Search Results (4,957)

As emergent material candidates for extreme environments, refractory high-entropy alloys (HEAs) or refractory multi-principal-element alloys (RMPEAs) comprising refractory metals feature qualities such as high radiation tolerance, corrosion resistance, and mechanical strength. A set of MoNbTi-based RMPEA samples with Al, Cr, V, and Zr additions are prepared by spark plasma sintering and investigated for their response to irradiation using 10 MeV Si⁺ ions with a dose of $1.43\times {10}^{15}$ ions/cm². Positron annihilation spectroscopy and transmission electron microscopy are employed as atomic- and meso- scale techniques to reveal how chemical complexity, nanotwinning, and phase fractions play an important role in radiation-induced defect accumulation and damage tolerance. The study provides experimental evidence of nanotwinning acting as an effective sink for radiation-induced point defects. Full article

Alkaline stress, driven by high pH and carbonate accumulation, results in severe physiological damage in plants. While the molecular mechanisms underlying alkaline tolerance have been partially elucidated in many crops, they remain largely unexplored in wheat. We hypothesize that alkaline stress tolerance in wheat is genotype-dependent. This study employed an integrated multi-omics approach to assess alkaline stress responses, combining genome-wide association study (GWAS) and RNA-seq analyses. Systematic phenotyping revealed severe alkaline stress-induced root architecture remodeling—with 57% and 73% length reductions after 1- and 3-day treatments, respectively—across 258 accessions. Analysis of the GWAS results identified nine significant alkaline tolerance QTLs on chromosomes 1A, 3B, 3D, 4A, and 5B, along with 285 associated candidate genes. Using contrasting genotypes—Dingxi 38 (tolerant) and TDP.D-27 (sensitive)—as experimental materials, physiological analyses demonstrated that root elongation was less inhibited in Dingxi 38 under alkaline stress compared to TDP.D-27, with superior root integrity observed in the tolerant genotype. Concurrently, Dingxi 38 exhibited enhanced reactive oxygen species (ROS) scavenging capacity. Subsequent RNA-seq analysis identified differentially expressed genes (DEGs) involved in ion homeostasis, oxidative defense, and cell wall remodeling. Integrated GWAS and RNA-seq analyses allowed for the identification of seven high-confidence candidate genes, including transcription factors (MYB38, bHLH148), metabolic regulators (ATP-PFK3), and transporters (OCT7), elucidating a mechanistic basis for adaptation to alkaline conditions. These findings advance our understanding of alkaline tolerance in wheat and provide candidate targets for molecular breeding of saline- and alkaline-tolerant crops. Full article

Hepatic oxidative stress is a key driver in liver injury pathogenesis, with D-galactose (D-gal) modeling serving as an established inducer of accelerated oxidative damage. Silibinin (SLB), a flavonolignan from milk thistle, shows therapeutic promise through potent antioxidant activity and gut–liver axis modulation. This study investigated whether the hepatoprotective effect of SLB against oxidative stress depends on gut microbiota regulation. Using mouse models with gut microbiota ablation by oral antibiotics or direct oxidative stress induction by D-gal (150 mg/kg), SLB treatment (200 mg/kg) was administered. The protective mechanisms were evaluated through the Nrf2/ARE pathway, target gene expression, gut microbiota profiling, and cecal metabolomics. Results demonstrated that SLB significantly alleviated D-gal-induced hepatic oxidative stress (e.g., reduced MDA by 33.3%), but this protection was markedly weakened after antibiotic-induced microbiota depletion (e.g., a loss of efficacy exceeding 50%). Integrated omics revealed that antibiotics caused a severe reduction in unclassified_Muribaculaceae (a butyrate producer, decreased by 80%), impairing butyrate-mediated Nrf2/Keap1 activation. Simultaneously, the absence of Parabacteroides led to accumulated primary bile acids and inhibited secondary bile acid production (e.g., taurochenodeoxycholate reduced by 75%), further disrupting redox homeostasis. Conclusion: Silibinin’s mitigation of hepatic oxidative stress is gut microbiota-dependent, highlighting the therapeutic potential of microbiota-targeted antioxidant strategies for oxidative stress-related pathologies. Full article

