Search Results (3,959)

The aryl hydrocarbon receptor (AhR) is highly expressed in keratinocytes and functions as an environmental sensor regulating xenobiotic metabolism, epidermal differentiation, and inflammatory responses. Particulate matter (PM), a major environmental pollutant containing reactive oxygen species (ROS), transition metals, and polycyclic aromatic hydrocarbons (PAHs), induces oxidative stress and inflammation, leading to skin barrier dysfunction. Transition metals generate ROS via Fenton-type reactions, whereas PAHs undergo AhR-mediated metabolism that further amplifies oxidative stress. Excessive ROS promotes inflammatory cytokine expression and disrupts barrier-related protein expression. In response, activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway induces antioxidant enzymes, including heme oxygenase-1 (HO-1), to counteract oxidative damage. However, sustained PM exposure may overwhelm these defense mechanisms, resulting in impaired cellular homeostasis. Although the roles of AhR and Nrf2 have been extensively investigated individually, their coordinated regulation in PM-induced skin injury remains underexplored. This review summarizes current evidence on the functional interplay between AhR and Nrf2 and discusses how coordinated activation of these pathways integrates xenobiotic metabolism, antioxidant defense, and barrier-associated functions. Overall, the available evidence supports a dual-pathway framework for maintaining epidermal homeostasis under PM-induced environmental stress. Full article

Nicotinamide adenine dinucleotide (NAD⁺) is a fundamental metabolic cofactor and signaling molecule that supports redox reactions, DNA repair, chromatin regulation, stress adaptation, inflammation, and neuronal maintenance. Age-associated NAD⁺ decline has been implicated in brain aging and neurodegenerative disorders, but the causal node and limiting compartment differ across tissues and disease states. Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT-1) catalyzes the final step in NAD⁺ biosynthesis and represents the major nuclear isoform of the mammalian NMNAT family. Direct human genetic evidence establishes NMNAT-1 as a causal gene in inherited retinal degeneration, whereas evidence linking endogenous NMNAT-1 to broader brain aging or sporadic neurodegeneration is mainly convergent preclinical, preliminary, or indirect. Beyond NAD⁺ synthesis, biochemical and Drosophila studies suggest possible chaperone-like and proteostasis-supporting functions, but a separable NAD⁺-independent function of endogenous mammalian NMNAT-1 has not yet been established in vivo. Here, we review the molecular structure, localization, and regulation of NMNAT-1, emphasizing calibrated distinctions among catalytic nuclear NAD⁺ supply, engineered axonal protection, pathway-adjacent NAD⁺ interventions, and putative non-catalytic protection. We further discuss how NMNAT-1 dysfunction may contribute to aging-associated genomic instability, neuroinflammation, synaptic impairment, retinal degeneration, selected neurodegenerative models, and glioma biology. Finally, we evaluate therapeutic strategies targeting NMNAT-1 and NAD⁺ pathways, noting that no human trial has yet established efficacy for an NMNAT-1-directed neurological therapy. A compartment-aware and evidence-stratified view is therefore essential for translating NMNAT-1 biology into interventions for age-related neural disease. Full article

Phenolic aerogels, owing to their low density, high char yield, large specific surface area, and well-defined three-dimensional topological networks, hold considerable promise for applications in extreme thermal protection and multifunctional material systems. The sol–gel process, a cornerstone methodology for constructing the three-dimensional nanoporous architecture of these materials, critically governs the resulting microstructural topology and macroscopic performance through its reaction kinetics, phase-separation behavior, and drying dynamics. This review systematically surveys recent advances in the sol–gel synthesis of phenolic aerogels, focusing on the polycondensation mechanisms operative under acidic and basic catalytic conditions, nucleation-and-growth kinetics, and strategies for tailoring multiscale pore structures. It further provides a comparative analysis of interfacial regulation mechanisms for capillary-stress elimination across supercritical drying, freeze-drying, and ambient-pressure drying routes. We also dissect the structure–property relationships underpinning Knudsen-effect-mediated gaseous thermal insulation, multi-scale hybrid network toughening, and inorganic phase-transition-induced in situ ceramization for thermal protection, demonstrating the synergistic optimization of thermal insulation, structural load-bearing, and ablation resistance. Finally, we summarise current applications in extreme thermal protection, environmental adsorption, electromagnetic interference shielding, and electrochemical energy storage and highlight future directions towards green, scalable manufacturing and intelligent materials design. Full article

