Search Results (12,441)

Grain quality in bread wheat is a complex trait determined by multiple genetic factors and their interaction with environmental conditions. This study investigated the genetic architecture of key grain quality traits in the Avalon × Cadenza double haploid (DH) population under contrasting climatic conditions in Kazakhstan. A set of 101 spring-type DH lines was evaluated over three years in three major wheat-growing regions of Kazakhstan, representing northern, central, and southern environments. Grain yield and nine grain quality traits were assessed, including amylose content (Amc, %), test weight per liter (TWL, g/L), grain protein content (GPC, %), gliadin content (Gli, %), glutenin content (Glu, %), grain hardness (GH, %), grain vitreousness (GV, %), falling number (FN, s), and sedimentation value determined in a 2% acetic acid solution (SV, mL). The objectives were to characterize phenotypic variation, examine trait relationships, and identify major and environmentally stable quantitative trait loci (QTLs) controlling grain quality. QTL mapping identified 89 QTLs associated with the nine studied traits, including 82 major QTLs explaining more than 10% of phenotypic variation and 16 stable QTLs detected in two or more environments. The largest numbers of QTLs were found for GPC, SV, and TWL. Stable QTLs were distributed across all three wheat genomes, with important regions detected on chromosomes 1A, 1B, 2D, 4A, 4D, 5A, 6A, and 7D. Several stable QTLs co-localized with genomic regions previously associated with grain quality and developmental regulation, including loci near Wx-B1, Rht-D1, and Ppd-D1, suggesting biologically meaningful links among gluten composition, starch biosynthesis, plant development, and grain physical properties. These results improve understanding of the genetic control of wheat grain quality across diverse environments in Kazakhstan and provide promising targets for marker-assisted selection to combine improved end-use quality with wide environmental adaptation. Full article

The dextran sodium sulfate (DSS) colitis model is the most widely used experimental model of inflammatory bowel disease (IBD) due to its simplicity and versatility, with over 7000 PubMed entries in the last decade and an exponential rise in recent years. Since its initial description in 1985, DSS colitis has been extensively evaluated across species, most notably in mice and rats, and has yielded substantial insights into IBD pathogenesis. However, the model’s multifactorial nature poses a dual challenge: it offers an opportunity but complicates study design, interpretation, and translational relevance. This complexity is worsened by inconsistent reporting, which hampers reproducibility and comparability across studies. The broad use of the DSS-induced colitis model yields numerous insights about the model, which help better understand its complexity, characteristics and limitations. Although DSS colitis is induced locally, inflammation in the colon and gut barrier destruction may also affect other organs (such as the liver and brain) and their metabolism and molecular responses, which, in turn, may interfere with colitis-underlying mechanisms and drug response, and may influence the interpretation of results. These intrinsic (intra-experimental) characteristics of the DSS model are summarised in the paper (colitis, gut–brain axis, gut–liver axis). In addition, the DSS model is heavily influenced by numerous extrinsic (inter-experimental) factors (environmental, microbiological, genetic), which may further complicate the colitis model, the study outcomes, and data interpretation, and these are also discussed in the paper. As science advances and new data accumulate, understanding the intricate interplay among internal mechanisms, external factors, and technical variables becomes increasingly essential for the accurate interpretation of DSS outcomes. This review synthesises the complexity and interdependence of factors shaping the DSS model, emphasising the need for meticulous reporting and consideration of methodological nuances to enhance reproducibility, interpretation, and translational value in DSS colitis research. In addition, the review provides practical guidance through a “traps and tricks” subsection and checklist table designed to provide a framework and practical recommendations to better understand, apply, and interpret DSS model results in the context of broader systemic and methodological considerations. Full article

The occurrence of Escherichia coli resistant to high-priority critically important antimicrobials (HPCIA) in the food chain is a growing concern for food safety and public health. This study aimed to evaluate whether HPCIA-resistant E. coli isolated from pork and chicken meat at retail markets in La Plata, Buenos Aires, Argentina, exhibit source-associated genomic differentiation through whole-genome sequencing. The isolates displayed a polyclonal population structure, encompassing multiple phylogenetic groups and sequence types. Virulence gene profiles were highly diverse, with chicken-derived isolates harbouring a substantially higher number of virulence genes than pork isolates. Notably, one pork isolate carried a complete set of virulence genes characteristic of diarrheagenic E. coli. Single Nucleotide Polymorphism-based phylogenetic analysis revealed several closely related subclusters, including strains recovered from both pork and chicken meat from the same retail markets, suggesting recent clonal sharing or cross-contamination at the point of sale. These findings highlight the circulation of genetically diverse HPCIA-resistant E. coli in retail meat, underscoring the potential public health risk and the importance of monitoring resistance and virulence determinants throughout the food production chain. Full article

