Search Results (2,065)

The rising global demand for lithium has led to substantial accumulation of lithium slag, a by-product of lithium carbonate production and a potential environmental contaminant. Leachates from this material contain various metal elements and may pose risks to ecosystems and organismal health. However, research on its neurotoxicity and underlying mechanisms remains limited. In this study, zebrafish embryos at 6 h post-fertilisation were exposed to varying concentrations of lithium slag leachate for 7 days. The leachate contained multiple metal ions (Li, Fe, Mn, Ni, Zn, As, Cr, Cu, Hg, Cd, Pb, etc.). Following exposure, significant metal accumulation was observed in larvae, accompanied by developmental malformations (yolk sac oedema, cardiac haemorrhage, and uninflated swim bladders). Behavioural assessment revealed reduced swimming distance and velocity, along with disrupted circadian rhythms. Biochemical analyses showed elevated Reactive oxygen species (ROS), Superoxide dismutase (SOD), Catalase (CAT), and Malondialdehyde (MDA), alongside decreased Glutathione (GSH), indicating oxidative stress. Transcriptomic analysis confirmed downregulation of core circadian genes. Neurotransmitter assays revealed decreased acetylcholine (Ach), noradrenaline (NE), and dopamine (DA), with increased gamma-aminobutyric acid (GABA) and serotonin (5-HT). These findings demonstrate that lithium slag leachate induces oxidative stress, circadian disruption, and neurobehavioural toxicity in zebrafish, providing important evidence for environmental risk assessment. Full article

Understanding the genetic architecture underlying growth variation is central to improving aquaculture species through genomic selection. Here, we performed a genome-wide association study (GWAS) on 303 individuals from a G₂ breeding population of channel catfish (Ictalurus punctatus) using whole-genome resequencing data. After stringent quality control, 5.64 million high-confidence single nucleotide polymorphisms (SNPs) were retained for association analyses of two key growth traits—monthly weight gain (MWG) and body depth (BH). We identified 15 and 28 loci significantly associated with MWG and BH, respectively, with the majority concentrated on chromosome 20. Two SNPs (Chr20:14,657,971 and Chr20:14,658,012) located in exon 9 of the rrp44 gene were significantly associated with both traits. Functional annotation and enrichment analyses revealed that the rrp44 gene, encoding an exoribonuclease subunit of the RNA exosome complex, participates in mitotic spindle regulation and post-transcriptional RNA decay, processes critical for cellular growth and metabolic homeostasis. We propose that rrp44 may influence growth through the modulation of feeding rhythm and circadian regulation, providing a potential molecular basis for growth heterogeneity in channel catfish. These findings enrich our understanding of growth-related genomic variation and offer valuable molecular markers for precision breeding and genetic improvement of catfish. Full article

Background/Objectives: Growing evidence suggests that disruption of circadian rhythms contributes to the pathogenesis of inflammation and inflammatory bowel disease; however, clinical data linking circadian gene variants to ulcerative colitis remain limited. In this study, we aimed to investigate associations between key circadian rhythm gene polymorphisms and clinical and treatment-related characteristics in ulcerative colitis. Methods: A total of 107 patients with ulcerative colitis and 80 healthy controls were included in this single-center cross-sectional study. The BMAL1 rs7950226, CLOCK rs1801260, and CRY1 rs2287161 polymorphisms were analyzed using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method. Genotype and allele frequency distributions were compared between patients and controls, and associations with clinical characteristics were evaluated within the ulcerative colitis cohort. Results: Genotype distributions of BMAL1 rs7950226 and CLOCK rs1801260 were similar between patients with ulcerative colitis and healthy controls; however, the G allele of BMAL1 was more frequent in patients (p = 0.028). Within the ulcerative colitis cohort, CLOCK rs1801260 genotypes were significantly associated with inflammatory and treatment-related characteristics, with the CC genotype linked to higher C-reactive protein levels (p = 0.021) and the TT genotype associated with increased azathioprine use (p = 0.006). Conclusions: These findings suggest a potential association between circadian rhythm gene variants and clinical features of ulcerative colitis, particularly in relation to inflammatory activity and treatment requirements, and provide preliminary clinical insight that warrants further investigation in larger and longitudinal studies. Full article

