Search Results (3,578)

Obesity is a multifaceted disorder influenced by various factors, with heredity being a significant contributor. Bariatric surgery is the most effective long-term intervention for morbid obesity and associated comorbidities, while outcomes vary significantly across individuals. Recent studies indicate that genetic and molecular determinants, particularly alterations in the leptin–melanocortin signalling pathway involving the fat mass and obesity-associated gene (FTO), pro-opiomelanocortin (POMC), melanocortin 4 receptor (MC4R), leptin (LEP), and leptin receptor (LEPR), influence the efficacy of weight loss and metabolic adaptations post-surgery. This narrative review consolidates evidence from peer-reviewed papers available in PubMed and Scopus until July 2025. The emphasis was on novel research and systematic reviews examining genetic polymorphisms, gene–environment interactions, and outcomes following bariatric procedures such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). Recent research emphasised the integration of genetic screening and precision medicine models into clinical bariatric workflows. Variants in FTO (e.g., rs9939609), MC4R (e.g., rs17782313), LEPR, and POMC are associated with diminished weight loss post-surgery, an increased likelihood of weight regain, and reduced metabolic enhancement. Patients with bi-allelic mutations in MC4R, POMC, or LEPR exhibited poor long-term outcomes despite receiving effective physical interventions. Furthermore, genes regulating mitochondrial metabolism (such as PGC1A), adipokine signalling (such as ADIPOQ), and glucose regulation (such as GLP1R) have been demonstrated to influence the body’s response to sugar and the extent of weight gain or loss. Two recent systematic reviews elucidate that candidate gene investigations are beneficial; however, larger genome-wide association studies (GWAS) and machine learning techniques are necessary to enhance predictive accuracy. Integrating genetic and molecular screening with bariatric surgery planning possesses significant therapeutic potential. Genotyping can assist in patient selection, procedural decisions, and medication additions, particularly for those with variants that influence appetite regulation or metabolic flexibility. Advancements in precision medicine, including the integration of polygenic risk scores, omics-based profiling, and artificial intelligence, will enhance the customisation of surgical interventions and extend the lifespan of individuals with severe obesity. The epigenetic regulators of energy balance DNA methylation, histone changes, and microRNAs that may affect individual differences in weight-loss patterns after bariatric surgery are also briefly contextualised. We discuss the concept that epigenetic modulation of gene expression, mediated by microRNAs in response to food and exercise, may account for variations in metabolic outcomes post-surgery. Full article

The reliability and lifetime of insulated gate bipolar transistors (IGBTs) are critical to ensuring the stability and safety of power electronic systems. IGBTs are widely used in electric vehicles, renewable energy systems, and industrial automation. However, their degradation over time poses a significant risk to system performance. Therefore, this paper proposes a data-driven approach based on a Long Short-Term Memory (LSTM) network optimized by a Genetic Algorithm (GA) to predict IGBT degradation. The study examines the health monitoring of insulated gate bipolar transistors from a device physics perspective. Degradation mechanisms that alter parasitics and electro-thermal stress produce characteristic changes in the turn-off overvoltage and the on-state voltage. Using power-cycling data from packaged half-bridge modules, an LSTM-based sequence model configured by a genetic algorithm search reduces error against an identically trained baseline (RMSE = 0.0073, MAE = 0.057, MAPE = 0.726%) under the shared protocol, with the clearest advantages in the early stage of degradation. These results support predictive maintenance and health management in power-electronic systems. Full article

Background/Objectives: Cystic fibrosis (CF) is a multisystemic and genetic disorder. Mutations in the CF transmembrane conductance regulator (CFTR) gene impair the function of the CFTR protein, leading to various complications in multiple organs, mainly the lungs. Methods: In this article, we have tried to investigate the potential impact of CFTR modulators on bone density, muscle mass, and strength in children and young adolescents with CF by using the existing literature and conducting a narrative (non-systematic) review. Results: It has been demonstrated that CFTR modulators may positively influence bone mineral density. On the other hand, the impact of CFTR modulators on muscle mass and strength seems to vary among studies. Conclusions: Besides the current literature, further studies are needed to validate the existing claims. Full article

