Search Results (3,942)

Depression is a complex mental and neurological disorder and has become one of the most serious public health issues in modern society. Trihexyphenidyl (THY) is a traditional drug used to treat Parkinson’s disease. Recent studies have suggested that it may play a role in regulating neurotransmitters and protecting neurons, but its potential for treating depression has not been fully explored, and how it works remains unclear. Therefore, we examined the effects of THY on depression-like behaviors in zebrafish caused by chronic unpredictable stress (CUS). Our results showed that THY significantly attenuated the CUS-induced decrease in exploratory behavior and shortened the CUS-induced increase in latency time. At the tissue level, THY effectively attenuated the thinning of the optic tectum and the loss of Nissl bodies caused by CUS. In addition, THY reversed the CUS-induced increase in stress hormone levels and reduction in neurotransmitter content. Through network pharmacology and transcriptome sequencing analysis, we found that the mechanisms underlying depression-like behaviors and the antidepressant effects of THY might be related to the MAPK signaling pathway. Further experiments showed that THY regulated the CUS-induced activation of the MAPK signaling pathway, improved the abnormal activation of microglia and damage to astrocytes, and reduced the expression of pro-inflammatory factors, thereby easing neuroinflammation and improving depression-like behaviors. In summary, this study explored the potential mechanism of THY ameliorating depressive-like behaviors and provided basic theoretical evidence. Full article

Vogt–Koyanagi–Harada syndrome (VKH) is a rare granulomatous autoimmune disease characterised by a systemic immune response directed against melanocytes. This multisystem condition primarily affects organs that are rich in melanocytes, such as the eyes, inner ear, meninges and skin. VKH might be responsible for the development of chronic uveitis and permanent visual impairment, particularly in cases where a diagnosis is delayed and treatment is not administered in a timely manner. A key factor in its pathogenesis is the loss of immune tolerance to melanocytes, driven by a T-cell–mediated immune response and genetic susceptibility, including the presence of HLA-DRB1*04 antigens. In recent years, immune checkpoint inhibitors (ICIs) have become the standard treatment in oncology, including non-small cell lung cancer and unresectable melanoma. However, it should be noted that their utilisation carries with it the potential for immune-related adverse events, including rare cases of VKH-like uveitis. The objective of this review is to outline the clinical features of VKH syndrome, examine current diagnostic and treatment approaches, and emphasise the immunopathological mechanisms associated with drug-induced forms of VKH, with a particular focus on programmed cell death protein 1 (PD-1) inhibitors. The article also includes an analysis of the genetic, epigenetic, and environmental factors that predispose individuals to the disease. This analysis facilitates a deeper understanding of the pathogenesis of the disease and assists in the identification of patients at increased risk of drug-induced VKH manifestations. Full article

Diabetic peripheral neuropathy (DPN) is a common and debilitating complication of diabetes mellitus which affects individuals with both type 1 and type 2 diabetes mellitus (T2DM), presenting with sensory loss, pain, and progressive nerve dysfunction. DPN pathogenesis is multifactorial: chronic hyperglycemia activates the polyol, hexosamine, and protein kinase C (PKC) pathways, increases advanced glycation end-products, and drives oxidative stress, mitochondrial dysfunction, inflammation, and impaired neurotrophic signaling. In addition to hyperglycemia-driven mechanisms, dyslipidemia and microvascular insufficiency exacerbate neural ischemia and metabolic stress. Recent mechanistic, animal, and associative human studies further implicate amyloidogenic toxicity, particularly from human islet amyloid polypeptide (hIAPP), as a plausible contributory factor in peripheral nerve degeneration in T2DM, linking protein misfolding and aggregation to axonal damage and demyelination in DPN. Despite increased understanding of these mechanisms, current treatments remain mainly symptomatic. Emerging therapeutic strategies, including antioxidants, anti-inflammatory agents, modulators of mitochondrial function, amyloid oligomer modulators, neurotrophic enhancers, and regenerative approaches such as stem cells and gene-based therapies, offer potential to modify disease progression. The strength of evidence across these methods varies, ranging from mechanistic and animal studies to early human research and, in some cases, randomized clinical trials. Therefore, although several candidates show potential to alter the disease, few have demonstrated consistent benefits on objective measures of nerve structure or function in large clinical trials. This review summarizes the key mechanisms driving DPN in T2DM and highlights promising therapeutic innovations poised for clinical translation. Full article