Alzheimer’s disease, a neurodegenerative brain disorder leading to the progressive decline in cognitive functions, is the most common type of dementia. The main risk factor for its development is aging. Recent studies indicate that cellular senescence mechanisms are among the major factors in a heterogeneous aging process. Cellular senescence is characterized by a permanent proliferative arrest. Many factors might initiate senescence, for example, damage of DNA, shortening of telomeres, dysfunction of mitochondria, and oncogene activation. These processes lead to alterations in the morphology and function of senescent cells. Research is still ongoing to identify one universal marker that could detect senescent cells and distinguish them from other non-proliferating cells. Those cells are involved in age-related pathologies through many heterogeneous processes, including secretion of pro-inflammatory senescence-associated secretory phenotype factors, which affect the brain differently. Alzheimer’s disease is an example of a neurodegenerative condition connected to cellular senescence. Senescent cells have been demonstrated to accumulate near Aβ plaques and neurofibrillary tangles. In this review, the multifactorial connection between Alzheimer’s disease and cellular senescence is discussed, including topics such as senescence of astrocytes, defective mitochondria, dysregulation of cellular autophagy, and the role of senescent microglia. Full article

Fractured rock masses in cold regions are subject to long-term seasonal freeze–thaw cycles. To investigate the fatigue damage characteristics of sandstone with different fracture inclinations under freeze–thaw cycling conditions, samples containing fractures of varying inclinations were prepared using sandstone from Altay, Xinjiang. After vacuum saturation and freeze–thaw cycling treatment (−30 °C to 30 °C), uniaxial cyclic loading tests were conducted to analyze strain, elastic modulus, Poisson’s ratio, and damage variables. The results showed that under cyclic loading, the strain of the sandstone exhibited a “stepwise accumulation” characteristic, with peak and residual strain increasing with the progression of the cycle. Among them, the specimen with a fracture angle of 45° exhibited the fastest strain increase before failure. The peak elastic modulus showed a “continuous decrease within each stage and an initial increase followed by a decrease between stages,” while the residual elastic modulus continued to decrease, with both experiencing a sudden, sharp drop at the end of the cycle. The peak Poisson’s ratio decreases with the number of cycles in the early stage, then transitions to logarithmic growth in the later stage, rapidly increases near failure, and finally, the residual Poisson’s ratio in the final cycle exceeds the peak Poisson’s ratio; the evolution of damage variables exhibits an S-shaped three-stage characteristic, with the initial stage showing an irreversible deformation growth rate exceeding 10% due to compaction. In the middle stage, it grows steadily due to microcrack propagation, and in the final stage, it approaches 1. Samples with steep inclination angles exhibit earlier damage initiation and faster growth rates. The study reveals that crack inclination angle influences the evolution rhythm by regulating the proportion of compaction and shear damage, providing a theoretical basis for assessing the engineering stability of fractured rocks in cold regions. Full article

Traditional pseudo-static loading tests fail to capture the unique characteristics of special ground motions, limiting their ability to accurately evaluate the seismic performance of steel-reinforced concrete (SRC) columns. In this study, eight SRC columns were subjected to pseudo-static tests using far-field, near-field, and traditional loading protocols to investigate their structural response under different seismic scenarios. The results show that far-field loading, characterized by repeated large displacement cycles, leads to increased damage accumulation, reduced hysteresis curve fullness, greater bearing capacity loss, significant stiffness degradation, and diminished ductility and energy dissipation. In contrast, near-field loading—dominated by an initial extreme displacement—results in fewer but less developed cracks and a larger concrete crushed zone at failure. The severe initial damage under near-field loading causes a noticeable decline in stiffness and strength during subsequent cycles. During the second loading stage, both the peak load and post-peak deformation capacity are further reduced, significantly impairing the columns’ ability to resist additional seismic demands. These findings highlight the critical role of loading history in shaping the seismic behavior of SRC composite columns. Full article

Gangliosides are essential for membrane functions, cell recognition, and maintenance of the nervous system. GM2 gangliosidosis is a group of rare genetic lysosomal storage diseases that includes Tay-Sachs disease (TSD), Sandhoff disease (SD), and AB variant. TSD and SD are characterized by deficient β-N-acetyl-hexosaminidase activity. This leads to decreased catabolism of β-N-acetyl-hexosamine-containing ganglioside GM2 in the lysosomes, damage to cells and tissues, and severe neurological symptoms. GM2 is a major ganglioside accumulating in TSD and SD, and is synthesized from GM3 by β1,4-N-acetylgalactosaminyltransferase 1 (B4GALNT1, GM2 synthase). Therapies under development for GM2 gangliosidosis include adeno-associated virus gene therapy, enzyme replacement, and substrate reduction therapy (SRT). The goal of this work was to express and purify human B4GALNT1, characterize its activity, and explore its structural features by protein modeling and substrate docking. We used a panel of synthetic compounds to study their potential inhibition of B4GALNT1 activity. This work can serve to develop SRT for GM2 gangliosidosis. Full article

