Search Results (7,592)

Alhagi camelorum is a dominant leguminous shrub distributed in the Taklamakan Desert, an area characterized by extreme drought and high soil salinization, which can complete its life cycle normally in salt-affected soils. However, the underlying molecular regulatory mechanism of its salt tolerance remains largely unclear. The AcABI5 gene was successfully cloned and characterized, and it encodes a typical nuclear-localized bZIP transcription factor. Functional characterization demonstrated that overexpression of AcABI5 markedly improved the salt stress tolerance of A. camelorum calli, whereas silencing of AcABI5 via virus-induced gene silencing (VIGS) rendered the plant more sensitive to salt stress. Further mechanistic investigations revealed that AcABI5 enhanced salt tolerance by regulating the expression of superoxide dismutase (SOD)- and peroxidase (POD)-related antioxidant genes. Compared with the wild type, AcABI5-overexpressing calli exhibited significantly increased SOD and POD activities and remarkably reduced malondialdehyde (MDA) content under salt treatment, whereas AcABI5-silenced lines exhibited the opposite physiological phenotypes. Furthermore, heterologous silencing of AcABI5 in Nicotiana benthamiana via virus-induced gene silencing (VIGS) produced comparable salt-sensitive phenotypes, similar to those observed in A. camelorum AcABI5-silenced lines. Collectively, these results provide insights into the molecular mechanism by which AcABI5 enhances salt tolerance in A. camelorum, and lay a solid theoretical foundation for the optimization of the A. camelorum genetic transformation system and the expansion of related salt-tolerant crop research. Full article

Antioxidant supplementation during in vitro maturation (IVM) has been proposed as a strategy to influence transcriptional responses in oocytes and cumulus–oocyte complexes. In this study, we investigated whether vitamin C, rosmarinic acid, or quercetin influence the expression of key fertilisation-associated genes (CD9, ITGA6, MFGE8, ZP2, and ZP3) in porcine cumulus–oocyte complexes (COCs). COCs were classified into three intrinsic quality groups (I–III) and matured in the presence or absence of antioxidants. Gene expression was quantified by RT-qPCR and analysed using a two-way ANOVA model to assess the effects of COC quality and treatment. ZP2 and ZP3 transcript levels were consistently lower in class II and III COCs than in class I controls (p < 0.001). Antioxidant supplementation was associated with treatment- and quality-dependent differences in gene expression. Quercetin was associated with the most pronounced upregulation, with Q I increasing ZP2 expression to 2.95-fold and ZP3 to 2.43-fold relative to class I controls (p < 0.001). Vitamin C was also associated with increased transcript abundance across several treatment groups, including class II and class III COCs, whereas rosmarinic acid exhibited more moderate and gene-specific effects. In contrast, MFGE8 expression, which was elevated in lower-quality COCs, was reduced in antioxidant-treated class II and III complexes. These findings provide transcript-level evidence that antioxidant exposure during IVM is associated with treatment- and quality-dependent changes in fertilisation-related gene expression in porcine COCs. Full article

Uterine microbiome homeostasis and antioxidant capacity are critical for sow fertility. While high-fiber diets and N-carbamylglutamate (NCG) individually enhance sow fertility, their synergistic effects on the antioxidant status, microbiota, metabolites, and transcriptome remain unclear. Here, sows were assigned to the low-fiber (3.73%) or high-fiber (7.46% crude fiber) group, each without or with 0.05% NCG, throughout the 114-day gestation. Sex hormones and antioxidants in serum were detected. Multi-omics approaches were employed to investigate the impact of a high-fiber diet supplemented with NCG (H + N) on uterine microbiota, metabolites, and gene expression profiles. The study revealed that H + N significantly increased total antioxidant capacity (T-AOC) level in serum. Metagenomic analysis revealed an increased abundance of Clostridium disporicum in the uterine microbiota. Plasma metabolomics identified hydroxylysine as a key metabolite mediating this effect, and this metabolite was positively correlated with elevated abundance of Clostridium disporicum. Subsequent transcriptomic profiling revealed activation of the PI3K-Akt signaling pathway, closely linked to improved T-AOC level. Overall, these findings demonstrated that H + N could modulate the uterine microbiota (specifically Clostridium disporicum), increase hydroxylysine production, and activate the PI3K-Akt signaling pathway. These effects further enhanced hormonal activity and antioxidant capacity, ultimately improving sow reproductive efficiency. Full article

