Search Results (7,459)

The gut microbiota of insects, shaped by extensive coevolution, plays a crucial role in host adaptability and ecological expansion. The fall armyworm (Spodoptera frugiperda J.E. Smith), a highly polyphagous and migratory invasive pest, infests more than 350 plant species worldwide, resulting in substantial crop losses and increased reliance on pesticide applications. In this study, we employed 16S rRNA high-throughput sequencing to investigate diet-induced alternations in the gut microbial communities of larvae fed corn, rice, or an artificial diet. The results showed that diet significantly influenced microbial diversity, with rice-fed larvae exhibiting the highest richness. Firmicutes, Proteobacteria, and Cyanobacteria were the predominant bacterial phyla. Genus-level analysis revealed notable diet-dependent shifts, with Enterobacter and other genera (e.g., Ochrobactrum and Allorhizobium–Neorhizobium–Pararhizobium–Rhizobium) only detected in plant-fed groups. Additionally, current findings suggest that gut microbial genera are more prevalent when S. frugiperda larvae feed on rice plants than on corn plants or an artificial diet and are closely linked to their metabolic activities. Dominant microbial genera are expected to support essential metabolic processes and exhibit increased abundance on rice. These results indicate that the gut microbiome of S. frugiperda is diet-driven reorganization, potentially facilitating its polyphagy. This study extends the current understanding by elucidating the specific gut microbial taxa and their putative metabolic associations that are responsive to diet in S. frugiperda, thereby providing a theoretical basis for its polyphagous capability and underscoring microbiota-based strategies for sustainable pest management. Full article

Background: The Tibetan Plateau, which is known for its high elevation and low oxygen levels, presents a challenging environment for its inhabitants. To adapt to these hypoxic conditions, species of Schizothoracine, a subfamily of Cyprinidae, have developed unique physiological mechanisms and functions. Transforming growth factor-β (TGF-β) is a multifunctional cytokine involved in the regulation of cell growth, differentiation, apoptosis, and the cellular immune response. However, its specific role in adaptation to hypoxia remains poorly understood. Methods: In this study, we aimed to characterize the TGF-β1 gene in Gymnocypris dobula (Gd) and Schizothorax prenanti (Sp) and to test whether TGF-β1 contributes to hypoxia adaptation in plateau Schizothoracine fish. The predicted protein for Gd-TGF-β1 contains several primary domains, including cwf21 (cdc5 protein 21), GYF (Glycine-Tyrosine-Phenylalanine), FN1 (Fibronectin 1), a conservative domain, and a signal peptide. Results: The results of tissue distribution revealed that the mRNA level of TGF-β1 in brain, heart, muscle, skin, gills, and spleen—which are key tissues involved in oxygen sensing, transport, and physiological adaptation to hypoxic environments—was significantly lower in G. dobula than that in S. prenanti. Western blotting analysis revealed that the expression of activated TGF-β1 in G. dobula was significantly higher than that in S. prenanti. To investigate whether TGF-β1 in G. dobula possesses hypoxic adaptive features, Gd-TGF-β1 and Sp-TGF-β1 were cloned into an expression vector and transfected into 293-T cells, which are widely used due to their ease of culture, high transfectability, and well-characterized properties. We found that the survival rate of cells transfected with Gd-TGF-β1 was significantly higher than that of cells transfected with Sp-TGF-β1 after hypoxia treatment. Conclusions: These findings suggest that G. dobula may promote hypoxic adaptation through the activation and increased expression of TGF-β1. Changes in TGF-β1 expression may play a role in the adaptation of G. dobula to hypoxic conditions. Full article

