This study evaluated the independent relationship between the serum uric acid-to-creatinine ratio (UA/Cr) and sarcopenia phenotypes under the latest AWGS 2025 criteria, alongside the moderating role of physical activity (PA). Data were analyzed from 3,685 participants (aged ≥ 50 years) in the 2015 China Health and Retirement Longitudinal Study (CHARLS). Firth’s logistic regression and linear models assessed associations between UA/Cr and muscle phenotypes, while diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. In the fully adjusted model, UA/Cr was significantly associated with increased sarcopenia risk (OR = 1.122, 95
China aster (Callistephus chinensis) is an economically important ornamental crop widely cultivated for cut flowers and landscaping. During field surveys conducted in three districts of Karnataka, India, China aster plants exhibiting chlorotic and necrotic ring spots, leaf deformation, and witches’ broom symptoms were collected and analyzed to determine the causal agents. Mechanical inoculation of symptomatic leaf sap onto cowpea (Vigna unguiculata cv. C-152) produced characteristic chlorotic and necrotic ring spots on newly emerging leaves indicating the presence of an infectious viral agent. Serological assay by DAC-ELISA followed by RT-PCR confirmed the presence of tomato spotted wilt virus (TSWV, Orthotospovirus tomatomaculae) in symptomatic plants. Similarly the plants exhibiting witches’ broom symptoms tested positive for phytoplasma infection using universal and Nested primers PCR assays targeting the 16S rRNA gene. Sequence analysis of TSWV CP gene revealed more than 97
This study reports the development of a recombinant Bacillus ligniniphilus L1 laccase–rice straw biochar composite and its application in deltamethrin bioremediation. The L1-laccase was heterologously expressed in E. coli BL21 (DE3), purified to a specific activity of 186 U/mg, and covalently immobilized on NaOH- and glutaraldehyde-modified rice straw biochar. Molecular docking against the AlphaFold2-predicted structure (UniProt E9PZ36) yielded a binding affinity of − 6.9 kcal/mol, with one hydrogen bond to MET216 (2.77 Å) and hydrophobic contacts with MET197, MET202, and MET210. However, 100 ns molecular dynamics simulations confirmed a conformationally stable complex (RMSD 0.42 nm, radius of gyration 2.21 nm, SASA 215 nm2). Immobilization shifted the activity optima from pH 7.5 and 45 °C (free) to pH 8.0 and 50 °C (immobilized) and markedly improved stability: the immobilized enzyme retained 74
Infantile hemangioma is a common vascular tumor in infants, and propranolol efficacy varies with drug form and signaling context. This study used an integrated analysis pipeline combining assays of hemangioma endothelial cells (HemECs), receptor–ligand simulation, transcriptomics, and pathway perturbation to compare R-propranolol, S-propranolol, and racemic propranolol. R-propranolol showed the strongest cellular inhibition, reducing 72-h viability to 44.2 ± 3.5
Glioma is an aggressive brain tumor with limited therapeutic options, highlighting the need for the development of effective nanomaterial-based anticancer agents. In the present study, silver (Ag)-doped nickel oxide (NiO) nanoparticles were green synthesized using Psidium guajava leaf extract and characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), UV–Vis spectroscopy, Fourier transform infrared (FTIR) spectroscopy, and dynamic light scattering (DLS). XRD confirmed the formation of crystalline cubic NiO with successful Ag incorporation, while FESEM revealed quasi-spherical nanoparticles with an agglomerated porous morphology. UV–Vis spectroscopy exhibited characteristic absorption bands at 268 and 398 nm, FTIR confirmed Ni–O vibrations and phytochemical functional groups involved in nanoparticle stabilization, and DLS analysis showed a median hydrodynamic diameter of 56.50 nm. The anticancer activity of the nanoparticles was evaluated against C6 rat glioma cells. Ag-doped NiO nanoparticles significantly decreased cell viability in a concentration-dependent manner after 72 h, with an IC₅₀ value of 24.67 µg/mL, and markedly increased lactate dehydrogenase (LDH) release, indicating enhanced cytotoxicity. Acridine orange/ethidium bromide staining demonstrated significant apoptosis induction, with apoptotic cells increasing to 36.67 ± 1.38
Microproteins, are tiny proteins encoded by small open reading frame (sORF), translation of these non-canonical open reading frames (ncORFs) has been implicated in diverse biological processes and diseases. This review summarizes recent developments in the discovery, biogenesis, and functional characterization of microproteins, and their involvement in various disease, with special focus on their roles in cancer, cardiovascular, metabolic, neurodegenerative and immune-related disorders. We emphasize the regulation of key cellular pathways by microproteins, including mitochondrial homeostasis, apoptosis, metabolic reprogramming, and immune signaling, all of which affect disease initiation and progression. Emerging evidence also supports their potential as disease biomarkers and therapeutic candidates for precision medicine. Finally, the review critically discusses the current challenges including discrepancies in microprotein annotation, the limitations of ribosome profiling and proteogenomic approaches, the gap between computationally predicted and experimentally validated microproteins, and the need for rigorous orthogonal validation by means of CRISPR-based genome editing, ribosome release assays, mutational analysis, high-resolution mass spectrometry, and functional studies. Finally, we review recent development of AI-assisted ORF prediction, single-cell translatomics, spatial proteomics, and integrated multi-omics as emerging technologies reshaping. Microprotein discovery and functional annotation. Finally, we discuss the translational potential of microproteins and highlight the remaining challenges to clinical application, including peptide stability, pharmacokinetics, tissue-specific delivery, immunogenicity, and the need for rigorous preclinical and clinical validation. Together, this review provides an updated and critical overview of the rapidly evolving microprotein field and highlights future research priorities for translating these molecules into clinically useful biomarkers and precision therapeutics.
