Search Results (7,357)

Antimicrobial resistance (AMR) represents a global health crisis, driven largely by the mobility of resistance determinants through mobile genetic elements (MGEs). These include plasmids, integrons, insertion sequences, transposons, integrative and conjugative elements (ICEs), and prophages, which together facilitate horizontal gene transfer (HGT) across bacterial species and ecosystems. This review aims to provide a comprehensive synthesis of current knowledge on the types, mechanisms, ecological drivers, and impacts of MGEs in the dissemination of antibiotic resistance genes (ARGs). Methods involved critical evaluation of recent genomic, epidemiological, and ecological studies, alongside case studies of clinically significant resistance outbreaks. Findings highlight how MGEs function as hubs for ARG capture, recombination, and stabilization, enabling the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens. We also explored their interactions with ecological pressures such as antibiotics, heavy metals, and biocides, as well as their role in One Health transmission pathways. The significance of this study lies in linking molecular insights with applied strategies, including genomic surveillance, MGE-targeted inhibitors, phage therapy, and CRISPR-based interventions. Understanding MGEs is essential for designing effective interventions to mitigate AMR and protect global health. Full article

Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disorder that, without treatment, can advance to fibrosis and cirrhosis. Although standard regimens with corticosteroids and thiopurines have significantly improved survival, many patients still experience relapses and drug-related toxicity, highlighting the urgent need for alternative strategies. Recent studies underscore AIH’s multifactorial nature, revealing intricate interactions among genetic susceptibility, environmental triggers, and dysregulated immune responses. Next-generation diagnostics, ranging from novel biomarkers to high-resolution imaging, are enhancing early detection and more precise disease classification. At the same time, multi-omics analyses and artificial-intelligence-based models are refining predictions of disease trajectory and therapeutic response. On the treatment horizon, investigational options such as targeted immunomodulators, B-cell–depleting therapies, and cell-based interventions aim to achieve durable remission while minimizing adverse effects. This review critically appraises these advances and explores how integrating epidemiological insights with cutting-edge research in pathogenesis, diagnostics, and therapy could pave the way for more personalized and effective management of AIH. Full article

Alternanthera philoxeroides is a highly invasive alien species in China that causes waterway blockages, agricultural yield loss, biodiversity decline, and ecosystem degradation. This study assessed the invasion risk and environmental drivers of A. philoxeroides in Guizhou Province, a karst mountainous region in Southwest China. Occurrence records were obtained from field surveys and the Chinese Virtual Herbarium. The genetic algorithm for rule-set production (GARP) model and the jackknife method were employed to identify 13 key environmental indicators for predicting invasion risk. The global invasion risk index (GIRI) was applied to quantify the overall invasion risk. Additionally, the Geodetector model was utilized to analyze the spatially differentiated effects of six environmental factors. The results showed that A. philoxeroides poses a high invasion risk in Guizhou Province, and the invasion risk in the Yangtze River Basin within Guizhou is higher than that in the Pearl River Basin. The environmental factors influencing invasion risk, in order of impact, were slope, elevation, land use, river density, rocky desertification, and soil pH. Moreover, interactions among these factors further amplify the invasion risk. These findings provide valuable insights for developing targeted management strategies for A. philoxeroides in karst mountainous regions and support biodiversity preservation and regional ecological sustainability. Full article

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

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

Autoimmune diseases arise from the failure of self-tolerance. The recognition of self-antigen peptide–MHC (pMHC) complexes by the T-cell receptor (TCR) is the fundamental event triggering autoimmune pathogenesis. While traditional immunosuppressants provide broad systemic effects, they often compromise global immunity. Emerging molecular strategies aim to selectively disrupt the trimolecular complex—comprising the TCR, the antigenic peptide, and the MHC molecule—to induce antigen-specific tolerance. This review highlights the pMHC–TCR interaction as the primary molecular checkpoint for antigen-specific intervention. We discuss the structural basis of these interactions and their potential to redefine the therapeutic landscape for autoimmune diseases (ADs). We examine the molecular drivers of tolerance breakdown—including genetic susceptibility, molecular mimicry, post-translational modifications (PTMs), and ectopic MHC II expression—that shape the autoreactive T-cell landscape. This review examines current advancements in biological and pharmacological interventions, such as pMHC-decorated nanoparticles and soluble pMHC, to reprogram pathogenic T-cell response. We also explored CAR-T therapy strategies for autoimmune diseases, such as CAR-Treg, designed to precisely modulate pMHC-TCR signaling. Collectively, these precision interventions in immunological synapse assembly during autoimmune response are considered the basis for safer, antigen-specific immunotherapy capable of restoring self-tolerance without global immunosuppression. Full article

