Search Results (102,575)

Gemykibivirus, an emerging single-stranded DNA (ssDNA) virus of the recently established genus in the family of Genomoviridae, had been discovered in human blood and cerebrospinal fluid and a variety of other body fluids. However, the molecular mechanisms of gemykibivirus entrance into the host cells and its pathogenicity remain poorly understood. To investigate the host response of gemykibivirus, we used an infectious clone of gemykibivirus previously established through molecular biology techniques to rescue virus in HEK293T cells and analyzed the changes in the host transcriptome during the infection period by RNA-Seq. Our findings indicate that gemykibivirus can both express viral proteins and accomplish replication, and high-throughput transcriptome analysis identified a total 1732 significantly different genes. Functional enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for differentially expressed genes (DEGs) showed gemykibivirus involving several important pathways, including MAPK signaling pathway, Chemical carcinogenesis-reactive oxygen species and Oxidative phosphorylation. Interestingly, mitochondrial DNA-encoded mRNAs exhibited varying levels of upregulation, suggesting that gemykibivirus may be involved in mitochondrial fission and the regulation of mitochondrial function. Subsequently, a series of experiments proved that gemykibivirus can lead an increase in mitochondrial DNA copy number, promote the release of mtDNA into the cytoplasm, enhance reactive oxygen species production and trigger other cellular antiviral responses. Overall, we lay a foundation for revealing the relationship between Gemykibivirus and human diseases through mitochondrial functional alterations. Full article

Electrochemical mechanical polishing is a critical technology for improving the surface quality of silicon carbide (SiC) substrates. However, the fundamental electrochemical corrosion mechanism of the SiC substrate remains incompletely understood. In this study, the electrochemical corrosion behavior of the SiC substrate is explored through comprehensive experiments and molecular dynamics simulations. Key findings demonstrated that the 4H-0° SiC exhibited the highest corrosion rate in a 0.6 mol/L NaCl electrolyte. The corrosion rate increased as the voltage rose within the range of 2 to 20 V. When the voltage was between 20 and 25 V, the system entered the stable passivation region, while when the voltage was 25 to 30 V, partial dissolution of the surface oxide layer occurred. Molecular dynamics simulations further revealed that both amorphization degree and reaction depth on the SiC surface showed a decreasing trend at elevated voltages, suggesting a corresponding reduction in the corrosion rate when the voltage exceeded the optimal range. OH⁻, O²⁻, and •OH generated by the electrolysis of water during electrochemical corrosion would rapidly react with the surface of the SiC anode, and subsequently form a SiO₂ modified layer. Moreover, these atomistic insights establish a scientific foundation for achieving superior surface integrity in large-diameter SiC substrates through optimized electrochemical mechanical polishing processes. Full article

Background: Tendinopathy is a degenerative condition caused by mechanical overload, accounting for approximately 30% of musculoskeletal healthcare cases. It progresses through a process characterized by collagen disorganization, altered vascularization, and neuronal ingrowth. Traditional conservative treatments, such as therapeutic exercises, non-steroidal anti-inflammatory drugs, and physical therapies, are useful, but their effectiveness is sometimes only partial and there is a need to search for new potential solutions. Recent interest in oxygen–ozone (O₂-O₃) therapy stems from preliminary observations suggesting potential anti-inflammatory and regenerative effects. Nevertheless, its clinical role remains speculative and warrants thorough investigation beyond anecdotal evidence. Considering the heterogeneity of clinical presentations and treatment responses among patients, O₂-O₃ therapy has been proposed as a promising tool for tailoring personalized treatment strategies for tendinopathy. This review critically appraises the available literature concerning the mechanistic rationale and clinical applications of O₂-O₃ therapy in tendinopathy, with attention to both its theoretical underpinnings and the quality of empirical evidence. Methods: A literature search was conducted on O₂-O₃ therapy for tendinopathy using PubMed, Cochrane, and Embase, filtering for full-text articles published between 2004 and 2024. Recent clinical trials were included irrespective of evidence level, while excluding systematic reviews, duplicates, and irrelevant studies. Results: Ozone has been shown to modulate oxidative stress, promote neovascularization, and suppress pro-inflammatory cytokines. Both clinical and in vivo studies indicate that O₂-O₃ therapy relieves pain, enhances tendon healing, and improves biomechanical properties. Some comparative studies suggest that O₂-O₃ therapy might provide more sustained symptoms control than corticosteroids, but the heterogeneity of follow-up durations and outcome measures prevents definitive conclusions. Conclusions: O₂-O₃ therapy emerges as a potentially valuable adjunct in the management of chronic tendinopathy, particularly in cases unresponsive to conventional treatments. However, its clinical role remains to be clearly defined and its possible role in personalized medicine needs further exploration, particularly in relation to patient stratification and individualized treatment protocols. Further high-quality randomized controlled trials are warranted to validate its efficacy, determine long-term outcomes, and standardize treatment protocols to ensure safety and reproducibility. Full article