Δ9 fatty acyl desaturase (Δ9 FAD) exerts important regulatory effects on fatty acid metabolism and membrane fluidity. However, its existence and the effects of nutritional regulation and ambient salinity on its expression are currently unknown in mud crab (Scylla paramamosain). In this study, the full cDNA sequence of Δ9 fad was isolated from the hepatopancreas of mud crab, which consists of 1468 bp and encodes a polypeptide of 347 amino acids. Sequence analysis revealed that the protein possessed typical characteristics of Δ9 FAD including three histidine-rich domains (HRLWSH, HRVHH and HNYHH), four transmembrane regions and three conserved motifs (FFSHMGW, QRKYY and PWDY). The results of tissue distribution indicated that the mud crab’s Δ9 fad expression was enriched in the hepatopancreas, with relatively lower levels found in the thoracic ganglia and cranial ganglia. Δ9 fad expression in the hepatopancreas was significantly influenced by dietary fatty acid profiles, and the replacement of fish oil with soybean oil markedly downregulated the transcriptional levels of hepatopancreatic Δ9 fad. Furthermore, the transcriptional levels of Δ9 fad were also significantly affected by ambient salinity. Under chronic salinity stress, the 7‰, 12‰, 17‰ and 22‰ salinity groups showed higher transcriptional levels of Δ9 fad in the hepatopancreas than the 27‰ salinity group, and the 7‰ salinity group significantly differed from the 27‰ salinity group. Under the acute salinity stress condition, the Δ9 fad transcriptional levels of muscle in the 14‰ and 4‰ salinity groups were higher than those in the 24‰ salinity group at 6 h and 12 h. By contrast, Δ9 fad in the hepatopancreas exhibited a slow response in reaction to low salinity stress, and only the 4‰ salinity group at 96 h had a higher value than the 24‰ salinity group. In addition, as for the starvation stress experiment, Δ9 fad expression in the starvation group was dramatically reduced when compared with the feeding group. These findings improve our understanding of the physiological roles of Δ9 fad and its regulatory mechanisms in crustaceans. Full article

Clinical trials and naturalistic studies describe psychedelics under markedly different exposure conditions. This narrative review searched PubMed/MEDLINE, the Cochrane Library, ClinicalTrials.gov, and regulatory sources through 15 July 2026, and examined safety and outcomes across four dimensions of exposure: dose, frequency, person, and context. In screened adults receiving one to three supervised doses, transient headache, nausea, anxiety, and cardiovascular activation are common; serious reactions are uncommon but include persistent anxiety, suicidality signals, and a recent case of hallucinogen persisting perception disorder. Evidence supports MDMA (3,4-Methylenedioxymethamphetamine) -assisted therapy for post-traumatic stress disorder and psilocybin-based interventions for depression, although functional unblinding, selected samples, inconsistent comparators, and a recent negative primary trial constrain certainty. Naturalistic studies suggest that vulnerability and context modify outcomes, but frequency is inconsistently measured and rarely linked to cumulative exposure or long-term health. Short-term microdosing trials show limited benefit, whereas long-term cardiac and psychiatric safety remains unresolved. Exposure-defined cohorts, prospective registries, echocardiographic surveillance, and blinding-aware comparative trials are priorities. Full article

Chinese Baijiu solid-state fermentation operates as a heterogeneous reaction bed in which heat, moisture, O₂, acidity, ethanol, and mass-transfer conditions vary across space and time. Because aroma-related microorganisms respond differently to these local stresses, abundance data alone cannot identify which populations remain active or contribute to ester formation at a particular layer, stage, or batch. This review therefore focuses on stress-tolerant functional units that sustain acid–alcohol–ester conversion and argues for spatially resolved sampling combined with activity-, enzyme-, and metabolite-based evidence. As a conceptual verification platform, rather than a reported experimental apparatus or a replacement for traditional pits, a gradient solid-state bioreactor could reproduce selected temperature, O₂, moisture, and interface gradients under controlled conditions. Coupling multipoint temperature, CO₂/O₂, moisture, and acidification-related signals with spectral fingerprints and volatile measurements, together with offline biological assays, could help define functional windows and improve the mechanistic reproducibility of Baijiu fermentation. Full article