Background: The STAG1 gene has been related to a poorly known form of intellectual disability, known as Intellectual Developmental Disorder, Autosomal Dominant 47 (MRD47). Functionally, MRD47 is part of the Cohesinopathies, a small family of rare genetic disorders caused by defective cohesin complex, whose activity is essential for sister chromatid cohesion and therefore for chromatin organization. Chromatin state modulation is an entangled process finely modulated by a large number of actors that, if altered, give rise to the so-called Chromatinopathies. The clinical and biological overlap among these families of conditions on one hand poses significant challenges during diagnostic definition, and, on the other, may help delineate more accurate management guidelines. Methods: Starting from the report of a novel pathogenic variant in the STAG1 gene, we performed a retrospective clinical and molecular review of all previously reported patients affected by this rare disorder. Once clinical and photographic data of all published patients were collected, we used Face2Gene deep learning technology to analyze STAG1 facial phenotype, comparing it to both Chromatinopathy and Cohesinopathy profiles. Results: Our clinical and molecular re-evaluation of reported cases confirms MRD47 as a mainly neurodevelopmental disorder. Through artificial intelligence technology, we were able to first create the gestaltic profile of MRD47. Face2Gene analyses of this composite phenotype, although limited by the tool’s analysis modalities, demonstrates the strong overlap of STAG1 disorder with Chromatinopathies. Conclusions: The present literature review, together with gestaltic analyses of the STAG1-related phenotype, underscores the strong resemblance of MRD47 to epigenetic machinery disorders. The present case brings to light once more the biological and phenotypical entanglement of Cohesinopathies and Chromatinopathies, hinting at STAG1 as the joining chain. Full article

Anti-A and anti-B antibodies are essential for monitoring adverse reactions in organ transplants and transfusions. However, their importance is also growing due to their involvement in the pathophysiology of various human diseases, such as infections, although this is currently the subject of heated debate. A characteristic heterogeneity in the titers and classes of anti-A and anti-B antibodies is observed among individuals. Several factors appear to be responsible, such as everyone’s specific immune profile, age, sex, microbiota composition, lifestyle, and health status. The immune profile, the result of a specific genetic predisposition and mediated and controlled by cytokines, shows a bidirectional relationship with ABO antigen expression, the gut microbiota, and the levels and class switching of anti-ABO antibodies. Associations between ABO groups and circulating levels of cytokines and chemokines further highlight this complex interaction. To better understand the role of the immune profile in this context, we evaluated, for the first time, the possible association between polymorphic variants in the regulatory regions of the genes encoding the cytokines IL-8, IL-1, IL-4, IL-6, IFN-γ, and IL-10 and anti-A and anti-B antibody titers and classes by group and in total. We also assessed the levels of these cytokines in each group and their correlations with anti-A and anti-B antibodies, as well as with age and associations with gender. Significant data were obtained that may contribute to a better understanding of the other roles of ABO antibody titers. Full article

Background/Objectives: With the acceleration of global industrialization and continuous population growth, the world is increasingly confronted with the dual challenges of food insecurity and cultivated land contamination. The screening and breeding of rice varieties with superior agronomic traits and low heavy metal accumulation have therefore become important strategies for ensuring food safety and sustainable agricultural production. Methods: In this study, rice varieties carrying the Gn1a-i gene and exhibiting specific cadmium (Cd) accumulation characteristics were screened using a combination of molecular marker detection and cadmium accumulation evaluation. Specific loop-mediated isothermal amplification (LAMP) primers targeting the Gn1a-i gene were designed and combined with a lateral flow dipstick (LFD) assay to enable rapid genetic screening of rice varieties. A six-day hydroponic experiment under cadmium stress was conducted across three temperature ranges (15–20 °C, 22–27 °C, and 30–35 °C), and cadmium accumulation in different plant organs (roots, stem sheath, and leaves) was analyzed. Results: Seven varieties carrying the Gn1a-i gene, including Xiangwanxian 12, were identified among ten tested rice varieties. Xiangwanxian 12 was subsequently selected for further evaluation, with the high-cadmium-accumulating variety Yuzhenxiang used as a control. At 144 h, the total Cd content in the measured organs of Xiangwanxian 12 was 9.6%, 4.0%, and 23.2% lower than that of Yuzhenxiang under low, medium, and high temperatures, respectively (one-tailed t-test, p < 0.01 for all three temperatures). Conclusions: The integration of LAMP-based genotyping and physiological evaluation provides a novel and reliable strategy for identifying low-Cd rice germplasm. Xiangwanxian 12, which carries the Gn1a-i allele and exhibits consistently lower Cd accumulation than Yuzhenxiang, suggests potential as a candidate for breeding high-yield, low-Cd rice cultivars. Full article