An imbalance of pro-oxidants and antioxidants causes oxidative stress, contributing to various chronic diseases. Lactic acid bacteria (LAB) have recognised antioxidant activities that can help reduce oxidative stress. This study isolated fifty LAB strains from various fermented foods and raw vegetable products and evaluated their radical scavenging activity using DPPH and ABTS assays. Among them, four strains Lacticaseibacillus paracasei D2, Lacticaseibacillus rhamnosus JL, Latilactobacillus sakei F1, and Weissella cibaria JLK were selected and assessed for their tolerance to hydrogen peroxide (H₂O₂). Antioxidant mechanisms were investigated at the molecular level. Genome analysis revealed that the catalase gene (katE) was present in L. sakei F1, while it was absent in other strains. After exposure to H₂O₂, expression of genes associated with various antioxidant systems in the bacterial strains were measured at different growth phases. The results revealed that NADH oxidase-peroxidase, thioredoxin, and glutathione peroxidase systems play a role in antioxidant activity in L. paracasei D2 and L. rhamnosus JL strains, while genes associated with these systems in L. sakei F1 and Weissella cibaria JLK strains showed no upregulation. A different antioxidant mechanism was observed in L. sakei F1. The findings suggest that the four LAB strains are promising probiotic candidates with significant enzymatic or non-enzymatic antioxidant properties, which may aid in developing antioxidant-rich functional foods. Full article

With the low-carbon transformation of the steel industry, using low-carbon raw materials is one of the important ways to achieve the “dual carbon” goals. Pellets have great physical and chemical properties as low-carbon furnace materials, which can significantly reduce blast furnace carbon emissions, exhibiting favorable overall environmental benefits. Increasing their proportion in the furnace is one of the important measures the steel industry can take to reduce carbon emissions. Binders play a critical role in the pelletizing process, and their properties directly influence pellet quality, thereby affecting the subsequent blast furnace smelting process. Compared with traditional bentonite, organic binders have become a potential alternative material due to their environmental friendliness, renewability, and ability to significantly reduce silica and alumina impurities in pellets while improving the iron grade. This work systematically elucidates the mechanism of organic binders, which primarily rely on the chemical adsorption of carboxyl groups and the hydrogen bonding of hydroxyl groups to enhance pellet strength, and then provides three typical examples of organic binders: lignosulfonate, carboxymethyl cellulose (CMC), and carboxymethyl starch (CMS). The common characteristic of these organic binders is that they are derived from renewable biomass through chemical modification, which is a derivative of biomass with renewable and abundant resources. However, the main problem with organic binders is that they burn and decompose at high temperatures. Current research has achieved technological breakthroughs in pellet quality by combining LD sludge, low-iron oxides, and nano-CaCO₃, including improved iron grade, reduced reduction swelling index (RSI), and enhanced preheating/roasting strength. Future studies should focus on optimizing the molecular structure of organic binders by increasing the degree of substitution of functional groups and the overall degree of polymerization. This approach aims to replace traditional bentonite while exploring applications of composite industrial solid wastes, effectively addressing the high-temperature strength loss issues in organic binders and providing strong support for the steel industry to achieve the green and low-carbon goals. Full article

