Search Results (1,625)

This study focused on the multifunctional characteristics and bioremediation potential of Paracoccus spp. A novel Gram-stain-negative, aerobic, non-motile, ellipsoidal bacterium, named Paracoccus qomolangmaensis S3-43^T, was isolated from moraine samples collected from the north slope of Mount Everest at an altitude of 6109 m above sea level (a.s.l.). To clarify the phylogenetic relationship of this strain within the Paracoccus genus and systematically characterize its features, analyses were conducted using polyphasic taxonomy and comparative genomics. Results revealed two distinct functional characteristics of strain S3-43^T: First, strain S3-43^T exhibits exceptional radiation resistance, particularly tolerance to ionizing radiation. Genome annotation indicates abundant DNA repair and antioxidant-related genes (e.g., vsr, mutL, mutS, ruvC, radA, addA, recA, recN, recO). Second, strain S3-43^T contained several pyrethroids degradation related genes, including cytochrome P450, monooxygenase, and aminopeptidase. The results of the genomic comparison of strain S3-43^T with related type strains also revealed differences and distribution of key genes related to stress response, environmental variables, and bioactive metabolites. Based on the results of the polyphasic taxonomic analysis, strain S3-43^T (=KCTC 8297^T = GDMCC 1.3460^T) should be classified as a novel species of the genus Paracoccus, designated as Paracoccus qomolangmaensis sp. nov. Full article

Two bacterial strains, designated LXY-1^T and LXY-4^T, were isolated from soil samples collected at a heavy metal smelting plant located in Guangxi, China. Phylogenetic analysis indicated that these strains formed two distinct lineages within the genus Neobacillus. Both strains were characterized as facultative anaerobic, Gram-positive staining, endospore-forming, non-motile, short-rod bacteria. The major cellular fatty acids identified in these strains included C_16:0, iso-C_15:0, antéiso-C_15:0, and antéiso-C_17:0. The predominant polar lipids comprised diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), and phosphatidylglycerol (PG). The average nucleotide identity (ANI) values between the newly isolated strains and their closest phylogenetic relatives, the type strains of the genus Neobacillus, were found to be below 95%, with corresponding digital DNA–DNA hybridization (dDDH) values remaining below 70%. Based on a comprehensive polyphasic taxonomic analysis incorporating chemotaxonomic, phenotypic, phylogenetic, and genomic data, we proposed that strains LXY-1^T and LXY-4^T represent two novel species of the genus Neobacillus, for which the names Neobacillus terrisolis sp. nov. and Neobacillus solisequens sp. nov. are designated. The type strains are LXY-1^T (= CGMCC 30313^T = JCM 37671^T) and LXY-4^T (= CGMCC 1.62901^T = JCM 37672^T), respectively. Full article

Fungal communities in the gut influence host immunity, yet most studies have focused on cell wall components rather than genetic materials. Here, we explore how fungal genomic DNA (gDNA) from Candida albicans, Saccharomyces cerevisiae, and Cryptococcus neoformans modulate immune responses in human CD4⁺ T cells, murine splenocytes, and THP-1-derived macrophages. We find that C. albicans gDNA promotes the development of regulatory T cells and increases IL-10, fostering immune tolerance and preserving CD4⁺ T cell viability in an inflammatory setting. S. cerevisiae gDNA induces moderate Treg responses with restrained effector T cell expansion and higher checkpoint gene expression, entirely consistent with its commensal nature. In contrast, C. neoformans gDNA elicits a strongly inflammatory profile, promoting Th1/Th17 cells and driving high cytokine production. Mechanistically, C. albicans and S. cerevisiae gDNA dampen DNA-sensing pathways and enhance immune checkpoint molecules that act as brakes against overactivation, while C. neoformans gDNA robustly activates innate sensing pathways with limited checkpoint induction. These species-specific signaling profiles reveal that fungal gDNA itself can influence whether the immune system adopts a tolerant or inflammatory response toward fungi. This discovery highlights fungal genomic DNA as a previously underappreciated regulator of host–fungus interactions, offering new insight into commensal persistence, pathogenic invasion, and the potential for DNA-based antifungal interventions. Full article

