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We measured diurnal variations in oxidative stress conditions of cyanobacteria utilizing field observations and laboratory experiments in order to evaluate photoinhibition effects. On clear summer days, transparent bottles filled with surface water were set up at several depths and were collected every three hours together with the measurement of the photosynthetically active radiation (PAR). In the laboratory experiment, two cyanobacterial species were exposed to gradually increasing and then decreasing light intensities. The samples were analyzed with the PAR-induced (H 2 O 2 ), along with the total hydrogen peroxide concentrations (total H 2 O 2 ), the catalase activities (CAT), OD 730 , protein (Protein), and chlorophyll a (Chl a) contents, and so on. Protein was significantly proportionate with OD 730 and Chl a, and was used as an indicator of cell biomass. Increasing PAR, H 2 O 2 concentration increased proportionately with the PAR intensity. Then, an oxidative stress indicator in a cell, H 2 O 2 /Protein is given by the PAR divided by cell volume, evaluated by Protein. CAT activity in a cell, far largest among antioxidant activities, solely followed total H 2 O 2 /Protein. The prediction model for H 2 O 2 /Protein was developed with the sufficient agreement with the experimental and field observation results. The model elucidated that the maximum H 2 O 2 /Protein in a day was larger with lower cell density even at the water surface, indicating that the higher photoinhibition was imposed at low density, in addition to the lower attenuation of PAR. These results indicate that H 2 O 2 /Protein is an effective biomarker to indicate the stress level of cyanobacteria; the observed levels of H 2 O 2 to freshwater may prove useful in designing the criteria for cyanobacteria management., Competing Interests: Competing interests: The authors declare no competing interests. Ethical permission: This study has been approved by the Saitama City Government (Besshonuma park Suishitsu Kaizen Taisaku Jisshi Keikaku Ritsuan Gyomu)., (© 2024. The Author(s).)

The hypothalamus senses the appetite-regulating hormones and also coordinates the metabolic function in alignment with the circadian rhythm. This alignment is essential to maintain the physiological conditions that prevent clinically important comorbidities, such as obesity or type-2 diabetes. However, a complete model of the hypothalamus that relates food intake with circadian rhythms and appetite hormones has not yet been developed. In this work, we present a computational model that accurately allows interpreting neural activity in terms of hormone regulation and sleep-wake cycles. We used a conductance-based model, which consists of a system of four differential equations that considers the ionotropic and metabotropic receptors, and the input currents from homeostatic hormones. We proposed a logistic function that fits available experimental data of insulin hormone concentration and added it into a short-term ghrelin model that served as an input to our dynamical system. Our results show a double oscillatory system, one synchronized by light-regulated sleep-wake cycles and the other by food-regulated feeding-fasting cycles. We have also found that meal timing frequency is highly relevant for the regulation of the hypothalamus neurons. We therefore present a mathematical model to explore the plausible link between the circadian rhythm and the endogenous food clock., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The chronotype of individuals has been found to be predictive of depression risk and associated with the severity of depression. However, since depression is a phenotypically heterogeneous disease, it seems improbable that chronotype plays a role in every instance of depression. This study investigates the association between the two, while considering possible symptom-specificity and non-linearity of the relationship, utilizing a large sample from the National Health and Nutrition Examination Survey (N = 5217; 54% female; Age: M = 52.65, SD = 18.76). Depression symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), and chronotype was determined by calculating sleep midpoints. Further, we also explored the potential mediating role of systemic inflammation, measured by C-reactive protein (CRP) levels, in the chronotype-depression link. The findings substantiate previous research indicating late chronotypes to be associated with higher PHQ-9 sum scores, with a minimum in PHQ-9 at a sleep midpoint of 02:49. The study further differentiates between individual depression symptoms, uncovering varying patterns of association with chronotype. No significant effect of chronotype on levels of CRP was found, suggesting that the link between chronotype and depression symptoms may not be directly mediated and appears to be stable and independent from systemic inflammation. The study highlights the non-linear and symptom-specific nature of the chronotype-depression connection and suggests the need for further, longitudinal studies to elucidate causal mechanisms and potential mediators., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Rumination shows a nocturnal rhythmic pattern in day-active ruminants. Although feeding has been shown to quantitatively modulate rumination, it is not clear yet if feeding rhythm plays a causal role in rumination rhythm. The present study was carried out to determine whether the daily rhythm of rumination in goats under natural environmental conditions is food-dependent or not, and whether it is modulated by the season. Rumination and locomotor activity (LA) were continuously monitored in four male Moroccan goats, fed once daily every morning, and then fasted for 4 days. The same experimental design was carried out in two different seasons (summer and winter). The results show that normally fed goats ruminate on average 281 ± 37 min in both seasons. Rumination shows a rhythmic 24-h profile with a late nocturnal peak. During the four-day food deprivation, rumination persisted while its total amount duration was significantly reduced in both seasons. Our results also illustrate the clear phase-opposition between the diurnal rhythm of LA and the nocturnal rhythm of rumination. This study characterized the daily rhythm rumination in goats according to seasons and fed/fasted states, and provided clear evidence that this rhythm is not generated by feeding behavior. Further investigations are required to determine whether rumination has an endogenous origin and is driven by the central circadian clock., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Artificial light at night (ALAN) changes animal behavior in multiple invertebrates and vertebrates and can result in decreased fitness. However, ALAN effects have not been studied in European honey bees (Apis mellifera), an important pollinator in which foragers show strong circadian rhythmicity. Colonies can be exposed to ALAN in swarm clusters, when bees cluster outside the nest on hot days and evenings, and, in limited cases, when they build nests in the open. We captured and maintained foragers in incubated cages and subjected them to constant light (LL), constant dark (DD), or 12 h light:12 h dark (LD) cycle, and observed them with infrared cameras. After 79 h, there was a significant interaction of treatment and time because LL bees slept less. In detail, the bees maintained a regular sleep pattern for three days but LL bees showed a shift on the fourth day. LL bees had the largest sleep differences from LD controls, with trends of lengthened periods and increased phase misalignment from both LD and DD bees. LL bees also experienced significantly more disturbances from their nestmates and preferred to sleep in the lower portion of the cages, which had significantly lower light intensity. These findings suggest that ALAN can disrupt the sleep of honey bee foragers, which has implications for their behavior and overall colony health., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

This study aimed to analyze vital sign characteristics of adult patients admitted at the Tertiary Hospital, and to define fever threshold and average body temperature by examining the tympanic temperatures of all patients. Retrospective medical data were extracted from 9195 patients aged > 21 years admitted to a tertiary hospital for elective surgeries between 2016 and 2020. Data regarding the patients' vital signs during their hospital stay, including tympanic body temperature, heart rate, and respiratory rate, were analyzed according to age, sex, and circadian rhythm. A normal-distribution graph was obtained when all the body temperature results were aligned. The average body temperature measured was 36.91 ± 0.45 °C (average ± standard deviation), indicating a potential fever threshold of 37.81 °C. When the participants were divided into age groups, the average temperature, heart rate, and respiratory rate exhibited parabolic trends. Patients in their 60s exhibited the lowest average temperature (36.88 °C), whereas those in their 50s had the lowest average heart rate (75.82/min) and lowest respiratory rate (19.08/min). Heart rate and respiratory rate tended to increase in elderly people older than 81 years. The average body temperature was greater in women than in men (36.94 ± 0.42 °C vs. 36.89 ± 0.47 °C), while the average heart (75.53 ± 10.04/min vs. 77.31 ± 11.52/min) and respiratory rates (19.13 ± 1.39/min vs. 19.29 ± 2.24/min) were lower in women than in men respectively. According to the time of measurement, the average temperature and heart rate appeared to follow a sinusoidal pattern, suggesting that the circadian rhythm was highest at 1 a.m. and lowest at 8 a.m. Tympanic temperature is a convenient measurement method preferred in hospital settings because it is noninvasive and easier to measure compared to other body parts. To develop an improved device and measurement method in the future, it is necessary to analyze tympanic temperature big data and compare it with past vital sign data or biometric information from other body parts., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

