Search Results (18,733)

Pear black spot disease is a serious fungal disease during pear production; salicylic acid is a core signaling molecule that regulates the expression of plant disease resistance genes. To elucidate the intrinsic association between salicylic acid-induced resistance to pear black spot disease and lignin biosynthesis, in vitro plantlets of two pear cultivars, ‘Xinli No.7’ and ‘Xueqing’, were employed as experimental materials. After 60 h SA pretreatment, the leaves were inoculated with the pathogen Alternaria alternata. Leaf samples were harvested at 0, 8, 16, 24, and 48 h post-inoculation to determine phenylalanine ammonia-lyase activity, quantify lignin content, and analyze the transcript levels of genes involved in lignin synthesis. The results demonstrated that, relative to the untreated control group, SA treatment significantly enhanced phenylalanine ammonia-lyase activity and promoted lignin accumulation in both ‘Xinli No.7’ and ‘Xueqing’. Moreover, multiple key genes associated with lignin biosynthesis—including PbrPAL1, Pbr4CL1, PbrCOMT, PbrCCoAOMT, PbrCAD, and PbrPOD—were markedly upregulated, with their expression levels increasing by 3.5–15 fold. Transcript profiles of PbrHCT1, PbrHCT4, and PbrC3H1 exhibited cultivar-specific divergence between the two varieties. Notably, the susceptible cultivar ‘Xueqing’ displayed a distinct lag phase and attenuated response in the expression of all lignin-related genes compared with the other cultivar. This study provides reference for green prevention and sustainable development of pear. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic (DAergic) neurons in the substantia nigra (SN) and the accumulation of misfolded α-synuclein (aSyn). In addition to neuronal pathology, activated microglia are recognized as key mediators of the neuroinflammatory milieu in PD, contributing to DAergic neuron vulnerability. Emerging evidence suggests that the immune system, particularly T-cell-mediated responses, plays a key role in the pathogenesis of PD. However, the heterogeneity of these immune responses across species and preclinical models with varying regenerative capacities remains poorly understood. A comparative analysis of T-cell infiltration, astroglial reactivity, and DAergic neuronal loss across multiple models and species was performed. These included acute DAergic degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), genetically modified mice with accumulation of aSyn (Thy1-aSyn L61 model), adult zebrafish exposed to MPTP-induced neurotoxicity and human post-mortem midbrain tissue obtained from PD patients. Zebrafish exhibited transient DAergic neurodegeneration, followed by neuronal regeneration and temporary CD4⁺ T-cell infiltration accompanied by an astroglial response and activation of microglia. In contrast, MPTP-treated mice showed a permanent neuronal loss, marked microglial activation, increased astrogliosis and CD8⁺ T-cell infiltration that was negatively correlated with neuronal survival. By contrast, L61 mice exhibited progressive aSyn accumulation with chronic astrogliosis, mild activation of microglia and CD4⁺ T-cell infiltration not directly linked to neuronal loss. Unlike age-matched controls, the SN from PD brains exhibited DAergic degeneration, aSyn aggregation, and elevated CD3⁺ T-cell infiltration, and increased microglial activation. These changes correlated with neuronal loss and aSyn burden. These findings emphasize the species- and model-specific immune profiles underlying PD pathology. Our results reveal that CD4⁺ T-cells contribute to neuronal regeneration following injury in zebrafish. This process is absent in the MPTP and L61 mouse models, which are instead driven by CD8⁺ or CD4⁺, respectively. This work underscores the potential of targeted immunomodulation aimed at T cell–glial interactions to slow neurodegeneration and promote repair in PD. Full article

