J Biol Rhythms
· 2026 Apr · PMID 41410213
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Obesity is a major public health concern, with disparities across racial and sex groups. While sleep duration has been extensively studied in relation to obesity, the role of sleep regularity remains less explored. In 2...Obesity is a major public health concern, with disparities across racial and sex groups. While sleep duration has been extensively studied in relation to obesity, the role of sleep regularity remains less explored. In 2 nationally representative samples of US adults in the National Health and Nutrition Examination Survey (NHANES 2011/2012 & 2013/2014, = 7085), we investigated the cross-sectional association between a sleep regularity index (SRI) derived from accelerometer data and obesity measures. Body mass index (BMI), waist circumference (WC), body roundness index (BRI), total fat mass, sagittal abdominal diameter (SAD), sagittal abdominal diameter to height ratio (SADHtR), fat mass index (FMI), lipid accumulation product (LAP), and visceral adiposity index (VAI) were derived from NHANES body measures. Multivariable-adjusted regression models were used to estimate multiplication factors (MF) and 95% confidence intervals (CIs) comparing mean BMI across quintiles of SRI and to test for effect modification by sex and ethnicity. Higher SRI was associated with significantly lower BMI (MF SRI: 0.92; 95% CI, 0.91-0.94; < 0.001), translating into 8% lower BMI among those with most versus least regular sleep. This association was more pronounced among women than men (MF SRI women: 0.92; 95% CI, 0.90-0.95; men: 0.98; 95% CI, 0.96-1.00), with strongest effects in non-Hispanic White and other/multi-racial women ( < 0.001). Similar inverse associations were observed for all other obesity measures. In conclusion, sleep regularity, measured by the SRI, was inversely associated with BMI and any other obesity measures. The observed disparities suggest sleep regularity may contribute differentially to obesity risk by sex and race/ethnicity.
Stone JE, Steven D, Cheng W
… +2 more, Cain SW, Phillips AJK
J Biol Rhythms
· 2026 Apr · PMID 41405486
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Light is the primary circadian time cue, but there are large interindividual differences in how sensitive the circadian system is to light. Currently, it is not well understood how individual differences in light sensiti...Light is the primary circadian time cue, but there are large interindividual differences in how sensitive the circadian system is to light. Currently, it is not well understood how individual differences in light sensitivity interact with real-world light environments to determine sleep and circadian timing. We used a validated computational model to simulate sleep and circadian timing (predicted dim light melatonin onset) under realistic assumptions about light and work schedules. Simulations were repeated varying light sensitivity (translated to equivalent ED50 values for interpretability), as well as evening, morning, and daytime illuminances. Brighter evening light led to later predicted circadian and sleep timing, with this effect being amplified by high light sensitivity. Reducing evening light was particularly beneficial for those with high light sensitivity or a long circadian period. Brighter morning light was beneficial for individuals with a long circadian period, or those with both high light sensitivity and high evening light. However, bright morning light could be maladaptive in individuals with a short circadian period or those with low light sensitivity and low evening light. Brighter daytime light attenuated the delaying effects of evening artificial light across conditions, indicating that increasing daytime light was the most universally beneficial lighting intervention. Our results demonstrate how circadian light sensitivity can be used to tailor individual-level solutions that support optimal sleep and circadian timing.
The purpose of this study was twofold: (a) to determine whether, and the extent to which, the challenge of a single night of total sleep deprivation (TSD) unmasks lingering brain health-related deficits in individuals wh...The purpose of this study was twofold: (a) to determine whether, and the extent to which, the challenge of a single night of total sleep deprivation (TSD) unmasks lingering brain health-related deficits in individuals who within the past 3 to 12 months had been diagnosed (yet medically cleared) with a mild traumatic brain injury (mTBI+), and (b) to determine whether mTBI+ results in any neurophysiobehavioral deficits in the ability to recover from TSD. Seven previously concussed (mTBI+) adults (24.5 ± 5.3 years old) and six non-concussed control (mTBI-) adults underwent 24 h TSD preceded by 8 h baseline sleep (BSL) and followed by 8 h recovery sleep (REC). Study measures included the psychomotor vigilance test (PVT) across the entire study and polysomnography during nighttime sleep and daytime nap tests. mTBI+ (vs mTBI-) subjects exhibited more minor lapses on the PVT across all study phases. NREM (N3) sleep and total sleep time (TST) amounts were lower and wake after sleep onset (WASO) was higher in mTBI+ subjects (vs mTBI) at baseline and REC. mTBI+ (vs mTBI-) subjects showed no main effects in maintenance of wakefulness across TSD. Although there is some evidence that TSD may unmask latent performance deficits in mTBI+ subjects, a definitive conclusion was precluded by differences in baseline sleep in mTBI+ (vs mTBI-) subjects, suggesting that they may habitually carry a relatively elevated sleep debt (vs mTBI- controls). Reversal of TSD-induced neurophysiobehavioral deficits following recovery sleep were comparable for both groups, revealing no significant abnormalities in the responsivity of the sleep homeostat in the mTBI+ subjects.
