Search Results (845)

The increasing interest in the presence of contaminants of emerging concern (CEC) in aquatic environments has driven research into biological mechanisms capable of eliminating pharmaceutical compounds like paracetamol, considering different plant species as model systems. Thus, the use of hairy roots (HRs) has become an interesting tool. This study explores the ability of tobacco HRs to remove paracetamol, with an emphasis on elucidating the main metabolism steps and key enzymes involved in the green liver detoxification process, as well as the antioxidant response. The deepening of these aspects has been carried out through gene expression and biochemical analysis under circadian regulation. Our results reveal that HRs efficiently removed paracetamol (100 mg L⁻¹) from the culture medium, achieving around 99% removal at ZT16 h (Zeitgeber Time 16). The early activation of antioxidant defense mechanisms, demonstrated by enhanced peroxidase (POD) activity and total antioxidant capacity (TAA) during the light phase, has been observed. Furthermore, glutathione S-transferase (GSTs) activity and glutathione (GSH) levels, potentially linked to paracetamol conjugation, were also assessed. Gene expression analyses confirmed GST gene upregulation in response to paracetamol treatment, with GSTF6-like and GSTF8-like maintaining circadian rhythms as in the control, and GSTZ1-like only displayed rhythmic expression upon treatment. Additionally, the modulation of core circadian clock genes (NtLHY1 and NtTOC1) suggests that the plant response to paracetamol is tightly regulated by the circadian system. Together, these findings shed light on the complex molecular and biochemical mechanisms underlying paracetamol detoxification in tobacco HRs and underscore the significant role of circadian regulation in orchestrating these responses. Full article

The circadian rhythm controls the sleep/wake cycle and a wide variety of metabolic and physiological functions. Clock genes regulate it in response to both external and endogenous stimuli, and their expression may change because of aging, leading to an increased risk of health problems. Despite the well-described benefits of physical exercise as a circadian synchronizer, there is a lack of literature regarding the role of chronic exercise intensity in clock gene expression during aging. This article aims to analyze the differential expression of genes that regulate the biological clock under the effects of variable-intensity aerobic swimming training in aging mice, determining whether these exercise regimens interfere with the genomic regulation of the circadian rhythm. For this purpose, the mice were exposed to low- and high-intensity exercise and had their heart and gastrocnemius tissues molecularly analyzed by cDNA synthesis and qPCR to determine the expression levels of the selected genes: Clock, Arntl, Per1, Per2, Cry1, Cry2, and Nr1d1. The results showed that low-intensity exercise, performed at workloads below the anaerobic threshold, significantly changed their expression in the gastrocnemius muscle (p < 0.05), while high-intensity exercise had no statistically significant effects (p > 0.05), with the heart being immune to exercise influence except when it comes to the Per1 gene, for which expression was increased (p = 0.031) by low-intensity exercise. Additionally, both body weight and lactate thresholds had no change during the experiment (p > 0.05), while the maximum supported workload was maintained for high-intensity exercise (p > 0.05) and increased for low-intensity exercise (p < 0.01), with the control group experiencing a decay instead (p < 0.05). Thus, the present study highlights the importance of chronic exercise in modulating clock genes and opens exciting possibilities for circadian medicine, such as improvements in exercise capacity, heart condition, and lipid metabolism for subjects of low-intensity regimens. Full article

Neutrophils are the most abundant immune cells in humans and the first responders to be recruited at the site of injury. They exhibit high microbicidal activity and a combination of cytotoxic mechanisms that may lead to bystander tissue damage. However, this classical and simplistic view of the neutrophil biology has recently dramatically changed. Emerging evidence indicates an active role for neutrophils in resolution of inflammation and tissue repair. This review specifically explores the mechanisms through which neutrophils perform their anti-inflammatory and tissue-repairing roles, which are also modulated by circadian rhythms—an aspect that influences immune activity and may have implications for treatment timing. A particular focus is placed on the role of platelet-derived products in modulating local neutrophil immune responses. The remarkable phenotypic plasticity of neutrophils and their crucial role in resolving inflammation and restoring homeostasis underscore their promise as a therapeutic approach. However, their activity must be finely regulated to prevent potential tissue damage. Full article

