Search Results (2,024)

Fyn is widely involved in diverse cellular physiological processes, including cell growth and survival, and has been implicated in the regulation of energy metabolism and the pathogenesis of diabetes mellitus through multiple pathways. Fyn plays a role in increasing fat accumulation and promoting insulin resistance, and it also contributes to the development of diabetic complications such as diabetic kidney disease and diabetic retinopathy. The primary mechanism by which Fyn modulates lipid metabolism is that it inhibits AMP-activated protein kinase (AMPK). Additionally, it affects energy homeostasis through regulating specific signal pathways affecting lipid metabolism including pathways related to CD36, through enhancement of adipocyte differentiation, and through modulating insulin signal transduction. Inflammatory stress is one of the fundamental mechanisms in diabetes mellitus and its complications. Fyn also plays a role in inflammatory stress-related signaling cascades such as the Akt/GSK-3β/Fyn/Nrf2 pathway, exacerbating inflammation in diabetes mellitus. Therefore, Fyn emerges as a promising therapeutic target for regulating glucolipid metabolism and alleviating type 2 diabetes mellitus. This review synthesizes research on the role of Fyn in the regulation of energy metabolism and the development of diabetes mellitus, while exploring its specific regulatory mechanisms. Full article

One hundred presumptive Pseudomonas isolates, recovered from 15 sites impacted by anthropogenic activity in the Foggia district (Italy), were screened for key adaptive and functional traits important for environmental applications. The isolates were phenotypically characterized for their ability to grow under combined pH (5.0–8.0) and temperature (15–37 °C) conditions, to produce proteolytic enzymes, pigments, and exopolysaccharides, and to tolerate SDS. Moreover, the resistance to six environmentally relevant heavy metals (Cd, Co, Cu, Ni, Zn, As) was qualitatively assessed. The results highlighted wide inter-strain variability, with distinct clusters of isolates showing unique combinations of stress tolerance, enzymatic potential, and resistance profile. PERMANOVA analysis revealed significant effects of both the isolation site and the metal type, as well as their interaction, on the observed resistance patterns. A subset of isolates showed co-tolerance to elevated temperatures and heavy metals. These findings offer an initial yet insightful overview of the adaptive diversity of soil-derived Pseudomonas, laying the groundwork for the rational selection of strains for bioaugmentation in contaminated soils. Full article

Background Plasma membrane proteins (PMPs) play key roles in cell signalling, adhesion, and trafficking, and are attractive therapeutic targets in cancer due to their surface accessibility. However, their typically low abundance limits detection by conventional proteomic approaches. Methods: To improve PMP detection, we employed a surface proteomics workflow combining cell surface biotinylation and affinity purification prior to LC-MS/MS analysis in cervical (SiHa) and bladder (UMUC3) cancer cell lines cultured under normoxic (21% O₂) or hypoxic (0.1% O₂) conditions. Results: In SiHa cells, 43 hypoxia-upregulated proteins were identified exclusively in the biotin-enriched fraction, including ITGB2, ITGA7, AXL, MET, JAG2, and CAV1/CAV2. In UMUC3 cells, 32 unique upregulated PMPs were detected, including CD55, ADGRB1, SLC9A1, NECTIN3, and ACTG1. These proteins were not observed in corresponding whole-cell lysates and are associated with extracellular matrix remodelling, immune modulation, and ion transport. Biotinylation enhanced the detection of membrane-associated pathways such as ECM organisation, integrin signalling, and PI3K–Akt activation. Protein–protein interaction analysis revealed links between membrane receptors and intracellular stress regulators, including mitochondrial proteins. Conclusions: These findings demonstrate that surface biotinylation improves the sensitivity and selectivity of plasma membrane proteomics under hypoxia, revealing hypoxia-responsive proteins and pathways not captured by standard whole-cell analysis. Full article

