Search Results (12,676)

Breast cancer has emerged as the preeminent global health crisis in oncology, currently standing as the most frequently diagnosed malignancy among women worldwide. Establishing novel predictive biomarkers is paramount to truly personalize treatment approaches, minimize unnecessary toxicity, and significantly improve long-term outcomes for patients with breast cancer. Breast cancer transcriptomic datasets were retrieved from the Gene Expression Omnibus and processed through standardized normalization procedures. Mutation-driven regulation of SYTL4 expression, treatment response to trastuzumab, cancer hallmark enrichment, and survival associations were evaluated using established bioinformatic tools and enrichment analysis based on integrated cancer hallmark gene sets. Additionally, DNA methylation profiles were analyzed. Herein, it is shown that SYTL4 mRNA expression is significantly (p = 2.01 × 10⁻⁴) diminished in breast cancer bearing BRCA1 mutations, suggesting a mechanistic interplay between BRCA1-driven genomic instability and SYTL4-regulated signaling cascades. Kaplan–Meier survival analysis demonstrated that elevated SYTL4 mRNA expression is significantly associated with improved overall survival in HER2-positive breast cancer patients (HR = 0.72; p = 0.034). Consistently, SYTL4 expression was significantly higher in patients who responded to trastuzumab therapy, supporting its potential as a biomarker of therapeutic response. Epigenetic analysis further revealed significant differential DNA methylation of SYTL4 between tumor and unaffected control tissues (p < 2.2 × 10⁻¹⁶), with region-specific hypomethylation in tumor regulatory regions. KEGG pathway and cancer hallmark enrichment analyses indicated that genes with prominent methylation changes are involved in cytokine signaling, growth factor pathways, and extracellular matrix remodeling, with the strongest associations observed for hallmarks related to genome instability, replicative immortality, resisting cell death, and metabolic reprogramming. In summary, we present that the gene SYTL4 is a prospective biomarker for survival and trastuzumab treatment responsiveness. Our observations posit that SYTL4 expression may signify a biological milieu conducive to sustained HER2 reliance and amplified therapeutic vulnerability. Full article

Bordetella petrii is an environmentally versatile Gram-negative bacterium with hydrocarbon-degrading capabilities, yet its genetic and metabolic characteristics remain poorly characterized. This study investigated the genomic features of a PAH-degrading Bordetella petrii strain P003 isolated from contaminated oil in Kuwait using bioinformatic approaches. The genome of B. petrii P003 was sequenced and analyzed for genomic islands, comparative genomics, and PAH degradation pathways. The draft genome assembly of B. petrii P003 was 5,011,660 bp with 49 contigs and 68.67% GC content. It contained 4687 coding sequences, 5 rRNAs, and 56 tRNAs. Prediction of genomic islands (GIs) revealed that strain P003 possessed 99 GIs, whereas the reference B. pertii DSM 12,804 had 58 unique GIs. Comparative genomics showed 279 locally collinear blocks with the reference strain. The P003 genome encoded multiple genes involved in PAH, naphthalene, and benzoate degradation pathways, including an 8-gene PAH operon (pht4, ph2, pht5, pht3, pcaG, pcaH, nahAb/nagAb/ndoA/nbzA). We found that pcaG and pcaH encode the enzymes responsible for the breakdown of PAH, protocatechuate 3,4-dioxygenase, alpha and beta subunits (EC: 1.13.11.3). The genomic analysis of B. petrii P003 provides insights into its PAH degradation capabilities and potential for bioremediation applications. The strain possesses an expanded repertoire of aromatic compound degradation genes compared to reference strains, suggesting enhanced metabolic versatility for degrading environmental pollutants. Full article

