Search Results (6,546)

Mastitis is a common inflammatory disease that harms mammary gland health. Its development is closely linked to dysregulated inflammatory signaling. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, has potential anti-inflammatory effects. However, its molecular mechanism in mastitis prevention remains unclear. In this study, we used both in vivo and in vitro models to evaluate how EPA pretreatment regulates mastitis-related inflammatory signaling. Transcriptome analysis showed that differentially expressed genes after EPA treatment were mainly enriched in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. In an LPS-induced mastitis model, EPA restored the LPS-reduced PPARγ protein level and suppressed NF-κB p65 activation, consistent with reduced nuclear translocation of p65. Similar effects were observed in mammary epithelial cells, where EPA inhibited NF-κB activation at 50 and 100 μM. Functional experiments further showed that a PPARγ agonist mimicked the inhibitory effect of EPA on p65, whereas PPARγ antagonist partially abrogated EPA-mediated inhibition of p65. Collectively, these data indicate that EPA attenuates mastitis-associated inflammation at least in part through the PPARγ–NF-κB axis. Full article

Rice is a globally important food crop, and its production is often affected by extreme climates such as drought and high temperatures. This study investigated how drought applied at different growth stages affects cadmium (Cd) uptake and accumulation in rice, as well as the underlying mechanisms. The results showed that drought treatments generally increased soil organic matter and alkali-hydrolyzed nitrogen content but decreased pH and available phosphorus content. The available Cd content in soil under the grain-filling stage drought treatment was lower than that under other treatments. Speciation analysis showed that under grain-filling stage drought, exchangeable Cd decreased by 3.04%, and residual Cd increased by 2.67%. Furthermore, drought treatments significantly enhanced soil urease and sucrase activities. Rice plant height and yield were significantly affected by the timing of drought, with the grain-filling stage drought treatment yielding the highest, while full growth stage and tillering stage drought treatments resulted in significantly lower yields. Cd content in various organs followed the order: root > stem > leaf > brown rice, with the brown rice Cd content being the lowest under grain-filling stage drought. In conclusion, drought treatment during the grain-filling stage had the least effect on Cd content in various rice tissues while maintaining a relatively high yield, providing a theoretical basis for water management in Cd-contaminated paddy fields. Full article

Leucine-rich repeat kinase 2 (LRRK2) is a multidomain serine/threonine kinase and a major genetic contributor to Parkinson’s disease (PD). Although LRRK2 has been extensively studied in neurodegeneration, emerging evidence indicates that it also plays a critical role in systemic metabolism. LRRK2 regulates glucose homeostasis through modulation of insulin signaling, vesicle trafficking, mitochondrial function, and inflammatory responses. Studies using LRRK2 knockout and knock-in models, including the pathogenic G2019S mutation, have revealed abnormalities in insulin sensitivity, adipose tissue inflammation, hepatic glucose production, and skeletal muscle metabolism. Mechanistically, LRRK2 phosphorylates Rab GTPases, thereby controlling insulin receptor trafficking and GLUT4 translocation. In addition, LRRK2 influences mitochondrial dynamics and reactive oxygen species production, linking metabolic stress to inflammatory signaling. Importantly, LRRK2 also regulates innate immune pathways, including TLR4–NFκB signaling and inflammasome activation, thereby connecting peripheral metabolic dysfunction to neuroinflammation. Here, we propose an integrated metabolic–neuroinflammatory crosstalk model in which LRRK2 functions as a molecular coordinator linking peripheral metabolic dysfunction to central neurodegeneration. In this framework, systemic metabolic stress—characterized by insulin resistance, chronic inflammation, advanced glycation end product (AGE) accumulation, and blood–brain barrier disruption—drives microglial activation and neurodegenerative processes. Understanding this systemic axis may provide new therapeutic opportunities targeting both metabolic dysfunction and neurodegeneration in PD. Full article