Regarding the issues arising from the addition of external curing agents in the application of epoxy resin in cement-based materials, this paper explores the feasibility of endogenous curing of epoxy resin in the alkaline environment of cement-based systems. It further analyzes and investigates the curing characteristics of epoxy resin without external curing agents and their impact on the performance of cement-based materials. Differential scanning calorimetry, mechanical property testing, microstructural observation, and electrochemical impedance spectroscopy were used to study the mechanism of sodium hydroxide (NaOH) catalyzing the process of bisphenol-A epoxy resin (E-51)-based curing, the influence of moisture and temperature on curing kinetics, and the performance of epoxy resins in mortar and self-healing concrete. The results showed that E-51 achieved self-curing under alkaline conditions in the absence of an external hardener. However, moisture significantly inhibited the reaction process. Elevating the temperature and reducing environmental humidity effectively promoted the curing reaction. In cement-based materials, E-51 exhibited endogenous curing by the inherent alkalinity of the system, remarkably enhancing the compressive strength of mortar. At 60 °C, mortar containing 10% E-51 (by cement mass) exhibited a 1.5-fold higher compressive strength than that of the control group without E-51 at 14 days of curing. It demonstrated higher healing efficiency in a microencapsulated self-healing concrete system than the traditional curing agent systems. Concrete specimens with damage induced by loading at 60% of their compressive strength exhibited 100% recovery of ultrasonic pulse velocity after storing indoors for 28 d. The findings of this study can provide theoretical basis and technical support for the application of epoxy resins in cement-based materials without the need for curing agents. Full article

In individuals with diabetes, dysregulation of inflammatory processes hinders the progression of wounds into the proliferative phase, resulting in chronic, non-healing wounds. Total saponins from Rhizoma Panacis majoris (SRPM), bioactive compounds naturally extracted from the rhizome of Panax japonicus C.A.Mey. var. major (Burk.) C.Y.Wu and K.M.Feng, have demonstrated extensive anti-inflammatory and immunomodulatory properties. This study aims to elucidate the molecular mechanisms underlying the facilitative effects of SRPM on diabetic wound healing, with particular emphasis on its anti-inflammatory actions. A high-fat diet combined with streptozotocin (STZ) administration was used to induce type 2 diabetes in rats. After two weeks of oral treatment with SRPM suspension, a wound model was established. Subsequently, a two-week course of combined local and systemic therapy was administered using both SRPM suspension and SRPM gel. SRPM markedly reduces the levels of pro-inflammatory mediators, including IL-1α, IL-1β, IL-6, MIP-1α, TNF-α, and MCP-1, in both rat tissues and serum. Concurrently, it increases the expression of anti-inflammatory cytokines such as IL-10, TGF-β1, and PDGF-BB, while also enhancing the expression of the tissue remodelling marker bFGF. Additionally, SRPM significantly decreases the accumulation of apoptotic cells within tissues by downregulating the pro-apoptotic gene Caspase-3, upregulating the anti-apoptotic gene Bcl-2, and increasing the expression of the apoptotic cell clearance receptor MerTK. Moreover, SRPM inhibits neutrophil infiltration and the release of neutrophil extracellular traps (NETs) in tissues, promotes macrophage polarisation towards the M2 phenotype, and activates the Wnt/β-catenin signalling pathway at the molecular level. SRPM promotes the healing of wounds in diabetic rats potentially due to its anti-inflammatory properties. Full article

