{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:48:15Z","timestamp":1791953295216,"version":"4.3.4"},"reference-count":79,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Disruption of the natural light regimen is considered a key pathogenetic factor in the development of desynchronosis and associated diseases. The pineal gland, as a neuroendocrine organ, is a central component of the circadian system and the primary target of the pathogenic effects of disrupted lighting. However, it remains unclear whether the mechanisms of pineal damage differ between different types of light stress. In this study, 120 male Wistar rats underwent a comprehensive analysis of the morphofunctional state of the pineal gland under two lighting regimens: constant lighting and intermittent constant light. Using light and electron microscopy, immunohistochemistry, ELISA, and cosinor analysis, it was established that the two regimens induce qualitatively different types of light stress. The obtained data indicate that constant lighting induces a degenerative phenotype with loss of rhythmic organization, whereas the shift regimen produces a phenotype of chronic re-adaptation with hyperactivation of the lysosomal system, paradoxical overexpression of clock genes, and pronounced metabolic disturbances. The identified differential markers may serve as a basis for preclinical evaluation of the efficacy of chronobiotic therapy and for the development of prevention strategies for disorders associated with shift work and light pollution.<\/jats:p>","DOI":"10.3390\/ijms27198817","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:14:56Z","timestamp":1790936096000},"page":"8817","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Constant Light Versus Intermittent Constant Light\/Recovery Regimen: Differential Effects on Pineal Ultrastructure, Clock Gene Protein Abundance, and Systemic Metabolism in Rats"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0011-1114","authenticated-orcid":false,"given":"Anna I.","family":"Anurkina","sequence":"first","affiliation":[{"name":"Petrovsky National Research Centre of Surgery, 119435 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Kozlova","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Centre of Surgery, 119435 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valery P.","family":"Chernikov","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Centre of Surgery, 119435 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2732-5676","authenticated-orcid":false,"given":"Nikita S.","family":"Gladyshev","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Centre of Surgery, 119435 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa E.","family":"Zavalishina","sequence":"additional","affiliation":[{"name":"Department of Pathological Anatomy, Russian Medical Academy of Continuous Professional Education, 125993 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris N.","family":"Kulbitskiy","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Centre of Surgery, 119435 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3006-6281","authenticated-orcid":false,"given":"David A.","family":"Areshidze","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Centre of Surgery, 119435 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20140121","DOI":"10.1098\/rstb.2014.0121","article-title":"Artificial light at night: Melatonin as a mediator between the environment and epigenome","volume":"370","author":"Haim","year":"2015","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1080\/07420528.2018.1527773","article-title":"Systematic review of light exposure impact on human circadian rhythm","volume":"36","author":"Partonen","year":"2019","journal-title":"Chronobiol. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1134\/S2079057017010131","article-title":"The role of circadian rhythms and the \u201ccellular clock\u201d in age-associated diseases","volume":"7","author":"Panchenko","year":"2017","journal-title":"Adv. Gerontol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41392-022-00899-y","article-title":"Molecular regulations of circadian rhythm and implications for physiology and diseases","volume":"7","author":"Fagiani","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1038\/s41591-018-0271-8","article-title":"The emerging link between cancer, metabolism, and circadian rhythms","volume":"24","author":"Masri","year":"2018","journal-title":"Nat. Med."},{"key":"ref_6","first-page":"35","article-title":"Light pollution, reproductive function and cancer risk","volume":"27","author":"Anisimov","year":"2006","journal-title":"Neuro Endocrinol. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Vasey, C., McBride, J., and Penta, K. (2021). Circadian Rhythm Dysregulation and Restoration: The Role of Melatonin. Nutrients, 13.","DOI":"10.3390\/nu13103480"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Peters, B., Vahlhaus, J., and Pivovarova-Ramich, O. (2024). Meal timing and its role in obesity and associated diseases. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1359772"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s40572-017-0155-y","article-title":"Night shift work and risk of breast cancer","volume":"4","author":"Hansen","year":"2017","journal-title":"Curr. Environ. Health Rep."