Search Results (743)

Background: We previously pioneered a multigene mRNA test, qMIDS^V2, validated through an international multicohort study with geographically and ethnically diverse oral squamous cell carcinoma (OSCC) patients from Europe and Asia. This study aimed to repurpose the qMIDS^V2 test for nasopharyngeal carcinoma (NPC). A molecular test independent of Epstein–Barr virus (EBV) status would be clinically useful for risk stratification in NPC patients with undetectable or low levels of EBV. Methods: This study investigated a Chinese cohort of 62 participants (18 donated normal nasopharyngeal mucosa (NPM) and 44 donated NPC tissue samples). Messenger RNA levels of 16 genes in each sample were quantified using the qPCR method, and an algorithm computed a malignancy index for cancer risk stratification. Results: We identified a unique 10-gene panel (containing eight target genes, namely NEK2, INHBA, FOXM1, TOP2A, BIRC5, CXCL8, NR3C1, and IVL, relative to two reference genes, YAP1 and POLR2A, collectively named qMIDS^NPC) that demonstrated the best overall diagnostic performance in segregating NPM from NPC, with AUC = 0.909 and positive/negative predictive values of 91% PPV and 78% NPV, respectively. Furthermore, we demonstrated prognostic value of qMIDS^NPC in segregating NPM from NPC stage III + IV, with AUC = 0.936, 92% PPV, and 84% NPV. Conclusions: Here, we present a simple qPCR-based 10-gene mRNA test, qMIDS^NPC, with potential clinical utilities for rapid (1 h) prognostic stratification of NPC. Further studies involving geographically and ethnically independent NPC cohorts would be needed to validate the clinical use of qMIDS^NPC in non-endemic NPC populations. Full article

Mitotic catastrophe refers to a complicated mechanism of cell death characterized by failure to complete the processes of mitosis correctly due to aberrant chromosome segregation and abnormal tubulin polymerization. Post-translational modifications (PTMs) play a crucial role in the functional diversity of the proteome by mediating the covalent attachment of functional groups to proteins, which regulates the proteolytic cleavage of subunits, facilitating the degradation of entire proteins. Recent studies suggest that PTMs of key proteins are closely implicated in the occurrence, regulation and potential therapeutic targets of mitotic catastrophe. Here, we summarize how multiple PTMs, including phosphorylation, ubiquitination, acetylation, methylation and other types of PTMs, regulate mitotic catastrophe. In addition, potential therapeutic approaches targeting mitotic catastrophe were also discussed. It is anticipated that the inducement of mitotic catastrophe can serve as a promising new therapeutic approach for various diseases in the future. Full article

Recombinogenic DNA damage can initiate chromosomal rearrangements that can alter gene expression or accelerate cancer progression in higher eukaryotes. Thus, there is a critical need to identify genes that suppress chromosomal rearrangements and environmental exposures that promote genetic instability. Cell cycle checkpoints modulate the cell cycle so that DNA repair occurs before the replication or segregation of damaged chromosomes. Saccharomyces cerevisiae (budding yeast) RAD9 was the first cell cycle checkpoint gene identified, which initiated intensive research studies into the mechanisms of checkpoint activation and the phenotypes of checkpoint mutants. The budding yeast Rad9 protein serves as both an adaptor and scaffold that facilitates downstream effector activation to orchestrate a DNA damage response at multiple stages of the cell cycle, which facilitates double-strand break (DSB) repair by sister chromatid recombination. However, the role of RAD9 in homologous recombination and in suppressing gross chromosomal rearrangements (GCRs) is not completely understood. In this review we discuss how RAD9 can promote genome instability resulting from aberrant DNA replication intermediates, while suppressing DSB-associated rearrangements. We also discuss possible mechanisms accounting for the synergistic increase in genomic instability in double mutants defective in both RAD9 and recombinational repair. We emphasize that while there is an overlap between checkpoint and recombinational repair pathways, RAD9 and checkpoint pathways can function independently to suppress chromosomal instability. These studies thus elucidate checkpoint mechanisms that control homologous recombination between repeated sequences. Full article