The functional deterioration of granulosa cells (GCs), essential for follicular growth, steroidogenesis, and oocyte competence, indicates ovarian aging and reduced fertility. An expanding corpus of research indicates that oxidative stress is a primary molecular contributor to granulosa cell dysfunction, culminating in mitochondrial impairment, reduced metabolic support for oocytes, and the activation of regulated apoptotic pathways that end in follicular atresia. Ferroptosis, an emergent type of iron-dependent lipid peroxidation, has been identified as a crucial mechanism contributing to chemotherapy-induced ovarian insufficiency, polycystic ovary syndrome (PCOS), and granulosa cell death in aging ovaries, in addition to conventional apoptosis. The SIRT1-Nrf2 axis acts as a crucial anti-oxidative and anti-ferroptotic system that protects GC viability, maintains mitochondrial homeostasis, and upholds redox equilibrium. SIRT1 promotes mitochondrial biogenesis and metabolic resilience by deacetylating downstream proteins, including FOXO3 and PGC-1α. Nrf2 simultaneously controls the transcriptional activation of detoxifying and antioxidant enzymes, including HO-1, SOD2, NQO1, and GPX4, which are critical inhibitors of ferroptosis. Disruption of SIRT1-Nrf2 signalling accelerates GC senescence, follicular depletion, and reproductive aging. In contrast, pharmaceutical and nutraceutical therapies, including metformin, melatonin, resveratrol, and agents that increase NAD⁺ levels, may reverse ovarian deterioration and reactivate SIRT1-Nrf2 activity. This narrative review highlights innovative treatment prospects for ovarian aging, fertility preservation, and assisted reproduction by synthesising current evidence on ferroptotic pathways, SIRT1-Nrf2 interactions, and oxidative stress in granulosa cells. An understanding of these interrelated biological networks enables the development of tailored therapies that postpone ovarian ageing and enhance reproductive outcomes for women receiving fertility therapy. Full article

Knowledge distillation achieves model compression by training a lightweight student network to mimic the output distribution of a larger teacher network. However, when the teacher becomes overconfident, its sharply peaked logits break the scale symmetry of supervision and induce high-variance gradients, leading to unstable optimization. Meanwhile, research that focuses only on final-logit alignment often fails to utilize intermediate semantic structure effectively. This causes weak discrimination of student representations, especially under class imbalance. To address these issues, we propose Scale Calibration and Pressure-Driven Knowledge Distillation (SPKD): a one-stage framework comprising two lightweight, complementary mechanisms. First, a dynamic scale calibration module normalizes the teacher’s logits to a consistent magnitude, reducing gradient variance. Secondly, an adaptive pressure-driven mechanism refines student learning by preventing feature collapse and promoting intra-class compactness and inter-class separability. Extensive experiments on CIFAR-100 and ImageNet demonstrate that SPKD achieves superior performance to distillation baselines across various teacher–student combinations. For example, SPKD achieves a score of 74.84% on CIFAR-100 for the homogeneous architecture VGG13-VGG8. Additional evidence from logit norm and gradient variance statistics, as well as representation analyses, proves the fact that SPKD stabilizes optimization while learning more discriminative and well-structured features. Full article

Drought stress represents a major constraint on global apple production, with the widely used semi-dwarfing rootstock ‘M.26’ being particularly vulnerable to water deficit. Although the osmolyte trimethylamine N-oxide (TMAO) has been shown to improve abiotic stress tolerance in the model plant Arabidopsis, its potential role in enhancing drought resilience in woody fruit trees remains largely unexplored. Under prolonged moderate drought stress, exogenous TMAO application significantly promoted plant growth, mitigating the drought-induced suppression of plant height by 5.3–12.2% compared to untreated drought-stressed controls and alleviating the decline in above-ground biomass. This improvement was underpinned by a substantial alleviation of root growth inhibition, with TMAO restoring total root length and biomass from 37% in the control to only 6.1–9.5%. TMAO also fine-tuned the root-to-shoot ratio to favor resource allocation to roots. Consequently, TMAO-treated plants maintained superior leaf water status, exhibiting higher relative water content (drought-induced reduction limited to ~17.5% with TMAO versus 26.3% in the control). Physiologically, TMAO alleviated the drought-induced stomatal limitation of photosynthesis, sustaining higher net photosynthetic rate, stomatal conductance, and transpiration rate. Crucially, under severe drought stress, TMAO pretreatment markedly enhanced ‘M.26’ survival rates from approximately 39% in the untreated control to 60–68%, representing a relative increase of approximately 74%. Collectively, this study demonstrates that exogenous application TMAO significantly enhances drought tolerance in apple rootstock ‘M.26’, highlighting its potential as an effective and environmentally safe plant growth regulator for more sustainable cultivation of fruit trees under irregular/erratic irrigation conditions. Full article