Freshwater salinization, an escalating global environmental stressor, poses a significant threat to freshwater biodiversity, including fish communities. This study investigates the grass carp (Ctenopharyngodon idellus), a species with the highest aquaculture output in China, to elucidate the molecular underpinnings of its physiological adaptations to fluctuating salinity gradients. We used high-throughput mRNA sequencing and differential gene expression profiling to analyze transcriptional dynamics in intestinal and kidney tissues of grass carp exposed to heterogeneous salinity stressors. Concurrent serum biochemical analyses showed salinity stress significantly increased Na⁺, Cl⁻, and osmolarity, while decreasing lactate and glucose. Salinity stress exerted a profound impact on the global transcriptomic landscape of grass carp. A substantial number of co-regulated differentially expressed genes (DEGs) in kidney and intestinal tissues were enriched in immune and metabolic pathways. Specifically, genes associated with antigen processing and presentation (e.g., cd4-1, calr3b) and apoptosis (e.g., caspase17, pik3ca) exhibited upregulated expression, whereas genes involved in gluconeogenesis/glycolysis (e.g., hk2, pck2) were downregulated. KEGG pathway enrichment analyses revealed that metabolic and cellular structural pathways were predominantly enriched in intestinal tissues, while kidney tissues showed preferential enrichment of immune and apoptotic pathways. Rigorous validation of RNA-seq data via qPCR confirmed the robustness and cross-platform consistency of the findings. This study investigated the core transcriptional and physiological mechanisms regulating grass carp’s response to salinity stress, providing a theoretical foundation for research into grass carp’s resistance to salinity stress and the development of salt-tolerant varieties. Full article

Activation of macrophages plays a key role in both inflammation and oxidative stress, key features of many chronic diseases. Pro-inflammatory M1-like macrophages, in particular, contribute to pro-oxidative environments and are a frequent focus of immunological research. This research examined the effects of kiwifruit allergen Act d 1, in comparison to LPS, on THP-1 macrophages in vitro differentiated under optimized conditions, both in the presence and in the absence of selected vanilloids. THP-1 monocyte differentiation was optimized by varying PMA exposure and resting time. Act d 1 induced M1-like phenotypic changes comparable to LPS, including upregulation of CD80, IL-1β and IL-6 secretion, gene expression of iNOS and NF-κB activation, in addition to increased reactive oxygen species (ROS) and catalase activity. Treatment with specific vanilloids mitigated these responses, primarily through reduced oxidative stress and NF-κB activation. Notably, vanillin (VN) was the most effective, also reducing CD80 expression and IL-1β levels. These results suggest that vanilloids can affect pro-inflammatory signaling and oxidative stress in THP-1 macrophages and highlight their potential to alter inflammatory conditions characterized by similar immune responses. Full article

Hydrogen-rich water (HRW) has shown neuroprotective effects in acute brain injury, but its role in chronic radiation-induced brain injury (RIBI) remains unclear. This study investigated the long-term efficacy of HRW in mitigating cognitive impairment and neuronal damage caused by chronic RIBI. Fifty male Sprague Dawley rats were randomly divided into five groups: control, irradiation (IR), IR with memantine, IR with HRW, and IR with combined treatment. All but the control group received 20 Gy whole-brain X-ray irradiation, followed by daily interventions for 60 days. Behavioral assessments, histopathological analyses, oxidative stress measurements, ¹⁸F-FDG PET/CT imaging, transcriptomic sequencing, RT-qPCR, Western blot, and serum ELISA were performed. HRW significantly improved anxiety-like behavior, memory, and learning performance compared to the IR group. Histological results revealed that HRW reduced neuronal swelling, degeneration, and loss and enhanced dendritic spine density and neurogenesis. PET/CT imaging showed increased hippocampal glucose uptake in the IR group, which was alleviated by HRW treatment. Transcriptomic and molecular analyses indicated that HRW modulated key genes and proteins, including CD44, CD74, SPP1, and Wnt1, potentially through the MIF, Wnt, and SPP1 signaling pathways. Serum CD44 levels were also lower in treated rats, suggesting its potential as a biomarker for chronic RIBI. These findings demonstrate that HRW can alleviate chronic RIBI by preserving neuronal structure, reducing inflammation, and enhancing neuroplasticity, supporting its potential as a therapeutic strategy for radiation-induced cognitive impairment. Full article

