Factors associated with chronotype, job burnout, and perceived stress among nurses in Chinese tertiary hospitals: A multicenter cross-sectional study.

Shift work is a recognized work pattern for nurses worldwide. The disruption of shift workers' biological clocks usually leads to sleep disorders and affects their awareness at work. Eveningness and occupational stress might be effective in causing burnout syndrome. Therefore, this study aimed to evaluate the chronotype, job burnout and perceived stress among Chinese tertiary hospital nurses, and understand the predictors of circadian rhythm in this group. Between July and September 2020, 23 hospitals were randomly selected from 113 tertiary hospitals in Hunan Province. Twenty-five percent of the nurses working in each hospital were targeted for selection. 28.1% and 17.6% of nurses reported eveningness type and morningness type, respectively. The scores for emotional exhaustion, depersonalization, and perceived stress of eveningness nurses were higher than those of morningness counterparts. Eveningness nurses also reported a lower sense of personal accomplishment. Risk factors of eveningness included being under 30 years old, never exercising, having the stressors of late-night shifts and career development, higher levels of emotional exhaustion, sleep latency, sleep duration, and hypnotic use. Shifts may be unavoidable for nurses, nevertheless, understanding the predictors and related factors of chronotype for nurses is necessary for nursing educators and managers to develop a reasonable shift system and appropriate measures to assist nurses in adjusting their work.

Sleep Apnea, Autonomic Disturbances, and Blood Pressure Variability.

Augmented blood pressure variability has emerged as a quantity predictive of adverse cardiovascular outcomes. Among the range of intrinsic and extrinsic factors shown to increase night-time, circadian, short-term, and long-term blood pressure variations, the presence and severity of obstructive sleep apnea have emerged as one of the most prevalent and potent. Obstructive sleep apnea alters acutely the normal nocturnal equilibrium between sympathetic and parasympathetic tone, magnifying nocturnal blood pressure oscillations, and induces sustained autonomic aftereffects with the capacity to amplify short-term and intersessional blood pressure variabilities. The object of this brief review is to synthesize the current understanding of the potential interrelations between obstructive sleep apnea, the acute and sustained autonomic disturbances that it elicits, and beat-to-beat blood pressure fluctuation during sleep, nocturnal dipping status, and day-to-day blood pressure variability and the consequences of these perturbations for cardiovascular risk.

Exploring the Role of Circadian Rhythms in Sleep and Recovery: A Review Article.

Sleep is essential for every living organism. Humans spend about one-third of their lives sleeping. Sleep has been studied extensively, and the role of sleep in psychological, mental, and physical well-being is established to be the best. The rhythm of the brain between wakefulness and sleep is called the circadian rhythm, which is mainly controlled by melatonin and the pineal gland. The imbalance of this rhythm can lead to devastating effects on health. Vigorous workouts close to bedtime can interfere with falling asleep. Meal timing and composition can significantly affect sleep quality. It is advised to avoid large meals, caffeine, and alcohol before bedtime. Heavy meals close to bedtime can lead to poor sleep and hormone disruption. By following these guidelines enumerated in the article, individuals can improve sleep quality and overall health. Sleep cycles, especially rapid eye movement sleep, have a profound influence on mental and physical health. Adhering to recommended sleep practices enhances bodily restoration, fortifies the immune system, and upholds metabolic equilibrium. Sleep hygiene aligned with circadian rhythms is crucial for disease prevention and well-being. Healthcare professionals should prioritize sleep optimization strategies for patient care and public health.

Study on the circadian rhythm and sleep state characteristics of patients with acute cerebral infarction accompanied by sleep-breathing disorders.

