Search Results (15,081)

Sodium p-perfluorous nonenoxybenzenesulfonate (OBS) has been proposed as a substitute for perfluorooctanesulfonic acid (PFOS), yet it has garnered increasing attention due to its environmental persistence and potential toxicity. Despite these concerns, the neurotoxic mechanisms of OBS remain unclear. This study investigates and compares the neurotoxic effects and mechanisms of OBS and PFOS in Caenorhabditis elegans. L4-stage worms were exposed to OBS (0.1–100 μM) or PFOS (100 μM) for 24 h. Neurobehavioral analysis showed that OBS exposure induced concentration-dependent neurobehavioral deficits, with 100 μM OBS significantly reducing pharyngeal pumping rate (29.8%), head swing frequency (23.4%), and body bending frequency (46.6%), surpassing the effects of PFOS. Both compounds decreased the fluorescence intensity of dopaminergic, glutamatergic, and γ-aminobutyric acid neurons and downregulated neurotransmitter-associated genes. They also increased ROS generation and inhibited antioxidant gene expression. Molecular docking revealed that OBS had a stronger binding affinity to p38 MAPK key protein (PMK-1) than PFOS. OBS and PFOS upregulated pmk-1 and skn-1, modulating oxidative stress and neuronal function. pmk-1 mutation differentially affected OBS-induced neurobehavioral changes and gene expression alterations. Our findings indicate that OBS exhibits stronger neurotoxicity than PFOS in Caenorhabditis elegans, mediated through the PMK-1 pathway. These results highlight the need for further investigation into the safety of OBS as a PFOS alternative. Full article

Gastrodia elata Blume is an important medicinal orchid, yet its large-scale cultivation is increasingly threatened by fungal diseases. The 4-coumarate–CoA ligase (4CL) gene family directs a key step in phenylpropanoid metabolism and plant defence, but its composition and function in G. elata have not been investigated. We mined the G. elata genome for 4CL homologues, mapped their chromosomal locations, and analysed their gene structures, conserved motifs, phylogenetic relationships, promoter cis-elements and codon usage bias. Publicly available transcriptomes were used to examine tissue-specific expression and responses to fungal infection. Subcellular localisation of selected proteins was verified by transient expression in Arabidopsis protoplasts. Fourteen Ge4CL genes were identified and grouped into three clades. Two members, Ge4CL2 and Ge4CL5, were strongly upregulated in tubers challenged with fungal pathogens. Ge4CL2 localised to the nucleus, whereas Ge4CL5 localised to both the nucleus and the cytoplasm. Codon usage analysis suggested that Escherichia coli and Oryza sativa are suitable heterologous hosts for Ge4CL expression. This study provides the first genome-wide catalogue of 4CL genes in G. elata and suggests that Ge4CL2 and Ge4CL5 may participate in antifungal defence, although functional confirmation is still required. The dataset furnishes a foundation for functional characterisation and the molecular breeding of disease-resistant G. elata cultivars. Full article

The fungal pathogen Puccinia striiformis f. sp. tritici, which causes yellow rust disease, poses a significant economic threat to wheat production not only in Uzbekistan but also globally, leading to substantial reductions in grain yield. This study aimed to develop yellow rust-resistance wheat lines by introgressing Yr10 and Yr15 genes into high-yielding cultivar Grom using the marker-assisted backcrossing (MABC) method. Grom was crossed with donor genotypes Yr10/6*Avocet S and Yr15/6*Avocet S, resulting in the development of F₁ generations. In the following years, the F₁ hybrids were advanced to the BC₂F₁ and BC₂F₂ generations using the MABC approach. Foreground and background selection using microsatellite markers (Xpsp3000 and Barc008) were employed to identify homozygous Yr10- and Yr15-containing genotypes. The resulting BC₂F₂ lines, designated as Grom-Yr10 and Grom-Yr15, retained key agronomic traits of the recurrent parent cv. Grom, such as spike length (13.0–11.9 cm) and spike weight (3.23–2.92 g). Under artificial infection conditions, the selected lines showed complete resistance to yellow rust (infection type 0). The most promising BC₂F₂ plants were subsequently advanced to homozygous BC₂F₃ lines harboring the introgressed resistance genes through marker-assisted selection. This study demonstrates the effectiveness of integrating molecular marker-assisted selection with conventional breeding methods to enhance disease resistance while preserving high-yielding traits. The newly developed lines offer valuable material for future wheat improvement and contribute to sustainable agriculture and food security. Full article

