Search Results (7,740)

Iron (Fe) and selenium (Se) deficiencies are global health concerns associated with adverse health outcomes. Plants constitute a dietary source of these elements, particularly for individuals following plant-based diets. However, plant Fe availability is limited by soil processes that reduce Fe mobility and uptake, whereas Se accumulation is constrained by the low abundance of Se in soils. Increasing Fe and Se concentrations in edible plant parts through biofortification represents a sustainable strategy to alleviate micronutrient deficiency. This review examines the mechanisms governing Fe and Se uptake, translocation, metabolism, and genetic regulation, and discusses current biofortification strategies, including agronomic practices, natural and microbial-based approaches, conventional breeding and marker-assisted selection, transgenic technologies, and nanoparticles. While cereals remain the principal targets of large-scale biofortification programs, recent advances in horticultural crops are also highlighted because of their growing nutritional and commercial importance. Current evidence indicates that integrated agronomic and genetic approaches are more effective than single interventions, although simultaneous Fe and Se biofortification remains largely underexplored. Successful biofortification is also strongly influenced by soil properties, nutrient interactions, and crop genotype. Emerging tools, including plant–microbe interactions and synthetic biology, offer promising opportunities to enhance micronutrient accumulation and bioavailability. Further research should optimize integrated Fe–Se biofortification strategies while addressing agronomic and socioeconomic constraints to support their large-scale adoption and contribute to sustainable food systems. Full article

Biomimetic optimization transfers biological information-processing mechanisms into computational systems. Ant colony optimization (ACO) is a canonical example: artificial ants functionally abstract pheromone-mediated stigmergy, decentralized exploration, trail decay through algorithmic evaporation, and adaptive path reinforcement. Building on this functional biological analogue, we present a controlled cross-paradigm evaluation of routing-heuristic generation. A standardized interface embeds human-designed rules, the genetic programming hyper-heuristic GHPP, a resource-constrained DeepACO-MLP proxy, and an offline ReEvo-style proxy into the same ACO solver. The methods are evaluated on held-out TSP and CVRP instances in terms of solution quality, reported generation or training cost, interpretability, and cross-scale behavior under a matched distribution. GHPP yields the shortest routes at all tested scales; the ReEvo-offline proxy and strong human-designed rules generally form a second tier, whereas the resource-constrained neural proxy degrades markedly as problem size increases. These results do not establish an intrinsic ranking of full-capability paradigms. Instead, they show that method selection depends on the operating constraint and on evidence provenance: longer locally measured offline search favors GHPP, while auditable explicit rules characterize the human and ReEvo-offline proxies. By holding the ant-inspired execution mechanism fixed and varying the source of heuristic information, the benchmark clarifies how evolutionary, neural, and LLM-style design strategies interact with a common biomimetic substrate. Full article

The growing demand for accurate and computationally efficient combustion mechanisms for simulations has driven significant advances in chemical kinetic mechanism reduction for multicomponent fuels. This review systematically examines the evolution of reduction methodologies, from early size- and stiffness-reduction techniques to modern construction-based and optimisation-driven strategies. Key approaches including directed relation graph (DRG) methods, sensitivity analysis, path flux analysis, computational singular perturbation (CSP), and genetic algorithms are critically assessed. The review further explores the foundational kinetic mechanisms of hydrocarbons, alcohols, ethers, and esters, highlighting the hierarchical role of C₀–C₄ core chemistry in multicomponent fuel oxidation. It provides a consolidated understanding of reduction strategies and workflows; highlights access to detailed kinetic mechanisms for practical fuels. A central finding is that co-oxidation interactions between fuel components significantly influence combustion behavior and must be explicitly retained in reduced mechanisms. Despite substantial progress, challenges remain in developing universal reduction frameworks, establishing standardised validation datasets, and achieving fully automated mechanism construction. This review provides a roadmap for researchers seeking to implement skeletal/reduced chemical kinetic models in multidimensional engine simulations while retaining chemical fidelity across wide operating conditions. Full article