Background/Objectives: Allergic rhinitis (AR) is a complex immune-mediated disorder characterized by defective regulatory mechanisms. Emerging evidence suggests that impaired immune tolerance mediated by regulatory B cell (Breg) plays a pivotal role in AR pathogenesis. This study investigates the therapeutic potential of Der p1 allergen-modified dendritic cells (DC) in enhancing Breg-mediated immunotherapy and explores novel mechanisms underlying AR immunomodulation. Methods: Breg and the inflammatory cytokines were detected before and after allergen immunotherapy (AIT) in AR patients. Dust mite gene-derived dendritic cells were used to induce Breg. AR mice were treated with Der p1-DCs, and changes in Breg and related inflammatory indicators, as well as the impact of the IL-10/STAT pathway on DC vaccine treatment, were observed. Results: Following 6-month AIT, AR patients exhibited significant alleviation of nasal symptoms alongside restored peripheral Breg and Treg. In vitro co-culture of Der p1-DC-induced Bregs with CD4⁺CD25⁻T cells revealed that IL-10 blockade markedly increased Th cell. In AR murine models, intraperitoneal Der p1-DC administration suppressed allergic symptoms, upregulated nasal mucosal IL-10 expression, and attenuated STAT3 phosphorylation via IL-10 overexpression. Conclusions: AIT establishes immune tolerance through Breg-mediated regulatory mechanisms, while Der p1-DCs potently induce Breg differentiation and drive tolerance induction via the IL-10/STAT3 signaling axis. Full article

Background: The association between liver disease and gut microbiota is being widely investigated. Probiotics, such as Bacillus amyloliquefaciens, are among the most notable microbiomes examined in this study. Bacillus amyloliquefaciens shows potential for promoting growth and effectively regulating gut microbiota, though its mechanism of action remains unclear. Methods: The early gavage administration of Bacillus amyloliquefaciens BA5 conferred protection against liver injury in carbon tetrachloride (CCl₄)-induced mice. Growth parameters (body weight and organ index), serum biochemical markers (ALT, AST, T-SOD, MDA, GSH-Px, and T-AOC), liver and jejunum histopathology, and gut microbiota composition were comprehensively evaluated. Results: BA5 supplementation restored serum T-AOC, T-SOD, and GSH-Px levels and attenuated CCl₄-induced increases in ALT, AST, and MDA, suggesting potent anti-oxidant properties. Furthermore, histopathologic assessment showed that CCl₄-induced mice developed acute liver injury and intestinal villi were destroyed, while the BA5 group restored the pathological changes in the tissues to the normal group level. In addition, immunohistochemical staining revealed that BA5 increased the expression level of Claudin-1 which was a key biomarker for assessing the integrity of epithelial/endothelial barriers. Regarding gut microbiota, BA5 significantly enhanced the abundance of beneficial bacteria (Lactobacillus) and decreased the abundance of hazardous bacteria (Fusobacterium, Lachnoclostridium, Phascolarctobacterium, and Escherichia–shigella) caused by CCl₄. Notably, BA5 alone remarkably increased gut microbial diversity compared with that of the Control group. Conclusions: Overall, these findings suggest that BA5 holds promise as a potential therapeutic agent for alleviating CCl₄-induced acute liver injury in mice by mitigating oxidative stress and modulating gut microbiota. Full article