Violations of Bell inequalities are commonly interpreted as evidence for nonlocal influences or as constraints on realist descriptions. We show that the failure of Bell-type factorizability arises naturally when observable outcomes are obtained through a non-injective mapping from an underlying configuration space. In this setting, the standard factorization assumption can be viewed as an implicit requirement that observable variables admit a jointly factorizable completion at the underlying level. We demonstrate that this requirement need not hold when the mapping from underlying configurations to observables is many-to-one. The resulting breakdown of probabilistic factorization does not rely on superluminal dynamics or hidden causal influences, but follows from information loss under projection. Observable outcomes correspond to equivalence classes of underlying configurations, preventing the assignment of independent local variables. We illustrate this mechanism with an explicit toy model producing Bell–CHSH violations while preserving operational no-signalling and statistical independence of measurement settings. The model is not intended to reproduce quantum correlations quantitatively, and may exceed the Tsirelson bound; its role is to isolate the structural origin of the violation. This analysis does not contradict Bell’s theorem, but identifies a class of effective descriptions for which its factorizability assumption does not apply. The framework preserves locality at the underlying level, introduces no additional hidden-variable dynamics, and does not modify quantum mechanics. It clarifies how classical factorization is recovered in regimes where the effective mapping becomes approximately injective. In the operator language of quantum theory, the same mechanism admits a natural reformulation in terms of reduction to an effective observable subalgebra by a noncommutative conditional expectation. Full article

Brucellosis, acting as a typical chronic zoonotic disease, is caused by the invasion of Brucella into the human body. Outer membrane protein 25 (Omp25), specifically localized on the Brucella membrane, is the main virulence factor of Brucella and participates in multiple links of the damage process. Omp25c, a porin protein of Brucella, is a paralog of Omp25 with high sequence identity. NADH dehydrogenase [ubiquinone] complex I assembly factor 2 (Ndufaf2) has a key function in cell energy metabolism, particularly in the formation and activity of the mitochondrial respiratory chain. Loss of Ndufaf2 results in oxidative stress and mitochondrial DNA (mtDNA) deletion. However, the functional relationship between Omp25c and Ndufaf2, the underlying mechanism of the proteins, remains unclear. In this work, we purified the Omp25c and Ndufaf2proteins. Our data revealed that Omp25c directly interacts with Ndufaf2, as determined using Biacore analysis. In addition, assays revealed that Ompa2c reshapes the host cell’s redox environment by decreasing the oxidized nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide (NAD⁺/NADH) ratioand adenosine triphosphate (ATP) production, whereas Ndufaf2 exerts an opposing regulatory effect; Co-expression results further revealed an antagonistic relationship between the two during metabolic processes. These findings provide a new perspective for elucidating the mechanisms of mitochondrial functional regulation in Brucella–host interactions and lay the theoretical and experimental foundation for drug development targeting metabolic interventions to eliminate intracellular pathogens. Full article