Age-related macular degeneration (AMD) is one of the leading causes of irreversible vision loss among the elderly, and is influenced by a combination of genetic and environmental risk factors. While genetic associations in AMD are well-established, the molecular mechanisms underlying disease onset and progression remain poorly understood. A growing body of evidence suggests that epigenetic modifications may serve as a potential missing link regulating gene–environment interactions. This review incorporates recent findings on DNA methylation, including both hypermethylation and hypomethylation patterns affecting genes such as silent mating type information regulation 2 homolog 1 (SIRT1), glutathione S-transferase isoform (GSTM), and SKI proto-oncogene (SKI), which may influence key pathophysiological drivers of AMD. We also examine histone modification patterns, chromatin accessibility, the status of long non-coding RNAs (lncRNAs) in AMD pathogenesis and in regulating pathways pertinent to the pathophysiology of the disease. While the field of ocular epigenetics remains in its infancy, accumulating evidence to date points to a burgeoning role for epigenetic regulation in AMD, pre-clinical studies have yielded promising findings for the prospect of epigenetics as a future therapeutic avenue. Full article

Sea buckthorn is a vital woody oil species valued for its role in soil conservation and its bioactive seed oil, which is rich in unsaturated fatty acids and other compounds. However, low seed oil content and small seed size are the main bottlenecks restricting the development and utilization of sea buckthorn. In this study, we tested the seed oil content and seed size of 12 sea buckthorn cultivars and identified the key genes and transcription factors involved in seed development and lipid biosynthesis via the integration of UID RNA-seq (Unique Identifiers, UID), WGCNA (weighted gene co-expression network analysis) and qRT-PCR (quantitative real-time PCR) analysis. The results revealed five cultivars (CY02, CY11, CY201309, CY18, CY21) with significantly higher oil contents and five cultivars (CY10, CY201309, CY18, CY21, CY27) with significantly heavier seeds. A total of 10,873 genes were significantly differentially expressed between the S1 and S2 seed developmental stages of the 12 cultivars. WGCNA was used to identify five modules related to seed oil content and seed weight/size, and 417 candidate genes were screened from these modules. Among them, multiple hub genes and transcription factors were identified; for instance, ATP synthase, ATP synthase subunit D and Acyl carrier protein 1 were related to seed development; plastid–lipid-associated protein, acyltransferase-like protein, and glycerol-3-phosphate 2-O-acyltransferase 6 were involved in lipid biosynthesis; and transcription factors DOF1.2, BHLH137 and ERF4 were associated with seed enlargement and development. These findings provide crucial insights into the genetic regulation of seed traits in sea buckthorn, offering targets for future breeding efforts aimed at improving oil yield and quality. Full article

Grafting serves as a crucial propagation technique for superior Camellia oleifera varieties, where rootstock–scion compatibility significantly determines survival and growth performance. To systematically evaluate grafting compatibility in this economically important woody oil crop, we examined 15 rootstock–scion combinations using ‘Xianglin 210’ as the scion, assessing growth traits and conducting physiological assays (enzymatic activities of SOD and POD and levels of ROS and IAA) at multiple timepoints (0–32 days post-grafting). The results demonstrated that Comb. 4 (Xianglin 27 rootstock) exhibited superior compatibility, characterized by systemic antioxidant activation (peaking at 4–8 DPG), rapid auxin accumulation (4 DPG), and efficient sugar allocation. Transcriptome sequencing and WGCNA analysis identified 3781 differentially expressed genes, with notable enrichment in stress response pathways (Hsp70, DnaJ) and auxin biosynthesis (YUCCA), while also revealing key hub genes (FKBP19) associated with graft-healing efficiency. These findings establish that successful grafting in C. oleifera depends on coordinated rapid redox regulation, auxin-mediated cell proliferation, and metabolic reprogramming, with Comb. 4 emerging as the optimal rootstock choice. The identified molecular markers not only advance our understanding of grafting mechanisms in woody plants but also provide valuable targets for future breeding programs aimed at improving grafting success rates in this important oil crop. Full article