Background: Antimicrobial resistance is a One Health problem driven by the intricate interactions across human, animal, and environmental interfaces that enable microbial exchange and movement of mobile genetic elements encoding resistance and virulence. This study investigated the genomic epidemiology of ESBL and non-ESBL Escherichia coli across One Health interfaces in Oman. Methods: This prospective cross-sectional study analyzed 295 non-duplicate Escherichia coli isolates derived from 104 clinical, 173 animal [diseased (123) and healthy (50)], 14 sewage and four water sources. Antimicrobial susceptibility testing was performed phenotypically, and a representative subset of 50 ESBL and non-ESBL Escherichia coli from the three interfaces underwent whole genome sequencing to determine MLST, phylogroups, resistance genes, virulence determinants and plasmid replicons. Results: ESBL prevalence was highest in human isolates (73%), followed by sewage (28.6%) and animals (16.3% diseased; 8% healthy). blaCTX-M-15 predominated in humans, whereas blaCTX-M-55 dominated in animals and sewage, suggesting ecological partitioning with partial overlap. Quinolone resistance was lowest in the animal interface. Sewage isolates harbored the most complex resistome, including rmtB and plasmid-mediated quinolone resistance genes. MLST analysis revealed high diversity in human isolates, including globally recognized ExPEC lineages (ST10, ST38, ST73, ST127, ST131), while ST224 dominated in animals with evidence of possible spillover to humans. ST167 was confined to sewage, consistent with environmental maintenance of high-risk clones. Phylogroup structuring showed predominance of A, B2 and D among human isolates and A, B1, and E among animal and sewage isolates. Virulence profiling demonstrated broader virulome diversity in humans, but shared core determinants (fimH, sitA, traT) across all domains. IncFIB(AP001918) was the dominant plasmid replicon, particularly among ESBL isolates, underscoring its role in horizontal gene dissemination. Alarmingly, mutation in pmrB (V161G) was identified in a healthy animal isolate, pointing to a need for greater colistin restriction in animal husbandry. Conclusions: This study highlights plasmid-mediated resistance and shared virulence determinants linking reservoirs; although AMR profile was quite distinct across the three interfaces, human isolates demonstrated greater resistance than animal isolates, suggesting healthcare-driven AMR in Oman. Continued integrated genomic surveillance is essential to monitor gene flow and inform coordinated antimicrobial stewardship strategies. Full article

Background: Colistin (Col) resistance and heteroresistance in extensively drug-resistant (XDR) Acinetobacter baumannii severely limit therapeutic options. We investigated the activity and mechanism of human albumin nanoparticles (haNPs) as colistin potentiators against genetically characterized clinical isolates. Methods: Sixteen clinical isolates were analyzed. Col MICs were determined by broth microdilution, and heteroresistance by population analysis profiling. Potentiation of Col activity was assessed using both Col-loaded haNPs (Col/haNPs) and free Col co-administered with empty haNPs, alongside the proton motive force (PMF) uncoupler carbonyl cyanide 3-chlorophenylhydrazone (CCCP). Assays included checkerboard synergy (FICI), membrane potential analysis (DiOC₂(3)), intracellular Col quantification (UPLC–MS/MS), zeta potential measurements, transmission electron microscopy (TEM), protein leakage, and ROS detection. Results: Heteroresistance was detected in 9/16 isolates. Col/haNPs reduced Col MICs by 4–64-fold in resistant strains and shifted MICs to ≤2 mg/L in most heteroresistant isolates. Empty haNPs displayed no intrinsic antibacterial activity yet selectively potentiated Col, with strong synergy (FICI down to 0.035). Membrane depolarization and increased intracellular Col accumulation under haNP-treated conditions paralleled the effects of CCCP, indicating that haNPs elicit a CCCP-like functional response. These findings are compatible with perturbation of membrane energetics and possible downstream effects on PMF-dependent transport processes. TEM and surface charge analyses supported direct nanoparticle–envelope interaction and progressive membrane disruption. Conclusions: haNPs enhance Col activity across genetically diverse A. baumannii isolates, with particularly strong effects in heteroresistant strains. The combined effects of PMF modulation, increased intracellular drug availability, and envelope interaction provide a mechanistic rationale for the use of albumin-based nanoparticles, either as Col carriers or in combination with free drug, to overcome Col resistance and heteroresistance. Full article