There is limited research on the circadian rhythm and sleep state in patients with acute cerebral infarction (ACI) accompanied by sleep-breathing disorders (SDB). This study aims to provide a scientific basis for individualized diagnosis and treatment for stroke-related SDB patients. The SC-500 sleep monitor was used to continuously monitor 1367 ACI patients over 5 days. Based on the apnea-hypopnea index (AHI), patients were divided into non-SDB group (normal) and SDB group (mild, moderate, severe, fluctuating). Interdaily stability (IS) and intradaily variability (IV) were calculated through heart rate monitoring, and sleep states and their correlations were analyzed. Compared to the non-SDB group, patients with moderate-to-severe ACI accompanied by SDB showed decreased IS, increased IV, and sleep fragmentation. Significant statistical differences were observed in total sleep time (TST), rapid eye movement latency (REML), sleep efficiency (SE), non-rapid eye movement stages 1-2 (NREM stages1-2), non-rapid eye movement stages 3-4 (NREM stages 3-4), proportion of non-rapid eye movement (NREM%), wake after sleep onset (WASO), and number of awakenings (NOA) between the SDB group and the non-SDB group (P < 0.05). AHI showed a strong negative correlation with IS and a strong positive correlation with IV. AHI was positively correlated with sleep latency (SL), REML, NREM stages1-2, NREM%, proportion of rapid eye movement (REM%), WASO, time out of bed (TOB), and NOA, and negatively correlated with TST, SE, NREM stages 3-4, and rapid eye movement (REM), all with statistical significance (P < 0.05). There were significant statistical differences in the Mini-Mental State Examination (MMSE) between patients with and without SDB, and among mild, moderate, severe, and fluctuating groups (P < 0.05). Patients with moderate-to-severe ACI accompanied by SDB are more likely to experience changes in circadian rhythm and sleep states, which in turn affect cognitive functions. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-024-00516-1.

Circadian variations influence anxiety-related behaviour, olfaction, and hedonic response in male Sprague-Dawley rats.

INTRODUCTION: Despite the acknowledged impact of circadian rhythms on various aspects of life, behavioural tests with laboratory animals often overlook alignment with their natural activity patterns. This study aims to evaluate the influence of circadian variations on the results, validity, and reliability of different behavioural tests in rats. METHODS: Three behavioural tests, the Light-Dark Box Test (LDB), assessing anxiety-related behaviour and locomotor activity; the Buried Pellet Test (BPT), revealing olfactory abilities and motivation issues; and the Sucrose Preference Test (SPT), studying the anhedonic response, were employed to encompass multiple daytime-dependent behavioural aspects in male Sprague-Dawley rats. RESULTS: Our findings underscore distinct circadian effects on locomotor activity, exploratory behaviour, olfactory acuity, motivation, and hedonic response. Notably, anxious behaviour remained unaffected by daytime conditions. Furthermore, decreased data variance was found to be correlated with conducting behavioural tests during the subjects' active phase. DISCUSSION: This study demonstrates extensive circadian influences on nearly all parameters investigated, coupled with a significant reduction in data variability during the active phase. Emphasising the importance of aligning experimental timing with rats' natural activity patterns, our results suggest that conducting tests during the active phase of the animals not only refines test sensitivity , reduces stress, and provides more representative data, but also contributes to ethical animal research (3 R) and improves test relevance. This, in turn, enhances the reliability and validity of experimental outcomes in behavioural research and promotes animal welfare.

Dysregulation of circadian clock gene expression patterns in a treatment-resistant animal model of depression.

Circadian rhythm (CR) disturbances are among the most commonly observed symptoms during major depressive disorder, mostly in the form of disrupted sleeping patterns. However, several other measurable parameters, such as plasma hormone rhythms and differential expression of circadian clock genes (ccgs), are also present, often referred to as circadian phase markers. In the recent years, CR disturbances have been recognized as an essential aspect of depression; however, most of the known animal models of depression have yet to be evaluated for their eligibility to model CR disturbances. In this study, we investigate the potential of adrenocorticotropic hormone (ACTH)-treated animals as a disease model for research in CR disturbances in treatment-resistant depression. For this purpose, we evaluate the changes in several circadian phase markers, including plasma concentrations of corticosterone, ACTH, and melatonin, as well as gene expression patterns of 13 selected ccgs at 3 different time points, in both peripheral and central tissues. We observed no impact on plasma corticosterone and melatonin concentrations in the ACTH rats compared to vehicle. However, the expression pattern of several ccgs was affected in the ACTH rats compared to vehicle. In the hippocampus, 10 ccgs were affected by ACTH treatment, whereas in the adrenal glands, 5 ccgs were affected and in the prefrontal cortex, hypothalamus and liver 4 ccgs were regulated. In the blood, only 1 gene was affected. Individual tissues showed changes in different ccgs, but the expression of Bmal1, Per1, and Per2 were most generally affected. Collectively, the results presented here indicate that the ACTH animal model displays dysregulation of a number of phase markers suggesting the model may be appropriate for future studies into CR disturbances.

