Search Results (111,639)

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive stage of metabolic dysfunction-associated steatotic liver disease characterized by lipid dysregulation, oxidative stress, inflammation, and fibrosis. Because these processes occur simultaneously, compounds targeting multiple pathways may offer therapeutic benefit. Naringin, a citrus-derived flavonoid, has reported antioxidant and anti-inflammatory properties, but its integrated effects in MASH remain unclear. In this study, the effects of naringin were evaluated using combined in silico analysis and in vivo experiments. Network pharmacology and molecular docking predicted targets related to lipid metabolism, oxidative stress, inflammation, and fibrosis, which were validated in a methionine- and choline-deficient diet-induced mouse model. Naringin reduced hepatic lipid accumulation and improved serum AST and ALT levels. It modulated oxidative stress-related genes, attenuated inflammatory responses, and reduced fibrogenic markers. Naringin also decreased Ly6Chigh inflammatory monocytes and Kupffer cell activation, and reduced hypothalamic microglial activation. These findings suggest that naringin exerts multi-target effects across hepatic, systemic, and central pathways, supporting its potential as a therapeutic candidate for MASH. Full article

Age-related decline in oocyte quality is closely associated with mitochondrial dysfunction and oxidative imbalance, which disrupt redox-sensitive meiotic signaling and compromise embryo developmental competence. Rescue in vitro maturation (r-IVM) enables the utilization of immature oocytes retrieved during conventional in vitro fertilization (IVF) cycles. However, the developmental potential of r-IVM oocytes remains limited, particularly in women of advanced maternal age. This study evaluated whether transient caffeine supplementation during r-IVM improves the developmental competence of immature human oocytes in clinical assisted reproduction technology cycles. Immature oocytes obtained during conventional IVF were cultured with or without short-term caffeine exposure during r-IVM prior to standard culture conditions. After maturation, metaphase II oocytes underwent intracytoplasmic sperm injection, and embryonic development was assessed by fertilization rate, day 3 good-quality embryo formation, and blastocyst development. Although caffeine supplementation did not significantly affect nuclear maturation rates, it significantly increased fertilization efficiency and the proportion of good-quality embryos compared with controls. These effects were most pronounced in women aged ≥ 37 years. Time-lapse morphokinetic analysis further revealed more synchronized developmental kinetics in embryos derived from caffeine-treated oocytes, resembling those derived from in vivo-matured oocytes. Collectively, these findings suggest that transient caffeine exposure during r-IVM enhances post-fertilization developmental competence. The underlying mechanisms remain to be elucidated, and future studies are required to determine whether redox-sensitive meiotic pathways and mitochondrial function are involved. Full article

Copper (Cu) contamination poses severe threats to agricultural productivity and food safety, particularly affecting economically important crops such as rapeseed (Brassica napus L.). This study investigated the protective effects of selenium nanoparticles (SeNPs) against Cu toxicity in four B. napus cultivars. Exposure to Cu (200 μM) caused severe reductions in growth and photosynthetic efficiency while significantly elevating oxidative stress markers across all cultivars. Application of SeNPs (25 μM) effectively mitigated these adverse effects, improving biomass, restoring chlorophyll content, and enhancing photosynthetic performance compared to Cu-stressed plants. SeNP treatment significantly enhanced antioxidant enzyme activities, with corresponding upregulation of antioxidant gene expression. Secondary metabolite profiling revealed cultivar-specific responses, with sensitive cultivar Zheda 622 exhibiting metabolic adaptation and higher volatile organic compound (VOC) accumulation, while tolerant cultivar Zheda 635 maintained metabolic stability. PCA analysis demonstrated distinct metabolic clustering patterns, reflecting differential stress-responsive strategies. The study demonstrates that SeNPs attenuate Cu-induced toxicity through integrated mechanisms encompassing diminished Cu acquisition, augmented antioxidant defense systems, and comprehensive metabolic reprogramming. Cultivar-specific responses highlighted substantial genetic variation in tolerance mechanisms across B. napus genotypes. These findings substantiate SeNPs as a viable and efficacious nanomaterial for sustainable agronomic management in Cu-contaminated edaphic environments. The approach offers dual benefits of improved crop productivity and reduced Cu accumulation, ensuring enhanced food safety. Full article