Biological control with beneficial bacteria offers a sustainable alternative to synthetic agrochemicals for managing plant pathogens and enhancing plant health. However, bacterial biocontrol agents (BCAs) remain underexploited due to regulatory hurdles (such as complex registration timelines and extensive dossier requirements) and limited strain characterization. Recent advances in omics technologies (genomics, transcriptomics, proteomics, and metabolomics) have strengthened the bioprospecting pipeline by uncovering key microbial traits involved in biocontrol. Genomics enables the identification of biosynthetic gene clusters, antimicrobial pathways, and accurate taxonomy, while comparative genomics reveals genes relevant to plant–microbe interactions. Metagenomics uncovers unculturable microbes and their functional roles, especially in the rhizosphere and extreme environments. Transcriptomics (e.g., RNA-Seq) sheds light on gene regulation during plant-pathogen-bacteria interactions, revealing stress-related and biocontrol pathways. Metabolomics, using tools like Liquid Chromatography–Mass Spectrometry (LC-MS) and Nuclear Magnetic Resonance spectroscopy (NMR), identifies bioactive compounds such as lipopeptides, Volatile Organic Compounds (VOCs), and polyketides. Co-culture experiments and synthetic microbial communities (SynComs) have shown enhanced biocontrol through metabolic synergy. This review highlights how integrating omics tools accelerates the discovery and functional validation of new BCAs. Such strategies support the development of effective microbial products, promoting sustainable agriculture by improving crop resilience, reducing chemical inputs, and enhancing soil health. Looking ahead, the successful application of omics-driven bioprospection of BCAs will require addressing challenges of large-scale production, regulatory harmonization, and their integration into real-world agricultural systems to ensure reliable, sustainable solutions. Full article

The plant Actinostemma tenerum is endemic to East Asia and has been used as a traditional medicinal herb for over 1400 years. Investigating the chloroplast genome characteristics and codon usage bias (CUB) is essential for advancing research on molecular markers and genetic diversity in A. tenerum. In this study, we sequenced the complete chloroplast genome of A. tenerum, revealing a length of 160,579 bp, with a GC content of 36.5%. The genome comprised 132 coding genes, including 87 protein-coding genes (CDSs), 8 rRNA genes, and 37 tRNA genes. Analysis of the 51 selected CDSs showed average GC1, GC2, and GC3 values of 46.95%, 39.52%, and 28.11%, respectively. The effective number of codons (ENC) ranged from 35.34% to 56.23%, with an average of 45.57%, indicating a weak CUB. Nucleotide composition analysis revealed unequal distribution of A, T, C, and G, with codon preference biased towards A or U. Neutrality plots, ENC-plots, and PR2-bias plots indicated that natural selection predominantly influences on CUB. A total of 18 optimal codons were identified. This study contributes genetic insights into A. tenerum and enhances our understanding of codon usage patterns in plant chloroplast genomes. Full article

Improving ovine reproductive efficiency is an important breeding goal that could substantially enhance economic viability in the sheep industry. The histone cell cycle regulator (HIRA) gene has been functionally validated as a reproductive regulator in model organisms such as Drosophila and murine species; however, research on the effects of HIRA on the prolificacy in sheep remains scarce. Thus, this study aimed to investigate the association between genetic variants of HIRA and litter size in sheep. In brief, we identified 15 novel exonic mutations in the Sonid sheep breed via direct sequencing. Notably, a linkage disequilibrium including the c.1521C>G, c.1572C>T, and c.1578G>A mutations on exon 14 of HIRA exhibited a significant association with litter size in Sonid sheep (p < 0.01). Meanwhile, it was predicted that mutations play a major role in enhancing the stability of the mRNA secondary structure by lowering the minimum free energy, and mutations were also thought to change the mRNA secondary structure of ovine HIRA. Therefore, these findings may provide potentially useful molecular markers for optimizing reproductive performance in Sonid sheep. Full article

To elucidate the molecular mechanisms underlying salt tolerance in rice (Oryza sativa L.), this study investigated differential transcriptional responses during the tillering stage. Salt-tolerant (N14) and salt-sensitive (N6) varieties were subjected to 0.3% and 0.6% NaCl treatments for 72 h, and their transcriptomes were analyzed via RNA-Seq. The results revealed distinct response strategies: 372 differentially expressed genes (DEGs) were identified in N14 and 393 in N6, with only 17 genes responding similarly. Gene Ontology (GO) analysis showed the tolerant N14 activated protein phosphorylation and lipid transport, primarily in the membrane and extracellular regions (e.g., ATP binding), whereas the sensitive N6 activated photosynthesis and protein folding, localized to chloroplasts and peroxisomes. KEGG analysis highlighted the activation of “Plant-pathogen interaction” in N14 versus “Metabolic pathways” in N6. Differential transcription factor activation was also observed, with N14 mobilizing 52 TFs (mainly WRKY and MYB) and N6 mobilizing 36 TFs (mainly MYB and b-ZIP). This study demonstrates that N14 and N6 utilize significantly different molecular pathways to cope with salinity, providing a crucial theoretical foundation for identifying novel salt tolerance genes and developing molecular breeding strategies. Full article