With the rapid progression of global industrialization and urbanization, heavy metal contamination has emerged as a major global threat, especially cadmium pollution. Consequently, optimizing remediation measures has become a pivotal means to solve cadmium contamination. Compared to traditional physical and chemical remediation methods, microbial remediation has great potential in addressing cadmium pollution. In this study, a novel bacterial strain, Chryseobacterium sp. HGX-24, exhibiting high cadmium resistance was successfully isolated and screened from cadmium-contaminated environments. A preliminary discussion of the response mechanisms of this strain under cadmium stress is provided. Additionally, preliminarily explored the synergistic remediation of microbial-plant in cadmium-contaminated soil. Under conditions of high cadmium concentration, cadmium ions were effectively adsorbed by strain HGX-24 through extracellular polymers and functional groups on the cell wall surface, including −COOH, −CONH−, −NH, −OH, and >C=O. Extracellular proteins and polysaccharides were secreted by strain HGX-24 to regulate the adverse effects of heavy-metal cadmium ions on bacterial growth. Furthermore, the expression of genes such as antioxidant defense and ROS scavenging (katG, fabG, ybjT), Fe-S cluster assembly (sufB, sufD), sulfur metabolism (cysAU), amino acid metabolism (hisA, cysD, aspC), phenylacetic acid catabolism (paaC), and ribosomal proteins (rplC, rpsC, rpsL, rplA, rplY, rpmC) was regulated, affecting the synthesis and metabolism of membrane transporters (ABC transporters and efflux RND transporters), antioxidant enzymes (SOD, COT, POD), Fe-S clusters, thioredoxin family proteins, and ribosomal proteins, thereby enhancing resistance to cadmium toxicity. Moreover, strain HGX-24 was found to regulate the activities of redox enzymes in Zea mays L., thereby alleviating oxidative stress and reducing the negative feedback effects of reactive oxygen species in Z. mays. Full article

Porcine epidemic diarrhea virus (PEDV) causes lethal enteritis in neonatal piglets, yet the mechanisms underlying rapid intestinal injury remain unclear. In particular, it is unknown whether different regulated cell death pathways act separately or cooperatively to worsen mucosal damage. To address this question, we performed multi-omics analyses of infected intestinal tissues and found concurrent activation of pyroptosis and ferroptosis during PEDV infection. PEDV infection activated the Caspa-se-1/GSDMD pathway in the duodenum and jejunum, as shown by generation of the Caspase-1 p20 fragment and cleavage of GSDMD into its active N-terminal form, indicating pyroptosis. At the same time, infected tissues displayed key features of ferroptosis, including weakened antioxidant defenses, increased lipid peroxidation, iron accumulation, lipid remodeling, and dysregulated ACSL4 and GPX4 expression. These two processes were closely linked and together contributed to tight junction disruption and barrier instability. Molecular docking further suggested that PEDV NSP1 and S proteins may interact with Caspase-1, providing a possible explanation for pyroptosis induction. Correlation analysis also showed strong associations between pyroptosis-related genes and ferroptosis-associated metabolites. Overall, our findings indicate that pyroptosis and ferroptosis cooperate to drive PEDV-induced intestinal inflammation and barrier damage, highlighting their joint inhibition as a potential strategy to reduce PEDV pathogenicity. Full article