Semi-circular bending tests were conducted on high-elasticity asphalt concrete under different aging conditions to investigate the effects of rubber particles and polyester fiber contents on its fracture properties. Results showed that the incorporation of approximately 3% rubber particles increased the fracture energy by 15%, whereas the addition of 1.2% polyester fibers increased the fracture toughness and fracture energy by 4% and 19%, respectively. Aging-induced oxidative hardening enhanced the overall elastic modulus and interfacial constraint effect of the asphalt mixture, thereby improving the stress transfer efficiency among the rubber particles, polyester fibers, and the surrounding matrix. As a result, both the peak load and fracture toughness increased. However, compared with the unaged state, aged asphalt concrete became more susceptible to brittle fracture, with a decrease in fracture energy and a change in the crack propagation path from a curved to a straight trajectory. Full article

Leukocyte telomere length (LTL) is shortened in adults with type 1 diabetes (T1D), but less data is available concerning pediatric cases. Multiple factors affect LTL, namely genes, epigenetics, environmental factors, oxidation, and psychological stress. Children with T1D and their families experience chronic stress. This study aimed to investigate LTL in children with T1D (n = 35) aged 6–13 years old, in comparison to age-matched healthy counterparts (n = 35), and assess any correlation of LTL with perceived stress. Relative LTL (rLTL) was assessed through real-time qPCR. Morning serum cortisol, high-sensitivity C-Reactive Protein (hsCRP), and glycated hemoglobin (HbA1c) were measured. Children completed the validated questionnaires “Stress in Children” and “Pediatric Quality of Life”. Parents answered the “Perceived Stress Scale”. Children with T1D had a lower rLTL (p = 0.02) compared to age-matched healthy controls, higher hsCRP (p = 0.031), and a lower estimated quality of life (p = 0.01). RLTL was found to be lower in females with T1D (p < 0.001) and was positively related to the ‘gender–social support’ factor (p = 0.002) and diabetes duration (p = 0.045), adjusted for children’s age, parental age, and sociodemographic characteristics. These pilot findings indicate early emergence of shorter rLTL in T1D, pointing to a sexual dimorphism pattern. Insights into preventing LTL shortening in pediatric T1D can be gained from large-scale studies examining the impact of gender and social support. Full article

Cisplatin is a potent chemotherapeutic agent whose clinical application is frequently limited by severe nephrotoxicity. N-acetylserotonin (NAS), a precursor of melatonin and a selective agonist of the TrkB receptor, has demonstrated significant antioxidant and neuroprotective properties. This study aimed to evaluate the potential renoprotective effects of NAS against cisplatin-induced acute kidney injury (AKI) in a rat model. Thirty-five Wistar Albino rats were divided into five groups: Control, Sham, NAS (5 mg/kg), Cisplatin (CP; 7.5 mg/kg), and CP + NAS. NAS was administered daily for seven days, while cisplatin was given as a single dose on the fourth day. Renal function was assessed via serum urea and creatinine. Oxidative stress markers, including Malondialdehyde (MDA), Superoxide Dismutase (SOD), Total Antioxidant Status (TAS), and Total Oxidant Status (TOS), were measured in kidney tissue. Comprehensive histopathological evaluations were performed to assess tubular and glomerular damage. Cisplatin administration significantly increased serum creatinine levels and induced severe histopathological damage (p < 0.05). While cisplatin reduced SOD and TAS levels, NAS treatment showed a trend toward biochemical recovery without reaching statistical significance in oxidative markers. Notably, NAS administration significantly ameliorated cisplatin-induced histopathological lesions, specifically reducing tubular epithelial loss, glomerular degeneration, interstitial inflammation, and vacuolization (p < 0.05). Our findings indicate that NAS exerts a profound structural protective effect against cisplatin-induced renal injury. The preservation of renal parenchyma, despite modest systemic biochemical shifts, suggests that NAS-mediated protection may involve localized TrkB-dependent pro-survival signaling and stabilization of mitochondrial integrity. NAS represents a promising therapeutic candidate for mitigating chemotherapy-induced nephrotoxicity. Full article