High plasma Epstein–Barr virus (EBV)-DNA load may be associated with host immune dysregulation and secondary infection in children, although the underlying mechanisms remain uncertain. This study analyzed peripheral blood samples from 34 children with high plasma EBV-DNA load and 31 children with low plasma EBV-DNA load using transcriptomic analysis, WGCNA, CIBERSORT-based deconvolution, LASSO regression, Random Forest, qPCR, ELISA, and flow cytometry to explore immune features associated with EBV-DNA load and secondary-infection status. A total of 459 differentially expressed genes were identified. In the high-load group, antiviral and inflammatory pathways were significantly upregulated, whereas adaptive immune pathways were suppressed, revealing a pattern of innate immune hyperactivation together with impaired adaptive cellular immunity. CIBERSORT analysis estimated higher neutrophil and monocyte proportions and lower CD8⁺ T-cell and NK-cell proportions in the high-load group; these deconvolution estimates should not be interpreted as direct cell counts. Multi-strategy integrative analysis prioritized STAT1, CXCL10, and IL6 as candidate immune-related markers; their expression was positively associated with plasma EBV-DNA load and was higher in the secondary-infection group than in the non-infection group. Within this cohort, the combined three-gene model yielded an AUC of 0.85 for discriminating secondary-infection status and should be considered exploratory pending independent validation. Experimental validation was directionally consistent with the bioinformatic findings and supports an association between high plasma EBV-DNA load, circulating immune dysregulation, and secondary-infection status; it does not establish a causal mechanism.
Genetic variability and habitat suitability of common juniper (Juniperus communis L. var. saxatilis Pall.) were investigated across seven natural populations (71 individuals) from the Western Himalayan Region (WHR), India using 22 ISSR and 11 DAMD markers coupled with ecological niche modelling. A cumulative polymorphism of 75.90
A significant surge in antimicrobial resistance has rendered the researchers to explore alternative management strategies based on medicinal plants to combat with sturdy infectious agents including biofilm forming strains. Desmodium gangeticum (DG) is employed as traditional medicine having significant pharmacological properties. Therefore, in this study, plant leaf extracts prepared in acetone, ethyl acetate and methanol were analysed to explore its phytochemical composition, antioxidant potential, antibacterial activity, antibiofilm property along with molecular docking studies of GC-MS based compounds. The antioxidant analyses collectively suggested that the methanolic extract had the highest antioxidant activity with an IC50 concentration of 84.37 ± 4.5 µg/mL against DPPH with antioxidant capacity of 159.1 ± 13.68 µg ascorbic acid equivalent/mg of dried extract. The antibacterial and antibiofilm evaluation of the extract revealed that ethyl acetate had the highest antibacterial activity with the lowest MIC (0.61 ± 0.2 mg/mL) with MBC of 3 mg/mL and the highest biofilm disruption (88.95 ± 0.77
Plant developmental stages represent important endogenous drivers shaping rhizosphere microbiome assembly and functional potential. However, how rhizosphere microbial communities of Artemisia lavandulifolia shift across distinct phenological stages remains largely unexplored. To address this knowledge gap, we employed high-throughput sequencing to comprehensively characterize the rhizosphere bacterial and fungal communities of A. lavandulifolia during the early vegetative stage (EVS) and late vegetative stage (LVS). Additionally, quantitative PCR was used to determine the absolute abundance of bacterial 16S rRNA, fungal ITS genes, and key functional genes related to carbon, nitrogen, and phosphorus cycling. The results revealed significantly higher α-diversity in both bacterial and fungal communities at LVS compared to EVS (p < 0.05). Co-occurrence network analysis revealed that microbial co-occurrence patterns became increasingly complex with plant development, as evidenced by greater numbers of nodes and edges in both bacterial (1189 vs. 1049 nodes; 98,550 vs. 76,390 edges) and fungal (373 vs. 230 nodes; 6932 vs. 4509 edges) networks during LVS. Notably, absolute abundances of functional genes mediating carbon fixation (cbbLR), nitrogen cycling (amoA), and phosphorus mineralization (phoD) were significantly elevated at LVS relative to EVS (p < 0.05). Collectively, these findings demonstrate that plant ontogeny is associated with stage-dependent shifts in the functional potential of the A. lavandulifolia rhizosphere microbiome, suggesting adaptive adjustments in microbially mediated nutrient cycling to meet heightened host metabolic demands during late vegetative growth.
