Search Results (972)

Background: Knee osteoarthritis (KOA) is one of the leading causes of chronic pain and long-term disability worldwide. Despite its high prevalence, KOA remains underrepresented in repetitive peripheral magnetic stimulation (rPMS) research. While total knee arthroplasty remains the definitive treatment, there is a growing need for non-invasive approaches to reduce symptoms in patients seeking conservative alternatives or awaiting surgery. Methods: Thirty patients with KOA underwent a non-invasive treatment program consisting of eight sessions of double-coil repetitive peripheral magnetic stimulation (rPMS) over three weeks. Outcome measures included pain intensity assessed by the Visual Analog Scale (VAS), functional ability evaluated by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Timed Up and Go test (TUG), and joint mobility measured as knee flexion and extension. Clinical relevance was evaluated using the Minimal Clinically Important Difference (MCID), and subgroup analyses were performed according to Kellgren-Lawrence (KL) grade. Results: Double-coil rPMS was associated with statistically and clinically significant improvements in all outcomes. MCID responder rates exceeded 80% for VAS and TUG, exceeded 70% for WOMAC, and approached 50% for joint mobility outcomes. Subgroup analysis indicated that patients with lower KL grades experienced greater pain reduction, whereas those with higher grades showed greater functional gains. Conclusions: Double-coil rPMS provided preliminary evidence of potential clinical benefit as a non-invasive approach in patients with KOA. Given the single-arm pilot design, the findings should be interpreted cautiously and require confirmation in adequately powered randomized controlled trials with longer follow-up. Full article

The aim of this research was to experimentally analyze the influence of drying method, temperature, and drying time on moisture content (MC), elemental composition (percentages of C, H, N, S, and O), and protein and fat content in sunflower seeds, as well as to apply and compare different existing machine learning regression models for moisture content prediction. The study was conducted on three sunflower hybrids (Sumiko, Pioneer, and Agromatic Lidea) using conduction, vacuum, and fluidized bed drying at temperatures from 50 to 80 °C and durations from 15 to 60 min. The results showed that temperature and time are the main controllable parameters of drying, while drying methods and hybrid also significantly influence the process. In moisture content modelling, artificial neural networks (ANN) achieved the best predictive performance (R² = 0.97; RMSE = 0.46), while SVR models showed slightly weaker but still high accuracy. The results indicate that machine learning models can be useful tools for predicting moisture content based on drying parameters and may support improved monitoring and management of the sunflower seed drying process. Full article

Effectively activating protective CD8⁺ T cell immunity specifically against cancer antigens is an important pathway to prevent the growth of various types of cancers. A major obstacle in this approach is variations in cancer antigens among patients. A valuable material to overcome the antigen variation among cancer patients is the use of each individual’s own cancer cells for immunization. In colorectal cancer (CRC), approximately one-third of the patients who receive curative surgical resection have a recurrence of cancer. Therefore, the use of surgically resected CRC for immunotherapy to specifically activate the protective CD8⁺ T cells against their own cancer cells is a valuable approach to prevent the recurrence of cancer. However, since cancer-specific antigens are often not strongly immunogenic, a potent immunostimulant is required as an adjuvant for efficiently facilitating the activation of cancer-specific protective CD8⁺ T cells. We recently identified that a protein molecule, the amino-terminus region of the dense granule protein 6 (GRA6Nt) of Toxoplasma gondii, selectively activates innate expressions of IFN-γ and IL-18 and functions as a powerful adjuvant when used in immunization with nonreplicable (treated with mitomycin C or irradiated) MC38 CRC cells to potently activate the cytotoxic activity and IFN-γ production of CD8⁺ T cells against cancer cells. In addition, immunization using the GRA6Nt protein adjuvant effectively inhibits the growth of identical CRC cells after its challenge implantation, which mimics a recurrence of the surgically resected CRC used for the immunizations. In contrast to the two nucleotide- or deoxynucleotide-based Toll-like receptor agonists currently being used as adjuvants in cancer immunotherapy in clinical settings, GRA6Nt is a protein molecule. Thus, the rGRA6Nt protein adjuvant provides a new pathway in cancer immunotherapy to effectively activate the protective CD8⁺ T cells specific for the individual’s cancer cells to prevent the recurrence of surgically resected CRC in patients. Full article