Fractured rock masses in cold regions are subject to long-term seasonal freeze–thaw cycles. To investigate the fatigue damage characteristics of sandstone with different fracture inclinations under freeze–thaw cycling conditions, samples containing fractures of varying inclinations were prepared using sandstone from Altay, Xinjiang. After vacuum saturation and freeze–thaw cycling treatment (−30 °C to 30 °C), uniaxial cyclic loading tests were conducted to analyze strain, elastic modulus, Poisson’s ratio, and damage variables. The results showed that under cyclic loading, the strain of the sandstone exhibited a “stepwise accumulation” characteristic, with peak and residual strain increasing with the progression of the cycle. Among them, the specimen with a fracture angle of 45° exhibited the fastest strain increase before failure. The peak elastic modulus showed a “continuous decrease within each stage and an initial increase followed by a decrease between stages,” while the residual elastic modulus continued to decrease, with both experiencing a sudden, sharp drop at the end of the cycle. The peak Poisson’s ratio decreases with the number of cycles in the early stage, then transitions to logarithmic growth in the later stage, rapidly increases near failure, and finally, the residual Poisson’s ratio in the final cycle exceeds the peak Poisson’s ratio; the evolution of damage variables exhibits an S-shaped three-stage characteristic, with the initial stage showing an irreversible deformation growth rate exceeding 10% due to compaction. In the middle stage, it grows steadily due to microcrack propagation, and in the final stage, it approaches 1. Samples with steep inclination angles exhibit earlier damage initiation and faster growth rates. The study reveals that crack inclination angle influences the evolution rhythm by regulating the proportion of compaction and shear damage, providing a theoretical basis for assessing the engineering stability of fractured rocks in cold regions. Full article

Background: The circadian rhythm regulates important functions in the body, such as metabolism, the cell cycle, DNA repair, and immune balance. Disruption of this rhythm can contribute to the development of cancer. Circadian rhythm genes (CRGs) are attracting attention for their connection to various cancers. However, their roles in LUAD are not yet well understood. Additionally, our knowledge of how they function at both the bulk tissue and single-cell levels is limited. This gap hinders a complete understanding of how CRGs impact the development and outcomes of LUAD. Methods: We selected 554 CRGs from public databases. We then obtained transcriptome data from TCGA and GEO. A total of 101 machine learning algorithm combinations were tested using 10 algorithms and 10-fold cross-validation. The best-performing model was based on Stepwise Cox regression and SuperPC. This model was validated with additional datasets. We also examined the relationships between CRGs, immune features, tumor mutation burden (TMB), and the response to immunotherapy. Drug sensitivity was also assessed. Single-cell data identified the cell types with active CRGs. Next, we performed qRT-PCR and other basic experiments to validate the expression of ARNTL2 in LUAD tissues and cell lines. The results indicated that ARNTL2 may play a key role in lung adenocarcinoma. Results: The CRG-based model clearly distinguished LUAD patients based on their risk. High-risk patients exhibited low immune activity, high TMB, and poor predicted responses to immunotherapy. Single-cell data revealed strong CRG signals in epithelial and fibroblast cells. These cell groups also displayed different communication patterns. Laboratory experiments showed that ARNTL2 was highly expressed in LUAD. It promoted cell growth, movement, and invasion. This suggests that ARNTL2 may play a role in promoting cancer. Conclusions: This study developed a machine learning model based on CRGs. It can predict survival and immune status in LUAD patients. The research also identified ARNTL2 as a key gene that may contribute to cancer progression. These findings highlight the significance of the circadian rhythm in LUAD and provide new perspectives for diagnosis and treatment. Full article

As a perceptual representation of ecosystem structure and function, the soundscape has become an important indicator for evaluating ecological health and assessing the impacts of human disturbances. Understanding the spatiotemporal heterogeneity of soundscapes is essential for revealing ecological processes and human impacts in protected areas. This study investigates such heterogeneity in Zhangjiajie National Forest Park using deep learning approaches. To this end, we constructed a dataset comprising eight representative sound source categories by integrating field recordings with online audio (BBC Sound Effects Archive and Freesound), and trained a classification model to accurately identify biophony, geophony, and anthrophony, which enabled the subsequent analysis of spatiotemporal distribution patterns. Our results indicate that temporal variations in the soundscape are closely associated with circadian rhythms and tourist activities, while spatial patterns are strongly shaped by topography, vegetation, and human interference. Biophony is primarily concentrated in areas with minimal ecological disturbance, geophony is regulated by landforms and microclimatic conditions, and anthrophony tends to mask natural sound sources. Overall, the study highlights how deep learning-based soundscape classification can reveal the mechanisms by which natural and anthropogenic factors structure acoustic environments, offering methodological references and practical insights for ecological management and soundscape conservation. Full article

