Search Results (40,894)

To identify chitinase genes from the genome of the mycoparasitic Cladosporium sp. strain SYC23, bioinformatical analyses and real-time quantitative PCR (RT-qPCR) were employed to screen mycoparasitism-associated genes at 12, 24, 48, and 72 h post-induction with Aecidium pourthiaea rust spores. A total of eight chitinase genes were identified from SYC23 via bioinformatics analysis and designated CaChi34, CaChi40, CaChi45, CaChi67, CaChi82, CaChi92, CaChi93, and CaChi286 based on sequence and phylogenetic analyses. Analysis of the chitinase protein sequence characteristics revealed molecular weights ranging from 33.86 to 286.03 kDa and theoretical isoelectric points from 4.48 to 7.7. All CaChi genes contained the conserved GH18 domain, and promoter analysis showed that each harbored MYB-binding sites and pathogen-responsive elements. Mycoparasitism-related sequence clustering analysis indicated that the chitinase sequences of SYC23 shared the closest phylogenetic relationship with those from Trichoderma sp. RT-qPCR results following rust spore induction showed that five CaChi genes reached their highest expression levels at 24 h post-induction, CaChi45 was most highly expressed at 72 h post-induction, CaChi93 was continuously upregulated, and CaChi82 was continuously downregulated throughout the induction period. His-tagged recombinant CaChi93 protein was purified from E. coli and characterized. The results demonstrate that the enzymatic activity of CaChi93 was 0.929 U/mg, with optimal reaction conditions at 65 °C and pH 7. Treatment of A. pourthiaea rust spores with the recombinant CaChi93 chitinase confirmed that CaChi93 could effectively dissolve rust spore walls. In conclusion, this study confirms that the mycoparasitic Cladosporium sp. strain SYC23 can secrete chitinase to degrade the rust spore wall and induce spore death, thereby providing novel gene resources and a theoretical basis for the biological control of A. pourthiaea. Full article

Silver nanoparticle (AgNP)-based products have been increasingly applied in aquaculture due to their antimicrobial properties and capacity to modulate host immunity. This study investigated the biological activities of synthesized silver nanowires (AgNWs), with particular emphasis on their anti-Vibrio efficacy and immunomodulatory effects, to evaluate their potential application in shrimp aquaculture. Antibacterial activity was assessed using nonlinear regression analysis to determine minimum inhibitory concentrations (MICs) against three major Vibrio pathogens, while cytotoxicity and immune responses were evaluated using white shrimp hemocytes through cell viability assays and in vitro gene expression analysis, respectively. AgNWs exhibited antibacterial effects on Vibrio parahaemolyticus, Vibrio alginolyticus, and Vibrio harveyi, with MIC values of 873.7, 58.78, and 672.1 μg/mL, respectively. Hemocyte viability remained above 90% at AgNW concentrations of up to 1000 mg/L, indicating good biocompatibility. AgNWs significantly upregulated immune-related lipopolysaccharide and β-1,3-glucan-binding protein (LGBP) and Toll gene expression at specific concentrations, indicating immunostimulation. These results suggest that AgNWs possess antibacterial activity and immunomodulatory potential with low cytotoxicity, supporting their promise as a novel functional agent for shrimp disease management. Full article