The study aimed to screen 40 lactic acid bacterial isolates from kimchi types to isolate Latilactobacillus (L.) sakei strains for their probiotic potential. Based on random amplified polymorphic DNA-based initial screening, 16 S rRNA-based phylogeny, and species-specific PCR, three sakei strains (RKA, RKC, and TAB) were selected for evaluating their probiotic and functional attributes. The selected strains demonstrated probiotic characteristics, including acid tolerance (33–85
Adenosine deaminase acting on RNA (ADAR)-mediated adenosine-to-inosine (A-to-I) RNA editing is of significant biological and clinical relevance in human tumors. Although papillary thyroid carcinoma (PTC) is frequently characterized as an “inert” tumor, it nonetheless presents a potential risk to human health. This study elucidates the regulatory mechanisms of both wild-type and modified microRNA-376a-3p (miR-376a-3p) in PTC. To assess miRNA and gene expression, RT-qPCR, Western blotting, and immunohistochemistry were employed. Functional assays included CCK-8, colony formation, 5-ethynyl-2′-deoxyuridine (EdU), wound healing, Transwell, and flow cytometry. Glycolytic activity was measured by glucose consumption, lactate production, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR). Downstream targets were identified via dual-luciferase reporter assay. In PTC tissues, the A-to-I editing level of miR-376a-3p was elevated. ADAR2 (ADARB1) was identified as the principal editing enzyme, contributing to PTC carcinogenesis. Functionally, A-to-I editing switched miR-376a-3p from an anti-tumorigenic to an oncogenic molecule. At the molecular level, edited miR-376a-3p (ed-miR-376a-3p) acquired HOXD10 as a novel target while losing its interaction with KPNA4. Mechanistically, ed-miR-376a-3p enhanced glycolysis in PTC cells by downregulating HOXD10. ADAR2-mediated A-to-I editing confers an oncogenic role on miR-376a-3p by shifting its target from KPNA4 to HOXD10, thereby facilitating PTC tumorigenesis through enhanced glycolysis.
Diabetic nephropathy is one of the leading microvascular complications of diabetes mellitus and a major cause of chronic kidney disease worldwide. Oxidative stress and chronic inflammation play central roles in its progression. Erucic acid is a naturally occurring monounsaturated omega-9 fatty acid with reported antioxidant and anti-inflammatory properties. We evaluated the renoprotective effects of erucic acid in streptozotocin (STZ)-induced diabetic nephropathy in rats using biochemical and histopathological analyses. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg), followed by oral administration of erucic acid (10 and 20 mg/kg) once daily for 8 weeks. Erucic acid significantly improved glycemic control by reducing blood glucose and HbA1c levels, increasing insulin and adiponectin levels, and decreasing resistin levels. It also ameliorated dyslipidemia by reducing total cholesterol and triglyceride levels and increasing HDL levels. Renal function was significantly improved, as evidenced by reduced serum creatinine, blood urea nitrogen, urinary albumin excretion, and 24-h urine volume, along with increased creatinine clearance and preservation of renal histoarchitecture. Erucic acid restored antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione), reduced malondialdehyde and nitric oxide levels, downregulated pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and decreased the renal injury biomarkers KIM-1 and NGAL. These findings demonstrate that erucic acid exerts antioxidant, anti-inflammatory, and renoprotective effects against STZ-induced diabetic nephropathy and may represent a promising therapeutic candidate for diabetic kidney disease.
Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance (IR), with chronic low-grade inflammation, oxidative stress, and mitochondrial dysfunction contributing to disease progression. Banxia Xiexin Decoction (BXXD), a classical traditional Chinese medicine (TCM) formula, has shown clinical efficacy against T2DM, but its bioactive components and molecular mechanisms remain unclear. This study aimed to elucidate the therapeutic mechanism of BXXD against T2DM by integrating network pharmacology, genetic causal inference, chemical profiling, and in vivo validation.Network pharmacology identified BXXD-T2DM overlapping targets and enriched pathways. Summary-data-based Mendelian randomization (SMR) and molecular docking assessed causality and binding affinity. Bioactive constituents were characterized by UHPLC-Q-Orbitrap HRMS. Mechanisms were validated in high-fat diet/streptozotocin (HFD/STZ)-induced diabetic C57BL/6J mice treated with BXXD for 8 weeks.Network pharmacology identified 217 targets, highlighting IL-1β, TNF-α, AKT1, PPARG, and SIRT1, with AMPK signaling highly enriched. SMR indicated that AKT1 and SIRT1 were causally associated with T2DM risk. UHPLC-Q-Orbitrap HRMS of BXXD-containing serum identified 18 prototype compounds and 53 metabolites, and quercetin, kaempferol, and wogonin stably bound the key targets. In vivo, BXXD lowered fasting blood glucose, HOMA-IR, and GTT/ITT AUCs; reduced TNF-α, IL-1β, ROS, and MDA; restored SOD activity; and preserved adipose tissue morphology. Mechanistically, BXXD activated AMPK/SIRT1 signaling, enhanced mitophagy (increased PINK1, Parkin, and LC3-II/LC3-I; decreased p62), and upregulated PPARG and p-AKT1.BXXD alleviates T2DM-associated metabolic dysregulation by activating the AMPK/SIRT1-mitophagy axis and suppressing inflammation, providing mechanistic evidence supporting further translational investigation of BXXD for T2DM.
CRISPR/Cas9-mediated targeted mutagenesis of GmMYB100 was used to generate genome-edited soybean (Glycine max (L.) Merrill cv. JS335) lines with enhanced isoflavone accumulation. A single guide RNA targeting the first exon of GmMYB100 was cloned into the pHSE401 vector and introduced into soybean via Agrobacterium tumefaciens strain EHA105. Molecular characterization of stable T0 plants confirmed the integration of the Cas9 and hptII genes, while sequence analysis identified insertion/deletion (indel) mutations at the target site, confirming successful genome editing. The edited lines (T0) showed significantly increased isoflavone accumulation, with daidzein and genistein contents increasing by 2.85-fold and 1.23-fold, respectively, compared with non-transformed plants. Quantitative RT-PCR analysis revealed significant upregulation of major isoflavone biosynthetic genes in immature cotyledons, mature cotyledons, and seeds, consistent with the enhanced metabolite accumulation. These results demonstrate that disruption of GmMYB100 relieves negative regulation of the isoflavonoid biosynthetic pathway, leading to increased isoflavone production in soybean seeds. The study establishes GmMYB100 as an effective target for CRISPR/Cas9-mediated metabolic engineering and provides a practical strategy for improving the nutritional quality of soybean through precise genome editing.
The biocatalytic production of D-tagatose, a valuable low-calorie sweetener, is often hindered by poor enzyme stability and limited reusability. To address this issue, a thermostable tagatose-4-epimerase (TpT4Ease) from Thermotoga petrophila was crosslinked with glutaraldehyde followed by immobilization on an amino-functionalized macroporous resin (LX-1000HA), resulting in TpT4Ease@LX-1000HA-GA.The effective synthesis of TpT4Ease@LX-1000HA-GA was verified by CD and SEM after optimization of the immobilization procedure. Kinetic analysis revealed that the conformational constraint within the porous support slightly compromised intrinsic turnover but effectively prevented thermal unfolding. Consequently, TpT4Ease@LX-1000HA-GA displayed improved thermal and storage stability, with its half-life at 70 °C extended to 15.4 h compared to 3.3 h for the free enzyme. Under optimized continuous-flow conditions (200 g/L fructose, 70 °C, 0.5 mL/min), TpT4Ease@LX-1000HA-GA achieved an efficient bioconversion of D-fructose to D-tagatose with a yield of 17.3
Gene and cell therapies have emerged as transformative approaches for treating a wide range of genetic and acquired diseases. Central to their success is the development of safe and effective gene delivery systems, categorized broadly into viral and non-viral vectors. Each system has its own advantages and limitations, requiring careful consideration of the target tissue, disease, and the balance between safety, efficacy, and scalability. Viral vectors, including adeno-associated viruses, retroviruses, lentiviruses, herpes simplex viruses, and adenoviruses, offer high transduction efficiency and specificity but raise concerns about immunogenicity and production challenges. Non-viral systems, such as lipid nanoparticles (LNPs) and other synthetic carriers, provide scalable, cost-effective, and potentially safer alternatives but often face hurdles in transduction efficiency and targeted delivery. This review provides a comprehensive overview of the current status of these vector systems for in vivo and ex vivo applications. Key comparisons are made across safety, efficacy, scalability, and immune responses, highlighting recent advancements and innovative approaches. We also discuss the outlook for next-generation gene transfer technologies, focusing on improvements in vector design, manufacturing, and application versatility. By addressing these considerations, we aim to inform the development of optimized therapeutic strategies that leverage the unique strengths of each delivery system.