Alzheimer’s disease (AD) research has primarily focused on amyloid beta (Aβ) and tau protein; however, drug development targeting these two proteins has been disappointing. Therefore, there is an urgent need to explore the novel pathogenic mechanisms underlying AD. Recently, we found that expression of the K670N/M671L-mutated amyloid precursor protein (APP) in 293T cells significantly reduced membrane ferroportin (FPN) levels. Furthermore, 2-month-old APP/PS1 mice exhibited a marked decrease in membrane FPN levels, while total FPN expression and Aβ levels remained unchanged. Further studies revealed that features of ferroptosis were present in the brains of 2-month-old APP/PS1 mice, and that treatment with ferroptosis inhibitors or iron chelation significantly alleviated early pathological changes and cognitive impairment in these animals. In addition, supplementation with an APP–FPN binding peptide during the early phase ameliorated AD-related pathologies, including Aβ deposition, neuroinflammation, oxidative stress, and synapse-associated protein deficits, in APP/PS1 mice. Collectively, our findings suggest that APP mutations may contribute to early brain pathological changes and subsequent memory impairment in AD by downregulating membrane trafficking of FPN and inducing ferroptosis, thereby providing new molecular targets for drug development. Full article

5-Fluorouracil (5-FU) is a cornerstone chemotherapeutic agent that is extensively utilized in the management of malignancies; however, its clinical utility is constrained by its narrow therapeutic index and dose-limiting toxicities. The study aimed to study the hepato-nephroprotective effects of epigallocatechin gallate (EGCG) and EGCG mediated selenium nanoparticles and their effect in mitigating the toxicity induced by 5-FU. EGCG-functionalized selenium nanoparticles (EGCG-SeNPs) were produced by mixing sodium selenite, with EGCG acting as both the reducing and stabilizing agent. Nanoparticles were characterized using UV-vis spectroscopy, FT-IR, dynamic light scattering, zeta potential analysis, and transmission electron microscopy. 35 adult rats were randomly assigned to control, 5-FU, 5-FU + Na₂SeO₃, 5-FU + EGCG, and 5-FU + EGCG-SeNPs groups. Hepatorenal toxicity was induced by intraperitoneal 5-FU administration during the final five days of the experiment. Serum biochemical markers, tissue oxidative stress, antioxidant enzyme, inflammatory cytokine levels, and apoptosis-related gene expression were evaluated. Immunohistochemical analysis of Nrf2 and Keap1 and histopathological examination of tissues were performed. 5-FU induced severe hepatorenal toxicity, evidenced by marked elevations in liver and kidney function biomarkers, excessive oxidative stress, inflammatory cytokine overproduction, NF-κB activation, and apoptotic signaling. Treatment with EGCG-SeNPs markedly ameliorated 5-FU-induced hepatic and renal dysfunction, restoring liver enzyme and kidney biomarker levels to near-normal levels more effectively than EGCG or sodium selenite alone. EGCG-SeNPs significantly suppressed lipid peroxidation, NGAL, and inflammatory mediators while robustly enhancing antioxidant defenses and activating the Nrf2/HO-1 pathway with concomitant Keap-1 downregulation, strongly inhibited NF-κB signaling, normalized cytokine balance, reduced poly (ADP-ribose) (PAR) activation, and attenuated apoptosis. EGCG–SeNPs confer superior protection against 5-FU–induced hepatorenal toxicity compared to EGCG or inorganic selenium alone. The potent protective effects of EGCG–SeNPs are mediated through coordinated antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, primarily via activation of the Nrf2/HO-1 axis and suppression of NF-κB signaling. Full article