Fungal communities in the gut influence host immunity, yet most studies have focused on cell wall components rather than genetic materials. Here, we explore how fungal genomic DNA (gDNA) from Candida albicans, Saccharomyces cerevisiae, and Cryptococcus neoformans modulate immune responses in human CD4⁺ T cells, murine splenocytes, and THP-1-derived macrophages. We find that C. albicans gDNA promotes the development of regulatory T cells and increases IL-10, fostering immune tolerance and preserving CD4⁺ T cell viability in an inflammatory setting. S. cerevisiae gDNA induces moderate Treg responses with restrained effector T cell expansion and higher checkpoint gene expression, entirely consistent with its commensal nature. In contrast, C. neoformans gDNA elicits a strongly inflammatory profile, promoting Th1/Th17 cells and driving high cytokine production. Mechanistically, C. albicans and S. cerevisiae gDNA dampen DNA-sensing pathways and enhance immune checkpoint molecules that act as brakes against overactivation, while C. neoformans gDNA robustly activates innate sensing pathways with limited checkpoint induction. These species-specific signaling profiles reveal that fungal gDNA itself can influence whether the immune system adopts a tolerant or inflammatory response toward fungi. This discovery highlights fungal genomic DNA as a previously underappreciated regulator of host–fungus interactions, offering new insight into commensal persistence, pathogenic invasion, and the potential for DNA-based antifungal interventions. Full article

Molecular chaperones are crucial for maintaining protein homeostasis by assisting in the proper folding, stabilization, and function of proteins. Among them, Heat shock protein 90 (Hsp90), represents a highly conserved protein family of molecular chaperones that plays an essential role in diverse biological processes and is fundamental to cellular health and survival. As a highly abundant molecular chaperone, Hsp90 comprises 1–2% of cellular proteins, increasing to 4–6% under stress conditions. It interacts with client proteins, assisting them in proper folding and stability. Unlike classical chaperonins, Hsp90 operates through a highly regulated, ATP-dependent cycle that involves multiple co-chaperones. This process allows Hsp90 to selectively engage with numerous client proteins, including signaling proteins, kinases, hormone receptors, and transcription factors. Recent discoveries have revealed its involvement in processes beyond protein folding, demonstrating its role in diverse cellular functions such as epigenetic regulation, immune signaling, and oncogenic transformation. This current review highlighted the specific characteristics of cytoplasmic and endoplasmic reticulum (ER) as well as mitochondrial paralogs and functions, focusing on its contribution to buffering genetic variation, facilitating oncogene addiction, and modulating disease phenotypes in conditions such as cancer, neurodegeneration, cardiovascular diseases (CVD), and diabetes. We also discuss the therapeutic potential of targeting Hsp90 and its co-chaperones, outlining the challenges and prospects in drug development. These insights not only reshape our understanding of chaperone biology but also present opportunities for precision medicine in various human diseases. Full article

Acute leukemias are highly aggressive hematologic malignancies that demand intensive chemotherapy regimens. However, drug toxicity remains a major barrier to treatment success and patient survival. In this context, pharmacogenomics offers a promising strategy by identifying single-nucleotide variants (SNVs) that influence drug metabolism, efficacy, and toxicity, ultimately impacting treatment outcomes. This study analyzed data from the ClinPGx/PharmGKB database to identify clinically annotated variants related to chemotherapy response in Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL). A total of 24 variants were curated for AML and 57 for ALL. Among these, nonsynonymous variants were most frequent in ALL (31.6%), while synonymous variants predominated in AML (33.3%). Although traditionally considered neutral, synonymous and intronic variants may influence gene expression through regulatory or splicing mechanisms. The analysis revealed clinically significant variants associated with chemotherapy response, particularly in the ABCB1 gene, observed in 12.5% of AML and 10.5% of ALL cases. Several variants, particularly TPMT, NUDT15, ABCC1, SLC28A3, and RARG, were associated with severe adverse effects such as myelotoxicity, mucositis, cardiotoxicity, and hepatotoxicity. This study reinforces the importance of genetic variants in modulating the therapeutic response and toxicity to chemotherapy drugs in acute leukemias. Analysis of ClinPGx/PharmGKB data emphasizes ABCB1 as a potential resistance marker and supports pre-treatment genotyping of genes like TPMT and NUDT15 to prevent severe toxicities. Future advances should include the expansion of pharmacogenetic studies in underrepresented populations and the clinical validation of new markers in prospective trials, aiming to consolidate precision medicine as a routine part of the therapeutic management of acute leukemias. Full article