Silicon deficiency is widespread in soils of Southeastern China and may constrain nitrogen (N)-use efficiency and yield formation in oilseed rape; therefore, this study aimed to identify an N-reduction window enabled by silicon (Si) fertilization and to clarify the underlying mechanisms. Field experiments were conducted in Putian, Fujian Province (2023–2025), with five treatments: conventional N (T1, 300 kg·N·ha⁻¹), conventional N plus Si (T1+Si, 150 kg·Si·ha⁻¹), and three N rates (120%, 80%, and 60% of conventional N; T2+Si, T3+Si, and T4+Si) under a fixed Si input. Yield, N-use efficiency, plant physiological traits, soil quality index (SQI), and nitrogen-cycle ecosystem multifunctionality were assessed. Compared with T1, T1+Si and T3+Si increased yield by 6.55% and 6.06%, respectively, accompanied by higher dry matter translocation (27.20% and 34.60%) and improved N-use efficiency (28.86% and 39.66%). SQI increased by 31.42% (T1+Si) and 33.03% (T3+Si), while nitrogen-cycle multifunctionality increased by 32.42% and 58.42%, respectively. Correlation and path analyses indicated that Si promoted yield formation by simultaneously alleviating soil constraints (lower exchangeable acidity and Al³⁺; higher cation exchange capacity) and enhancing plant assimilation and allocation processes, thereby reducing potential N losses and strengthening N cycling. Overall, applying 150 kg·Si·ha⁻¹ combined with a 20% reduction in N (240 kg·N·ha⁻¹) achieved stable yield gains and coordinated improvements in soil quality, providing an operational fertilization window for Si-enabled N management in regional oilseed rape systems. Full article

Encephalomyocarditis virus (EMCV) belongs to the genus Cardiovirus of the family Picornaviridae. It is a non-enveloped, positive-sense, single-stranded RNA virus and an important pathogen causing encephalomyocarditis (EMC). Tripartite motif 13 (TRIM13) is a member of the tripartite motif (TRIM) family and serves as an important effector molecule in antiviral innate immunity. However, its antiviral activity and underlying molecular mechanisms during EMCV infection remain unknown. In this study, we identified TRIM13 as a regulator of NF-κB activation. TRIM13, dependent on its E3 ubiquitin ligase activity, directly binds to IκBα and dose-dependently increases its phosphorylation level. To determine the chain type of IκBα polyubiquitination, antibodies specific for K48-linked and K63-linked ubiquitin were used. Our data indicated that IκBα was subjected to polyubiquitination independent of K48 and K63 linkages. This interaction promotes non-K48/K63-linked polyubiquitination of IκBα, thereby inducing NF-κB nuclear translocation. Subsequently, nuclear NF-κB activates the secretion of pro-inflammatory cytokines, exacerbating inflammatory responses and ultimately facilitating EMCV infection. Full article

Background: Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, is increasingly recognized as a thromboinflammatory disorder involving coagulation, innate immunity, endothelial dysfunction, and vascular homeostasis. Emerging evidence suggests that gut microbiome-related inflammatory and metabolic signals may influence pathways potentially relevant to VTE through intestinal barrier dysfunction, microbial translocation, and microbiome-derived metabolites. This review critically examines the direct and indirect evidence relating gut dysbiosis to mechanisms potentially relevant to venous thrombogenesis. Methods: A structured literature search of PubMed, Scopus, and Web of Science was conducted from database inception to February 2026. Observational, translational, experimental, preclinical, and selected genetic studies were narratively synthesized across heterogeneous evidence types. Results: Available evidence suggests that intestinal barrier dysfunction and microbial translocation may increase systemic exposure to lipopolysaccharide and other microbial products, potentially contributing to inflammatory signaling and procoagulant responses. Proposed downstream effects include tissue factor (TF) activation, platelet reactivity, neutrophil extracellular traps (NETs) formation, complement signaling, endothelial perturbation, and impaired balance of anticoagulant and fibrinolytic pathways. Microbiome-derived metabolites, including trimethylamine N-oxide (TMAO), phenylacetylglutamine (PAGln), bile acids, and short-chain fatty acids (SCFAs), have been linked, mainly in experimental or non-VTE settings, to thrombosis-related biology. However, most evidence remains indirect, associative, or experimental, whereas direct human VTE-specific evidence is limited and heterogeneous. Conclusions: The gut microbiome–VTE axis is biologically plausible and supported mainly by mechanistic and indirect evidence, but current data are insufficient to support strong causal conclusions. Further longitudinal, well-phenotyped, mechanistically informed studies are needed to determine whether microbiome-related pathways have measurable clinical relevance in human VTE. Full article