Background: Long noncoding RNAs (lncRNAs) have emerged as critical regulators of hepatic metabolism and disease progression. The hepatocyte nuclear factor 1 alpha antisense 1 (HNF1A-AS1) lncRNA modulates liver-specific transcription factors; however, its physiological role in diet-dependent lipid homeostasis remains poorly defined. Methods: In this study, we investigated the mouse ortholog, Hnf1a opposite strand 1 (Hnf1aos1), using AAV-mediated knockdown in C57BL/6J mice fed either a chow diet (10% kcal from fat) or a high-fat diet (HFD; 60% kcal from fat) for 12 weeks. Metabolic phenotyping included hepatic lipid quantification, histological analysis, serum biochemistry, and quantitative gene expression profiling. Results: Loss of Hnf1aos1 produced distinct, diet-dependent alterations in hepatic lipid handling. Under chow conditions, knockdown mice exhibited selective hepatic cholesterol accumulation (6.10 ± 2.9 mg/g tissue vs. 3.51 ± 1.1 mg/g in controls), accompanied by dysregulation of cholesterol clearance pathways. In contrast, under HFD conditions, knockdown precipitated severe macrovesicular degeneration, with hepatic triglyceride levels approximately doubled relative to HFD-fed controls (51.72 ± 19.8 mg/g vs. 26.34 ± 11.9 mg/g) and a numerically elevated triglyceride-to-cholesterol ratio (TG:TC ≈ 6.1:1; p = 0.0621, trend). Chow/Kd mice gained significantly less weight than chow-fed controls, whereas HFD/Kd mice exhibited weight gain comparable to HFD controls despite severe hepatic steatosis. This paradoxical phenotype suggests impaired metabolic feedback at the post-transcriptional level, in which compensatory upregulation of Hnf1a mRNA is insufficient to suppress lipid-associated genes such as Cd36, despite profound lipid overload; however, HNF1A protein levels were not directly measured in this study. Conclusion: Collectively, these findings identify Hnf1aos1 as a regulator of hepatic lipid homeostasis whose loss produces a phenotype consistent with inappropriate lipid accumulation during nutrient excess, without defining the underlying molecular mechanism. Our results support a role for Hnf1aos1 in shaping hepatic metabolic plasticity and provide insight into lncRNA-associated MASLD phenotypes. Full article

Thaumasite sulfate attack (TSA) under elevated water pressure has important implications for the durability of deep underground concrete structures, yet the deterioration process and the coupled effect of water pressure and carbonate supply remain insufficiently understood. In this study, laboratory pressurized sulfate exposure tests were conducted to investigate the evolution of macroscopic performance and microstructure of cement mortars with different limestone powder contents (0%, 15%, and 30%) under water pressures of 0, 2.5, and 5.0 MPa. The results show that elevated water pressure promotes sulfate ingress into the mortar and accelerates later-stage strength loss; this interpretation is supported by the depth-dependent distribution of soluble SO₄²⁻ measured in mortars without limestone powder. Two-way ANOVA indicates that both water pressure and limestone powder content have significant effects on compressive strength, and their interaction becomes statistically significant at 120 d. XRD, FT-IR, and SEM/EDS results show that, under elevated water pressure and high limestone powder content, the corrosion products gradually evolve from gypsum-related products to ettringite- and thaumasite-related products, with a certain spatial differentiation. Specifically, the gray–white, mud-like surface products are consistent with thaumasite-rich assemblages, whereas the needle- and column-like crystals in the interior are consistent with ettringite-rich assemblages. Overall, elevated water pressure mainly promotes sulfate transport, while limestone powder mainly increases carbonate availability. These two factors may jointly intensify TSA deterioration in mortar through a pathway involving transport enhancement, carbonate supply, corrosion product evolution, and aggravated macroscopic damage. This study provides a reference for understanding the sulfate deterioration mechanism of limestone powder-containing cement-based materials in deep underground environments under elevated water pressure. Full article