Measuring activity-rest rhythms under different acclimation periods in a marine fish using automatic deep learning-based video tracking.

Most organisms synchronize to an approximately 24-hour (circadian) rhythm. This study introduces a novel deep learning-powered video tracking method to assess the stability, fragmentation, robustness and synchronization of activity rhythms in Xyrichtys novacula. Experimental X. novacula were distributed into three groups and monitored for synchronization to a 14/10 hours of light/dark to assess acclimation to laboratory conditions. Group GP7 acclimated for 1 week and was tested from days 7 to 14, GP14 acclimated for 14 days and was tested from days 14 to 21 and GP21 acclimated for 21 days and was tested from days 21 to 28. Telemetry data from individuals in the wild depicted their natural behavior. Wild fish displayed a robust and minimally fragmented rhythm, entrained to the natural photoperiod. Under laboratory conditions, differences in activity levels were observed between light and dark phases. However, no differences were observed in activity rhythm metrics among laboratory groups related to acclimation period. Notably, longer acclimation (GP14 and GP21) led to a larger proportion of individuals displaying rhythm synchronization with the imposed photoperiod. Our work introduces a novel approach for monitoring biological rhythms in laboratory conditions, employing a specifically engineered video tracking system based on deep learning, adaptable for other species.

Dysrhythmic saliva microbiota in mobile phone addicts with sleep disorders and restored by acupuncture.

Background: Mobile phone addiction (MPA) greatly affects the biological clock and sleep quality and is emerging as a behavioral disorder. The saliva microbiota has been linked to circadian rhythms, and our previous research revealed dysrhythmic saliva metabolites in MPA subjects with sleep disorders (MPASD). In addition, acupuncture had positive effects. However, the dysbiotic saliva microbiota in MPASD patients and the restorative effects of acupuncture are unclear. Objectives: To probe the circadian dysrhythmic characteristics of the saliva microbiota and acupunctural restoration in MPASD patients. Methods: MPASD patients and healthy volunteers were recruited by the Mobile Phone Addiction Tendency Scale (MPATS) and the Pittsburgh Sleep Quality Index (PSQI). Saliva samples were collected every 4 h for 72 h. After saliva sampling, six MPDSD subjects (group M) were acupuncturally treated (group T), and subsequent saliva sampling was conducted posttreatment. Finally, all the samples were subjected to 16S rRNA gene sequencing and bioinformatic analysis. Results: Significantly increased MPATS and PSQI scores were observed in MPDSD patients (p< 0.01), but these scores decreased (p<0.001) after acupuncture intervention. Compared with those in healthy controls, the diversity and structure of the saliva microbiota in MPASD patients were markedly disrupted. Six genera with circadian rhythms were detected in all groups, including Sulfurovum, Peptostreptococcus, Porphyromonas and Prevotella. There were five genera with circadian rhythmicity in healthy people, of which the rhythmicities of the genera Rothia and Lautropia disappeared in MPASD patients but effectively resumed after acupuncture intervention. Conclusions: This work revealed dysrhythmic salivary microbes in MPASD patients, and acupuncture, as a potential intervention, could be effective in mitigating this ever-rising behavioral epidemic.