In animals, the brain contains circadian clock neurons that regulate activity rhythms. The fruit fly exhibits a bimodal activity pattern characterized by two peaks, in the morning (M) and evening (E), known as the M and...In animals, the brain contains circadian clock neurons that regulate activity rhythms. The fruit fly exhibits a bimodal activity pattern characterized by two peaks, in the morning (M) and evening (E), known as the M and E peaks. These activity peaks are orchestrated by a network of approximately 240 clock neurons. The neuropeptide pigment-dispersing factor (PDF) is expressed in two sets of clock neurons, the large ventrolateral neurons (l-LN) and the small ventrolateral neurons (s-LN). Mutants of , as well as flies lacking PDF neurons, exhibit a characteristic E activity that is commonly simplified to a phase-advanced pattern under 12 h:12 h light-dark cycles. Previous studies have demonstrated that l-LN neurons regulate the phase of the E peak; however, this effect is evident only under long photoperiod conditions. Therefore, the E peak phenotype observed in mutants remains incompletely explained. In this study, we employed genetic cell ablation and RNA interference using Gal4 lines specific to l-LN neurons in a well-controlled genetic background. Under long photoperiod conditions, flies lacking l-LN, s-LN, or both neuronal groups exhibited an early termination of E activity prior to lights-off, resulting in a phase-advanced E peak. Similar results were obtained in knockdown flies. Notably, l-LN neurons had a stronger effect on the timing of E activity termination than s-LN neurons. These findings demonstrate that LN neurons control the phase of E activity by modulating the timing of its offset, providing new insights into the neuronal mechanisms that shape daily activity patterns.
J Biol Rhythms
· 2026 Feb · PMID 41355593
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Chronobiology is one of the broadest disciplines in science - we can study and apply this system from molecules to shiftwork, from individuals to populations, from physiology to psychology, from mechanisms to medicine. S...Chronobiology is one of the broadest disciplines in science - we can study and apply this system from molecules to shiftwork, from individuals to populations, from physiology to psychology, from mechanisms to medicine. Since I have an aversion against thinking in boxes, chronobiology was the only discipline I could faithfully live in for the past 55 years, giving me the privilege to witness its epitaxy from its pioneers to circadian medicine. I have tackled chronobiological questions with many different methods, but by far my favorite tool to understand are concepts.
Weed L, Jamgochian A, St Hilaire MA
… +3 more, Cheng P, Kochenderfer MJ, Zeitzer JM
J Biol Rhythms
· 2026 Feb · PMID 41342262
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While current mathematical models of human circadian rhythms accurately predict circadian phase responses to light in controlled laboratory experiments, they show reduced performance in the real world, especially among s...While current mathematical models of human circadian rhythms accurately predict circadian phase responses to light in controlled laboratory experiments, they show reduced performance in the real world, especially among shift workers with irregular schedules and downstream erratic light diets. The source of the discrepancy between in-laboratory and ambulatory performance remains unclear. We evaluate the impact of initialization strategy, recording duration, and light exposure characteristics on model performance using wearable data from both individuals on regular schedules and shift workers. We implement a probabilistic initialization framework to account for unknown starting phase and assess model performance in prediction of phase from light input data against an in-lab measure of circadian phase (dim light melatonin onset). In participants with regular schedules, accuracy improved with longer recordings, while shift workers show no accuracy gains when having more nights of data. Light exposure patterns differed significantly between groups, with brighter and more regular day-to-day light exposure being weakly to moderately associated with improved model estimates, whereas fragmented patterns of light exposure increased uncertainty. These findings suggest that current models require adaptation, particularly in light sensitivity, to generalize to free-living, irregular conditions and support robust, scalable circadian tracking in real-world populations.