Wastewater-based epidemiology has emerged as a valuable complementary tool for population-level monitoring. This study evaluated the early warning value of wastewater surveillance for monitoring SARS-CoV-2 and its correlation with COVID-19 infection trends. From May 2024 to December 2025, 526 wastewater samples were collected from five treatment plants. Spearman correlation and a quasi-Poisson generalized additive model (adjusting for wastewater temperature) were used to assess relationships between SARS-CoV-2 RNA concentration, the number of reported cases, and lag associations. Wastewater viral loads (copies/mL) significantly correlated with reported cases. Wastewater temperature was positively correlated with both viral concentrations and case numbers. A significant lagged association was observed for the N gene, with relative risk peaking at a 10-day lag. Although the ORF1ab gene was not significant for most lag periods, its temporal trend was consistent with that of the N gene. Wastewater surveillance of SARS-CoV-2, particularly targeting the N gene, can effectively predict COVID-19 infection dynamics with a 10-day lead time, thereby supporting wastewater surveillance as an early warning tool for public health monitoring. Full article

Fusarium graminearum infection of maize induces complex transcriptional reprogramming, yet existing differential-expression and local graph convolutional approaches struggle to capture long-range and multi-scale regulatory dependencies. We propose DC-FusionGNN, a dual-channel fusion graph neural network for key resistance-gene identification. Based on the transcriptome dataset GSE174508, we first construct a comprehensive gene interaction network by integrating a WGCNA co-expression network with a STRING-based interaction network. The left channel combines structure-aware propagation with a Transformer-based global self-attention mechanism to model long-range cross-module dependencies, while the right channel couples GraphSAGE with a GCN to capture local topology and neighborhood heterogeneity. Embeddings from the two channels are concatenated to form a unified gene representation, trained via self-supervised link prediction. Compared with baseline graph neural networks, DC-FusionGNN achieves competitive and overall improved performance across multiple metrics, and robustness and independent cross-species (rice, GSE39635) experiments further confirm its stability and generalization ability. GO and KEGG enrichment analyses show that the top-ranked candidate genes are significantly enriched in plant defense responses, hormone signaling, and secondary metabolism, supporting the biological relevance of the model’s predictions. Full article

To clarify the compositional characteristics and functional mechanisms of gut microbial communities in wild earwigs (Dermaptera) and explore the potential of earwigs for development and utilization as natural enemies, this study conducted a comparative analysis of the gut microbial diversity and community structure of two earwig species, Timomenus komarovi (Semenov, 1901) and Eudohrnia metallica (Dohrn, 1865), which are widely distributed in mulberry orchards and cornfields of Guizhou Province, China. It also predicted the microbial functions based on the third-generation high-throughput sequencing technology targeting the 16S rRNA gene. The results showed that the two earwig species across different habitats and geographical regions harbored a similar core microbial flora. The dominant phyla of gut microbiota were Proteobacteria, Firmicutes. PICRUSt2 functional prediction analysis revealed that the functions of intestinal bacteria in earwigs were mainly concentrated in metabolism-related pathways. Through multi-dimensional analysis, it was confirmed that the gut microbial communities of earwigs were constructed following the “core-specialization” model. The core microbial communities exhibited high conservatism. Host species were the core factor shaping the composition of earwig gut microbial communities. Habitats could further regulate the commonness and diversity characteristics of the microbial communities, while geographical regions had an extremely weak impact on the gut microbial communities. Significant differences were observed in the gut microbial adaptation strategies between the two earwig species, which determined their distinct development potential and application scenarios as natural enemy insects: T. komarovi is suitable for development as a broad-spectrum natural enemy, while E. metallica is more appropriate for targeted development based on its microbial community characteristics. All data supporting the findings of this study are accessible in the NCBI database under BioProject accession number PRJNA1449822. This study provides a theoretical basis for exploring the functional mechanisms of intestinal microbes in dermapteran insects and supporting the development and utilization of these natural enemy resources. Full article