The widespread application of WE43 (Mg-4Y-2Nd-1Gd-0.5Zr) alloy castings in aerospace components is hindered by the frequent formation of defects such as cracks, pores, and especially yttria inclusions. These defects necessitate subsequent welding. However, using homologous WE43 filler wires often exacerbates these issues, leading to high crack susceptibility and reintroduction of inclusions. Herein, we propose a novel strategy of tailoring Y content in filler wires to achieve high-quality welded joint of WE43 sand castings. Systematic investigations reveal that reducing Y content to 2 wt.% (WE23) effectively suppresses oxide inclusion formation and significantly enhances the integrity of the joint. The fusion zone microstructure evolves distinctly with varying Y levels: grain size initially increases, peaking at 24 μm with WE43 wire, then decreases with further Y addition. Moreover, eutectic compounds transition from a semi-continuous to a continuous network structure with increasing Y content, deteriorating mechanical performance. Notably, joints welded with WE23 filler exhibit minimal performance loss, with ultimate tensile strength, yield strength, and elongation reaching 93.0%, 98.0%, and 97.4% of the sand-cast base metal, respectively. The underlying strengthening mechanisms and solute-second phase relationships are elucidated, highlighting the efficacy of optimizing Y content in welding wire design. This study provides valuable insights toward defect-free welding of high-performance Mg-RE alloy castings. Full article

Frequent and increasingly severe freezing events threaten citrus production in northern Florida, underscoring the need for strategies that enhance freezing resilience in citrus cultivars. Grafting scions onto tolerant rootstocks provides a physiologically integrative approach to improve stress tolerance. This study aims to elucidate how these interactions modulate physiological and metabolic responses under freezing stress, thereby identifying mechanisms that contribute to enhanced freeze resilience in citrus. Here, we grafted Citrus reticulata (cv. UF-950) onto eight rootstocks (Bitters, Blue-1, C-146, Sour Orange, UFR07TC, UFR09TC, UFR5, and US942) to evaluate scion–rootstock interactions under normal (20 °C) and freezing (−6 °C) conditions. Freezing stress caused a sharp increase in oxidative stress markers, lipid peroxidation, and membrane damage while reducing photosynthetic performance across most combinations. Antioxidant capacity, osmolyte accumulation, and carbon–nitrogen metabolic responses varied significantly among rootstocks, revealing strong genotype-dependent modulation of scion physiology. Among the tested combinations, UF-950 grafted onto UFR5 displayed the highest freezing tolerance, characterized by robust activation of antioxidant enzymes, elevated proline and glycine betaine accumulation, reduced oxidative damage, and sustained carbon–nitrogen metabolic fluxes under freezing stress. These results demonstrate that rootstock genotype governs the extent of scion defense activation and metabolic homeostasis under freezing conditions. Our findings identify UFR5 as a promising rootstock for enhancing freezing resilience in citrus and provide mechanistic insight into how scion–rootstock interaction orchestrates integrative stress tolerance pathways. Future work should focus on multi-omics dissection of rootstock-mediated signaling networks and long-term field validation to optimize rootstock selection for enhanced cold resilience under variable climatic conditions. Full article