Carvalhas-Almeida C, Noya SB, Wu T
… +4 more, Rita Álvaro A, Cavadas C, Williams JA, Sehgal A
J Biol Rhythms
· 2026 Feb · PMID 41342187
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Rhythmicity is a central feature of behavioral and physiological processes, including sleep, immune responses, and metabolism. Research on brain control of these processes has largely focused on neurons, with less known...Rhythmicity is a central feature of behavioral and physiological processes, including sleep, immune responses, and metabolism. Research on brain control of these processes has largely focused on neurons, with less known about the role of clock genes in glial cells. In this study, we addressed the function of glial clocks by targeting the expression of key clock genes in glia of Loss of the ) gene in glia increases sleep following aseptic injury and loss of either or ( significantly reduces locomotor activity in light:dark cycles and in constant dark, but other than this, the major effect of clock gene loss in glia is on metabolic function. We demonstrate that disruption of either or in glia affects glycogen stores and reduces metabolic rate. Disruption of either or in glia also affects rhythms of feeding and overall food consumption. Notably, these effects of clock disruption are mediated by distinct glial subtypes, especially cortex glia. We propose that the major role of glial clocks is in the control of energy homeostasis and metabolic rhythms, which likely also accounts for effects on locomotor activity. These findings link metabolism and behavior via circadian regulation in glia.
J Biol Rhythms
· 2026 Feb · PMID 41321322
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The circadian clock in eukaryotes keeps time via transcriptional feedback loops. In the transcriptional feedback loop of animals, CLOCK activator complexes drive expression of PER repressor complex components which feedb...The circadian clock in eukaryotes keeps time via transcriptional feedback loops. In the transcriptional feedback loop of animals, CLOCK activator complexes drive expression of PER repressor complex components which feedback to inhibit CLOCK activation until PER complexes are degraded, thus initiating the next round of CLOCK activation ~24 h later. Recently, we showed that a region of monarch CLOCK (CLK) analogous to that encoded by mammalian CLOCK exon 19 (CLKe19r) and the methyltransferase TRITHORAX (TRX) are required for CLK activation, PER-CLK binding, and PER repression and that TRX-dependent methylation of Heat Shock Protein 68 (HSP68) at arginine 45 (R45) is necessary for PER-CLK binding and PER repression. Given that CLK activation and PER repression complexes in Drosophila are comprised of different core components than in monarchs, we tested whether similar mechanisms are used for CLK activation and PER repression in Drosophila. We found that the CLKe19r, TRX and HSP68 are all required for CLK activation yet only HSP68, but not HSP68 R45 methylation, is required for PER repression in Drosophila. These results reveal a well-conserved CLK activation mechanism and a PER repression mechanism that retains HSP68 function but does not require TRX-dependent methylation.
J Biol Rhythms
· 2026 Feb · PMID 41299814
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We present a comprehensive analysis of the historical fluctuations and rephasing of seasonal birth rates in the United Kingdom from 1955 to 2015. We analyzed monthly live-birth records for England and Wales together with...We present a comprehensive analysis of the historical fluctuations and rephasing of seasonal birth rates in the United Kingdom from 1955 to 2015. We analyzed monthly live-birth records for England and Wales together with national photoperiod and surface-temperature series to track the annual rhythm of human reproduction. Fast Fourier transforms confirmed a robust 12-month component across the entire record, but breakpoint tests located a sharp phase shift in 1974-1976. Before this transition, peak conceptions clustered tightly around the summer solstice and yielded a stable March birth maximum. After 1976, the rhythm decoupled: the spring peak in births collapsed, a secondary autumn peak emerged, and inter-annual phase variability more than doubled. Cross-correlation analyses showed that, up to 1974, photoperiod led birth counts by ≈11 months whereas temperature played only a minor role. Post 1976, photoperiod correlations disappeared and a weaker, inverse link with temperature persisted. Sliding-window statistics indicate that variability has narrowed again since the mid-1990s, hinting at partial re-stabilization of the seasonal pattern, now centered in late autumn conceptions. These results demonstrate that the mid-1970s marked a singular disruption of the United Kingdom's reproductive calendar, coincident with the nationwide roll-out of freely available hormonal contraception and other social shifts. The findings urge caution when pooling pre- and post-1974 cohorts in genetic or epidemiological studies-such as those using UK Biobank-to explore season-of-birth effects. More broadly, they highlight the plasticity of human annual timing and the need to disentangle biological from socio-environmental drivers of reproduction.