During development, tissues or organs are organized into distinct cell populations that do not intermix. The precise spatiotemporal arrangement of these populations establishes tissue boundaries and ensures proper morphogenesis. Signaling between membrane-bound Eph receptors and their ephrin ligands underlies the formation of multiple developmental boundaries, including those between germ layers, rhombomeres, and eye fields. Moreover, accumulating evidence indicates that actomyosin contractility serves as an important mechanical driver of Eph/ephrin-cell segregation and boundary formation. However, the mechanism by which Eph/ephrin signaling regulates actomyosin contractility have received relatively limited attention in previous reviews, particularly in the context of boundary sharpening. In this review, we focus on the interplay between Eph/ephrin signaling and actomyosin contractility and discuss how this interaction contributes to cell segregation and boundary formation. Full article

Although 45 steel is widely used in the manufacture of mechanical parts, its application in harsh working conditions is limited owing to its low hardness, poor wear resistance, and corrosion resistance. Laser cladding can enhance the performance of the working surface without sacrificing substrate toughness. CoCuNiTi HEACs with different cBN additions were successfully prepared on a 45-steel substrate. The phase structure, microstructure, elemental composition, wear, and corrosion behavior of CoCuNiTi + x cBN (x = 0.0, 0.5, and 1.0 wt.%) HEACs were investigated using XRD, OM, SEM, EDS, friction and wear tester, and electrochemical workstation, respectively. The results show that all three coatings exhibit a dual-phase structure composed of FCC and BCC phases. The addition of cBN transforms the alloy phase structure from the original FCC main phase to the BCC main phase. The incorporation of cBN significantly reduces the lattice constant and cell volume of the alloy phase. The change in the alloy phase density is negatively correlated with the cell volume. CoCuNiTi + x cBN (x = 0.0, 0.5, and 1.0 wt.%) alloys have a dendritic structure. No pores were observed in the cBN-containing sample. The content of Ti in the primary phase is the highest. Co is enriched in the dendrite region, and Cu is enriched in the interdendrite region. The significant reduction in the average segregation coefficient for cBN-containing samples is attributed to the heterogeneous nucleation of the alloy melt at lower undercooling levels and the significant increase in the diffusion rate. The friction coefficient of the alloy decreases significantly with increasing cBN content. The sample with 1.0 wt.% cBN shows the best wear resistance, mainly due to the combined effects of hard particle support, solid solution strengthening, phase interface reduction, and high thermal conductivity of cBN. The sample with 1.0 wt.% cBN has the largest capacitive arc radius and charge-transfer resistance, along with the lowest annual corrosion rate, indicating optimal corrosion resistance. This is primarily related to the reduction in pore defects caused by cBN addition, hindrance of uniform penetration of the corrosive medium by dispersed cBN particles, and increased complexity of the anodic dissolution process. CoCuNiTi HEACs reinforced by cBN can simultaneously improve the wear and corrosion resistance of the surface of the 45-steel substrate, providing a feasible strategy for the design of high-performance protective coatings. Full article