The NAC (NAM, ATAF1/2, and CUC1/2) family of transcription factors (TFs) play critical roles in regulating salt tolerance across diverse plant species. This study identified and characterized 101 NAC TFs in eggplant (Solanum melongena L.), revealing their diverse physicochemical properties, chromosomal distributions, and evolutionary relationships. Based on its salt stress-induced expression pattern and homology to known salt-responsive NAC factors, SmNAC28 was selected as a key candidate for functional investigation of salt tolerance. Expression profiling indicated that SmNAC28 is preferentially expressed in roots and stems, and its transcript levels are modulated by salt stress. Subcellular localization confirmed that SmNAC28 localizes to both the plasma membrane and nucleus, a dynamic distribution regulated by S-palmitoylation. Under normal conditions, SmNAC28 is anchored to the plasma membrane and nucleus via S-palmitoylation; upon salt stress exposure, it undergoes depalmitoylation and translocates to the nucleus. Using a hairy root transformation system in eggplant, we demonstrated that overexpression of SmNAC28 in roots significantly enhanced salt tolerance by mitigating oxidative damage, maintaining ion homeostasis, and promoting osmotic adjustment. Analysis of transcript levels further revealed that SmNAC28 overexpression upregulated ion transporter genes (NHX2, CHXs), signaling genes (CIPKs), and the proline biosynthesis gene (P5CS), which demonstrated that SmNAC28 integrates antioxidant defense, ion homeostasis, and osmotic regulation to confer salt tolerance. This study reveals the response mechanism of SmNAC28 to salt stress of the eggplant transcription factor SmNAC28 under salt stress, and provided a research foundation for salt tolerance breeding. Full article

Ultraviolet B (UVB), as a major component of solar radiation, is a key factor in inducing skin photoaging. The epidermis serves as the primary defensive barrier of the skin and absorbs the majority of UVB. This study aims to elucidate the protective effect of Alk against UVB-induced photoaging and further uncover its underlying molecular mechanisms. In vitro, Alk-pretreated HaCaT cells were exposed to UVB. Cell viability, ROS, senescence, antioxidant enzymes, and protein expression were analyzed. Mechanisms were examined using CETSA, DARTS, Co-IP, and NRF2 knockout. In vivo, Alk hydrogel was tested in UVB-exposed BALB/c mice, with protection assessed via histology and immunohistochemistry. In vitro, Alk directly binds to Keap1, disrupts Keap1–Nrf2 interaction, promotes nuclear translocation of Nrf2, and upregulates the expression of its downstream target HO-1. Consequently, intracellular ROS generation is reduced, cellular senescence is alleviated, and the expression of inflammatory factors (TNF-$\alpha$, COX-2) and MMP-9 is suppressed. In vivo, topical application of the Alk hydrogel prevented UVB-induced skin thickening and collagen degradation. Alk exerts a preventive effect on UVB-induced photoaging in HaCaT cells and skin, providing strong support for developing Alk as a potential plant-derived active ingredient for preventing skin photoaging. Full article

Glucose transporter type 4 (GLUT4), encoded by the SLC2A4 gene, is the final effector of insulin-stimulated glucose uptake in insulin-sensitive tissues: skeletal muscle, adipose tissue, and cardiac muscle. Its dynamic localization, retained intracellularly under basal conditions and extensively translocated to the plasma membrane upon stimulation, makes it a master regulator of glycemic homeostasis. While the canonical insulin pathway (PI3K/Akt/TBC1D4) is the most potent and specific mechanism in the postprandial state, its dysfunction is centrally associated with insulin resistance and type 2 diabetes mellitus (T2DM). Crucially, robust alternative signaling networks function completely independently of insulin to regulate GLUT4 synthesis and translocation. Prominent among these are contraction-mediated pathways in skeletal muscle, which employ calcium signaling (via CaMKII), mechanical/metabolic stress sensors (via p38 MAPK γ/δ), and AMP-activated protein kinase (AMPK). This review critically integrates current knowledge, linking the molecular architecture and post-translational modifications of GLUT4 to the complex, tissue-specific signaling networks that govern its vesicular trafficking. We emphasize the hierarchy, redundancy, and interdependence of these pathways, highlighting differences between acute translocation and chronic transcriptional adaptations. Finally, we discuss how deciphering insulin-independent mechanisms offers promising therapeutic opportunities, particularly in identifying pharmacological targets that mimic the metabolic benefits of physical exercise. Full article

