfusion injury","volume":"181","author":"Furuichi","year":"2008","journal-title":"J Immunol"},{"key":"B66","doi-asserted-by":"publisher","first-page":"RP88942","DOI":"10.7554\/eLife.88942","article-title":"Single-cell transcriptome analysis of cavernous tissues reveals the key roles of pericytes in diabetic erectile dysfunction","volume":"12","author":"Bae","year":"2024","journal-title":"Elife"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.874915","article-title":"Single-cell rna sequencing of human corpus cavernosum reveals cellular heterogeneity landscapes in erectile dysfunction","volume":"13","author":"Fang","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2022.106343","article-title":"Heterogeneity of fibroblasts is a hallmark of age-associated erectile dysfunction","volume":"156","author":"Liu","year":"2023","journal-title":"Int J Biochem Cell Biol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-6109.2008.01105.x","article-title":"Fibrosis and loss of smooth muscle in the corpora cavernosa precede corporal veno-occlusive dysfunction (Cvod) induced by experimental cavernosal nerve damage in the rat","volume":"6","author":"Ferrini","year":"2009","journal-title":"J Sex Med"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.3390\/ijms19061712","article-title":"he impact of the nitric oxide (No)\/soluble guanylyl cyclase (Sgc) signaling cascade on kidney health and disease: A preclinical perspective","volume":"19","author":"Krishnan","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1111\/jsm.12613","article-title":"Hydroxyl fasudil, an inhibitor of rho signaling, improves erectile function in diabetic rats: A role for neuronal rock","volume":"11","author":"Sezen","year":"2014","journal-title":"J Sex Med"},{"key":"B72","doi-asserted-by":"publisher","first-page":"22","DOI":"10.3390\/antiox13091099","article-title":"Role of phytochemicals in treatment of aging and cancer: focus on mechanism of foxo3 activation","volume":"13","author":"Park","year":"2024","journal-title":"Antioxidants (Basel)"},{"key":"B73","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.3390\/cells11061017","article-title":"Aging of the immune system: focus on natural killer cells phenotype and functions","volume":"11","author":"Brauning","year":"2022","journal-title":"Cells"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/j.gpb.2021.08.001","article-title":"The genome sequence archive family: toward explosive data growth and diverse data types","volume":"19","author":"Chen","year":"2021","journal-title":"Genomics Proteomics Bioinf"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab951","article-title":"Database resources of the national genomics data center, China national center for bioinformation in 2022","volume":"50","author":"Xue","year":"2022","journal-title":"Nucleic Acids Res"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1671482\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T05:30:20Z","timestamp":1761715820000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1671482\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,29]]},"references-count":75,"alternative-id":["10.3389\/fendo.2025.1671482"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1671482","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,29]]},"article-number":"1671482"}}