Phosphorus Starvation Tolerance 1 in rice (OsPSTOL1, known as Phosphorus uptake 1, Pup1) is a receptor-like cytoplasmic protein kinase that confers tolerance to phosphorus deficiency. The OsPSTOL1 gene possesses a Ser/Thr kinase and shows high amino-acid sequence similarity with the leaf rust receptor-like kinase (OsLrK10). We hypothesise that the putative wheat genes TaPSTOL1 and TaLrK10 have a common ancestral origin and that putative TaPSTOL1 diverged recently, acquiring new structural modifications and biological functions in the process. In this study, we identified all putative TaPSTOL1 homeologs and examined the evolutionary relationship between TaPSTOL1 and TaLrK10 in Triticum species. Our results indicate that the putative TaPSTOL1 diverged recently without possessing the amino-terminal domain, which is a typical characteristic of TaLrK10. We observed numerous conversion tracts between these two genes, and the substitution pattern of randomly selected amino acids indicates that dynamic selection pressures acted on both genes. The putative TaPSTOL1 shows high nucleotide diversity compared to TaLrK10 within Triticum species. Further, a multiple-sequence analysis reveals that the third exon of TaLrK10 appears to have been duplicated and diverged as a putative single-exon-based TaPSTOL1 in bread wheat. Overall, our comparative analysis indicates that both TaPSTOL1 and TaLrK10 appear to have diverged from a common ancestor, acquiring distinct structural organisations and biological functions. Full article

Background/Objectives: Pathogenic variants in GNAO1, encoding the inhibitory G protein subunit Gαo, cause severe neurodevelopmental disorders that remain largely refractory to pharmacological treatments. Gαo transduces inhibitory signals downstream of multiple G protein-coupled receptors (GPCRs) involved in motor control. Here, we used gene-edited Caenorhabditis elegans models carrying goa-1 variants, the ortholog of GNAO1, to investigate GPCR contributions to Gαo-dependent locomotor phenotypes. Methods: We combined pharmacological screening of dopamine- and cannabinoid-targeting ligands in goa-1 mutants with structural analysis of ligand-binding pocket conservation and genetic perturbation of receptor function using RNAi and knockout approaches. Results: Pharmacological modulation of GPCR signaling produced non-linear and context-dependent effects. Compounds predicted to further increase excitability may instead promote phenotypic improvement, consistent with compensatory network rebalancing. Structural analyses revealed substantial divergence in ligand-binding pocket conservation for several GPCR-ligand pairs, suggesting that altered binding affinity and selectivity may also contribute to the observed phenotypic outcome. Pharmacological experiments performed in GPCR-depleted mutants allowed for the correlation of structural findings with functional effects for selected receptor-ligand pairs. Finally, genetic reduction in GPCRs coupled to stimulatory G proteins ameliorated hyperactive locomotion in goa-1 mutants, whereas reduction in GPCRs coupled to inhibitory G proteins is largely insufficient to induce or exacerbate locomotor defects. Conclusions: Our findings identify excessive excitatory GPCR input as a key modulator of motor dysfunction in the context of impaired Gαo signaling. They also show that structural conservation is a necessary but not sufficient condition to predict functional responses. Overall, this study establishes C. elegans as a suitable platform to dissect GPCR-mediated signaling and highlights the value of integrating pharmacological and genetic approaches to guide target selection in GNAO1-related disorders. Full article