Obesity-associated adipose tissue dysfunction represents a key driver of metabolic disorders, including type 2 diabetes, cardiovascular diseases, and fatty liver disease. Emerging evidence highlights the vitamin D/vitamin D receptor (VD/VDR) axis as an important regulator of adipose tissue homeostasis. Beyond its classical role in mineral metabolism, vitamin D influences adipogenesis, inflammation, and insulin sensitivity, thereby modulating systemic metabolic health. In this review, we summarize the current understanding of the VD/VDR axis in adipose tissue biology, from molecular pathways controlling lipid turnover and immune responses to experimental and clinical evidence linking vitamin D status with obesity-related complications. We also discuss the role of genetic variability and tissue-specific VDR signaling in shaping metabolic outcomes. While results from supplementation trials remain inconsistent, maintaining adequate vitamin D levels appears crucial for the prevention of adipose tissue dysfunction and its cardiometabolic consequences. Future studies are warranted to define optimal strategies for harnessing the VD/VDR axis in therapeutic approaches to obesity and metabolic disease. Full article

Background: Food allergies are increasingly recognized as a global health concern, influenced by early-life nutrition and the gut microbiome. This systematic review examined randomized controlled trials from 2005 to 2025 assessing the effects of probiotics, prebiotics, and synbiotics in preventing food allergies. Methods: Fourteen studies involving 5685 participants, including pregnant women, infants, and children with or without diagnosed food allergies, were analyzed. While several interventions demonstrated modulation of gut microbiota and immune responses, most trials reported no statistically significant reduction in IgE-mediated food allergy compared with placebo. Results: Some evidence suggested benefits from early exposure to allergenic foods and specific probiotic strains, such as Lactobacillus rhamnosus GG, particularly in cow’s milk allergy. However, heterogeneity in study designs, strains, dosages, and diagnostic criteria limited generalizability. Conclusions: Overall, microbiome-targeted nutritional interventions show biological plausibility but inconsistent clinical efficacy. Future large-scale, standardized, and mechanistic studies integrating microbiome, genetic, and environmental data are warranted to define optimal strategies for allergy prevention. Full article

Modern crop breeding requires efficient tools for genetic identity and parentage verification to manage large-scale programs. To address this, we present GIPA (Genomic Identity and Parentage Analysis), a high-performance toolkit designed for these tasks. GIPA integrates key innovations: a sliding-window algorithm enhances accuracy by correcting genotyping errors, an intelligent system classifies samples by heterozygosity to streamline parentage analysis, and an integrated engine generates intuitive chromosome-level heatmaps. We demonstrate its utility in a soybean backcrossing scenario, where it identified a donor line with 98.02% genomic identity to the recipient, providing a strategy to significantly shorten the breeding program. In maize, its parentage module accurately identified the known parents of commercial hybrids with match scores exceeding 97%, validating its use for variety authentication and quality control. By transforming complex SNP data into clear, quantitative, and visual insights, GIPA provides a robust solution that accelerates data-driven decision-making in plant breeding. Full article

Breaking the maize yield plateau necessitates the development of density-tolerant varieties, for which recurrent selection is a key breeding strategy. However, a systematic understanding of how the interaction between selection density (parental screening environment) and evaluation density (variety testing environment) modulates genetic gain remains a critical knowledge gap. This study aimed to systematically elucidate this interaction and its impact on genetic gain and combining ability. We established two F2 base populations from distinct heterotic groups: Zheng 58 × LH196 (Stiff Stalk, SS) and Chang 7-2 × MBUB (Non-Stiff Stalk, NSS). Through bulk selection, we advanced populations for three cycles (C0, C2, C4) under three selection densities: low (60,000 plants/ha), medium (90,000 plants/ha), and high (120,000 plants/ha). Hybrids were generated using a double tester design and evaluated in multi-environment trials at Shijiazhuang in Hebei province and Xinxiang in Henan province in 2023 across matching density gradients. We employed analysis of variance (ANOVA) and general combining-ability (GCA) estimates to assess the genetic gains for yield and combining ability across 14 parental materials and 28 hybrids. Our results demonstrate that density compatibility between selection and evaluation environments is paramount. Genetic gain decreased by 0.89–26.52% with a density discrepancy of >30,000 plants/ha and plummeted by 19.71–77.44% when the discrepancy exceeded 60,000 plants/ha, underscoring the necessity of aligning selection density with the target environment. Under matched densities, population yield increased significantly with escalating density, with the high-density selection regime showing a maximum yield improvement of 53.78% from C0 to C4. Materials selected under high density exhibited superior performance and significantly higher combining ability (averaging a 238.35% increase) and genetic gain (averaging a 263.39% improvement) in medium-to-high-density environments, confirming strong positive selection pressure. Conversely, materials from low-density selection processes were better adapted to environments of ≤60,000 plants/ha. This study provides a crucial theoretical and practical foundation for establishing density-optimized recurrent breeding systems to directionally enhance genetic gain in maize. Full article