Background/Objectives: Patients with epilepsy commonly experience patterns of seizures that change with sleep/wake behavior or diurnal rhythms. The cellular and molecular mechanisms that underlie these patterns in seizure activity are not well understood but may involve non-neuronal cells, such as astrocytes. Our previous studies show the critical importance of one specific astrocyte factor, the brain-type fatty acid binding protein Fabp7, in the regulation of time-of-day-dependent electroshock seizure threshold and neural activity-dependent gene expression in mice. Here, we examined whether Fabp7 influences differential seizure activity-dependent protein expression, by comparing Fabp7 knockout (KO) to wild-type (WT) mice under control conditions and after reaching the maximal electroshock seizure threshold (MEST). Methods: We analyzed the proteome in cortical–hippocampal extracts from MEST and SHAM groups of WT and KO mice using mass spectrometry (MS), followed by Gene Ontology (GO) and pathway analyses. GO and pathway analyses of all groups revealed a diverse set of up- and downregulated differentially expressed proteins (DEPs). Results: We identified 65 significant DEPs in the comparison of KO SHAM versus WT SHAM; 33 proteins were upregulated and 32 were downregulated. We found downregulation in mitochondrial-associated proteins in WT MEST compared to WT SHAM controls, including Slc1a4, Slc25a27, Cox7a2, Cox8a, Micos10, and Atp5mk. Several upregulated DEPs in the KO SHAM versus WT SHAM comparison were associated with the 20S proteasomal subunit, suggesting proteasomal activity is elevated in the absence of Fabp7 expression. We also observed 92 DEPs significantly altered in the KO MEST versus WT MEST, with 49 proteins upregulated and 43 downregulated. Conclusions: Together, these data suggest that the astrocyte Fabp7 regulation of time-of-day-mediated neural excitability is modulated by multiple cellular mechanisms, which include proteasomal pathways, independent of its role in activity-dependent gene expression. Full article

In mammals, the suprachiasmatic nucleus (SCN), located in the hypothalamus serves as the master biological clock and precisely regulates circadian rhythms through a complex network structure. As a central pacemaker, the SCN has two primary functions: one is to synchronize the daily rhythms in physiological and behavioral activities; the other is to entrain the endogenous rhythms to the external light–dark cycle. A deep understanding of the SCN network structure is crucial for elucidating the functional mechanisms of the biological clock system. In this review, we systematically summarized the impact of the SCN network structure on functional regulation under light stimulation based on mathematical models. Studies have shown that the coupling between the light-sensitive subgroups in the left and right nuclei of the SCN can enhance the entrainment ability. As an integrated network structure, the SCN may have the characteristics of the small-world network or the scale-free network, as these properties are more conducive to the realization of functions. Additionally, the higher-order coupling mechanism within the SCN can effectively expand the entrainment range. These theoretical research results offer new insights into the relationship between the SCN network and functions and provide crucial theoretical guidance and validation directions for subsequent experimental research. Full article

Plants grow, develop, and reproduce within a rhythmic environment. Environmental cues—such as light, temperature, nutrition, water—initiate, sustain, or terminate basic physiological processes within the plant, such as photosynthesis, respiration, nutrient uptake, water management, transpiration, growth, and hormone regulation. Simultaneously, inside the plant, internal “living clocks” are ticking and helping plants to synchronize internal processes with environmental cues and defend themselves against stressful conditions. These clock-regulated processes underlie a variety of plant traits, such as germination capability, growth and development rate, time of flowering, fruiting and yielding, development of plant shape, and size and biomass production. Most of these physiological traits are important attributes of crop plants. In recent years, the growing understanding of environmental rhythms as environmental cues and the mechanisms underlying plant internal clocks has begun to play an increasingly important role in agricultural practices. This is an emerging area of research that integrates insights from chronobiology with practices in plant agriculture. In this review, this new research area is studied and mapped using Scopus, Web of Science, Google Scholar, Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA protocol), and VOSviewer1.6.20 software. The analyses were carried out on 18 July–27 August 2025. For the VOSviewer author keywords co-occurrence analysis, all 1022 documents covering the time range of the last 7.5–2.5 years (2018–July 2025) were included and three maps were generated. Additionally, 59 review documents covering the last 27 years (1988–July 2025) were extracted by relevance using Google Scholar. In this review, recent advances and topics in plant chronobiology were examined. The issue of how these advances respond to key challenges in plant agriculture was explored. The bidirectional influence between chronobiology and practices in plant agriculture were also considered. Full article