This study presents a systematic topological progression and multi-objective optimization of a Permanent Magnet-assisted Non-overlapping Winding Line-Start Synchronous Reluctance Motor (PMaNWLS-SynRM) for industrial applications. To explicitly highlight the core contribution, the research establishes a rigorous comparative framework evaluating the transition from a conventional 4-pole/36-slot distributed winding (DW) to a 2 × 12-slot non-overlapping winding (NW) architecture. Baseline results demonstrate that the NW configuration shortens end-turns, successfully reducing total electromagnetic losses from 417 W to 349 W and improving steady-state efficiency from 93.7% to 95.1%. To overcome the inherent starting limitations of pure synchronous reluctance machines, an aluminum squirrel-cage is integrated to enable robust direct-on-line (DOL) synchronization, while NdFeB permanent magnets are embedded within the rotor flux barriers to mitigate asynchronous spatial harmonics and elevate torque density. Finite element analysis (FEA) confirms this magnetic assistance raises the average synchronous torque to 65.8 Nm while suppressing absolute torque ripple to 1.37 Nm. Finally, an evolutionary genetic algorithm is deployed across 440 iterative configurations to resolve geometric multi-physics conflicts. The finalized optimized design achieves a 13.2 kW output power at 1800 rpm, maximizing average torque to 70.12 Nm and strictly dampening absolute torque ripple to an industry-acceptable 1.04 Nm. Operating with an aggregated total loss of 1382 W, the optimized PMaNWLS-SynRM yields a 90.5% operational efficiency, definitively validating its suitability as an ultra-premium IE4/IE5 alternative to conventional induction motors. Full article

Epilepsy is associated with impaired reproductive function and testicular pathologies. Intermittent fasting (IF) is a nonpharmacological metabolic intervention with anti-inflammatory and antioxidant effects. This study investigated the protective effects of IF on testicular damage in a genetic absence epilepsy rat model (GAERS), focusing on histomorphology, oxidative stress parameters, and hormonal profiles. Testicular tissues from Wistar control (WC), Wistar + IF (WIF), GAERS control (GC), and GAERS + IF (GIF) groups (total n = 20; 5 rats per group) were evaluated using hematoxylin and eosin and Periodic Acid–Schiff staining. Apoptosis and spermatogenic cell integrity were assessed using caspase-3, P-element-induced wimpy testis (PIWI), and Deleted in Azoospermia-Like (DAZL) immunohistochemistry. Johnsen’s score, seminiferous tubule diameter, and epithelial thickness were quantified. Oxidative stress markers, including catalase, malondialdehyde, glutathione, myeloperoxidase, and superoxide dismutase, were measured using spectrophotometric methods, and serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were determined using ELISA kits. The GC group showed significantly reduced Johnsen scores, tubular diameters, and epithelial thickness, along with disrupted basement membrane integrity and increased caspase-3 immunoreactivity. IF significantly improved histological parameters, restored basement membrane integrity, reduced apoptosis, and increased PIWI and DAZL expression in the GIF group. IF also ameliorated oxidative stress and elevated reproductive hormone levels, indicating positive modulation of the hypothalamic–pituitary–gonadal axis. In conclusion, IF reduces oxidative stress and preserves seminiferous tubules and hormonal function in genetic absence epilepsy, highlighting its potential as a supportive nonpharmacological approach to protect male reproductive health. Full article

Nephrocalcinosis, defined as the deposition of calcium salts within the renal parenchyma, represents a radiologic and pathologic endpoint shared by a broad spectrum of metabolic and monogenic disorders. Advances in genomic medicine have identified more than 30 genes involved in tubular transport, mineral and acid–base homeostasis, oxalate metabolism, mitochondrial function, ciliary signaling, and nephron development, reframing nephrocalcinosis as a heterogeneous manifestation of discrete molecular defects rather than a single disease entity. Despite this diversity, these conditions converge on common physicochemical pathways of tubular supersaturation, crystal nucleation, growth, and intrarenal retention. These processes are amplified by the intrinsic vulnerability of the renal medulla—characterized by hyperosmolality, hypoxia, and slow tubular flow—and by epithelial injury, loss of crystallization inhibitors, and impaired ciliary signaling. Distinct genotype–phenotype signatures, including age at onset, biochemical profiles, and extrarenal manifestations, provide important diagnostic clues and help differentiate major monogenic entities. The increasing availability of targeted gene panels, whole-exome sequencing, and whole-genome sequencing has substantially improved diagnostic yield, particularly in pediatric populations. Molecular diagnosis now directly informs therapeutic decision-making and long-term management, enabling a shift toward precision nephrology. This narrative review integrates genetic, mechanistic, and clinical perspectives to illustrate how molecular diagnosis reshapes the evaluation, prognosis, and treatment of nephrocalcinosis. Full article

