Search Results (996)

Ulomoides dermestoides (Yangchong) is a tenebrionid beetle used in traditional medicine across Asia and Latin America. While crude extracts show effects on inflammation, oxidative stress, and other conditions, systematic integration of its bioactive substances, mechanisms, and translational potential is lacking. This review consolidates its chemical basis, comprising volatile benzoquinones, terpenes, and alkenes, alongside non-volatile fatty acids, proteins (antioxidant enzymes, glycoproteins), and phenolics. Pharmacological evidence indicates multi-target modulation of reactive oxygen species (ROS), cytokines, leukocyte recruitment, endothelial activation, and thromboinflammation. Recent advances include proteomic identification of antioxidant protein complexes, neuroprotection in a Parkinson’s disease model, chromosome-level genome assembly, and isolation of the UDP-glucose pyrophosphorylase 2a (UGP2A) glycoprotein, which alleviates thrombosis partly via toll-like receptor 4/myeloid differentiation primary response 88 (TLR4/MyD88)-mediated endothelial anti-inflammatory effects. However, most evidence remains preclinical, relying on non-standardized crude extracts, and benzoquinone-containing fractions display potential cytotoxicity and genotoxicity. Future research should integrate bioassay-guided isolation, structural characterization, multi-omics, pharmacokinetic/pharmacodynamic (PK/PD) analysis, standardized quality markers, and rigorous safety evaluation to transform U. dermestoides from an empirical insect-derived medicinal resource into a scientifically validated source of preclinical antioxidant and anti-inflammatory candidate substances. Full article

Seven indigenous strains of Bradyrhizobium japonicum subsp. saratovii isolated from soybean nodules (Glycine max (L.) Merr.) grown in the arid Lower Volga region of Russia were investigated. A complete set of the major symbiotic genes was detected in all strains. Single synonymous nucleotide substitutions were identified in nifH and nifD, whereas a missense mutation, Ser149Phe, was found in the nifK gene of strain II-2. Homology modelling showed that this substitution did not cause any noticeable rearrangement of the overall structure of the nitrogenase β-subunit, although it was located near the conserved Cys152 residue. The nodB and nodC genes were completely conserved; the nodC sequence corresponded to symbiovar glycinearum. Structural disruptions in the nap operon were detected in strains II-2 and III-2, which was consistent with the absence of nitrate-reducing activity. Comparison of the genomic data with the inoculation results showed that the most effective strain, II-2, combined strong growth-promoting and yield-enhancing effects with the presence of a complete set of symbiotic genes and disruption of napA. These findings indicate that the integration of genomic analysis with phenotypic assessment improves the accuracy of selecting promising indigenous Bradyrhizobium strains for soybean inoculation. Full article

Ribonucleotides are frequently incorporated into DNA during the replication of genetic information and, if missed during ribonucleotide excision repair, they may undergo phosphodiester bond rearrangement or cleavage. These changes can in turn lead to deformation of the spatial geometry of the local double helix and potentially interfere with charge transfer through ds-DNA. This process is believed to support long-range communication between proteins involved in genome replication and repair. This study theoretically explores how a single embedded riboadenosine (A₃) affects the structure, electronic properties, and charge-transfer properties of double-stranded DNA ([A₁G₂A₃G₄A₅]*[T₅C₄T₃C₂T₁]). In particular, the study focuses on four products formed at the ribonucleotide site: native 3′,5′-linkage (R-DNA), the 2′,3′-cyclic phosphate intermediate (IM-R-DNA), rearranged 2′,5-linked (RE-R-DNA), and the single-strand-break cleavage product (SSB-R-DNA). This theoretical investigation was performed at the M06-2X/6-31++G**//M06-2X/D95** level of theory in the aqueous phase. Significant spatial geometry perturbations were found at the central part of ds-oligonucleotides, i.e., the A₃T₃|G₄C₂ region, where the modified linkage affected the base overlap and stacking interactions most strongly; in the rearranged and cleaved forms, stacking at this site decreased by about 7 kcal•mol⁻¹ relative to native DNA. Global electronic analysis showed that R-DNA had the highest ionisation potential and the lowest electron affinity, whereas SSB-R-DNA displayed the lowest adiabatic ionisation potential and the highest adiabatic electron affinity, indicating a much greater tendency to stabilise excess charge. At the base-pair level, G₂C₄ was usually the preferred hole sink, except in RE-R-DNA, where G₄C₂ was favoured. In contrast, electron localisation was generally favoured at G₄C₂, while, in SSB-R-DNA, the A₃T₃ pair became the most favourable electron-accepting site. Overall, the results show that even a single ribonucleotide, depending on its linkage chemistry, can substantially reshape charge migration through ds-DNA and may therefore influence lesion recognition, repair efficiency, and genome stability. Full article