Mechanism of action of the Banxia-Xiakucao herb pair in sleep deprivation: New comprehensive evidence from network pharmacology, transcriptomics and molecular biology experiments.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herb pairs are the most basic and compressed examples of Chinese herbal combinations and can be used to effectively explain the fundamental concepts of traditional Chinese medicine prescriptions. These pairings have gained significant interest due to their subtle therapeutic benefits, minimal side effects, and efficacy in treating complicated chronic conditions. The Banxia-Xiakucao Chinese herb pair (BXHP) consists of Pinellia ternata (Thunb.) Breit. (Banxia) and Prunella vulgaris L. (Xiakucao). This formula was documented in The Medical Classic of the Yellow Emperor approximately 2000 years ago，and clinical research has demonstrated that BXHP effectively treats insomnia. AIM OF THE STUDY: This study aimed to evaluate the efficacy and therapeutic mechanism of the BXHP through a comprehensive strategy involving network pharmacology, molecular docking, transcriptomics, and molecular biology experimental validation. MATERIALS AND METHODS: The composition of BXHP was characterized using the UPLC-Q-TOF-MS. The active compounds were screened to find drug-likeness compounds by analyzing the ADME data. To predict the molecular mechanism of BXHP in sleep deprivation (SD) by network pharmacology and molecular docking. We established a rat model of SD and the in vivo efficacy of BXHP was verified through the pentobarbital sodium righting reflex test, behavioral assays, enzyme-linked immunosorbent assay, transmission electron microscopy, HE staining, and Nissl staining, and the underlying molecular mechanism of BXHP in SD was revealed through transcriptomic and bioinformatic analyses in conjunction with quantitative real-time PCR, Western blot, and immunofluorescence staining. RESULTS: In the present study, we showed for the first time that BXHP reduced sleep latency, prolongs sleep duration, and improves anxiety; lowered serum CORT, IL6, TNF-α and MDA levels; decreased hypothalamic Glu levels; and elevated hypothalamic GABA and 5-HT levels in SD rats. We found 16 active compounds that acted on 583 targets, 145 of which are related to SD. By modularly dissecting the PPI network, we discovered three critical targets, Akt1, CREB1, and PRKACA, all of which play important roles in the effects of BXHP on SD. Molecular docking resulted in the identification of 16 active compounds that strongly bind to key targets. The results of GO and KEGG enrichment analyses of network pharmacology and transcriptomics focused on both the regulation of circadian rhythm and the cAMP signaling pathway, which strongly demonstrated that BXHP affects SD via the cAMP-PKA-CREB-Circadian rhythm pathway. Molecular biology experiments verified this hypothesis. Following BXHP administration, PKA and CREB phosphorylation levels were elevated in SD rats, the cAMP-PKA-CREB signaling pathway was activated, the expression levels of the biological clock genes CLOCK, p-BMAL1/BMAL1, and PER3 were increased, and the rhythmicity of the biological clock was improved. CONCLUSIONS: The active compounds in BXHP can activate the cAMP-PKA-CREB-Circadian rhythm pathway, improve the rhythmicity of the biological clock, promote sleep and ameliorate anxiety, which suggests that BXHP improves SD through a multicomponent, multitarget, multipathway mechanism. This study is important for the development of herbal medicines and clinical therapies for improving sleep deprivation.

A diagnostic model for Parkinson's disease based on circadian rhythm-related genes.