Background: Polygenic risk scores (PRS) have proven valuable for disease risk prediction, but their predictive utility often remains limited because human traits result from complex interactions between environmental and genetic factors. Blood lipid levels are heritable and clinically important risk factors for cardiovascular disease, yet it remains unclear whether multi-omics integration can enhance lipid trait prediction beyond PRS alone. Methods: We first constructed single-omics scores, where gene expression, plasma protein, and plasma/serum metabolite levels were genetically predicted and weighted by effect sizes estimated via LASSO regression. Subsequently, we implemented two integration strategies to develop composite multi-omics risk scores (MoRS): step-MoRS, which integrates single-omics scores using stepwise regression, and Lasso-MoRS, which directly models all predicted features across omics layers using LASSO regression. Both approaches were evaluated across European, South Asian, and African ancestries within the UK Biobank. Results: MoRS-based methods consistently demonstrated superior predictive accuracy compared to PRS alone for four lipid traits across diverse populations. Notably, Lasso-MoRS prioritized key biomarkers with predictive utility complementary to genomic data. Conclusions: These findings confirm that integrating multi-omics biomarkers with genomic data significantly enhances lipid trait prediction across diverse ancestries, offering biological insights into the molecular regulation of lipid metabolism. Full article

Cardiomyopathies have traditionally been regarded as disorders driven primarily by cardiomyocyte injury resulting from genetic defects, infection, metabolic stress, or toxic exposure. This paradigm has substantially advanced diagnosis and treatment. Still, it does not fully account for the marked heterogeneity in disease progression, persistent fibrosis, or variable therapeutic responses among patients with similar phenotypes. Increasing evidence indicates that immune remodeling is not merely a secondary consequence of myocardial injury but a dynamic process that actively shapes disease evolution. In this review, we integrate recent advances in cardiovascular immunology, single-cell and spatial transcriptomics, immunometabolism, and systems biology to propose a unified framework of immunological reprogramming in cardiomyopathies. We discuss how danger-associated molecular patterns, inflammasome activation, trained immunity, the cGAS–STING pathway, fibroblast–immune interactions, and the cardio–bone marrow axis converge to establish chronic inflammatory circuits that promote fibrosis, electrical remodeling, and progressive ventricular dysfunction. We further examine the emerging concept of immunotypes, emphasizing that distinct immune programs may underlie the biological heterogeneity of cardiomyopathies beyond conventional phenotypic or genetic classification. Finally, we discuss the translational potential of immune profiling, advancing a shift toward viewing cardiomyopathies as disorders of a dysregulated cardiac immune ecosystem. We propose that immune ecosystem organization constitutes an additional biological dimension that complements traditional phenotypic and genetic classifications of cardiomyopathies. Full article

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory diseases resulting from complex interactions between host genetics, environmental factors, immune dysregulation, and the gut microbiome. Among environmental exposures, antibiotics have emerged as important factors of IBD risk and disease course because of their profound effects on intestinal microbial communities. This review synthesizes current evidence on the class-specific effects of antibiotics on IBD, integrating epidemiological, mechanistic, and clinical studies to examine how different antibiotic classes influence disease susceptibility, progression, and microbiome recovery. Current evidence indicates that antibiotic-associated IBD risk varies according to antibiotic class, cumulative exposure, age at exposure, and antimicrobial spectrum, with broad-spectrum and anti-anaerobic agents showing the strongest associations. Mechanistically, antibiotics promote dysbiosis by depleting beneficial commensal bacteria, disrupting microbial metabolite production, expanding pathobionts and the intestinal resistome, and impairing epithelial barrier integrity and immune homeostasis. The review also discusses microbiome-preserving and microbiome-restorative approaches, including antimicrobial stewardship, fecal microbiota transplantation, prebiotics, probiotics, synbiotics, postbiotics, and dietary interventions, as potential strategies to mitigate antibiotic-associated dysbiosis. Overall, the evidence highlights the class-specific effects of antibiotics in IBD and underscores the importance of microbiome-informed antimicrobial stewardship and precision therapeutic strategies to optimize patient outcomes while minimizing long-term disruptions of host–microbiome homeostasis. Full article