A significant number of individuals being treated for hypertension still have uncontrolled blood pressure (BP). In Japan, renal denervation (RDN) is being introduced into clinical practice as an adjunctive treatment for hypertension that is uncontrolled despite adequate lifestyle changes and maximal antihypertensive drug therapy. The pivotal SPYRAL ON-MED trial showed that there was a significant reduction in trough office and nighttime ambulatory BP values in the RDN group compared with sham control group, although 24-h and daytime BP values were not significantly different between the two groups. The trough office BP measurement (taken before morning antihypertensive dosing) is similar to guideline recommendations for taking morning home BP before taking the morning antihypertensive drug dose. Recent guidelines recommend the measurement of nighttime BP because nighttime BP is a stronger predictor of cardiovascular event risk than daytime BP. It is particularly important to assess nighttime BP in medicated individuals with hypertension because the up- or down-titration of antihypertensive drug dosing is primarily based on office and daytime BPs in clinical practice. This means that there may be significant risk relating to nocturnal hypertension during longer follow-up. Because RDN results in persistent, "always-on" 24-h BP-lowering effects, the best BP metrics to assess the potential benefit of RDN are nighttime BP (determined using home or ambulatory BP monitoring) and morning BP (determined using home BP monitoring or morning trough office BP measurement). The variability of office, home, and ambulatory BP values is another important metric to assess the quality of RDN-related BP lowering., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Physical inactivity as well as breakfast skipping is known as risk factor for various metabolic diseases, such as obesity and type 2 diabetes. We have previously reported that a breakfast skipping model, in which the timing of feeding is delayed, induces abnormal lipid metabolism by altering the circadian rhythm of lipid metabolism-related genes in rats. The purpose of this study was to elucidate the synergistic effect of physical inactivity and breakfast skipping on lipid metabolism. We adopted sciatic neurectomized rats as physically inactive models, because we confirmed that the rats mildly decreased their spontaneous locomotor activity compared to sham-operated rats. And then the physically inactive model rats were fed a mild high-fat diet during zeitgeber time (ZT) 12-0 in the control group and ZT16-0 in the breakfast skipping group for 11 days. Body weight gain and total food intake were similar in both groups. Breakfast skipping induced a significant visceral fat accumulation, which was not observed in our previous breakfast skipping or physically inactive studies. The mRNA levels of clock and lipogenesis-related genes were altered by breakfast skipping in the liver and epididymal adipose tissue, and serum insulin level was altered by breakfast skipping. These results suggest that physical inactivity and breakfast skipping synergistically induces drastic visceral fat accumulation due to the alteration of circadian clock and lipid metabolism in the liver and adipose tissue. Therefore, regular feeding timing plays an important role in the health of a sedentary modern society., (© 2024. The Author(s).)

The suprachiasmatic nucleus (SCN) contains a population of cell-autonomous circadian oscillators essential for entrainment to daily light-dark (LD) cycles. Synchrony among SCN oscillators is modified by photoperiod and determines functional properties of SCN clock cycling, including its amplitude, phase angle of entrainment, and free running periodicity (τ). For many species, encoding of daylength in SCN output is critical for seasonal regulation of metabolism and reproduction. C57BL/6 mice do not show seasonality in these functions, yet do show photoperiodic modulation of SCN clock output. The significance of this for brain systems and functions downstream from the SCN in these species is largely unexplored. C57BL/6 mice housed in a long-day photoperiod have been reported to perform better on tests of object, spatial and fear memory compared to mice in a standard 12 h photoperiod. We previously reported that encoding of photoperiod in SCN output, evident in τ in constant dark (DD), can be blocked by limiting food access to a 4 h mealtime in the light period. To determine whether this might also block the effect of long days on memory, mice entrained to 18 h:6 h (L18) or 6 h:18 h (L6) LD cycles were tested for 24 h object memory (novel object preference, NOP) and spatial working memory (Y-maze spontaneous alternation, SA), at 4 times of day, first with food available ad libitum and then during weeks 5-8 of daytime restricted feeding. Photoperiod modified τ as expected, but did not affect performance on the NOP and SA tests, either before or during restricted feeding. NOP performance did improve in the restricted feeding condition in both photoperiods, eliminating a weak time of day effect evident with food available ad-libitum. These results highlight benefits of restricted feeding on cognitive function, and suggest a dose-response relationship between photoperiod and memory, with no benefits at daylengths up to 18 h., (© 2024. The Author(s).)

Circadian rhythms are self-sustaining oscillations within biological systems that play key roles in a diverse multitude of physiological processes. The circadian clock mechanisms in brain and peripheral tissues can oscillate independently or be synchronized/disrupted by external stimuli. Dental enamel is a type of mineralized tissue that forms the exterior surface of the tooth crown. Incremental Retzius lines are readily observable microstructures of mature tooth enamel that indicate the regulation of amelogenesis by circadian rhythms. Teeth enamel is formed by enamel-forming cells known as ameloblasts, which are regulated and orchestrated by the circadian clock during amelogenesis. This review will first examine the key roles of the circadian clock in regulating ameloblasts and amelogenesis. Several physiological processes are involved, including gene expression, cell morphology, metabolic changes, matrix deposition, ion transportation, and mineralization. Next, the potential detrimental effects of circadian rhythm disruption on enamel formation are discussed. Circadian rhythm disruption can directly lead to Enamel Hypoplasia, which might also be a potential causative mechanism of amelogenesis imperfecta. Finally, future research trajectory in this field is extrapolated. It is hoped that this review will inspire more intensive research efforts and provide relevant cues in formulating novel therapeutic strategies for preventing tooth enamel developmental abnormalities., (© 2024. The Author(s).)