The Longmen Shan Fault Zone is marked by intricate geological structures and frequent seismic activity, which gives rise to persistent seismic hazards. To tackle the challenge of capturing the multi-temporal characteristics of earthquake frequency, this study combines machine learning with time series analysis to conduct earthquake frequency prediction research. Based on the 1970–2023 seismic dataset from the China Earthquake Networks Center, the seismic records were structured into four temporal scales: daily, weekly, monthly and quarterly. The minimum completeness magnitude (Mc) was determined as M3.0 by applying the G–R relationship. After conducting white noise tests and data normalization, ACF and PACF were utilized to select the optimal time-step parameters for the LSTM model. Considering the inherent characteristics of the seismic data, the 99th percentile of the frequency series was set as the threshold, and an auxiliary parameter was introduced to label high-frequency earthquake days for the construction of the LSTM model. Upon the completion of LSTM model fitting, heteroscedasticity tests were performed on the residuals between the predicted and observed values. Confirming the presence of significant heteroscedasticity, the GARCH model was incorporated to process these residuals, thus establishing a complete LSTM-GARCH coupled model. The results reveal that seismic activity in this region is normally low-frequency with occasional high-frequency occurrences. The proposed model achieves R² above 0.80 across all four temporal scales, accompanied by superior performance in all error metrics. This study validates that the LSTM-GARCH model can effectively extract the multi-scale patterns of earthquake frequency, with the best performance observed at the daily scale. Ablation experiments further demonstrate that this coupled model outperforms both the ARIMA and single LSTM models, providing reliable technical support for short-to-long-term earthquake prediction and regional disaster risk assessment. Full article

Volcanic lava has a complete primary succession; the plant community composition can explain a great part of the variation of soil microbial diversity and community structure. Bacteria dominate the soil microbial communities in abundance and diversity, and they are important drivers of organic matter decomposition and nutrient cycling. With 16S rRNA Illumina Miseq sequencing techniques, we analyzed the soil bacterial communities and diversities associated with different vegetation types in Wudalianchi. Shrub soils had the highest pH, MC, TOC, TN, AP, AN and NN, whereas moss soils had the lowest. The Shannon, Ace, and Pd indices of bacteria showed significant differences in the different vegetation types (p < 0.05). Bacterial Ace, Shannon, and Simpson indices peaked in Herb and Shrub is highest. The Proteobacteria, Actinobacteriota, Acidobacteriota, Planctomycetota and Chloroflexota were the most abundant groups at phyla level. Bacterial community composition varied significantly across vegetation types (p < 0.05). At the family level, Pseudonocardiaceae predominated in moss soils. Redundancy analysis and correlation analysis revealed MC, pH, and TP as key environmental factors shaping bacterial communities. Functional predictions based on taxonomic data indicated that chemoheterotrophy and aerobic chemoheterotrophy were the predominant functional groups. In conclusion, although soil microbial composition and diversity differed markedly across vegetation types following volcanic eruptions, functional groups prioritized carbon fixation strategies. Full article

This study aims to examine the relationships between perceived financial health indicators, lived financial experiences, and actions taken to cope with economic crises, as well as exploring potential gender differences. A non-experimental, quantitative, cross-sectional design is applied to a sample of 499 working professionals who graduated from universities in Veracruz, Mexico, and were employed in the public or private sector. A 24-item Likert scale instrument assessed financial health perceptions, experiences, and crisis-related behaviors. In this study, reliability indices (Cronbach’s alpha and McDonald’s omega) exceeded the acceptability threshold of 0.70. Data were analyzed using Exploratory Factor Analysis, Structural Equation Modeling, and Bayesian estimation to examine gender effects. The results supported a four-factor structure explaining 64.86% of the variance. Financial wellbeing showed a moderate association with resilience (r = 0.32), a weaker relationship with financial experiences (r = 0.18), and a strong association between experiences and crisis-related actions (r = 0.47). No statistically significant gender differences were identified. These findings contribute to understanding how experiential and behavioral components interact to shape financial outcomes, and we propose a refined three-factor framework linking financial experiences and adaptive actions to overall financial wellbeing. Full article

Ultraviolet (UV) radiation induces DNA damage and oxidative stress in melanocytes, shaping pigmentation phenotypes and elevating photocarcinogenesis risk. Human models that capture donor-linked genetic determinants of UV sensitivity remain limited. Here, we establish a genotype-informed UV response model using induced pluripotent stem cell (iPSC)-derived melanocytes from donors carrying defined MC1R variants. Differentiated cells recapitulated melanocytic morphology, marker expression, and pigmentation consistent with donor sun-sensitivity traits. Following narrowband UVB exposure, melanocyte lines with higher UV sensitivity showed reduced survival, prolonged checkpoint activation, and CPD-associated DNA damage signaling dynamics. Mechanistic analysis suggests that the interferon-regulated GTPase MX2 is associated with amplification of UV-induced p53 and p38 activation while promoting apoptosis independently of AKT. These findings support MX2 as a physiological enhancer of DNA damage signaling in normal melanocytes, distinct from its interferon-mediated role in melanoma. Our study provides a human-relevant platform linking pigmentation genotype to UV resilience and supports iPSC-derived systems as new approach methodologies (NAMs) for mechanistic and translational phototoxicology. Full article