Xipi lacquer texture generation and interactive product design are important tasks for the digital preservation and creative use of lacquerware cultural heritage. However, existing methods still face limitations in reconstructing process-dependent Xipi lacquer textures and supporting interactive design. These limitations include the difficulty of parameterizing the traditional layering-polishing process, insufficient representation of nonlinear structural features in generated textures, and user fatigue in multidimensional interactive design. Inspired by geographic contour lines, this study proposes a design framework based on Vector Quantized Variational Autoencoder (VQ-VAE) and Interactive Genetic Algorithm (IGA). The framework uses pseudo-contour inputs to guide Xipi lacquer texture generation and integrates the generated textures into a user-guided 3D bracelet evolution process. Experiments on a self-compiled dataset show that the proposed model achieved PSNR $\left(25.2\right)$, SSIM $\left(0.855\right)$, LPIPS $\left(0.285\right)$, and FID $\left(38.2\right)$. User evaluation further showed the performance of the improved IGA in structural stability $\left(4.52\right)$, color exploration $\left(4.38\right)$, evolutionary rhythm $\left(4.65\right)$, innovation retention ($4.25)$, and interaction efficiency $\left(4.42\right)$. The generated assets are further integrated into augmented-reality and virtual fashion-rendering scenarios, indicating the potential applicability of the proposed framework to the digital preservation and interactive design of lacquerware cultural heritage. Full article

Porcine reproductive and respiratory syndrome, a highly contagious disease, poses a severe threat to the global swine industry. Its causative agent, PRRSV, induces reproductive disorders (abortion, stillbirth) in pregnant sows and respiratory disease in piglets. The host immune system is disrupted by PRRSV, and no specific antiviral drugs are currently available. Thus, vaccination is regarded as the primary strategy for PRRS prevention and control. GP4, a key minor structural protein of PRRSV with an estimated molecular weight of 32 kDa, contains four conserved N-glycosylation sites at residues 37, 84, 120 and 130. Critical neutralizing epitopes are harbored in its extracellular domain (amino acids 40–79). PRRSV binding to the host CD163 receptor is mediated by GP4, which also regulates viral assembly and release, and induces protective immune responses. Hence, GP4 is identified as a central target for PRRS vaccine development. In this review, GP4’s structural characteristics, genetic evolution and interaction mechanisms are summarized. Its roles in viral life cycle, virulence, immune evasion and potential applications are discussed, providing a theoretical reference for PRRSV control. Full article

The voltage-gated sodium channel Nav1.7 is a strongly validated target for the development of novel, non-opioid analgesics due to its genetic link to pain signaling. To accelerate the discovery of safe Nav1.7 modulators, this study outlines an integrated computational pipeline to repurpose FDA-approved drugs. A structurally complete model of the Nav1.7 central pore was generated via homology modeling from a high-resolution cryo-EM structure (PDB: 7W9K) to ensure a physically consistent model suitable for dynamic simulations. We conducted a structure-based virtual screening of 2296 FDA-approved compounds, identifying four promising candidates (DB04868, DB00941, DB01419, and DB15982) with strong predicted affinities ranging from −11.38 to −12.57 kcal/mol. Interaction fingerprinting revealed that binding is predominantly driven by hydrophobic contacts with conserved pore-lining residues, including Phe1503, Leu1010, and Ile1500. To validate these static predictions, the top protein–ligand complexes were subjected to single-replica 250 ns molecular dynamics (MD) simulations. Comprehensive trajectory analyses, including RMSD, RMSF, and principal component analysis, revealed a notable discrepancy between static docking scores and dynamic stability. The highest-scoring docking candidate, DB04868, exhibited substantial conformational flexibility and reduced stabilization under simulated physiological conditions. Conversely, DB01419, despite a lower initial docking rank, demonstrated the highest structural stability across all metrics and uniquely formed intermittent stabilizing hydrogen bonds. These findings underscore the value of post-docking MD validation in computational drug discovery and nominate DB01419 and DB15982 as candidate scaffolds that warrant subsequent experimental validation, including electrophysiological characterization and Nav-isoform selectivity profiling. We emphasize that these are computational predictions: in silico binding stability is not equivalent to functional inhibition of Nav1.7 currents, and the lead designations reported here remain hypothesis-generating until confirmed by patch-clamp and biochemical assays. Full article