There is scarce evidence of the role of clinic and ambulatory BP indices, as well as blood pressure phenotypes in the prognosis of stroke survivors. We aimed to evaluate the association between ambulatory BP indices and mortality in patients with a previous stroke. Our study was an observational cohort study from individuals included in the Spanish Ambulatory Blood Pressure Registry from March 2004 to December 2014. The Cox model was used to estimate associations between usual clinic and ambulatory BP and mortality, adjusted for confounders and additionally for alternative measures of BP. Two thousand one hundred and eighty-three patients with a previous stroke were included. During a median of 9.2 years, 632 (28.9%) patients died: 236 (10.8%) from cardiovascular causes. In the confounder-adjusted model, clinic systolic BP was not associated with the risk of all-cause or cardiovascular mortality. In contrast, systolic BP indices obtained through ABPM (24 h, day and night) were all associated with all-cause and cardiovascular death. In the simultaneous adjustment of daytime and night-time systolic BP, only night-time systolic BP remained significantly associated with all-cause and cardiovascular death: HR 1.35 (95% CI 01.21-1.51) and 1.44 (1.20-1.72), respectively. For diastolic BP, only night-time BP was associated with all-cause and cardiovascular mortality: HR 1.32 (1.18-1.48) and 1.57 (1.31-1.88), respectively. According to the circadian pattern, a riser pattern was associated with all-cause and cardiovascular mortality: HR 1.49 (1.18-1.87) and 1.70 (1.14-2.52), respectively. In conclusion, in patients who have suffered a stroke, night-time BP is the BP estimate most closely associated with all-cause and cardiovascular mortality., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Increasing attention has recently been paid to discrepancies between office and ambulatory blood pressure (BP) control in patients with chronic kidney disease (CKD), but information on mechanisms underlying circadian BP variations in CKD remains scarce. We described circadian BP patterns and their predictors in patients with CKD stages 1 to 5 referred for kidney function testing in a French tertiary hospital: 1122 ambulatory BP measurements from 635 participants. Factors associated with daytime and nighttime systolic BP (SBP) as well as with nocturnal SBP dipping (ratio of average nighttime to daytime SBP) were analyzed with linear mixed regression models. Participants (mean age 55 ± 16 years; 36% female, mean GFR 51 ± 22 mL/min/1.73m 2 ) had a mean daytime and nighttime SBP of 130 ± 17 and 118 ± 18 mm Hg, respectively. The prevalence of impaired dipping (nighttime over daytime SBP ratio ≥ 0.9) increased from 32% in CKD stage 1 to 68% in CKD stages 4-5. After multivariable adjustment, measured GFR, diabetes, and sub-Saharan African origin were more strongly associated with nighttime than with daytime SBP, which led to significant associations with altered nocturnal BP dipping. For a 1 SD decrease in measured GFR, nighttime BP was 2.87 mmHg (95%CI, 1.44-4.30) higher and nocturnal SBP dipping ratio was 1.55% higher (95%CI, 0.85-2.26%). In conclusion, the prevalence of impaired nocturnal BP dipping increases substantially across the spectrum of CKD. Along with sub-Saharan African origin and diabetes, lower measured GFR was a robust and specific predictor of higher nighttime BP and blunted nocturnal BP decline., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

The circadian clock is the inner rhythm of life activities and is controlled by a self-sustained and endogenous molecular clock, which maintains a ~ 24 h internal oscillation. As the core element of the circadian clock, BMAL1 is susceptible to degradation through the ubiquitin-proteasome system (UPS). Nevertheless, scant information is available regarding the UPS enzymes that intricately modulate both the stability and transcriptional activity of BMAL1, affecting the cellular circadian rhythm. In this work, we identify and validate UBR5 as a new E3 ubiquitin ligase that interacts with BMAL1 by using affinity purification, mass spectrometry, and biochemical experiments. UBR5 overexpression induced BMAL1 ubiquitination, leading to diminished stability and reduced protein level of BMAL1, thereby attenuating its transcriptional activity. Consistent with this, UBR5 knockdown increases the BMAL1 protein. Domain mapping discloses that the C-terminus of BMAL1 interacts with the N-terminal domains of UBR5. Similarly, cell-line-based experiments discover that HYD, the UBR5 homolog in Drosophila, could interact with and downregulate CYCLE, the BMAL1 homolog in Drosophila. PER2-luciferase bioluminescence real-time reporting assay in a mammalian cell line and behavioral experiments in Drosophila reveal that UBR5 or hyd knockdown significantly reduces the period of the circadian clock. Therefore, our work discovers a new ubiquitin ligase UBR5 that regulates BMAL1 stability and circadian rhythm and elucidates the underlying molecular mechanism. This work provides an additional layer of complexity to the regulatory network of the circadian clock at the post-translational modification level, offering potential insights into the modulation of the dysregulated circadian rhythm., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Disrupted sleep due to nighttime eating can raise various concerns, impacting both physical health and overall well-being. Nevertheless, there is a lack of direct evidence linking nighttime eating with the female reproduction system, possibly due to the absence of suitable models. Here, we use the laying hen, a diurnal animal maintained under ad libitum feeding, as a vertebrate model to quantify the impact of nighttime eating on reproduction and aging. To do this, we have built an Arduino-based setup that regulates food availability and exclusively tracks the eating events of individuals. Our data indicate that synchronizing food availability with the natural sleep-wake rhythm substantially improves reproduction and extends healthspan in hens. With reproductive aging becoming progressively more prevalent in contemporary society due to the trend of delayed childbearing, synchronizing eating with the natural rhythm could help mitigate reproductive aging in vertebrates and potentially in humans as well., (© 2024. The Author(s).)

Under total sleep deprivation, both inhibitory and motor control are impaired. However, how circadian rhythm sleep loss caused by irregular sleep pattern affects motor inhibition and execution in continuous actions remains unknown. This study utilized a pointing task to investigate the question over 30 days. During regular trials, participants were instructed to tap on a specified location, while in countermanding trials, they were required to countermand their current action. Additionally, there was a control group performed the same task following a normal 24-h rhythm. The results indicated that the decrease in accuracy and the increase in movement time in countermanding trials were more prominent in the shift work group. In contrast, there was no significant difference in reaction time between the two groups. Notably, the shift work group outperformed the control group in terms of movement time in regular trials and radial displacement in countermanding trials. Overall, these results show that circadian rhythm sleep loss predominantly affects inhibitory control, rather than motor control, underscoring the nuanced impacts of sleep disruption on differential aspects of cognitive and motor functions., (© 2024. The Author(s).)

Changes in the amount of daylight (photoperiod) alter physiology and behaviour 1,2 . Adaptive responses to seasonal photoperiods are vital to all organisms-dysregulation associates with disease, including affective disorders 3 and metabolic syndromes 4 . The circadian rhythm circuitry is implicated in such responses 5,6 , yet little is known about the precise cellular substrates that underlie phase synchronization to photoperiod change. Here we identify a brain circuit and system of axon branch-specific and reversible neurotransmitter deployment that are critical for behavioural and sleep adaptation to photoperiod. A type of neuron called mrEn1-Pet1 7 in the mouse brainstem median raphe nucleus segregates serotonin from VGLUT3 (also known as SLC17A8, a proxy for glutamate) to different axonal branches that innervate specific brain regions involved in circadian rhythm and sleep-wake timing 8,9 . This branch-specific neurotransmitter deployment did not distinguish between daylight and dark phase; however, it reorganized with change in photoperiod. Axonal boutons, but not cell soma, changed neurochemical phenotype upon a shift away from equinox light/dark conditions, and these changes were reversed upon return to equinox conditions. When we genetically disabled Vglut3 in mrEn1-Pet1 neurons, sleep-wake periods, voluntary activity and clock gene expression did not synchronize to the new photoperiod or were delayed. Combining intersectional rabies virus tracing and projection-specific neuronal silencing, we delineated a preoptic area-to-mrEn1Pet1 connection that was responsible for decoding the photoperiodic inputs, driving the neurotransmitter reorganization and promoting behavioural synchronization. Our results reveal a brain circuit and periodic, branch-specific neurotransmitter deployment that regulates organismal adaptation to photoperiod change., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