Background/Objectives: Circadian rhythm disruption is linked to cognitive decline, yet it remains unclear how behavioral and physiological rhythm markers are differently associated with cognition in amnestic mild cognitive impairment (aMCI). The primary aim of this study was to compare sleep–wake timing, rest–activity rhythm (RAR), and dim light melatonin onset (DLMO) between patients with aMCI and cognitively normal controls. Exploratory analyses further examined their associations with domain-specific cognitive performance. Methods: Eighteen aMCI patients and 21 cognitively normal controls (NC) enrolled. Cognitive function was assessed using the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Battery (CERAD-K). Participants underwent 5-day actigraphy to assess sleep–wake timing and non-parametric RAR variables, including interdaily stability (IS), intradaily variability (IV), and relative amplitude (RA). DLMO was determined from hourly salivary melatonin samples collected over five hours before sleep onset under dim-light conditions. Group comparisons of circadian markers were conducted as the primary analyses, and generalized linear models were used for exploratory analyses of associations between circadian markers and cognitive outcomes. Results: Groups did not significantly differ in sleep–wake timing, RAR parameters and DLMO. Sleep–wake timing variables and DLMO were not significantly associated with cognitive performance. Higher IS was associated with better visuospatial memory and executive function, whereas higher RA was associated with poorer verbal memory among aMCI patients. Conclusions: Although sleep–wake timing and melatonin phase did not differ between groups nor predict cognitive performance, higher daily rhythm stability was linked to better non-verbal memory and executive functioning. In contrast, high RA may relate to poorer verbal memory in aMCI, suggesting that elevated RA may not reflect true circadian robustness required for optimal cognition. Full article

Light exposure is a primary zeitgeber for the human circadian system and plays a key role in shaping sleep–wake patterns during adolescence, a period marked by biological sensitivity and social constraints. How the temporal organization and spectral composition of daily light exposure differ between weekdays and weekends remains poorly understood. Eighteen adolescents (15–17 years) were monitored for seven days using wrist actigraphy with integrated light sensors. Sleep parameters, nonparametric circadian rhythm indices, and time-resolved profiles of ambient and spectral (blue, green, and red) light exposure were analyzed. Repeated-measures ANOVA tested the effects of time of day and day type. Total sleep time and time in bed were longer on weekdays than on weekends (p < 0.05), while sleep latency and WASO did not differ. Circadian indices indicated preserved rhythmic organization. Light exposure showed a robust diurnal profile, with higher spectral irradiance on weekends (p < 0.001), especially in the morning and early afternoon. Significant time × day-type interactions were observed across all spectral bands (p < 0.001), indicating systematic reshaping of daily light profiles. Adolescents exhibit weekday–weekend differences in the temporal and spectral organization of light exposure, affecting the amplitude and shape of overall daily profiles. Full article

Melatonin is reported to exert two types of actions: those based on its interaction with cognate receptors (characterized by very high affinities—1 nM and below), and those mediated by unknown targets (characterized by high concentrations—100 µM and above). Whereas receptor-mediated activities are known to regulate circadian rhythm, the high-dose effects are reported to be independent of these receptors and to produce literally dozens of beneficial effects in almost all human diseases, including cancer, neurodegenerative disorders, viral infections, obesity and many others. In the present opinion paper, we discuss this extensive set of claims and place them in perspective with a sum of evidence that collectively challenges the validity of these alleged beneficial effects. Full article

This comparative cross-sectional study simultaneously investigated the dual health burden of body mass index (BMI) and common mental disorders (CMDs) driven by occupational stressors in two stepwise regression models. By classifying stress exposure into three clinically relevant tiers (low, moderate, and severe) in two distinctive populations—a hospital and a manufacturing company—we used the validated SDS-30 and SRQ-20 instruments. The robust multiple regression models uncovered a highly nuanced landscape of employee well-being that highlights the context-dependent nature of psychosocial hazards. The most compelling findings emerged from the interaction analyses, which demonstrated that the physical and mental consequences of severe stress do not impact the workforce uniformly. Regarding mental health, severe occupational stress proved to be a potent catalyst for CMD symptoms, but this psychological toll was significantly magnified within the hospital sector relative to the manufacturing environment. An opposite, yet equally context-dependent, pattern emerged regarding physical health. In the main-effects-adjusted model, the severity of occupational stressors did not demonstrate a statistically significant linear association with an overall increase in BMI. However, the interaction model revealed a hidden vulnerability: employees in operational field roles who report severe stress are highly susceptible to severe BMI increases compared with admin personnel. While administrative staff may face sedentary risks, field workers under severe stress likely endure higher physiological allostatic load, erratic shift patterns that disrupt circadian metabolic rhythms, and potentially poorer dietary coping mechanisms during active labor. This combination of physical exhaustion and severe psychological tension severely disrupts metabolic homeostasis, forcing the redistribution of adipose tissue and driving the observed BMI spike. Full article