Background: Monochorionic twin pregnancies provide a unique model to investigate fetal phenotypic discordance, because both fetuses share a single placenta and interconnected vascular circulation. Although most monochorionic twins are monozygotic, clinically relevant differences may arise through genetic, epigenetic, placental, and stochastic developmental mechanisms. Methods: This systematic review was conducted according to PRISMA 2020 and registered in PROSPERO (CRD420261432361). PubMed/MEDLINE, Embase, and Scopus were searched from inception to June 2026. Eligible studies included monochorionic monozygotic twin pairs with discordant congenital, developmental, or syndromic phenotypes, confirmed or clearly inferable monochorionicity, and at least one genomic, cytogenetic, or epigenetic investigation; studies describing confirmed monochorionic dizygotic twinning were excluded. Findings were synthesized qualitatively. Results: The search identified 1357 records. After duplicate removal and screening, 48 studies fulfilled the eligibility criteria, comprising 441 monozygotic twin pairs; 37 were single-pair case reports, whereas one large retrospective cohort study alone contributed 193 pairs (44% of the entire pooled sample). Reported phenotypes included congenital heart disease, chromosomal abnormalities, disorders of sex development, imprinting disorders, neurodevelopmental disease, endocrine disorders, renal anomalies, skeletal disorders, and multisystem malformations. Molecular methods included karyotyping, FISH, chromosomal microarray, array-CGH, CNV analysis, WES, WGS, targeted sequencing, and methylation profiling. Proposed mechanisms included postzygotic chromosomal errors, somatic mutations, tissue-specific mosaicism, discordant or shared CNVs, differential methylation, imprinting defects, variable expressivity, blood chimerism, unequal placental sharing, TTTS, TAPS, sFGR, and uteroplacental insufficiency. Conclusions: Phenotypic discordance in monochorionic twins is rarely explained by a single mechanism. Available evidence supports a multifactorial model in which postzygotic genetic events, epigenetic regulation, placental vascular factors, and stochastic developmental processes interact. Full article

Nereistoxin (NTX) and its derivative insecticides cartap and monosultap have been used for decades to control lepidopteran pests by targeting nicotinic acetylcholine receptors (nAChRs). Unlike neonicotinoid agonists that induce excitatory neurotoxicity, nereistoxin insecticides act as antagonists, blocking cholinergic neurotransmission. However, the molecular target and mechanism of action of these compounds remain incompletely understood. Here, we elucidated the mode of action of cartap and monosultap in Drosophila melanogaster through integrated genetic and computational approaches. Bioassays with Drosophila nAChR subunit mutants demonstrated that the α6 subunit is critically required for insecticidal activity of both compounds, with α6 knockout conferring approximately 10-fold resistance to monosultap and 7-fold resistance to cartap. Molecular docking of protonated NTX into an α6 homopentameric channel model revealed a “dual-anchor” blocking mechanism: the protonated amine forms electrostatic interactions with residue Glu267, while the dithiolane ring creates steric hindrance at residue Thr270. Pore diameter measurements showed an optimal binding cavity of 5.96–6.22 Å in the 267–270 region, narrowing dramatically to 1.64 Å at the deep gate (Ser278), explaining how NTX binding physically occludes the channel. Collectively, these results identify α6-containing nAChRs as the primary target of nereistoxin insecticides and provide a structural framework for understanding channel blockade, with important implications for resistance monitoring and the development of next-generation channel-blocking insecticides. Full article

Background/Objectives: Cleft lip and palate (CL/P) are among the most common congenital craniofacial anomalies, arising from disruptions in facial development during early embryogenesis. These conditions show significant clinical and genetic heterogeneity and are broadly classified into syndromic and nonsyndromic forms. The objective of this review is to summarize current knowledge on the embryological, genetic, and molecular mechanisms underlying CL/P and to highlight their clinical implications. Methods: A comprehensive review of the literature was conducted, focusing on studies in developmental biology, human genetics, and genomics related to CL/P. Emphasis was placed on both syndromic and nonsyndromic forms, including findings from genome-wide association studies, gene mutation analyses, and investigations of gene–environment interactions. Results: Syndromic clefting is frequently associated with pathogenic variants in genes such as IRF6, TP63, and TBX22, which play key roles in epithelial differentiation, transcriptional regulation, and palatal development. In contrast, nonsyndromic CL/P results from complex interactions between multiple genetic variants and environmental factors. Genome-wide association studies have identified numerous susceptibility loci, many located in noncoding regulatory regions active during craniofacial development. Environmental influences, including maternal nutrition, smoking, alcohol exposure, and folate metabolism, have been shown to significantly modify risk. Conclusions: CL/P is a multifactorial condition involving intricate interactions between genetic and environmental factors. Advances in genomics and developmental biology have enhanced understanding of its etiology and are contributing to improved risk assessment, diagnosis, and the development of future precision medicine approaches. Full article