The current study holds major socio-economic importance of East Kolkata Wetland (EKW) in India, a Ramsar site, presently under constant threat of anthropogenic wastes that could accelerate antibiotic resistance (AR). The underlying mechanism behind the spread of AR in EKW requires proper investigation. Towards this direction, we focused on the isolation of antibiotic resistant bacteria (ARB) from EKW with adequate characterization by employing biochemical, molecular and antibiotic sensitivity tests. Thus, water samplings were carried out and a total of 32 ARB were isolated from three different study sites at EKW by selective agar plating. The isolates exhibited diverse biochemical properties with multi-antibiotic resistance (MAR) index exceeding 0.2 against 14 antimicrobial agents. MAR is strongly linked with biofilm formation. For comprehensive understanding of MAR among the isolates, their biofilm forming ability was checked. Henceforth, 14 potent biofilm formers were identified by measuring the total biofilm biomass through crystal violet (CV) assay and light microscopy. Furthermore, extracellular polymeric substance (EPS), metabolic activity, auto-aggregation property along with their motility pattern also confirmed their strong biofilm forming ability. Considering their pathogenicity, few exhibited hemolytic activities. Subsequently, these potent biofilm formers were identified by 16S rRNA gene and phylogenetic approach. These biofilm forming ARB in waterbodies of EKW requires vigilant monitoring before it is recycled for household, aquaculture and agricultural activities. Hence this study requires attention from the viewpoint of Sustainable Developmental Goals (SDGs) particularly related to good health (SDG 3) in the context of ensuring clean, sanitary water (SDG 6) and managing life below water (SDG 14).
The current hypothesis investigated the neurotrophic effect of magnolol (ML) against MPTP/p-induced neurotoxicity in Parkinson’s disease (PD) mice, focusing on the molecular mechanisms of PI3K/Akt/GSK3β and MAPK signalling pathways. To determine the effective dose, 6 mice/group were employed for the dose-dependent study and brain-protective study. Behavioural deficits (open field test, narrow beam walking), dopamine (DA) depletion, lipid peroxidation, antioxidant levels, histology (H E, PAS, and MT), inflammatory cytokines, DAT and VMAT2 expressions, SN region expressions of BDNF, GDNF, VEGF, and TrkB, RT-PCR of p38, MAPK, ERK, and JNK, and GSK3β/mTOR/PI3K/Akt signalling protein marker expression were evaluated. After 5 weeks of ML therapy, motor impairment significantly decreased, and lipid peroxidation, antioxidant levels, and inflammatory cytokines were restored. ML increased tropomyosin receptor kinase B (TrkB) expression, dopamine insufficiency, and MPTP/p-induced neurotrophic factors. ML therapy significantly decreased mRNA activation associated with MAPK/p38/JNK. Furthermore, ML increased PI3K, Akt, GSK3β, and mTOR phosphorylation, suggesting ML controlled the PI3K/Akt/mTOR signalling pathway. Altogether, this study offers a more thorough examination of the brain-protective effect of ML on dopaminergic neurons when combined with chronic PD. Additionally, it brings up the possibility of using ML as a new preventive and therapeutic drug. Study limitations include use of an acute MPTP/p model rather than progressive PD, absence of pharmacokinetic data, and no pathway confirmation using inhibitors. Long-term efficacy and clinical translation require further investigation.
Taro leaf blight, caused by Phytophthora colocasiae, is the most destructive disease of taro (Colocasia esculenta L. Schott), resulting in severe yield losses and posing a major constraint to sustainable cultivation. The present study investigated the biocontrol potential and plant growth-promoting attributes of 24 antagonistic bacterial endophytes isolated from healthy taro plants. Antagonism by diffusible metabolites exhibited stronger antagonistic activity than volatile metabolites, with mycelial growth inhibition ranging from 19.77 to 76.29