The potential for creating composite cements by incorporating fly ash is demonstrated. Analysis revealed that the fly ash examined consists of 69.66 wt. % silicon oxide, 21.34 wt. % aluminum oxide, 1.57 wt. % calcium oxide and 2.78 wt. % iron oxide. Fly ash mainly consists of quartz (SiO₂), goethite (FeO(OH)) and mullite (3Al₂O₃·2SiO₂). The properties of the cement composition containing 5 to 25 wt. % fly ash were studied. Incorporating fly ash enhances system dispersion, promotes mixture uniformity, and stimulates the pozzolanic reaction. Compositions of composite cements consisting of 90% CEM I 42.5 and 10% fly ash were developed. The cement stone based on the obtained composite cement had a compacted structure with a density of 2.160 g/cm³, which is 9.4% higher than the control sample. It is shown that when composite cement containing 10% fly ash interacts with water, hydration reactions of cement minerals (C₃S, C₂S, C₃A and C₄AF) begin first. This is accompanied by the formation of hydrate neoplasms, such as calcium hydroxide (Ca(OH)₂) and calcium hydrosilicates (C-S-H). Fly ash particles containing amorphous silica progressively participate in a pozzolanic reaction with Ca(OH)₂, leading to the formation of additional calcium hydrosilicates phases. This process enhances structural densification and reduces the porosity of the cement matrix. After 28 days of curing, the compressive strength of the resulting composite cements ranged from 42.1 to 54.2 MPa, aligning with the strength classes 32.5 and 42.5 as specified by GOST 31108-2020. Full article

Exposure to hypoxia at high altitudes is significantly associated with impairments in learning and memory functions, as well as abnormalities in neuronal function and synaptic plasticity. Recent research has indicated that mitochondrial reactive oxygen species (mtROS) play a role in regulating microglial activation and mediating neurotoxic damage in the hippocampal CA1 region. Nicotinamide riboside (NR), upon absorption, is rapidly converted into nicotinamide adenine dinucleotide (NAD+), which is involved in the production of mitochondrial adenosine triphosphate (ATP). The potential of NR to protect dendritic spine plasticity in hippocampal CA1 neurons following hypoxia exposure, potentially through the inhibition of microglial activation, warrants further investigation. To this end, a mouse model simulating hypoxia at an altitude of 6000 m over a two-week period, along with a BV2 cells and conditional co-culture of BV2 cells and HT22 cells 1%O₂ hypoxia model, was developed. Behavioral assessments indicated that, relative to the normoxia group, mice subjected to hypoxia exhibited a significant reduction in the time spent in the target quadrant, the distance traveled within the target quadrant, the number of platform crossings, and the novel object recognition index. Furthermore, Golgi staining revealed a marked decrease in the density of dendritic spines in the hippocampal CA1 region in the hypoxia-exposed mice compared to the normoxia group. Subsequently, A daily dosage of 400 mg/kg of NR was administered for two weeks and 0.5 mM NR was used in a conditional co-culture model. Results demonstrated that, in comparison to the hypoxia group, the group receiving combined hypoxia and NR treatment showed significant improvements in the time spent in the target quadrant, the distance traveled within the target quadrant, the number of platform crossings, the novel object recognition index, and the density of dendritic spines in the hippocampal CA1 region. Additionally, transmission electron microscopy indicated a significant increase in the synaptic density of hippocampal neurons in the combined hypoxia exposure and NR treatment group compared to the hypoxia exposure group. Simultaneously, when compared to the hypoxia group, the combination of hypoxia and NR treatment resulted in an increased concentration of mitochondrial ATP. This treatment also partially restored mitochondrial membrane integrity, reduced mtROS levels, decreased the percent of Iba1⁺CD68⁺Iba1⁺ microglia, and lowered the interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), and inducible nitric oxide synthase (iNOS) mRNA levels. These findings indicate that NR treatment may mitigate neurotoxic damage in the hippocampal CA1 region induced by hypoxia exposure, primarily through the attenuation of microglial activation and the reduction in mtROS production. Full article