Background: In the Kingdom of Saudi Arabia, various COVID-19 vaccines were administered during the pandemic. However, region-specific real-word comparative data on their immunogenicity remain limited. This study aimed to assess the serological responses to Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and AstraZeneca (ChAdOx1 nCoV-19) vaccines in a diverse population living in KSA. Methods: This observational study included 236 adults recruited from vaccination sites in Riyadh. Participants provided serum samples at predefined intervals: before the first dose, after the first dose, after the second dose, and post-vaccination infection (if applicable). IgG and neutralising antibodies were quantified using ELISA assays. Demographic and vaccination data, and their associations with antibody responses, were evaluated. Results: At baseline, 75.4% of participants were positive for SARS-CoV-2 IgG, suggesting high prior exposure. Marked incremental increases in IgG levels were observed after each vaccine dose. Both Moderna and Pfizer elicited stronger responses, with Pfizer inducing the strongest early response and Moderna achieving the highest overall titres. Among IgG-positive individuals, neutralising antibodies were detected in 98.1%. There were no statistically significant differences by age or gender, although males tended to show higher mean titres. Heterologous vaccine schedules induced comparable or enhanced immunogenicity relative to homologous schedules, supporting their use in flexible immunisation strategies. Conclusions: All COVID-19 vaccines administered in Saudi Arabia elicited robust antibody responses, particularly the mRNA-based vaccines. Our findings support their continued use and justify varied vaccination approaches, including mix-and-match booster strategies, to enhance community immunity. Full article

Background and Objectives: Breast cancer (BC) is a complex disease requiring a comprehensive treatment approach due to its diverse characteristics. Critical molecular determinants of BC have been identified using advanced genomic, transcriptomic, and proteomic approaches. Assessing the biomarkers associated with the onset of early-stage BC may help identify the risk of metastasis and inform treatment decisions. A previous bioinformatic analysis using two large BC cohorts identified pumilio RNA binding family member 1 (PUM1) as a key gene in invasive BC. However, no study has yet examined the prognostic and predictive value of PUM1 in invasive BC and its correlation with aggressive tumor behavior. This study aimed to fill this need. Materials and Methods: Correlations between PUM1 expression and patients’ clinicopathological characteristics and outcomes were explored in publicly available BC transcriptomic data acquired using DNA microarrays (n = 10,872) and RNA sequencing (n = 4421) using BC Gene-Expression Miner v5.0. PUM1 expression in samples from 100 patients with invasive BC at King Abdul Aziz Specialist Hospital, Saudi Arabia, was assessed immunohistochemically. Correlations between PUM1 expression and patients’ clinicopathological characteristics (e.g., age, tumor grade, tumor size, and outcome) were assessed. The online platform ROC Plotter was also used to investigate the predictive significance of PUM1. Results: High PUM1 gene and protein expression correlated positively with aggressive features of BC, including high histological grade, high Ki-67 expression, negative hormone receptors, and the triple-negative BC molecular subtype. High PUM1 expression correlated with poor outcomes, and high PUM1 expression was associated with a lower pathological complete response to anti-endocrine treatment but a high response to chemotherapy. Conclusions: These results indicate that PUM1 may serve as a potential prognostic and predictive biomarker in patients with invasive BC. PUM1 may serve as a therapeutic target in BC cases with unfavorable prognoses. However, further validation in larger, multi-center cohorts and further functional assessment are required to deepen our understanding of PUM1’s role in BC. Full article

Extracellular vesicles (EVs) from mesenchymal stem cells hold therapeutic promise for inflammatory and degenerative diseases; however, limited delivery and targeting capabilities hinder their clinical use. In this study, we sought to enhance the anti-inflammatory and chondroprotective effects of EVs through CAP-LAMP2b (chondrocyte affinity peptide fused to an EV membrane protein) engineering and ADAMTS4 gene editing hybrid vesicle formation. Human umbilical cord MSCs (hUCMSCs) were characterized via morphology, immunophenotyping, and trilineage differentiation. EVs from control and CAP-LAMP2b-transfected hUCMSCs were fused with liposomes carrying CRISPR-Cas9 ADAMTS4 gRNA. DiI-labeled EV uptake was assessed via fluorescence imaging. CAP-LAMP2b was expressed in hUCMSCs and their EVs. EVs exhibited the expected size (~120 nm), morphology, and exosomal markers (CD9, CD63, CD81, HSP70). CAP-modified hybrid EVs significantly enhanced chondrocyte uptake compared to control EVs and liposomes. IL-1β increased ADAMTS4 expression, whereas CAP-LAMP2b-ADAMTS4 EVs, particularly clone SG3, reversed these effects by reducing ADAMTS4 and restoring aggrecan. Western blotting confirmed suppressed ADAMTS4 and elevated aggrecan protein. CAP-LAMP2b-ADAMTS4 EVs, therefore, showed superior uptake and therapeutic efficacy in inflamed chondrocytes, attenuating inflammatory gene expression and preserving matrix integrity. These results support engineered EVs as a promising cell-free approach for cartilage repair and osteoarthritis treatment. Full article