Background/Objectives: Alloantigen H is one of thirteen systems in the chicken. Little is known about this system which has two serological alleles. The objectives of this study were (1) to identify the genetic region encoding the chicken alloantigen H, and (2) to develop DNA detection-based methods to aid H system allele identification. Methods: SNP genotypes from Axiom chicken SNP arrays were established for samples with known H system serological types. Sources of DNA included two elite Hy-Line White Leghorn lines segregating for alloantigen H, non-pedigreed samples from the Northern Illinois University (NIU) DNA bank, plus inbred line samples. Sequence information was also available for the commercial and inbred lines. Results: GWAS results from the elite Hy-Line lines and NIU DNA bank samples showed a very strong peak in the same 4.20–4.30 Mbp region on chromosome 24. Predicted cell membrane expression and the presence of non-synonymous SNP were criteria to identify candidate genes. Seven genes in this region have membrane-associated products: MCAM (CD146), THY1, MFRP, CLDN25, KCNJ14L, ABCG4, and PDZD3. However, only MCAM had an SNP variation that matched the serological haplotypes. Lines known to be segregating for the H system had concordance rates between serological results and SNP haplotype of 95% for both the elite HYL lines and 99% for the NIU samples, indicating that the MCAM (CD146) gene encodes the chicken H blood system. Conclusions: The gene product is a cell adhesion molecule affecting multiple activities including angiogenesis, development, cell differentiation, cell migration, signaling transduction, and immune responses. Long, short, and soluble isoforms are found in chickens. The described DNA-based typing methods facilitate future investigations to examine H haplotype frequencies in lines with identified differential responses such as growth or immune responses. Determining H haplotype association with egg production, feed conversion, and other traits with economic importance will aid in determining the significance of this immune-related gene in overall poultry health. Full article

Phytophthora infestans, a devastating oomycete pathogen responsible for late blight in solanaceous crops, relies on cellulose synthase (CesA) complexes for cell wall biosynthesis and virulence. Unlike plant CesAs that form homomeric trimers, oomycete CesA complexes are hypothesized to assemble as heteromeric units, yet their structural organization remains poorly defined. Here, we employed AlphaFold-Multimer and molecular docking to resolve the structural assembly of the PiCesA1–PiCesA2–PiCesA4 heterotrimer in P. infestans and identify potential ligand-binding sites for targeted inhibition. Structural modeling revealed a conserved transmembrane architecture combined with a distinctive cytosolic organization, in which N-terminal pleckstrin homology domains play a central role in heteromeric assembly. AlphaFold-Multimer consistently predicted a stable heterotrimer stabilized by cyclic interactions between pleckstrin homology domains and glycosyltransferase-A domains, forming an extensive interface network that is spatially segregated from the conserved UDP-glucose–binding catalytic core. Structure-guided docking identified potential ligands targeting pleckstrin homology–glycosyltransferase interface regions. Notably, these sites are absent or structurally divergent in plant cellulose synthases, underscoring their potential for pathogen-selective targeting. This work advances mechanistic understanding of cellulose biosynthesis in filamentous pathogens and proposes new avenues for selective disease control in agriculture. Full article

Cell division is a highly regulated process that actively involves dynamic changes to the genetic material within the nucleus. DNA is faithfully replicated in the S-Phase of the cell cycle, being converted from loose, relaxed chromatin into tight, condensed chromosomes to be segregated in mitosis. In addition to scaffolding proteins that shape these mitotic chromosomes, post-translational modifications of histones within nucleosomes modulate chromosome dynamics throughout the cell cycle. In this review, we use a comparative approach to highlight some of the major epigenetic marks affected by the cell cycle during embryogenesis of Caenorhabditis elegans: H4K20me1, H3S10ph, H4S1ph, H2AS1ph, and H3T118ph. These five histone post-translational modifications will be specifically highlighted in the context of the mitotic cell cycle, as they are well documented in the C. elegans literature. Full article