Purpose: Accurate preoperative risk stratification in endometrial cancer (EC) is essential for guiding surgical and therapeutic decisions. This study aimed to evaluate the discriminative performance of [18F]-FDG PET/CT-derived radiomic features combined with machine learning models for differentiating low-risk (LRH-EC) and high-risk histology (HRH-EC) subtypes. Methods: A total of 159 patients with histopathologically confirmed EC who underwent preoperative [18F]-FDG PET/CT were retrospectively analyzed. Radiomic features were extracted using LIFEx version 7.4.0 software following IBSI guidelines. After FDR correction and Pearson correlation–based redundancy reduction (|r| > 0.80), 16 radiomic features were retained for modeling. Three feature configurations (Conventional PET parameters, Radiomics16, and Combined) were evaluated. Machine learning models were developed using stratified 5-fold cross-validation. Model performance was assessed using AUC, accuracy, sensitivity, specificity, F1-score, Wilson confidence intervals, DeLong’s test, and McNemar’s test. Results: Artificial Neural Network (ANN) (AUC = 0.709) and Random Forest (RF) (AUC = 0.686) achieved the highest discriminative performance within the Radiomics16 feature set. No statistically significant superiority between algorithms or feature configurations was observed by DeLong analysis. However, McNemar’s test demonstrated significant patient-level classification differences for the Combined ANN model (p < 0.001). NGTDM_Coarseness and SUVmin emerged as the most influential features, reflecting tumor heterogeneity and metabolic activity. Conclusions: [18F]-FDG PET/CT-based radiomics combined with machine learning provides moderate yet consistent discrimination between LRH-EC and HRH-EC. While external validation is required, this approach may support noninvasive preoperative risk stratification in endometrial cancer. Full article

DNA polymerase beta (Polβ) is a 39 kDa, single polypeptide enzyme that possesses both gap tailoring and nucleotidyl transferase activity and is the key polymerase involved in base excision repair (BER) and the final steps of active gene demethylation. We demonstrated that residues in the mouse Polβ protein, L301 and V303, are critical for Polβ’s interaction with the BER scaffolding protein X-ray repair cross-complementing 1 (XRCC1), and mutation of these residues impairs Polβ’s ability to bind to XRCC1, negatively impacting BER complex assembly. We developed Polβ^{L301R-V303R/L301R-V303R} knock-in mice to explore how defects with this essential protein complex impact genome stability in the mouse. We found these mice to be viable and fertile yet exhibited a modest reduction in body weight. Here, we examined the protein and mRNA levels in tissues from wild-type (WT), heterozygous (HET), and homozygous (HOM) Polβ^{L301R-V303R/L301R-V303R} mice and the derived fibroblast cell lines. We show that HOM mice have significantly diminished Polβ protein levels, as compared to WT mice, in several tissues, yet Polβ mRNA levels were not significantly different, suggesting the decreased levels of Polβ protein could not be attributed to lower gene expression. Upon examination of Polβ stability in mouse ear fibroblasts derived from WT and HOM mice, results are consistent with human cell studies that the Polβ^L301R-V303R protein is unstable and undergoes proteasome-mediated degradation. Finally, we evaluated WT, and HOM, liver and brain genomic DNA samples for 5-methylcytosine/5-hydroxymethylcytosine (5mC/5hmC) levels by nanopore sequencing to investigate the impact of suppressed Polβ protein levels on active gene demethylation. As expected, we found tissue-specific trends in methylation, when comparing the brain and liver. However, we were unable to discern substantial differences in methylation levels between WT and HOM mice, suggesting that in the absence of external stressors, low Polβ levels do not impact methylation patterns. Full article