Dendrobium lindleyi is an orchid species valued for both ornamental and medicinal purposes; its secondary metabolites possess heat-clearing and fluid-generating properties. Dirigent (DIR) proteins play a key regulatory role in plant lignin polymerization and responses to abiotic and biotic stresses; however, systematic studies of DIR family genes in D. lindleyi are lacking. The objective of this study was to systematically characterize the DIR gene family in D. lindleyi. To achieve this, bioinformatics methods were used to identify DIR genes genome-wide, followed by analyses of their post-translational modifications, gene and protein structures, phylogeny, promoter cis-regulatory elements, expression patterns, and subcellular localization. The results show that 15 DIR family genes were identified in the D. lindleyi genome. The DIR family is divided into five subfamilies: DIR-a, DIR-b/d, DIR-c, DIR-e, and DIR-g, among which DIR-b/d has the most members (9), and DlDIR2 and DlDIR4 exhibit a fragment duplication event. The promoter regions are rich in light-responsive, ABA, MeJA, MYB, MYC, WRKY, and oxidative stress-related elements, suggesting that DIR genes in D. lindleyi may be involved in multiple signaling pathways. Transcriptomic and qRT-PCR analyses revealed that DlDIR8 exhibits a strong response to ABA treatment, with ABA inducing its downregulation. Subcellular localization studies revealed that the DlDIR8 protein is localized to the nucleus. These findings provide a foundation for the functional characterization of the DIR gene family in D. lindleyi and highlight DlDIR8 as a candidate in the ABA-mediated stress response, offering a theoretical basis for the potential genetic improvement of this species. Full article

The genus Aegilops comprises important wild relatives of cultivated wheat and represents a valuable genetic resource for wheat improvement. In this study, the complete chloroplast genomes of five Aegilops species (Ae. crassa, Ae. cylindrica, Ae. juvenalis, Ae. tauschii, and Ae. triuncialis) collected from Kazakhstan and Uzbekistan were sequenced, assembled, and comparatively analyzed. The chloroplast genomes exhibited a conserved quadripartite structure consisting of a large single-copy (LSC), a small single-copy (SSC), and two inverted repeat (IR) regions. Genome sizes ranged from 135,612 to 136,840 bp, with an identical GC content of 38% across all species. Comparative analyses revealed high structural conservation among chloroplast genomes, particularly within IR regions, whereas greater sequence divergence was observed in the non-coding regions of the LSC and SSC. Sliding-window analysis identified several highly polymorphic regions, including rpl32-trnL(UAG), ndhF-rpl32, trnC(GCA)-rpoA, psbA, and ndhD, which may serve as potential DNA barcodes and informative markers for phylogenetic studies. A total of 850 chloroplast simple sequence repeats (SSRs) were detected, predominantly A/T-rich mononucleotide repeats. Codon usage analysis demonstrated a conserved preference for A/U-ending codons across all species. Ka/Ks analysis indicated that most chloroplast protein-coding genes are under strong purifying selection, although relatively elevated evolutionary rates were detected in rpoA and ycf4. Phylogenetic analyses based on complete chloroplast genomes strongly supported sectional relationships within Aegilops and confirmed close maternal relationships among several species. Overall, this study provides chloroplast genome resources for Aegilops and contributes to understanding chloroplast genome evolution, phylogeny, and molecular marker development. Full article