This study aimed to explore the relationship between shift-working nurses' social jetlag and body mass index (BMI) and provide a theoretical basis for nursing managers to develop appropriate health interventions. Shift work is unavoidable in nursing and is associated with circadian rhythm disorders. Social jetlag is prevalent in shift-working nurses and is associated with adverse health outcomes (particularly metabolism-related indicators). BMI is a significant metabolic indicator, and research has demonstrated its effectiveness in predicting the formation of metabolic syndrome. The relationship between social jetlag and BMI can be explained by considering physiological, psychological, and behavioral factors. However, most studies on social jetlag and health status are focused on non-shift nurse populations, with fewer studies on shift workers. Five tertiary hospitals located at similar latitudes in Southwest China were selected for the study. We surveyed 429 shift-working nurses using sociodemographic data, the Munich Chronotype Questionnaire for Shift Workers, and BMI. The restricted cubic spline model was used to analyze the relationship between social jetlag and BMI among shift-working nurses, and segmented linear regression was performed around the inflection point using multiple linear regression analysis. The results revealed that social jetlag (82.0 [85.0] min) was experienced by 64.6% of the shift-working nurses. After controlling for confounding variables, the model with seven knots had the lowest accepted Akaike information criterion value, and there was a U-shaped relationship between shift-working nurses' BMI and social jetlag in this model; its inflection (lowest) point of 20.7 was considered the cut-off point. Segmented regression showed that for BMI < 20.7, BMI was significantly negative with standardized social jetlag; whereas with BMI > 20.7, BMI was significantly positive with standardized social jetlag. BMI has a U-shaped relationship with social jetlag, and attention should be paid to overweight or underweight shift-working nurses to detect early circadian rhythm disorder. Shift-working nurses with high social jetlag tended to have higher/lower BMI, which should be further investigated in the future, to minimize metabolic diseases among them., (© 2024. The Author(s).)

Robust circadian rhythms are essential for optimal health. The central circadian clock controls temperature rhythms, which are known to organize the timing of peripheral circadian rhythms in rodents. In humans, however, it is unknown whether temperature rhythms relate to the organization of circadian rhythms throughout the body. We assessed core body temperature amplitude and the rhythmicity of 929 blood plasma metabolites across a 40-h constant routine protocol, controlling for behavioral and environmental factors that mask endogenous temperature rhythms, in 23 healthy individuals (mean [± SD] age = 25.4 ± 5.7 years, 5 women). Valid core body temperature data were available in 17/23 (mean [± SD] age = 25.6 ± 6.3 years, 1 woman). Individuals with higher core body temperature amplitude had a greater number of metabolites exhibiting circadian rhythms (R 2  = 0.37, p = .009). Higher core body temperature amplitude was also associated with less variability in the free-fitted periods of metabolite rhythms within an individual (R 2  = 0.47, p = .002). These findings indicate that a more robust central circadian clock is associated with greater organization of circadian metabolite rhythms in humans. Metabolite rhythms may therefore provide a window into the strength of the central circadian clock., (© 2024. The Author(s).)

Healthy mammalian cells have a circadian clock, a gene regulatory network that allows them to schedule their physiological processes to optimal times of the day. When healthy cells turn into cancer cells, the circadian clock often becomes cancer specifically disturbed, so there is an interest in the extraction of circadian features from gene expression data of cancer. This is challenging, as clinical gene expression samples of cancer are snapshot-like and the circadian clock is best examined using gene expression time series. In this study, we obtained lists of intersecting circadian genes in public gene expression time series data of lung tissue of mouse and baboon. We base our circadian gene lists on correlations of gene expression levels of circadian genes, which are closely associated to the phase differences between them. Combining circadian gene expression patterns of diurnal and nocturnal species of different ages provides circadian genes that are also important in healthy and cancerous human lung tissue. We tested the quality of the representation of the circadian clock in our gene lists by PCA-based reconstructions of the circadian times of the mouse and baboon samples. Then we assigned potential circadian times to the human lung tissue samples and find an intact circadian clock in the healthy human lung tissue, but an altered, weak clock in the adjacent cancerous lung tissue., (© 2024. The Author(s).)

Most organisms possess three biological oscillators, circadian clock, cell cycle, and redox rhythm, which are autonomous but interact each other. However, whether their interactions and autonomy are beneficial for organisms remains unclear. Here, we modeled a coupled oscillator system where each oscillator affected the phase of the other oscillators. We found that multiple types of coupling prevent a high H 2 O 2 level in cells at M phase. Consequently, we hypothesized a high H 2 O 2 sensitivity at the M phase and found that moderate coupling reduced cell damage due to oxidative stress by generating appropriate phase relationships between three rhythms, whereas strong coupling resulted in an elevated cell damage by increasing the average H 2 O 2 level and disrupted the cell cycle. Furthermore, the multicellularity model revealed that phase variations among cells confer flexibility in synchronization with environments at the expense of adaptability to the optimal environment. Thus, both autonomy and synchrony among the oscillators are important for coordinating their phase relationships to minimize oxidative stress, and couplings balance them depending on environments., (© 2024. The Author(s).)

Blood pressure (BP) assessment during exercise testing has the capacity to identify exaggerated exercise BP (EEBP). BP has a circadian rhythm; therefore, exercise BPs may change throughout the day complicating EEBP identification. The purpose of this study was to determine the effect of time of day on exercise BP in healthy young adults. Thirty-one participants [48% female; 23(4) years] completed a modified Bruce treadmill protocol in the morning (M), afternoon (A), and evening (E). Submaximal (stage 4) and peak (highest value) systolic BP (SBP) were determined and ΔSBP was calculated (peak SBP-pre-exercise SBP). Repeated-measures tests were used to compare SBP data. EEBP was defined as a submaximal SBP ≥ 170 mmHg. Chronotype was assessed using the Morning-Eveningness Questionnaire (MEQ) and Pearson correlations were used to determine the relationship between MEQ score and ΔSBP during all tests. Significance was set at P < 0.05. Submaximal SBP (M:159(25); A:156(16); E:162(24) mmHg; P = 0.295), peak SBP (M:177(32); A:184(25); E:185(26) mmHg; P = 0.087) and ΔSBP (M:62(29); A:67(23); 65(20) mmHg; P = 0.546) were similar across time points. Eight participants had an EEBP on at least two tests. MEQ scores were correlated with ΔSBP during the A test (r = 0.357, P = 0.049) and E test (r = 0.363, P = 0.045). In conclusion, time of day had no effect on SBP responses to exercise, but our correlational analysis suggests changes in SBP may differ between chronotypes depending on the time of day of exercise. Given the clinical value of EEBP, it is notable that 26% of our healthy young sample had EEBP., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Daylight saving time (DST) is currently utilized in many countries with the rationale that it enhances the alignment between daylight hours and activity peaks in the population. The act of transitioning into and out of DST introduces disruptions to the circadian rhythm, thereby impacting sleep and overall health. Despite the substantial number of individuals affected, the consequences of this circadian disruption have often been overlooked. Here, we employ a mathematical model of the human circadian pacemaker to elucidate how the biological clock interacts with daytime and evening exposures to both natural and electrical light. This interaction plays a crucial role in determining the adaptation to the 1 hour time zone shift imposed by the transition to or from DST. In global discussions about DST, there is a prevailing assumption that individuals easily adjust to DST transitions despite a few studies indicating that the human circadian system requires several days to fully adjust to a DST transition. Our study highlights that evening light exposure changes can be the main driving force for re-entrainment, with chronobiological models predicting that people with longer intrinsic period (i.e. later chronotype) entrain more slowly to transitions to or from DST as compared to people with a shorter intrinsic period (earlier chronotype). Moreover, the model forecasts large inter-individual differences in the adaptation speed, in particular during the spring transition. The predictions derived from our model offer circadian biology-based recommendations for light exposure strategies that facilitate a more rapid adaptation to DST-related transitions or travel across a single time zone. As such, our study contributes valuable insights to the ongoing discourse on DST and its implications for human circadian rhythms., (© 2024. The Author(s).)