Sleep is tightly regulated by thermoregulatory processes that include core body temperature (CBT) modulation, the distal–proximal temperature gradient (DPG), and melatonin rhythms. In this review, we examine how these factors intersect with sleep physiology and contribute to the pathophysiology of common sleep disorders such as ADHD, insomnia, narcolepsy, Obstructive Sleep Apnea (OSA), depression, and Restless Legs Syndrome (RLS). We discuss evidence showing that delayed or disrupted CBT minima, impaired DPG, and altered melatonin secretion can prolong sleep latency, fragment rest, and lead to daytime symptoms. In addition, we explore temperature-based interventions, including foot baths, passive body heating, whole-body hyperthermia, and adjustments in room temperature, which have demonstrated potential to mitigate symptoms and enhance sleep quality. Collectively, these findings emphasize the need for personalized interventions to address thermoregulatory disruptions, presenting a noninvasive avenue for more effective sleep disorder management. Full article

Sleep is a cardinal biological process that backstops central nervous system function, which also plays a crucial role in regulating systemic homeostasis, including immune activities. Cytokines, particularly interleukin-1β and tumor necrosis factor-α, act as mediators bridging sleep and inflammation, also influencing both sleep architecture and sleep–wake cycle. Sleep deprivation and sleep disorders such as insomnia, narcolepsy, hypersomnia, or obstructive sleep apnoea may disrupt cytokine production, alter their circadian rhythm of release, and shift secretion peaks from night to day. These changes contribute to daytime fatigue, impaired cognitive and physical performance, increased susceptibility to infections and/or systemic inflammation. Molecular studies indicate that insufficient sleep primes immune cells to enhance pro-inflammatory responses, creating a feedback loop with neuroendocrine pathways that further exacerbates sleep patterns and inflammatory dysregulation. Understanding the bidirectional relationship between sleep and cytokines may highlight the role of sleep as an active component of immunity regulation and underscore the potential usefulness of multilevel interventions that include complementary and integrative health approaches restoring sleep, normalizing cytokine rhythms and mitigating inflammation. Full article

The present review discusses vitamin A/retinoid metabolism as a cross-organ axis in which hepatic clock-dependent retinoid handling may affect immune clock gene expression through the stimulation of retinoic acid 6–Janus kinase 2–signal transducer and activator of transcription 5 signaling, potentially promoting pro-inflammatory monocyte states. We further highlight mechanosensory signaling as a second convergent layer that integrates hemodynamic forces with tissue microenvironmental cues. Among these pathways, G protein-coupled receptor 68, a proton- and flow-sensitive G protein-coupled receptor, is discussed as a representative druggable node linking mechanical and inflammatory signaling in chronic kidney disease-associated cardiac injury. Finally, we outline potential therapeutic directions, including (i) circadian alignment/chronopharmacology, (ii) modulation of retinoid metabolism and signaling, and (iii) targeted inhibition of primary immune and mechanosensory effectors. Full article