Background/Objectives: Vitamin D deficiency is a global health concern, yet circulating 25-hydroxyvitamin D (25OHD) concentrations vary substantially across geographical regions and ancestral groups. Genetic predisposition may contribute to these differences. This systematic review aimed to synthesize evidence from genome-wide association studies (GWAS) on genetic variation associated with circulating 25OHD across populations from different ancestral backgrounds and to evaluate linkage disequilibrium (LD) between reported variants. Methods: A systematic review was conducted according to PRISMA 2020 guidelines. PubMed and the GWAS Catalog were searched to identify genome-wide association studies (GWAS) on circulating 25-hydroxyvitamin D (25OHD) concentrations. Studies were screened against predefined eligibility criteria, and data were extracted using a standardized framework. Methodological quality was assessed using a standardized tool, and study power adequacy was assessed formally. Genome-wide significant SNPs were extracted, and unique variants between studies were grouped by ancestry. Among these, dbSNP-indexed variants were grouped into genomic cluster windows and evaluated for LD structure. Results: Fifteen GWAS were included. Across these studies, 349 genome-wide significant SNP associations were identified, corresponding to 294 unique variants, of which 283 were indexed in dbSNP and retained for genomic and LD analyses. Variant discovery was dominated by large-scale European-ancestry studies, although African, Middle Eastern, East Asian, Hispanic/Latino, South Asian, and trans-ethnic studies also contributed signals. Some evidence of ancestry-specific variation was apparent, yet not conclusive due to lower study power in non-European cohorts. Variant aggregation was strongest at biologically relevant vitamin D loci, including GC, CYP2R1, DHCR7/NADSYN1, and FLG. Fifteen variants were replicated in at least two independent cohorts. LD-based clustering identified several high LD groups comprising variants identified across studies, with the strongest LD appearing between variants within established vitamin D-related loci, particularly GC, CYP2R1, DHCR7/NADSYN1, and FLG. Conclusions: Circulating 25OHD appears to be influenced by shared core loci involved in vitamin D metabolism, across ancestries. Although some evidence of ancestry-specific variation was identified, findings should be interpreted with caution, in light of the predominance of European-ancestry GWAS and scarcity of sufficiently powered GWAS for other ancestral populations. Larger GWAS in non-European populations are essential for improving ancestry-specific variant discovery and interpretation. Full article

Three-dimensional (3D) spatial interaction data are fundamental to understanding genome architecture. Multi-modal deep learning models that jointly learn from 3D spatial data and orthogonal modalities, such as gene expression, face a critical computational challenge: the 3D spatial modality dominates computation by over one order of magnitude, creating a structural memory bottleneck that renders heavyweight model instances untrainable on single GPU. Existing distributed training methods rely on cost-model searching and treat model components uniformly, overlooking modality-specific memory asymmetries. We propose Automatic Modality-aware Parallelization (AMP), a framework that diagnoses memory bottlenecks from data configuration signals and prescribes a set of five strategies. At the core of this framework is a hidden-dimension tensor parallelism strategy ($S_5$) that partitions the 3D decoder’s hidden dimension across GPUs, transforming five non-standard operators into sharded forms with formal equivalence proofs. Evaluated on Hi-C data and RNA-seq from the HiRES single-cell mouse brain dataset across lightweight and heavyweight configurations, AMP converts out-of-memory (OOM) failures into successful training runs. Scaling from four to eight GPUs under heavyweight configurations, the 500 kb and 100 kb variants achieve 2.0× and 3.8× training speedups respectively, with mathematical equivalence to single GPU computation guaranteed by formal proofs. Full article