Acmella oleracea (L.) R.K. Jansen is an herbaceous plant cultivated globally as an annual ornamental species. While conventional propagation methods exist, the lack of a standardized in vitro protocol limits research and industrial applications that require genetically and morphologically uniform plant material. In this study, in vitro cultures of A. oleracea were established via seed germination. Well-developed in vitro shoots were dissected into individual nodal segments to serve as explants. Multiple media were evaluated for regeneration and growth, including full-, half, and quarter-strength Murashige and Skoog (MS) media, as well as full- and half-strength McCown Woody Plant media. Two carbohydrate sources, saccharose and glucose, were tested at concentrations of 1%, 2%, and 3% (w/v) in the multiplication medium. Subsequently, the effects of different cytokinins were assessed at concentrations of 4.4 µM and 13.2 µM. The findings demonstrated that 13.2 µM meta-Topolin with 3% saccharose, or 13.2 µM Benzyladenine with 2% glucose was most beneficial for shoot multiplication of A. oleracea. The multiplied shoots were rooted in vitro within 13 days, then potted and acclimatized within 8 days. This protocol facilitates future industrial applications of A. oleracea, particularly in the cosmetics sector, where the use of standardized biomass is essential. Full article

Atherosclerosis, the leading cause of death worldwide, is a chronic inflammatory disease leading to the accumulation of lipid-rich plaques within the artery wall. Accumulating evidence indicates that intestinal microbiota plays an important regulatory role in atherosclerosis at all stages of the disease. Through numerous metabolites, the intestinal microbiota can regulate immune and inflammatory cells and their mediators, as well as lipid metabolism, thereby contributing to the development and progression of atherosclerosis. With these assumptions in mind, we investigated the possibility of using Limosilactobacillus fermentum MC1 (L. fermentum MC1) and its exopolysaccharides (EPSs) in the reduction of lipid and atherogenic parameters as a preventive strategy in preventing the occurrence of cardiovascular diseases (CVD). We investigated the effect of L. fermentum MC1 and its EPSs on the health status of mice by monitoring the following parameters: body weight, colon length and weight, relative weight of organs, hematological (Hgb, WBC, number of erythrocytes, MCHC, MCV, MCH), and biochemical blood parameters including glucose, serum enzymes (ALT, ALP, amylase), urea, creatinine and lipid profile (total cholesterol, triglycerides, HDL, VLDL, LDL), different atherogenic parameters, blood biomarkers such as lymphocyte-to-monocyte (LMR) and neutrophil-to-lymphocyte (NLR) ratios, molecular inflammatory markers (IL1β, IL6, MCP1, IL1α, TLR4, TNFα, CD68, TGFβ), apoptosis markers (BCL2, AIFM1, IGF-1R), and endoplasmic reticulum stress markers (CHOP and GRP94) as well as oxidative stress (NOX2) markers in the colon. Furthermore, the level of lipid peroxidation, nitric oxide and glutathione concentrations in the liver, kidneys and spleen were measured. L. fermentum MC1 and its EPSs may prevent the development of atherosclerosis and the progression of CVD through antioxidant, anti-inflammatory, immunomodulatory activities, and regulation of the gut microbiome and lipid metabolism. The observed reduction in lipid and atherogenic determinants suggests that L. fermentum MC1 and its EPSs may contribute to atheroprotection and confer multiple health benefits. Full article

Background: The principal glial cells of the retina, Müller glia, play a central role in retinal regeneration in teleost fish and have recently attracted attention as potential sources of neuronal regeneration in mammals. Objectives: In this study, we examined whether SV40-immortalized rat Müller glia could be directed toward neuronal differentiation using a non-genetic approach with defined culture conditions. Methods: Comprehensive transcriptomic profiling by RNA sequencing indicated that changes in culture medium alone could induce transcriptional reprogramming toward a neuronal lineage. Results: Specifically, expression of Müller glia-related genes decreased, while a subset of photoreceptor-related transcription factors and specific genes showed altered expression, suggesting early-stage induction toward a photoreceptor-like fate. This finding suggests that even immortalized cells may exhibit activation of neuronal genes through non-genetic culture interventions. Gene set enrichment analysis further revealed upregulation of pathways related to the synaptic vesicle cycle, metabolic activation, oxidative stress defense, and lysosomal function, consistent with initiation of neuronal differentiation. Conversely, pathways associated with cell cycle regulation and stemness signaling were downregulated, reflecting a transition from a proliferative to a differentiation-prone state. Collectively, these results provide preliminary molecular markers for early neuronal induction and potential targets for chemical screening. Conclusions: Importantly, this strategy enables neuronal-like differentiation of Müller glia without genetic manipulation, offering a safe and cost-effective platform. Overall, our findings may support the development of in vitro models for retinal neuroregeneration and facilitate research toward regenerative therapies for retinal disorders. Full article