Background/Objective: Cellular senescence is increasingly recognized as a key mechanism underlying sarcopenia, an age-related muscle disorder with no effective therapeutic. 6,4′-Dihydroxy-7-methoxyflavanone (DMF), a flavonoid isolated from Dalbergia odorifera T. Chen, has shown anti-senescence potential. This study aimed to investigate the protective effects of DMF against myoblasts senescence and elucidate the underlying molecular mechanisms. Method: A cellular model of senescence was established in C2C12 myoblasts using D-galactose (D-gal). The effects of DMF pretreatment were evaluated by assessing senescence phenotypes, myogenic differentiation, and mitochondrial function. The role of Sirtuin3 (SIRT3) was confirmed using siRNA-mediated knockdown. Results: DMF Pre-treatment effectively attenuated D-gal-induced senescence, as indicated by restored proliferation, reduced senescence-associated β-galactosidase activity, decreased DNA damage, and the downregulation of p53, p21^Cip1/WAF1 and p16^INK4a. Furthermore, DMF rescued myogenic differentiation capacity, enhancing the expression of Myoblast determination protein 1, Myogenin, Myosin heavy chain and Muscle-specific regulatory factor 4, and promoting myotube formation. Mechanistically, DMF was identified as a SIRT3 activator. It enhanced SIRT3 expression and activity, leading to the deacetylation and activation of the mitochondrial antioxidant enzyme superoxide dismutase 2. This consequently reduced mitochondrial reactive oxygen species, improved mitochondrial membrane potential and ATP production, and suppressed the NF-κB pathway by inhibiting IκBα phosphorylation and p65 acetylation/nuclear translocation. Crucially, all the beneficial effects of DMF—including oxidative stress reduction, mitochondrial functional recovery, anti-inflammatory action, and ultimately, the attenuation of senescence and improvement of myogenesis—were abolished upon SIRT3 knockdown. Conclusions: Our findings demonstrate that DMF alleviates myoblasts senescence and promotes myogenic differentiation by activating the SIRT3-SOD2 pathway, thereby reducing oxidative stress and NF-κB-driven inflammation responses. DMF emerges as a promising therapeutic candidate for sarcopenia. Full article

Upon reacting with cellular components, Hg(II) ions elicit the production of reactive oxygen species (ROS). While the ROS-promoted cytotoxic and genotoxic effects induced by Hg(II) have been widely described in eukaryotes, such effects have been less studied in bacteria. In this work, the prokaryotic environmental model Bacillus subtilis was employed to evaluate the cytotoxic and genotoxic impact of Hg(II) over strains proficient or deficient in SOS, general stress and antioxidant responses, as well as the global transcriptional response elicited by this ion. The exposure to HgCl₂ significantly increased the mutation frequency to rifampicin resistance (Rif^R) in WT and mutant strains, suggesting a major contribution of these pathways in counteracting the genotoxic effects of Hg(II). Detection of A → T and C → G transversion mutations in the rpoB gene of Hg(II)-exposed cells suggested the generation of 8-oxo-guanines (8-OxoGs) and other oxidized DNA bases. The RNA-seq study revealed upregulation of genes involved in efflux and/or reduction of metal ions, synthesis of sulfur-containing molecules, and downregulation of genes implicated in iron metabolism and cell envelope stress. Therefore, our results indicate that metal extrusion and scavenging of Hg(II) by thiol-rich molecules may constitute a line of defense of B. subtilis that counteracts the noxious effects of ROS resulting from an imbalance in iron metabolism elicited by this ion. Full article

