Search Results (37,655)

Diabetes mellitus is a chronic metabolic disorder that facilitates the formation of advanced glycation end products (AGEs), which contribute to oxidative stress, inflammation, and vascular damage, causing complications including nephropathy, neuropathy, and atherosclerosis. AGEs are primarily synthesized through the Maillard reaction, alongside various signaling pathways. Activation of the receptor for AGE (RAGE) triggers inflammatory signaling pathway cascades, exacerbating tissue damage. Phenolic compounds found in plant-based foods, such as quercetin and resveratrol, have shown promise in counteracting AGE-related complications through their antioxidant and anti-inflammatory effects that inhibit AGE formation, reduce oxidative stress, and modulate RAGE signaling, while also enhancing insulin sensitivity and improving glucose homeostasis. Indeed, quercetin can help prevent AGE accumulation and reduce diabetic nephropathy, while resveratrol activates the SIRT1 pathway, improving insulin sensitivity. This review examines the mechanisms through which phenolic compounds mitigate AGE-induced diabetic complications, using computational, in vitro, preclinical, and clinical evidence. This review also explores the synergistic effects of these compounds with conventional antidiabetic drugs, addresses bioavailability challenges, and suggests future research directions. Overall, this review offers a comprehensive understanding of the role of phenolic compounds in managing diabetes, underscoring their potential as complementary agents in diabetes therapy and developing more effective natural treatments. Full article

Cryptotanshinone (CPT), the main active compound of Salvia miltiorrhiza, is known for its anti-inflammatory, antioxidative, and antifibrotic effects. In this study, the hepatoprotective effect and mechanisms of CPT were explored using transcriptome and network pharmacology. A carbon tetrachloride-induced acute liver injury (ALI) mouse model was established. The anti-ALI effects of different doses of CPT were evaluated by analysis of biochemical indicators, histopathological staining, and immunohistochemical analysis. Combining network pharmacology with transcriptomic analysis revealed therapeutic targets, which were subsequently validated through polymerase chain reaction and Western blotting. CPT (40 mg/kg) treatment significantly reduced the levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, tumor necrosis factor-α, interleukin-6, and interleukin-1β in model mice and regulated oxidative stress indicators, including malonaldehyde, superoxide dismutase, glutathione, and catalase. MCP-1 protein expression in the liver was inhibited by treatment with CPT. Network pharmacology revealed 72 core targets involved in the treatment of ALI by CPT. By combining transcriptomic data from liver tissue, three key targets—TNF-α, TLR9, and ADORA2B—were identified, along with the TLR, IL-17, and TNF signaling pathways. Furthermore, PCR and Western blot assays revealed that CPT significantly decreased TNF-α, TLR9, and ADORA2B expression levels in the livers of ALI mice. In conclusion, the hepatoprotective effects of CPT may be related to the suppression of TNF-α-, TLR9-, and ADORA2B-mediated inflammation, oxidative stress, and apoptosis. These results provide a foundation for the development of CPT as a potential therapeutic agent for ALI. Full article

The 60 kg/m U75V rail serves as the predominant rail type within China’s high-speed rail network. This study comprehensively evaluates the fatigue behavior of U75V rails through experimental investigations encompassing monotonic tensile testing, high-cycle fatigue characterization, and fatigue crack propagation analysis. All specimens were extracted from standardized 60 kg/m high-speed rail sections to ensure material consistency. Firstly, monotonic tensile tests were conducted to determine the fundamental mechanical properties of the U75V rail. Secondly, uniaxial tension–compression fatigue tests were conducted to establish the S-N and P-S-N relationships of the U75V rail. Lastly, fatigue crack propagation analysis was carried out on three compact tension specimens under three incremental loading forces. Monotonic tensile test results demonstrated full compliance of the material’s basic mechanical properties with Chinese national standards. Fatigue crack propagation results indicated that the crack growth rate of the U75V rail was not only related to the stress-intensity range ∆K but was also correlated with the loading force range ∆F due to a typical crack tip shielding effect, i.e., plasticity-induced crack closure effect. The derived fatigue performance parameters and crack growth mechanism provide essential inputs for predictive fatigue life modeling of high-speed rail infrastructure and development of refined finite element models for fatigue analysis. Full article