},{"key":"ref_10","unstructured":"Feingold, K.R., Adler, R.A., Ahmed, S.F., Anawalt, B., Blackman, M.R., Chrousos, G., Corpas, E., de Herder, W.W., Dhatariya, K., and Dungan, K. (2022). Physiology of the Pineal Gland and Melatonin. Endotext, MDText.com, Inc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"110687","DOI":"10.1016\/j.mce.2019.110687","article-title":"Temporal organization of pineal melatonin signaling in mammals","volume":"503","author":"Gorman","year":"2020","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1152\/physiol.00011.2014","article-title":"Melatonin: Exceeding Expectations","volume":"29","author":"Reiter","year":"2014","journal-title":"Physiology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/0166-4328(96)00083-6","article-title":"Neural control of the pineal gland","volume":"73","author":"Moore","year":"1996","journal-title":"Behav. Brain Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Reiter, R.J., Rosales-Corral, S.A., Tan, D.X., Acuna-Castroviejo, D., Qin, L., Yang, S.F., and Xu, K. (2017). Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18040843"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1111\/ejn.14298","article-title":"Circadian disruption and human health: A bidirectional relationship","volume":"51","author":"Abbott","year":"2020","journal-title":"Eur. J. Neurosci."},{"key":"ref_16","first-page":"501","article-title":"Artificial lighting in the industrialized world: Circadian disruption and breast cancer","volume":"17","author":"Stevens","year":"2006","journal-title":"Cancer Causes Control"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"R271","DOI":"10.1093\/hmg\/ddl207","article-title":"Molecular components of the mammalian circadian clock","volume":"15","author":"Ko","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41580-019-0179-2","article-title":"Molecular mechanisms and physiological importance of circadian rhythms","volume":"21","author":"Patke","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1177\/074873001129001980","article-title":"Mammalian photoperiodic system: Formal properties and neuroendocrine mechanisms of photoperiodic time measurement","volume":"16","author":"Goldman","year":"2001","journal-title":"J. Biol. Rhythm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1126\/science.1132009","article-title":"Characterizing a mammalian circannual pacemaker","volume":"314","author":"Lincoln","year":"2006","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1159\/000327430","article-title":"A noradrenergic sensitive endogenous clock is present in the rat pineal gland","volume":"94","author":"Wongchitrat","year":"2011","journal-title":"Neuroendocrinology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1159\/000535567","article-title":"3-Dimensional Ultrastructural Analysis of the Rat Pinealocyte: Presence of Secretory Bulbous Projections Delineated from the Cell Body by Junctional Complexes","volume":"114","author":"Midtgaard","year":"2024","journal-title":"Neuroendocrinology"},{"key":"ref_23","first-page":"405","article-title":"Ultrastructure of the pineal gland in the adult rat","volume":"138","author":"Calvo","year":"1984","journal-title":"J. Anat."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"226","DOI":"10.15386\/mpr-1235","article-title":"The morphological and functional characteristics of the pineal gland","volume":"92","author":"Gheban","year":"2019","journal-title":"Med. Pharm. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s00441-002-0580-5","article-title":"The anatomy and innervation of the mammalian pineal gland","volume":"309","author":"Baeres","year":"2002","journal-title":"Cell Tissue Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e70074","DOI":"10.1111\/jpi.70074","article-title":"Morten M\u00f8ller: In Memoriam","volume":"77","author":"Korf","year":"2025","journal-title":"J. Pineal Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s00441-008-0627-3","article-title":"Active zone proteins are dynamically associated with synaptic ribbons in rat pinealocytes","volume":"333","author":"Maus","year":"2008","journal-title":"Cell Tissue Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"E463","DOI":"10.1210\/jc.2010-2098","article-title":"Exposure to room light before bedtime suppresses melatonin onset and shortens melatonin duration in humans","volume":"96","author":"Gooley","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1615\/CritRevOncog.v13.i4.30","article-title":"Light at night, chronodisruption, melatonin suppression, and cancer risk: A review","volume":"13","author":"Reiter","year":"2007","journal-title":"Crit. Rev. Oncog."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/j.1600-079X.1984.tb00224.x","article-title":"Effect of acute light exposure upon melatonin content, NAT activity, and nuclear volume in the gerbil pineal complex","volume":"1","author":"Rollag","year":"1984","journal-title":"J. Pineal Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/jez.a.10210","article-title":"Two morphological types of pineal window in catfish in relation to photophase and scotophase activity: A morphological and experimental study","volume":"295","author":"Srivastava","year":"2003","journal-title":"J. Exp. Zool. A Comp. Exp. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1093\/micmic\/ozad101","article-title":"Changes in Rat Adrenal Cortex and Pineal Gland in Inverted Light-Dark Cycle: A Biochemical, Histological, and Immunohistochemical Study","volume":"29","author":"Shawky","year":"2023","journal-title":"Microsc. Microanal."