Flores Ramos S, Fogelson KA, Muti VB
… +5 more, Zhong W, Hu J, Hosseini M, Loomba R, Zarrinpar A
J Biol Rhythms
· 2026 Feb · PMID 41250304
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Time-restricted feeding (TRF), a dietary intervention that consolidates food intake to specific hours of the day, ameliorates key metabolic risk factors for metabolic-associated steatohepatitis (MASH), including adiposit...Time-restricted feeding (TRF), a dietary intervention that consolidates food intake to specific hours of the day, ameliorates key metabolic risk factors for metabolic-associated steatohepatitis (MASH), including adiposity, insulin resistance, and liver steatosis. However, whether TRF can directly mitigate steatohepatitis or fibrosis remains uncertain. Moreover, whether the protective effects of TRF against MASH-related complications, such as inflammation and fibrosis, depend exclusively on improvements in insulin sensitivity or involve additional mechanisms remains unknown. Here, we examine the impact of 8-hour TRF on the development of fibrosis and steatohepatitis using a streptozotocin/high-fat diet (STAM/HFD) model, which recapitulates key MASH characteristics, including steatohepatitis and fibrosis, in an insulin-deficient context. TRF does not prevent the development of MASH in STAM/HFD male mice where insulin signaling is impaired. Unlike diet-induced obesity models, which exhibit greatly perturbed feeding and circadian behaviors under HFD conditions, STAM/HFD mice did not develop obesity and maintained regular or less-pronounced disruptions to circadian behaviors. This may explain why TRF failed to produce beneficial effects in this model. These findings indicate that intact insulin signaling is likely essential for TRF to effectively protect against MASH.
Finn KT, Francioli Y, Thorley J
… +1 more, Zöttl M
J Biol Rhythms
· 2026 Feb · PMID 41235772
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Animals often show distinct activity rhythms which may align their behavior with favorable environmental conditions. In terrestrial species, daily and seasonal activity patterns are largely influenced by changes in photo...Animals often show distinct activity rhythms which may align their behavior with favorable environmental conditions. In terrestrial species, daily and seasonal activity patterns are largely influenced by changes in photoperiod and temperature. However, subterranean animals experience weak or absent environmental variation due to minimal light exposure and reduced daily temperature fluctuations. Despite these conditions, many subterranean rodents display pronounced diel rhythms in physiological processes and locomotor activity, though the extent of seasonal variation remains unclear. In this study, we used radio frequency identification technology on wild groups of subterranean Damaraland mole-rats to assess their daily activity patterns. Our results show a population-wide daily activity peak around midday, which coincides with the minimum temperature at nesting depths and increasing temperature at foraging depths. The timing of this peak shifts by approximately 2 h between seasons. Neither individual nor group characteristics predicted the occurrence and timing of the activity peak, suggesting that temperature fluctuations, rather than social factors, are the main driver of seasonal variation in activity timing. Although Damaraland mole-rats remain active at low levels throughout the day, they display clear diurnal foraging rhythms at the group level that change little across seasons.
Sepsis is a syndrome caused by a dysregulated host response to pathogens, representing the leading cause of death from infection. Various murine models of sepsis have shown a time-dependent response based on the time of...Sepsis is a syndrome caused by a dysregulated host response to pathogens, representing the leading cause of death from infection. Various murine models of sepsis have shown a time-dependent response based on the time of induction. Mice stimulated with high doses of bacterial lipopolysaccharide (LPS) at the end of the day exhibit a higher mortality rate (~80%) compared with those inoculated in the middle of the night (~30%). In this work, we assessed the differences in serum proteins of septic mice during the day and night. Through this proteomic study, we found significant variations in metabolic pathways, including glucose metabolism, which were associated with a better prognosis. Therefore, we studied the glucose response to LPS during the day and night. In this context, we found an early peak of LPS-induced glucose exclusively at the time of worse prognosis. We also observed a hypoglycemic response to LPS, which was independent of the time of sepsis induction. Finally, we performed a set of metabolic manipulations to study how hyperglycemia influences sepsis severity in mice. We observed that suppressing the glucose peak during the day, through metformin administration, reduced sepsis severity. In contrast, nocturnal glucose administration with LPS was rapidly metabolized and also decreased sepsis severity. In conclusion, sepsis severity may be influenced by the metabolic state at the time of the stimulus. Metabolic rhythms could lead to differences in early glucose management, affecting the outcome of this pathology.