Backgroud. Endometriosis is a chronic, estrogen-dependent inflammatory disease characterized by the ectopic presence of endometrial-like tissue. Although genome-wide association studies (GWAS) have identified susceptibility variants, their tissue-specific regulatory impact remains poorly understood. Objective. To functionally characterize endometriosis-associated variants by exploring their regulatory effects as expression quantitative trait loci (eQTLs) across six physiologically relevant tissues: peripheral blood, sigmoid colon, ileum, ovary, uterus, and vagina. Methods. GWAS-identified variants were cross-referenced with tissue-specific eQTL data from the GTEx v8 database. We prioritized genes either frequently regulated by eQTLs or showing the strongest regulatory effects (based on slope values, which indicate the direction and magnitude of the effect on gene expression). Functional interpretation was performed using MSigDB Hallmark gene sets and Cancer Hallmarks gene collections. Results. A tissue specificity was observed in the regulatory profiles of eQTL-associated genes. In the colon, ileum, and peripheral blood, immune and epithelial signaling genes predominated. In contrast, reproductive tissues showed the enrichment of genes involved in hormonal response, tissue remodeling, and adhesion. Key regulators such as MICB, CLDN23, and GATA4 were consistently linked to hallmark pathways, including immune evasion, angiogenesis, and proliferative signaling. Notably, a substantial subset of regulated genes was not associated with any known pathway, indicating potential novel regulatory mechanisms. Conclusions. This integrative approach highlights the com-plexity of tissue-specific gene regulation mediated by endometriosis-associated variants. Our findings provide a functional framework to prioritize candidate genes and support new mechanistic hypotheses for the molecular pathophysiology of endometriosis. Full article

Human milk bacteria contribute to gut microbiome establishment in breastfed infants. Although breastfeeding is recommended throughout infancy, temporal variation in the milk microbiome—particularly beyond solid food introduction—remains understudied. We analyzed 539 milk samples from 83 mother–infant dyads between 1 week and 12 months postpartum using full-length 16S rRNA gene sequencing. The microbiota was dominated by Streptococcus (34%), Cutibacterium (12%), and Staphylococcus (9%), with marked inter-individual variation. Microbiome profiles remained largely stable across lactation, with only six taxa showing temporal fluctuations, including increases in typical oral bacteria such as Streptococcus salivarius, Streptococcus lactarius, Rothia mucilaginosa, and Granulicatella adiacens. Richness and evenness were higher at 1 week compared to 1 month postpartum (p = 0.00003 and p = 0.007, respectively), then stabilized. Beta diversity also remained stable over time. Maternal pre-pregnancy BMI was positively associated with Gemella haemolysans (p = 0.016), while Haemophilus parainfluenzae was more abundant in milk from mothers with allergies (p = 0.003) and those who gave birth in autumn or winter (p = 0.006). The introduction of solid food was linked to minor taxonomic shifts. Overall, the milk microbiome remained robustly stable over the first year of lactation, with limited but notable fluctuations in specific taxa. This study supports the role of human milk as a consistent microbial source for infants and identifies maternal BMI, allergy status, and birth season as key variables warranting further investigation. Full article

Ferroptosis is a distinct form of regulated cell death driven by iron-dependent lipid peroxidation participating in various diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a central regulator of cellular redox homeostasis and a key determinant of ferroptosis resistance. Nrf2 activates the expression of downstream antioxidant genes to protect cells from oxidative stress and ferroptosis. Consequently, precise regulation of Nrf2 expression is crucial. Recent studies have revealed that complex epigenetic mechanisms involving DNA methylation, histone modifications, and non-coding RNA networks regulate Nrf2 expression. DNA methylation usually suppresses while histone acetylation promotes Nrf2 expression. The influences of histone methylation on NFE2L2 are site- and methylation degree-dependent. m6A modification stabilizes NFE2L2 mRNA to promote Nrf2 expression and thereby inhibit ferroptosis. This article summarizes current understanding of the epigenetic mechanisms controlling Nrf2 expression and Nrf2-mediated ferroptosis pathways and their implications in disease models. The challenges associated with the epigenetic regulation of Nrf2 and future research directions are also discussed. A comprehensive understanding of this regulatory interplay could open new avenues for intervention in ferroptosis-related diseases by fine-tuning cellular redox balance through the epigenetic modulation of Nrf2. Full article