Post-Infectious Bronchiolitis Obliterans (PIBO) is a rare chronic obstructive lung disease characterized by irreversible airflow limitation due to inflammation, fibrosis, and obliteration of the small airways following severe lower respiratory tract infection. Adenovirus is the most frequently associated pathogen, followed by other viruses and atypical bacteria. PIBO pathogenesis appears to result from a complex interaction between severe epithelial injury, dysregulated immune response, persistent neutrophilic inflammation, abnormal tissue repair, and genetic susceptibility. Epithelial damage triggers the release of inflammatory cytokines and epithelial-derived alarmins, promoting chronic inflammation and airway remodeling through fibrosis and airway obliteration driven by activation of the TGF-β/CTGF pathway, epithelial–mesenchymal transition, macrophage–fibroblast interactions, and extracellular matrix deposition. Genetic factors affecting mucociliary clearance, innate immunity, and fibrotic pathways may further predispose certain individuals to abnormal repair and fibrosis consequently. Histologically, PIBO progresses from inflammatory bronchiolitis to fibroproliferative remodeling and constrictive bronchiolitis with luminal obliteration. Understanding these mechanisms supports a stage-based therapeutic approach targeting inflammation in early disease and fibrotic remodeling in advanced stages. Full article

In November 2024, a highly mutated descendant of the Omicron BA.3 subvariant, designated BA.3.2, emerged in South Africa carrying 39 spike mutations, two large N-terminal domain (NTD) deletions and a novel four-amino acid insertion. A key feature of BA.3.2 is extensive NTD remodeling, including a major deletion spanning residues 135–148 affecting the β-hairpin region and contributing to the loss of most of the N1 loop. This study compares the evolutionary dynamics and structural features of BA.3.2 with BA.3. Phylodynamic analyses show that BA.3 underwent early demographic stability followed by a decline in genetic diversity, consistent with limited circulation, whereas BA.3.2 displays recent emergence and a progressive reduction in effective population size without rapid expansion. Selection analyses indicate BA.3 evolution is mainly driven by changes in the receptor-binding domain, while BA.3.2 shows dispersed signals across spike regions, including codon 1162. Structural and molecular dynamic analyses reveal increased flexibility and a broader conformational landscape in the BA.3.2 NTD, driven by the deletion and resulting loss of stabilizing interactions. Overall, BA.3.2 follows a distinct evolutionary trajectory characterized by antigenic remodeling of the spike NTD, underlining the need for continued surveillance of emerging SARS-CoV-2 descendant lineages. Full article

Background/Objectives: Multiple sclerosis (MS) is a chronic immune-mediated neurological disorder for which few modifiable risk factors are established. Vitamin C, due to its antioxidant and neuroprotective properties, has been hypothesized to reduce MS risk, but epidemiological evidence remains inconsistent. Methods: We conducted a prospective cohort study using UK Biobank data, including 486,908 adults aged 37–70 years free of neurological disease. Regular vitamin C supplementation was self-reported at recruitment. Incident MS cases were identified during a median follow-up of 13.5 years. Propensity score weighting was used to balance a wide range of demographic, lifestyle, and health-related confounders. Weighted Cox proportional hazards models were used to estimate hazard ratios (HRs). Effect modification by polygenic risk score (PRS) for MS was assessed, and multiple sensitivity analyses were performed. Results: During follow-up, 452 participants were diagnosed with MS. Vitamin C supplementation was reported by 8.8% of participants (missingness = 1.5%) and was associated with a lower risk of incident MS (HR = 0.51, [95%CI: 0.32; 0.82], p = 0.004). The estimate was consistent across multiple sensitivity analyses. The association varied according to genetic susceptibility, with significant nonlinear multiplicative interaction (p = 0.004) and additive interaction (p < 0.001). Specifically, significant associations were observed only among those with average or high MS-PRS. Conclusions: Vitamin C supplementation was associated with a lower risk of incident MS, with the association varying across levels of genetic susceptibility. Although residual confounding cannot be excluded, sensitivity analyses did not identify similar associations for overall supplement use or multivitamin use, providing some reassurance against a generalized healthy-user effect. Replication in independent cohorts is warranted. Full article