N₂O (Nitrous oxide) is a potent greenhouse gas with a global warming potential nearly 300 times that of CO₂ and poses a critical environmental challenge, particularly in semiconductor and display manufacturing, where it is emitted during plasma processes. However, catalytic N₂O abatement in O₂-rich environments remains inefficient because O₂ competitively occupies active sites and hinders the turnover of surface oxygen species. To clarify how support properties govern this inhibition, Co-based catalysts supported on beta zeolite, CeO₂, and TiO₂, together with unsupported Co₃O₄, were comparatively evaluated for direct N₂O decomposition. Among them, Co/Beta exhibited the highest performance, achieving >95% N₂O conversion at 450 °C in the presence of 5% O₂ with excellent long-term stability. Co/Beta possessed a high specific surface area (649 m² g⁻¹) and a mesoporous framework that favored uniform Co dispersion and reactant accessibility, while its high Co²⁺/(Co²⁺ + Co³⁺) ratio (75.5%) and large fraction of chemisorbed oxygen species (79.9%) promoted oxygen-vacancy formation and facile oxygen exchange. These results indicate that the ability of Co/Beta to maintain high activity in the presence of oxygen stems from support-modulated cobalt surface states and enhanced oxygen turnover behavior. These findings provide a support-design principle for stable N₂O decomposition under oxygen-containing exhaust conditions. Full article

This paper presents a novel Multi-Scale Temporal Uncertainty-aware Hierarchical Adaptive Ensemble (MSTU-HAE) algorithm for intelligent ship emission monitoring and prediction in maritime environmental compliance applications. The maritime shipping industry contributes approximately 3% of global CO₂ emissions and significant amounts of nitrogen oxides and sulfur oxides, necessitating advanced predictive monitoring systems. The proposed MSTU-HAE algorithm integrates three key innovations: multi-scale temporal feature extraction using causal convolutions at short-term (5 samples), medium-term (20 samples), and long-term (60 samples) windows; gas-specific attention mechanisms that automatically weight temporal scales based on individual emission gas characteristics; and three-level hierarchical uncertainty quantification encompassing individual model uncertainty, ensemble disagreement, and regulatory compliance risk assessment. Experimental validation was conducted using emission data collected from a fishing vessel over 3 operational days (1732 original samples), augmented to 17,320 samples via controlled replication with noise injection to support model training. Rigorous temporal data splitting with 70%/15%/15% train/validation/test partitioning ensures no data leakage. Comparative analysis against six baseline methods (XGBoost, LSBoost, AdaBoost, Ridge Regression, Random Forest, and K-Nearest Neighbors) demonstrates that MSTU-HAE achieves superior average performance, with R² = 0.9670 and NSE = 0.9670 across all emission gases. This research contributes a robust, interpretable, and scalable prediction framework that advances the state of the art in maritime environmental monitoring through novel algorithmic innovations in temporal feature learning and uncertainty quantification. Full article