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1126\/science.142.3595.1071","article-title":"Melatonin synthesis in the pineal gland: Control by light","volume":"142","author":"Wurtman","year":"1963","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1126\/science.169.3950.1093","article-title":"Indole metabolism in the pineal gland: A circadian rhythm in N-acetyltransferase","volume":"169","author":"Klein","year":"1970","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4233","DOI":"10.1074\/jbc.R600036200","article-title":"Arylalkylamine N-acetyltransferase: \u201cthe Timezyme\u201d","volume":"282","author":"Klein","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_36","first-page":"309","article-title":"Constant light and dark affect the circadian rhythm of the hypothalamic-pituitary-adrenal axis","volume":"47","author":"Fischman","year":"1988","journal-title":"Neuroendocrinology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s00360-025-01615-2","article-title":"Adaptation under constant light or dark: A challenge to the pineal","volume":"195","author":"Becin","year":"2025","journal-title":"J. Comp. Physiol. B"},{"key":"ref_38","unstructured":"Zvereva, Y.Y., Bol\u2019shakova, O.V., and Bessalova, Y.Y. (2016). Ultrastructure of pineal gland cells in white rats. Spring Anatomical Readings, Grodno State Medical University. (In Russian)."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/jpi.12360","article-title":"Melatonin as an antioxidant: Under promises but over delivers","volume":"61","author":"Reiter","year":"2016","journal-title":"J. Pineal Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Chitimus, D.M., Popescu, M.R., Voiculescu, S.E., Panaitescu, A.M., Pavel, B., Zagrean, L., and Zagrean, A.-M. (2020). Melatonin\u2019s Impact on Antioxidative and Anti-Inflammatory Reprogramming in Homeostasis and Disease. Biomolecules, 10.","DOI":"10.3390\/biom10091211"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1016\/j.freeradbiomed.2010.02.020","article-title":"Oxidative stress, mitochondrial bioenergetics, and cardiolipin in aging","volume":"48","author":"Paradies","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1007\/s10517-010-1076-z","article-title":"Morphological changes in the pineal gland of rats under conditions of long-term exposure to bright light","volume":"150","author":"Gerasimov","year":"2010","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Tan, D.X., Xu, B., Zhou, X., and Reiter, R.J. (2018). Pineal Calcification, Melatonin Production, Aging, Associated Health Consequences and Rejuvenation of the Pineal Gland. Molecules, 23.","DOI":"10.3390\/molecules23020301"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Kubi\u0161tov\u00e1, A., Spi\u0161sk\u00e1, V., Petr\u017eelkov\u00e1, L., Hrubcov\u00e1, L., Moravcov\u00e1, S., Maierov\u00e1, L., and Bendov\u00e1, Z. (2020). Constant Light in Critical Postnatal Days Affects Circadian Rhythms in Locomotion and Gene Expression in the Suprachiasmatic Nucleus, Retina, and Pineal Gland Later in Life. Biomedicines, 8.","DOI":"10.3390\/biomedicines8120579"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"170","DOI":"10.2174\/1874609811205030002","article-title":"Light-at-night-induced circadian disruption, cancer and aging","volume":"5","author":"Anisimov","year":"2012","journal-title":"Curr. Aging Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"221","DOI":"10.3109\/07853890.2014.892296","article-title":"Cross-talk between the circadian clock and the cell cycle in cancer","volume":"46","year":"2014","journal-title":"Ann. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/nrn3393","article-title":"The circadian clock: A framework linking metabolism, epigenetics and neuronal function","volume":"14","author":"Masri","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1080\/07420520500482108","article-title":"The avian pineal gland","volume":"23","author":"Csernus","year":"2006","journal-title":"Chronobiol. Int."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Galan, L., Solcan, G., and Solcan, C. (2025). The Influence of Different Light Spectra on Broiler Chicken Endocrine Systems and Productivity. Animals, 15.","DOI":"10.3390\/ani15213209"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1007\/s00018-014-1579-2","article-title":"Extrapineal melatonin: Sources, regulation, and potential functions","volume":"71","author":"Escames","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Bocheva, G., Bakalov, D., Iliev, P., and Tafradjiiska-Hadjiolova, R. (2024). The Vital Role of Melatonin and Its Metabolites in the Neuroprotection and Retardation of Brain Aging. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25105122"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Tobeiha, M., Jafari, A., Fadaei, S., Mirazimi, S.M.A., Dashti, F., Amiri, A., Khan, H., Asemi, Z., Reiter, R.J., and Hamblin, M.R. (2022). Evidence for the Benefits of Melatonin in Cardiovascular Disease. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.888319"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.cell.2013.10.026","article-title":"RNA-methylation-dependent RNA processing controls the speed of the circadian clock","volume":"155","author":"Fustin","year":"2013","journal-title":"Cell"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Chen, M., Chen, M., Lu, D., Wang, Y., Zhang, L., Wang, Z., and Wu, B. (2021). Period 2 Regulates CYP2B10 Expression and Activity in Mouse Liver. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.764124"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Ze\u010devi\u0107, K., Popovi\u0107, N., Vuksanovi\u0107 Bo\u017eari\u0107, A., Vukmirovi\u0107, M., Rizzo, M., and Muzurovi\u0107, E. (2023). Timing Is Important-Management of Metabolic Syndrome According to the Circadian Rhythm. Biomedicines, 11.","DOI":"10.3390\/biomedicines11041171"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4642","DOI":"10.1038\/emboj.2011.322","article-title":"Temporal orchestration of circadian autophagy rhythm by C\/EBP\u03b2","volume":"30","author":"Ma","year":"2011","journal-title":"EMBO J."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Won, E., Na, K.S., and Kim, Y.K. (2021). Associations between Melatonin, Neuroinflammation, and Brain Alterations in Depression. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010305"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s10522-013-9437-4","article-title":"Melatonin prevents the development of the metabolic syndrome in male rats exposed to different light\/dark regimens","volume":"14","author":"Vinogradova","year":"2013","journal-title":"Biogerontology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"E211","DOI":"10.1152\/ajpendo.91014.2008","article-title":"Central role of ceramide biosynthesis in body weight regulation, energy metabolism, and the metabolic syndrome","volume":"297","author":"Yang","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Ma, K., Xiao, R., Tseng, H.T., Shan, L., Fu, L., and Moore, D.D. (2009). Circadian dysregulation disrupts bile acid homeostasis. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006843"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.jhep.2019.03.020","article-title":"The circadian clock and liver function in health and disease","volume":"71","author":"Mukherji","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.yfrne.2013.11.003","article-title":"Sex differences in circadian timing systems: Implications for disease","volume":"35","author":"Bailey","year":"2014","journal-title":"Front. Neuroendocrinol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"101926","DOI":"10.1016\/j.smrv.2024.101926","article-title":"Sex differences in sleep, circadian rhythms, and metabolism: Implications for precision medicine","volume":"75","author":"Lok","year":"2024","journal-title":"Sleep Med. Rev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1159\/000516148","article-title":"The Crosstalk between Melatonin and Sex Steroid Hormones","volume":"112","author":"Amaral","year":"2022","journal-title":"Neuroendocrinology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1146\/annurev-nutr-062122-014528","article-title":"Eating Around the Clock: Circadian Rhythms of Eating and Metabolism","volume":"44","author":"McHill","year":"2024","journal-title":"Ann. Rev. Nutr."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1111\/j.1365-2559.2006.02514.x","article-title":"Quantification of immunohistochemistry\u2014Issues concerning methods, utility and semiquantitative assessment I","volume":"49","author":"Walker","year":"2006","journal-title":"Histopathology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1186\/s13000-014-0221-9","article-title":"Different approaches for interpretation and reporting of immunohistochemistry analysis results in the bone tissue\u2014A review","volume":"9","author":"Fedchenko","year":"2014","journal-title":"Diagn. Pathol."},{"key":"ref_68","unstructured":"Challet, E. (2019). Circadian clocks and food intake. Nutrients, 11."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/j.1749-6632.1985.tb11812.x","article-title":"Action spectra, dose-response relationships, and temporal aspects of light\u2019s effects on the pineal gland","volume":"453","author":"Reiter","year":"1985","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"6405","DOI":"10.1523\/JNEUROSCI.21-16-06405.2001","article-title":"Action spectrum for melatonin regulation in humans: Evidence for a novel circadian photoreceptor","volume":"21","author":"Brainard","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1179\/016164102101200690","article-title":"Effects of euthanasia on brain physiological activities monitored in real-time","volume":"24","author":"Mayevsky","year":"2002","journal-title":"Neurol. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1258\/002367796780739871","article-title":"Recommendations for euthanasia of experimental animals: Part 1. DGXI of the European Commission","volume":"30","author":"Close","year":"1996","journal-title":"Lab Anim."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1258\/002367797780600297","article-title":"Recommendations for euthanasia of experimental animals: Part 2. DGXT of the European Commission","volume":"31","author":"Close","year":"1997","journal-title":"Lab Anim."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Howard, V., and Reed, M. (2004). Unbiased Stereology: Three-Dimensional Measurement in Microscopy, Garland Science.","DOI":"10.4324\/9780203006399"},{"key":"ref_75","unstructured":"Mutak, A. (2025, June 16). Cosinor2: Extended Cosinor Analysis of Rhythms. R Package Version 0.2.1. Available online: https:\/\/CRAN.R-project.org\/package=cosinor2."},{"key":"ref_76","first-page":"305","article-title":"Methods for cosinor-rhythmometry","volume":"6","author":"Nelson","year":"1979","journal-title":"Chronobiologia"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1742-4682-11-16","article-title":"Cosinor-based rhythmometry","volume":"11","author":"Cornelissen","year":"2014","journal-title":"Theor. Biol. Med. Model."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.edurev.2010.12.001","article-title":"Eta squared and partial eta squared as measures of effect size in educational research","volume":"6","author":"Richardson","year":"2011","journal-title":"Educ. Res. Rev."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"du Sert, N.P., Hurst, V., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., and Dirnagl, U. (2020). The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000410"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8817\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:15:14Z","timestamp":1791951314000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,2]]},"references-count":79,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["ijms27198817"],"URL":"https:\/\/doi.org\/10.3390\/ijms27198817","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,2]]}}}