Difficult, extreme operating conditions of parabolic antennas under precipitation and sub-zero temperatures require the creation of effective heating systems. The purpose of the research is to develop a multilayer coating containing two metal-ceramic layers, epoxy composite layers, carbon fabric, and an outer layer of basalt fabric, which allows for effective heating of the antenna, and to study the properties of this coating. The multilayer coating was formed on an aluminum base that was subjected to abrasive jet processing. The first and second metal-ceramic layers, Al₂O₃ + 5% Al, which were applied by high-speed multi-chamber cumulative detonation spraying (CDS), respectively, provide maximum adhesion strength to the aluminum base and high adhesion strength to the third layer of the epoxy composite containing Al₂O₃. On this not-yet-polymerized layer of epoxy composite containing Al₂O₃, a layer of carbon fabric (impregnated with epoxy resin) was formed, which serves as a resistive heating element. On top of this carbon fabric, a layer of epoxy composite containing Cr₂O₃ and SiO₂ was applied. Next, basalt fabric was applied to this still-not-yet-polymerized layer. Then, the resulting layered coating was compacted and dried. To study this multilayer coating, X-ray analysis, light and raster scanning microscopy, and transmission electron microscopy were used. The thickness of the coating layers and microhardness were measured on transverse microsections. The adhesion strength of the metal-ceramic coating layers to the aluminum base was determined by both bending testing and peeling using the adhesive method. It was established that CDS provides the formation of metal-ceramic layers with a maximum fraction of lamellae and a microhardness of 7900–10,520 MPa. In these metal-ceramic layers, a dispersed subgrain structure, a uniform distribution of nanoparticles, and a gradient-free level of dislocation density are observed. Such a structure prevents the formation of local concentrators of internal stresses, thereby increasing the level of dispersion and substructural strengthening of the metal-ceramic layers’ material. The formation of materials with a nanostructure increases their strength and crack resistance. The effectiveness of using aluminum, chromium, and silicon oxides as nanofillers in epoxy composite layers was demonstrated. The presence of structures near the surface of these nanofillers, which differ from the properties of the epoxy matrix in the coating, was established. Such zones, specifically the outer surface layers (OSL), significantly affect the properties of the epoxy composite. The results of industrial tests showed the high performance of the multilayer coating during antenna heating. Full article

Cutaneous malignant melanoma is an extraordinarily aggressive and heterogeneous cancer that contains a small subpopulation of tumor stem cells (CSCs) responsible for tumor initiation, metastasis, and recurrence. Identification and characterization of CSCs in melanoma is challenging due to tumor heterogeneity and the lack of specific markers (CD271, ABCB5, ALDH, Nanog) and the ability of cells to dynamically change their phenotype. Phenotype-maintaining signaling pathways (Wnt/β-catenin, Notch, Hedgehog, HIF-1) promote self-renewal, treatment resistance, and epithelial–mesenchymal transitions. Tumor plasticity reflects the ability of differentiated cells to acquire stem-like traits and phenotypic flexibility under stress conditions. The interaction of CSCs with the tumor microenvironment accelerates disease progression: they induce the formation of cancer-associated fibroblasts (CAFs) and neo-angiogenesis, extracellular matrix remodeling, and recruitment of immunosuppressive cells, facilitating immune evasion. Emerging therapeutic strategies include immunotherapy (immune checkpoint inhibitors), epigenetic inhibitors, and nanotechnologies (targeted nanoparticles) for delivery of chemotherapeutic agents. Understanding the role of CSCs and tumor plasticity paves the way for more effective innovative therapies against melanoma. Full article

Cadmium (Cd) is a highly toxic heavy metal that disrupts development and reproduction, primarily through oxidative stress. In this context, sulforaphane (SFN), an antioxidant compound, may serve as a promising agent to counteract Cd-induced oxidative damage and prevent developmental and reproductive abnormalities. This study aimed to evaluate the effect of SFN on reproductive toxicity induced by cadmium chloride (CdCl₂) in the nematode Caenorhabditis elegans (C. elegans). Five experimental groups were established: (I) Control: no treatment, (II) dimethyl sulfoxide (DMSO): 48 h with 0.01% DMSO, (III) CdCl₂: 24 h with 4600 µM CdCl₂, (IV) SFN + CdCl₂: 24 h with 100 µM SFN followed by 24 h with both SFN and CdCl₂, and (V) SFN: 48 h with 100 µM SFN. Co-exposure to SFN and CdCl₂ prevented the reduction in the percentage of adult nematodes and increased egg-laying. It also significantly improved hatching rates, allowing more embryos to reach the larval stage, and prevented reductions in body size. However, no effects were observed on glutathione S-transferase-4 (GST-4) levels in the transgenic CL2166 strain. In conclusion, SFN substantially prevents Cd-induced reproductive toxicity in C. elegans. Future studies should investigate the molecular mechanisms by which SFN enhances egg-laying and offspring viability in this model. Full article