This study assessed the impact of untreated wastewater discharge in the Danube River on four native fish species: barbel (Barbus barbus), vimba bream (Vimba vimba), perch (Perca fluviatilis), and white bream (Blicca bjoerkna). Biomarkers of exposure and effect were evaluated, including metal and metalloid bioaccumulation in gills, liver, and gonads, DNA damage (comet assay), chromosomal abnormalities (micronucleus assay), liver enzyme activities (ALT, AST), and erythrocyte maturation. White bream showed the highest genotoxic damage (TI% = 22.57), particularly in liver tissue, indicating high sensitivity to pollution. Perch had elevated DNA damage in blood (TI% = 22.69) and strong biomarker responses, likely due to its predatory behavior. Barbel displayed notable DNA damage in gills (TI% = 30.67) and liver (TI% = 20.35), aligning with sediment exposure due to its benthic habits. Vimba bream had the lowest responses, possibly reflecting reduced exposure or resilience. Element accumulation varied across tissues and species, with perch showing the highest overall levels. Hepatic enzyme activities (highest values: ALT = 105.69 in barbel; AST = 91.25 in white bream) and changes in erythrocyte profiles supported evidence of physiological stress. Integrated Biomarker Response (IBR) analysis identified white bream as the most sensitive species, followed by perch and barbel. These results emphasize the value of multi-species biomonitoring and the importance of species-specific traits in freshwater ecotoxicology. Full article

Soil salinization critically threatens global agricultural productivity by impairing plant growth and soil fertility. This study investigated the potential of a consortium, comprising Acinetobacter calcoaceticus DP25, Staphylococcus epidermidis DP28, and Enterobacter hormaechei DP29, to enhance the saline–alkali tolerance of alfalfa and improve soil properties. The experiments comprised five germination treatments (saline control, each strain alone, consortium) and three pot treatments (non-saline control, saline control, consortium). Under saline–alkali stress, co-inoculation with the consortium significantly (p < 0.05) increased alfalfa seed germination rates, emergence rates, and biomass (shoot and root dry weight), while promoting root development. Physiological analyses revealed that the bacterial consortium mitigated stress-induced damage by enhancing photosynthetic efficiency, chlorophyll content, and antioxidant enzyme activities (superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)), while decreasing malondialdehyde (MDA) levels. Moreover, the inoculant improved osmoprotectant accumulation (soluble sugars, soluble proteins, and proline) and modulated soil properties by reducing pH and electrical conductivity (EC), while elevating nutrient availability and soil enzyme activities. Correlation and principal component analyses (PCA) confirmed strong associations among improved plant growth, physiological traits, and soil health. These findings demonstrate that the bacterial consortium effectively alleviates saline–alkali stress in alfalfa by improving soil health, offering a sustainable strategy for ecological restoration and improving agricultural productivity in saline–alkali regions. Full article

Neurodegenerative diseases are associated with the senescence of functional neurons, which hampers brain functions. These diseases are caused by the accumulation of reactive oxygen species, reactive nitrogen species, cholinesterase malfunction, neuronal inflammation, and mitochondrial dysfunction. The incidence of neurodegenerative disease has been on the rise. Current therapeutic interventions are expensive, exhibit poor efficacy, and have numerous side effects. Several studies have explored the potential of crucial dietary substances rich in antioxidants and micronutrients in alleviating the clinical manifestations of such deadly diseases. Consumption of sufficient antioxidants, fatty acids, and polyphenols in regular diets delays the onset of neurodegenerative diseases. Several medicinal plants, such as Withania somnifera, Curcuma longa, Panax ginseng, Ginkgo biloba, aloe vera, Punica granatum, and various phytoextracts, contain such micronutrients in reasonable amounts. Specific dietary interventions, supplements, and patterns such as the Mediterranean-DASH intervention for neurodegenerative delay, ketogenic, paleolithic, and Wahls elimination diets have been beneficial in neurodegenerative conditions. These diet interventions and other functional foods can be an attractive, non-invasive, and inexpensive approach in the management and prevention of neurodegenerative conditions. This review discusses potential pharmacological bases involved in neurodegeneration, covering mitochondrial damage, impaired mitophagy, neuroinflammation, ferroptosis, glymphatic clearance dysfunction, brain–body interactions, and disruption of vagus nerve stimulation. The review further highlights clinical diet interventions and assorted functional foods, including fruits, vegetables, vitamins, specific supplements, and special diets, for neurodegenerative conditions. The discussion extends insights into clinical research and trials of these functional foods under neurodegenerative conditions. Overall, dietary interventions show promise in the prevention and management of neurodegenerative conditions. Full article