Necroptosis and dysfunction of ovarian granulosa cells are major contributors to follicular atresia and reduced fertility in cattle, processes that are closely associated with endoplasmic reticulum stress (ERS). Ginseng polysaccharides (GPSs) are known to reduce ER stress, display anti-inflammatory properties, and modulate reproductive function; however, whether GPS can protect against granulosa cell injury and the underlying mechanisms remain unclear. To address this gap, this study aimed to investigate the protective effects of GPS on ERS-induced bovine granulosa cell damage and to elucidate the associated mechanisms. An ERS model was established in bovine granulosa cells using tunicamycin (Tm), and cellular responses were evaluated via flow cytometry, ELISA, and EdU assays. Further, a mouse model was used to validate the protective effects of GPS against Tm-induced ovarian injury. The results showed that 40 μg/mL of GPS significantly alleviated ERS-induced granulosa cell damage, inhibited necroptosis, and mitigated ERS. Moreover, using the PI3K/Akt pathway inhibitor LY294002, we demonstrated that the inhibitor antagonized the effects of GPS, indicating that GPS promotes granulosa cell proliferation and restores estrogen secretion via activating the PI3K/Akt pathway. In vivo experiments further confirmed that GPS effectively attenuates ERS-induced ovarian damage in mice. Collectively, these findings reveal that GPS improves granulosa cell function and ovarian tissue integrity by modulating the ERS network and the PI3K/Akt pathway, yielding a theoretical basis for preventing follicular atresia and enhancing reproductive efficiency in cattle. Full article

Forkhead box class O1 (FOXO1) and fas-associated death domain (FADD) regulate cell death pathways and homeostatic processes such as cell cycle progression and apoptosis. FADD phosphorylation promotes nuclear localization of FOXO1, and FOXO1 regulates FADD expression. Therefore, it is plausible that FOXO1 and FADD have synergistic or antagonistic effects on cell cycle regulation and the response to anticancer drug treatment in cancer cells. In the present study, we report that AS1842856-mediated inhibition of FOXO1 reverses anticancer drug-induced cytotoxicity, while FADD knockdown increases anticancer drug-induced cytotoxicity in osteosarcoma (OS). Reversed anticancer drug-induced cytotoxicity was accompanied by G2/M cell cycle arrest and increased expression of p21. The anticancer function of FOXO1 was further supported by the observation that OS cells that express higher basal levels of FOXO1 had increased sensitivity to camptothecin-induced cytotoxicity. FADD knockdown reversed the FOXO1 inhibition-induced increase in p21 expression. The results presented in this study indicate that FOXO1 has a tumor suppressor function, while FADD has a tumor-promoting function in OS following anticancer drug treatment. The experimental approach used in this investigation also indicates that FADD antagonizes the effect of FOXO1 on p21 expression in OS. Full article

Reactive oxygen species (ROS)-induced aberrant oncogenic signalling has been proposed to mediate the progression and development of pleural mesothelioma (PM). In this study, we demonstrate how ROS promote oncogenic signalling, especially in the context of cell migration and immune evasion via YB-1 phosphorylation in mesothelial and PM cell models. Xanthine (X)- and xanthine oxidase (XO)-generated ROS exposure led to increased migration and a more elongated cell shape in mesothelial and PM cells in live-cell videomicroscopy analyses. These effects were associated with the enhanced phosphorylation of ERK, AKT, and YB-1 and the elevated gene expression of PD-L1 and PD-L2, which were analysed with immunoblotting and quantitative real-time RT-PCR, respectively. The pharmacological inhibition of AKT (ipatasertib), MEK (trametinib), and RSK (BI-D1870) resulted in the reversal of ROS-induced effects, with the strongest effects observed upon the inhibition of YB-1 phosphorylation by BI-D1870. The results suggest that ROS exposure has a strong impact on cell migration and immune evasion not only in PM cells but also in mesothelial cells, from which PM arises. Interfering with ROS-responsive kinase pathways, particularly YB-1 phosphorylation, could counteract pro-migratory and immune-evasive effects in PM. Full article