Stock market investors and traders operate in high-pressure environments marked by volatility, uncertainty, financial risk, and intense performance demands. These conditions lead to substantial psychological distress, increasing vulnerability to psychiatric disorders and suicidal behavior. Key psychological risk factors in this population include acute financial loss, chronic stress, impulsivity, perfectionism, and identity fusion with professional performance. Evidence from behavioral psychology and clinical psychiatry indicates elevated rates of mood disorders, anxiety, and burnout in trading environments. Resilience—including emotional regulation, effective stress-coping mechanisms, strong social support, and cognitive flexibility—emerges as a critical protective factor that mitigates suicide risk and promotes adaptive functioning. Strengthening psychological resilience and implementing evidence-based mental-health strategies may help reduce suicide risk and support overall well-being. The medico-legal dimensions of this issue encompass duty of care within high-stress financial workplaces, clinical obligations related to suicide risk assessment and documentation, confidentiality and safety considerations, and questions of foreseeability of suicide in cases involving severe or catastrophic financial loss. Despite growing awareness of mental health challenges in financial professions, the intersection of suicide risk, resilience, and medico-legal responsibilities in this population remains underexplored. Further research is needed to refine assessment frameworks and develop targeted suicide prevention interventions for this at-risk group. Full article

The radial heat transfer mechanism of compacted conductors in overhead insulated cables is unclear, and the insulation layer complicates the thermal boundary conditions, limiting the direct applicability of existing ampacity calculation methods. Based on the Morgan model framework, this paper proposes an ampacity calculation method that accounts for the “plastic-then-elastic” deformation characteristics of compacted conductors. Material plastic flow and elastic deformation of the substrate are incorporated to refine the formulations for interlayer thermal contact conductance and thin-layer air gap thickness, while the equivalent distance of air voids is corrected using the fill factor. An iterative convergence procedure for the insulation outer surface temperature is established to accurately evaluate conductor Joule losses. Validated by wind tunnel tests on JKLGYJ 240/30 cables, the proposed method yields a radial temperature difference of 2.41 °C, closely matching the measured 2.6 °C, with an error of 7.4% compared to 13.5% for the conventional Morgan model. Parametric analysis reveals that equivalent radial thermal conductivity is independent of external environmental factors. Conductor stress has a negligible effect on the ampacity (variation < 0.1%). Under low wind speeds (0–5 m/s), the ampacity increases substantially with wind speed. Full article

Wood coatings play a critical role in protecting wood substrates from environmental degradation, particularly ultraviolet (UV)-induced photodegradation. This review comprehensively examines the mechanisms of wood coating photodegradation, the factors influencing their durability, and current anti-aging strategies. Photodegradation arises from polymer chain scission, chemical structure reorganization, and photo-oxidation of lignin and cellulose, leading to coating chalking, cracking, gloss loss, and color changes, ultimately compromising wood mechanical properties and service life. Key anti-aging strategies include UV absorbers, which convert harmful UV radiation into heat; hindered amine light stabilizers (HALSs) that capture free radicals and quench excited-state molecules; barrier and shielding materials that form dense physical or nanostructured networks to block UV penetration and enhance mechanical and water resistance; and antioxidants that neutralize free radicals or decompose peroxides at the molecular level. Each approach can be employed individually or synergistically to enhance coating durability. Challenges remain in achieving long-term outdoor stability, balancing transparency and UV shielding, optimizing nanoparticle dispersion, and maintaining the activity of natural antioxidants. Future research should focus on multifunctional composite coatings integrating bio-based materials and nanotechnology, smart responsive systems, adaptive protection mechanisms, and standardized long-term evaluation protocols. These advancements will facilitate the development of high-performance, sustainable wood coatings and promote the value-added utilization of wood resources. Full article