Background/Objectives: Severe and recurrent infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa necessitate alternative antimicrobial strategies. Fermented cacao beans represent a niche microbial ecosystem with the potential to harbor beneficial lactic acid bacteria (LAB). This study aimed to isolate and characterize LAB strains from fermented cacao beans in southern Thailand and to evaluate their probiotic potential and antimicrobial activity against MDR P. aeruginosa. Methods and Results: Five Lactiplantibacillus plantarum isolates were identified via MALDI-TOF MS and whole-genome sequencing (WGS). All strains demonstrated antimicrobial activity against 17 clinical MDR P. aeruginosa isolates and CR14 exhibited the largest inhibition zone. The isolates displayed robust probiotic traits, including survival under simulated gastrointestinal conditions. Acid tolerance (pH 2.0) reached 61.15 ± 7.75%, while resistance to pepsin, pancreatin, and bile salts exceeded 88%, 91%, and 92%, respectively. Strong adhesion was confirmed via auto-aggregation (55.02 ± 1.75%), hydrophobicity (45.58 ± 0.96%) and Caco-2 cell attachment (up to 98.11 ± 3.28%). WGS revealed multiple plantaricin-encoding clusters. Coarse-grained molecular dynamic simulations showed that two-peptide plantaricins (plnJ/K and plnNC8-αβ) self-assembled and formed stable pores in bacterial membrane models, confirming a pore-forming antimicrobial mechanism. The strains lacked acquired resistance genes and virulence factors, confirmed by in silico safety assessments. Conclusions: Thus, these L. plantarum strains are promising probiotics for managing MDR P. aeruginosa via functional foods or adjunct therapies. Full article

The safety of titanium dioxide (TiO₂), widely used in foods and personal care products, has been of on-going concern. Adverse effects of TiO₂ have been reported, suggesting risk to human health. To evaluate its potential epigenotoxicity, the effect of exposure to a TiO₂ product, to which humans could be exposed, on microRNA (miRNA) expression (a primary epigenetic mechanism) was investigated using human cell lines (Caco-2, HCT116 (colorectal) and HepG2, SNU387 (liver)) relevant to human exposure. The effect of TiO₂ nanomaterial exposure on expression levels of miRNA was determined using the TaqMan Array Human microRNA A+B Card Set v3.0 platform. Differentially expressed miRNAs were identified (SNU387 (n = 112), HepG2 (n = 97), Caco-2 (n = 94), and HCT116 (n = 53)). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) functional enrichment analysis of target genes provided insights into the roles of modulating pathways, which can be associated with diseases. Top 10 KEGG pathways in each cell line included MAPK signaling pathway, Axon guidance, cell cycle, Hippo signaling pathway, and Endocytosis. Findings from the study clearly demonstrate the impact of TiO₂ exposure on miRNA expression, supporting the potential involvement of this epigenetic mechanism in its biological responses. Hence, epigenetic studies are important for the complete assessment of the potential risk from exposure. Full article

Background: Tumor cells can reprogram their metabolism, constituting a hallmark of cancer that plays a crucial role in tumor progression. As tumor cells exhibit an increased demand for nutrients, e.g., amino acids, they rely on extracellular sources and show deregulation of transport proteins. Among these, SNAT1 (SLC38A1) is described as the loader for glutamine that is responsible for the main influx of this amino acid. The aim of this study was to assess the molecular function of SNAT1 in melanoma regarding its role in amino acid transport and regulation of cellular metabolism. Methods: siPool-mediated downregulation of SNAT1 expression in melanoma cell lines was used to investigate the molecular function of this protein. Glutamine transport was assessed by measuring the intracellular and extracellular concentrations of glutamine. Regulation of downstream effectors was evaluated with qRT-PCR and Western Blot. Metabolism was investigated by performing Seahorse flux analysis. Mitochondrial staining was examined via flow cytometry. Protein interaction was assessed with Co-IP, and in silico modeling of protein interaction was performed with AlphaFold3. Results: In this study, we uncovered the new finding that SNAT1 is not primarily implicated in glutamine influx into melanoma cells but in signaling in response to extracellular glutamine. We identified P62 and cMYC as downstream effectors of SNAT1. By activating the P62/cMYC-axis and target genes of cMYC, SNAT1 modulates the metabolism of melanoma cells depending on the glutamine level. SNAT1 and P62 are interaction partners. Conclusions: This finding newly suggests that SNAT1 may function as a sensor or receptor (“transceptor”) for glutamine rather than being a direct and primary glutamine transporter, and could open up new therapeutic options targeting melanoma cells. Full article