The light input pathways and the molecular clock are tightly linked, with light serving as the most potent zeitgeber that entrains the clock to the external environment. Our present study focuses on the populations that...The light input pathways and the molecular clock are tightly linked, with light serving as the most potent zeitgeber that entrains the clock to the external environment. Our present study focuses on the populations that have evolved with a precise circadian clock as a correlated response to selection for adult emergence in a narrow window of time over 335 generations. The results of our study showed that flies from populations selected for the timing of adult emergence sleep more during the night phase compared to controls. This sleep was even more enhanced when the light intensity was reduced to 1 lux under a 12 h light:12 h dark cycle. In addition, a significantly higher percentage of these flies exhibited free-running period rather than arrhythmicity compared to the control flies under constant light (1 lux). Moreover, the larvae from selected populations exhibited an increased preference toward darkness than light indicating that the effect of selection extends beyond the adult circadian light input pathway, influencing the innate circadian regulated photobehavior in larvae. We examined the transcript oscillation of the circadian photoreceptor (), along with the core clock genes () and () in adult flies to explore the molecular basis of the evolved precise circadian clocks and to determine whether selection influences the circadian light input pathway. Flies from the selected population exhibited a phase advance in the transcript oscillation of , , and , indicating that the molecular circadian clock and its light input pathway evolve as a correlated response to the selection for the timing of adult emergence in populations.
Circadian clocks regulate the immune system, rendering humans more susceptible to infections at certain times of the day. Circadian modulation of SARS-CoV-2 infection has not yet been clearly established, nonetheless the...Circadian clocks regulate the immune system, rendering humans more susceptible to infections at certain times of the day. Circadian modulation of SARS-CoV-2 infection has not yet been clearly established, nonetheless the circadian control of other respiratory viruses such as influenza A makes apparent the need to study the interaction between circadian rhythms and COVID-19 disease progression. We incorporated circadian oscillations into a mechanistic model of SARS-CoV-2 dynamics and immune response fit to viral load data from COVID-19 patients. The model predicts that circadian variation of parameters associated with the innate immune response and viral death rate lead to faster clearance of the virus, whereas circadian variation of parameters representing the susceptible cell infection rate, the viral production rate, and the adaptive immune response lead to slower clearance of the virus. We then used a model of remdesivir to simulate antiviral therapy. Our model simulations predict that the effectiveness of the treatment depends on the time of day the drug is administered. This prediction is conditional on the plausible, but entirely hypothetical, circadian interactions added to the model. Based on our proof-of-concept modeling results, we advocate for experimental and clinical studies to assess the impact that dosing time of day may have on the efficacy and toxicity of current COVID-19 antiviral drugs.
J Biol Rhythms
· 2026 Feb · PMID 41103170
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Early childhood represents a period of profound developmental changes for sleep and circadian biology. Although the relationship between sleep and circadian timing has been well characterized in older populations, such d...Early childhood represents a period of profound developmental changes for sleep and circadian biology. Although the relationship between sleep and circadian timing has been well characterized in older populations, such data in young children remain limited. Here, we provide fundamental data on the relationship between endogenous circadian phase and sleep timing in a sample of preschool-aged children. Participants were 49 healthy children ages 3.1 to 6.0 years ( = 4.44 years, = 0.69 years, 27 female). After 7 days of maintaining a consistent, parent-selected sleep schedule, children completed an in-home, dim-light circadian assessment. Saliva samples were collected in 30-min intervals throughout the evening to determine the timing of children's dim-light melatonin onset (DLMO). Children's DLMOs occurred an average of 35.0 ± 35.3 min before their bedtimes, with parent-selected bedtime occurring before DLMO for 18.4% of children. Children with later DLMOs had significantly later bedtimes ( = 0.65), sleep onset times ( = 0.74), midsleep times ( = 0.74), and wake times ( = 0.66) (all < 0.001). For every hour later that DLMO occurred, average bedtime and sleep onset time were 28.0 and 33.4 min later, respectively. In addition, children with later DLMOs had higher scores on a parent-reported measure of chronotype ( = 0.56, < 0.001), indicating greater eveningness. No association between DLMO time and sleep duration or social jetlag was observed. These data extend previous findings in toddlers, demonstrating a consistent relationship between circadian phase and sleep timing, as well as chronotype, throughout early childhood.