Anthocyanins are plant polyphenols widely regarded as antioxidants, yet they can exert concentration-dependent effects and act as pro-oxidants in specific contexts. Although their protective role in stressed testicular cells is established, their impact on Leydig cell steroidogenesis under non-pathological conditions remains poorly understood. Here, we investigated how an anthocyanin-enriched fraction from Callistemon citrinus (0–1.00 μg/mL) affects androgen synthesis in murine TM3 Leydig cells. Cell viability, intracellular ROS, antioxidant capacity, mitochondrial function, androstenedione production, steroidogenic gene expression, and the exometabolome by ¹H-NMR were assessed. The fraction exhibited biphasic, dose-dependent effects. At 0.01 μg/mL, it induced a mitohormetic response, upregulating mitochondrial complexes III and V. Conversely, higher concentrations (0.10–1.00 μg/mL) reduced metabolic activity, increased intracellular ROS, and significantly suppressed androstenedione synthesis independently of Star. These concentrations also induced dose-dependent repression of Cyp17a1, concomitant with upregulation of Nr0b2, encoding the transcriptional repressor Small Heterodimer Partner (SHP). Overall, the data support a redox-dependent mechanism whereby elevated ROS promotes Nr0b2 expression, leading to Cyp17a1 suppression and impaired androstenedione production. These findings challenge the view of anthocyanins as uniformly beneficial for male fertility and identify Callistemon citrinus as a sustainable source of bioactive anthocyanins capable of modulating redox–endocrine homeostasis in a dose-dependent manner under basal conditions. Full article

Thalassemia is an inherited hemoglobin disorder characterized by chronic hemolytic anemia and substantial long-term healthcare needs. In β-thalassemia major, patients typically require regular red blood cell transfusions with iron chelation to prevent transfusional iron overload. Although supportive care has markedly improved survival, it is associated with a high treatment burden and does not provide a cure. In recent years, curative and disease-modifying therapies have expanded the treatment landscape. Allogeneic hematopoietic stem cell transplantation (HSCT) offers a potentially curative option for selected patients, while autologous gene therapy and gene-editing approaches have shown the capacity to achieve transfusion independence in clinical studies. In parallel, pharmacologic advances—including luspatercept, a transforming growth factor-beta (TGF-β) ligand trap—have been shown to enhance erythropoiesis and reduce transfusion requirements, and emerging agents such as fetal hemoglobin inducers (e.g., thalidomide) and the oral pyruvate kinase activator mitapivat have demonstrated clinically meaningful hemoglobin improvements in selected populations. Adjunctive strategies, including antioxidants, are under investigation to mitigate oxidative stress, and applications of artificial intelligence are increasingly used to support screening, diagnosis, and longitudinal monitoring of iron overload. This review synthesizes recent advances in curative therapies, novel pharmacologic agents, supportive strategies, and AI-enabled tools and highlights priorities for future clinical development and implementation. Full article

ERF/AP2 is a family of transcription factors that plays a broad role in plant growth and development and in responses to various environmental stresses. In our previous studies, we found that the transcription factor LoERF4 indirectly induces the breaking of dormancy in lily bulbs by regulating its downstream gene, LoXTH23. To further investigate the function of LoERF4, we overexpressed it in Arabidopsis thaliana. Paraffin section analysis revealed that root cells in OE-LoERF4 transgenic Arabidopsis thaliana lines exhibited significantly longer average cell lengths compared to the wild type. In the overexpression lines, the expression of multiple modified genes, including AtXTHs and AtEXPAs was significantly upregulated, and these lines exhibited earlier lateral root emergence and a significant increase in primary root length. Under 100 mM sodium chloride treatment, the overexpression lines exhibited significantly higher numbers of lateral roots, true leaves, and primary root length compared with the wild type (WT). In the OE-LoERF4 line, antioxidant enzyme (SOD, POD, CAT) activity was enhanced, oxidative damage was reduced (decreased MDA content), and root survival rate was improved (as reflected by TTC reduction). This confirms that LoERF4 may promote root development in the overexpression line by positively regulating downstream AtXTHs and AtEXPAs, while simultaneously enhancing the salt tolerance of the overexpression line. Full article