Silent information regulator type 1 (SIRT1), a NAD⁺-dependent deacetylase, is a central regulator of cancer cell adaptation to oxidative stress and senescence. By deacetylating redox-sensitive transcription factors, such as p53, FOXOs, PGC-1α, and NF-κB, SIRT1 suppresses apoptosis, delays senescence, enhances mitochondrial function, and attenuates pro-inflammatory senescence-associated secretory phenotypes. These mechanisms collectively promote tumor progression and contribute to resistance to therapy. Reactive oxygen species (ROS), long regarded as damaging byproducts, are now recognized as critical modulators of cancer biology. Although moderate ROS levels drive oncogenic signaling, excessive ROS accumulation triggers DNA damage, oxidative stress, and senescence. To survive these hostile conditions, cancer cells reinforce antioxidant defenses and exploit the NAD⁺–SIRT1 axis to maintain redox balance and evade senescence. The objective of this review was to provide an integrated framework linking SIRT1-mediated deacetylation to redox regulation and senescence control in cancer. We synthesized mechanistic insights into SIRT1 interactions with its substrates, highlighted cancer type-specific functions in ovarian, breast, liver, lung, and gastrointestinal malignancies, and critically evaluated the dual role of SIRT1 as both a longevity factor and an oncogenic driver. Finally, we explored the therapeutic implications of the pharmacological inhibition of SIRT1 as a strategy to restore senescence, increase ROS vulnerability, and overcome therapy resistance. This synthesis underscores the potential of the SIRT1–redox–senescence axis as a promising target in precision oncology. Full article

Alpha-1 antitrypsin deficiency (AATD) represents a paradigmatic genetic disorder with well-characterized hepatic manifestations but relatively underexplored pulmonary implications. While liver involvement has been extensively reviewed, the underlying mechanisms of lung disease progression remain poorly understood, particularly regarding immunological pathways and inflammatory processes. The pathophysiology involves defective alpha-1 antitrypsin (AAT) production, including AAT variants that induce neutrophil elastase activity, causing progressive alveolar destruction and sustained inflammation, leading to emphysema, as one of the main components of chronic obstructive pulmonary disease (COPD). AATD and smoking represent major risk factors for COPD, the third leading cause of death worldwide at present. In AATD patients, neutrophils, which constitute the majority of circulating leukocytes, become dysregulated. Under normal conditions, cells perform essential functions, including phagocytosis and neutrophil extracellular trap formation (NETosis); in AATD, however, they accumulate excessively in alveolar spaces due to impaired elastase control. The accumulation of Z-AAT polymers within epithelial cells creates a pathological cycle, acting as chemoattractants that sustain pro-inflammatory responses and contribute to chronic obstructive pulmonary disease development. In addition, monocytes, representing a smaller fraction of leukocytes, migrate to inflammatory sites and differentiate into macrophages while secreting AAT with anti-inflammatory properties. However, in PiZZ patients, this protective mechanism fails, as polymer accumulation within cells reduces both AAT secretion and the number of protective human leukocyte antigen(HLA)-DR-monocyte subsets. In particular, macrophages demonstrate remarkable plasticity, switching between pro-inflammatory M1 (classically activated macrophages) and tissue-repairing M2 (alternatively activated macrophages) phenotypes based on environmental cues. In AATD, this adaptive capability becomes compromised due to intracellular polymer accumulation, leading to impaired phagocytic function and dysregulated cytokine production and ultimately perpetuating chronic inflammation and progressive tissue damage. Recent advances in induced pluripotent stem cell (iPSC) technology have facilitated alveolar epithelial cell (AEC) generation, in addition to the correction of AATD mutations through gene editing systems. Despite the limitations of AAT correction, iPSC-derived organoid models harboring AATD mutations can deliver important insights into disease pathophysiology, while gene editing approaches help demonstrate causality between specific mutations and observed phenotypes. Therefore, in this review, we investigated recent studies that can serve as tools for gene editing and drug development based on recently developed iPSC-related technologies to understand the pathogenesis of AATD. Full article