The suprachiasmatic nucleus (SCN) is the mammalian central circadian pacemaker with heterogeneous neurons acting in concert while each neuron harbors a self-sustained molecular clockwork. Nevertheless, how system-level SCN signals encode time of the day remains enigmatic. Here we show that population-level Ca 2+ signals predict hourly time, via a group decision-making mechanism coupled with a spatially modular time feature representation in the SCN. Specifically, we developed a high-speed dual-view two-photon microscope for volumetric Ca 2+ imaging of up to 9000 GABAergic neurons in adult SCN slices, and leveraged machine learning methods to capture emergent properties from multiscale Ca 2+ signals as a whole. We achieved hourly time prediction by polling random cohorts of SCN neurons, reaching 99.0% accuracy at a cohort size of 900. Further, we revealed that functional neuron subtypes identified by contrastive learning tend to aggregate separately in the SCN space, giving rise to bilaterally symmetrical ripple-like modular patterns. Individual modules represent distinctive time features, such that a module-specifically learned time predictor can also accurately decode hourly time from random polling of the same module. These findings open a new paradigm in deciphering the design principle of the biological clock at the system level., (© 2024. The Author(s).)

Artificial light at night (ALAN) disrupts 24-h variability of blood pressure, but the molecular mechanisms underlying these effects are unknown. Therefore, we analysed the daily variability of pulse pressure, the maximum value of acceleration rate of aortic pressure (dP/dt (max) ) measured by telemetry and protein expression in the thoracic aorta of normotensive male rats exposed to ALAN (1-2 lx) for 3 weeks. Daily, 24-h variability of pulse pressure and dP/dt (max) was observed during a regular light/dark regimen with higher values during the dark compared to the light phase of the day. ALAN suppressed 24-h variability and enhanced ultradian (<12-h) periods of pulse pressure and dP/dt (max) in duration-dependent manners. From beat-to-beat blood pressure variability, ALAN decreased low-frequency bands (a sympathetic marker) and had minimal effects on high-frequency bands. At the molecular level, ALAN decreased angiotensin II receptor type 1 expression and reduced 24-h variability. ALAN caused the appearance of 12-h oscillations in transforming growth factor β1 and fibulin 4. Expression of sarco/endoplasmic reticulum Ca 2+ -ATPase type 2 was increased in the middle of the light and dark phase of the day, and ALAN did not affect its daily and 12-h variability. In conclusion, ALAN suppressed 24-h variability of pulse pressure and dP/dt (max) , decreased the power of low-frequency bands and differentially affected the expression of specific proteins in the rat thoracic aorta. Suppressed 24-h oscillations by ALAN underline the pulsatility of individual endocrine axes with different periods, disrupting the cardiovascular control of central blood pressure., (© 2024. The Author(s).)

The blacklegged tick, Ixodes scapularis, is an ectoparasitic arachnid and vector for infectious diseases, including Lyme borreliosis. Here, we investigate the diurnal activity and respiration of wild-caught and lab-reared adult ticks with long-term video recording, multi-animal tracking and high-resolution respirometry. We find male and female ticks are in a more active, more arousable state during circadian night. We find respiration is augmented by light, with dark onset triggering more frequent bouts of discontinuous gas exchange and a higher overall volume of CO 2 respired. Observed inactivity during the day meets the criteria of sleep: homeostatic in nature, rapidly reversible, a characteristic pose, and reduced arousal threshold. Our findings indicate that blacklegged ticks are in a distinct, heightened state of activity and arousability during night and in dark, suggesting this period may carry higher risk for tick bites and subsequent contraction of tick-borne diseases., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Coronary atherosclerotic heart disease (CAD) is among the most prevalent chronic diseases globally. Circadian rhythm disruption (CRD) is closely associated with the progression of various diseases. However, the precise role of CRD in the development of CAD remains to be elucidated. The Circadian rhythm disruption score (CRDscore) was employed to quantitatively assess the level of CRD in CAD samples. Our investigation revealed a significant association between high CRDscore and adverse prognosis in CAD patients, along with a substantial correlation with CAD progression. Remarkably distinct CRDscore distributions were also identified among various subtypes. In summary, we have pioneered the revelation of the relationship between CRD and CAD at the single-cell level and established reliable markers for the development, treatment, and prognosis of CAD. A deeper understanding of these mechanisms may offer new possibilities for incorporating "the therapy of coronary heart disease based circadian rhythm" into personalized medical treatment regimens., (© 2024. The Author(s).)

Proper alignment of activity-rest and light-dark patterns allows for healthy bodily functions to occur at optimal times of the day. Disruptions to this alignment may cause poor sleep as well as physical, mental, and cognitive problems. The purpose of this cross-sectional study was to determine if poorer circadian alignment was associated with decreased cognitive functioning among older (> 60 years) participants in the National Health and Nutrition Examination Survey. We utilized actigraphy-based rest-activity and dark-light measurements to calculate phasor magnitude (strength of circadian alignment coupling) and phasor angle (phase difference between activity-rest and light-dark cycles). Multiple linear regression models were used to determine associations of phasor magnitude and angle with performance in various cognitive tests, including Digit Symbol Substitution Test score (DSSS), CERAD Savings Percentage (CSP), and Animal Fluency Test (AFT) score. The results showed that a lower phasor magnitude (which indicates decreased strength of alignment coupling between rest-activity and dark-light cycles) was significantly associated with decreased DSSS (indicating slower processing speed and poorer working memory) when controlling for many important sociodemographic factors. However, this association became non-significant when accounting for sleep duration and total physical activity. Phasor angle did not have a significant association with any of the cognitive scores. Overall, we provided evidence indicating that circadian alignment may be a predictor of cognitive performance. Future studies should investigate whether improving circadian alignment may improve cognitive function and prevent cognitive decline., (© 2024. The Author(s).)