Background: Growth factor therapy often fails in diabetic foot ulcers (DFUs). The reason remains unclear. Standard differential expression analysis may miss functionally critical genes with modest expression changes. Methods: We performed a secondary computational analysis of a longitudinal DFU transcriptomic dataset (Dryad; 17 patients, 117 serial biopsy samples, 12-week follow-up). Co-expression networks were built separately for healed (n = 37) and non-healed (n = 80) samples. Virtual gene knockout (VGK) was used to rank genes by topological impact on network cohesion. Single-cell analysis (GSE165816) assessed the association between endogenous KIF13A expression and keratinocyte migration-related signatures. A conceptual Hill-equation simulation was used to illustrate the transport-signaling threshold relationship. Drug repurposing used DSigDB enrichment. An independent bulk DFU cohort (GSE134431) was used for external validation. Results: KIF13A showed no differential expression (log₂FC = 0.173, p = 0.263) yet ranked first by VGK topological impact. In keratinocytes, high KIF13A expression correlated with greater migration scores versus zero-detection cells (p = 0.0058). A clear threshold effect emerged: below the 30th expression percentile, EGF, PDGF, and FGF pathway activation scores remained near baseline. In a structural-equation model, transport activity negatively predicted inflammation (standardized β = −0.92, p < 0.001). HIF1A showed the strongest positive correlation with KIF13A in keratinocytes (Spearman ρ = 0.26, p < 0.001), and FOS showed a negative correlation in the single-cell analysis (ρ = −0.16, p < 0.001) and in the bulk longitudinal cohort (ρ = −0.32, p < 0.001, n = 117). Recurrent AKR1B1-related drug signatures nominated the aldose-reductase pathway, and epalrestat was therefore prioritized as a hypothesis-generating candidate compound rather than a direct top-ranked enrichment hit. External validation confirmed consistent upregulation of KIF13A (Fold-Change = 1.58, adj. p = 0.0075), EPN1, and CLIP1 in DFU tissue. Despite population-level upregulation, a subset of cells fell below the functional signaling threshold. Conclusions: These computational findings suggest that KIF13A-associated vesicle transport impairment may represent a candidate systems-level bottleneck for growth-factor responsiveness in DFUs, a network-level pattern not captured by standard differential-expression analysis. Epalrestat, an AKR1B1 inhibitor prioritized through recurrent AKR1B1-related drug signatures, is presented as a candidate compound for further evaluation. As the present analysis is observational and computational, the findings should be interpreted as hypothesis-generating; experimental perturbation studies and prospective clinical validation are required. Full article

Poor bone quality in osteoporotic patients remains a major challenge for achieving predictable osseointegration. This study serves as a mechanistic complement to previously reported structural data, aiming to investigate the molecular pathways underlying the synergy between nanostructured surfaces and autologous blood concentrates in compromised bone. Ninety-six Wistar rats were divided into healthy (SHAM) and osteoporotic (OVX) groups. Implants with nanostructured hydroxyapatite (NanoHA) or dual acid-etched (DAE) surfaces were installed in the tibiae, associated or not with leukocyte- and platelet-rich fibrin (L-PRF). Gene expression (RT-qPCR) for Runx2, Alpl, Bglap, Spp1, Tnfrsf11, and Tnfrsf11b was assessed at 7 and 30 days. In compromised systemic conditions (OVX), the NanoHA + L-PRF association promoted a robust “molecular rescue” of bone metabolism. At 30 days, this synergistic group exhibited a significant upregulation of Alpl (mean: 11.69 ± 1.65) and Runx2 (mean: 4.49 ± 0.82) compared to DAE controls (p < 0.05). Crucially, the therapy orchestrated a protective remodeling environment by significantly inducing Tnfrsf11b expression (5.50 ± 0.88), effectively balancing the Tnfrsf11/Tnfrsf11b ratio. Late-stage maturation markers (Bglap and Spp1) were also significantly elevated, effectively mimicking healthy physiological levels observed in the SHAM group. NanoHA biofunctionalization, synergistically with L-PRF, triggers a transcriptional reprogramming of the peri-implant microenvironment, mitigating the catabolic effects of estrogen deficiency. These findings provide a biological foundation for enhanced clinical predictability in high-risk patients, suggesting that local interfacial modifications can overcome systemic bone compromise. Full article

