Search Results (4,779)

Lithium metal batteries (LMBs) have been widely studied due to their high energy density; however, the practical implementation of LMBs is limited by issues of uncontrolled dendrite growth, continuous electrolyte decomposition, and poor Coulombic efficiency (CE). Highly concentrated electrolytes (HCEs) have emerged as a promising approach to addressing the above issues. In this work, we propose a new HCE system based on a single carbonate solvent of 2,2,2-trifluoroethyl methyl carbonate (FEMC) with a high concentration of lithium bis(fluorosulfonyl)imide (LiFSI). The resulting electrolytes exhibit enhanced anodic stability and improved compatibility with lithium metal anodes and high-voltage cathodes. The optimized 4 M LiFSI–FEMC HCE achieved the highest CE for Li plating/stripping in Li/Cu cell and lowest overpotential in Li/Li symmetric cells, outperforming both low-concentration FEMC and ethyl methyl carbonate (EMC)-based electrolytes. In full-cell configurations with LiNi_0.8Co_0.1Mn_0.1O₂ (NCM811) cathodes, the HCE demonstrates stable cycling with minimal capacity fade over 250 cycles. Importantly, the HCE enables stable operation of 4.6 V high-voltage NCM811/Li cells for more than 120 cycles with a high-capacity retention of 88.61%. Post-mortem analysis revealed a more uniform and compact solid electrolyte interphase and a thinner cathode electrolyte interphase, contributing to the enhanced cycling performance. Full article

Munronia pinnata (Meliaceae), a medicinal plant used in Zhuang traditional medicine, is recognized as a rich source of structurally diverse limonoids. In our continuing investigation of bioactive constituents from Guangxi medicinal plants, four new prieurianin-type limonoids, munropins G–J (1–4), were isolated from their aerial parts. Their structures were determined through comprehensive spectroscopic analysis, including nuclear magnetic resonance and high-resolution mass spectrometry, and further supported by quantum chemical calculations for electronic circular dichroism and statistical probability analysis. Munropins G (1) and H (2) feature an unprecedented C-12 β-D-glucosylated α-methyl-2′-hydroxypentanoate side chain and a C-17 β-substituted furan ring, with 1 being the 7-O-acetyl derivative of 2. Munropins I (3) and J (4) possess a formyl group at C-11, a 3-methyl-2-hydroxypentanoate ester at C-12, and a C-17 γ-hydroxy-α,β-unsaturated γ-lactone unit (21-hydroxy for 3, 23-hydroxy for 4), each existing as an equilibrating mixture of C-21 epimers—a phenomenon observed for the first time within a prieurianin-type framework. The absolute configurations of 1 and 2 were established by quantum chemical electronic circular dichroism calculations, while those of 3 and 4 remain to be assigned. All compounds were evaluated for cytotoxicity against human lung (A549), liver (HepG2), breast (MCF-7), and colon (HCT116) cancer cell lines and for anti-inflammatory activity in lipopolysaccharide-induced RAW 264.7 murine macrophages, but none exhibited significant effects at a concentration of 80 μM. This study expands the chemical diversity of Munronia limonoids and provides new molecular scaffolds for future structure–activity relationship investigations and chemotaxonomic markers for the Meliaceae family. Full article

Organophosphorus pesticide residues (OPPs) pose significant threats to ecological systems and human health, and conventional detection techniques are cumbersome, time-consuming, and costly. Herein, a facile electrochemical biosensor has been constructed based on a methyl green/chitosan (MG/Chi) composite membrane-modified electrode for the selective detection of OPPs, using isazofos (Isa) as the model analyte. Experimental results demonstrated that Isa significantly decreases the redox peak current of the modified electrode in buffer solution, and a good linear relationship was observed between the change in peak current and Isa concentration within a specific range. This biosensor exhibits excellent anti-interference capability and high sensitivity, with a limit of detection (LOD) as low as 0.60 μM. Furthermore, it was successfully applied for the quantitative determination of OPPs in real food and environmental samples, which confirms its reliable practical applicability and potential for on-site monitoring. Full article

Host receptors can detect traces of non-self-pathogenic RNAs within a sea of cellular mRNA molecules. In host cells, mRNA cap methylation occurs in the nucleus, generating Cap1 and Cap2 structures (m⁷GpppNm and m⁷GpppNmNm, respectively). By contrast, alphavirus genomes carry a Cap0 structure (m⁷GpppN), which lacks 2′-O-methylation. This difference in the structure of the host and viral caps serves as a molecular signature that enables discrimination between self and non-self RNAs. Several host immune sensors, such as RIG-I and IFIT1, recognize the alphavirus Cap0 structure and trigger an antiviral response to restrict viral replication. It has been proposed that IFIT1 sequesters aberrant RNAs, preventing their translation by host ribosomes and blocking viral protein synthesis. However, alphaviruses have evolved molecular strategies to circumvent IFIT1-mediated restriction and facilitate infection in mammalian cells. One such strategy involves the folding of a 5′ RNA structure that hides the cap from host immune sensors. This highlights the dynamic interplay between viral evasion tactics and host immune defenses. This review will discuss how specific modifications at the 5′ end of alphavirus RNA modulate host defenses and how a deeper understanding of the virus–host interaction may inform the development of novel vaccine strategies. Full article