Lack of the typical nocturnal blood pressure (BP) fall, i.e non-dipper, has been known as a cardiovascular risk. However, the influence of non-dipper on atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) has been unclear. We investigated the clinical impact of non-dipping as evaluated by 24-hour ambulatory BP monitoring on the long-term outcome of AF recurrence post-PVI in 76 AF patients with a history of increased BP. The PVI procedure was successful in all 76 patients (mean age, 66±9years; antihypertensive medication, 89%; non-paroxysmal AF, 24%). Twenty patients had AF recurrence during a median follow-up of 1138 days. There was no difference in BP levels between the AF recurrence and non-recurrence groups (average 24 h systolic BP:126 ± 17 vs.125 ± 14 mmHg; P = 0.84). On the other hand, the patients with non-dipper had a higher AF recurrence than those with dipper (38.9% vs.15.0%; P = 0.018). In Cox hazard analysis adjusted by age, non-paroxysmal AF and average 24-hr systolic BP level, the non-dipper was an independent predictor of AF recurrence (HR 2.78 [95%CI:1.05-7.34], P = 0.039). Non-dipper patients had a larger left atrial (LA) volume index than the dipper patients (45.9 ± 17.3 vs.38.3 ± 10.2 ml/m 2 , P = 0.037). Among the 58 patients who underwent high-density voltage mapping in LA, 11 patients had a low-voltage area (LVA) defined as an area with a bipolar voltage < 0.5 mV. However, there was no association of LVA with non-dipper or dipper (22.2% vs.16.1%, P = 0.555). Non-dipper is an independent predictor of AF recurrence post-PVI. Management of abnormal diurnal BP variation post-PVI may be important., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

The nocturnal blood pressure (BP) surge in seconds (sec-surge) is defined as a brief, acute transient BP elevation over several tens of seconds, triggered by obstructive sleep apnea (OSA) and sympathetic hyperactivity. Sec-surge imposes a significant strain on the cardiovascular system, potentially triggering cardiovascular events. Quantitative evaluation of sec-surge level could be valuable in assessing cardiovascular risks. To accurately measure the detailed sec-surge, including its shape as BP rises and falls, we developed a beat-by-beat (BbB) BP monitoring device using tonometry. In addition, we developed an automatic sec-surge detection algorithm to help identify sec-surge cases in the overnight BbB BP data. The device and algorithm successfully detected sec-surges in patients with OSA. Our results demonstrated that sec-surge was associated with left ventricular hypertrophy and arterial stiffness independently of nocturnal BP level or variability. Sec-surge would be worth monitoring for assessing cardiovascular risks, in addition to nocturnal BP level. Nocturnal blood pressure (BP) surge in seconds (sec-surge) places heavy load on the cardiovascular system and can trigger cardiovascular events. To identify sec-surges, we developed a beat-by-beat BP monitoring device and a sec-surge detection algorithm. Furthermore, sec-surge was more related to cardiovascular risks than conventional nocturnal BP parameters., (© 2024. The Author(s).)

Objectives: To compare intraocular pressure (IOP) during the water drinking test (WDT) and modified diurnal tension curve (mDTC) in open-angle glaucoma (OAG) patients, using multimodal, observer-masked tonometry., Methods: Open-angle glaucoma subjects were prospectively enroled, excluding those who had undergone glaucoma filtration or laser surgery. Two-hourly mDTC Goldmann applanation (GAT) and rebound tonometry (RT) was performed between 8:00 and 16:00, and every 15 min for 45 min after ingestion of 800mls of water. Blood pressure, heart rate, pupillometry measurements, and optical coherence tomography (AS-OCT) were also recorded., Results: Forty-two subjects' right eyes were included. 48% were using topical glaucoma medication. Mean baseline IOP was 14.9 ± 4.52 mmHg, with mean visual field mean deviation (±SD) -5.05 ± 5.45 dB. Strong association was found between maximum IOP during mDTC and WDT (r = 0.90, 95% CI 0.82-0.95 p < 0.0001) with agreement (mDTC-WDT) bias -0.82 mmHg, 95% LoA -1.46 to -0.18. During the WDT, mean systolic blood pressure (±SD) increased from 140.0 ± 20.0 to 153.3 ± 24.0 mmHg (p < 0.0001), mean heart rate ( ± SD) reduced from 69.5 ± 11.3 bpm to 63.6 ± 10.0 bpm (p < 0.0001), and temporal iridocorneal angle increased from 29.2 ± 6.0° to 29.6 ± 5.2° (p = 0.04)., Conclusion: This study presents repeated, observer-masked IOP data showing strong correlation between maximum IOP during mDTC and WDT using multimodal tonometry. This supports WDT as a meaningful alternative to mDTC when investigating diurnal IOP characteristics in clinic, with reduced time requirements and associated costs., (© 2024. The Author(s).)

Emerging evidence has documented that circadian rhythm disorders could be related to cardiovascular diseases. However, there is limited knowledge on the direct adverse effects of circadian misalignment on the heart. This study aimed to investigate the effect of chronic circadian rhythm disorder on heart homeostasis in a mouse model of consistent jetlag. The jetlag model was induced in mice by a serial 8-h phase advance of the light cycle using a light-controlled isolation box every 4 days for up to 3 months. Herein, we demonstrated for the first time that chronic circadian rhythm disorder established in the mouse jetlag model could lead to HFpEF-like phenotype such as cardiac hypertrophy, cardiac fibrosis, and cardiac diastolic dysfunction, following the attenuation of the Clock-sGC-cGMP-PKG1 signaling. In addition, clock gene knock down in cardiomyocytes induced hypertrophy via decreased sGC-cGMP-PKG signaling pathway. Furthermore, treatment with an sGC-activator riociguat directly attenuated the adverse effects of jetlag model-induced cardiac hypertrophy, cardiac fibrosis, and cardiac diastolic dysfunction. Our data suggest that circadian rhythm disruption could induce HFpEF-like phenotype through downregulation of the clock-sGC-cGMP-PKG1 signaling pathway. sGC could be one of the molecular targets against circadian rhythm disorder-related heart disease., (© 2024. The Author(s).)

Altered blood pressure (BP) circadian rhythmicity has been increasingly linked with cardiovascular risk. However, little is known about BP circadian rhythm change with age and its possible sociodemographic, anthropometric, and genetic moderators. Twenty-four-hour ambulatory BP was measured up to 16 times over a 23-year period in 339 European Americans (EAs) and 293 African Americans (AAs), with an average age of 15 years at the initial visit. BP circadian rhythms were indexed by amplitude and percent rhythm (a measure of rhythm integrity) and calculated using Fourier analysis. BP amplitude and percent rhythm increased with age and average BP (BP mesor). AAs were more likely to have lower BP amplitude and percent rhythm than their EA counterparts. BP amplitude and percent rhythm also decreased with adiposity (BMI and waist circumference). The summer season was associated with lower BP amplitude in AAs and lower percent rhythm in both AAs and EAs. Sex, height, socioeconomic status, physical activity, and family history of essential hypertension did not have an independent impact on BP amplitude or percent rhythm. The results of the present study suggest that BP circadian rhythm increases with age and BP mesor from childhood to young adulthood, decreases with adiposity, and that AAs are more likely to have lower circadian rhythm than EAs. Furthermore, we demonstrated that the summer season is associated with lower BP rhythmicity., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The degree to which burrowing, soil-dwelling caecilian amphibians spend time on the surface is little studied, and circadian rhythm has not been investigated in multiple species of this order or by manipulating light-dark cycles. We studied surface-activity rhythm of the Indian caecilians Ichthyophis cf. longicephalus and Uraeotyphlus cf. oxyurus (Ichthyophiidae) and Gegeneophis tejaswini (Grandisoniidae), under LD, DD and DL cycles. We examined daily surface activity and the role of light-dark cycles as a zeitgeber. All three species were strictly nocturnal and G. tejaswini displayed the least surface activity. Four out of thirteen individuals, two I. cf. longicephalus, one G. tejaswini and one U. cf. oxyurus, displayed a more or less distinct surface-activity rhythm in all three cycles, and for the nine other animals the activity patterns were not evident. An approximately 24 h free-run period was observed in the three species. When the light-dark cycle was inverted, surface activity in the three species shifted to the dark phase. The findings of this study suggest that caecilians have a weak circadian surface-activity rhythm, and that the absence of light can act as a prominent zeitgeber in these burrowing, limbless amphibians., (© 2024. The Author(s).)