BACKGROUND: Circadian rhythm (CR) disturbance is intricately associated with Parkinson's disease (PD). However, the involvement of CR-related mechanisms in the pathogenesis and progression of PD remains elusive. METHODS: A total of 141 PD patients and 113 healthy participants completed CR-related clinical examinations in this study. To further investigate the CR-related mechanisms in PD, we obtained datasets (GSE7621, GSE20141, GSE20292) from the Gene Expression Omnibus database to identify differentially expressed genes between PD patients and healthy controls and further selected CR-related genes (CRRGs). Subsequently, the least absolute shrinkage and selection operator (LASSO) followed by logistic algorithms were employed to identify the hub genes and construct a diagnostic model. The predictive performance was evaluated by area under the curve (AUC), calibration curve, and decision curve analyses in the training set and external validation sets. Finally, RT‒qPCR and Western blotting were conducted to verify the expression of these hub genes in blood samples. In addition, Pearson correlation analysis was utilized to validate the association between expression of hub genes and circadian rhythm function. RESULTS: Our clinical observational study revealed that even early-stage PD patients exhibited a higher likelihood of experiencing sleep disturbances, nocturnal hypertension, reverse-dipper blood pressure, and reduced heart rate variability compared to healthy controls. Furthermore, 4 CR-related hub genes (AGTR1, CALR, BRM14, and XPA) were identified and subsequently incorporated as candidate biomarkers to construct a diagnostic model. The model showed satisfactory diagnostic performance in the training set (AUC = 0.941), an external validation set GSE20295 (AUC = 0.842), and our clinical centre set (AUC = 0.805). Additionally, the up-regulation of CALR, BRM14 and the down-regulation of AGTR1, XPA were associated with circadian rhythm disruption. CONCLUSION: CR disturbance seems to occur in the early stage of PD. The diagnostic model based on CR-related genes demonstrated robust diagnostic efficacy, offering novel insights for future clinical diagnosis of PD and providing a foundation for further exploration into the role of CR-related mechanisms in the progression of PD.

Molecular circadian clock disruption in the leukocytes of individuals with type 2 diabetes and overweight, and its relationship with leukocyte-endothelial interactions.

AIMS/HYPOTHESIS: Alterations in circadian rhythms increase the likelihood of developing type 2 diabetes and CVD. Circadian rhythms are controlled by several core clock genes, which are expressed in nearly every cell, including immune cells. Immune cells are key players in the pathophysiology of type 2 diabetes, and participate in the atherosclerotic process that underlies cardiovascular risk in these patients. The role of the core clock in the leukocytes of people with type 2 diabetes and the inflammatory process associated with it are unknown. We aimed to evaluate whether the molecular clock system is impaired in the leukocytes of type 2 diabetes patients and to explore the mechanism by which this alteration leads to an increased cardiovascular risk in this population. METHODS: This is an observational cross-sectional study performed in 25 participants with type 2 diabetes and 28 healthy control participants. Clinical and biochemical parameters were obtained. Peripheral blood leukocytes were isolated using magnetic bead technology. RNA and protein lysates were obtained to assess clock-related gene transcript and protein levels using real-time PCR and western blot, respectively. Luminex XMAP technology was used to assess levels of inflammatory markers. Leukocyte-endothelial interaction assays were performed by perfusing participants' leukocytes or THP-1 cells (with/without CLK8) over a HUVEC monolayer in a parallel flow chamber using a dynamic adhesion system. RESULTS: Participants with type 2 diabetes showed increased BMAL1 and NR1D1 mRNA levels and decreased protein levels of circadian locomotor output cycles kaput (CLOCK), cryptochrome 1 (CRY1), phosphorylated basic helix-loop-helix ARNT like 1 (p-BMAL1) and period circadian protein homologue 2 (PER2). Correlation studies revealed that these alterations in clock proteins were negatively associated with glucose, HbA1c, insulin and HOMA-IR levels and leukocyte cell counts. The leukocyte rolling velocity was reduced and rolling flux and adhesion were enhanced in individuals with type 2 diabetes compared with healthy participants. Interestingly, inhibition of CLOCK/BMAL1 activity in leukocytes using the CLOCK inhibitor CLK8 mimicked the effects of type 2 diabetes on leukocyte-endothelial interactions. CONCLUSIONS/INTERPRETATION: Our study demonstrates alterations in the molecular clock system in leukocytes of individuals with type 2 diabetes, manifested in increased mRNA levels and decreased protein levels of the core clock machinery. These alterations correlated with the impaired metabolic and proinflammatory profile of the participants with type 2 diabetes. Our findings support a causal role for decreased CLOCK/BMAL1 activity in the increased level of leukocyte-endothelial interactions. Overall, our data suggest that alterations in core clock proteins accelerate the inflammatory process, which may ultimately precipitate the onset of CVD in patients with type 2 diabetes.

