Search Results (297)

Carbon monoxide (CO) is a gasotransmitter generated by heme oxygenase (HO) isoforms during heme catabolism. The inducible HO-1 produces CO under conditions of redox imbalance, such as oxidative stress and inflammation. On the other hand, HO-2 constitutively generates CO, primarily during the physiological turnover of heme. Extensive evidence indicates that CO exerts autocrine effects by targeting hemoproteins, including soluble guanylyl cyclase, cyclooxygenase, and cytochromes. Furthermore, CO regulates many biological processes within the brain, including mitochondrial biogenesis, potassium channel activity, mitogen-activated protein kinase and phosphatidylinositol-3-kinase/Akt signaling. It also controls the activity of transcription factors, such as hypoxia-inducible factor-1 and peroxisome proliferator-activated receptor-γ. Through these mechanisms, CO modulates inflammatory gene expression, promotes anti-apoptotic signaling, and contributes to local stress responses. Conversely, CO produced in the hypothalamus inhibits the stress-induced release of corticotropin-releasing hormone and arginine vasopressin under pro-inflammatory conditions, resulting in reduced adrenocorticotropin hormone release and cortisol secretion from the anterior pituitary and adrenal cortex, respectively. Moreover, hypothalamic CO acts in a paracrine manner to modulate glucocorticoid release during psychological stress, including restraint or water deprivation. Together, these findings support the view that endogenous CO is a key modulator of the stress axis, exerting pleiotropic effects that integrate neuroendocrine, immune, and metabolic responses. Full article

The effective length factor method cannot account for variations in axial forces between columns and the mutual assistance among columns, resulting in overestimation of the critical load of columns that receive assistance and underestimation of that of columns that provide assistance. Moreover, this method is not readily applicable to bent frames and frame structures with multi-story tie beams. The phenomenon of critical load redistribution among columns under non-uniform loading conditions is revealed in this paper, and its underlying mechanical mechanism is elucidated. Based on this, a two-stage loading procedure for critical load redistribution analysis is proposed, in which the instability process of irregular structures is divided into two stages: independent loading of individual columns and combined loading of the assembly. By superimposing the critical load of columns in regular structures with the remaining load capacity, a formula for evaluating the overall stability critical capacity of bent and frame structures is established. The proposed method effectively accounts for the restraint provided by tie beams between columns, eliminating the need for iterative solutions of transcendental equations or the construction of complex total potential energy equations, thereby significantly simplifying the computational process. Comparative analyses of numerical examples demonstrate that the proposed method achieves high accuracy and enables quantitative assessment of mutual assistance between columns. It provides a conceptually clear, computationally efficient, and reliable practical tool for the stability design of bent and frame structures under complex loading conditions. Full article

Coastal continuous girder bridges are exposed to coupled environmental and seismic hazards during long-term service, including chloride-induced corrosion, freeze–thaw damage, scour, near-field ground motions, and structural irregularity. These factors can progressively reduce structural capacity, amplify seismic demand, redistribute component responses, and affect post-earthquake functionality and recovery. This paper reviews recent advances in the time-dependent seismic vulnerability and resilience assessment of reinforced concrete and prestressed concrete coastal continuous girder bridges. Based on 229 screened publications, the review first summarizes deterioration mechanisms and modelling approaches for chloride corrosion, freeze–thaw damage, and scour, with emphasis on their effects on material degradation, component capacity, foundation restraint, and seismic fragility. The demand-side effects of near-field vertical excitation and pulse-like ground motions are then discussed, followed by the seismic response characteristics of irregular continuous girder bridges, including curved alignments, unequal pier heights, and skewed supports. Existing studies indicate that environmental deterioration can shift fragility curves toward lower intensity levels, near-field vertical excitation can modify axial force, bearing contact state, girder–bearing separation, and impact response, while structural irregularity may concentrate seismic demand in critical components. Furthermore, the review clarifies the transition from time-dependent fragility analysis to functionality loss, recovery modelling, and lifecycle resilience assessment. The main research gaps include simplified deterioration representation, insufficient coupling of deterioration–hazard–irregularity effects, limited validation of time-dependent fragility models, and weak integration between component damage, bridge functionality, recovery trajectories, and resilience indicators. Future studies should develop more unified, uncertainty-informed, and lifecycle-oriented frameworks for coastal bridge vulnerability and resilience assessment. Full article