Background/Objectives: Vascular inflammation and impaired endothelial regeneration contribute to chronic degenerative disorders, including ocular neovascularization and retinal degeneration. Nutritional bioactives that modulate molecular pathways governing angiogenesis and tissue remodeling represent promising adjunct strategies for vascular health. This study investigated whether cocoa powder (CP) regulates hypoxia-driven molecular signaling and attenuates vascular inflammation and degeneration. Methods: The vascular-modulatory effects of CP were examined in human umbilical vein endothelial cells (HUVECs) and in murine models of alkali-induced corneal neovascularization and N-methyl-N-nitrosourea (MNU)-induced retinal degeneration. Hypoxia-inducible factor-1α (HIF-1α) signaling and downstream angiogenic targets were assessed by Western blotting and quantitative PCR. Endothelial migration, tube formation, and transwell assays were performed to evaluate angiogenic responses. In vivo, oral CP (50 or 200 mg/kg) was administered, and vascular growth, inflammatory and remodeling markers, and retinal structural integrity were analyzed by histology, immunofluorescence, and protein expression. Results: At non-cytotoxic concentrations (0.1–1.0 μg/mL), CP suppressed hypoxia-induced HIF-1α protein stabilization without altering HIF-1α mRNA levels and reduced expression of VEGFA, EPO, and GLUT1. CP significantly inhibited VEGF-A-induced endothelial migration, network formation, and chemotactic invasion. In alkali-injured corneas, CP reduced the neovascularized area and downregulated VEGF, MMP2, MMP9, α-smooth muscle actin, and Ninj1, indicating attenuation of vascular inflammation and fibrotic remodeling. In the MNU model, CP preserved outer nuclear layer thickness, reduced glial activation (GFAP), maintained rhodopsin expression, and decreased MMP9 induction. Conclusions: CP functions as a nutritional modulator of hypoxia-responsive and inflammatory pathways, suppressing pathological angiogenesis while supporting structural preservation in degenerative vascular conditions. These findings highlight the translational potential of dietary polyphenol-rich interventions in regulating vascular inflammation and regeneration. Full article

Glucosylceramide synthase (GCS) catalyzes ceramide glycosylation in response to cell stress that produces glucosylceramide and other glycosphingolipids. GCS overexpression is a cause of drug resistance and enriches cancer stem cells (CSCs) during cancer chemotherapy. Previous studies showed that GCS modulates the expression of p53 mutants and oncogenic gain-of-function (GOF) in heterozygous knock-in cell models (TP53 R273H^−/+). However, it is unclear whether GCS can modulate the effects of homozygous p53 mutations, which are common in many cancer cases. We report herewith that inhibition of GCS, via UGCG knockout and using an inhibitor (Genz-161), effectively re-sensitizes drug resistance and diminishes CSCs in colon cancer cells carrying the homozygous p53 R273H mutation. In aggressive WiDr cells carrying TP53 R273H mutation, knockout of UGCG gene using CRISPR/Cas9 editing or inhibition of GCS with Genz-161 sensitized cancer cells to oxaliplatin, irinotecan and paclitaxel. With decreased ceramide glycosylation in lipidomic profiling, both UGCG knockout and Genz-161 treatments substantially decreased wound healing, and diminished CSCs and tumor growth under chemotherapy. Interestingly, inhibition of RNA m⁶A methylation by neplanocin A markedly increased p53 function and reversed drug resistance. Mechanistic investigation revealed that GCS inhibition downregulated methyltransferase-like 3 (METTL3) expression and decreased RNA-m⁶A modification on mutant p53 R273H effects. Altogether, our findings demonstrate that ceramide glycosylation promotes METTL3 expression and RNA m⁶A methylation in response to drug-induced stress, thereby promoting mutant p53 expression and associated GOF. Conversely, inhibition of GCS can diminish CSCs and drug resistance via reduction in m⁶A modification and advance of p53-assocaited tumor suppressive function. GCS inhibition is an achievable approach for mutant cancer treatment. Full article