The HIV-1 epidemic continues to challenge global public health, especially in sub-Saharan Africa. The rise in drug-resistant viruses, particularly pan-resistant strains, threatens treatment effectiveness, hindering progress toward UNAIDS viral suppression goals. This is critical in low-to-middle income countries (LMICs) like Zimbabwe, where treatment options and access to drug resistance testing are limited. This cross-sectional study analyzed 102 genotypes from patients with HIV-1 RNA ≥ 1000 copies/mL after at least 6 months on a dolutegravir (DTG)-based ART. HIV-1 genotyping and drug resistance interpretation were performed using the Stanford HIV Drug Resistance Database. Overall, 62% of genotypes harbored at least one drug resistance mutation, with 27% showing integrase strand transfer inhibitor (INSTI)-associated mutations. High-level resistance to DTG and cabotegravir was found in 14% and 23% of integrase sequences, respectively, primarily driven by G118R and E138K/T mutations. Pan-resistance was observed in 18% of complete genotypes, with one case of four class resistance. These results highlight the emergence of INSTI resistance in LMICs. The study underscores the urgent need for enhanced HIV drug resistance testing, continuous surveillance, and strategic optimization of ART regimens in resource-constrained settings to ensure effective HIV management. Full article

Damping-off disease hinders rice seedling growth and reduces yield. Current control methods, such as seed or soil sterilization, rely on chemicals that cause environmental pollution and promote pathogen resistance. As a sustainable alternative, we targeted the damping-off resistance-related gene OsDGTq1 using CRISPR/Cas9. Field experiments first verified OsDGTq1’s significance in resistance. The CRISPR/Cas9 system, delivered via Agrobacterium-mediated transformation, was used to edit OsDGTq1 in rice cultivar Ilmi. Lesions from major damping-off pathogens, Rhizoctonia solani and Pythium graminicola, were observed on G₀ plants. All 37 regenerated plants contained T-DNA insertions. Among them, edits generated by sgRNA1-1, sgRNA1-2, and sgRNA1-3 resulted in the insertion of two thymine bases as target mutations. Edited lines were assigned names and evaluated for agronomic traits, seed-setting rates, and pathogen responses. Several lines with edited target genes showed distinct disease responses and altered gene expression compared to Ilmi, likely due to CRISPR/Cas9-induced sequence changes. Further studies in subsequent generations are needed to confirm the stability of these edits and their association with resistance. These results confirm that genome editing of OsDGTq1 alters resistance to damping-off. The approach demonstrates that gene-editing technology can accelerate rice breeding, offering an environmentally friendly strategy to develop resistant varieties. Such varieties can reduce chemical inputs, prevent pollution, and minimize seedling loss, ultimately enhancing food self-sufficiency and stabilizing rice supply. Full article

The Sterile alpha motif domain-containing protein 4 (SAMD4) family consists of two evolutionarily conserved and highly homologous RNA-binding proteins, SAMD4A and SAMD4B. Previous studies have established SAMD4A as a tumor suppressor that is downregulated in breast cancer, while the function of SAMD4B in tumorigenesis remains poorly defined. In this study, we observed that SAMD4B expression is upregulated in breast cancer. Functional assays demonstrated that SAMD4B facilitated breast cancer cell proliferation, migration, and invasion by inducing epithelial–mesenchymal transition (EMT). Furthermore, SAMD4B accelerated G1-to-S phase cell cycle progression by modulating p53 expression, collectively supporting an oncogenic function of SAMD4B in breast cancer. Mechanistically, we found that SAMD4B enhanced TCF/LEF transcriptional activity and upregulated the expression of β-catenin, Cyclin D1, c-Myc, and Axin2. Further investigations confirmed that SAMD4B activated the Wnt/β-catenin pathway by stabilizing β-catenin mRNA and increasing β-catenin protein expression level. Importantly, treatment with XAV-939, a specific Wnt/β-catenin pathway inhibitor, abrogated the pro-oncogenic effects of SAMD4B overexpression, including Wnt/β-catenin pathway activation, enhanced proliferation, and increased metastatic capacity. These results confirm that SAMD4B promotes the malignant phenotypes of breast cancer cells in a manner dependent on the Wnt/β-catenin pathway. In summary, our findings clarify that SAMD4B exerts an oncogenic role in breast cancer progression by activating the Wnt/β-catenin pathway. These data identify SAMD4B as a potential therapeutic target in breast cancer, although further in vivo investigations are required to validate its clinical relevance. Full article