Neutrophils are the most abundant circulating leukocytes and are characterized by a proteome in which granule-associated proteins synthesized during granulopoiesis constitute a major fraction of total cellular protein, reflecting their preloaded effector nature in innate immune defense. A striking feature of neutrophil biology is the unusual abundance of the calcium-binding proteins S100A8 and S100A9, which together form the heterodimeric complex known as calprotectin. Early biochemical studies estimated that S100A8/A9 constitutes a substantial fraction of the soluble cytosolic proteome in neutrophils, with later studies often describing it as one of the most abundant protein complexes in these cells. Despite extensive studies on the antimicrobial and inflammatory activities of calprotectin, the biological rationale for this unusual abundance remains incompletely understood. In this review, we examine the structural, biochemical, and regulatory features of S100A8/A9 and explore the potential explanations for its high abundance in the neutrophil cytosol. We first discuss the unique organization of the neutrophil proteome and the transcriptional programs governing granulopoiesis that lead to large-scale production of neutrophil effector proteins. We then review the structural and biochemical properties of S100A8/A9, including its calcium-dependent conformational dynamics and high-affinity transition metal binding, which contribute to antimicrobial defense through nutritional immunity. Several functional hypotheses are considered to explain calprotectin abundance, including roles as an antimicrobial reservoir, a metal-sequestering molecule, a regulator of oxidative stress, and a source of damage-associated molecular patterns. Finally, we discuss the evolutionary logic of neutrophil protein preloading and the implications of calprotectin biology in inflammatory diseases and the tumor microenvironment. Resolving the abundance paradox of S100A8/A9 may reveal fundamental principles governing the organization of innate immune cell proteomes and provide new insights into the strategies used by neutrophils to achieve rapid and effective host defense. Full article

Rapid urbanization has intensified challenges regarding urban waterlogging and vehicle exhaust pollution. While permeable asphalt mixtures mitigate waterlogging and nano-TiO₂ offers photocatalytic exhaust degradation capabilities, the direct application of nano-TiO₂ is hindered by agglomeration and low photocatalytic efficiency. This study developed a composite modified nano-TiO₂ via metal ion doping and support treatment to enhance its performance in asphalt pavements. Specifically, nano-TiO₂ was doped with Fe³⁺, Ag⁺, and La³⁺ via the sol–gel method, and supported on activated carbon (AC) or Al₂O₃. The exhaust degradation performance was evaluated using a custom-built system, while dispersion properties were assessed via fluorescence microscopy and UV-Vis spectrophotometry. Furthermore, X-ray diffraction (XRD) and Fourier-transform infrared (FTIR) spectroscopy were conducted to investigate the microstructural mechanisms underlying the doping modification and support treatment. Photocatalytic permeable asphalt mixtures were prepared by partially replacing mineral powder with the composite modified nano-TiO₂ to validate exhaust degradation and pavement performance. The results indicated that metal doping substituted Ti⁴⁺ in the lattice, inducing defects and reducing crystallite size to boost photocatalytic activity. The optimal doping concentrations are determined to be 1.0% for Fe³⁺, 1.5% for Ag⁺, and 1.0% for La³⁺. Among these, Fe³⁺-doped nano-TiO₂ at 1.0% content exhibits superior exhaust degradation, achieving 46.7% efficiency for hydrocarbons (HC) and 33.5% for nitrogen oxides (NO). Regarding dispersion, while AC performs better at low support content, Al₂O₃ at 40% content provides superior dispersion properties by increasing active sites and surface hydroxyl groups. For photocatalytic permeable asphalt mixtures, replacing 40–50% of mineral filler with the composite modifier is recommended. The optimized mixture demonstrates superior exhaust degradation performance while maintaining the required high-temperature stability, low-temperature cracking resistance, water stability, and fatigue life. Specifically, compared to the control group, these indicators for the mixture with 50% of the mineral filler replaced by the composite modifier increases by 7.0%, 12.5%, 13.4%, and 22.9%, respectively. This study presents a viable technical solution for developing multifunctional asphalt mixtures with photocatalytic functionality as the core innovation and mechanical performance as the application baseline. Full article

Ischemic stroke remains a leading cause of death and disability worldwide. While thrombolysis and endovascular thrombectomy are current mainstays of treatment, their clinical efficacy is often undermined by ischemia–reperfusion injury (I/R). This injury induces secondary brain damage, primarily via disruption of the blood–brain barrier (BBB). No approved therapies directly target BBB protection. This review reinterprets the pathophysiological mechanism of BBB disruption after stroke through a dynamic spatiotemporal framework. The pathological cascade reaction is clearly divided into two core stages: the ischemic phase is mainly driven by energy failure and calcium overload; the reperfusion phase is further divided into four consecutive and progressive sub-stages, namely, oxidative stress burst, amplification of inflammatory response, matrix metalloproteinase 9 (MMP-9)-mediated barrier degradation and programmed cell death. This review critically assesses current therapies and identifies major clinical translation gaps, including a temporal mismatch between preclinical and clinical windows, unacceptable toxicity, lack of durable efficacy and biphasic effects. Matching specific interventions to the different pathophysiological stages of blood–brain barrier disruption is essential for optimizing clinical outcomes. Full article