The aim of the study was to investigate the relationship between air pollution exposure and gut microbiota-related biomarkers among a cohort of healthy school-age children. A cross-sectional biomonitoring study was conducted among 11-year-old healthy children living in central Italy. Selected urinary (u) volatile organic compounds (VOCs) (benzene, toluene, ethylbenzene, xylenes, methyl tertbutyl ether, ethyl tert-butyl ether, 2-methyl-2-butyl methyl ether, and diisopropyl ether) were measured as exposure biomarkers while u-indican and faecal (f) zonulin were assessed as indicators of gut dysbiosis and intestinal permeability, respectively. Socio-demographic and lifestyle data were collected through questionnaires. u-VOCs showed higher geometric means among children exposed to environmental tobacco smoke, living in urban areas, and those spending a longer time in motor vehicles. u-Ethylbenzene and u-toluene were the most abundant compounds (mean ± SD: 307 ± 118 ng/L and 188 ± 94 ng/L, respectively). Mean f-zonulin and mean u-indican were, respectively, 49.09 ± 18.41 ng/mL and 5.97 ± 3.50 mg/dL. A statistically significant positive correlation was observed between u-ethylbenzene and u-indican (p = 0.02) and between u-toluene and f-zonulin (p = 0.05). These findings provide preliminary evidence that air pollution may influence gut microbial metabolic activity and intestinal barrier regulation in children, supporting the need for larger longitudinal studies. Full article

Idiopathic Parkinson’s disease (iPD) represents the most prevalent form of Parkinson’s disease; however, the molecular mechanisms underlying its development remain only partially understood. N6-methyladenosine (m6A), the most abundant internal RNA modification in eukaryotic mRNA, has emerged as a key regulator of gene expression and has been implicated in neurodegenerative disorders. In this study, we performed integrated differential expression, weighted gene co-expression network analysis (WGCNA), and differential co-expression (DECO) analyses using peripheral blood RNA-seq data from Latin American controls and early iPD patients to investigate m6A-associated transcriptional alterations. WGCNA and differential expression analyses identified 1207 hub genes and 237 differentially expressed genes, respectively. The integration of these datasets with curated m6A-related genes yielded 12 overlapping candidate genes associated with early iPD. Subsequent DECO analysis revealed three significant m6A regulator–target differential co-expression links involving the m6A factors VIRMA, YTHDF3, and HNRNPA2B1. Experimental validation in an independent exploratory cohort confirmed altered expression of these regulators and increased m6A enrichment of NRCAM and PKHD1 transcripts. To our knowledge, this study represents the first integrative transcriptomic evaluation of m6A-associated regulatory patterns in early iPD within a Latin American population. Collectively, our findings suggest that selective m6A-associated transcriptional network alterations may contribute to the systemic molecular signatures observed in early iPD, warranting further validation in larger and mechanistically oriented studies. Full article

Background/Objectives. The actin-binding protein EPLIN (epithelial protein lost in neoplasm), also known as LIMA1, contributes to the maintenance of cytoskeleton structure and dynamic. This protein, which interacts with multiple partners to regulate cell adhesion and migration, has been implicated in the progression of solid tumors and in tumor metastasis. Consequently, small molecules binding to EPLIN are actively searched. EPLIN has been characterized as a molecular target for the antitumor antibiotic albacarcin V which affects the cytoskeletal structure and induces cell growth arrest. Methods. We have modeled the binding of albacarcin and naturally occurring derivatives to EPLIN conformers, in order to locate the drug-binding site and to identify additional EPLIN binders. Nineteen compounds were studied, including albacarcins V (vinyl) and M (methyl), five gilvocarcins, four ravidomycins, two chrysomycins, and six related products (including polycarcin and fucomycin). Results. The modeling analysis confirmed the capacity of albacarcin V to bind to EPLIN and identified a few better binders. In particular, ravidomycin V bearing a dimethylamino sugar unit were identified as the best binders in the series, along with the two related anticancer natural products FE35A-B. Structure-binding relationships are discussed. The drug-binding site has been localized near the central residue Asn34 in the conformationally constrained domain between the two zinc-binding regions. Conclusions. This study provides guidance to the design of EPLIN inhibitors based on the ravidomycin core structure. Full article