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a systemic ciliopathy resulting from loss-of-function mutations in the PKD1 and PKD2 genes, which encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively. PC1 and PC2 regulate mechanosensation, calcium signaling, and key pathways controlling tubular epithelial structure and function. Loss of PC1/PC2 disrupts calcium homeostasis, elevates cAMP, and activates proliferative cascades such as PKA–B-Raf–MEK–ERK, mTOR, and Wnt, driving cystogenesis via epithelial proliferation, impaired apoptosis, fluid secretion, and fibrosis. Recent evidence also implicates novel signaling axes in ADPKD progression including, the Hippo pathway, where dysregulated YAP/TAZ activity enhances c-Myc-mediated proliferation; the stimulator of interferon genes (STING) pathway, which is activated by mitochondrial DNA release and linked to NF-κB-driven inflammation and fibrosis; and the TWEAK/Fn14 pathway, which mediates pro-inflammatory and pro-apoptotic responses via ERK and NF-κB activation in tubular cells. Mitochondrial dysfunction, oxidative stress, and maladaptive extracellular matrix remodeling further exacerbate disease progression. A refined understanding of ADPKD’s complex signaling networks provides a foundation for precision medicine and next-generation therapeutics. This review gathers recent molecular insights and highlights both established and emerging targets to guide targeted treatment strategies in ADPKD. Full article

Seed oil represents a key trait in soybeans, which holds substantial economic significance, contributing to roughly 60% of global oilseed production. This research employed genome-wide association mapping to identify genetic loci associated with oil content in soybean seeds. A panel comprising 341 soybean accessions, primarily sourced from Northeast China, was assessed for seed oil content at Heilongjiang Province in three replications over two growing seasons (2021 and 2023) and underwent genotyping via whole-genome resequencing, resulting in 1,048,576 high-quality SNP markers. Phenotypic analysis indicated notable variation in oil content, ranging from 11.00% to 21.77%, with an average increase of 1.73% to 2.28% across all growing regions between 2021 and 2023. A genome-wide association study (GWAS) analysis revealed 119 significant single-nucleotide polymorphism (SNP) loci associated with oil content, with a prominent cluster of 77 SNPs located on chromosome 8. Candidate gene analysis identified four key genes potentially implicated in oil content regulation, selected based on proximity to significant SNPs (≤10 kb) and functional annotation related to lipid metabolism and signal transduction. Notably, Glyma.08G123500, encoding a receptor-like kinase involved in signal transduction, contained multiple significant SNPs with PROVEAN scores ranging from deleterious (−1.633) to neutral (0.933), indicating complex functional impacts on protein function. Additional candidate genes include Glyma.08G110000 (hydroxycinnamoyl-CoA transferase), Glyma.08G117400 (PPR repeat protein), and Glyma.08G117600 (WD40 repeat protein), each showing distinct expression patterns and functional roles. Some SNP clusters were associated with increased oil content, while others correlated with decreased oil content, indicating complex genetic regulation of this trait. The findings provide molecular markers with potential for marker-assisted selection (MAS) in breeding programs aimed at increasing soybean oil content and enhancing our understanding of the genetic architecture governing this critical agricultural trait. Full article

The chickpea (Cicer arietinum L.) is a key legume crop in Mediterranean agriculture, valued for its nutritional profile and adaptability. However, its productivity is severely impacted by drought stress. To identify microbial solutions that enhance drought resilience, we isolated seven Mesorhizobium strains from chickpea nodules collected in southern Spain and evaluated their cultivar-specific symbiotic performance. Two commercial cultivars (Pedrosillano and Blanco Lechoso) and twenty chickpea germplasms were tested under growth chamber and greenhouse conditions, both with and without drought stress. Initial screening in a sterile substrate using nodulation assays, shoot/root dry weight measurements, and acetylene reduction assays identified three elite strains (ISC11, ISC15, and ISC25) with superior symbiotic performance and nitrogenase activity. Greenhouse trials under reduced irrigation demonstrated that several strain–cultivar combinations significantly mitigated drought effects on plant biomass, with specific interactions (e.g., ISC25 with RR-98 or BT6-19) preserving over 70% of shoot biomass relative to controls. Whole-genome sequencing of the elite strains revealed diverse taxonomic affiliations—ISC11 as Mesorhizobium ciceri, ISC15 as Mesorhizobium mediterraneum, and ISC25 likely representing a novel species. Genome mining identified plant growth-promoting traits including ACC deaminase genes (in ISC11 and ISC25) and genes coding for auxin biosynthesis-related enzymes. Our findings highlight the potential of targeted rhizobial inoculants tailored to chickpea cultivars to improve crop performance under water-limiting conditions. Full article