Diffusion models for 3D genome structures make inference an ensemble-generation and tiling problem. In the released ChromoGen workflow, millions of independent denoising trajectories are executed through a single-GPU path, while overlapping genomic windows are sampled without enforcing consistency of their shared physical interval. We introduce ParaChromo, a parallel inference framework for conditioned, tiled 3D genome diffusion workloads built around the trained diffusion U-Net and distance-map interface. ParaChromo organizes the workload into three inference-layer modules: a workload-dispatch module schedules region, guidance, and sample chunks across worker groups; an encoder-aware sharded-conditioning module scales and shards the EPCOT front end with FSDP while keeping the inner-loop U-Net replicated; and a seam-coherent tiled-synchronization module projects the shared 12-bead overlap of adjacent reverse chains in distance-map space. On eight A6000 GPUs, the combined reduced-step and task-parallel systems path raises throughput from $2.356\pm 0.003$ to $235.71\pm 1.120$ samples/s, a $100.04\pm 0.486$-fold gain over the released single-GPU baseline. The reduced-step setting is supported by a sweep from 50 to 1000 DDIM steps, where distance-distribution and Hi-C-based metrics remain stable across four chromosomes. For the synchronization module, the chr22 seam discrepancy falls from 150.9 pm to 7.9 pm, while matched internal and Hi-C-based quality metrics are preserved. The synchronized chr22 run also gives a chromosome-scale coordinate rendering over 32 paper-aligned tiles. Together, these results show that conditioned, tiled 3D genome diffusion can be executed as a scalable workload when throughput parallelism, sampler length, encoder placement, and spatial consistency are treated as separate but compatible constraints. Full article

Background: This study investigated the relationships among mitochondrial energy metabolism, immune function, and gut microbiota in mice under a fatigued state, providing preliminary evidence for future nutrition-related mechanistic and intervention studies. Methods: Mice were adaptively fed for 4 days and then randomly divided into a normal control group (NC) and a fatigue model group (NM). Immune organ indices, serum IgG levels, thigh muscle ATP content, mitochondrial respiratory chain complex I–IV activities, and gut microbiota composition were assessed using enzyme-linked immunosorbent assay (ELISA), microplate assays, and 16S rRNA gene sequencing. Results: Compared with the NC, the NM showed a significantly reduced spleen index, serum IgG levels, mitochondrial respiratory chain complex I, III, and IV activities, along with reduced ATP content. Regarding gut microbiota, mice in the NM exhibited disordered intestinal villus arrangement, inflammatory cell infiltration in the crypts and muscular layers, and markedly reduced intestinal microbial activity as well as protease and sucrase activities. 16S rRNA sequencing revealed fewer ASVs in the NM, with enrichment of Lactobacillaceae, Limosilactobacillus, and Ligilactobacillus, whereas the NC was characterized by Borkfalkiaceae and Borkfalkia. Linear discriminant analysis effect size (LEfSe) analysis identified Lactobacillaceae, Firmicutes_D, and Lactobacillales as characteristic taxa of the NM. Kyoto Encyclopedia of Genes and Genomes (KEGG) prediction indicated that fatigue-associated microbial functions were mainly related to carbohydrate, amino acid, and lipid metabolism. Correlation and RDA analyses further suggested that alterations in gut microbiota structure were closely associated with mitochondrial energy-related indicators and immune-related parameters. Conclusions: Fatigue was associated with alterations in energy metabolism, immune function, and gut microecology in mice. The “gut microbiota–energy metabolism–immunity” framework may represent a potential association-based framework and provides biological information to support future nutrition-related intervention studies. Full article