Aspergillus flavus, a ubiquitous phytopathogen, produces mycotoxins, especially aflatoxin B₁ (AFB₁), and infects crops worldwide. Glycerol-3-phosphate dehydrogenase (G3PDH) is a key enzyme in the glycerol synthesis and metabolic pathway catalyzing the reversible conversion reaction between glycerol-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP). However, the biological function of G3PDH in A. flavus remains uncharacterized. In this study, the glycerol-3-phosphate dehydrogenase GfdA and GfdB recombinant proteins of A. flavus were expressed, and the enzymatic activity of the GfdA protein was successfully determined. Subsequently, single-gene knockout strains (ΔgfdA, ΔgfdB), double-gene knockout strains (ΔgfdAΔgfdB) and their corresponding complemented strains (gfdA^C, gfdB^C) were constructed by a homologous recombination method to explore the biological functions of these two genes in A. flavus. The phenotypic analyses revealed that although both gfdA and gfdB encoded glycerol-3-phosphate dehydrogenases, gfdA plays major roles in colony growth, conidiation, sclerotium formation, crop infection and osmotic stress tolerance in A. flavus. Notably, the performance of the ΔgfdAΔgfdB strains is almost similar to that of the ΔgfdA strain. Biochemical assays demonstrated that the intracellular glycerol content increased significantly in all mutants compared to the wild type (WT) under both normal and osmotic stress conditions. Furthermore, we found that exogenous glycerol supplementation rescued the growth defect of the ΔgfdA and ΔgfdAΔgfdB strains. Taken together, GfdA is important for glycerol synthesis, while GfdB is functionally redundant with respect to GfdA. This study preliminarily explores the main biological functions of GfdA and GfdB, providing a theoretical basis for the study of glycerol anabolic pathways of A. flavus and also offering novel insights into the development of strategies to control aflatoxin contamination. Full article

Background: Male infertility, largely driven by declining sperm quality, is a growing global concern. Radix Bupleuri Chinensis (Chaihu, CH)—a key component of traditional formulas such as Chaihu Shengjing Tang and Chaihu Shugan San—has been clinically used to enhance sperm quality. However, the specific role and mechanism of CH as a single entity in ameliorating spermatogenic dysfunction remain unclear. This study aimed to determine whether CH extract ameliorates spermatogenic dysfunction and whether GnRH/GnRHR signaling and taurine biosynthesis are involved. Methods: Male Kunming (KM) mice and GC-1 spermatogonial cells were used to establish experimental models. Histopathological and cellular changes were examined via hematoxylin and eosin (H&E) staining and immunofluorescence. Enzyme and hormone levels were quantified, while gene and protein expression were analyzed using quantitative real-time polymerase chain reaction, Western blotting, and high-content imaging. Results: CH extract mitigated DOX-induced spermatogenic dysfunction by activating the GnRHR signaling pathway, enhancing taurine biosynthesis, and reducing oxidative stress. In vitro, saikosaponin D alleviated DOX-induced injury in GC-1 cells and was associated with changes in GnRHR-related signaling and taurine-biosynthesis-related proteins, supporting its potential role as a candidate bioactive constituent of CH. Conclusions: CH extract alleviated DOX-induced spermatogenic impairment in mice. The in vivo cetrorelix experiments support the involvement of the GnRHR signaling pathway, whereas the concurrent changes in taurine, CDO1, and FMO1 are consistent with enhanced taurine biosynthesis. These findings provide experimental support for further investigation of CH as a potential intervention for chemotherapy-related reproductive injury. Full article

Reactive aldehydes—formaldehyde (FA), malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and acrolein—occupy a central role in epigenetic regulation, lipid peroxidation, ferroptosis, and cardiovascular disease, yet their transient nature and low intracellular concentrations have long made them difficult to quantify in living systems. Over the past decade, reaction-based small-molecule fluorescent probes have emerged as the principal tool for addressing this challenge, and this review provides a systematic account of that progress. We compare the six main conjugation chemistries that underlie current probe design—2-aza-Cope/Mannich cascade, hydrazone/oxime formation, Michael addition, Schiff base condensation, and 2-aminothiophenol cyclization—alongside the three photophysical strategies used to convert these reactions into quantitative signals: intensity turn-on, ratiometric dual-emission, and fluorescence lifetime imaging (FLIM). Attention is given to advances reported between 2020 and 2025, including organelle-targeted ratiometric formaldehyde sensors (MitoRFAP-2, NucRFAP-2), the first ratiometric acrolein probe for visualizing ferroptosis, lysosome-targeted malondialdehyde reporters for atherosclerosis staging, and near-infrared-compatible platforms validated in three-dimensional organoids and in vivo models. This review also critically examines the limitations that continue to constrain the field, including insufficient selectivity testing under physiologically relevant conditions, the pH-dependence of hydrazone equilibria, the frequently overlooked distinction between probes that report free aldehyde concentration and those that report ALDH enzyme activity, and the continued absence of reversible, real-time sensors. Closing these gaps will determine whether aldehyde imaging grows from a set of smart probes into a quantitative, widely trusted platform for studying redox and carbonyl biology in living systems. Reaching that point will depend on three criteria: better NIR fluorophores, effective bioconjugation chemistry, and machine-learning tools that guide probe design. Full article