Background: Severe neurocognitive decline is often seen in elderly glioblastoma patients after treatment with radiation and chemotherapy. But the mechanism behind their deterioration is unclear. We describe one such patient with concomitant primary age-related tauopathy (PART) in bilateral hippocampi. Case presentation: An 88-year-old woman experienced unsteadiness, memory loss, and slurred speech that was caused by an epithelioid glioblastoma with wild-type isocitrate dehydrogenase-1 and methylated promoter of O⁶-methylguanine-DNA methyltransferase. She was treated with gross total resection, followed by intensity-modulated radiotherapy and daily temozolomide. Shortly after starting treatment, she developed fatigue, anorexia, and neurocognitive impairment, which were refractory to corticosteroids. After two cycles of adjuvant temozolomide, she experienced impulsivity, disorientation, hallucinations, somnolence, and incontinence despite stable neuroimaging findings. Treatment was subsequently discontinued, and she died 20 months from the time of her glioblastoma diagnosis. Autopsy revealed tau-positive neurofibrillary tangles, but rare Aβ plaques, in the trans-entorhinal and entorhinal cortices of both hippocampi. These findings are consistent with a diagnosis of PART. Conclusions: Undiagnosed tauopathy could be a negative modifier of glioblastoma treatment. The identification of PART and other tauopathies as risk factors in the elderly population may be important to guide treatment decision. Full article

Acid rain is a severe global environmental issue, and clarifying its impacts on litter decomposition and underlying mechanisms is critical for accurately forecasting future climate change. Litter consists of components (e.g., non-structural carbohydrates, lignin, cellulose, and hemicellulose) with distinct decomposition resistance, but how acid rain affects these components to modulate overall litter decomposition across different decomposition stages remains unclear. Therefore, a microcosm experiment was conducted to determine decomposition rates of Chinese fir (Cunninghamia lanceolata) litter and its components based on litter mass loss under different simulated acid rain intensities (pH 4.5, moderate acid rain, MA; pH 3.0, severe acid rain, SA; and pH ≈ 7.0, tap water, CK) over two decomposition stages (0–5 months: initial decomposition stage; 6–16 months: late decomposition stage). Meanwhile, to analyze the factors influencing the litter decomposition rate, soil samples were collected at 5 and 16 months of decomposition for soil property analysis. Results showed that MA had no significant effect on litter decomposition in either stage. Conversely, SA led to a significant 43.7% increase in the litter decomposition rate in the initial decomposition stage, driven by its acid dissolution effect that accelerated the decomposition of cellulose and hemicellulose. However, SA significantly decreased the decomposition rate by 42.0% in the late decomposition stage by inhibiting the decomposition of lignin, cellulose, and hemicellulose, which was due to the reduced activities of soil peroxidase and xylosidase under soil acidification. Notably, neither MA nor SA significantly affected the litter decomposition rate over the entire decomposition period (0–16 months). This study indicates that acid rain’s effect on litter decomposition depends on its intensity and decomposition stage, emphasizing the necessity of distinguishing litter components and decomposition stages to explore its underlying mechanisms and precisely predict global climate change. Full article

Cotton, as a globally significant economic crop, is intricately regulated in its growth and development by the key genes for SA (Salicylic acid) biosynthesis. In the present study, a systematic analysis of genes related to SA biosynthesis was conducted across four cotton species, leading to the identification of 70 genes. Specifically, the tetraploid species Gossypium hirsutum and G. barbadense were found to harbor 22 and 23 genes, respectively, representing a substantial expansion compared to the 12 and 13 genes identified in the diploid progenitors G. arboreum and G. raimondii. Comprehensive characterization of chromosomal localization, phylogeny, domain architecture, and promoter cis-elements revealed a uniform distribution of key genes involved in SA biosynthesis across A/D sub-genomes of tetraploids with extensive interspecific collinearity; whole-genome and segmental duplication act as the dominant drivers for the expansion of this gene family, while partial gene loss following polyploidization results in non-doubled gene copy numbers in tetraploids relative to diploids, which reflects the evolutionary selection for genomic dosage balance. The key genes for SA biosynthesis demonstrate a high degree of conservation in protein sequences, protein structures, and conserved motifs, which constitute the structural basis for the stable maintenance of their core functions in the SA biosynthesis pathway during plant evolution. This is closely related to their core function in the salicylic acid (SA) synthesis pathway and serves as the structural basis for the stable maintenance of gene functions during evolution. Analysis of cis-elements revealed that the expression of key genes involved in SA biosynthesis is governed by a complex interplay of phytohormones, stress signals, and transcription factors. Yeast one-hybrid (Y1H) assays confirmed the interaction between the GhPAL and GhICS gene and predicted candidate transcription factors, specifically the binding of GhWRKY21 to GhICS2-1 promoter and GhMYB12 to GhPAL1-2 promoter, thus elucidating their stage-specific regulatory mechanisms in cotton fiber development and reflecting their evolution. This study provides a fundamental basis for investigating the role of the SA signaling pathway in cotton development and offers support for cotton molecular breeding. Full article