High-density lipoprotein-binding protein (HDLBP), also called Vigilin, is a multifunctional RNA-binding protein with established roles in RNA transport and regulation, chromosome segregation, lipid homeostasis, and translational regulation. Frequently detected to be perturbed in phosphoproteome analysis, phosphorylation is indicated as a major mechanism in the regulation of HDLBP functions; however, its phosphorylation landscape remains unexplored. We performed a meta-phosphoproteome analysis of HDLBP to map site-specific functional and regulatory roles of its two most frequently detected phosphosites, S31 and S944. Co-occurrence analysis across multiple datasets indicated that they can be phosphorylated together, suggesting potential co-ordinated regulation. Site-specific co-regulation analysis revealed distinct phospho-regulatory networks, with upstream kinases identified exclusively for S944. Functional enrichment of co-regulated protein phosphosites (CPPs) highlighted its role in RNA metabolism, chromosome organization, and nucleoplasmic transport, while functional annotation of site-specific phosphorylation of CPPs indicates its involvement in cell cycle regulation, apoptosis, and carcinogenesis. Additionally, the potential role of CPPs in the lipid homeostasis network was explored. Furthermore, the differential expression of HDLBP phosphosites across multiple cancers was observed using UALCAN, suggesting a potential role for phospho-regulation of HDLBP in tumor-associated pathways. Together, these findings provide the first integrated view of HDLBP phosphorylation and could serve as a valuable framework for future targeted studies to elucidate the mechanistic roles of site-specific HDLBP phosphorylation in cellular and pathophysiological processes. Full article

Thousand-seed weight (TSW) is a critical determinant of yield in rapeseed (Brassica napus L.). Developing germplasm with high TSW is therefore a key strategy in high-yield rapeseed breeding. However, the genetic and molecular mechanisms underlying TSW in rapeseed remain poorly understood. In our earlier work, we identified a mutant, designated GRG177, which exhibits a remarkably high TSW exceeding 7 g. To unravel the mechanisms driving this elevated TSW, we conducted a comprehensive analysis of GRG177, integrating morphological, genetic, developmental, anatomical, and physiological approaches. Compared with the control germplasm GRD328 (TSW ≈ 3.5 g), GRG177 displayed a significant increase in seed weight and seed volume, larger silique surface area, and higher yield per plant. However, it also showed a notable reduction in both silique number per plant and seed number per silique. Genetic analysis of a segregating population revealed that the high-TSW trait in GRG177 is governed by two pairs of dominant epistatic major genes plus polygenes. Endogenous hormone analysis revealed significantly higher zeatin riboside (ZR) content in the early stage of seed development in GRG177, whereas indole-3-acetic acid (IAA) and abscisic acid (ABA) levels were significantly up-regulated in the late stage of seed development. Anatomical observation using paraffin sections further confirmed that enhanced cell division activity in the early stage and improved cell expansion capacity in the later stage underpin the formation of high TSW. Furthermore, BSA-seq was utilized to map four TSW-related Quantitative Trait Loci (QTLs) and screen 13 candidate genes involved in IAA, ZR, and ABA signaling pathways. In conclusion, these findings provide novel insights into the regulatory mechanisms governing high-TSW formation in rapeseed and present valuable genetic resources for high-yield breeding. Full article

We report a comprehensive spectroscopic, microscopic, and device-level investigation of the ambient-driven degradation of PTQ10:IDIC bulk-heterojunction organic solar cells (BHJ-OSCs), up to 500 h. The power conversion efficiency dropped from 9.51% to 7.69% (≈19% relative loss), primarily due to a decrease in short-circuit current density (J_SC 15.93 to 13.82 mA cm⁻²), while the open-circuit voltage remained largely stable (0.92 to 0.90 V). Atomic force microscopy reveals surface smoothing upon ageing, with the root-mean-square roughness decreasing from 4.29 to 3.45 nm, and the UV–vis absorption spectra show negligible changes, indicating preserved bulk light-harvesting capability. In contrast, X-ray photoelectron spectroscopy indicates pronounced surface compositional evolution, with a decrease in oxygen (5.18 to 3.18%) and a substantial increase in fluorine content (3.23 to 7.23%), consistent with fluorine-rich surface segregation or reorientation. Ultraviolet photoelectron spectroscopy further reveals a 0.48 eV reduction in surface work function, indicative of surface dipole modification and near-surface electronic reorganization. Collectively, these results demonstrate that ambient ageing primarily impacts interfacial chemistry and morphology rather than bulk optoelectronic properties, highlighting interfacial engineering and encapsulation as effective strategies for improving long-term device stability. Full article