Drowsiness while driving negatively impacts road safety, especially in truck drivers. The present study investigated the feasibility and alerting effects of a daylight-supplementing in-truck lighting system (DS) providing short-wavelength enriched light before, during, and after driving. In a within-participants design, eight truck drivers drove a fully-loaded truck under wintry Scandinavian conditions (low daylight levels) with a DS or placebo system for five days. Subjective and objective measures of alertness were recorded several times daily, and evening melatonin levels were recorded three times per study condition. DS significantly increased daytime light exposure without causing negative side effects while driving. In addition, no negative carry-over effects were observed on evening melatonin and sleepiness levels or on nighttime sleep quality. Moreover, objective alertness (i.e., psychomotor vigilance) before and after driving was significantly improved by bright light exposure. This effect was accompanied by improved subjective alertness in the morning. This field study demonstrated that DS was able to increase daytime light exposure in low-daylight conditions and to improve alertness in truck drivers before and after driving (e.g., during driving rest periods). Further studies are warranted to investigate the effects of daylight-supplementing in-cabin lighting on driving performance and road safety measures., (© 2024. The Author(s).)

REV-ERBα, a therapeutically promising nuclear hormone receptor, plays a crucial role in regulating various physiological processes such as the circadian clock, inflammation, and metabolism. However, the availability of chemical probes to investigate the pharmacology of this receptor is limited, with SR8278 being the only identified synthetic antagonist. Moreover, no X-ray crystal structures are currently available that demonstrate the binding of REV-ERBα to antagonist ligands. This lack of structural information impedes the development of targeted therapeutics. To address this issue, we employed Gaussian accelerated molecular dynamics (GaMD) simulations to investigate the binding pathway of SR8278 to REV-ERBα. For comparison, we also used GaMD to observe the ligand binding process of STL1267, for which an X-ray structure is available. GaMD simulations successfully captured the binding of both ligands to the receptor's orthosteric site and predicted the ligand binding pathway and important amino acid residues involved in the antagonist SR8278 binding. This study highlights the effectiveness of GaMD in investigating protein-ligand interactions, particularly in the context of drug recognition for nuclear hormone receptors., (© 2024. The Author(s).)

Disrupted or atypical light-dark cycles disrupts synchronization of endogenous circadian clocks to the external environment; extensive circadian rhythm desynchrony promotes adverse health outcomes. Previous studies suggest that disrupted circadian rhythms promote neuroinflammation and neuronal damage post-ischemia in otherwise healthy mice, however, few studies to date have evaluated these health risks with aging. Because most strokes occur in aged individuals, we sought to identify whether, in addition to being a risk factor for poor ischemic outcome, circadian rhythm disruption can increase risk for vascular cognitive impairment and dementia (VCID). We hypothesized that repeated 6 h phase advances (chronic jet lag; CJL) for 8 weeks alters cerebrovascular architecture leading to increased cognitive impairments in aged mice. Female CJL mice displayed impaired spatial processing during a spontaneous alternation task and reduced acquisition during auditory-cued associative learning. Male CJL mice displayed impaired retention of the auditory-cued associative learning task 24 h following acquisition. CJL increased vascular tortuosity in the isocortex, associated with increased risk for vascular disease. These results demonstrate that CJL increased sex-specific cognitive impairments coinciding with structural changes to vasculature in the brain. We highlight that CJL may accelerate aged-related functional decline and could be a crucial target against disease progression., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The circadian clock regulates daily rhythms of numerous physiological activities through tightly coordinated modulation of gene expression and biochemical functions. Circadian disruption is associated with enhanced tumor formation and metastasis via dysregulation of key biological processes and modulation of cancer stem cells (CSCs) and their specialized microenvironment. Here, we review how the circadian clock influences CSCs and their local tumor niches in the context of different stages of tumor metastasis. Identifying circadian therapeutic targets could facilitate the development of new treatments that leverage circadian modulation to ablate tumor-resident CSCs, inhibit tumor metastasis and enhance response to current therapies., (© 2024. Springer Nature America, Inc.)

We evaluated the association of cardiovascular autonomic neuropathy (CAN), blood pressure (BP) and Vitamin D (VD) levels before and after high-dose cholecalciferol supplementation (4000/10,000) UI/day) for 12 weeks in patients (N = 67) with type 1 diabetes mellitus (T1DM). Based on this prospective controlled pilot study, patients were divided into group 1 (N = 23 with CAN) and group 2 (N = 44 without CAN). At baseline, group 1 had higher systolic BP (SBP) during sleep (115 ± 14 vs. 107 ± 12 mmHg, p = 0.04) and lower nocturnal dipping (3 ± 5 vs. 8 ± 6%, p = 0.009). Among those with loss of nocturnal dipping, 45.4% (20/44) had CAN, while in normal nocturnal dipping group it occurred only in 13% (3/23) (p = 0.007). Non-dipper group had worse CAN parameters when compared to dipper group [Very low frequency (VLF) (2.5 ± 0.5vs.2.8 ± 0.4 s, p = 0.01), total power (TP) (2.9 ± 0.6 vs. 3.3 ± 0.4 s, p = 0.01), Valsalva coefficient (1.5 ± 0.4 vs. 1.8 ± 0.6, p = 0.06)]. After VD, only group 1 improved CAN parameters [TP (2.5 ± 0.4 vs. 2.8 ± 0.6, p = 0.01) and VLF (2.2 ± 0.4 vs. 2.4 ± 0.5, p = 0.03). Group 1 presented a reduction in morning SBP (120 ± 20 vs. 114 ± 17 mmHg, p = 0.038) and in morning SBP surge (13 ± 13 vs. 5 ± 14, p = 0.04). High-dose VD was associated with improved CAN parameters and reduced awake SBP and morning SBP surge. These findings suggest that VD may benefit patients with cardiovascular autonomic neuropathy. ISRCTN32601947, registration date: 31/07/2017., (© 2024. The Author(s).)

Axonal terminals of the small ventral lateral neurons (sLNvs), the circadian clock neurons of Drosophila, show daily changes in their arborization complexity, with many branches in the morning and their shrinkage during the night. This complex phenomenon is precisely regulated by several mechanisms. In the present study we describe that one of them is autophagy, a self-degradative process, also involved in changes of cell membrane size and shape. Our results showed that autophagosome formation and processing in PDF-expressing neurons (both sLNv and lLNv) are rhythmic and they have different patterns in the cell bodies and terminals. These rhythmic changes in the autophagy activity seem to be important for neuronal plasticity. We found that autophagosome cargos are different during the day and night, and more proteins involved in membrane remodeling are present in autophagosomes in the morning. In addition, we described for the first time that Atg8-positive vesicles are also present outside the sLNv terminals, which suggests that secretory autophagy might be involved in regulating the clock signaling network. Our data indicate that rhythmic autophagy in clock neurons affect the pacemaker function, through remodeling of terminal membrane and secretion of specific proteins from sLNvs., (© 2024. The Author(s).)