Trypanosoma evansi (T. evansi) infection poses a significant health threat to equines. This study was aimed to assess the prevalence, risk factors, hematobiochemical alterations, and oxidative stress-mediated genotoxicity associated with equine trypanosomiasis in the Rahim Yar Khan District. This cross-sectional study was conducted on 384 equines from October 2024 to September 2025. Blood samples were collected for thin blood film microscopy and PCR assay using RoTat 1.2 primers. Hematological indices were analyzed with an automated hematology analyzer; serum biochemical parameters were quantified via standard assays. Oxidative stress markers, including malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH), were also measured. Genotoxicity was evaluated using the alkaline comet assay. Statistical analyses included the chi-square test, logistic regression, and independent t-tests. T. evansi was detected in 5.99% of samples by microscopy and 10.16% by PCR, with no significant association with species, age, or sex. Infected equines exhibited significant reductions in hemoglobin (5.4 ± 0.6 vs. 10.8 ± 0.5 g/dL; p < 0.0001), total serum protein (2.1 ± 0.3 vs. 5.8 ± 0.2 g/dL; p < 0.0001), albumin, and globulin, alongside elevated hepatic enzymes, blood urea nitrogen, and creatinine (all p < 0.01). Oxidative stress was confirmed by increased MDA (p < 0.0001) and decreased CAT activity (p < 0.001). Genotoxicity was significantly higher in infected animals (genetic damage index; 1.12 ± 0.08 vs. 0.40 ± 0.01; p < 0.01). This study provides the first integrated assessment of molecular epidemiology and oxidative stress-mediated genotoxicity in equines in this region, suggesting the pathogenic impact of the infection and targeted diagnostics for disease management strategies. Full article

This article describes a study on the synthesis and annealing processes of thin-film coatings of vanadium oxide on flat, parallel substrates made of quartz glass, sapphire, and silicon, as well as optical fibers using an organometallic precursor, triisopropoxy vanadium (V) oxide. For the first time, optical constants of nanomaterials were estimated in real time during synthesis and subsequent annealed using the lossy-mode resonance effect. The coatings produced in an inert atmosphere after deposition were amorphous, comprising a mixture of VO₂, V₂O₅, V₆O₁₃, and V₃O₅. This method allowed for accurate determination of the threshold temperature for the transformation of oxide mixtures into a monocomponent phase. Optimal conditions for synthesis and annealing were determined for the production of vanadium dioxide (VO₂) and pentoxide (V₂O₅). Morphological changes in coated surfaces were observed as a result of heat treatment. The composition and properties of these samples were studied using optical, terahertz and Raman spectroscopy, as well as temperature-dependent analysis of electrical resistance. The morphology of the coating surface was determined using a scanning electron microscope and an atomic force microscope. The reduction of VO_x to VO₂ was studied in an atmosphere of hydrogen and argon during annealing after deposition, with its effectiveness being compared. It was shown for the first time that the reduction of higher vanadium oxides is due to the presence of elemental carbon in the volume of the material formed from a metalorganic precursor during growth of vanadium oxide. Coatings obtained by annealing in hydrogen had a smaller hysteresis loop width (~5 °C) during phase transition compared to coatings obtained by argon annealing (~9 °C). Both types of coatings demonstrated a 50–60% increase in transmission at 1 THz frequency and in the IR region, accompanied by a 10³–10⁴-fold change in electrical resistance. Full article