By imposing finite order constraints on Fibonacci anyon braid relations, we construct the finite quotient $G={\mathbb{Z}}_5⋊2I$, where $2I$ is the binary icosahedral group. The Gröbner basis decomposition of its $SL(2,\mathbb{C})$ character variety yields elliptic curves whose L-function derivatives $L^{\prime }(E,1)$ remarkably match fundamental biological structural ratios. Specifically, we demonstrate that the Birch–Swinnerton-Dyer conjecture’s central quantity: the derivative $L^{\prime }(E,1)$ of the L-function at 1 encodes critical cellular geometries: the crystalline B-DNA pitch-to-diameter ratio ($L^{\prime }(E,1)=1.730$ matching $34\AA /20\AA =1.70$), the B-DNA pitch to major groove width ($L^{\prime }=1.58$) and, additionally, the fundamental cytoskeletal scaling relationship where $L^{\prime }(E,1)=3.570\approx 25/7$, precisely matching the microtubule-to-actin diameter ratio. This pattern extends across the hierarchy ${\mathbb{Z}}_5⋊2P$ with $2P\in \{2O,2T,2I\}$ (binary octahedral, tetrahedral, icosahedral groups), where character tables of $2O$ explain genetic code degeneracies while $2T$ yields microtubule ratios. The convergence of multiple independent mathematical pathways on identical biological values suggests that evolutionary optimization operates under deep arithmetic-geometric constraints encoded in elliptic curve L-functions. Our results position the BSD conjecture not merely as abstract number theory, but as encoding fundamental organizational principles governing cellular architecture. The correspondence reveals arithmetic geometry as the mathematical blueprint underlying major biological structural systems, with Gross–Zagier theory providing the theoretical framework connecting quantum topology to the helical geometries that are essential for life. Full article

The genus Agave (family Asparagaceae) represents the second-most important group of plants in Mexico. Several fungal species have been identified as causal agents of leaf spot disease affecting Agave salmiana and A. lechuguilla, producing necrotic lesions that compromise plant health and productivity. Pathogenicity experiments were conducted under greenhouse conditions, field tests were performed, and in vitro antagonism using Trichoderma asperellum strain JEAB02 against selected pathogenic isolates was evaluated. Phylogenetic analysis of genomic DNA fragments allowed the identification of 26 fungal isolates belonging to Curvularia lunata, C. verruculosa, Bipolaris zeae, Alternaria alternata, Fusarium lactis, Epicoccum sorghinum, Myrmaecium rubricosum, Penicillium diversum, and Aspergillus oryzae. In pathogenicity assays under greenhouse conditions on A. salmiana and A. lechuguilla, treatments T5–T12 exhibited statistically similar levels of disease severity (33.10–37.29%), caused mainly by C. verruculosa, A. alternata, B. zeae, and F. lactis. In field tests, Agave plants inoculated with the selected pathogenic fungi (T4, T5, T7, T8, T10, and T11) showed 21.07–36.73% leaf damage after 75 days. The antagonistic effect of T. asperellum JEAB02 caused complete (100%) growth inhibition of the pathogenic isolate JCPN27 and inhibition levels from 99.81 to 99.98% for isolates JCPN18, JCPN24, JCPN28, JCPN29, JCPN31, and JCPN33, demonstrating its high potential as a biological control agent. Full article

Thai medicinal flowers, namely Mesua ferrea L. (Bunnak), Mammea siamensis T. Anderson (Saraphi), and Clitoria ternatea (Anchan) have long been valued for their traditional medicinal. This study investigated their phytochemical composition and bioactivities, with a particular focus on antioxidant and antibacterial properties. Methods: Ethanolic flower extracts were analyzed by high-performance liquid chromatography (HPLC) and liquid chromatography–mass spectrometry (LC–MS). Antioxidant activities were determined by DPPH, ABTS, and FRAP assays. Antibacterial activity against Escherichia coli, E. coli O157:H7, Salmonella Typhi, Shigella dysenteriae, and Vibrio cholerae were assessed by agar well diffusion, broth dilution methods, and time–kill assays. Biofilm formation, biofilm disruption, and bacterial adhesion to Caco-2 cells were evaluated. Morphological changes in E. coli O157:H7 were examined using scanning electron microscopy (SEM), and leakage of intracellular contents (DNA, RNA, proteins) were quantified. Results: HPLC analysis revealed the highest level of gallic acid in M. ferrea and quercetin in M. siamensis. LC–MS analysis identified fifteen putative metabolites across the flower extracts, including quercetin, kaempferol, catechin, and luteolin derivatives, with species-specific profiles. C. ternatea extract exhibited the greatest total flavonoid content and antioxidant activity. Among the extracts, M. ferrea exhibited the strongest inhibitory effect, with inhibition zone of 13.00–15.00 mm and MIC/MBC values of 31.25–62.5 mg/mL. All extracts exhibited time-dependent bactericidal activity, significantly inhibited biofilm formation, disrupted established biofilms, and reduced bacterial adhesion to intestinal epithelial cells. SEM revealed membrane disruption in E. coli O157:H7 and leakage of intracellular components. Conclusions: Thai medicinal flower extracts, particularly M. ferrea, possess strong antioxidant and antibacterial activities. Their ability to inhibit biofilm formation, interfere with bacterial adhesion, and disrupt bacterial membranes highlights their potential as natural alternatives for preventing or controlling enteric bacterial infections. Full article