This review explores the biofilm architecture and drug resistance of Enterococcus faecalis in clinical and environmental settings. The biofilm in E. faecalis is a heterogeneous, three-dimensional, mushroom-like or multilayered structure, characteristically forming diplococci or short chains interspersed with water channels for nutrient exchange and waste removal. Exopolysaccharides, proteins, lipids, and extracellular DNA create a protective matrix. Persister cells within the biofilm contribute to antibiotic resistance and survival. The heterogeneous architecture of the E. faecalis biofilm contains both dense clusters and loosely packed regions that vary in thickness, ranging from 10 to 100 µm, depending on the environmental conditions. The pathogenicity of the E. faecalis biofilm is mediated through complex interactions between genes and virulence factors such as DNA release, cytolysin, pili, secreted antigen A, and microbial surface components that recognize adhesive matrix molecules, often involving a key protein called enterococcal surface protein (Esp). Clinically, it is implicated in a range of nosocomial infections, including urinary tract infections, endocarditis, and surgical wound infections. The biofilm serves as a nidus for bacterial dissemination and as a reservoir for antimicrobial resistance. The effectiveness of first-line antibiotics (ampicillin, vancomycin, and aminoglycosides) is diminished due to reduced penetration, altered metabolism, increased tolerance, and intrinsic and acquired resistance. Alternative strategies for biofilm disruption, such as combination therapy (ampicillin with aminoglycosides), as well as newer approaches, including antimicrobial peptides, quorum-sensing inhibitors, and biofilm-disrupting agents (DNase or dispersin B), are also being explored to improve treatment outcomes. Environmentally, E. faecalis biofilms contribute to contamination in water systems, food production facilities, and healthcare environments. They persist in harsh conditions, facilitating the spread of multidrug-resistant strains and increasing the risk of transmission to humans and animals. Therefore, understanding the biofilm architecture and drug resistance is essential for developing effective strategies to mitigate their clinical and environmental impact. Full article

Viral outbreaks have caused significant mortality and economic losses in aquaculture, highlighting the urgent need for effective therapies and a deeper understanding of antiviral and immune mechanisms in key species. This study investigates the constitutive and virus-induced antiviral responses in juvenile rainbow trout (Oncorhynchus mykiss) following infection with viral hemorrhagic septicemia virus (VHSV). Trout (30 g) were infected by immersion with VHSV (TCID₅₀ = 10⁵ mL⁻¹) for two hours. Samples were collected at 24, 72, and 120 h post-infection to assess hematology, innate immunity, viral load, and transcriptomic response. At 24 h post-infection, no immune response or increase in viral load was detected, suggesting the host had not yet recognized the virus and was still in the incubation phase. By 72 h, viral replication peaked, with high viral loads observed in mucosal tissues (skin and gills) and immune organs (kidney, spleen, liver), alongside strong up-regulation of antiviral genes, such as viperin. This gene maintained high expression through the final sampling point, indicating its key role in the antiviral response. At this stage, reduced immune competence was observed, marked by elevated nitric oxide and circulating thrombocytes. At 120 h, modest increases in peripheral monocyte, plasma lysozyme, and peroxidase activity were detected; however, these responses were insufficient to reduce viral load, suggesting the resolution phase had not yet begun. In summary, while a limited immune response was observed by the end of the trial, the consistent antiviral activity of viperin from peak infection to 120 h post-infection underscores its importance in the defence against VHSV in rainbow trout. Full article

Background/Objectives: Non-coding microRNA-34a (miR-34a) regulates the expression of key factors involved in several cellular processes, such as differentiation, apoptosis, proliferation, cell cycle, and senescence. Deregulation of the expression of these factors is implicated in the onset and progression of several human diseases, including cancer, neurodegenerative disorders, and pathologies associated with viral infections and inflammation. Despite numerous studies, the molecular mechanisms regulated by miR-34a remain to be fully understood. The present study aimed to generate miR-34a knockout cell lines to identify novel genes potentially regulated by its expression. Methods: We employed the CRISPR-Cas9 gene editing system to knock out the hsa-miR-34a gene in HeLa and 293T cell lines, two widely used models for studying molecular and cellular mechanisms. We compared proliferation rates and gene expression profiles via RNA-seq and qPCR analyses between the wild-type and miR-34a KO cell lines. Results: Knockout of miR-34a resulted in a decreased proliferation rate in both cell lines. Noteworthy, the ablation of miR-34a resulted in increased expression of the long non-coding RNA MALAT1. Additionally, miR-34a-5p silencing in the A375 melanoma cell line led to MALAT1 overexpression. Conclusions: Our findings support the role of the miR-34a/MALAT1 axis in regulating proliferation processes. Full article