Background/Objectives: Understanding the mechanisms of drug response plays an essential role in predicting effects prior to drug administration and advancing personalized medicine by optimizing treatment strategies. This study aimed to identify gene combinations that can predict the antitumor activity of lenvatinib, which is a multi-targeted tyrosine kinase inhibitor. Methods: Cancer- and drug-response-related gene sets were identified by mapping gene expression profiles of previously reported syngeneic mouse tumor models onto a protein–protein interaction network and extracting subnetworks comprising nodes where high expression levels were clustered. The scores for these network modules were calculated using the expression data of mouse tumor models prior to drug administration. These scores were used to train a machine learning (ML) model of drug response to lenvatinib by narrowing down the parameter space using hepatocellular carcinoma patient-derived xenograft (HCC PDX) models acquired in this study. Results: Using this integrative framework, we identified several network modules including those involved in the nerve growth factor signaling pathway, Wnt signaling pathway, and interleukin signaling pathways, that were consistently prioritized as informative features across PDX models and human patient data from The Cancer Genome Atlas. Conclusions: These network modules exhibit biological functions that are linked to the known targets of lenvatinib in the cancer cells or the tumor microenvironment, highlighting their potential relevance as determinants of drug response. Full article

Background: Among gynecological malignancies, ovarian cancer (OC) remains a leading cause of mortality worldwide, often characterized by the highest fatality-to-case ratio due to its asymptomatic progression and late-stage detection. Despite substantial investigation, the root cause of disease development and pathology remains unknown. Early detection is critical for improving OC prognosis. Unfortunately, because of the lack of identifiable symptoms in the early stages, the disease is frequently detected late. As a result, regular check-ups, being aware of risk factors, and paying attention to unusual symptoms can all help discover OC early. Apolipoproteins (APOs) and Annexins (ANXs) have recently been linked to OC. Aim: We conducted a cutting-edge bioinformatics investigation to find novel therapeutic targets and precise biomarkers linked to OC against APO and ANX. Methods: We started by compiling the ANX and APO families via HUGO Gene Nomenclature Committee (HGNC) homepage. Next, we accessed GEPIA2 to compare the relative messenger RNA (mRNA) expression levels of all ANX and APO family members across the cancer genome atlas (TCGA)-OC cohort and matched normal and GTEx data. Prognostic analysis of all significantly expressed ANXs and APOs was performed via Kaplan–Meier (KM) plotter. cBioPortal was used for mutational analysis of prognostic ANXs and APOs. Finally, we ran functional enrichment, molecular docking, and molecular dynamics (MD) simulation analyses. Results: Overall, the results suggest that ANXA2 and its related genetic changes represent potential focal points for precision oncology, offering a computational rationale for the development of target-driven therapeutic interventions in OC. Conclusions: Molecular docking and MD simulation analyses identified curcumin as a potential inhibitor of ANXA2, demonstrating stable binding affinity and structural conservation throughout the simulation period. These computational findings characterize curcumin as a promising candidate for targeting ANXA2 in OC, warranting further experimental validation to confirm its therapeutic efficacy. Full article

Seeds of Paeonia lactiflora Pall. ‘Hangshao’ contain over 20% oil, of which more than 90% are unsaturated fatty acids, showing its high potential as an oil crop. Triacylglycerol (TAG) is the main storage form of fatty acids, and diacylglycerol acyltransferase 2 (DGAT2) is a key enzyme in TAG biosynthesis. In this study, the full-length cDNA of PlDGAT2 (326 amino acids) was cloned. Subcellular localization assays further indicated that it localized in the endoplasmic reticulum. Functional verification showed that silencing PlDGAT2 in herbaceous peony decreased the level of total fatty acids, palmitic acid (C16:0, PA) and α-linolenic acid (C18:3, ALA), but increased linoleic acid (C18:2, LA) in leaves. Overexpressing PlDGAT2 in tobacco elevated the content of total fatty acids, PA, and ALA in seeds, while also enlarging the seed sizes, but it reduced the LA content in tobacco seeds. This study suggests that PlDGAT2 contributes to the accumulation of ALA and total fatty acids, offering a potential gene target for improving the oil quality of herbaceous peony seeds. Full article