Background: Oxidative stress is a critical factor contributing to male infertility, impairing spermatogonial stem cells (SSCs) and disrupting normal spermatogenesis. This study aimed to isolate and characterize human SSCs and to investigate oxidative stress-related gene expression, protein interaction networks, and developmental trajectories involved in SSC function. Methods: SSCs were enriched from human orchiectomy samples using CD49f-based magnetic-activated cell sorting (MACS) and laminin-binding matrix selection. Enriched cultures were assessed through morphological criteria and immunocytochemistry using VASA and SSEA4. Transcriptomic profiling was performed using microarray and single-cell RNA sequencing (scRNA-seq) to identify oxidative stress-related genes. Bioinformatic analyses included STRING-based protein–protein interaction (PPI) networks, FunRich enrichment, weighted gene co-expression network analysis (WGCNA), and predictive modeling using machine learning algorithms. Results: The enriched SSC populations displayed characteristic morphology, positive germline marker expression, and minimal fibroblast contamination. Microarray analysis revealed six significantly upregulated oxidative stress-related genes in SSCs—including CYB5R3 and NDUFA10—and three downregulated genes, such as TXN and SQLE, compared to fibroblasts. PPI and functional enrichment analyses highlighted tightly clustered gene networks involved in mitochondrial function, redox balance, and spermatogenesis. scRNA-seq data further confirmed stage-specific expression of antioxidant genes during spermatogenic differentiation, particularly in late germ cell stages. Among the machine learning models tested, logistic regression demonstrated the highest predictive accuracy for antioxidant gene expression, with an area under the curve (AUC) of 0.741. Protein oxidation was implicated as a major mechanism of oxidative damage, affecting sperm motility, metabolism, and acrosome integrity. Conclusion: This study identifies key oxidative stress-related genes and pathways in human SSCs that may regulate spermatogenesis and impact sperm function. These findings offer potential targets for future functional validation and therapeutic interventions, including antioxidant-based strategies to improve male fertility outcomes. Full article

Glutathione peroxidase (GPX) is crucial in mediating plant responses to abiotic stresses. In this study, bioinformatics methods were used to identify the GPX gene family in quinoa. A total of 15 CqGPX genes were identified at the quinoa genome level and conducted preliminary analysis on their protein characteristics, chromosome distribution, gene structure, conserved domain structure, cis-acting elements, and expression patterns. Phylogenetic analysis showed that the GPX genes of quinoa, Arabidopsis, soybean, rice, and maize were divided into three groups. Most of the CqGPXs had the three characteristic conserved motifs and other conserved sequences and amino acid residues. Six types of cis-acting elements were identified in the CqGPX gene promoter, with stress and hormone response-related cis-acting elements constituting the two main categories. Additionally, the expression patterns of CqGPX genes across various tissues and their responses to treatments with NaCl, PEG, CdCl₂, and H₂O₂ were also investigated. The qRT-PCR results showed significant differences in the expression levels of the CqGPX genes under stress treatment at different time points. Consistently, the activity of glutathione peroxidase enzymes increased under stresses. Heterologous expression of CqGPX4 and CqGPX15 conferred stress tolerance to E. coli. This study will provide a reference for exploring the function of CqGPX genes. Full article

Background/Objectives: Psychosocial (PS) factors and cognitive dysfunction (CD) in patients with atrial fibrillation (AF) may negatively impact treatment compliance. The PS profile covers multiple psychological and socio-economic factors, although research is mostly limited to depression, anxiety, and work stress. This study assessed the prevalence of a broad range of PS factors in patients with AF and their relationship with cognitive decline. Methods: We retrospectively analyzed data from patients referred to a cardiovascular rehabilitation clinic between March 2017 and April 2023 who underwent standardized assessments of PS factors, cognition, and quality of life. Results: Of the 798 included patients, 230 (28.8%) had AF, with a mean age of 68.07 years (SD 9.60 years). Six of nine PS factors were present in more than half of the overall sample. Compared to non-AF patients, those with AF showed significantly higher levels of social isolation, depression, and hostility, whereas low socioeconomic status, family and work-related stress, and other mental disorders were more frequent in the non-AF group. CD was present in 67.4% of the total cohort and was more prevalent in AF patients with a higher PS burden. Patients with permanent AF reported the poorest health status. Conclusions: Integrating assessments of PS factors and cognition in cardiac rehabilitation is feasible and supports a more comprehensive, patient-centred model of care in AF. Full article