This study was conducted to evaluate the effect of varying dietary energy levels on milk production, feed intake, nutrient digestion and metabolism, and antioxidation function of lactating donkeys, and integrating 16S rRNA gene sequencing, metabolomics, and proteomics to comprehensively reveal the underlying regulatory networks. A single-factor, completely randomized design was used in this study. Twenty-four Dezhou donkeys with similar milk yield (3.25 ± 0.46 kg/d), lactation days (29 ± 4.34 d), parities (4.17 ± 1.17), and body weight (256 ± 34 kg) were randomly divided into three dietary treatments (n = 8), and either a fed high-energy diet (DE = 13.1 MJ/kg, HED), medium-energy diet (DE = 12.4 MJ/kg, MED), and low-energy diet (DE = 11.7 MJ/kg, LED). The experiment period included 2 weeks for adaptation and 8 weeks for data and sample collection. Orthogonal polynomial contrasts were used to evaluate the linear and quadratic effects of increasing dietary energy. There were no significant interaction effects between dietary energy level and lactation week on any milk production and quality variables (p > 0.05). Increasing dietary energy level increased DMI, milk production, milk production efficiency, and milk components (linear and quadratic; p < 0.05). Increasing dietary energy improved the digestibility of DM and neutral detergent fiber (linear; p < 0.05), and crude protein digestibility, energy digestibility and metabolism, and nitrogen metabolism (quadratic; p < 0.05). However, it decreased BHBA and NEFA concentrations (linear; p < 0.05). Furthermore, increasing dietary energy first increased then decreased the activities of GSH-PX, SOD, and T-AOC (linear and quadratic; p < 0.05), while increasing the MDA content (linear; p < 0.05). Compared with HED and MED, LED increased the relative abundance of the genera unclassified_f_Syntrophomonadaceae, Christensenellaceae_R-7_group and Treponema_2. Compared with HED, MED increased the relative abundance of the genera Ruminiclostridium_5, Ruminiclostridium_1, Family_XIII_UCG-001, unclassified_o__Clostridiales and norank_f__PL-11B10. Thyroid hormone synthesis, tyrosine metabolism, and glutathione metabolism pathways are critical metabolic routes; these pathways can enhance energy metabolism and antioxidant function, thereby improving the milk production performance of lactating donkeys. In conclusion, the digestible energy of 12.40 MJ/kg was optimal for the milk performance of lactating donkeys, whereas excessively high dietary energy (13.1 MJ/kg) may reduce milk performance. Full article

Chronic Obstructive Pulmonary Disease (COPD) is characterized by persistent inflammation and structural alterations in the lung triggered mainly by oxidative stress. Colonization by the opportunistic fungus Pneumocystis has been associated with worse clinical outcomes in COPD, yet its role in airway remodeling remains unclear. To this end, an elastase-induced COPD model was established, followed by colonization with Pneumocystis. Lung tissue was analyzed histologically and molecularly to assess epithelial thickness, alveolar morphometric parameters (mean linear intercept [MLI], D₀, D₁, D₂), inflammation, collagen deposition, and the expression of remodeling and oxidative stress markers. Emphysematous damage parameters MLI, D₀, D₁, and D₂ were markedly elevated in co-exposed animals, indicating enhanced alveolar enlargement. Animals with COPD and Pneumocystis colonization showed a significant increase in airway inflammation compared with control, COPD, and Pneumocystis groups. Airway epithelial thickness, mucus metaplasia, and collagen deposition exhibited a summative increase in the COPD/Pneumocystis group. Redox-responsive markers, such as superoxide dismutase (SOD) and catalase, were upregulated. Moreover, protein and mRNA levels of nuclear factor erythroid 2–related factor 2 (Nrf2) and its downstream gene heme oxygenase-1 (Hmox1) were significantly increased, with the strongest activation observed in co-exposed animals. Integrative correlation analysis showed that Pneumocystis burden positively correlated with lung damage, inflammation, and epithelial remodeling. These structural alterations were accompanied by coordinated activation of the antioxidant pathway Nrf2. Taken together, Pneumocystis colonization is associated with enhanced pulmonary remodeling and modulation of antioxidant signaling in experimental COPD, promoting structural and molecular changes that may contribute to disease progression. These findings suggest that Pneumocystis acts as an amplifying factor in COPD-associated lung damage. Full article