Beach sands may harbor human pathogens and antibiotic resistance genes, prompting the proposal of low-dose quicklime (CaO; 1–3% w/w) as a remediation strategy to improve microbiological quality in highly contaminated areas. After application, CaO is converted into calcium carbonate (CaCO₃), yet the ecological effects of this residual compound on benthic fauna remain poorly understood. This study evaluated the short-term impact of CaCO₃-enriched sediment (3% w/w) on the Manila clam, Ruditapes philippinarum, under controlled mesocosm conditions. Adult clams were exposed for one week, and survival, burrowing behavior, feeding- and metabolism-related parameters (clearance, ingestion, absorption efficiency and rate, ammonia excretion), and oxidative stress (malondialdehyde, MDA) were assessed using a hierarchical design, with a tank as the experimental unit. No significant differences were detected between control and CaCO₃-enriched treatments for any measured endpoint. Survival remained high, functional responses showed overlapping ranges, and MDA levels did not differ significantly between groups. Although limited to short-term exposure and a single concentration, these findings suggest that residual CaCO₃ derived from quicklime application did not induce detectable adverse effects in adult R. philippinarum under the tested conditions. Further long-term and multi-species studies are needed to confirm ecological safety. Full article

Purpose: Hearing loss (HL) is a prevalent condition significantly impairing quality of life, with genetic mutations accounting for a substantial proportion of congenital cases, notably those involving the GJB2 gene encoding connexin 26. This study aims to analyze the current knowledge, feasibility, and challenges of gene therapy targeting GJB2-related HL, emphasizing both embryonic and postnatal interventions. Methods: A comprehensive scoping review was conducted across electronic databases up to October 2025, including studies focusing on GJB2-associated HL, gene therapy approaches, and the timing of interventions. Data extraction encompassed mutation types, animal models, delivery strategies, outcomes, and ethical considerations. Results: The results indicated over 467 GJB2 variants which could impair cochlear ion homeostasis and development. Animal models, mainly murine, demonstrated early-onset degeneration with limited recovery following delayed gene therapy, while early postnatal intervention showed greater efficacy. Viral vectors like AAV have been employed for targeted gene delivery via cochlear injections, achieving partial restoration of connexin expression and cochlear function, yet they have faced limitations including transduction efficiency, immune responses, and long-term stability. Challenges in translating these findings to humans have been compounded by anatomical, immunological, ethical, and safety issues, particularly regarding embryonic gene therapy and germline modifications. Ethical frameworks can vary internationally, highlighting the necessity for careful regulation. Conclusions: While promising advances in gene therapy for GJB2-related HL have been achieved in preclinical studies, significant scientific, technical, and ethical barriers must be addressed before clinical application, especially during embryogenesis. A multidisciplinary, cautious approach is essential to realize the potential of gene therapy in restoring natural hearing while safeguarding individual and societal interests. Full article

Acyl-CoA carboxylase (YCC) complexes generate essential starter and extender units for fatty acid and polyketide biosynthesis in Actinobacteria. In Streptomyces coelicolor, two tri-subunit YCC complexes, acetyl-CoA carboxylase (ACC) and propionyl-CoA carboxylase (PCC), have been characterized. However, comparative genomic analyses indicate that β/ε subunits are more diversified than currently appreciated. Here, we identify a previously unrecognized β/ε pair, AccB2 and AccE2, and demonstrate that they assemble with the canonical α subunit to form a functional YCC complex. Both genes are transcribed in vivo, and co-immunoprecipitation (Co-IP) reveals association with AccA1 and AccA2, with AccE2 showing stronger relative association with AccA1-containing pull-downs. In vitro reconstitution confirms carboxylation activity toward acetyl-CoA, propionyl-CoA, and butyryl-CoA, which is strongly dependent on AccE2. These findings expand the YCC repertoire in S. coelicolor and support a modular assembly model in which alternative β/ε combinations contribute to functional diversification of YCC complexes. Full article