This study aimed to translate, culturally adapt, and validate the Arabic version of the 6-Item Lubben Social Network Scale (LSNS-6). The LSNS-6 was translated, culturally adapted, and administered, alongside the Medical Outcomes Study Social Support Survey (MOS-SSS), to 327 Arabic-speaking adults aged 60 years and older. Internal consistency was examined using Cronbach’s alpha and McDonald’s omega. Confirmatory factor analysis (CFA) tested the hypothesized two-factor structure (Family and Friends), and measurement invariance was evaluated across key sociodemographic and lifestyle variables. Convergent validity was assessed through correlations with MOS-SSS domains. Item response theory (IRT) analyses examined item discrimination and threshold parameters. Latent class analysis (LCA) explored whether the LSNS-6 could identify subgroups with distinct patterns of social connectedness and perceived support. The Arabic LSNS-6 demonstrated good internal consistency (α = 0.83; ω = 0.84) and supported the expected two-factor structure with satisfactory model fit (CFI = 0.963; TLI = 0.931; SRMR = 0.03). Convergent validity was evidenced by moderate correlations with overall perceived social support (r = 0.51). IRT analyses indicated strong discrimination for most items, and LCA identified four distinct latent classes. Overall, the Arabic LSNS-6 is a reliable and valid tool for assessing social isolation among older Arabic-speaking adults. Full article

Type 2 diabetes (T2D) features insulin resistance that promotes cerebrovascular injury, yet the immune signals linking metabolic stress to vascular dysfunction remain unclear. We tested the hypothesis that insulin resistance and soluble vascular cell adhesion molecule-1 (sVCAM1) act through complementary pathways in mast cells (MCs) to raise circulating histamine levels and impair cerebral vascular function. In a high-fat diet (HFD) plus low-dose streptozotocin (STZ) model, plasma histamine rose sharply after the onset of insulin resistance and remained elevated. Plasma sVCAM1 levels also increased after insulin resistance. In vitro, recombinant sVCAM1 upregulated histidine decarboxylase (HDC) in native MCs in a dose-dependent manner, indicating a shift toward histamine synthesis, but did not enhance degranulation. In contrast, pharmacological inhibition of Akt with MK2206 activated Glycogen Synthase Kinase 3 beta (GSK3β) and increased MC degranulation without affecting HDC expression. Diabetic endothelial cell monolayers exhibited a ~twofold reduction in transendothelial electrical resistance consistent with impaired blood–brain barrier (BBB) integrity. Diabetic cerebral arteries showed receptor remodeling that favored constriction with histamine H1 receptor (H1R) expression increasing in vascular smooth muscle, while endothelial H1R and histamine H2 receptor (H2R) decreased. Functionally, insulin treatment lowered HOMA2-IR in T2D mice but did not restore cerebral artery myogenic tone or improve stroke outcomes after distal middle cerebral artery occlusion (dMCAO). Neutralizing VCAM1 with a monoclonal antibody reduced circulating sVCAM1 and histamine levels, and, together with the GSK3β inhibitor Tideglusib, stabilized MCs, normalized cerebral artery tone, and reduced post-MCAO infarct size and edema. These findings identify two distinct yet complementary mast cell pathways in T2D, highlight an immune-vascular interface that drives cerebrovascular dysfunction, and propose sVCAM1 blockade plus GSK3β inhibition as rational strategies to protect cerebral vascular function in the diabetic brain. Full article

Mast cells (MCs) are multifunctional innate immune cells that regulate inflammation, tissue repair, and immune responses, and they are increasingly recognized as contributors to chronic liver disease. In parallel, the aryl hydrocarbon receptor (AhR) has emerged as a key environmental sensor activated by gut-derived tryptophan metabolites such as kynurenine and microbial indoles. The current literature separately describes the role of AhR in MC signaling, as well as the contributions of MCs to liver pathology and the disrupted gut–liver axis, which drives immune dysfunction in chronic liver disease. However, these aspects have been rarely considered together. This review aims to bridge these fragmented areas, providing an integrated framework where AhR-driven MC responses are examined within the gut–liver axis along with their impacts on liver inflammation and fibrosis. We discuss how this microbial–immune dialogue shapes autoimmune and cholestatic liver diseases, including autoimmune hepatitis, primary sclerosing cholangitis, and primary biliary cholangitis. Finally, we highlight translational perspectives, from microbiota modulation to AhR-targeting approaches, as potential strategies to control MC-driven hepatic inflammation. By integrating these currently separate concepts, this review offers a novel perspective on the role of MCs as important mediators at the interface of gut-derived signals and liver pathology via AhR signaling, while highlighting innovative therapeutic avenues through the modulation of the microbiota, targeting of AhR, and regulation of MC responses. Full article