{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T02:13:21Z","timestamp":1782526401279,"version":"3.54.5"},"reference-count":55,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:00:00Z","timestamp":1634860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["Project-ID 394046635 \u2013 SFB 1365"],"award-info":[{"award-number":["Project-ID 394046635 \u2013 SFB 1365"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endothelial dysfunction (ED) comes with age, even without overt vessel damage such as that which occurs in atherosclerosis and diabetic vasculopathy. We hypothesized that aging would affect the downstream signalling of the endothelial nitric oxide (NO) system in the vascular smooth muscle (VSM). With this in mind, resistance mesenteric arteries were isolated from 13-week (juvenile) and 40-week-old (aged) mice and tested under isometric conditions using wire myography. Acetylcholine (ACh)-induced relaxation was reduced in aged as compared to juvenile vessels. Pretreatment with L-NAME, which inhibits nitrix oxide synthases (NOS), decreased ACh-mediated vasorelaxation, whereby differences in vasorelaxation between groups disappeared. Endothelium-independent vasorelaxation by the NO donor sodium nitroprusside (SNP) was similar in both groups; however, SNP bolus application (10\u22126 mol L\u22121) as well as soluble guanylyl cyclase (sGC) activation by runcaciguat (10\u22126 mol L\u22121) caused faster responses in juvenile vessels. This was accompanied by higher cGMP concentrations and a stronger response to the PDE5 inhibitor sildenafil in juvenile vessels. Mesenteric arteries and aortas did not reveal apparent histological differences between groups (van Gieson staining). The mRNA expression of the \u03b11 and \u03b12 subunits of sGC was lower in aged animals, as was PDE5 mRNA expression. In conclusion, vasorelaxation is compromised at an early age in mice even in the absence of histopathological alterations. Vascular smooth muscle sGC is a key element in aged vessel dysfunction.<\/jats:p>","DOI":"10.3390\/ijms222111412","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T09:18:09Z","timestamp":1634894289000},"page":"11412","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Age Impairs Soluble Guanylyl Cyclase Function in Mouse Mesenteric Arteries"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5422-3766","authenticated-orcid":false,"given":"Cheng","family":"Zhong","sequence":"first","affiliation":[{"name":"Institute of Vegetative Physiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minze","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Vegetative Physiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seng\u00fcl","family":"Boral","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Summer","sequence":"additional","affiliation":[{"name":"Bayer AG, Research & Development, 42113 Wuppertal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3849-2288","authenticated-orcid":false,"given":"Falk-Bach","family":"Lichtenberger","sequence":"additional","affiliation":[{"name":"Institute of Vegetative Physiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6319-0978","authenticated-orcid":false,"given":"Cem","family":"Erdo\u011fan","sequence":"additional","affiliation":[{"name":"Institute of Vegetative Physiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maik","family":"Gollasch","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center (ECRC), Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 13125 Berlin, Germany"},{"name":"Department of Internal and Geriatric Medicine, University of Greifswald, Geriatric Medicine, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9868-1873","authenticated-orcid":false,"given":"Stefan","family":"Golz","sequence":"additional","affiliation":[{"name":"Bayer AG, Research & Development, 42113 Wuppertal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pontus B.","family":"Persson","sequence":"additional","affiliation":[{"name":"Institute of Vegetative Physiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Schleifenbaum","sequence":"additional","affiliation":[{"name":"Institute of Vegetative Physiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1088-6875","authenticated-orcid":false,"given":"Andreas","family":"Patzak","sequence":"additional","affiliation":[{"name":"Institute of Vegetative Physiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9platz 1, 10117 Berlin, 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Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1016\/S0140-6736(17)30763-8","article-title":"From arterial ageing to cardiovascular disease","volume":"389","author":"Koopman","year":"2017","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.cardiores.2004.12.027","article-title":"Endothelial aging","volume":"66","author":"Brandes","year":"2005","journal-title":"Cardiovasc. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1161\/01.CIR.88.1.77","article-title":"Effects of age on endothelium-dependent vasodilation of resistance coronary artery by acetylcholine in humans","volume":"88","author":"Egashira","year":"1993","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1161\/01.STR.19.7.892","article-title":"Effects of aging and hypertension on endothelium-dependent vascular relaxation in rat carotid artery","volume":"19","author":"Hongo","year":"1988","journal-title":"Stroke"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"157","DOI":"10.4149\/gpb_2019055","article-title":"Epac-mediated relaxation in murine basilar arteries depends on membrane permeability of cyclic nucleotide analogues and endothelial aging","volume":"39","author":"Welter","year":"2020","journal-title":"Gen. Physiol. Biophys."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1042\/cs1020595","article-title":"Ageing is associated with impairment of nitric oxide and prostanoid dilator pathways in the human forearm","volume":"102","author":"Singh","year":"2002","journal-title":"Clin. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"F193","DOI":"10.1152\/ajprenal.00272.2020","article-title":"Role of soluble guanylyl cyclase in renal afferent and efferent arterioles","volume":"320","author":"Wennysia","year":"2021","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.exer.2013.01.012","article-title":"Contribution of nitric oxide synthase isoforms to cholinergic vasodilation in murine retinal arterioles","volume":"109","author":"Gericke","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3181\/00379727-211-43950A","article-title":"Nitric oxide and cyclic GMP signaling","volume":"211","author":"McDonald","year":"1996","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"322","DOI":"10.14336\/AD.2017.0523","article-title":"Age-Dependent Decrease in Adropin is Associated with Reduced Levels of Endothelial Nitric Oxide Synthase and Increased Oxidative Stress in the Rat Brain","volume":"9","author":"Yang","year":"2018","journal-title":"Aging Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1113\/jphysiol.2003.057042","article-title":"Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing","volume":"556","author":"Eskurza","year":"2004","journal-title":"J. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1161\/01.HYP.37.2.529","article-title":"Superoxide excess in hypertension and aging: A common cause of endothelial dysfunction","volume":"37","author":"Hamilton","year":"2001","journal-title":"Hypertension"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1161\/ATVBAHA.119.313129","article-title":"Mechanisms of Arterial Stiffening: From Mechanotransduction to Epigenetics","volume":"40","author":"Lacolley","year":"2020","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ma, L., Wang, K., Shang, J., Cao, C., Zhen, P., Liu, X., Wang, W., Zhang, H., Du, Y., and Liu, H. (2014). Anti-peroxynitrite treatment ameliorated vasorelaxation of resistance arteries in aging rats: Involvement with NO-sGC-cGKs pathway. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0104788"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1093\/cvr\/cvy212","article-title":"Endothelial SIRT1 prevents age-induced impairment of vasodilator responses by enhancing the expression and activity of soluble guanylyl cyclase in smooth muscle cells","volume":"115","author":"Guo","year":"2019","journal-title":"Cardiovasc. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e00200","DOI":"10.1002\/prp2.200","article-title":"Translational value of mechanical and vasomotor properties of mouse isolated mesenteric resistance-sized arteries","volume":"3","author":"Outzen","year":"2015","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5323","DOI":"10.1021\/acs.jmedchem.0c02154","article-title":"Discovery of the Soluble Guanylate Cyclase Activator Runcaciguat (BAY 1101042)","volume":"64","author":"Hahn","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"R35","DOI":"10.1530\/VB-20-0013","article-title":"The aging endothelium","volume":"3","author":"Ting","year":"2021","journal-title":"Vasc. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/j.1751-7176.2012.00606.x","article-title":"Impaired vasodilation in the pathogenesis of hypertension: Focus on nitric oxide, endothelial-derived hyperpolarizing factors, and prostaglandins","volume":"14","author":"Giles","year":"2012","journal-title":"J. Clin. Hypertens."