This study investigates the construction method of longitudinal displacement profiles (LDPs) for elastic–brittle–plastic tunnel-surrounding rock using numerical simulation. First, an axisymmetric numerical model of a circular tunnel is established based on the physical–mechanical parameters of granite at 630 m depth, with customized model parameters covering varying ratios of in situ stress to the global strength of the rock mass. Second, tunnel excavation is simulated using an elastic–brittle–plastic model, yielding radial displacement evolution data at the excavation boundary as a function of distance from the tunnel face. A quantitative relationship between these displacements and distances is derived, forming the proposed LDP construction method. Third, the calculated displacement evolution data (using the proposed method) show high consistency with both simulated and field-monitored data, validating the proposed method’s accuracy and reliability. Finally, a set of LDPs for elastic–brittle–plastic tunnel-surrounding rock is established, enabling the efficient determination of optimal support timing and streamlined tunnel support design. Full article

Given the environmental threats, the adoption of green and clean mobility is crucial for decarbonizing the mobility sector. Green mobility will bring a mass integration of electric vehicle charging stations (EVCSs) to ensure sufficiency for electric vehicle (EVs) users. To achieve this, intelligently distributing the charging load of EVs is essential to prevent stress on local electrical grids. The uneven distribution of EV charging at specific EVCSs leads to load imbalances compared to underutilized stations, necessitating dynamic load-balancing (in real time) mechanisms to optimize grid demands and prevent overloading. To address this challenge, the authors propose an algorithm for balancing EV loads at EVCSs using dynamic charging prices. This algorithm is intended to be integrated into the OCPP. Simulation results indicate that lower pricing at Station A (0.22 $/kWh) attracts more users, reducing congestion at higher-priced Stations B (0.31 $/kWh) and E (0.29 $/kWh). The proposed model encourages users to utilize less crowded stations, achieving a fairer distribution of EV charging demand while providing cost benefits to users selecting those stations. Full article

This study investigates the protective effects and underlying mechanisms of Mao Jian Black tea ethanol extract (MJBT_EE) on a mouse model of acute alcohol-induced liver injury (ALI). The animal model was established using the NIAAA method, and C57BL/6 mice were divided into the following groups: negative control group (NC), model control group (MG), silibinin positive control group (SL, 54 mg/kg), and MJBT_EE high- and low-dose groups (40 mg/mL, 20 mg/mL). The results showed that, compared to the MG, MJBT_EE significantly reduced serum levels of ALT, AST, TC, TG, LDL-C, TBIL, ALP and inflammatory cytokines IL-6, TNF-α, and IL-1β (p < 0.01), while upregulating HDL-C (p < 0.01). It also enhanced the activity of hepatic antioxidant enzymes SOD and GSH (p < 0.01) and reduced MDA content (p < 0.01). Further histopathological examination of liver tissue revealed that MJBT_EE_H markedly alleviated hepatocellular hydropic degeneration, swelling, and steatosis. The mechanism of action of MJBT_EE_H primarily involved activation of the PI3K/Akt pathway and suppression of excessive p-NF-κB activation. These findings indicate that Maojian black tea ethanol extract exerts significant protective effects against alcohol-induced liver injury, potentially through improving lipid metabolism, reducing oxidative stress and inflammatory responses, and modulating the PI3K/Akt/NF-κB signaling pathway. Full article