Background/Objectives: In recent years, silver complexes have shown strong antibacterial, antifungal, and antitumor activity with high selectivity toward cancer cells. Their cytotoxic effects are mainly linked to apoptosis induction, DNA damage, and enzyme inhibition, while the antitumor activity of silver(I) complexes with S-alkyl thiosalicylic acid derivatives remains unexplored. Methods: Silver(I) complexes with S-alkyl derivatives of thiosalicylic acid (C1–C5) were obtained through the direct reaction of silver(I) nitrate, the corresponding ligand of thiosalicylic acid, and a sodium hydroxide solution. The interactions between the complexes and CT-DNA/BSA were studied using UV-Vis, fluorescence spectroscopy, and molecular docking studies. The cytotoxic capacity of the newly synthesized complexes was assessed by an MTT assay. Results: Complexes C1–C5 exhibited strong cytotoxicity against murine and human breast (4T1, MDA-MB-468), colon (CT26, HCT116), and lung (LLC1, A549) cancer cell lines. The C3 complex significantly diminished tumor progression in an orthotropic mammary carcinoma model while demonstrating good systemic tolerance. Conclusions: The tested complex C3 triggered apoptosis in 4T1 cells by altering the delicate balance between pro- and anti-apoptotic Bcl-2 family members, increasing reactive oxygen species (ROS) levels, and reducing mitochondrial membrane depolarization. Moreover, the C3 arrested the 4T1 cell cycle in G0/G1 phase, decreasing the expression of cyclin D3 and increasing the expression of p16, p21, and p27. Full article

Background: As a key contributor to metabolic disorders, obesity is recognized as a critical global health challenge. Adipocyte differentiation depends on the mitotic clonal expansion (MCE) phase, which is controlled by oxidative balance and transcription factors like C/EBPβ. Sesaminol, a lignan derived from Sesamum indicum, has potent antioxidant properties. This study aimed to investigate whether sesaminol suppresses adipogenesis by modulating ROS signaling, MCE, and the Nrf2-ARE pathway. Methods: In the early period of adipogenic induction, 3T3-L1 preadipocytes received treatment with sesaminol. Adipogenic development was evaluated through Oil Red O staining together with the assay of GPDH activity. Assays of cell proliferation and expression of cell cycle-related proteins, along with ROS measurement, qRT-PCR, Western blotting, and immunofluorescence, were performed to evaluate the effects on oxidative stress, transcriptional regulation, and AMPK-Nrf2 signaling. Results: Sesaminol significantly inhibited lipid accumulation and GPDH activity without cytotoxicity. It suppressed MCE by inhibiting DNA synthesis and reducing the expression of cyclin E1/E2 and CDK2. Sesaminol decreased C/EBPβ expression and its nuclear localization, resulting in lower levels of C/EBPα and PPARγ. It also reduced intracellular ROS, promoted nuclear translocation of Nrf2, and upregulated antioxidant genes HO-1 and GCLC. AMPK phosphorylation was concurrently enhanced. Conclusions: Sesaminol inhibits early adipogenesis by suppressing ROS-mediated MCE and activating the AMPK-Nrf2-ARE signaling pathway, leading to downregulation of key adipogenic transcription factors. The present study supports the potential of sesaminol as an effective strategy for obesity prevention. Full article