An investigation was conducted to explore the freeze–thaw resistance of 60–90 MPa high-strength concrete blended with multiple industrial byproducts (limestone powder, fly ash, etc.) and mixed sand (machine-made/tailings sand), aiming to clarify freeze–thaw degradation mechanisms and build reliable damage prediction models. Three water-binder (w/b) ratios (0.30, 0.25, 0.20) and 15 mix proportions were designed, with 30–45% cement replaced by mineral admixtures and 90–100% natural sand by mixed sand. Results show lower w/b ratios improve resistance: the 0.20 ratio yields merely 0.06% mass loss and 96% relative dynamic elastic modulus retention after 400 cycles. Optimized silica fume and limestone powder refine pore structures; fly ash-slag synergy boosts durability via secondary hydration under specific dosage ratios. A 7:3 machine-made/tailings sand mix shows better frost resistance due to improved particle packing and interfacial transition zones. Three damage models were established, with Model III demonstrating high accuracy. This work’s novelty lies in multi-byproduct synergy and multi-factor models, supporting green concrete use in cold regions. Full article

Elevated temperatures due to global climate change adversely affect plant growth and development, which has become a major factor restricting wheat (Triticum aestivum L.) production. Despite the introduction of dwarfing genes that have enhanced lodging resistance as well as productive potential in wheat breeding, lodging still affects wheat yields. Plant growth regulators are widely recognized as effective agents in mitigating crop lodging. Few studies have investigated the high-temperature lodging sensitivity of wheat genotypes from different breeding periods, nor have they examined how uniconazole-sucrose regulates lodging resistance under heat stress. To fill this research gap, an experiment was conducted in which two contrasting wheat genotypes from different periods, Bima 1 (BM1, ~135 cm tall, a historical genotype released in 1953, lodging-susceptible) and Shannong 28 (S28, ~75 cm tall, a modern genotype released in 2014, lodging-resistant), were exposed to high temperature stress combined with uniconazole-sucrose application. The results showed that high-temperature-induced increases in plant gravity center height, together with decreased stem diameter coefficient, stem plumpness, and lignin deposition, were the main factors responsible for the reduction in bending section factor and mechanical strength of wheat stems. These modifications are associated with reduced lodging resistance, increased susceptibility to lodging, and significant yield losses. Nevertheless, exogenous application of uniconazole-sucrose lowers plant gravity center height, enhances stem diameter coefficient, stem plumpness, and lignin content, thus alleviating lodging risk and boosting wheat yield under high temperature stress. High temperature stress was associated with downregulated relative expression levels of key genes involved in lignin metabolism and reduced activities of the corresponding key enzymes, as well as inhibited lignin biosynthesis and accumulation in stems and increased incidence of wheat lodging. Conversely, foliar spraying of uniconazole-sucrose alleviated these suppressive effects on lignin biosynthesis, thus enhancing stem mechanical strength and reducing the lodging index of wheat. Moreover, these indicators were more sensitive to heat stress or uniconazole-sucrose treatment in BM1. The two genotypes examined suggested a potential trend that S28 may exhibit reduced sensitivity to high temperature in terms of mechanical traits and lignin synthesis, which could contribute to enhanced lodging resistance under heat stress. Full article