Shearing is a stressful procedure for sheep, combining isolation, restraint, and the mechanical action of shearing, which activates the hypothalamic–pituitary–adrenal axis and induces oxidative stress. This study investigated whether melatonin—a pleiotropic hormone with well-documented antioxidant properties—administration could modulate the stress response and oxidative stress in Sarda sheep during shearing. Forty lactating ewes (aged 3–5 years, mean body weight 41 ± 1.1 kg) were randomly assigned to four groups (n = 10 each): two groups received a subcutaneous melatonin implant (18 mg); two remained untreated as controls. Within each category, one group was shorn and the other subjected only to restraint. Blood samples were collected before, during, and after shearing to measure cortisol, glucose, reactive oxygen metabolites (ROMs), biological antioxidant potential (BAP), and oxidative stress index (OSI). Procedures elevated cortisol, glucose, ROMs, and OSI in all groups, but melatonin treatment significantly reduced these parameters and increased BAP relative to untreated animals at all sampling points (p < 0.05). No significant differences were observed between shorn and unshorn animals within the same treatment, suggesting that the handling, restraint, and isolation associated with the shearing procedure represent the major sources of stress, rather than the mechanical act of shearing itself. In conclusion, melatonin administration blunts the stress response and reduces oxidative stress in sheep during routine shearing-related handling procedures, suggesting its potential as a practical tool to improve animal welfare during routine management practices. Full article

Background/Objectives: Anshen Bunao Oral Liquid (ABOL) is a traditional medicinal formula comprising Cornu Cervi Pantotrichum, Radix Polygoni Multiflori Preparata and other ingredients. It replenishes essence, nourishes qi and blood, and soothes the spirit. It is used in clinical practice to treat neurasthenia and insomnia (emotion-related symptoms), and its key component, glycyrrhizin, exhibits anxiolytic properties. This aligns with the holistic approach of traditional Chinese medicine (TCM) to regulating neuropsychiatric disorders. The aim of this study is to evaluate the anxiolytic efficacy of ABOL in rats with anxiety induced by chronic restraint stress (CRS), and to clarify its mechanism by focusing on modulation of the gut–brain axis (microbiota and metabolism). Methods: Sprague-Dawley rats underwent three hours of restraint per day for 28 days to induce anxiety. ABOL was administered intragastrically in three doses. Anxiety-like behaviours were assessed using OFT, EPM and SPT. Serum, tissue and faecal samples were analysed using ELISA, histopathology, immunohistochemistry, non-targeted metabolomics, 16S rRNA sequencing and RT-qPCR. Results: CRS induced anxiety-like behaviours, impaired weight gain and perturbed the balance of neurotransmitters (decreasing 5-HT, GABA, NE and DA, while increasing CORT), inducing inflammation/oxidative stress, hippocampal neuronal injury, intestinal barrier dysfunction and gut microbiota/metabolic dysregulation. ABOL effectively reversed these abnormalities by restoring the balance of neurotransmitters and the HPA axis, suppressing inflammation and oxidation, protecting neurons and the intestinal barrier, remodelling the gut microbiota (enriching Akkermansia and balancing Firmicutes/Bacteroidota) and regulating sphingolipid and glycerophospholipid pathways. The interaction between the gut microbiota and metabolites may contribute to this pharmacological effect. Conclusions: ABOL exerts anxiolytic effects by modulating the gut–brain axis at multiple targets, involving microbiota remodelling, regulation of lipid metabolism and improvement of pathology. This validates its ethnopharmacological value, linking traditional Chinese medicine to the development of modern anxiolytics. Full article