Background/Objectives: Epigenetic regulation plays a fundamental role in controlling the spatiotemporal expression of genes in plants under stressful environmental conditions. While LIKE HETEROCHROMATIN PROTEIN 1 (LHP1) is known to be involved in histone modification, its function in regulating the biosynthesis of specialized metabolites, particularly monoterpenoid indole alkaloids (MIAs) in Catharanthus roseus, remains elusive. Methods: CrLHP1 was identified by mining the C. roseus proteome and characterized through sequence alignment, phylogenetic analysis, and conserved domain assessment. Virus-induced gene silencing (VIGS) was employed to suppress CrLHP1 expression, after which the transcript levels of jasmonic acid (JA)-responsive genes and key MIA biosynthetic genes, as well as the accumulation of vindoline and catharanthine, were analyzed. Furthermore, deep learning-based protein structure prediction (AlphaFold3) and yeast two-hybrid (Y2H) assays were conducted to explore protein-protein interactions. Results: CrLHP1 was confirmed as the ortholog of Arabidopsis thaliana LHP1 (AtLHP1). Exposure to 75 μM MeJA upregulated MIA upstream pathway genes while downregulating CrLHP1 transcription. Silencing CrLHP1 significantly upregulated JA-responsive and MIA biosynthetic genes, leading to enhanced catharanthine accumulation. Additionally, the structural prediction and Y2H assays revealed a physical interaction between CrLHP1 and CrJAZ1. Conclusions: These findings suggest that CrLHP1 negatively regulates MIA biosynthesis, potentially by modulating JA signal transduction through interaction with CrJAZ1. This study provides new insights into the possible epigenetic mechanisms governing alkaloid production in C. roseus. Full article

Breast cancer is prevalent and deadly, affecting women worldwide. Increasing research suggests that lysine lactylation (KLA) and DNA damage repair (DDR) play critical roles in tumor progression and that KLA and DDR are interconnected, as KLA can modulate DDR protein function, thereby influencing genome stability and drug response, while DDR signaling can reciprocally reshape lactate metabolism and KLA activity. In this study, we developed a novel prognostic gene signature (KLA and DDR index, KLDRI) based on KLA- and DDR-related genes. Model genes (PGK1, MORF4L2, RAD54B, RPA3, CCND2) were generated via LASSO-Cox regression. Patients were stratified into high- and low-risk groups according to KLDRI, the robust prognostic value of which was demonstrated via survival and validation analyses in the TCGA cohort and the METABRIC and GSE96058 cohorts, respectively. Tumor microenvironment analysis indicated an immunologically suppressed phenotype in high-risk patients, whereas low-risk patients exhibited an immune-inflamed microenvironment. Drug sensitivity analysis indicated reduced sensitivity to multiple chemotherapy and targeted therapy drugs in the high-risk group. Single-cell transcriptomic analysis revealed differential gene expression patterns between risk groups. A prognostic nomogram based on KLDRI was developed to predict overall survival. Furthermore, functional experiments demonstrated that RPA3 knockdown suppressed cancer cell proliferation and migration, sensitized cells to cisplatin treatment, and reduced global lactylation, which may serve as a novel biomarker and potential therapeutic target. These findings enhance our understanding of the interplay between KLA, DDR, and breast cancer progression, facilitating the development of personalized therapeutic strategies. Full article

Phytophthora infestans is the causal agent of late blight, one of the most destructive diseases of potato and tomato worldwide. Although qPCR-based methods are widely used to estimate pathogen biomass in infected tissues, methods for specifically assessing sporangial proliferation remain limited. In this study, we developed an RT-qPCR-based assay using PITG_13011, which encodes a predicted major facilitator superfamily transporter, as a sporangia-associated molecular marker in P. infestans. Among five candidate genes selected from transcriptomic data, PITG_13011 showed the strongest association with sporangia-associated samples in our validation assays. PITG_13011 transcripts were detectable from cDNA and genomic DNA derived from as few as 100 sporangia, and transcript abundance showed a strong positive correlation with sporangial number under controlled experimental conditions. In detached leaf inoculation assays, PITG_13011 transcript levels were associated with differences in sporangia-associated proliferation during infection. These results indicate that PITG_13011-based RT-qPCR can serve as a complementary molecular approach for estimating sporangia-associated proliferation of P. infestans in laboratory experiments. This method will be useful when sporangial production, rather than total pathogen biomass alone, is the parameter of interest. Full article