This review aims to evaluate the potential of endometriosis models, especially patient-derived iPSC models, to gain deeper insights into the disease, thereby advancing our understanding and treatment of endometriosis. This comprehensive narrative review utilized a structured search of the PubMed, Scopus, and Web of Science databases, primarily covering literature published between January 2000 and May 2025. An expansive search strategy was employed to capture the full breadth of the field using keywords such as “endometriosis,” “induced pluripotent stem cells (iPSCs),” “patient-derived organoids,” “disease modeling,” and “epigenetics” without restrictive filtering, ensuring the integration of both foundational theories and emerging biotechnological advances. In total, over 170 peer-reviewed publications were analyzed, ranging from landmark genomic meta-analyses that have identified significant risk loci to state-of-the-art 3D-culture systems for modeling patient-specific endometrial disease. By synthesizing these diverse sources, the review bridges the gap between traditional anatomical classifications and modern molecular modeling to evaluate the potential of iPSC platforms for personalized medicine and therapeutic discovery. Endometriosis is a multifactorial gynecological condition that affects 176 million women worldwide and can significantly impair quality of life. It occurs when endometrium-like tissue grows outside the uterus, responsive to ovarian hormones, causing inflammation, pain, and discomfort, and leading to fibrotic tissue. World Health Organization estimates indicate that 6–10% of women suffer from this disorder, which can cause infertility and increase the risk of developing various types of cancer and autoimmune disorders. The use of patient-derived iPSC models serves to gain deeper insights into the disease by mimicking the endometrial tissue or lesions observed in affected individuals, thereby advancing our understanding and treatment of endometriosis. Full article

The Manila clam (Ruditapes philippinarum) is an economically important bivalve widely cultured in coastal aquaculture systems of China. However, the genome-wide genetic background and germplasm differentiation of geographically distinct populations remain unclear, which constrains germplasm conservation and the development of selective breeding programs. In this study, 50 individuals from five representative coastal populations (QZ, ZZ, ZP, CL, and NH) in China were subjected to whole-genome resequencing, producing 126.67 Gb of clean data and 92,593,087 SNPs after stringent filtering. Genetic diversity analyses showed that nucleotide diversity (π) ranged from 0.2453 to 0.2588, observed heterozygosity (Ho) from 0.1316 to 0.1492, and expected heterozygosity (He) from 0.2303 to 0.2435, with the CL population exhibiting relatively lower diversity. Population differentiation was low to moderate, with pairwise F_ST values ranging from 0.0454 to 0.0557. Principal component analysis, neighbor-joining phylogenetic analysis, and Admixture clustering consistently indicated limited population structure and extensive genetic admixture. TreeMix analysis further revealed directional gene flow among populations. Rapid linkage disequilibrium decay and predominantly positive Tajima’s D values suggested relatively stable demographic histories. Despite low genome-wide differentiation, combined F_ST and nucleotide diversity ratio analyses identified localized selective sweep signals in specific genomic regions. These results provide preliminary genome-wide insights into genetic diversity, population connectivity, and candidate localized differentiation signals in R. philippinarum. Given the low sequencing depth, the findings should be interpreted as population-level observations that require further validation using higher-depth genomic datasets before being applied to germplasm conservation and selective breeding programs. Full article

The re-emergence of Coxsackievirus A6 (CV-A6) as a predominant pathogen in hand, foot, and mouth disease (HFMD) underscores the need for ongoing molecular surveillance to clarify local evolutionary dynamics. This study aimed to characterize the genetic features of CV-A6 strains circulating in Baotou, Inner Mongolia, from 2023 to 2024. Throat swabs collected from HFMD patients were screened using real-time quantitative PCR; the VP1 region and complete genomes of representative CV-A6-positive samples were amplified and sequenced. Phylogenetic and recombination analyses were subsequently performed. Among 266 clinical specimens, 169 (63.53%) tested positive for enterovirus, of which 146 (86.39%) were identified as CV-A6. The local epidemic displayed an autumn–winter seasonality and predominantly affected children aged 4–6 years. Phylogenetic reconstruction of 133 VP1 sequences revealed that all Baotou CV-A6 isolates belonged to subgenotype D3c, and analysis of complete genomes identified a predominant recombinant form. These findings demonstrate that the D3c subgenotype, characterized by a specific recombinant structure, was responsible for HFMD outbreaks in Baotou during the study period, providing essential molecular evidence for regional public health strategies and vaccine development. Full article