Effect of electroacupuncture pre-conditioning on the expression rhythm of core clock gene Bmal1 in uterine tissue of controlled hyperstimulation rats. / ç”µé’ˆé¢„å¤„ç†å¯¹ä¿ƒæŽ’åµå¤§é¼ å­å®«ç»„ç»‡æ ¸å¿ƒæ—¶é’ŸåŸºå› Bmal1表达节律的影响.

OBJECTIVES: To observe the effect of electroacupuncture (EA) pre-conditioning on the expression rhythm of clock gene Bmal1 in the uterine tissue of rats with controlled ovarian hyperstimulation(COH), so as to explore its mechanisms underlying improvement of the endometrial receptivity of ovarian superovulation during implantation. METHODS: Seventy-two female SD rats with typical estrous cycles were randomly divided into normal control, model and EA pre-conditioning (pre-EA) groups, with 24 rats in each group. The COH model was established by giving the rats with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (HCG) by intraperitoneal injection. The rats of the pre-EA group received EA stimulation (1 Hz/5 Hz, a tolerable strength) of "Guanyuan"(CV4) and "Sanyinjiao"(SP6) for 15 min each time, once daily (at 21：00 every day). After successive EA intervention during the first two estrous cycles, the modeling began in the third estrus cycle and the EA intervention was continued till the end of modeling, followed by raising the rats with superovulation induction and male rats undergoing vasoligation in one cage (1∶1). The rats during the estrum in the normal control group or those of the model group at the end of modeling were raised together with the male rats undergoing vasoligation in one cage. On the 5th day (04：00 AM) after raising in one cage, the rats in the three groups were sacrificed in six batches every 4 hours, with 4 rats in each group in each batch. The H.E. staining was used for revealing alterations of the endometrial thickness, number of glands and blood vessels and tissue histology, and ELISA employed to ascertain the contents of estradiol (E2) and progesterone (Pg) in serum. The expression rhythm of core clock gene Bmal1 ［In the present study, Zeitgeber time (ZT) is an artificially set laboratory time, i.e., ZT7 (07：00) is light on and ZT19 (19：00) is light off.］ and the expression of endometrial HoxA10 and leukemia inhibitory factor (LIF) mRNAs were detected by quantitative real-time PCR. The Western blot was employed to detect the expression levels of HoxA10 and LIF proteins. RESULTS: Findings of the clock gene Bmal1 level showed that the expression peak was at ZT12 and the valley value at ZT20 in the normal control group, and that of the peak value was at ZT20 and valley value at ZT12 in the model group, while in the pre-EA group, the peak value was at ZT8, and the valley value at ZT4. The difference of Bmal1 levels among the three groups was most significant at ZT12 (12：00), therefore, the tissue samples were taken at ZT12 in this study for comparison of the levels of different indexes among the 3 groups. Compared with the control group, the endometrial thickness, number of glands and blood vessels, HoxA10 and LIF mRNAs and proteins were significantly down-regulated (P<0.01, P<0.05), and contents of serum E2 and Pg were considerably up-regulated in the model group (P<0.01, P<0.05). Relevant to the model group, the pre-EA group had an apparent increase in the endometrial thickness, number of glands and blood vessels, and expression levels of HoxA10 and LIF mRNAs and proteins (P<0.05, P<0.01), and a marked decrease in the serum Pg (P<0.05). At the ZT12 (12：00 noon), compared with the normal control group, the mRNA level of Bmal1 was significantly decreased in the model group (P<0.01)；and compared with the model group, the level of Bmal1 mRNA was significantly increased in the pre-EA group (P<0.05). In addition, at the node of ZT16, the mRNA level of Bmal1 was significantly decreased in the model group in comparison with the normal control group (P<0.01). CONCLUSIONS: EA preconditioning can improve the endometrial receptivity during the implantation window period in rats with COH, which may be related to its functions in regulating the expression of clock gene Bmal1 in the uterine tissue and in correcting the disturbance of clock gene rhythm.