Background: Ozone (O₃) pollution disrupts pulmonary circadian rhythms, yet the molecular mechanisms remain elusive. The Notch signaling pathway, critical for lung homeostasis, may crosstalk with the circadian clock system. Objective: This study elucidates the role of the Notch signaling pathway in O₃-induced lung circadian rhythm disruption. Methods: C57BL/6J mice were acutely exposed to O₃ (1.0 ppm, 3 h). Lung tissues were collected 24 h post exposure. Transcriptome sequencing coupled with GSEA identified dysregulated pathways; IHC and RT-qPCR validated core genes; GEO dataset (GSE58244) reanalysis assessed Notch3/4 knockout effects. Results: O₃ activated Notch signaling (NES = 1.85, FDR = 0.034) and disrupted the circadian pathway (NES = 1.84, FDR = 0.029), downregulating Bmal1 while upregulating Per2/3 and Notch3/4 (p < 0.05). Strong correlations (r > 0.8) existed between core genes of both pathways. Notch3/4 knockout exacerbated circadian disruption in a time-dependent manner upon O₃ exposure. Conclusion: O₃ induces lung circadian disruption via Notch3/4 activation, which provides novel mechanistic insights into pollutant-induced lung injury. Full article

Leptin, an adipocyte-derived hormone, plays a central role in the regulation of energy homeostasis by acting on distinct hypothalamic nuclei. This review explores recent advances in our understanding of leptin’s region-specific actions within the arcuate nucleus, ventromedial hypothalamus, dorsomedial hypothalamus, and lateral hypothalamus, highlighting their contributions to appetite regulation, energy expenditure, and neuroendocrine function. In the hypothalamic arcuate nucleus, leptin’s differential regulation of pro-opiomelanocortin and agouti-related peptide/neuropeptide Y neurons is now complemented by the identification of novel leptin-responsive neuronal populations—such as those expressing prepronociceptin, basonuclin 2, and Pirt—as well as a growing array of cellular and molecular modulators, including secreted factors like angiopoietin-like growth factor, zinc-α2-glycoprotein, and spexin, intracellular regulators such as Rap1, growth factor receptor-bound protein 10, and spliced X-box binding protein 1. In the ventromedial hypothalamus, leptin integrates with both peripheral (e.g., cholecystokinin) and central (e.g., pituitary adenylate cyclase-activating polypeptide) signals, while epigenetic mechanisms, such as those mediated by Jumonji domain-containing protein D3, regulate leptin receptor expression and sensitivity. The dorsomedial hypothalamus is increasingly recognized for coordinating leptin’s effects on metabolism, circadian rhythms, and respiration through distinct neuronal populations, including a subset of neurons co-expressing GLP-1 receptors that mediate leptin’s metabolic effects. In the lateral hypothalamus, leptin modulates reward-driven feeding via GABAergic neuronal populations—circuits that are particularly susceptible to disruption following early life trauma. Together, these insights reveal a sophisticated neurobiological framework through which leptin orchestrates systemic physiology. Understanding the heterogeneity of leptin signaling opens new avenues for restoring leptin sensitivity and developing personalized therapeutic strategies to combat obesity and related metabolic disorders. Full article

The circadian rhythm of the central brain clock in the suprachiasmatic nucleus (SCN) is synchronized by light. White adipose tissue (WAT) is one of the metabolic endocrine organs containing a molecular clock, and it is synchronized by the SCN. Excess WAT is a risk factor for health issues including type 2 diabetes mellitus (DM2). We hypothesized that bright-light exposure would affect the human WAT transcriptome. Therefore, we analyzed WAT biopsies from two previously performed randomized cross-over trials (trial 1: n = 8 lean, healthy men, and trial 2: n = 8 men with obesity and DM2). From 7:30 h onwards, all the participants were exposed to either bright or dim light. Five hours later, we performed a subcutaneous abdominal WAT biopsy. RNA-sequencing results showed major group differences between men with obesity and DM2 and lean, healthy men as well as a differential effect of bright-light exposure. For example, gene sets encoding proteins involved in oxidative phosphorylation or respiratory chain complexes were down-regulated under bright-light conditions in lean, healthy men but up-regulated in men with obesity and DM2. In addition to evident group differences between men with obesity and DM2 and healthy lean subjects, autonomic or neuroendocrine signals resulting from bright-light exposure also differentially affect the WAT transcriptome. Full article