The ecological restoration of degraded sandy land in the Yarlung Zangbo River Valley is constrained by the metabolic functions of soil microorganisms. This study investigates the dynamic mechanisms of microbial elemental use efficiency in walnut plantations, with a focus on seasonal variations in soil chemical stoichiometry, extracellular enzyme activity, and microbial nutrient efficiency in rhizosphere and bulk soils. This paper explores the effects of conventional organic fertilizer (CF) and organic–inorganic compound fertilizer (OIF) on microbial nutrient use strategies and their seasonal dynamics. The results showed significant seasonal fluctuations in soil active nutrients and microbial biomass, while the total nutrient content remained stable. OIF enhanced microbial chemical stoichiometric homeostasis but simultaneously triggered a “carbon–phosphorus metabolic trade-off”, leading to a restraint of microbial carbon use efficiency (CUE) during the growing season. Microbial elemental use efficiency (EUE) exhibited clear seasonal differentiation: CUE was higher in summer, promoting biomass accumulation, whereas NUE and PUE increased in winter and spring, reflecting a nutrient conservation strategy. The EUE pathways were decoupled between rhizosphere and non-rhizosphere microenvironments. The rhizosphere was more directly driven by soil chemical stoichiometry and microbial biomass, while the non-rhizosphere was influenced by nutrient limitation states, represented by vector characteristics. This study provides insights into the seasonal adaptability and microenvironmental heterogeneity of microbial metabolism during the restoration of cold sandy land. It is suggested that future ecological management should focus on N-P balanced fertilization and consider the differential responses between rhizosphere and non-rhizosphere zones to enhance ecosystem productivity and soil carbon, nitrogen, and phosphorus sequestration potential. Full article

Depression is increasingly linked to microbiota–gut–brain axis dysfunction, yet current monoaminergic antidepressants show limited efficacy. This study investigated the therapeutic potential and underlying mechanisms of GV-971, a marine-derived oligosaccharide, in a chronic restraint stress (CRS) mouse model. We first established that 8 h of daily restraint for 4–8 weeks induces a stable depression-like phenotype characterized by behavioral despair and significant reduction in peripheral monoamine neurotransmitters (5-HT and norepinephrine). GV-971 treatment robustly attenuated CRS-induced depression- and anxiety-like behaviors, restored hippocampal serotonin levels, reduced elevated plasma corticosterone concentrations, and ameliorated CRS-induced adrenal cortical hyperplasia. Mechanistically, GV-971 significantly suppressed neuroinflammation by inhibiting microglial hyperactivation in the prefrontal cortex and hippocampus. Concurrently, it repaired intestinal barrier dysfunction, evidenced by reduced permeability, restored mucosal integrity, and recovered goblet cell numbers. Crucially, integrated shot-gun metagenomics and plasma metabolomics revealed that GV-971 not only reshaped microbial taxonomy but also functionally recalibrated the gut ecosystem. It enriched beneficial taxa (e.g., Bifidobacterium pseudolongum, Bacteroides uniformis) and specific metabolic pathways, leading to increased short-chain fatty acids (valeric and caproic acids) and a significant reduction in plasma levels of tryptophan–kynurenine pathway metabolites, specifically the neurotoxic compounds kynurenine and quinolinic acid. Fecal microbiota transplantation (FMT) from GV-971-treated donors partially recapitulated the antidepressant and gut-protective effects in CRS recipients, confirming a causal role for the remodeled microbiota. Collectively, GV-971 exerts antidepressant effects by coordinately remodeling the gut microbiota, normalizing tryptophan and SCFA metabolism, restoring gut barrier integrity, and dampening central neuroinflammation, supporting its potential as a novel gut–brain axis-targeted therapy for depression. Full article