This work conducted a transcriptome analysis of canine intestinal epithelial cells (cIECs) treated with nicotinamide mononucleotide (NMN), a physiologically active nucleotide with a pyridine base known for its anti-aging and anti-inflammatory effects. In our experiment, cIECs were cultured and segregated into a control group (Ctrl) and an NMN-treated group. The finding demonstrated that NMN significantly affects cell proliferation in cIECs in comparison to the Ctrl. The transcriptome analysis indicated a high enrichment of genes associated with the cell cycle, proliferation, cellular senescence, and inflammatory pathways in NMN-treated cIECs, showing that NMN has the capacity to modify these biological processes. Compared to the Ctrl group, NMN treatment significantly increased ATP, SOD, CAT and GSH levels and decreased the activities of ROS and MDA. NMN treatment also significantly increased the activity of the relative complex I, III and V enzymes compared to the Ctrl group. Furthermore, the expression of MAPK13, EDN1, TNFAIP6, TNFSF15 and SLC7A11 were decreased significantly, while ACOX2, CPT1C, CCNA1 and CCNE1 were increased significantly in NMN-5μM treatment compared to Ctrl. NMN-treated significantly decreased the expression of Hdac2, Hdac6 and Hdac8, while increasing the expression of Kdm5a, Kdm5b and Kdm5c compared to the Ctrl group. Additionally, ChIP-qPCR use discovered that NMN-treatment significantly downregulated the enrichment of EDN-1 at target loci of NR4A1, SRC1, P300, Pol II and Ser5- Pol II compared to the Ctrl group. Expression of the NR4A1 gene suggests that its exert in biological activities by inhibiting inflammatory responses and anti-aging pathways. Then, we detected the transcriptional activation linked histone markers and found that H3K23ac and H3K27ac were significantly downregulated, while H3K27me3 was significantly upregulated in the NMN-treatment compared to the Ctrl group. We conclude that NMN regulates EDN-1 expression in cIECs through mechanisms involving NR4A1 and histone modifications, highlighting its potential role in canine intestinal health. Full article

Hollowness of the cucumber fruit, caused by carpel separation during growth, severely impacts fruit quality. Several Sikkim cucumber accessions originating from the India–Pakistan region exhibit pronounced internal cavities. We previously identified the QTL mfh2.1 as a key contributor to this phenotype. In this study, we investigated the genetic and physiological basis of fruit hollowness in the Sikkim cucumber line WI7120 through an integrative analysis combining histological staining, HPLC for hormonal profiling, and fine mapping using a large F2 segregation population. Comparative analysis between the hollow-fruited WI7120 and the non-hollow line 9930 revealed distinct growth dynamics: WI7120 displayed accelerated radial expansion and aberrant cell patterning at carpel junctions. Histological examination using paraffin sectioning uncovered disorganized endocarp cell arrangements in WI7120 occurring as early as pre-anthesis (0 days post-pollination), with enlarged suture cells that likely facilitate tissue separation during fruit enlargement. Hormonal assays indicated elevated levels of gibberellin (GA) and zeatin (ZT), along with reduced indole-butyric acid (IBA) in WI7120, suggesting that a hormonal imbalance and mechanical stress contribute to compromised cell adhesion. By screening ~2000 F₂ individuals with SSR and InDel markers, we refined the mfh2.1 locus to a 50.92 kb interval on chromosome 2, pinpointing CsRPT4Bb—encoding a 26S proteasome subunit—as the candidate gene. A non-synonymous SNP (I135V) in CsRPT4Bb was associated with tissue-specific expression patterns during cavity formation, implicating proteasome-mediated cellular remodeling in carpel cohesion. Spatial-temporal expression analysis further revealed upregulation of CsRPT4Bb in the WI7120 exocarp during fruit expansion, potentially influencing cell wall dynamics. This study demonstrates a coordinated interplay among genetic, hormonal, and mechanical factors underlying cucumber fruit hollowness, offering new avenues for breeding cultivars with improved fruit integrity and postharvest quality. Full article