The Yezo virus (YEZV) is a recently discovered tick-borne orthonairovirus with pathogenic potential, causing acute febrile illness in humans. Viral nucleoproteins (N) play a key role in genome packaging, replication, and modulation of host immune responses, making their structural characterization essential for understanding viral pathogenesis and developing targeted countermeasures. However, the absence of structural data for YEZV proteins significantly hinders these efforts. This study presents the first solution structure of the YEZV N domain 1 (D1). A highly purified, soluble, tag-free recombinant YEZV N D1 was produced from the native sequence of the clinical YEZV isolate. The native-state conformation was resolved through an integrated approach combining size-exclusion chromatography coupled with small-angle X-ray scattering (SEC-SAXS), AlphaFold 3 structure prediction, and all-atom molecular dynamics simulations. The YEZV N D1 structure adopts a stable, predominantly α-helical globular fold that remains monomeric under near-physiological conditions. SEC-SAXS data show excellent agreement with computational models, revealing moderate conformational flexibility. The characterized recombinant YEZV N D1 and its first solution structure reported here providing essential insights into understanding of YEZV molecular architecture. These findings lay a foundation for rational serological assay development and structure-guided therapeutic design against this and other emerging orthonairoviruses. Full article

Potato (Solanum tuberosum L.) is the world’s fourth-largest staple crop. Alkaline salt stress is a major abiotic stress factor that severely limits the growth, yield, and quality of potatoes; however, little is known about the molecular basis of potatoes’ response to alkaline salt stress or the stress-alleviation mechanism mediated by 24-epibrassinoside. In this study, we conducted a genome-wide identification of the potato miR482 family and analyzed its response patterns under alkaline salt stress and 24-epibrassinoside-mediated stress relief. We identified a total of 9 mature stu-miR482 sequences and 5 precursor sequences; all precursors form typical stable hairpin structures and exhibit high evolutionary conservation among Solanaceae plants. Promoter analysis revealed multiple cis-acting elements in the promoter region associated with light signaling, plant hormones, and stress signaling. A total of 64 potential target genes were predicted, encompassing transcription factors, disease resistance, and signal transduction-related genes, forming a complex regulatory network. Phenotypic analysis confirmed that EBR significantly alleviates the growth inhibition in potatoes induced by alkaline salt stress. qRT-PCR analysis indicated that stu-miR482a-5p is the primary stress-responsive member in leaves; stu-miR482d-3p/5p exhibited the strongest regulatory response to EBR in roots; in potato stolons, all members of the miR482 family were significantly upregulated under alkaline salt stress, with stu-miR482d-5p showing extremely significant upregulation across all treatment groups. In summary, this study represents the first systematic characterization of the potato miR482 family, revealing its tissue differential functions in alkaline salt stress and EBR-mediated stress relief. Full article

The stingless bee Geniotrigona thoracica is an ecologically and economically important pollinator in Southeast Asia, yet comprehensive genomic resources for this species remain limited. In this study, we sequenced, assembled, and annotated the complete mitochondrial genome (mitogenome) of G. thoracica to investigate its genomic architecture and phylogenetic position. The circular mitogenome is 16,061 bp in length and comprises the typical set of 37 genes, including 13 protein-coding genes (PCGs), 22 transfer RNA genes, and two ribosomal RNA genes. The genome exhibits a strong A + T bias, consistent with other hymenopteran mitogenomes, and codon usage patterns reflect this nucleotide composition. Most tRNAs display the canonical cloverleaf secondary structure, although minor structural variations were observed. Comparative analyses revealed several gene rearrangements, including transposition and inversion events, suggesting lineage-specific rearrangements, including transposition of the cox1–trnL–cox2–trnD–atp8–atp6–cox3 block and transposition with inversion of the trnF–nad5–nad4–nad4l–trnP block, relative to the ancestral hymenopteran gene order. Phylogenomic analyses based on concatenated mitochondrial genes strongly supported the monophyly of Meliponini and placed G. thoracica within a well-supported Indo-Malayan clade, closely related to Tetragonula, Heterotrigona, and Lepidotrigona. Furthermore, stingless bees were recovered as more closely related to bumblebees than to honeybees, consistent with previous studies. Overall, this study provides a complete, annotated mitogenomic resource for G. thoracica and contributes to a better understanding of mitochondrial genome evolution, phylogenetic relationships, and biogeographic patterns in stingless bees. Full article