Background: Neuroinflammation and gut–brain axis (GBX) dysregulation are key pathological drivers of stress-related neuropsychiatric disorders. Zhi-Zi-Chi Decoction (ZZCD), a classic Traditional Chinese Medicine (TCM) formula, has been clinically used to alleviate mental disturbances via the TCM principle of “clearing heat and relieving restlessness.” Still, its modern neuroprotective mechanisms, especially its links to gut microbiota and central signaling pathways, remain incompletely elucidated. Purpose: This study aimed to systematically investigate the therapeutic effects of ZZCD on chronic restraint stress (CRS)-induced neurodysfunction in mice and clarify its mechanisms from the perspectives of TCM theory, material basis, gut microbiota–metabolite axis, and central signaling pathways. Method: CRS mice were treated with ZZCD or protocatechuic acid. Behavioral tests evaluated depression- and anxiety-like behaviors. UHPLC-Q-TOF/MS identified ZZCD’s chemical constituents; 16S rRNA sequencing and untargeted metabolomics analyzed gut microbiota and metabolite changes. Western blot, immunofluorescence, and proteomics examined neuroinflammation, microglial polarization, and signaling pathway activity (PI3K/Akt/mTOR, AMPK). Results: ZZCD reversed CRS-induced depression- and anxiety-like behaviors and suppressed neuroinflammation. Mechanistically, UHPLC-Q-TOF/MS identified 424 ZZCD constituents, with prenol lipids, organooxygen compounds, and flavonoids as the most abundant. ZZCD reversed CRS-induced imbalance in gut microbiota, reducing pro-inflammatory Prevotella and enriching beneficial Lactobacillus, and mediated the enrichment of the prebiotic metabolite PCA in colonic and serum samples, which crossed the blood–brain barrier (BBB) to exert neuroprotection. Additionally, ZZCD and PCA normalized the PI3K/Akt/mTOR pathway and activated AMPK, promoting M2 microglial polarization and restoring synaptic plasticity. Conclusions: ZZCD exerts antidepressant effects by a gut-microbiota-dependent modulation of PCA-PI3K/Akt/mTOR and AMPK dual axes that converts microglia from M1 to M2, providing ethnopharmacological evidence and a mechanistic rationale for its clinical application in major depressive disorder. Full article

Expansive soil slopes are highly susceptible to rainfall-induced shallow failures due to cyclic swelling–shrinkage behavior governed by matric suction variation. This study proposes a composite frame–geosynthetic system (CFGS), comprising a rigid frame integrated with high-performance turf reinforcement mats (HPTRMs), for expansive soil slope protection. The performance of the CFGS was evaluated through geometrically scaled, materially representative physical model tests under repeated wetting–drying cycles and further examined using coupled hydro-mechanical numerical simulations in COMSOL Multiphysics. A bare slope and an HPTRM-protected slope were used for comparison. Under identical laboratory conditions, CFGS reduced cumulative erosion to approximately 13% of that of the bare slope. It also moderated the internal hydraulic response, reducing pore-water pressure fluctuation by approximately 26%, and restrained swelling–shrinkage deformation, with an average deformation attenuation of up to 61%. The numerical simulations showed consistent response trends with the physical model tests, supporting the proposed mechanism of hydraulic regulation, deformation restraint, and stress redistribution. Overall, the results demonstrate the comparative effectiveness of CFGS in mitigating wetting–drying-induced deterioration of expansive soil slopes. Full article

The reliable discrimination between magnetizing inrush currents and internal faults is essential for effective power transformer protection and has a direct impact on the security and stability of modern power systems. Although the second-harmonic restraint method has been widely adopted in transformer differential protection, its dependability can be affected by several operating conditions, including asymmetric energization, current transformer saturation, and the use of modern low-loss cores with reduced harmonic content. This paper presents a comprehensive and critical review of advanced techniques for distinguishing inrush currents from internal faults. The reviewed methods are classified into five main methodological categories: harmonic-based methods, time-domain approaches, signal-processing techniques, artificial intelligence-based schemes, and hybrid strategies. For each category, the fundamental operating principles, key advantages, and inherent limitations are discussed. A comparative assessment is also provided to highlight the trade-offs among detection accuracy, operating speed, robustness under adverse conditions, and practical implementation feasibility. The review shows a clear shift toward intelligent and data-driven protection schemes that combine effective feature extraction or deep learning with fast decision-making mechanisms. However, several challenges remain, particularly in relation to cross-site generalization, guaranteed response time, and hardware implementation constraints. Finally, the paper outlines a future research agenda for adaptive and computationally efficient transformer protection, emphasizing the need for benchmark datasets that include field cases, reproducible evaluation protocols, and the co-design of protection algorithms with embedded hardware platforms. Full article