Acute mountain sickness (AMS) arises from hypobaric hypoxia at high altitude and still lacks effective pharmacological treatments. Although hypoxic preconditioning via gradual ascent prevents AMS, the underlying molecular adaptations have not yielded therapeutics. Here, inspired by metabolic reprogramming during stepwise altitude adaptation, we screened for anti-hypoxia compounds and identified H0802 (N-(pyridin-2-yl) pyridine-2-carbothioamide) as the most promising candidate. H0802 markedly enhances hypoxic tolerance in mice, prolongs survival under acute hypoxia, improves survival during simulated high-altitude exposure, and attenuates hypoxia-induced lung injury, accompanied by combined anti-inflammatory and antioxidant effects. Transcriptomic profiling shows that H0802 elicits a gene expression signature resembling hypoxia, including key hypoxia-related genes (Edn1, Angptl4, Mt1, Gdf15, Slc7a5, and Hif-3α) involved in glucose and oxygen metabolism. Mechanistically, H0802 stabilizes endogenous hypoxia-inducible factor (HIF) proteins under normoxia by preventing ubiquitin-dependent degradation, thereby activating hypoxia-responsive genes. In vivo, H0802 pretreatment lowers circulating glucose and hepatic glycogen while increasing brain glucose uptake, suggesting a metabolic shift that preserves cerebral energy during acute hypoxic stress; it also modulates whole-body oxygen consumption. H0802 represents a candidate for anti-AMS therapy, and phenotypic optimization of H0802 provides a potential route for drug discovery. Full article

Carotenoids contribute to photoprotection and abiotic stress adaptation in plants, and lycopene cyclases (LCYs) occupy a key branch point in carotenoid biosynthesis. However, the composition and stress-responsive divergence of LCY genes in pepper remain insufficiently characterized. In this study, we identified six CaLCY genes in Capsicum annuum and analyzed their structural features and expression patterns under drought and salt stress. CaLCYB1 showed the strongest and most consistent induction under both drought and salt stresses and was positively correlated with carotenoid accumulation, whereas the other CaLCY members exhibited distinct or negligible expression patterns. Transient overexpression of CaLCYB1 significantly increased β-carotene and total carotenoid contents by 117.6% and 45.1%, respectively, relative to the empty-vector control, and also augmented ABTS^•+ radical scavenging activity as well as ascorbate peroxidase (APX) activity. Conversely, virus-induced gene silencing (VIGS) of CaLCYB1 led to marked reductions in all of these parameters. Correlation analysis, together with gain- and loss-of-function assays, supports an important role of CaLCYB1 in carotenoid accumulation and β,β-branch-related antioxidant responses under stress. Yeast two-hybrid screening identified three potential interactors of CaLCYB1, namely CaUBQ, CaLHP1, and CaLARP6B. This study provides a family-level characterization of LCY genes in pepper and identifies CaLCYB1 as a major stress-responsive member that directs carotenoid flux and enhances antioxidant capacity under abiotic stress. Full article