Natural rock materials, containing micro-cracks and pore defects, significantly alter their mechanical behavior. This study investigated fracture interactions of red sandstone containing double close-round holes (diameter: 10 mm; bridge angle: 30°, 45°, 60°, 90°) using acoustic emission (AE) monitoring and the discrete element simulations method (DEM), which was a novel methodology for revealing dynamic failure mechanisms. The uniaxial compression tests showed that hole geometry critically controlled failure modes: specimens with 0° bridge exhibited elastic–brittle failure with intense AE energy releases and large fractures, while 45° arrangements displayed elastic–plastic behaviors with stable AE signal responses until collapse. The quantitative AE analysis revealed that the fracture-type coefficient k had a distinct temporal clustering characteristic, demonstrating the spatiotemporal synchronization of tensile and shear crack initiation and propagation. Furthermore, numerical simulations identified a critical stress redistribution phenomenon, that axial compressive force chains concentrated along the loading axis, forming continuous longitudinal compression zones, while radial tensile dispersion dominated hole peripheries. Crucially, specimens with 45° and 90° bridges induced prominently symmetric tensile fractures (85° to horizontal direction) and shear-dominated failure near junctions. These findings can advance damage prediction in discontinuous geological media and offer direct insights for optimizing excavation sequences and support design in cavern engineering. Full article

Reservoir landslides undergo saturated–unsaturated transitions under hydrological variations. Matric suction significantly influences slip-zone soil strength. Existing studies lack analysis of suction–rate–strength coupling, while Amontons’ model fails for cohesive soils. This study investigated Huangtupo landslide slip-zone soil in the upper reaches of the Yangtze River using pressure plate and saturated salt solution methods to determine the soil–water characteristic curve. Suction-controlled ring shear tests were conducted under three matric suction levels ($\Psi$ = 0, 200, and 700 kPa) across net normal stresses (${\sigma }_{net}$ = 100–800 kPa) and shear rates ($\dot{\gamma }$ = 0.05–200 mm/min). Key findings revealed the following: (1) significant suction–rate coupling effects were shown, with 700 kPa suction yielding 30% higher residual strength than saturated conditions, validating matric suction’s role in enhancing effective stress and particle contact strength; (2) residual cohesion showed strong logarithmic correlation with shear rate, with the fastest growth below 10 mm/min, while the residual friction angle varied minimally (0.68°), contributing little to overall strength; (3) a bivariate model relating residual cohesion to $\dot{\gamma }$ and $\Psi$ was established, overcoming traditional single-factor limitations. The study demonstrates that dual-parameter Coulomb modeling effectively captures multi-field coupling mechanisms in unsaturated slip-zone soils, providing theoretical foundations for landslide deformation prediction and engineering design under dynamic hydrological conditions. Full article

When excavating roadways in underground mines, stress redistribution within the surrounding rock mass leads to stress concentration and release. Should the concentrated stresses exceed the rock mass’s tensile or shear strength, rock deformation and failure occur. Thus, a knowledge of stress distribution around the roadway is of great significance for revealing the roadway instability mechanism and design support methods. In this work, the powerful complex variable function theory was used to solve the surrounding rock stress around the triple-arched roadway and the analytical results were verified with the on-site stress state. The results show that the tensile stress occurs on the roadway roof and floor under low lateral stress coefficients, while concentrated compressive stress emerges on the two sidewalls. However, the surrounding stress distribution exhibits an opposite characteristic under high stress levels. Beyond five times the roadway radius, the stress in the surrounding rock is unaffected by the roadway and approaches the in-situ stress. For the +1890 m level trackless transport roadway in Kunyang No. 2 phosphate mine, it is further calculated that the minimum stress concentration factor in the rib area of the roadway within the stress relief zone is 0.34, while the maximum stress concentration factor in the concentrated stress zone of the roof, floor, and sidewalls of the roadway is 5.87. The measured stress values of two monitoring points in the surrounding rock of this roadway are fairly consistent with the analytical values, suggesting the complex variable method for solving excavation-induced stresses are effective and reliable. Full article