The common bean (Phaseolus vulgaris L.) is a major food legume and an important plant genetic resource for sustainable agriculture. Effective use of this diversity requires integrated evaluation of phenotypic variation and agronomic performance, with preliminary assessments of line performance across seasons. In this study, phenotypic diversity was evaluated in a subsample of the INCREASE R-core collection, a large and well-defined core set of common-bean SSD lines derived from heterogeneous germplasm lines. A total of 507 lines were characterized using 57 agro-morphological traits. Multivariate analyses revealed wide phenotypic diversity structured mainly by growth habit, phenology, and yield-related traits, with clear differentiation among lines. Mixed-data clustering identified cluster 4 as the main phenotypic group associated with higher seed- and yield-related performance and composed predominantly of indeterminate climbing landraces. Multi-trait selection indices generally ranked lines from this group highest, while early, small-seeded types tended to show lower overall performance. Evaluation of a selected subset of 19 lines across two growing seasons revealed marked year-to-year variation in yield performance, indicating contrasting responses among otherwise high-performing lines. The multi-trait genotype–ideotype distance index further distinguished lines with balanced performance across traits and years. Overall, this study shows that large-scale phenotypic characterization combined with multi-trait evaluation can provide a useful exploratory basis for identifying breeding-relevant ideotypes and promising lines for further validation for common-bean improvement. Full article

Accounting for over 1.2 million new diagnoses worldwide in 2022, non-melanoma skin cancer (NMSC) represents the most common human cancer, predominantly manifesting as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). NMSC serves as a powerful natural model for studying how environmental exposure, the exposome, reprograms the epigenome to drive carcinogenesis. Chronic ultraviolet radiation (UVR), the dominant risk factor, induces DNA damage and inflammation that dysregulate epigenetic enzymes (e.g., DNMTs, HDACs). These effects are layered with perturbations from β-HPV infection and cutaneous dysbiosis, altering DNA methylation, histone modifications, and non-coding RNA and miRNA expression in a multistep carcinogenic process. This review synthesizes the central role of epigenetic regulation as the critical interface between genetic susceptibility and cumulative exposome factors in NMSC pathogenesis. We integrate how UVR, HPV, and inflammation converge to remodel the keratinocyte epigenome. Finally, we evaluate the translational potential of this knowledge for refined risk stratification through epigenetic biomarkers and discuss emerging therapeutic strategies, including epidrugs, that target these dysregulated pathways for advanced NMSC management. Full article

Introduction: Major Depressive Disorder (MDD) has been increasingly associated with inflammatory dysregulation, particularly involving tumor necrosis factor-alpha (TNF-α). Genetic polymorphisms within the TNFA promoter region have been investigated as potential modulators of depressive susceptibility, symptom expression, treatment response, and inflammatory comorbidity. However, findings remain inconsistent across populations and clinical contexts. Methods: This systematic review adhered to PRISMA 2020 guidelines and was registered in PROSPERO (CRD420251242724). Observational and interventional studies evaluating associations between TNFA polymorphisms—specifically rs1800629 (−308 G/A), rs1799724 (−857 C/T), and rs1799964 (−1031 T/C)—and MDD-related outcomes in adults were included. Data extraction and methodological quality assessment were performed independently using an adapted GRIPS framework. Results: Eleven studies met the inclusion criteria, with eight investigating MDD without cardiovascular comorbidity and three assessing cardiovascular populations. Across diverse cohorts, rs1800629 and rs1799724 did not demonstrate consistent associations with MDD susceptibility. Although isolated population-specific findings were reported, genotype and allele distributions were generally comparable between cases and controls. Rs1799724 was associated with symptom dimensions and altered TNF-α expression in two cohorts. Rs1799964 was not linked to disease occurrence but showed potential association with antidepressant response and adverse cardiovascular outcomes in patients with chronic heart failure and comorbid depression. Overall, findings were heterogeneous and influenced by population characteristics, sample size, and clinical context. Conclusions: Current evidence does not support a robust etiological role for TNFA promoter polymorphisms in major depressive disorder. These variants may exert context-dependent modulatory effects on symptom expression, treatment response, or inflammatory-cardiovascular interactions rather than serving as primary susceptibility determinants. Larger, ethnically diverse studies integrating genetic, inflammatory, and clinical data are required to clarify the contribution of inflammatory genetic variability in depressive disorders. Full article