Vitamin D deficiency is highly prevalent in Pakistan, but there is limited data on its genetic aspects. This case–control pilot study aimed to determine the association of rs782153744, rs200183599, rs118204011, and rs28934604 with vitamin D deficiency along rs7041 which has been studied in our population. The DNA of a total of 600 subjects (300 cases and 300 controls) was extracted and genotyped by tetra ARMS PCR, followed by Sanger DNA sequencing of exon 4 of the CYP2R1 and CYP27B1 genes and exon 8 of the GC gene. SNP Stat was employed to analyze the data, while logistic regression was used to calculate the p-values and odds ratios (ORs). The R package version R studio (2025.05.1) Build 513 was used to statistically analyze rs782153744. In silico modeling of wild and mutant CYP2R1 and GC proteins was performed in Swiss-Model, Swiss-Dock, Discovery Studio, and PyMol using 3c6g and IJ78 as templates to perform binding pocket analysis of vitamin D3. The rs782153744 showed a protective association in the additive (OR: 0.15, 95% CI: 0.08–0.27, p-value < 0.001), recessive (OR: 0.19, 95% CI: 0.10–0.33, p-value < 0.001), and dominant (OR: 0.19, CI = 0.10–0.33, p-value < 0.001) models, while GC rs7041 (T > A, T > G) displayed a p-value < 0.0001 across all genetic models. Sanger sequencing yielded insignificant results, and the SNPs rs200183599, rs118204011, and rs28934604 had no significant association with vitamin D deficiency. The molecular pocket analysis of wild and mutant CYP2R1 proteins carrying rs782153744 polymorphisms revealed no changes. GC proteins carrying the rs7041 polymorphism revealed a shift in their 3D and 2D configuration, as well as a change in the amino acid residue of the binding pocket of VD3. The risk-associated rs7041 and protective rs782153744 variants back genetic screening for vitamin D deficiency risk stratification, allowing targeted supplementation in predisposed subjects and assisting in formulating a genotype-specific therapeutic approach. Full article

Pseudorabies virus (PRV), a major swine pathogen, causes severe neurological, respiratory, and reproductive disorders, resulting in substantial economic losses to the global swine industry. Previous studies have shown that the gD glycoprotein of PRV has an effective protective effect. In this study, we constructed a plasmid DNA vaccine (pVAX1-GD-Fc) encoding a gD protein fused with pig IgG Fc and evaluated the adjuvant effects of porcine cGAS, the universal STING complex mimic (UniSTING), or IFN-α in mice. The mice were immunized three times (days 0, 14, and 21) with pVAX1-GD-Fc in the presence or absence of an adjuvant, followed by lethal challenge with PRV-HLJ8 3 days after the final immunization. The results revealed that the pVAX1-GD-Fc group exhibited 20% mortality (1/5 mice) on day 7 postchallenge, and all adjuvanted groups achieved 100% survival during the 14-day observation period. Flow cytometric analysis of splenocytes one week after the second immunization revealed significantly greater CD8+ T cell proportions in the adjuvant groups than in both the mock and pVAX1-GD-Fc-only control groups (p < 0.01). Furthermore, T cell proliferation assays demonstrated a significantly increased stimulation index in the adjuvant-treated mice, confirming enhanced cellular immunity. These findings demonstrate that cGAS, UniSTING, and IFN-α can serve as effective vaccine adjuvants to rapidly enhance cellular immune responses to PRV, highlighting their potential application in veterinary vaccines. Full article