Genetic polymorphisms contribute to inter-individual variation in liver detoxification, influencing susceptibility to exposures and responses to interventions. While urinary biomarkers reflect Phase II activity, the impact of genotype on supplementation response remains unclear. In a pilot, prospective, open-label cohort study, 30 Austrian adults completed an 8-week multi-ingredient liver support supplementation regimen (e.g., glutathione, N-acetylcysteine, α-lipoic acid). First-morning urine was collected at baseline and follow-up for measurement of D-glucaric acid, mercapturic acids, and creatinine. Dried blood spots were genotyped for polymorphisms in detoxification genes (CYP1A1, GSTM1, GSTP1, GSTT1, and NQO1), and participants were stratified into normal (NDC) or limited (LDC) detoxification capacity groups. Adherence was monitored through logs, mid-study interviews, and product counts. The intervention led to modest reductions in body weight (−0.87 kg, p < 0.05) and BMI (−0.31 kg/m², p < 0.05), and significant increases in urinary D-glucaric acid (p < 0.05) and mercapturic acids (p < 0.01), with consistent responses across detoxification genotype groups (p > 0.05). The pattern of biomarker responses based on clinically defined categories did not differ significantly between the study groups (adjusted odds ratio = 2.88, p > 0.05). The observed increases in urinary biomarkers and reductions in weight and BMI are consistent with potential modulation of detoxification pathways following liver support supplementation, independent of genetic polymorphisms influencing detoxification capacity. Full article

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation that leads to tissue damage and disability. RA affects approximately 0.5–1% of the global population and is driven by a complex interplay of genetic susceptibility, environmental factors, and immune dysregulation. While biologic and targeted synthetic DMARDs improved RA treatment, they have limitations in efficacy, safety, and accessibility. B-cell-targeting therapies, such as anti-CD20, have shown effectiveness, but only with broad immunosuppression, which can increase infection risk and compromise humoral immunity. Therefore, there is an unmet need for more selective therapeutic strategies that modulate pathogenic immune pathways while preserving protective immune functions. It has been suggested that targeting the BAFF pathway may offer a more favorable therapeutic approach compared to targeting CD20. Objectives: In this study, we evaluated the therapeutic potential of V3-46s mIgG2a, an anti-BAFF-R (BR3) antibody in a mouse RA model, hypothesizing that it would offer a more selective and effective strategy. Methods: We expressed and purified four antibody variants and assessed their binding and neutralizing activity in vitro. V3-46s mIgG2a was selected for in vivo evaluation in a collagen-induced arthritis (CIA) model. Results: Treatment with this antibody delayed disease onset and reduced arthritis severity, spleen index, and B-cell populations. Conclusions: These findings highlight the potential of BAFF-R-targeting antibodies as a therapeutic approach for RA treatment. This preclinical work lays the groundwork for future development of BAFF-R blockade as a complementary or alternative strategy to current biologic treatments. Full article