Background: Circadian disruption exacerbates type 2 diabetes mellitus (T2DM). Time-restricted feeding (TRF) and exercise (EX) improve metabolic health, but their combinatory effect remains unclear. This study investigated whether combined TRF and EX additively ameliorates metabolism via circadian reprogramming in db/db mice. Methods: Eight-week-old male db/db mice were assigned to control (Con), diabetic model (DM), TRF (8 h feeding window), EX (treadmill, 60 min/day, 5 days/week), or combined TRF + EX groups for 8 weeks (n = 8/group). Body weight, glucose/insulin tolerance, and 24 h energy metabolism (CLAMS) were assessed. Mitochondrial function, oxidative stress, inflammation, and expression of mitophagy (Pink1, Park2, Bnip3, Fundc1) and thermogenic (Ucp1, Pgc1a, Prdm16, Cidea) genes were measured. Results: Compared with the con group, DM mice showed obesity, hyperglycemia and blunted circadian metabolic rhythm. The TRF and EX groups improved these defects. Specifically, combined TRF + EX reduced fasting blood glucose from 25.3 ± 3.1 mmol/L (DM) to 13.2 ± 1.8 mmol/L (p < 0.05), body weight from 49.8 ± 2.5 g to 39.5 ± 1.7 g (p< 0.05), and body fat percentage from 45.6 ± 3.2% to 32.1 ± 2.2% (p < 0.05). GTT area under the curve (AUC) decreased from 3711.0 ± 186.5 (DM) to 2118.0 ± 112.4 (p < 0.05), and ITT AUC decreased from 2617.5 ± 135.8 to 1260.0 ± 68.9 (p < 0.05). Notably, the combination of TRF + EX produced greater effects than either intervention alone: body weight, fasting blood glucose, and glucose/insulin tolerance were greatly improved (p < 0.05). In addition, compared with the DM group, the diurnal metabolic amplitude and phase were improved in the TRF or EX group; the combination group showed further improvements in these parameters. Furthermore, TRF and EX each resulted in significantly higher expression of key thermogenic genes (Ucp1, Pgc1a, Prdm16, Cidea) in white adipose tissue (WAT) and brown adipose tissue (BAT) (p < 0.05), and the TRF + EX group showed the highest expression levels. Combined intervention also restored skeletal muscle SOD activity (31.2 ± 2.9 U/mg prot vs. DM 20.1 ± 2.5 U/mg prot, p < 0.05) and reduced serum TNF-α (28.5 ± 4.5 pg/mL vs. DM 65.8 ± 8.5 pg/mL, p < 0.05) and IL-6 (21.6 ± 3.8 pg/mL vs. DM 50.3 ± 7.1 pg/mL, p < 0.05). Conclusions: TRF + EX additively restores metabolic homeostasis in diabetes by re-entraining circadian energy rhythms, improving mitochondrial quality, and activating adipose thermogenesis, supporting further investigation of integrated lifestyle timing as a potential therapeutic strategy. Full article

Circadian clocks generate daily rhythms of gene expression that influence physiology, disease, and responses to therapeutics, yet how circadian transcription differs between juvenile and adult organisms remains unresolved. Here, we used genome-wide eXcision Repair sequencing (XR-seq) to quantify transcription-coupled repair as an indirect, high-sensitivity measure of transcription. We profiled the brain, liver, kidney, and testis from juvenile and adult C57BL6/J mice across a 24 h cycle and show that XR-seq enables sensitive circadian transcription mapping. In all organs except the testis, rhythmic transcription phases clustered near dawn and dusk. While core clock gene rhythms are largely preserved between juveniles and adults, rhythms of many clock-controlled genes differ markedly by age. Rhythmic genes are strongly organ-specific yet their overlap between ages is limited, indicating substantial developmental changes in circadian control. Together, these data provide a multi-organ map of juvenile versus adult circadian transcription and indicate that adult therapeutic schedules may not translate to juveniles. Full article

A high-fat (HF) diet disrupts metabolic homeostasis and impairs peripheral circadian rhythms in key metabolic tissues. β-Hydroxybutyrate (BHB), a major circulating ketone body, functions not only as an energy substrate but also as a signaling metabolite regulating nutrient-sensing and inflammatory pathways. However, its role in modulating metabolic–circadian interactions under conditions of nutrient excess remains unclear. In this study, we investigated whether BHB supplementation influences metabolic signaling and circadian clock oscillations in liver, skeletal muscle and adipose tissue under chow and HF conditions. Male C57BL/6 mice were fed chow or HF with or without BHB supplementation (500 mg/kg body weight in the diet) for 7 weeks. Metabolic parameters were assessed by indirect calorimetry, and tissues were collected every 4 h across the circadian cycle. HF feeding increased body weight and adiposity (p < 0.01), reduced AMPK activation, enhanced AKT/mTOR signaling, elevated NF-κB levels and dampened clock gene rhythmicity. BHB supplementation significantly decreased food intake in HF-fed mice (p < 0.01) and partially reversed several molecular alterations in a tissue-specific manner. In skeletal muscle and adipose tissue, BHB increased AMPK activation and reduced mTOR and NF-κB signaling (p < 0.05), whereas hepatic effects were more modest. Notably, BHB modulated circadian gene expression, restoring aspects of rhythmic amplitude and/or phase, particularly in adipose tissue. These findings may indicate that BHB supplementation modulates nutrient-sensing pathways and partially restores peripheral circadian rhythms under HF conditions. While some effects may be influenced by reduced energy intake, BHB may serve as a metabolic signal linking nutrient status to circadian regulation. Full article