Ischemic stroke is a leading cause of disability worldwide, often triggered by atherothrombotic or embolic events. A growing body of evidence highlights the role of neuroinflammation as a central mechanism in post-stroke damage, influenced by modifiable systemic risk factors. Emerging evidence suggests that oxidative stress mediates the impact of several modifiable risk factors by activating redox-sensitive pathways (such as NF-κB), impairing nitric oxide bioavailability, and promoting matrix metalloproteinase activity that disrupts vascular integrity and contributes to ischemic injury. In this context, our meta-analysis examined major modifiable risk factors for ischemic stroke, with a particular focus on their shared ability to promote oxidative stress and neuroinflammatory cascades. By emphasizing these redox-dependent mechanisms, our work supports the biological plausibility of exploring antioxidant strategies as complementary approaches to mitigate stroke risk. Hypertension, diabetes, dyslipidemia, smoking, atrial fibrillation, and transient ischemic attacks all contribute to oxidative damage through mechanisms such as endothelial dysfunction, vascular inflammation, and excessive free radical exposure. We searched PubMed, PubMed Central, Web of Science, and Scopus for observational studies published within the last five years, identifying 23 studies (691,524 participants) meeting eligibility criteria. Using a random-effects model, we found significant associations between stroke risk and hypertension (OR = 1.58, 95% CI: 1.28–1.94), smoking (OR = 1.61, 95% CI: 1.13–2.28), type 2 diabetes (OR = 1.53, 95% CI: 1.29–1.81), atrial fibrillation (OR = 1.88, 95% CI: 1.28–2.75), and prior transient ischemic attack (OR = 1.62, 95% CI: 1.24–2.11). These risk factors are known to contribute to systemic inflammation, potentially exacerbating neuroinflammatory cascades post-stroke. Despite limitations such as heterogeneity and low certainty of evidence, our findings reinforce the relevance of targeting inflammation-driven risk factors in stroke prevention strategies and future research. Full article

This research explored the connections between Work Support, Satisfaction with Life, and experienced stress among workers from the automotive sector, with a focus on the indirect influence of job support in the relationship between satisfaction with life and perceived stress using a cross-sectional design. The sample comprised 672 employees (52.98% females). Most participants were aged between 30 and 39 years old (33.48%) or between 40 and 49 years old (29.46%). The primary analysis indicated that Work Support had a partial effect on the connection between Satisfaction with Life and Perceived Stress. Satisfaction with Life was found to directly predict Perceived Stress (B = −0.210, p < 0.001), and there was also a significant indirect effect of Work Support (B = −0.036, 95% CI: −0.051, −0.020). Taken in combination, these results provide several contributions to our comprehension of the mechanisms connecting these constructs, particularly in the car industry. Although Satisfaction with Life showed direct links on Perceived Stress, a significant indirect association via Work Support indicates that a portion of these links are influenced by this route, with potential implications for occupational health. Full article

This study investigates the microscale mechanisms underlying the compressibility of biochar-amended soils through combined discrete element method (DEM) simulations and laboratory consolidation tests. A three-dimensional discrete element model was established based on the MatDEM platform, accounting for the particle crushing process of biochar particles and its impact on soil mechanical properties. The biochar agglomerate particles generated in the simulation exhibit irregular morphology, and particles within different size ranges were selected for investigation. According to the model and experimental results, the average relative error is about 7%. Results demonstrate that moderate biochar content effectively reduces soil compressibility by enhancing load transfer through stable force chains formed by biochar particles, which exhibit larger contact areas and higher stiffness compared to native soil particles. However, when the biochar content exceeds approximately 40%, particle crushing intensifies, particularly under high initial void ratios, leading to increased soil compressibility. Furthermore, a larger initial void ratio weakens interparticle confinement, promotes microcrack propagation, and thereby exacerbates compressive deformation. Biochar fragmentation progresses through three stress-dependent stages: initial compaction (<100 kPa), skeletal damage (100–800 kPa), and crushing saturation (>800 kPa). Increased biochar particle size correlates with higher fragmentation rates, refined particle gradation, and reduced coordination numbers, collectively weakening the soil skeleton and promoting deformation. These findings underscore the importance of optimizing biochar content and applying graded loading strategies to balance enhanced soil performance with material integrity. These findings emphasize the necessity of optimizing biochar application rates to balance enhanced soil performance with resource efficiency, providing critical insights for sustainable geotechnical practices. Full article