A novel method for measurements of sleep/wake states, feeding and drinking behaviors using the tracking technique of 3D positions in freely moving mice.

We have previously developed a 3D video tracking system which enables us to analyze long-term quantitative analysis of gene expression in freely moving mice. In the present study, we improved 3D video tracking and developed a system that analyzes more detailed behavioral data. We succeeded in simultaneously analyzing sleep-wake, feeding, and drinking behavior rhythms in the same individual using our tracking system. This system will make it possible to measure gene expression in each tissue in vivo in real time in relation to the various behavioral rhythms mentioned above.

Exosomes, Circadian Rhythms, and Cancer Precision Medicine: New Frontiers.

"The environment shapes people's actions," a well-known proverb, strongly dictates that a change in our way of life changes our behavior. Circadian rhythms have been identified as a mechanism for maintaining homeostasis in the body, which, if disrupted by sleeping patterns, could result in significant metabolic alterations that adversely affect our health. The changes induced by circadian rhythm alter the secretion and cargo selection in exosomes which are nanovesicles important for intercellular communication. Exosomes were formerly known as "junk particles" but are now recognized as miniature copies of a cell's genetic material. Dysregulation of circadian rhythm has shown that it changes the gene expression of a cell to some extent and significantly alters the exosomal release. Meanwhile, cells secrete exosomes continuously to align the rhythmicity of the biological clock. In this study, we integrate circadian rhythms and exosomes with precision medicines to find better approaches to early diagnosis and treatment of disease.

Functional and regulatory diversification of Period genes responsible for circadian rhythm in vertebrates.

The Period genes (Per) play essential roles in modulating the molecular circadian clock timing in a broad range of species, which regulates the physiological and cellular rhythms through the transcription-translation feedback loop. While the Period gene paralogs are widely observed among vertebrates, the evolutionary history and the functional diversification of Per genes across vertebrates are not well known. In this study, we comprehensively investigated the evolution of Per genes at the copy number and sequence levels, including de novo binding motif discovery by comparative genomics. We also determined the lineage-specific transcriptome landscape across tissues and developmental stages and phenotypic effects in public RNA-seq data sets of model species. We observed multiple lineage-specific gain and loss events of Per genes, though no simple association was observed between ecological factors and Per gene numbers in each species. Among salmonid fish species, the per3 gene has been lost in the majority, whereas those retaining the per3 gene exhibit not a signature of relaxed selective constraint but rather a signature of intensified selection. We also determined the signature of adaptive diversification of the CRY-binding region in Per1 and Per3, which modulates the circadian rhythm. We also discovered putative regulatory sequences, which are lineage-specific, suggesting that these cis-regulatory elements may have evolved rapidly and divergently across different lineages. Collectively, our findings revealed the evolution of Per genes and their fine-tuned contribution to the plastic and precise regulation of circadian rhythms in various vertebrate taxa.

Health Benefits of Intermittent Fasting.

We propose that intermittent fasting (time-restricted eating), in agreement with the conclusions of other biologists, as revealed in recent publications, promotes the achievement of numerous health benefits including the extension of human and animal lifespans. Background: There is evidence, obtained both with animal model systems and with humans, that intermittent fasting has health benefits. These benefits include extended longevity, weight loss, and counteracting various disease conditions. Such procedures positively influence the benefits of human tissue-specific microbiomes and minimize the consequences of organellar apoptosis. Key Messages: In this review, we attempt to summarize the predominant evidence, published in the scientific literature, relevant to the conclusions that in general, and in many specific instances, intermittent fasting has long-term benefits to animals, including humans, with respect to overall and specific organismal health and longevity.

Sleep Disturbance in Rodent Models and Its Sex-Specific Implications.