Frenken KG, Chong MY, Breukink SO
… +12 more, Janssen-Heijnen M, Keulen ETP, Konsten J, Bijnens W, Buffart LM, Meijer K, Scheer FAJL, Steindorf K, de Vos-Geelen J, Weijenberg MP, Bours MJL, van Roekel EH
J Biol Rhythms
· 2025 Dec · PMID 41035201
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Disrupted diurnal rest-activity rhythms (RAR), that is, daily 24-h patterns of rest and activity, have been associated with fatigue and decreased quality of life among survivors of colorectal cancer (CRC). To identify po...Disrupted diurnal rest-activity rhythms (RAR), that is, daily 24-h patterns of rest and activity, have been associated with fatigue and decreased quality of life among survivors of colorectal cancer (CRC). To identify potential targets for interventions to improve RAR, we investigated longitudinal associations of time spent in sedentary behavior and physical activity with RAR parameters after CRC treatment. In a prospective cohort study, repeated measurements were performed among 268 survivors of stage I-III CRC at 6 weeks, 6 months, and 1, 2, and 5 years after treatment. Thigh-worn accelerometers were used to determine hours/day spent in sedentary behavior, standing, and total physical activity during waking time, as well as RAR parameters including mesor, amplitude, circadian quotient (CQ), dichotomy index (I < O) and 24 h-autocorrelation (R24). Self-reported light-intensity physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) were determined via the validated SQUASH questionnaire. Longitudinal associations were analyzed using confounder-adjusted linear mixed models. More sedentary time was statistically significantly associated with a lower mesor, amplitude, I < O and R24 over the 5-year post-treatment period. More standing time was associated with a higher mesor, amplitude, CQ, and I < O but not with R24. Higher levels of objectively assessed total physical activity as well as self-reported MVPA were associated with higher values for all RAR parameters. LPA was not associated with any of the RAR parameters. In the years after CRC treatment, less sedentary behavior and more standing and physical activity were generally associated with higher RAR parameters indicating a more robust rhythm. Future studies should provide more insight into causality of these associations as RAR may be a potential new target for interventions to reduce fatigue after CRC.Trial registration: EnCoRe study NL6904 (https://www.Onderzoekmetmensen.nl/).
Sengupta S, Lee Y, Tao JQ
… +8 more, Akolia I, Louneva N, Forrest K, Paul O, Brooks TG, Grant GR, Sehgal A, Chatterjee S
J Biol Rhythms
· 2025 Dec · PMID 40947518
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Circadian rhythms are endogenous oscillations that occur with a 24-h periodicity and support organismal homeostasis. While the role of the circadian clock in systemic vasculature is well known, its role in pulmonary vasc...Circadian rhythms are endogenous oscillations that occur with a 24-h periodicity and support organismal homeostasis. While the role of the circadian clock in systemic vasculature is well known, its role in pulmonary vasculature, specifically in the pulmonary endothelium, has remained unexplored. We hypothesized that the circadian clock directly regulates pulmonary endothelium to control lung inflammation. Using pulmonary artery segments and endothelial cells isolated from lungs of mPer2luciferase transgenic mice, we monitored circadian rhythms and observed that lipopolysaccharide (LPS) treatment disrupted rhythmicity. This disruption was mediated by reactive oxygen species (ROS) generated via NADPH oxidase 2 (NOX2). Remarkably, the pharmacologic inhibition of NOX2 before LPS exposure restored circadian rhythmicity in the pulmonary endothelium. In wild-type (WT) mice, LPS activated a NOX2-NLRP3 signaling axis that drove inflammation as evidenced by increased polymorphonuclear neutrophil (PMN) accumulation and intercellular adhesion molecule-1 (ICAM-1) expression on the pulmonary endothelium. In contrast, disruption of the clock using two different clock mutants (1 and ) resulted in a sustained baseline elevation of PMN and ICAM-1, which changed minimally with LPS. This effect was attributed to aberrant activation of the NLRP3 inflammasome at baseline in the clock mutants, as supported by lung transcriptomic data and reversal of the phenotype with an NLRP3 inhibitor. Importantly, these findings also reveal an intriguing bidirectional relationship: while the circadian clock modulates inflammatory responses, inflammatory stimuli in turn alter circadian rhythmicity via the NOX2 pathway. Together, our results identify a novel mechanism by which circadian control of pulmonary endothelial inflammation may be leveraged to mitigate the consequences of clock disruption in lung disease.