Novel coronavirus (SARS-CoV-2) is highly infectious and pathogenic. Novel coronavirus infection can not only cause respiratory diseases but also lead to multiple organ damage through direct or indirect mechanisms, in which the liver is one of the most frequently affected organs. It has been reported that 15–65% of coronavirus disease 2019 (COVID-19) patients experience liver dysfunction, mainly manifested as mild to moderate elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Severe patients may progress to liver failure, develop hepatic encephalopathy, or have poor coagulation function. The mechanisms underlying this type of liver injury are complex. Pathways—including direct viral infection (via ACE2 receptors), immune-mediated responses (e.g., cytokine storm), ischemic/hypoxic liver damage, thrombosis, oxidative stress, neutrophil extracellular trap formation (NETosis), and the gut–liver axis—remain largely speculative and lack robust clinical causal evidence. In contrast, drug-induced liver injury (DILI) has been established as a well-defined causative factor using the Roussel Uclaf Causality Assessment Method (RUCAM). Treatment should simultaneously consider antiviral therapy and liver protection therapy. This article systematically reviewed the mechanism, clinical diagnosis, treatment, and management strategies of COVID-19-related liver injury and discussed the limitations of current research and the future directions, hoping to provide help for the diagnosis and treatment of such patients. Full article

In underground mine roadways, enlarged cross-sections have led to escalating surrounding rock stress, resulting in frequent support failures, elevated accident risk, and increased maintenance costs. However, the potential of fiber reinforcement to improve shotcrete under these high-stress conditions remains under-investigated. To address these issues, this study developed a novel fiber-reinforced cement-based composite using field construction-grade washed sand. The effects of binder-to-material ratios, fiber types (polyvinyl alcohol (PVA), polypropylene (PP), and basalt (BF)), and fiber dosages (1%, 2%, and 3%) were systematically investigated under uniaxial tension, uniaxial compression, and variable-angle shear. Based on the experimental results, an optimal mix formulation was determined via orthogonal experimental design to meet mining operational requirements. The findings demonstrate that fiber incorporation significantly enhances mechanical performance. Notably, PP fiber reinforcement increased the tensile strength by up to 675%, while BF fibers improved compressive strength by up to 198.5%, relative to unreinforced shotcrete. This study provides a theoretical foundation for optimizing fiber-reinforced shotcrete mix designs for mining and offers technical insights for field applications. Full article

Ribosome hibernation is a conserved translational stress response in bacteria, regulated by the hibernation-promoting factor (HPF). Plastid-specific ribosomal protein 1 (PSRP1) is the chloroplast ortholog of bacterial HPF. Although bacterial HPFs have been extensively characterized, both structurally and mechanistically, the physiological roles and mechanisms of PSRP1 in plant chloroplasts remain unclear. Here, we aimed to clarify the role of PSRP1 in chloroplast ribosome hibernation by examining its function under dark-stress conditions in the moss Physcomitrium patens. The PSRP1 knockout mutant exhibited moderate but statistically significant growth defects under both long- and short-day conditions compared to those of the wild-type plants. Moreover, the mutant displayed pronounced growth delay when co-cultured with wild-type plants, indicating a competitive disadvantage. Under dark conditions, wild-type plants exhibit increased PSRP1 protein accumulation, whereas the knockout mutant displayed reduction in chloroplast rRNA content. Notably, although PSRP1 is capable of inducing 100S dimers, we detected no chloroplast 100S dimers either in vivo or in vitro, suggesting a chloroplast-specific ribosome protection mechanism distinct from that of bacteria. These findings reveal PSRP1-mediated chloroplast ribosome protection and could provide new insights into plant stress tolerance. Full article