Hexavalent chromium, a widespread heavy metal, induces apoptosis via the mitochondrial pathway through Bax (pro-apoptotic) and Bcl2 (anti-apoptotic) proteins. Hypericum perforatum, rich in antioxidants, can neutralise free radicals. This study investigated the effects of CrVI on the pancreas and the protective role of Hypericum perforatum. Five groups of animals were used: control, Cr (CrVI for 3 months), CrH (CrVI + 2.5% Hypericum perforatum extract made from flowers, for 3 months), Cr2 (CrVI for 3 months + distilled water for 1 month), and CrH2 (CrVI for 3 months + Hypericum perforatum extract for 1 month). Samples were collected for histological analysis, gene expression (qRT-PCR), and blood glucose level analysis. CrVI exposure (Cr, Cr2) caused pancreatic damage: oedema, reduced islet size, endocrine cell vacuolisation, and endothelial swelling. Lesions were milder in CrH, while CrH2 resembled the control group. The Bax/Bcl2 ratio increased under CrVI (highest in Cr2), indicating apoptosis, but decreased toward control values in CrH and CrH2. Blood glucose levels confirmed these findings. CrVI proved toxic to the endocrine pancreas, inducing structural and molecular alterations that impaired carbohydrate metabolism. Administration of Hypericum perforatum extract reduced these effects, confirming its antioxidant action and potential as a protective agent against CrVI-induced oxidative stress. Full article

Down syndrome (DS), caused by trisomy 21, is the most prevalent genetic condition associated with accelerated aging and near-universal development of early-onset Alzheimer’s disease (AD). Beyond gene-dosage imbalance, trisomy 21 induces widespread transcriptional, metabolic, and proteomic remodeling that establishes a chronic state of proteotoxic and oxidative stress from early development. Increasing evidence identifies DS as a disorder of proteostasis network failure, in which sustained translational pressure, redox disequilibrium, and degradation pathway insufficiency progressively erode cellular resilience. In the DS brain, persistent endoplasmic reticulum stress with PERK-dominant signaling, mitochondrial dysfunction characterized by oxidative phosphorylation deficits and excessive reactive oxygen species production, and impaired antioxidant responses create a highly vulnerable intracellular environment. Concomitantly, degradation systems become compromised: proteasomal catalytic activity declines, ubiquitin-dependent signaling is remodeled, and chronic mTOR hyperactivation suppresses autophagic and mitophagic flux. The coordinated impairment of the ubiquitin–proteasome system and autophagy establish a feed-forward cycle of proteotoxic accumulation and redox amplification. Within this framework, Alzheimer-like neuropathology in DS emerges not solely from amyloid precursor protein triplication but as the late manifestation of decades-long proteostasis exhaustion. Therapeutic strategies aimed at restoring global proteostasis and redox balance may therefore represent a more effective systems-level approach to mitigating neurodegeneration in DS. Full article

Aquaculture sustainability in rapidly urbanizing regions is increasingly threatened by heavy metal contamination originating from complex anthropogenic land-use patterns. This study used an integrated model to evaluate the molecular-to-human health continuum in hybrid catfish (Clarias gariepinus × Clarias macrocephalus) sourced from Pathum Thani, Thailand’s primary aquaculture hub. We integrated geospatial land-use data with heavy-metal quantification, oxidative-stress biomarkers, and transcriptional profiling to assess how canal-specific water quality modulates fish health and consumer risk. The results revealed significant spatial heterogeneity in metal concentrations, corresponding to the province’s 27% urban–industrial land-use footprint. While water quality generally met regulatory limits, a pronounced aqueous–biotic discrepancy, “bioaccumulation paradox” was identified at certain sites, where muscle and hepatic tissues exhibited lead (Pb), chromium (Cr), and nickel (Ni) levels that substantially exceeded international safety standards. Biochemical and molecular analyses provided functional evidence of physiological distress, specifically significantly elevated malondialdehyde (MDA) levels, and the transcriptional modulation of cat, cyp1a, gpx, met, tnf, and star genes indicated that chronic metal exposure overwhelmed antioxidant defenses and induced potential endocrine disruption. Moreover, human health risk assessments revealed that the hazard index (HI) and target cancer risk (TR) exceeded unacceptable thresholds at multiple hotspots, indicating that Cr is a primary carcinogenic driver. These findings highlight a “GAP Paradox,” where farm-level certifications are insufficient to mitigate risks posed by the surrounding canal network. This study presents vital evidence-based risk profiles that necessitate a transition to a spatially based regulatory framework, incorporating geospatial land-use monitoring into national food safety policies to protect both aquaculture viability and public health. Full article