Background: Plant architecture, particularly branching patterns, plays a crucial role in plant growth, photosynthetic performance, and yield. Spur-type apple, characterized by compact growth, early fruiting, high productivity, and manageable canopy structure, represent valuable germplasm for establishing dwarf and high-density apple orchards. While hybrid breeding of spur-type varieties offers significant potential for genetic advancement, severe segregation of traits in hybrid progeny and the difficulty of combining multiple favorable traits still significantly limit breeding efficiency. Moreover, the genetic basis and molecular mechanisms of the spur-type trait remain poorly understood at the genomic level, hindering the development of precise molecular breeding approaches. Methods: To address this, we used the spur-type line ‘0301-13-14’ and the non-spur-type line ‘0301-50-32’ from hybrid progenies of the spur-type cultivars ‘Miyazaki Spur Fuji’ and ‘Starkrimson’ to elucidate the regulatory mechanisms underlying apple branch formation and spur-type trait development by characterizing their branching traits, performing whole-genome resequencing analysis, and identifying candidate genes using bioinformatics analyses. Results: Anatomical observations revealed that the spur-type line ‘0301-13-14’ possessed smaller cells with a more compact spatial arrangement compared to the non-spur-type line ‘0301-50-32’. Whole-genome resequencing generated 5,003,968 high-quality single-nucleotide polymorphisms (SNPs) and 577,886 high-quality insertions/deletions (InDels). We further identified 29,157 candidate genes harboring predicted deleterious mutations (classified as high or moderate impact). Gene Ontology (GO) enrichment analysis indicated that genes associated with the spur-type trait were mainly enriched in molecular function and biological process categories. Specifically, variant genes related to molecular function were enriched in transferase and catalytic activities, while those in biological process were mainly involved in phosphorylation and phosphorus metabolism. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that candidate genes were significantly enriched in environmental information processing and metabolic pathways. Conclusions: These results will provide a genomic foundation for identifying genes controlling spur-type branching traits and facilitate the genetic improvement of spur-type apple. Full article

Long bone formation in vertebrates proceeds via endochondral ossification, a sequential process that begins with mesenchymal condensation, advances through cartilage anlage formation, and culminates in its replacement by mineralized bone. Recent advances in inducible lineage tracing and single-cell genomics have revealed that, rather than being a uniform event, mesenchymal condensation rapidly segregates into progenitor pools with distinct fates. Centrally located Sox9⁺/Fgfr3⁺ chondroprogenitors expand into the growth plate and metaphyseal stroma, peripheral Hes1⁺ boundary cells refine condensation via asymmetric division, and outer-layer Dlx5⁺ perichondrial cells generate the bone collar and cortical bone. Concurrently, dorsoventral polarity established by Wnt7a–Lmx1b and En1 ensures that dorsal progenitors retain positional identity throughout development. These lineage divergences integrate with signaling networks, including the Ihh–PTHrP, FGF, BMPs, and WNT/β-catenin networks, which impose temporal control over chondrocyte proliferation, hypertrophy, and vascular invasion. Perturbations in these programs, exemplified by mutations in Fgfr3, Sox9, and Dlx5, underlie region-specific skeletal dysplasias, such as achondroplasia, campomelic dysplasia, and split-hand/foot malformation, demonstrating the lasting impacts of embryonic patterning errors. Based on these insights, regenerative strategies are increasingly drawing upon developmental principles, with organoid cultures recapitulating ossification centers, biomimetic hydrogels engineered for spatiotemporal morphogen delivery, and stem cell- or exosome-based therapies harnessing developmental microRNA networks. By bridging developmental biology with biomaterials science, these approaches provide both a roadmap to unravel skeletal disorders and a blueprint for next-generation therapies to reconstruct functional bones with the precision of the embryonic blueprint. Full article