Rotavirus remains a leading cause of acute gastroenteritis worldwide, particularly in young children, despite widespread vaccination efforts. This study aims to evaluate rotavirus circulation at the population level through wastewater-based epidemiology (WBE), offering a non-invasive, complementary approach to clinical surveillance. Between 2024 and 2025, a total of 172 composite 24 h samples were collected from eight urban wastewater treatment plants across Northern, Central, and Southern Italy. Viral RNA was concentrated by PEG precipitation and quantified using digital RT-PCR, while genotypes were determined via nested PCR targeting VP7 and VP4 genes. Rotavirus RNA was detected in 143 out of 172 samples (83.1%), with viral loads ranging between 4.2 × 10² to 7.3 × 10⁵ genome copies per liter (g.c./L). Genotyping revealed G3 as the predominant VP7 type, followed by G1, G2, G6, and G9. All VP4-positive samples were classified as P8. This investigation expands current knowledge of rotavirus epidemiology in Italy using molecular surveillance of urban wastewater. By combining digital RT-PCR and genotyping, it offers a robust framework for integrating WBE into rotavirus monitoring programs, especially in settings where clinical surveillance is limited. Full article

RNA-based therapeutics offer transformative potential for treating devastating diseases. However, current RNA delivery technologies face significant hurdles, including inefficient tissue targeting, insufficient selectivity, and severe side effects, leading to the termination of many clinical trials. This review critically assesses the landscape of RNA-derived medicines, examining world-renowned mRNA vaccines (Spikevax, BNT162b2/Comirnaty) and RNA-based therapeutics like Miravirsen (anti-miR-122). It details the composition and clinical trial results of numerous modified short RNA drugs (e.g., siRNAs, miRNA mimetics/inhibitors) targeting various conditions. Prospects for RNA-based medicines are analysed for diseases with substantial societal impact, such as cancer, autoimmune disorders, and infectious diseases, with a focus on evolving delivery methods, including lipid nanoparticles, viral vectors, and exosomes. RNA-mediated macrophage reprogramming emerges as a promising strategy, potentially enhancing both delivery and clinical efficacy. This review highlights that while approved RNA therapies primarily target rare diseases due to delivery limitations, novel approaches in RNA modification, targeted delivery systems, and enhanced understanding of molecular mechanisms are crucial for expanding their application to prevalent diseases and unlocking their full therapeutic potential. Full article

Background/Objectives: Gestational weight gain (GWG) is a crucial factor influencing mother and fetal health, as high GWG is associated with adverse pregnancy outcomes and an increased long-term risk of obesity and metabolic issues in the children. In addition to controlling weight, maternal physical activity (PA) during pregnancy may influence fetal development through potential epigenetic mechanisms, including histone modifications, DNA methylation, and the production of non-coding RNA. Methods: This narrative review synthesizes evidence from randomized controlled trials (RCTs; n = 11, 3654 participants) investigating the impact of aerobic PA on GWG, while also highlighting emerging, primarily indirect findings on maternal–fetal epigenetic programming. Results: The majority of RCTs found that supervised PA interventions, especially when paired with nutritional counseling, decreased both the incidence of excessive GWG and total GWG. Enhancements in lipid metabolism, adipokine profiles, and maternal insulin sensitivity point to likely biochemical mechanisms that connect PA to epigenetic modification of fetal metabolic genes (e.g., IGF2, PGC-1α, LEP). Animal and observational studies suggest that maternal activity may influence offspring epigenetic pathways related to obesity and cardiometabolic conditions, although direct human evidence is limited. Conclusions: In addition to potentially changing gene–environment interactions throughout generations, prenatal PA is a low-cost, safe method of improving maternal and newborn health. Future RCTs ought to incorporate molecular endpoints to elucidate the epigenetic processes by which maternal exercise may provide long-term health benefits. Full article