Acquired Immunodeficiency Syndrome (AIDS) is caused by Human Immunodeficiency Virus (HIV), and continues to be responsible for a substantial number of deaths worldwide each year. Development of a robust and efficient HIV-1 vaccine remains a critical priority. Structural analysis of viral proteins provides a foundational approach to designing peptide-based immunogenic vaccines. In the current experiment, we used computational prediction approaches alongside molecular docking and molecular dynamics (MD) simulations to identify potential epitopes within gp120 and Nef proteins. The selected co-epitopes were fused with the HBsAg-binding protein (SBP), a 344-amino acid protein previously identified in our laboratory through screening of a human liver cDNA expression library against HBsAg, to facilitate efficient delivery to and uptake by dendritic cells (DCs), thereby enhancing antigen (Ag) presentation. Flexible linkers are used to connect B cells, Helper T Lymphocytes (HTLs), and Cytotoxic T Lymphocytes (CTLs) in a sequential manner. The assembled vaccine construct comprises 757 amino acids, corresponding to a recombinant protein of 83.64 kDa molecular weight. Structural analysis through docking studies, MD simulations, and 3D structure validation revealed that the designed protein exhibits high structural stability and potential for interaction with Toll-like receptors (TLRs). These findings support the vaccine’s ability to enhance cellular and humoral feedback, including the stimulation of T and B cells and induction of antibody (Ab) production. The results underscore the promise of this in silico designed co-epitope vaccine as a viable candidate for HIV-1 prevention and suggest that such constructs may serve as effective immunogens in future HIV-1 vaccine strategies. Full article

Background: Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic diabetes forms that are frequently misclassified as type 1 or type 2 diabetes due to overlapping phenotypic features. The true prevalence of MODY is likely substantially underestimated. As DNA-based diagnostics become increasingly accessible, an expanding number of novel genetic variants are being identified. Objectives: The aim of this study was to characterize the clinical and genetic features of patients carrying rare variants in the BLK, KLF11, PAX4, PDX1, and CEL genes, with attention to population-specific aspects, family history, and treatment outcomes. Methods: Targeted next-generation sequencing (NGS) using a custom-designed panel covering 27 genes implicated in MODY, neonatal diabetes, and related hereditary syndromes was performed on the Illumina NovaSeq 6000 platform (Illumina). Results: We identified 21 variants in five genes associated with rare MODY subtypes among 24 unrelated patients. MODY9 was diagnosed in two unrelated patients of Russian ethnicity harboring an identical heterozygous missense mutation in exon 5 of the PAX4 gene (HG38, chr7:127615049G>A, c.191C>T, p.Thr64Ile), which has not been previously described in patients with diabetes. MODY11 was diagnosed in a patient carrying the c.773-1G>A variant in the BLK gene. A patient with a de novo c.40_41dupGC (p.Val15Glnfs*41) variant in the KLF11 gene was clinically diagnosed with type 1 diabetes. Conclusion: Our findings expand the current understanding of rare MODY subtypes and contribute to the growing body of evidence on the spectrum and frequency of potentially pathogenic variants in BLK, CEL, KLF11, PDX1, and PAX4 genes across ethnically diverse populations worldwide. Full article

Taste and odor (T&O) compounds in freshwater are frequently produced by certain cyanobacteria; however, their occurrence remains difficult to predict. This study examined the temporal and spatial variations in the mibC gene, which encodes a critical enzyme in the biosynthesis of 2-methylisoborneol (2-MIB), by analyzing environmental DNA (eDNA) and RNA (eRNA) in the North Han River, Republic of Korea, from July 2019 to October 2021. Surface water was sampled at twelve sites and analyzed for mibC DNA copy number, RNA expression, cyanobacterial cell density, and 2-MIB concentration using quantitative PCR (qPCR), microscopy, and gas chromatography–mass spectrometry (GC–MS). The mibC gene was present throughout the year, exhibiting peaks from late summer to early winter; higher concentrations typically initiated upstream and subsequently moved downstream. RNA expression was elevated from summer to autumn, rapidly declined following heavy rainfall, and reliably preceded increases in 2-MIB concentrations by 2–4 weeks. RNA levels were strongly correlated with 2-MIB concentrations (r = 0.879, p < 0.001) but showed only a moderate association with Pseudanabaena cell density, whereas DNA demonstrated weaker correlations. More than 95% of total 2-MIB was dissolved, limiting the ability to directly estimate concentrations from eRNA data alone. The results indicate that eRNA monitoring is an effective early warning tool for T&O events. In addition, combining eDNA and eRNA analyses enables a more accurate evaluation of T&O-producing cyanobacteria, presenting practical benefits for proactive management of drinking water. Full article