Soil salinization is a source of major abiotic stress that severely limits the production of alfalfa (Medicago sativa L.), a globally critical forage legume for sustainable livestock production. Its complex autotetraploid genome and self-incompatibility greatly hinder salt tolerance genetic improvement, while the post-transcriptional regulatory mechanism of alfalfa salt stress response remains largely uncharacterized. This study aimed to narrow the gap between genome-wide genetic signals and causal regulatory mechanisms and identify core post-transcriptional regulators of alfalfa salt tolerance via a multi-layered integrative analysis pipeline. We performed a genome-wide association study (GWAS) using 220 globally collected alfalfa accessions, combined with public transcriptome integration, co-expression network analysis, 3′ untranslated region (3′UTR) motif discovery, and AlphaFold2-based protein-RNA docking simulation. We identified 20 significant salt tolerance-associated loci and prioritized the CCCH-type zinc-finger RNA-binding protein (RBP) MsCCCH20 as the core candidate regulator. We further screened 35 high-confidence target genes of MsCCCH20, detected conserved AU/AG-rich 3′UTR motifs, and provided structural predictions consistent with potential sequence-specific interactions (ipTM 0.70–0.79). Our findings establish a robust framework linking genetic association signals to post-transcriptional regulatory networks and provide high-confidence candidate genes and functional markers for the molecular breeding of salt-tolerant alfalfa. Full article

Breast cancer represents a major public health problem worldwide. Despite radical surgery for localized disease, a substantial proportion of patients experience disease recurrence. The aim of this study was to evaluate the expression of the mammaglobin and CK19 genes in sentinel lymph node biopsies from patients with early breast cancer. This descriptive study included 301 sentinel lymph node biopsies from patients with stage I–II breast cancer treated at the San Carlos Clinical Hospital in Madrid, Spain. Metastases were identified using conventional histopathology (H&E), immunohistochemistry (IHC), and molecular detection of mammaglobin and CK19 using PCR-based methods. Associations between variables were assessed using Fisher’s exact test with a 95% confidence level. Statistical analyses were performed using STATA 12.0. The predictive value for metastatic involvement was 12.29% for CK19 and 16.61% for mammaglobin, increasing to 19.27% when conventional staining was combined with immunohistochemistry. The overall sensitivity was 68.9%, and the specificity was 93.42%. Mammaglobin showed slightly better diagnostic performance than CK19, and the combined molecular detection of both genes improved diagnostic accuracy when compared with individual markers. Intraoperative molecular evaluation of sentinel lymph nodes using mammaglobin and CK19 is comparable to conventional histopathological assessment combined with immunohistochemistry. The combined RT-PCR detection of both genes improves diagnostic performance and represents a clinically useful complementary tool for the detection of metastatic involvement in early breast cancer. Full article

SMXL proteins serve as central regulators of strigolactone (SL) and karrikin (KAR) signaling pathways, orchestrating key developmental processes including shoot branching, floral transition, photomorphogenesis and stress responses. However, the SMXL gene family has not been systematically characterized in Lavandula angustifolia. We identified 37 LaSMXL genes in the lavender genome. Phylogenetic and synteny analyses classified these proteins into four subgroups (Groups I–IV) and indicated that family expansion in lavender was mainly driven by whole-genome and segmental duplications, with most duplicated pairs evolving under strong purifying selection. Gene structure and motif analyses revealed high conservation within each subgroup. Promoter cis-element analysis suggested that LaSMXL genes are integrated into light-, hormone- and stress-responsive regulatory networks. RNA-seq profiling showed that most LaSMXL genes are weakly expressed, but a small subset displays pronounced tissue specificity and clear transcriptional responses to low temperature. Protein–protein interaction predictions and co-expression network analysis further placed highly expressed LaSMXLs within conserved SL/KAR and chloroplast/light-associated modules, alongside D14, KAI2, MAX2, CCD7/CCD8, and CYP711A. Together, these findings provide the first comprehensive overview of the SMXL gene family in lavender and identify candidate LaSMXL genes for future functional studies aimed at optimizing plant architecture and inflorescence-derived essential oil biosynthesis. Full article