Extreme surface winds and wave heights of tropical cyclones (TCs)—pose serious threats to coastal community, infrastructure and environments. In recent decades, progress in numerical wave modeling has significantly enhanced the ability to reconstruct and predict wave behavior. This review offers an in-depth overview of TC-related wave modeling utilizing different computational schemes, with a special attention to WAVEWATCH III (WW3) and Simulating Waves Nearshore (SWAN). Due to the complex air–sea interactions during TCs, it is challenging to obtain accurate wind input data and optimize the parameterizations. Substantial spatial and temporal variations in water levels and current patterns occurs when coastal circulation is modulated by varying underwater topography. To explore their influence on waves, this study employs a coupled SWAN and Finite-Volume Community Ocean Model (FVCOM) modeling approach. Additionally, the interplay between wave and sea surface temperature (SST) is investigated by incorporating four key wave-induced forcing through breaking and non-breaking waves, radiation stress, and Stokes drift from WW3 into the Stony Brook Parallel Ocean Model (sbPOM). 20 TC events were analyzed to evaluate the performance of the selected parameterizations of external forcings in WW3 and SWAN. Among different nonlinear wave interaction schemes, Generalized Multiple Discrete Interaction Approximation (GMD) Discrete Interaction Approximation (DIA) and the computationally expensive Wave-Ray Tracing (WRT) A refined drag coefficient (C_d) equation, applied within an upgraded ST6 configuration, reduce significant wave height (SWH) prediction errors and the root mean square error (RMSE) for both SWAN and WW3 wave models. Surface currents and sea level variations notably altered the wave energy and wave height distributions, especially in the area with strong TC-induced oceanic current. Finally, coupling four wave-induced forcings into sbPOM enhanced SST simulation by refining heat flux estimates and promoting vertical mixing. Validation against Argo data showed that the updated sbPOM model achieved an RMSE as low as 1.39 m, with correlation coefficients nearing 0.9881. Full article

Cadmium (Cd) is a highly toxic heavy metal that can greatly affect crops and pose a threat to food security. Plant growth-promoting rhizobacteria (PGPR) are capable of alleviating the harm of Cd to crops. In this research, a Cd-tolerant PGPR strain was isolated and screened from the root nodules of semi-wild soybeans. The strain was identified as Pseudomonas sp. strain KM25 by 16S rRNA. Strain KM25 has strong Cd tolerance and can produce indole-3-acetic acid (IAA) and siderophores, dissolve organic and inorganic phosphorus, and has 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity. Under Cd stress, all growth indicators of soybean seedlings were significantly inhibited. After inoculation with strain KM25, the heavy metal stress of soybeans was effectively alleviated. Compared with the non-inoculated group, its shoot height, shoot and root dry weight, fresh weight, and chlorophyll content were significantly increased. Strain KM25 increased the superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities of soybean seedlings, reduced the malondialdehyde (MDA) content, increased the Cd content in the roots of soybeans, and decreased the Cd content in the shoot parts. In addition, inoculation treatment can affect the community structure of endophytic bacteria in the roots of soybeans under Cd stress, increasing the relative abundance of Proteobacteria, Bacteroidetes, Sphingomonas, Rhizobium, and Pseudomonas. This study demonstrates that strain KM25 is capable of significantly reducing the adverse effects of Cd on soybean plants while enhancing their growth. Full article

Background: This study presents an innovative approach to cardiovascular disease (CVD) risk prediction based on a comprehensive analysis of clinical, immunological and biochemical markers using mathematical modelling and machine learning methods. Baseline data include indices of humoral and cellular immunity (CD59, CD16, IL-10, CD14, CD19, CD8, CD4, etc.), cytokines and markers of cardiovascular disease, inflammatory markers (TNF, GM-CSF, CRP), growth and angiogenesis factors (VEGF, PGF), proteins involved in apoptosis and cytotoxicity (perforin, CD95), as well as indices of liver function, kidney function, oxidative stress and heart failure (albumin, cystatin C, N-terminal pro B-type natriuretic peptide (NT-proBNP), superoxide dismutase (SOD), C-reactive protein (CRP), cholinesterase (ChE), cholesterol, and glomerular filtration rate (GFR)). Clinical and behavioural risk factors were also considered: arterial hypertension (AH), previous myocardial infarction (PICS), aortocoronary bypass surgery (CABG) and/or stenting, coronary heart disease (CHD), atrial fibrillation (AF), atrioventricular block (AB block), and diabetes mellitus (DM), as well as lifestyle (smoking, alcohol consumption, physical activity level), education, and body mass index (BMI). Methods: The study included 52 patients aged 65 years and older. Based on the clinical, biochemical and immunological data obtained, a model for predicting the risk of premature cardiovascular aging was developed using mathematical modelling and machine learning methods. The aim of the study was to develop a predictive model allowing for the early detection of predisposition to the development of CVDs and their complications. Numerical methods of mathematical modelling, including Runge–Kutta, Adams–Bashforth and backward-directed Euler methods, were used to solve the prediction problem, which made it possible to describe the dynamics of changes in biomarkers and patients’ condition over time with high accuracy. Results: HLA-DR (50%), CD14 (41%) and CD16 (38%) showed the highest association with aging processes. BMI was correlated with placental growth factor (37%). The glomerular filtration rate was positively associated with physical activity (47%), whereas SOD activity was negatively correlated with it (48%), reflecting a decline in antioxidant defence. Conclusions: The obtained results allow for improving the accuracy of cardiovascular risk prediction, and form personalised recommendations for the prevention and correction of its development. Full article