In this study, 310S austenitic stainless-steel was welded using a laser with varying amounts of Nb to systematically investigate the effect of Nb on solidification cracking susceptibility, mechanical properties, and corrosion resistance of the weld. Under the present experimental conditions, the critical restraint width was higher for the 0.58 wt.% Nb and 1.45 wt.% Nb welds than for the Nb-free and 2.3 wt.% Nb welds, indicating that Nb addition affected the solidification cracking response of the weld. At low-to-moderate Nb contents, Nb can aggravate compositional segregation and increase the presence of low-melting-point liquid films, thereby increasing cracking susceptibility. At higher Nb contents, the reduced cracking susceptibility was accompanied by microstructural refinement and changes in the distribution of Nb-rich constituents during solidification. With increasing Nb content, the number of precipitated phases in the weld increases, mainly distributed at the austenite grain boundaries in granular, elongated, and chain-like forms. The introduction of Nb generally increases the microhardness and tensile strength of the welded joint, attributed to grain refinement strengthening and solid-solution strengthening. The reduction in area first increased and then decreased, suggesting that excessive Nb addition may reduce ductility because of the increased amount of grain-boundary precipitates and local strengthening heterogeneity. With increasing Nb content, the Ir/Ia ratio decreased from 67.6% to 52.2%, suggesting improved intergranular corrosion resistance. This improvement is likely related to the preferential reaction of Nb with carbon, which may suppress the formation of Cr-depleted zones at grain boundaries. Overall, Nb addition improved the corrosion resistance and increased the hardness and tensile strength of the weld; however, its effect on solidification cracking susceptibility was non-monotonic, indicating that careful control of Nb content is required to balance cracking susceptibility, mechanical properties, and corrosion resistance. Full article

Tryptophan (Trp) metabolism sits at the intersection of nutrition, the microbiome, mucosal immunity, and tumor adaptation. The broad observation that microbial indoles can support barrier function, whereas tumors exploit kynurenine-pathway metabolism to suppress immunity, is already established in publications. The specific contribution of this review is to organize that literature into a context- and network-based translational framework. Rather than treating indoleamine 2,3-dioxygenase 1 (IDO1) as a single bottleneck, we frame tumor Trp metabolism as a compensatory system linking IDO1, tryptophan 2,3-dioxygenase (TDO2), interleukin-4-induced gene 1 (IL4I1), amino-acid transport, amino-acid stress sensing, and downstream aryl hydrocarbon receptor (AHR) signaling. In healthy tissue, especially the gut, dietary Trp and microbiota-derived indoles can promote epithelial integrity, interleukin-22 (IL-22)-associated programs, and mucosal restraint. In tumors, the same substrate pool is redirected toward Kynurenine, kynurenic acid, indole-3-pyruvate, and related catabolites that impair cytotoxic lymphocytes, expand regulatory T-cell (Treg) and suppressive myeloid compartments, and reinforce invasion and treatment resistance. We also argue that the potential metabolite biomarker interpretation should be context-dependent. Finally, we propose a clinical-context–specific framework for intervention. Dietary and microbiome-based strategies may be most effective in prevention, premalignant states, or supportive care, whereas established cancers are more likely to require biomarker-guided targeting of tumor-associated catabolic pathways and convergent signaling mechanisms. The “paradox” is therefore not that Trp changes chemistry across settings, but that the same nutrient is routed through different cellular contexts, enzymes, ligands, and cell states. Full article