The harsh environment in Arctic regions presents significant challenges to ship stability, particularly when ice accumulation and hull damage occur simultaneously, potentially increasing the risk of instability. This study addresses this critical issue by proposing a comprehensive stability assessment framework for ships operating in Arctic regions. Utilizing the DTMB-5415 ship model, the evaluation integrates both static and dynamic stability under combined ice accumulation and damage conditions. Firstly, an ice accumulation prediction model was developed to estimate ice accumulation over various durations. Subsequently, the static stability of damaged ships with ice accumulation was evaluated. Computational Fluid Dynamics (CFD) simulations were then conducted to calculate roll damping coefficients and analyze the effects of damage location and ice accumulation on free roll decay behavior. A single-degree-of-freedom (SDOF) roll motion model was constructed, incorporating roll damping coefficients and wave excitation moments to simulate roll responses in random wave environments. Extreme value prediction was employed to estimate the short-term extreme response distribution of roll motions. The results indicate that ship stability decreases significantly when ice accumulation and hull damage occur simultaneously. This integrated framework provides a systematic foundation for evaluating ship stability in the Arctic environment, specifically accounting for the combined effects of ice accretion and hull damage. Full article

A finite element simulation was conducted to analyze the thermal damage caused by a 532nm nanosecond pulsed laser on a CCD detector. A three-dimensional model was developed to study the temperature field variations within the detector. The simulation was centered on the laser-induced temporal progression of thermal damage in the CCD. Results showed that higher laser fluence led to increased heat accumulation, resulting in the expansion of the thermal damage area. Different thermal damage patterns were observed in the light sensor region and the light-shielded region. In the light sensor region, the melting of the silicon substrate expanded more in the transverse direction compared to the longitudinal direction with increasing laser fluence, while damage in the light-shielded region extended from the edges towards the center as laser fluence increased. These distinct damage patterns were attributed to different energy deposition patterns and structural differences between the light sensor region and the light-shielded region. Full article

Cadmium (Cd) is a major co-occurring, highly toxic heavy metal in uranium (U) tailings that poses synergistic risks to ecological and human health. This study aimed to investigate the effects of Cd on U accumulation and phytotoxicity in plants using radish (Raphanus sativus L.) as a model organism under hydroponic conditions. Treatments included U alone (25 μM and 50 μM), low-concentration Cd alone (10 μM), and U + Cd co-treatments (U25 + Cd and U50 + Cd). Results revealed that exposure exerted minimal phytotoxicity, whereas U treatment induced severe root toxicity, characterized by cell death and an 11.9–63.8% reduction in root biomass compared to the control. Notably, U + Cd co-treatment exacerbated root cell death and biomass loss relative to U alone. Physiologically, elevated U concentrations significantly increased superoxide anion radical (O₂⁻) production rate, hydrogen peroxide (H₂O₂) content, and malondialdehyde (MDA)—a marker of oxidative damage—inducing cellular oxidative stress. Under U + Cd co-treatment, O₂⁻ production, H₂O₂ content, and MDA levels in radish roots were all significantly higher than under U alone. Concurrently, activities of antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], and peroxidase [POD]) were lower in U + Cd-treated roots than in U-treated roots, further exacerbating oxidative damage. Regarding heavy metal accumulation, the content of U in radish under U + Cd treatment was significantly higher than that in the U treatment group. However, no significant differences were observed in the expression of uranium (U)-related transport genes (MCA1, MCA3, and ANN1) between the single U treatment and the U-Cd co-treatment. Notably, the inhibitory effect of NRAMP3—a gene associated with Cd transport—was weakened under the coexistence of U, indicating that U exacerbates toxicity by promoting Cd transport. This study shows that Cd appears to enhance the accumulation of U in radish roots and exacerbate the phytotoxicity of U. Full article