Fibromyalgia (FM) is a complex chronic syndrome marked by widespread musculoskeletal pain, neurocognitive dysfunction (“fibro-fog”), and autonomic disturbances. Clinical management remains challenging due to subjective symptom reporting and the lack of definitive diagnostics. Emerging evidence points to a multifactorial origin involving central sensitization, neuroendocrine imbalance, and systemic immune-inflammatory alterations. A wide array of candidate biomarkers has been reported in FM, encompassing neurotransmitters (serotonin, norepinephrine), excitatory and inhibitory amino acids, metabolic and glycolytic enzymes, stress-related proteins, autoantibodies, oxidative stress markers and pro-inflammatory cytokines. This molecular heterogeneity reflects the systemic and multidimensional nature of FM. However, most of these biomarkers have been primarily investigated in serum or plasma, where analytical validation and reference ranges are more established. In contrast, the exploration of salivary biomarkers—although highly attractive due to its non-invasive, stress-free, and repeatable collection—remains comparatively limited. Saliva contains a reduced concentration range of many systemic markers and is strongly influenced by circadian rhythms, stress, flow rate, and oral health conditions. While promising candidates such as α-amylase, cortisol, calgranulins, and selected metabolic enzymes have shown potential in saliva, many proposed FM-related biomarkers lack full analytical validation, standardized protocols, and clinically defined reference intervals in this matrix. In this context, non-invasive electrochemical biosensors represent a transformative technological approach. Advanced electrode architectures incorporating nucleic acid probes, redox reporters, and nanostructured materials offer high sensitivity in low-volume and low-concentration biofluids such as saliva. The integration of multiplexed biomarker panels into portable platforms could enable real-time, longitudinal monitoring of FM pathophysiology, supporting phenotype stratification, personalized therapeutic adjustment, and objective disease activity tracking. Full article

Circadian rhythms maintain healthy neural function, and their disruption links to pathological brain states including epilepsy. Current diagnostic approaches for epilepsy, which predominantly focus on transient ictal events or static spectral features in intracranial EEG, suffer from a temporal myopia that neglects the rich spatiotemporal dynamics of long-term neural activity. To address this limitation, this study aims to establish multi-band circadian biomarkers as diagnostic signatures for epileptogenic tissue identification and patient subtyping. In this article, we developed a comprehensive biomarker extraction pipeline that analyzes long-term intracranial EEG recordings (72+ h) from 38 drug-resistant epilepsy patients, quantifying multi-band rhythm features from delta to gamma frequencies (1–100 Hz). The pipeline captures three circadian signatures: rhythm amplitude, temporal stability, and cross-frequency coupling. Epileptogenic tissue showed systematic circadian dysregulation: 43.2% reduction in delta band circadian amplitude (p < 0.001), 31.5% impairment in delta–gamma coupling (quantified as a power–envelope correlation proxy for phase–amplitude coupling), and progressive temporal instability across sleep–wake transitions. Using unsupervised clustering, we identified three chronobiological subtypes—Circadian-Preserved (36.8%), Coupling-Deficient (39.5%), and Pan-Dysrhythmic (23.7%)—each with distinct pathophysiological mechanisms and surgical outcomes. Our machine learning classification achieved clinically significant discrimination (AUC = 0.865), with circadian amplitude and coupling strength as the most informative features. These multi-band circadian biomarkers provide interpretable, physiologically grounded signatures for epilepsy diagnosis and subtype stratification, offering a temporal framework for personalized surgical planning and chronotherapy interventions. Full article