Background: Stress is regarded as one of the natural and unavoidable elements of human life and, at the same time, one of the key determinants of physical and mental health. Stress is not a new phenomenon; it has accompanied human beings since the beginning of life as a reaction to everyday challenges. This study aimed to assess the prevalence and severity of stress, as well as stress-coping strategies, in a group of patients treated for oncological reasons. Methods: The study included 108 patients hospitalized at the Independent Public Clinical Hospital No. 1 in Lublin, Poland, in the following departments: the 2nd Department of General, Gastroenterological and Gastrointestinal Oncological Surgery; the Department of Oncological Surgery; and the Department of Hemato-Oncology and Bone Marrow Transplantation. Three standardized questionnaires were used: the Perceived Stress Scale (PSS-10), the Type D Personality Scale (DS-14), and the “How Do I Cope” Inventory (JSR). Statistical analysis was performed with IBM SPSS Statistics, version 25; statistical significance was set at α < 0.05. Results: Patients treated for oncological reasons constitute a group exceptionally exposed to stress, which accompanies them at every stage of the disease, from diagnosis, through treatment, to the terminal phase. In patients whose treatment resulted in remission, stress related to the possibility of recurrence accompanies every follow-up examination and every worrying symptom. Given the range of situations that provoke stress, the overall level of stress in this group can be regarded as high. Stress-coping strategies among oncological patients are shaped by multiple factors, including selected sociodemographic characteristics; taking into account the diversity of these factors, coping strategies varied considerably across the sample. The level of coping strategies was not associated with age or sex but was significantly associated with educational attainment. Conclusions: Oncological patients experience a high and pervasive level of stress that persists throughout diagnosis, treatment, and follow-up. Stress-coping strategies are heterogeneous, are not determined by age or sex, but are shaped by education, indicating a need for individualized psychosocial and educational support integrated into routine oncological care. Full article

Thanks to the rapid development of advanced analytical methods, researchers can now identify new, so far unknown applications for existing drugs. This expanding knowledge about the mechanisms of drug action, including interactions with various molecules and molecular pathways, not only enables more effective use of available therapies but also reduces both the time and cost of developing new therapeutic options. One of the proteins reported to interact with numerous drugs and chemicals is Translationally Controlled Tumor Protein (TCTP). Numerous studies have demonstrated that TCTP plays a crucial role in diverse biological processes, including cell growth, cell cycle regulation, cellular proliferation, allergic reactions, stress response, inhibition of apoptosis, calcium ion binding, interacting with microtubules and actin microfilaments, the progression of various cancers, and tumor reversion. Therefore, this review article aims to compile a list of drugs and substances shown to interact with TCTP and that, given TCTP’s numerous cellular functions, could be repurposed for other therapies. Full article

Background/Objectives: The relationship between diet and mental wellbeing is bidirectional: nutritional psychiatry examines effects of diet on mental health, whereas emotional-eating research focuses on the reverse. Although dose–response links between nutrient intake and health outcomes are well studied, few have analyzed such relationships between food-group intake and stress. Using cross-sectional data from a regional observational study of Japanese adolescents and young adults (males: n = 48, age = 32.3 ± 5.23; females: n = 124, age = 29.8 ± 5.77), we estimated dose–response associations between intake frequency of various food groups and stress responses. Methods: Mental and physical health was assessed using the response values for the mental and physical stress-reaction items in the Brief Job Stress Questionnaire. Intake frequency for each food group was obtained from a food frequency questionnaire (FFQ). Although the FFQ provides ordinal frequency categories, we demonstrate that structural equation modeling allows these data to be treated as integer values representing monthly intake frequency, enabling the estimation of associations with stress responses. Results: The analysis showed that, in females, the presence or absence of intake—rather than the frequency of intake—of dark-green and yellow vegetables was associated with the magnitude of stress responses. In contrast, for bread, noodles, and starchy foods, a monotonic positive association was observed between intake frequency and fatigue. Conclusions: Although these associations do not disentangle the bidirectional causal relationship between diet and mental–physical health, they provide evidence on the linear and nonlinear associations between food-group–specific intake frequencies and stress responses in the AYA population. Full article