Evidence about the relationship between meal and sleep time and CVD in children is scarce. The aims of this study were to describe the association between life rhythm patterns and blood pressure in children. This research was conducted among 5,608 children aged 6 to 15 years old in Chongqing and Sichuan provinces in 2021 and 2022. Dietary and sleep rhythms information was collected. The time of the first meal and last meal, and sleep time, were obtained. The mean age was 10.48 ± 2.24 years old, with 2958 (52.75%) male participants. The mean feeding window on weekdays was 11.69 h, 12.42 h, and 13.23 h for participants aged 6-7 years old, 8-12 years old and 13-15 years old, respectively. Weekday feeding window and last mealtime were positively correlated with blood pressure levels. And the changes in the feeding window between weekdays and weekends were significantly correlated with BP. Sleep duration and change in wake time were significantly correlated with SBP. Based on these results, this study identified the optimal combination of dietary and sleep rhythm interventions for children younger than 12 years of age and aged 12 and older, respectively. Disorder dietary and sleep rhythms disorders may correlate with elevated blood pressure levels, suggesting developing optimal dietary and sleep rhythm patterns could prevent the incidence of CVDs in children. The optimal dietary rhythm was defined by the indexes of breakfast time, dinner time and daily feeding window. As good meal patterns are defined as satisfied the following three items: for children younger than 12 years should have breakfast after 7:30 am; aged 12 years and over should have breakfast after 7 am; having dinner before 6 pm; daily feeding window less than 12.5 h. And less optimal dietary rhythm should satisfy any condition or eat dinner between 6 pm and 8 pm; and poor dietary rhythm should not satisfy any of the three criteria and eat dinner after 8 pm. Children with optimal dietary rhythm (in group A) had lower SBP (P < 0.001), DBP (P = 0.002) and MAP (P < 0.001) than those in group C., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Cognitive impairment (CI) is frequently a comorbid condition in heart failure (HF) patients, and is associated with increased cardiovascular events and death. Numerous factors contribute to CI in HF patients. Decreased cerebral blood flow, inflammation, and activation of neurohumoral factors are all thought to be factors that exacerbate CI. Hypoperfusion of the brain due to decreased systemic blood flow, cerebral venous congestion, and atherosclerosis are the main mechanism of CI in HF patients. Abnormal circadian BP rhythm is one of the other conditions associated with CI. The conditions in which BP does not decrease sufficiently or increases during the night are called non-dipper or riser BP patterns. Abnormal circadian BP rhythm worsens CI in HF patients through cerebral congestion during sleep and atherosclerosis due to pressure overload. Interventions for CI in HF patients include treatment for HF itself using cardiovascular drugs, and treatment for fluid retention, one of the causes of abnormal circadian rhythms. Proposed pathways of cognitive impairment in heart failure through abnormal circadian blood pressure rhythm., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Obstructive sleep apnea (OSA) and associated nocturnal blood pressure (BP) surges is associated with non-dipper. On the other hand, the relationship between neurodegenerative diseases and non-dipper hypertension has been reported. To date, few studies have evaluated the relationships of nocturnal BP dipping patterns and OSA in relation to neurodegenerative diseases, particularly Alzheimer's disease (AD). This review examines the etiology of the association between OSA and the non-dipper pattern of hypertension and how both are involved in the development of AD. To set the stage for this review, we first focus on the pathophysiology of AD, which is interrelated with sleep apnea and non-dipper through dysregulation of central autonomic network., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Circadian rhythms play a crucial role in the regulation of various physiological processes, including cardiovascular function and metabolism. Exercise provokes numerous beneficial adaptations in heart, including physiological hypertrophy, and serves to shift circadian rhythms. This study investigated the impact of time-restricted exercise training on exercise-induced adaptations in the heart and locomotor activity rhythms. Male mice (n = 45) were allocated to perform voluntary, time-restricted exercise in the early active phase (EAP), late active phase (LAP), or remain sedentary (SED) for 6 weeks. Subsequently, mice were allowed 24-h ad libitum access to the running wheel to assess diurnal rhythms in locomotor activity. Heart weight and cross-sectional area were measured at sacrifice, and cardiac protein and gene expression levels were assessed for markers of mitochondrial abundance and circadian clock gene expression. Mice rapidly adapted to wheel running, with EAP mice exhibiting a significantly greater running distance compared to LAP mice. Time-restricted exercise induced a shift in voluntary wheel activity during the 24-h free access period, with the acrophase in activity being significantly earlier in EAP mice compared to LAP mice. Gene expression analysis revealed a higher expression of Per1 in LAP mice. EAP exercise elicited greater cardiac hypertrophy compared to LAP exercise. These findings suggest that the timing of exercise affects myocardial adaptations, with exercise in the early active phase inducing hypertrophy in the heart. Understanding the time-of-day dependent response to exercise in the heart may have implications for optimizing exercise interventions for cardiovascular health., (© 2023. The Author(s).)

The relationship between declining nocturnal blood pressure (BP) and adverse cardiovascular outcomes is well-recognized. However, the relationship between diurnal BP profile and the risk of chronic kidney disease (CKD) progression is unclear. Herein, we examined the association between nocturnal systolic SBP (SBP) dipping and CKD progression in 1061 participants at the Cardiovascular and Metabolic Disease Etiology Research Center-High Risk (CMERC-HI). The main exposure was diurnal systolic BP (SBP) profile and diurnal SBP difference ([nighttime SBP-daytime SBP] × 100/daytime SBP). The primary outcome was CKD progression, defined as a composite of ≥ a 50% decline in the estimated glomerular filtration rate from baseline or the initiation of kidney replacement therapy. During 4749 person-years of follow-up (median, 4.8 years), the composite outcome occurred in 380 (35.8%) participants. Compared to dippers, the hazard ratios (HRs) for the risk of adverse kidney outcomes were 1.02 (95% confidence interval [CI], 0.64-1.62), 1.30 (95% CI, 1.02-1.66), and 1.40 (95% CI, 1.03-1.90) for extreme dipper, non-dipper, and reverse dipper, respectively. In a continuous modeling, a 10% increase in diurnal SBP difference was associated with a 1.21-fold (95% CI, 1.07-1.37) higher risk of CKD progression. Thus, decreased nocturnal SBP decline was associated with adverse kidney outcomes in patients with CKD. Particularly, patients with non-dipping and reverse dipping patterns were at higher risk for CKD progression than those with a dipping pattern., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Light exerts powerful and pervasive effects on physiology and behaviour. These effects can be indirect, through clock synchronization and phase adjustment of circadian rhythms, or direct, independent of the circadian process. Exposure to light at inappropriate times, as commonly experienced in today's society, leads to increased prevalence of circadian, sleep and mood disorders as well as cognitive impairments. In mice, exposure to an ultradian 3.5 h light/3.5 h dark cycle (T7) for several days has been shown to impair behaviour through direct, non-circadian, photic effects, a claim we challenge here. We first confirmed that T7 cycle induces a lengthening of the circadian period resulting in a day by day phase-delay of both activity and sleep rhythms. Spatial novelty preference test performed at different circadian time points in mice housed under T7 cycle demonstrated that cognitive deficit was restrained to the subjective night. Mice under the same condition also showed a modification of stress-induced despair-like behaviour in the forced swim test. Therefore, our data demonstrate that ultradian light cycles cause time-of-day-dependent alteration of cognition and mood through clock period lengthening delaying circadian sleep phase, and not through a direct photic influence. These results are of critical importance for the clinical applications of light therapy in the medical field and for today's society to establish lighting recommendations for shift work, schools, hospitals and homes., (© 2023. The Author(s).)