Feline calicivirus (FCV) is a major pathogen that threatens feline health worldwide. Its global prevalence, extensive genetic variability, and limited cross-protection among strains present significant challenges for vaccine development. In this study, an infectious clone of the FCV-GDJM202201 strain was constructed using the eukaryotic expression plasmid pcDNA3.1 under the control of the cytomegalovirus (CMV) promoter. The rescued virus, rGDJM-A4822T, exhibited growth kinetics comparable to those of the parental strain in vitro. Subsequently, two recombinant viruses, rGDJM-VP1_JL and rGDJM-VP1_SH, were generated by replacing the VP1 gene in the GDJM202201 backbone with those from heterologous FCV strains. Notably, these recombinant viruses exhibited reduced viral titers compared to rGDJM-A4822T. Finally, neutralization assays revealed differential neutralizing antibody titers among the recombinant FCVs, with rGDJM-A4822T inducing higher neutralizing antibody titers and cross-neutralizing activity. Collectively, this study establishes an FCV infectious clone that can be used to rescue recombinant viruses carrying heterologous VP1 proteins and to evaluate neutralizing antibody responses. Full article

For over a decade, non-integrating Sendai virus vectors have been the gold standard for induced pluripotent stem cell (iPSC) reprogramming. However, as the field shifts toward regenerative and precision medicine and large-scale biorepositories, Sendai virus workflow necessitates dedicated viral-clearance testing, specialized manufacturing controls, and heightened regulatory oversight, leading to increased cost. While mRNA-based reprogramming offers a non-viral alternative, traditional mRNA delivery methods like electroporation are often physiologically disruptive. This study evaluates an mRNA-reprogramming platform that delivers lipid nanoparticles (mRNA-LNPs) via receptor-mediated endocytosis. By utilizing both Sendai virus and mRNA-LNP approaches to reprogram PBMCs from the same donor, we established a genetically identical starting point. Results demonstrate that mRNA-LNP-reprogrammed iPSCs maintain genomic integrity, retain the donor KCNH2 c.2398+5G>T variant, and exhibit characteristic colony morphology, pluripotency markers, and trilineage differentiation capacity consistent with the Sendai-reprogrammed counterparts. The mRNA-LNP-reprogrammed iPSCs differentiate into iPSC-derived cardiomyocytes presenting sarcomeric structures and electrophysiological activity, recapitulating a disease-specific phenotype. Notably, the mRNA-LNP workflow reached these milestones in significantly fewer passages than the Sendai virus workflow, markedly shortening timelines and reducing costs. These findings highlight mRNA-LNP reprogramming as a potentially attractive and effective, virus-independent platform to support future regenerative and precision medicine initiatives and scalable biobanking. Full article

Coking coal flotation is a typical nonlinear, multi-variable, and multi-objective process in which concentrate quality and combustible matter recovery must be balanced under fluctuating feed and operating conditions. To improve both predictive reliability and decision support, this study proposes an integrated data-driven framework that combines particle swarm optimization-back propagation (PSO-BP) prediction, SHapley Additive exPlanations (SHAP) based interpretation, Non-dominated Sorting Genetic Algorithm II (NSGA-II) optimization, and entropy-weighted Technique for Order Preference by Similarity to Ideal Solution (Entropy-TOPSIS) decision-making. After three-sigma outlier screening, 2000 valid distributed control system (DCS) samples were retained for model development and temporal holdout evaluation, and an additional 200 later-period industrial samples were used for independent validation. The data were partitioned chronologically, with months 1–4, month 5, and month 6 used for training, validation, and temporal holdout testing, respectively, while the months 7–8 dataset was reserved for later-period validation. The results show that PSO-BP consistently outperformed conventional BP under both temporal holdout and later-period validation. SHAP analysis identified raw coal ash and collector dosage as the dominant factors for product-quality prediction, while collector dosage and frother dosage contributed most strongly to tailing heat of combustion. NSGA-II further revealed the trade-off among clean coal ash, clean coal sulfur, and tailing heat of combustion, and Entropy-TOPSIS converted the Pareto-optimal candidate set into a practically balanced operating recommendation. Sensitivity and robustness analyses indicated acceptable stability of both the optimization process and the final decision result. Overall, the proposed framework provides an interpretable prediction–optimization–decision workflow for coking coal flotation and offers a practical basis for future DCS-assisted intelligent regulation. Full article