Mining activities in Chile generate massive amounts of tailings, creating significant environmental risks due to heavy metal contamination. Phytoremediation offers an eco-friendly solution, yet studies on native Chilean species are scarce. This study evaluates the effects of ethylenediamine tetraacetic acid (EDTA) and nanoscale zero-valent iron (nZVI) on the potential of the native Cistanthe grandiflora for the phytoremediation of copper mine tailings. A six-month pot experiment was conducted with four treatments: EDTA 300 mg·kg⁻¹, EDTA 600 mg·kg⁻¹, nZVI 500 mg·kg⁻¹, and a control group without additions. The results indicate that Cistanthe grandiflora primarily acts as a phytostabilizer, accumulating higher metal concentrations in roots than in aerial parts. The application of EDTA significantly enhanced the Bioconcentration Factor for Cu, Ni, Pb, and Mo, increasing BCF values from 0.5 to 1.0 or more in several cases. Specifically, a lower dose of EDTA (300 mg·kg⁻¹) successfully increased the Translocation Factor (TF) of cadmium to 1.3, suggesting a potential for phytoextraction for this element. Conversely, nZVI application showed a limited impact, slightly improving the Translocation factor for copper and chromium but without exceeding unity. These findings demonstrate that Cistanthe grandiflora, assisted by EDTA, is a promising candidate for the phytostabilization of heavy metals in mine tailings. Full article

Pseudomonas plecoglossicida causes bacterial hemorrhagic ascites in ayu (Plecoglossus altivelis), a lethal disease characterized by abdominal distension with hemorrhagic ascites, multifocal organ hemorrhages, and histopathologically evident hepatocellular necrosis and inflammatory infiltration. The lack of effective treatments exacerbates mass mortalities, posing a significant threat to aquaculture. Given the severe pathogenesis of P. plecoglossicida infection—which involves bacterial colonization, tissue necrosis, and host immune dysregulation—effective therapeutic strategies are urgently needed. Through a screen of traditional Chinese medicine monomers, we identified harmine, an indole alkaloid derived from Peganum harmala seeds, as a potent agent against this pathogen. In vivo, harmine exhibited direct bactericidal activity by disrupting membrane integrity, as evidenced by increasing membrane permeability, and inhibiting biofilm formation. In an ayu infection model, harmine significantly increased host survival, reduced tissue bacterial load, and enhanced innate immunity by augmenting monocyte/macrophage phagocytosis and bactericidal capacity while suppressing pro-inflammatory cytokine release and apoptosis. Mechanistically, the Drug Affinity Responsive Target Stability assay was used to identify the molecular target of harmine, followed by functional validation through PRDX6−knockdown experiments. Harmine exhibited direct bactericidal activity by disrupting membrane integrity and inhibiting biofilm formation. In the ayu infection model, harmine significantly increased host survival, reduced tissue bacteria1 load, and enhanced innate immunity by augmenting monocyte/macrophage system and bactericidal capacity while suppressing pro-inflammatory cytokine release and apoptosis, the latter likely through modulation of PRDX6−mediated oxidative stress and downstream caspase signaling. Mechanistically, DARTS revealed that harmine binds to peroxiredoxin 6 (PRDX6), a multifunctional enzyme possessing peroxidase, phospholipase A₂, and lysophosphatidylcholine acyltransferase activities. This binding liberates TNF receptor-associated factor 6 (TRAF6), facilitating its mitochondrial translocation and association with the ECSIT signaling integrator complex, thereby amplifying mitochondrial reactive oxygen species (mROS) production and potentiating macrophage-mediated bacterial killing. These findings establish harmine as a promising therapeutic candidate for controlling P. plecoglossicida infections and underscore the value of host-directed immunomodulation derived from natural products in aquaculture medicine. Full article

Bladder cancer is one of the most common malignancies of the urinary system. Identifying new potential therapeutic targets and exploring molecular mechanisms are crucial for improving treatment and prognosis. The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel 2, known to play a key role in various physiological and pathological processes, has an unclear function and mechanism of action in bladder cancer. We employed bioinformatics analysis and immunohistochemistry to assess the role of HCN2 in bladder cancer, integrating in vitro and in vivo models to evaluate the impact of HCN2 on cell behavior. Molecular interactions were characterized using immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays. Our investigation revealed a significant upregulation of HCN2 in bladder cancer tissues, which was predictive of a poorer clinical outcome. Functionally, HCN2 knockdown in bladder cancer impeded cell proliferation, induced apoptosis, and curtailed migration and invasion. Mechanistically, the overexpression of HCN2 contributed to the translocation of the REST transcription factor into the nucleus and facilitated its binding to the BGN promoter for transcriptional activation of its expression. This regulatory mechanism was shown to suppress ferroptosis, a form of regulated cell death, thereby enhancing the proliferative and tumorigenesis of bladder cancer cells. This study uncovers the novel mechanism by which HCN2 regulates ferroptosis via the REST-BGN axis, affecting bladder cancer cell behavior, and provides new perspectives and strategies for future clinical treatment. Full article