A generalized eigenvalue formulation is developed for the free vibration analysis of anisotropic rectangular plates with rotationally restrained edges using the finite integral transform method. For free vibration problems, casting the governing equations into a generalized eigenvalue problem is particularly advantageous because it enables the direct and systematic extraction of multiple natural frequencies and their associated mode shapes within a unified framework, while avoiding the need for assumed trial functions or solution searching near initial guesses. In the present study, a two-dimensional sine integral transform is introduced into the governing equation of anisotropic plates with bending-twisting coupling, and the mechanical description of rotationally restrained boundary conditions is incorporated simultaneously, thereby converting the original partial differential boundary value problem into a generalized eigenvalue problem. The corresponding analytical solution is then established through the finite integral transform framework. The accuracy and reliability of the proposed method are verified through comparisons with finite element results and published data. Based on the obtained analytical solution, the effects of boundary conditions, rotational stiffness coefficients, aspect ratio, and key stiffness components on the vibration characteristics of anisotropic rectangular plates are further examined. The present study provides an effective analytical framework for free vibration analysis of anisotropic plates with nonclassical rotational restraints and offers theoretical support for the dynamic design and optimization of advanced composite plate structures. Full article

In recent years, plant stress biology has moved beyond single-pathway descriptions toward an integrated framework in which stress perception, hormonal control, and gene regulation are tightly interconnected. Early events such as membrane-associated sensing, calcium influx, reactive oxygen species (ROS) generation, and kinase activation converge with phytohormonal networks to shape context-dependent responses. Within this framework, abscisic acid, salicylic acid, jasmonates, ethylene, auxin, cytokinins, gibberellins, brassinosteroids, and strigolactones function not as isolated regulators but as components of a dynamic signaling matrix that balances survival, defense, growth restraint, and recovery. These hormonal signals are ultimately translated into adaptive outcomes through extensive transcriptional and post-transcriptional reprogramming mediated by transcription factors, RNA-based regulators, chromatin remodeling, and stress memory mechanisms. This review synthesizes current understanding of how plants integrate stress perception, phytohormonal crosstalk, and transcriptional regulation to establish stress tolerance. We first examine the molecular basis of stress sensing and early signaling. We then discuss the central functions of major phytohormones and the logic of hormone–hormone interaction networks in coordinating stress adaptation. Next, we analyze transcriptional, post-transcriptional, and epigenetic mechanisms that determine response specificity, intensity, and persistence. We further highlight points of convergence between abiotic and biotic stress responses and discuss how combined stresses challenge traditional single-stress models. Finally, we consider the roles of omics, systems biology, and translational technologies in decoding and engineering stress-resilient phenotypes. By integrating these perspectives, this review presents plant stress tolerance as a multilevel systems property and outlines key priorities for future research aimed at developing climate-resilient crops. Full article

Excavation and dewatering are the primary factors governing diaphragm wall deformation and ground surface settlement in deep foundation pits. However, their coupled effects in soft-over-hard composite strata remain insufficiently understood. This study investigates a deep metro foundation pit in Jinan, China, and develops a three-dimensional hydro-mechanical coupled model in ABAQUS to simulate the complete staged excavation and dewatering process. The evolution of diaphragm wall lateral displacement, ground surface settlement, and pore-water pressure was systematically analyzed, and the simulation results were validated against field monitoring data. The results show that both excavation and dewatering induced significant wall deformation and surface settlement, with excavation playing the dominant role. The incremental lateral displacement of the diaphragm wall caused by excavation was approximately 2.6–3.8 times that caused by dewatering, while the corresponding ground surface settlement was 7.9–10.7 times greater. Owing to the strong restraint provided by the underlying rock stratum, the maximum lateral displacement of the diaphragm wall occurred at approximately 0.67 H_e, where H_e is the final excavation depth. The primary influence zone of ground surface settlement extended to approximately 2 H_e. In addition, dewatering altered the seepage field inside and outside the pit, leading to a continuous decrease in pore-water pressure within the pit, whereas the external pore-water pressure remained largely unchanged because of the seepage-barrier effect of the diaphragm wall. These findings provide practical guidance for the design and construction of deep foundation pits under similar geological conditions. Full article