Background/Objectives: The rapid progression of stroke often results in irreversible brain damage and poor outcomes when treatment is delayed. Prophylactic administration of FAD012 (3,5-dimethyl-4-hydroxycinnamic acid), a synthetic derivative of ferulic acid (FA), has demonstrated cerebroprotective effects in ischemic models through antioxidant and endothelial protective mechanisms. This study investigated the effects of FAD012 on cerebral infarction and blood–brain barrier (BBB) integrity using a photothrombotic stroke model in rats. Methods: Male Sprague Dawley rats received a single intraperitoneal injection of FAD012 or FA (100 or 300 mg/kg) 60 min prior to stroke induction. Under isoflurane anesthesia, the middle cerebral artery was exposed, and stroke was induced by intravenous administration of Rose Bengal followed by green laser irradiation. Cerebral blood flow (CBF) was monitored by laser Doppler flowmetry. BBB disruption was evaluated by Evans Blue extravasation and immunohistochemistry for tight junction (TJ) proteins. Results: Control rats exhibited extensive infarction, BBB disruption, and reduced expression of claudin-5, occludin, and ZO-1, along with fragmented collagen IV. In contrast, FAD012 (300 mg/kg) significantly attenuated CBF reduction, reduced infarct size, preserved BBB integrity, and maintained TJ protein expression, with greater efficacy than an equivalent dose of FA. FAD012 also preserved the expression and phosphorylation of endothelial nitric oxide synthase (eNOS), a key marker of vascular integrity. The CBF-preserving effect of FAD012 was completely abolished by N^G-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor. Conclusions: These findings suggest that FAD012 protects endothelial function, thereby contributing to the maintenance of CBF and BBB integrity, supporting its potential as a prophylactic therapeutic agent for ischemic stroke. Full article

Foodborne illness outbreaks from fresh produce underscore the urgent demand for sanitizing strategies that ensure safety while minimizing harmful by-products from high-dose chemical disinfectants such as sodium hypochlorite (NaOCl). Low-concentration combinations of organic acids and washing sanitizers were systematically evaluated to identify synergistic antibacterial effects, and citric acid (CA) was found to markedly potentiate the activity of NaOCl against Salmonella Typhimurium through a sequential assault on the cell envelope. A low-dose combination of sub-inhibitory concentrations (1/2 MIC of CA and 1/4 MIC of NaOCl) exhibited robust synergy, achieving a >6 log CFU/cm² reduction in the pathogen on a cherry tomato model within 3 min. Moreover, this synergistic entry leads to profound disruption of membrane integrity, resulting in leakage of nucleic acids and proteins, extensive oxidative damage, hyperpolarization, and cell lysis, as confirmed by electron and confocal microscopy together with physicochemical assays. Mechanistic investigation revealed that oxidative damage from NaOCl amplified CA-induced membrane acidification and permeability, facilitating deeper sanitizer penetration and accelerating envelope destruction. Collectively, these findings uncover a membrane-targeted synergistic mechanism, providing a solid scientific basis for the development of novel, low-residue, and high-efficacy food safety interventions. Full article

This study investigates the structural, morphological, and gas-sensing properties of pure and strontium-doped lanthanum cobaltite (La_1−xSr_xCoO₃) perovskite thin films obtained by Pulsed Electron Deposition (PED). This sustainable ablative technique successfully produced high-quality, dense, nanocrystalline films on Si and MgO substrates, demonstrating excellent stoichiometric transfer from the source targets. A comprehensive analysis using XRD, SEM, TEM, AFM, and XPS was conducted to characterize the films. The results show that Sr-doping significantly refines the microstructure, leading to smaller crystallites and a more uniform surface topography. Gas sensing measurements, performed in a temperature range of 100–450 °C, revealed that all films exhibit a characteristic p-type semiconductor response to nitrogen dioxide (NO₂). The La_0.8Sr_0.2CoO₃ composition, in particular, demonstrated the most promising performance, with enhanced sensitivity and excellent operational stability at temperatures up to 350 °C. These findings validate that PED is a reliable and precise method for fabricating complex oxide films and confirm that Sr-doped LaCoO₃ is a highly promising material for developing high-temperature NO₂ gas sensors. Full article