Background: Oncolytic virus (OV) therapy couples direct tumor lysis with systemic immune priming, yet clinical benefit remains heterogeneous and the predictive biomarker landscape is poorly defined. We undertook a systematic review and meta-analysis to quantify the efficacy and safety of OV therapy in solid tumors and to synthesize current evidence on response-modulating biomarkers. Methods: Following PRISMA 2020 guidelines, MEDLINE, Embase, Cochrane CENTRAL, ProQuest and Scopus were searched from inception to May 2025. Phase II–III randomized trials of genetically engineered or naturally occurring OV reporting objective response rate (ORR), progression-free survival (PFS), overall survival (OS) or biomarker data were eligible. Hazard ratios (HRs) or odds ratios (OR) were pooled with random-effects models; heterogeneity was assessed with I² statistics. Qualitative synthesis integrated genomic, immunologic and microbiome biomarkers. Results: Thirty-six trials encompassing around 4190 patients across different tumor types met inclusion criteria. Compared with standard therapy, OV-based regimens significantly improved ORR nearly three-fold (pooled OR = 2.77, 95% CI 1.85–4.16), prolonged PFS by 11% (HR = 0.89, 95% CI 0.80–0.99) and reduced mortality by 16% (OS HR = 0.84, 95% CI 0.72–0.97; I² = 59%). Benefits were most pronounced in melanoma (ORR 26–49%; OS HR 0.57–0.79) and in high-dose vaccinia virus for hepatocellular carcinoma (HR = 0.39). Grade ≥ 3 adverse events were not increased versus control (risk ratio 1.05, 95% CI 0.89–1.24); common toxicities were transient flu-like symptoms and injection-site reactions. Biomarker synthesis revealed that high tumor mutational burden, interferon-pathway loss-of-function mutations, baseline CD8⁺ T-cell infiltration, post-OV upregulation of IFN-γ/PD-L1, and favorable gut microbial signatures correlated with response, whereas intact antiviral signaling, immune-excluded microenvironments and myeloid dominance predicted resistance. Conclusions: OV therapy confers clinically meaningful improvements in tumor response, PFS and OS with a favorable safety profile. Integrating composite genomic–immune–microbiome biomarkers into trial design is critical to refine patient selection and realize precision viro-immunotherapy. Future research should prioritize biomarker-enriched, rational combination strategies to overcome resistance and extend benefit beyond melanoma. Full article

This paper presents a hierarchical and step-by-step multi-objective genetic optimization method for the multi-port composite flux-modulated (MP-CFM) machine, aiming to propose a simpler and high-accuracy optimization strategy for such multi-port composite machines. As a specialized machine well-suited for hybrid power systems, the optimization design is innovatively conducted based on an analysis of the fundamental operating principles and working modes of the MP-CFM machines. Specifically, considering the complex structure of such composite machines, sensitivity analysis is employed, applying differentiated strategies based on parameter sensitiveness evaluation. Furthermore, to ensure the rationality of the optimization results, and also to reduce computational cost and improve convergence, the optimization is artfully developed hierarchically with multi-steps, in accordance with the multi-modes of the machine. Specific optimization objectives and variables are defined, respectively, for each mode to enhance the optimization efficiency. Finite element analysis results demonstrate the effectiveness of the proposed optimization strategy for such MF-CFM machines for hybrid power system applications. Full article

Fusarium oxysporum-induced root rot severely threatens global soybean production, yet limited understanding of resistance mechanisms constrains breeding progress. This study conducted comparative transcriptomic analysis between highly resistant (Xiaoheiqi) and susceptible (L83-4752) soybean accessions following pathogen inoculation across four time points (8–17 days post-infection). RNA-seq analysis identified 1496 differentially expressed genes following pathogen challenge. KEGG pathway enrichment analysis revealed significant enrichment in MAPK signaling pathway (12 genes) and plant–pathogen interaction pathway (13 genes). Eight genes co-occurred in both pathways, with GmCML (Glyma.10G178400) exhibiting the most dramatic differential expression among these candidates. This gene encodes a 151-amino acid calmodulin-like protein showing 185-fold higher expression in resistant plants at 17 days post-inoculation, confirmed by qRT-PCR validation. Functional validation through transgenic hairy root overexpression demonstrated that GmCML significantly enhanced disease resistance by coordinately activating antioxidant defense systems. Overexpression of GmCML in transgenic soybean enhanced resistance to F. oxysporum by modulating the activity of antioxidant enzymes (superoxide dismutase, SOD; peroxidase, POD; catalase, CAT) and the accumulation of osmoregulatory substances (proline and soluble sugars). Population genetic analysis of 295 diverse soybean accessions revealed three GmCML haplotypes based on promoter region polymorphisms. Two favorable variants (Hap2 and Hap3) conferred significantly lower disease indices and exhibited evidence of positive selection during domestication, indicating evolutionary importance in disease resistance. This research provides the first comprehensive characterization of GmCML’s role in soybean–Fusarium interactions, establishing this calmodulin-like protein as a regulatory hub linking calcium signaling to coordinated defense responses. The identified natural variants and functional mechanisms offer validated targets for both marker-assisted breeding and genetic engineering approaches to enhance soybean disease resistance. Full article