Research on the effects of polyunsaturated fatty acids on children’s sleep has made significant advancements. This study explores the unique pathways through which polyunsaturated fatty acids, particularly docosahexaenoic acid and eicosapentaenoic acid from the n-3 series, influence sleep regulation in children. Neurobiologically, docosahexaenoic acid and eicosapentaenoic acid have been shown to bi-directionally modulate neurotransmitters and circadian rhythms via the gut–brain axis, reshaping gut microbiota and affecting brain signaling. In terms of inflammation and immune regulation, this study is the first to confirm that Maresin1, produced from n-3 fatty acids, can inhibit the activation of specific inflammasomes, thereby mitigating the disruptive effects of pro-inflammatory cytokines on sleep. The analysis of clinical applications indicates that newly developed medium- and long-chain triglyceride formulations rich in docosahexaenoic acid exhibit excellent digestive absorption in infants’ gastrointestinal systems, paving the way for new products designed to enhance infant sleep. However, current research has limitations concerning the precise dosing of docosahexaenoic acid, the representativeness of samples, and the overall rigor of study designs. Mechanistically, polyunsaturated fatty acids may exert their effects through various pathways, including neurobiology, inflammation, immune regulation, and endocrine modulation. In clinical studies, different formulations of fish oil show varying safety profiles and bioavailability. Future research should prioritize high-quality studies to clarify how different doses of polyunsaturated fatty acids affect children’s sleep, assess long-term safety, and investigate interactions with other factors, ultimately providing solid theoretical and practical guidance for improving children’s sleep. Full article

Background: Wilson’s disease (WD) is a rare autosomal recessive disorder characterized by abnormal copper metabolism and accumulation in the liver and brain. While hepatic and neurological manifestations are well-recognized, psychiatric symptoms remain underdiagnosed and frequently precede other clinical signs, leading to delayed diagnosis and poorer outcomes. Objective: This opinion paper aims to explore the emerging understanding of psychiatric features in WD, particularly mood disturbances and their overlap with bipolar spectrum disorders, through a translational lens. Opinion: Psychiatric manifestations—including irritability, aggression, disinhibition, and mood instability—are observed in up to 100% of symptomatic WD patients. Accumulated copper induces oxidative stress and astrocyte dysfunction, which may disrupt neural circuits involved in emotion regulation. There is increasing evidence of shared pathophysiological mechanisms between WD and bipolar disorder, including redox imbalance and circadian rhythm dysregulation. Future Directions: The timely recognition of psychiatric symptoms is essential. Future research should investigate biomarkers of early psychiatric involvement, evaluate psychotropic medication safety in WD, and implement psychoeducational strategies to improve adherence and quality of life. A translational approach can foster individualized interventions and provide insights into broader mood disorders. Full article

The kynurenine (KYN) metabolic pathway sits at the crossroads of immunity, metabolism, and neurobiology, yet its clinical translation remains fragmented. Emerging spatial omics, wearable chronobiology, and synthetic microbiota studies reveal that tryptophan (Trp) metabolism is regulated by distinct cellular “checkpoints” along the gut–brain axis, finely modulated by sex differences, circadian rhythms, and microbiome composition. However, current interventions tackle single levers in isolation, leaving a key gap in the precision control of Trp’s fate. To address this, we drew upon an extensive body of the primary literature and databases, mapping enzyme expression across tissues at single-cell resolution and linking these profiles to clinical trials investigating dual indoleamine 2,3-dioxygenase 1 (IDO1)/tryptophan 2,3-dioxygenase (TDO) inhibitors, engineered probiotics, and chrono-modulated dosing strategies. We then developed decision-tree algorithms that rank therapeutic combinations against biomarker feedback loops derived from real-time saliva, plasma, and stool metabolomics. This synthesis pinpoints microglial and endothelial KYN hotspots, quantifies sex-specific chronotherapeutic windows, and identifies engineered Bifidobacterium consortia and dual inhibitors as synergistic nodes capable of reducing immunosuppressive KYN while preserving neuroprotective kynurenic acid. Here, we highlight a framework that couples lifestyle levers, bio-engineered microbes, and adaptive pharmaco-regimens into closed-loop “smart protocols.” By charting these intersections, this study offers a roadmap for biomarker-guided, multidisciplinary interventions that could recalibrate KYN metabolic activity across cancer, mood, neurodegeneration, and metabolic disorders, appealing to clinicians, bioengineers, and systems biologists alike. Full article