Sucralose, a persistent and widely used artificial sweetener, has emerged as a significant contaminant in aquatic environments, raising concerns about its ecological and physiological effects on aquatic species. This study investigates the impact of environmentally relevant concentrations of sucralose on the muscle quality of common carp (Cyprinus carpio), a bioindicator species. Using High-Performance Liquid Chromatography (HPLC), sucralose was quantified in water and fish muscle tissues, revealing its persistence and bioaccumulation. Sucralose exposure disrupted critical physicochemical, textural, and structural properties of fish muscle. Protein carbonyl content increased up to 10-fold, while lipid peroxidation levels rose significantly, indicating oxidative stress. Sulfhydryl groups were reduced by more than 40%, and water-holding capacity decreased by 12%, compromising muscle functionality. Textural profile analysis revealed alterations in hardness, cohesiveness, and elasticity, linked to covalent bond formation induced by protein oxidation. Furthermore, electrophoretic analysis confirmed myosin degradation, underscoring sucralose’s role as a pro-oxidant, even at low concentrations. These findings demonstrate that sucralose can adversely affect aquatic organisms by impairing muscle integrity, with potential consequences for their survival, ecological roles, and food web dynamics. This study underscores the urgent need to regulate and monitor artificial sweeteners in aquatic systems to mitigate long-term ecological impacts. Full article

Endocrine cells are dedicated to the production and processing of hormones, from peptides to small molecules, to regulate key physiological processes, including glucose homeostasis and metabolism. Because of this relatively high productivity, endocrine cells must handle a variety of stresses from oxidative stress to the unfolded protein response of the endoplasmic reticulum (UPR^ER). While much is known about the major pathways regulating the UPR^ER, the roles of endocrine cell type-specific, context-dependent, and time-dependent transcriptional changes are not well explored. To identify unique and shared responses to the UPR^ER across a subset of endocrine cell types, we tested representative lines for β-cells (insulin), α-cells (glucagon), δ-cells (somatostatin), X/A-cells (ghrelin), L-cells (glucagon-like peptide 1 (GLP1)), and thyrotropes (thyroid hormone and thyroglobulin). We exposed each cell type to the canonical ER stressor thapsigargin for 6 and 24 h, or vehicle for 24 h, and performed mRNA sequencing. Analysis of the data showed all lines responded to thapsigargin. Comparisons of differentially expressed genes between each line revealed both shared and unique transcriptional signatures. These data represent a valuable mineable set of candidate genes that may have cell type-specific functions during the UPR^ER and have the potential to lead to a new understanding of how different endocrine cells mitigate or succumb to ER stress. Full article

Investigating atmospheric volatile organic compounds (VOCs) is critical for understanding their sources, chemical reactivity, and impacts on air quality, climate, and human health, especially in remote regions like the Tibetan Plateau where baseline data remains scarce. In this study, ambient VOCs species were simultaneously measured at four remote background sites on the Tibetan Plateau (Nyingchi, Namtso, Ngari, and Mount Everest) from 2012 to 2014 to investigate their concentration, composition, sources, and chemical reactivity. Weekly integrated samples were collected and analyzed using a Gas Chromatograph-Mass Spectrometer/Flame Ionization Detector (GC-MS/FID) system. The total VOC mixing ratios exhibited site-dependent variability, with the highest levels observed in Nyingchi, followed by Mount Everest, Ngari and Namtso. The VOC composition in those remote sites was dominated by alkanes (25.7–48.5%) and aromatics (11.4–34.7%), followed by halocarbons (19.1–28.1%) and alkenes (11.5–18.5%). A distinct seasonal trend was observed, with higher VOC concentrations in summer and lower levels in spring and autumn. Source analysis based on correlations between specific VOC species suggests that combustion emissions (e.g., biomass burning or residential heating) were a major contributor during winter and spring, while traffic-related emissions influenced summer VOC levels. In addition, long-range transport of pollutants from South Asia also significantly impacted VOC concentrations across the plateau. Furthermore, reactivity assessments indicated that alkenes were the dominant contributors to OH radical loss rates, whereas aromatics were the largest drivers of ozone formation potential (OFP). These findings highlight the complex interplay of local emissions and regional transport in shaping VOC chemistry in this high-altitude background environment, with implications for atmospheric oxidation capacity and secondary pollutant formation. Full article