Background/Objectives: Musculoskeletal soft-tissue injuries are common among physically active individuals and arise from complex interactions between environmental and biological factors. Genetic variation in genes involved in extracellular matrix (ECM) organization may contribute to individual susceptibility to such injuries. This study investigated whether polymorphisms in aggrecan (ACAN, rs2351491 and rs1042631) and fibromodulin (FMOD, rs7543148) genes are associated with susceptibility to sports-related injuries. Methods: The study included 335 physically active Caucasians, comprising 202 participants with a history of non-contact sports-related musculoskeletal injuries and 133 uninjured controls. Genotyping was performed using real-time polymerase chain reaction. Results: No significant associations were observed between the analyzed polymorphisms and overall injury occurrence after correction for multiple comparisons. A nominal association was observed for ACAN rs2351491 in the overall injury comparison under the overdominant model (p = 0.0457), where CT heterozygotes were more frequent among injured participants. The ACAN rs1042631 variant showed nominal associations with anterior cruciate ligament (ACL) injury under the codominant (p = 0.0179), recessive (p = 0.0243), and overdominant (p = 0.0346) models, with the TT genotype associated with lower odds of ACL injury under the recessive model (OR = 0.15, 95% CI: 0.02–1.22). No significant associations were observed for FMOD rs7543148 or for haplotype analysis of ACAN variants. Conclusions: No robust associations were identified between the investigated variants and susceptibility to musculoskeletal soft-tissue injury after correction for multiple testing. Nominal signals observed for ACAN variants, particularly in ACL-focused analyses, warrant further investigation but should be interpreted cautiously and confirmed in larger, independent cohorts. 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

Mating-type identification is fundamental to studies of genetic diversity and genetic breeding in fungi, especially for tetrapolar basidiomycetes, whose mating types are determined by two multiallelic loci, A and B. Traditional mating-type identification of monokaryons relies on manual inference based on hybridization experiments; however, this process is highly complex, time-consuming, and error-prone when applied to large-scale studies. In this study, we isolated 30 monokaryons from protoplasts derived from 15 dikaryons of Flammulina velutipes and developed a software tool, Mating-Type Imputation (MTI), to automatically, rapidly, and accurately infer monokaryon mating types in tetrapolar fungi using a combinatorial pruning traversal algorithm. Using a compatibility matrix derived from 435 hybridization experiments involving these 30 monokaryons, MTI required only a few minutes to accurately infer the mating types of all monokaryons-a task that typically takes several days for manual inference by experienced investigators. Furthermore, MTI enabled us to investigate how false-positive and false-negative interactions influence mating-type inference results. Using a simulated compatibility matrix, we found that MTI could accurately detect potential false negatives in compatibility and successfully infer the true mating-type combinations even in the presence of limited false negatives; conversely, the tool was easily misled by any false positives, resulting in incorrect mating-type combinations. This indicates that false-positive records in hybridization experiments must be strictly eliminated during mating-type inference. In summary, MTI provides an efficient tool for inferring the mating types of tetrapolar fungi, offering technical support for mating-type studies of edible and medicinal fungi, and holds significant theoretical value and broad application potential in the fields of fungal genetic diversity and breeding research. Full article

Quercus oxyphylla (E. H. Wilson) Hand.-Mazz. is a threatened evergreen subalpine tree species with fragmented habitats native to China. Here, we present a de novo chromosome-level genome assembly of this oak species by integrating PacBio long-read high-fidelity (HiFi) sequencing and Hi-C mapping technologies. The assembled genome size of Q. oxyphylla in this study is 824.15 megabases (Mb) in length with 12 putative chromosomes. Genome annotation of this oak species identified 514.09 Mb of repeat sequences, 53,730 protein-coding genes and 1048 non-coding RNA sequences. Genomic analyses of whole-genome duplication (WGD) and long terminal repeat retrotransposon (LTR-RT) insertion events in Q. oxyphylla revealed no species-specific WGD and recent accumulation of LTR-RTs in the genome within the last seven million years. A phylogenomic analysis with eight oak representatives confirmed the framework phylogeny of genus Quercus and indicated that Q. oxyphylla possibly split with the ancestor of Cerris oaks about 20.4 million years ago. We identified 2074 expanded and 903 contracted gene families across the genome assembly of Q. oxyphylla, while the significantly expanded gene families had notable disease resistance-related genes that were mainly enriched in plant–pathogen interaction pathways. The high-quality genome assembly of Q. oxyphylla generated in this study provides a valuable genome resource for the genetic conservation and management of Q. oxyphylla, and may facilitate our understanding of genome evolution and species adaptation of the oak lineage. Full article