The management of estuarine ecosystem sustainability is a complex problem that requires models that are physically sound, socially meaningful, and interpretable from a mechanistic standpoint. Even though classical AI has demonstrated promise in environmental forecasting, black-box models typically fall short of meeting basic conservation requirements or accounting for anthropogenic stresses that alter water quality. This work introduces a novel framework based on Deep Physics-Informed Neural Networks (Deep PINNs) to predict the dynamics of dissolved oxygen (DO) in the Bouregreg Estuary (Morocco). We advance baseline standards by directly integrating the non-linear advection–diffusion–reaction (ADR) transport equations into the loss function of a deep residual architecture (ResNet with 12–20 layers). This integration ensures that the model takes into account two important aspects of estuarine hydrodynamics: gravitational circulation and the salt wedge effect. The incorporation of a socio–hydro–physical nexus, which uses regional water-pricing indices and urban wastewater discharge volumes from the Rabat-Salé municipal area $(\sim \mathrm{120,000} {\mathrm{m}}^3/\mathrm{d}\mathrm{a}\mathrm{y})$ as proxy variables for anthropogenic pressure, is a unique aspect of this work. The Deep PINN achieves a better coefficient of determination ($R^2=0.998$) and a Nash–Sutcliffe efficiency ($\mathrm{N}\mathrm{S}\mathrm{E}=0.997$), outperforming the traditional ANFIS and ANN baselines by $89.1\%$ in terms of predictive error reduction ($\mathrm{R}\mathrm{M}\mathrm{S}\mathrm{E}=0.041\pm 0.002 \mathrm{m}\mathrm{g}/\mathrm{L}$). In situations where unconstrained data-driven models fall short, the framework exhibits physical robustness in capturing vertical DO stratification in addition to numerical accuracy. Urban effluent volumes have a significant impact on predictive variance, accounting for 28% of the model internal attribution—more than the relative influence of thermal solubility, according to mechanistic feature attribution analysis using SHAP (Shapley Additive exPlanations). Finally, exploratory management scenarios suggest that summer hypoxia could hypothetically be mitigated through a $20\%$ reduction in discharge volumes. This study bridges the gap between scientific modeling and policy implementation by providing a physics-consistent digital twin framework for environmental stewardship in support of UN SDG 6 and Morocco’s National Water Plan. Full article

Elite athletes experience diverse biological, psychological, and social challenges during injury rehabilitation, yet few qualitative studies have explored these experiences and their interactions from a biopsychosocial perspective. This exploratory qualitative study investigated the biopsychosocial experiences of elite athletes during injury rehabilitation and the interactions among these experiences through semi-structured interviews with five participants, using inductive content analysis. Athletes reported biological experiences including musculoskeletal symptoms, limitations in daily activities, adverse drug reactions, psychosomatic symptoms, and physical development; psychological experiences including negative emotions (anger, anxiety, and depression) and positive experiences (restoration and psychological resilience); and social experiences including informational, instrumental, and emotional support, as well as negative social influences such as blame and pressure to return to play. Participants perceived that these biological, psychological, and social experiences were closely interconnected throughout rehabilitation. Biological experiences, such as pain and physical impairment, were perceived to contribute to negative emotions, including anxiety, whereas negative emotions were associated with stress-related psychosomatic symptoms, such as gastrointestinal symptoms and headaches. Emotional support was associated with positive emotional experiences, whereas negative social influences, including blame and pressure to return to play, were associated with negative emotional responses. These findings contribute to an understanding of the multidimensional experiences of injured elite athletes and may inform development of integrated rehabilitation approaches that address biological, psychological, and social aspects of recovery. Full article

Glycogenolysis is an important contributor to ATP production in contracting skeletal muscle. However, the activation of glycogen phosphorylase in resting muscle does not by itself trigger significant glycogenolysis. To elucidate the mechanisms underlying this regulation, we analyzed the functional coupling between glycogenolysis and glycolysis using a mathematical model of energy metabolism in mammalian fast-twitch (white) skeletal muscle. A system-level analysis of the model reveals an important role for inorganic phosphate (a substrate for glycogen phosphorylase) in regulating glycogenolysis rates in both resting and contracting muscle. In contracting muscle, at sufficiently high concentrations of inorganic phosphate, the activation of glycogen phosphorylase markedly increases the rate of glycogenolysis, thereby enhancing ATP production and stabilizing the cellular energy charge. In contrast, glycogen phosphorylase activation in resting muscle is unable to support glycogen breakdown due to a significant decrease in inorganic phosphate levels. Moreover, the analysis shows that forced acceleration of the glycogen phosphorylase reaction under resting conditions does not increase ATP production; instead, it promotes the accumulation of phosphorylated glycolytic intermediates, which may induce osmotic stress and cause damage to muscle cells. Full article