Background: MicroRNAs (miRNAs) are stable, small non-coding RNAs involved in asthma-related pathways and are promising diagnostic biomarkers and therapeutic targets in childhood asthma. Objective: To identify miRNAs differentially expressed in preschool wheezing and childhood asthma, evaluate their association with asthma diagnosis and severity-related phenotypes, and explore their potential translational relevance through exploratory bioinformatic analyses. Methods: A systematic search of Medline, Embase, SCOPUS, PubMed, CINAHL, and Web of Science was conducted for English-language articles published up to March 19, 2025. Eligible human studies reported that miRNAs were differentially expressed in children with wheeze or asthma versus healthy controls (p < 0.05, fold change ≥ 1.5). Bioinformatic analysis identified hub genes, constructed protein–protein interaction networks, and predicted drug–gene interactions. Results: Forty-seven studies met the inclusion criteria, yielding 58 differentially expressed miRNAs (31 up, 27 down). Recurrently reported miRNAs included miR-497, let-7e, miR-98, miR-21, miR-126a, miR-196a2, miR-1, miR-146a-5p, miR-210-3p, miR-145-5p, and miR-200c-3p across blood, nasal swabs, BALF, and exhaled breath condensate. miR-26a showed strong diagnostic performance (sensitivity 83%, specificity 93%; p < 0.002, 95% CI 0.831–0.987). Functional enrichment implicated 56 differentially expressed genes in metabolic and immune processes. Ten hub genes (including TNF, IL5, IL13, TLR4) were linked to 339 potential therapeutic agents; the exploratory network analysis highlighted overlap between predicted miRNA-regulated hub genes and existing asthma-relevant drug targets, including approved biologics. Conclusions: Our review findings suggest that several miRNAs are promising candidate biomarkers for childhood asthma phenotyping and severity assessment; however, their diagnostic utility remains exploratory and requires rigorous external validation and standardisation before clinical application. Full article

This study estimates the association between respiratory outcomes among employees of a secondary aluminum plant and airborne pollutants. Additionally, it looks into the relationship between pulmonary dysfunction in workers and X-Ray repair cross-complementing one (XRCC1) gene polymorphisms. 110 exposed workers and 58 non-exposed workers were enrolled in the study. Measurements were conducted on sulfur dioxide (SO₂), nitrogen dioxide (NO₂), and particulate particles. Pulmonary function was tested. Eosinophil cationic protein (ECP), C-reactive protein (CRP), matrix metalloproteinase-1 (MMP-1), interleukin 6 (IL6), granulocyte-macrophage colony-stimulating factor (GM-CSF), XRCC1 protein, and genotyping of XRCC1 gene polymorphisms were examined. The annual average concentrations of particulate matter (PM_2.5, PM₁₀), total suspended particulates (TSP), SO₂, and NO₂ were lower than the permissible limit. The areas around ovens, evaporators, and cold rolling mills exhibited the highest amounts. The majority of employees in these departments had impaired lung function. Prolonged exposure was associated with a significant decrease in forced expiratory volume in 1 s (FEV1%) and forced vital capacity (FVC%) among the exposed group (p = 0.001 & 0.04, respectively). Serum XRCC1 levels were significantly higher among exposed workers (p = 0.02). Inflammatory biomarkers showed no statistically significant differences between groups. Aluminum workers are at risk of developing respiratory disorders. The level of serum XRCC1 may serve as a potential biomarker for detecting susceptible workers. Full article