Sleep disturbances, encompassing altered sleep physiology or disorders like insomnia and sleep apnea, profoundly impact physiological functions and elevate disease risk. Despite extensive research, the underlying mechanisms and sex-specific differences in sleep disorders remain elusive. While polysomnography serves as a cornerstone for human sleep studies, animal models provide invaluable insights into sleep mechanisms. However, the availability of animal models of sleep disorders is limited, with each model often representing a specific sleep issue or mechanism. Therefore, selecting appropriate animal models for sleep research is critical. Given the significant sex differences in sleep patterns and disorders, incorporating both male and female subjects in studies is essential for uncovering sex-specific mechanisms with clinical relevance. This review provides a comprehensive overview of various rodent models of sleep disturbance, including sleep deprivation, sleep fragmentation, and circadian rhythm dysfunction. We evaluate the advantages and disadvantages of each model and discuss sex differences in sleep and sleep disorders, along with potential mechanisms. We aim to advance our understanding of sleep disorders and facilitate sex-specific interventions.

Ticking Brain: Circadian Rhythm as a New Target for Cerebroprotection.

Circadian rhythm is a master process observed in nearly every type of cell throughout the body, and it macroscopically regulates daily physiology. Recent clinical trials have revealed the effects of circadian variation on the incidence, pathophysiological processes, and prognosis of acute ischemic stroke. Furthermore, core clock genes, the cell-autonomous pacemakers of the circadian rhythm, affect the neurovascular unit-composing cells in a nonparallel manner after the same pathophysiological processes of ischemia/reperfusion. In this review, we discuss the influence of circadian rhythms and clock genes on each type of neurovascular unit cell in the pathophysiological processes of acute ischemic stroke.

Variability in sleep architecture and alterations in circadian rhythms in patients with acute cerebral infarction accompanied by sleep-disordered breathing.

PURPOSE: To continuously and dynamically monitor the sleep status of patients in the acute phase of cerebral infarction, and to investigate the characteristics of acute cerebral infarction(ACI)associated with sleep-disordered breathing (SDB), variations in sleep structure, and changes in sleep circadian rhythms. METHODS: Patients with ACI within 48 h of onset who were admitted to the Department of Neurology at Kailuan General Hospital from November 2020 to December 2022 were selected. Detailed baseline information such as age, gender, smoking history, drinking history, were recorded for the selected participants. From the beginning of their hospitalization, the selected participants were monitored for their sleep status continuously for 5 days using the Intelligent Mattress-based Sleep Monitoring Platform System(IMSMPS). Based on the heart rate data obtained from the monitoring, the interdaily stability (IS) and intradaily variability (IV) of the sleep circadian rhythm were calculated. RESULTS: 1,367 patients with ACI were selected. Monitoring results over 5 days indicated 147 cases (10.75%) without SDB, and 1,220 cases (89.25%) with SDB. Among the group with SDB, there were 248 cases (18.14%) with continuous mild SDB, 395 cases (28.90%) with moderate SDB, 295 cases (21.58%) with severe SDB, and 282 cases (20.63%) that fluctuated between different severity levels. Within this fluctuating group, 152 cases (53.90%) fluctuated between two severity levels, 120 cases (42.55%) between three levels, and 10 cases (3.55%) among all four levels. There were statistically significant differences (P < 0.05) in the sleep latency, sleep efficiency, non-rapid eye movement stages 1-2, rapid eye movement, proportion of non-rapid eye movement, proportion of rapid eye movement, wake after sleep onset, time out of bed, number of awakenings, respiratory variability index, and heart rate variability index among patients with ACI monitored from day 1 to 5. However, other monitored sleep structure parameters did not show statistically significant differences (P > 0.05). The coefficient of variation for all sleep monitoring parameters ranged between 14.54 and 36.57%. The IV in the SDB group was higher than in the group without SDB (P < 0.05), and the IS was lower than in the group without SDB (P < 0.05). CONCLUSION: Patients in the acute phase of cerebral infarction have a high probability of accompanying SDB. The sleep structure of these patients shows significant variability based on the onset time of the stroke, and some patients experience fluctuations among different severity levels of SDB. ACI accompanied by SDB can further reduce the IS of a patient's sleep circadian rhythm and increase its IV.