Haplosporidium edule is a haplosporidian parasite originally described in the common edible cockle (Cerastoderma edule) along the European Atlantic coast. In this study, we report the first detection of H. edule in the olive-green cockle (Cerastoderma glaucum) from the northern Adriatic Sea, representing both a novel host record and a new geographic occurrence. During a cross-sectional study conducted in May 2019, 90 C. glaucum specimens were collected from three lagoon sites in northeastern Italy. Histological examination of soft tissues revealed haplosporidian developmental stages, including plasmodia, sporoblasts and mature spores, within connective tissues of the mantle, digestive gland, gills and between gonadal tubules in eight individuals from the Goro Lagoon. Molecular characterization based on a fragment of the small subunit ribosomal DNA showed high similarity with the previously published H. edule sequence. Host identification was confirmed through cytochrome c oxidase subunit I barcoding together with morphological and histological analyses. These findings indicate that H. edule has a broader host range than previously recognized. Although prevalence was relatively low, the detection of this parasite in a new host species and geographic area highlights the importance of continued surveillance, particularly in the context of climate change, shellfish translocations and the expansion of aquaculture activities. Full article

Background: Late-onset anaerobic prosthetic joint infection (PJI) is uncommon but may indicate underlying, previously asymptomatic colorectal malignancy. While the association between Streptococcus bovis group (SBG) bacteremia and colorectal cancer is well established, links between anaerobic PJIs and colorectal neoplasia are rarely reported. Anaerobic organisms originating from the gastrointestinal tract may translocate via the hematogenous route, and their presence in PJI should prompt clinicians to consider occult colorectal pathology. Methods: All periprosthetic arthroplasty infection cases between 2015 and 2025 were reviewed. Clinical records, diagnostic findings, microbiological data, and treatment outcomes were analyzed. Results: Three female patients (mean age 76.3 years) presented with late-onset PJI occurring at least five years after primary total knee arthroplasty. Causative organisms included Bacteroides fragilis, Morganella morganii, and Klebsiella pneumoniae. All patients underwent two single-stage revision surgeries and one debridement, antibiotics and implant retention (DAIR) procedure. Cross-sectional computed tomography imaging of the abdomen and pelvis (CT-AP) performed to evaluate hematogenous sources of infection consistently revealed previously undiagnosed colorectal malignancy. One patient had additional metastatic disease. Postoperative complications included one case of pulmonary embolism; no other major complications were observed. Conclusions: Anaerobic PJIs are rare, and their association with colorectal malignancy is not well established. These cases highlight the importance of evaluating potential gastrointestinal sources, including occult colorectal cancer, in patients presenting with late-onset anaerobic PJI. Full article

Background/Objectives: Non-small-cell lung cancer (NSCLC) involves oxidative stress and inflammation, driving chemoresistance. Paclitaxel (PTX), a first-line chemotherapy, is limited by these factors. Danggui Buxue Tang (DBT), a polyphenolic-rich traditional Chinese herbal formula, was investigated for its ability to potentiate PTX efficacy by inducing ferroptosis via the Nrf2/GPX4 axis. Methods: Effects of DBT + PTX on cell viability, lipid peroxidation, iron accumulation, and Nrf2/GPX4/SLC7A11 expression were evaluated in A549/HCC827 cells with/without ferrostatin-1 (Fer-1). Findings were validated in an A549 xenograft model. Results: DBT significantly enhanced PTX’s anti-tumor effects in vitro and in vivo, an effect reversed by Fer-1. Combination therapy increased ROS, MDA, and iron while suppressing GPX4/SLC7A11 and promoting Nrf2 nuclear translocation. DBT + PTX synergistically reduced tumor volume and proliferation markers (Ki67/PCNA). Crucially, DBT attenuated PTX-induced hepatotoxicity and nephrotoxicity. Conclusions: DBT potentiates PTX efficacy in NSCLC by disrupting the Nrf2/GPX4 axis to induce ferroptosis while mitigating chemotherapy-related toxicity, supporting its potential as an adjuvant strategy targeting oxidative stress pathways. Full article