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1097\/HJH.0b013e328353e501","article-title":"Defining vascular aging and cardiovascular risk","volume":"30","author":"Laurent","year":"2012","journal-title":"J. Hypertens."},{"key":"ref_22","first-page":"11","article-title":"Age-related endothelial dysfunction with respect to nitric oxide, endothelium-derived hyperpolarizing factor and cyclooxygenase products","volume":"49","author":"Matz","year":"2000","journal-title":"Physiol. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"H805","DOI":"10.1152\/ajpheart.00681.2017","article-title":"Superoxide inhibition restores endothelium-dependent dilatation in aging arteries by enhancing impaired adherens junctions","volume":"314","author":"Chang","year":"2018","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"II-3-10","DOI":"10.1002\/j.1932-8737.1997.tb00006.x","article-title":"Biology of the endothelium","volume":"20","author":"Luscher","year":"1997","journal-title":"Clin. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1152\/japplphysiol.00490.2011","article-title":"Aging alters the contribution of nitric oxide to regional muscle hemodynamic control at rest and during exercise in rats","volume":"111","author":"Hirai","year":"2011","journal-title":"J. Appl. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1152\/japplphysiol.00138.2006","article-title":"Impaired shear stress-induced nitric oxide production through decreased NOS phosphorylation contributes to age-related vascular stiffness","volume":"101","author":"Soucy","year":"2006","journal-title":"J. Appl. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"H1307","DOI":"10.1152\/ajpheart.00792.2002","article-title":"Influence of coronary artery diameter on eNOS protein content","volume":"284","author":"Laughlin","year":"2003","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/j.cjca.2020.02.003","article-title":"How Structure, Mechanics, and Function of the Vasculature Contribute to Blood Pressure Elevation in Hypertension","volume":"36","author":"Schiffrin","year":"2020","journal-title":"Can. J. Cardiol."},{"key":"ref_29","first-page":"H632","article-title":"Endogenous nitric oxide buffers blood pressure variability between 0.2 and 0.6 Hz in the conscious rat","volume":"272","author":"Nafz","year":"1997","journal-title":"Am. J. Physiol."},{"key":"ref_30","first-page":"H521","article-title":"The blood pressure buffering capacity of nitric oxide by comparison to the baroreceptor reflex","volume":"267","author":"Just","year":"1994","journal-title":"Am. J. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1146\/annurev-biochem-050410-100030","article-title":"Structure and regulation of soluble guanylate cyclase","volume":"81","author":"Derbyshire","year":"2012","journal-title":"Annu. Rev. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1089\/ars.2016.6693","article-title":"Structure and Activation of Soluble Guanylyl Cyclase, the Nitric Oxide Sensor","volume":"26","author":"Montfort","year":"2017","journal-title":"Antioxid. Redox Signal."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1023\/A:1014252309493","article-title":"Isoforms of NO-sensitive guanylyl cyclase","volume":"230","author":"Russwurm","year":"2002","journal-title":"Mol. Cell Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1172\/JCI60119","article-title":"Genetic modifiers of hypertension in soluble guanylate cyclase alpha1-deficient mice","volume":"122","author":"Buys","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7699","DOI":"10.1073\/pnas.0609778104","article-title":"Fatal gastrointestinal obstruction and hypertension in mice lacking nitric oxide-sensitive guanylyl cyclase","volume":"104","author":"Friebe","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1161\/CIRCULATIONAHA.109.890962","article-title":"Smooth muscle-specific deletion of nitric oxide-sensitive guanylyl cyclase is sufficient to induce hypertension in mice","volume":"121","author":"Groneberg","year":"2010","journal-title":"Circulation"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Mergia, E., Thieme, M., Hoch, H., Daniil, G., Hering, L., Yakoub, M., Scherbaum, C.R., Rump, L.C., Koesling, D., and Stegbauer, J. (2018). Impact of the NO-Sensitive Guanylyl Cyclase 1 and 2 on Renal Blood Flow and Systemic Blood Pressure in Mice. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19040967"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1172\/JCI27657","article-title":"Spare guanylyl cyclase NO receptors ensure high NO sensitivity in the vascular system","volume":"116","author":"Mergia","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.niox.2020.10.005","article-title":"Preserved activity of soluble guanylate cyclase (sGC) in iliac artery from middle-aged rats: Role of sGC modulators","volume":"106","author":"Justo","year":"2021","journal-title":"Nitric Oxide"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1042\/CS20140753","article-title":"Phosphodiesterase 1 regulation is a key mechanism in vascular aging","volume":"129","author":"Durik","year":"2015","journal-title":"Clin. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Stegbauer, J., Friedrich, S., Potthoff, S.A., Broekmans, K., Cortese-Krott, M.M., Quack, I., Rump, L.C., Koesling, D., and Mergia, E. (2013). Phosphodiesterase 5 attenuates the vasodilatory response in renovascular hypertension. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0080674"},{"key":"ref_42","first-page":"663","article-title":"Phosphodiesterase 3A expression is modulated by nitric oxide in rat pulmonary artery smooth muscle cells","volume":"61","author":"Busch","year":"2010","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1007\/s00424-017-2106-8","article-title":"Phosphodiesterase 3A expression and activity in the murine vasculature is influenced by NO-sensitive guanylyl cyclase","volume":"470","author":"Dunnes","year":"2018","journal-title":"Pflugers Arch."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1111\/bph.13800","article-title":"Activation of alpha1A -adrenoceptors desensitizes the rat aorta response to phenylephrine through a neuronal NOS pathway, a mechanism lost with ageing","volume":"174","author":"Arce","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s13105-014-0343-2","article-title":"Different vasoactive effects of chronic endothelial and neuronal NO-synthase inhibition in young Wistar rats","volume":"70","author":"Cacanyiova","year":"2014","journal-title":"J. Physiol. Biochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e14341","DOI":"10.14814\/phy2.14341","article-title":"Heterogeneous effect of aging on vasorelaxation responses in large and small arteries","volume":"8","author":"Luttrell","year":"2020","journal-title":"Physiol. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/j.exger.2013.08.003","article-title":"Aging-related endothelial dysfunction in the aorta from female senescence-accelerated mice is associated with decreased nitric oxide synthase expression","volume":"48","author":"Novella","year":"2013","journal-title":"Exp. Gerontol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1152\/japplphysiol.00408.2004","article-title":"Shear stress induces eNOS mRNA expression and improves endothelium-dependent dilation in senescent soleus muscle feed arteries","volume":"98","author":"Woodman","year":"2005","journal-title":"J. Appl. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1046\/j.1365-201X.2003.01100.x","article-title":"Exercise training improves ageing-induced decrease in eNOS expression of the aorta","volume":"178","author":"Tanabe","year":"2003","journal-title":"Acta Physiol. Scand."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1161\/01.HYP.31.2.643","article-title":"Alterations of nitric oxide synthase expression with aging and hypertension in rats","volume":"31","author":"Chou","year":"1998","journal-title":"Hypertension"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1161\/01.RES.83.3.279","article-title":"Expression of constitutive and inducible nitric oxide synthases in the vascular wall of young and aging rats","volume":"83","author":"Cernadas","year":"1998","journal-title":"Circ. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1161\/01.RES.41.1.19","article-title":"Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats","volume":"41","author":"Mulvany","year":"1977","journal-title":"Circ. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/260617a0","article-title":"Mechanical properties of vascular smooth muscle cells in situ","volume":"260","author":"Mulvany","year":"1976","journal-title":"Nature"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_55","unstructured":"(2014). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: http:\/\/www.r-project.org\/."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/21\/11412\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:21:15Z","timestamp":1760167275000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/21\/11412"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,22]]},"references-count":55,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["ijms222111412"],"URL":"https:\/\/doi.org\/10.3390\/ijms222111412","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,22]]}}}