This review aggregates the latest reports on the role of environmental factors in the male reproductive system and cancer development. We analyzed environmental pollution-related studies and disorders of mechanisms responsible for defense against the impact of xenobiotics on prostate cancer. We focused on polymorphisms that, when exposed to environmental stressors, might exacerbate an organism’s defense mechanisms against the effects of xenobiotics. It is well known that environmental factors, such as toxic heavy metal pollution, xenobiotic exposure, and undue and differentiated stressors, affect the human reproductive system. There were many studies suggesting an association between these factors and prostate cancer development, but there are still no unambiguous or conclusive results. Investigations of specific marker changes that occur in response to varied environmental stressors are also critical to mutual relations. They focus on the influence of chemical element destabilization and heavy metal pollution on organisms and the environment. Simultaneously, antioxidant enzymatic mechanisms in conditions of anthropogenic impact and the influence of polymorphisms in genes involved in genetic material damage under stress conditions were also studied. This review aims to provide essential data suggesting the role of environmental factors in the initiation and development of carcinogenic processes in the male reproductive system based on prostate cancer cases. It further clarifies this field’s current needs and research directions. It is possible to conclude that there is a relationship between the studied polymorphisms and antioxidant mechanisms, lipoperoxidation, and trace element concentrations in the blood of men with prostate cancer. The results indicate the need to consider environmental factors as necessary in assessing the risks resulting from exposure to oxidative stress in prostate cancer patients. Available data suggest the existence of interactions between exposure to environmental stressors and increased susceptibility to cancers, including male reproductive system cancers. Differentiated chemical elements introduced into the body may play a significant role. Individuals with cancer have a disturbed antioxidant enzyme status, which could be a basis for decreased defense against carcinogenic factors or the effect of disturbed body balance caused by the carcinogenic process. In turn, studies of repair gene polymorphism may indicate disorders of proteins needed for the organism’s defense against xenobiotics. The analysis presented provides data for conclusive population-based studies of the impact of environmental factors on the carcinogenic process in the male reproductive system. This review provides a basis for constructing current needs and the research direction in the discussed field of knowledge. This will allow for a precise study of the explanation of possible multilateral interactions between exposure to varied environmental stressors and the increased incidence of male reproductive system cancer at present. Full article

This study systematically elucidated the developmental characteristics and molecular regulatory mechanisms of the testis during the critical period of sexual maturation in Kazakh horses by combining histological observation of one- and two-year-old testicular tissues with transcriptomic sequencing. In the testes of one-year-old horses, no obvious lumen was observed, and the interior is mainly comprising supporting cells and spermatogonia on the basement membrane; in contrast, in the testes of two-year-old horses, the tubular lumen was complete with spermatogonia, spermatocytes, and spermatozoa, indicating that spermatogenic function had approached maturity. Transcriptome profiling identified 979 differentially expressed genes (DEGs), with 209 up-regulated genes, including CYP11A1 and CATSPER2, and 770 down-regulated genes, including CD9. Gene Ontology (GO) annotation indicated primary enrichment of DEGs in biological processes related to multicellular organism development, cell membrane composition, and ion binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed significant enrichment of DEGs in the calcium signaling pathway, cell adhesion molecules, and neuroactive ligand–receptor interaction, among other key pathways. Protein–protein interaction (PPI) network analysis further highlighted core genes, including TNF, CATSPER2, and CDH13. Validation by RT-qPCR confirmed the reliability of the RNA-Seq data. Our findings reveal the dynamics of testicular development in Kazakh horses through histological and molecular analyses, thereby providing a theoretical framework and candidate genes to further elucidate regulatory mechanisms and guide genetic improvement in reproductive traits. Full article

Background/Objectives: Mild cognitive impairment (MCI), the prodromal stage of Alzheimer’s disease, may be influenced by nutritional status and genetic susceptibility. This systematic review synthesised evidence on how nutritional biomarkers interact with genetic variants, particularly APOE ε4, to influence cognitive outcomes in individuals with MCI. Methods: Following PRISMA 2020 guidelines, seven studies were included (three longitudinal, two randomised controlled trials, and two cross-sectional) involving adults aged ≥55 years with MCI. Nutritional exposures comprised plasma or serum concentrations of vitamins A, D, E, the vitamin B group, lipids, selenium, and ketogenic medium-chain triglycerides. Genetic risk was assessed primarily through APOE ε4 status. Risk of bias was assessed using RoB 2 and ROBINS-I, and certainty of evidence using GRADE. Due to heterogeneity in biomarkers, cognitive tools, and study designs, findings were synthesised narratively. Results: Across nutrient categories, higher concentrations of vitamin D, selenium, and antioxidants were associated with better cognitive outcomes. kMCT supplementation improved episodic memory and brain energy metabolism. Evidence for nutrient–gene interactions was mixed: APOE ε4 modified responses to vitamin B group and selenium but showed limited influence on vitamin D, lipids, or kMCT effects. Heterogeneity in biomarker assays, cognitive tools, and genetic stratification limited comparability across studies. Conclusions: Nutritional biomarkers appear to influence cognitive trajectories in MCI, and some associations may differ by APOE ε4 status. However, small samples and limited genetic stratification constrain interpretation. Future research should prioritise standardised biomarker measurement, genetically stratified cohorts, and individual participant data meta-analyses to clarify nutrient–gene interactions in MCI. Full article