Background: Gout is an inflammatory arthritis associated with increased bone anabolism and a higher risk of ectopic bone formation. Colchicine, used to prevent and treat acute gouty flares, inhibits microtubule polymerization and has been described to promote osteoblastogenesis. In bone disorders such as osteoporosis, disruption of the osteoblast–adipocyte balance contributes to pathology, yet no therapies directly target bone marrow adiposity. Thus, we decided to investigate the impact of colchicine on the osteoblast-adipocyte balance. Methods: C3H10T1/2 mesenchymal stem cells were differentiated to both cell fates in the presence or absence of colchicine. Differentiation was assessed by studying differentiation phenotypes as well as adipocytic and osteoblastic marker genes. Disrupting microtubule homeostasis through stathmin (STMN1) silencing was employed to mimic colchicine effects on differentiation. Proteomic analysis was performed to gain further insight into colchicine’s effects on adipogenesis. Results: Colchicine promoted transcriptional changes consistent with osteoblastogenic commitment and inhibited adipogenesis, as evidenced by reduced intracellular lipid accumulation and downregulation of adipogenic marker genes. These effects were observed following both continuous and transient exposure (median fold change across adipogenic markers 0.41 and 0.59, respectively). Consistent with colchicine-induced microtubule destabilisation, microtubule disruption by STMN1 silencing also suppressed adipogenic differentiation (median fold change = 0.66), suggesting that colchicine’s anti-adipogenic effect may be due to its impact on the cytoskeleton. Conclusions: These findings indicate that colchicine can suppress adipogenic differentiation while favouring osteoblast commitment in mesenchymal stem cells. Although further validation in relevant preclinical models is required, its efficacy following transient exposure supports the exploration of site-specific strategies that limit systemic toxicity. Full article

Silicon oxide/graphite (SiO_x/Gr) anodes are promising candidates for high energy-density lithium-ion batteries. However, their complex multiphysics degradation mechanisms pose challenges for accurately interpreting and predicting capacity fade behavior. In particular, existing multiphysics models typically treat gas generation and solid electrolyte interphase (SEI) growth as independent or unidirectionally coupled processes, neglecting their bidirectional interactions. Here, we develop an electro–thermal–mechanical–gaseous coupled model to capture the dominant degradation processes in SiO_x/Gr anodes, including SEI growth, gas generation, SEI formation on cracks, and particle fracture. Model validation shows that the proposed framework can accurately reproduce voltage responses under various currents and temperatures, as well as capacity fade under different thermal and mechanical conditions. Based on this validated model, a mechanistic analysis reveals two key findings: (1) Gas generation and SEI growth are bidirectionally coupled. SEI growth induces gas release, while accumulated gas in turn regulates subsequent SEI evolution by promoting SEI formation through hindered mass transfer and suppressing it through reduced active surface area. (2) Crack propagation within particles is jointly governed by the magnitude and duration of stress. High-rate discharges produce large but transient stresses that restrict crack growth, while prolonged stresses at low rates promote crack propagation and more severe structural degradation. This study provides new insights into the coupled degradation mechanisms of SiO_x/Gr anodes, offering guidance for performance optimization and structural design to extend battery cycle life. Full article

The immunosuppressive T regulatory cells (Tregs) regulate immune responses and maintain immune homeostasis, yet their functions in metabolic dysfunction-associated steatotic liver disease (MASLD) remain controversial. Here we report increased accumulation of Tregs and effector T cells within the liver parenchyma of mice fed a Western diet (WD). This pattern was also observed in MASH patients, where an increase in intrahepatic Tregs was noted. In the absence of adaptive immune cells in Rag1 KO mice, WD promoted accumulation of intrahepatic neutrophils and macrophages and exacerbated hepatic inflammation and fibrosis. Similarly, targeted Treg depletion exacerbated WD-induced hepatic inflammation and fibrosis. In Treg-depleted mice, hepatic injury was associated with increased accumulation of neutrophils, macrophages, and activated T cells in the liver. Conversely, induction of Treg numbers using recombinant IL2/αIL2 mAb cocktail reduced hepatic steatosis, inflammation, and fibrosis in WD-fed mice. Analysis of intrahepatic Tregs from WD-fed mice revealed a phenotypic signature of impaired Treg function in MASLD. Ex vivo functional studies showed that glucose and palmitate, but not fructose, impaired the immunosuppressive ability of Treg cells. The findings indicate that the liver microenvironment in MASLD impairs the ability of Tregs to suppress effector immune cell activation, thus perpetuating chronic inflammation and driving MASLD progression. Full article