Background/Objectives: Dihydroartemisinin (DHA), a bioactive metabolite of Artemisia annua, displays potent antitumor activity in multiple cancers. However, its dose-dependent transcriptional regulatory networks in colorectal cancer (CRC) remain insufficiently understood. This study aimed to clarify the molecular mechanisms of low- and high-dose DHA in human CRC cells and reveal the dose-dependent crosstalk among related biological processes. Methods: We integrated RNA-seq transcriptomic profiling and functional validation in HCT116 cells treated with 20 μM (low-dose) or 50 μM (high-dose) DHA. Differentially expressed genes (DEGs) were screened at FDR ≤ 0.05 and |log₂(fold change)| ≥ 1, followed by GO and KEGG enrichment analyses. Results: DHA inhibited cell viability dose-dependently, with an IC₅₀ of 50 μM. We identified 280 and 678 DEGs in low-and high-dose groups, respectively. Low-dose DHA induced apoptosis via GADD45α/β and ATF4/DDIT3-mediated endoplasmic reticulum stress and triggered senescence through G2/M phase arrest. High-dose DHA mainly modulated gene expression signatures associated with ferroptosis by regulating iron homeostasis and lipid peroxidation at the transcriptional level. Both doses suppressed glycolysis, lipid, and folate metabolism; high-dose DHA also inhibited MGAT5B-mediated glycosylation. DHA regulated five core signaling pathways dose-dependently, with high-dose DHA further repressing Wnt3a/16 and BMP4/6. Conclusions: This study first identifies ferroptosis-related gene networks as key transcriptional targets. It reveals dose-dependent crosstalk among cell death, senescence, metabolic reprogramming, and signaling, providing a transcriptomic framework and gene targets for optimizing DHA-based colorectal cancer therapy. Full article

Background: Cardiovascular complications stemming from diabetes pose a grave threat to patients’ survival. Both type 1 diabetes (T1D) and type 2 diabetes (T2D) significantly increase the risk of heart failure, yet no reports have clarified whether there are differences in the pathway alterations involved in these two conditions. Investigating the heterogeneity of the cardiac remodeling between these two types of diabetes is conducive to reducing the incidence of cardiovascular events in diabetic patients in clinical practice. Methods: T1D and T2D models were established in adult mice, and the hearts were collected for RNA sequencing. Differential expression analysis (DEA) was performed. Integrating functional enrichment analyses, we probed into gene and pathway heterogeneity. Subsequently, we compared single-cell RNA sequencing (scRNA-seq) data of hearts from T1D and T2D mice, focusing on three cell populations (endothelial cells, macrophages, and fibroblasts) to identify gene and pathway differences. Finally, we evaluated shared genes and common signaling pathway changes across these three cell populations in both diabetes types. Results: We have successfully established T1D and T2D models in mice. Compared with shared genes, the two types of diabetes had more consistent pathway changes. Further scRNA-seq analysis identified endothelial cells, macrophages, and fibroblasts as significantly associated with the diabetic phenotype. In shared pathway, endothelial cells were significantly enriched in pathways related to endothelial proliferation and angiogenesis; macrophages were enriched in immune response pathways; and fibroblasts were enriched in pathways involving fibrosis, cell proliferation, and apoptosis. In endothelial cells, inflammatory response and fatty acid metabolism pathways were predominantly enriched in T1D, while energy metabolism pathways were dominant in T2D. In macrophages, antiviral immune pathways were specifically enriched in T1D, whereas macrophages in T2D were additionally implicated in the regulation of cardiomyocyte function. In fibroblasts, immune-related pathways were characteristically enriched in T1D, while cell respiration and energy supply pathways were prominent in T2D. Common functional enrichment pathways across the three cell types in both diabetes types mainly involved innate immune responses and cardiac morphogenesis, with the proportion of shared pathways being significantly higher than that of shared genes. Conclusions: This study, by combining RNA sequencing and scRNA-seq, revealed that cardiac pathologies induced by T1D and T2D exhibit a higher degree of consistent pathway changes compared to shared gene changes. Interventions targeting these common pathways may hold greater value in preventing and treating diabetic cardiomyopathy. Full article