Oral fungal infections resulting from non-albicans Candida species and new opportunistic yeasts are increasingly linked to antifungal resistance, especially in individuals with periodontal disease. Bioactive compounds may serve as potential alternatives; nevertheless, there is a paucity of research that has comprehensively assessed their antifungal and antibiofilm efficacy against clinically defined oral yeast isolates. This study aimed to (i) describe the variety and antifungal resistance profiles of oral yeasts isolated from women with various periodontal diseases; (ii) assess four ethanolic extracts of Aseer medicinal plants (Foeniculum vulgare, Solanum incanum, Forsskaolea tenacissima, and Abutilon pannosum) for their antifungal and antibiofilm properties; and (iii) correlate phytochemical composition determined by GC–MS with biological activity. Oral samples (saliva and subgingival plaque) were collected from 50 female participants with documented periodontal parameters. Fungal isolates were identified using morphological, biochemical (VITEK 2), and molecular (ITS rDNA sequencing) methods. Testing for antifungal susceptibility was performed according to CLSI guidelines. Plant extracts were evaluated for antifungal activity (disk diffusion, MIC, MFC), antibiofilm activity (crystal violet assay and light microscopy), and phytochemical profiling (GC–MS). Fungal growth was detected in 37 of 50 samples (74%), yielding six yeast species: Nakaseomyces glabratus (40.5%), Candida tropicalis (18.9%), C. parapsilosis (13.5%), Pichia kudriavzevii (10.8%), Rhodotorula mucilaginosa (8.1%), and Aureobasidium melanogenum (8.1%). N. glabratus demonstrated reduced susceptibility to fluconazole. A. pannosum and F. vulgare exhibited the strongest in vitro antifungal activity (inhibition zones up to 19.2 mm; MIC 0.19–0.78 mg/mL; MFC 0.39–1.56 mg/mL), significantly greater than F. tenacissima (p < 0.0001). Sub-MIC concentrations of A. pannosum reduced C. tropicalis biofilm biomass by 59.6%. GC–MS analysis identified methyl salicylate (20.3–40.2%) and cyclohexanol derivatives (8.0–23.2%) as major constituents. Antifungal activity showed a trend in relation to methyl salicylate content (R² = 0.78). However, because only four plant extracts were included, this relationship should be interpreted as a descriptive observation rather than a statistically testable association. Ethanolic extracts of Abutilon pannosum and Foeniculum vulgare demonstrated significant in vitro antifungal and antibiofilm activity against clinically relevant oral yeasts, including azole-tolerant Nakaseomyces glabratus. The observed trends between phytochemical composition and biological activity warrant further investigation into their potential as adjunct therapeutic agents for oral fungal infections. Further studies are required to confirm these results and see if they can be used in therapeutic settings. Full article

Background: Breast cancer susceptibility gene 1 (BRCA1) is a pivotal regulator of DNA repair, and its loss through germline mutations is strongly linked to the development of aggressive breast cancers with characteristic clinical and pathological features. Beyond genetic disruption, epigenetic silencing via promoter hypermethylation has emerged as a non-mutational mechanism of tumour suppressor inactivation and a potential biomarker for guiding therapeutic decisions. Here, we investigate BRCA1 promoter methylation, its impact on gene expression, and its association with clinicopathological features in a cohort of African women with breast cancer. Methods: Matched tumour and adjacent normal tissues from 27 Black African women with breast cancer were analysed for BRCA1 promoter methylation and gene expression using bisulfite pyrosequencing and quantitative real-time PCR. Associations with clinicopathological variables were assessed using Spearman’s correlation analyses. Results: Five CpG sites within the BRCA1 promoter were significantly hypermethylated in breast tumours compared with matched adjacent normal tissues and showed an inverse association with BRCA1 mRNA expression. Elevated promoter methylation was enriched in hormone receptor-negative and triple-negative breast cancer subtypes and was not influenced by neoadjuvant chemotherapy. BRCA1 promoter methylation occurred independently of BRCA1 mutational status. No significant associations were observed between BRCA1 methylation and age, body mass index, smoking status, or alcohol consumption. Conclusions: Our findings provide evidence of BRCA1 epigenetic silencing in breast tumours from African women, particularly within aggressive hormone receptor-negative subtypes. These results suggest that BRCA1 promoter methylation may represent a clinically informative biomarker for patient stratification and highlight the importance of validation in larger, population-representative cohorts before clinical translation. Full article

Background: Heterogeneous nuclear ribonucleoprotein L-like (HNRNPLL) is an RNA-binding protein involved in alternative splicing and immune regulation; however, its role in liver hepatocellular carcinoma (LIHC) remains unclear. Methods: We performed integrative multi-omics analyses using data from TCGA, GEO, and the Human Protein Atlas to evaluate the expression patterns, prognostic value, and potential biological functions of HNRNPLL. Functional enrichment and immune-related analyses were conducted to explore associated pathways. Experimental validation was performed in LIHC cell lines using Western blotting, RT-qPCR, CCK-8, colony formation, and Transwell assays, along with a xenograft mouse model. Results: HNRNPLL was significantly upregulated in LIHC at both transcriptomic and proteomic levels and was associated with advanced clinicopathological features and poor overall survival. Multivariate Cox regression analysis identified HNRNPLL as an independent prognostic factor. Enrichment analyses suggested that HNRNPLL-related genes are mainly involved in cell cycle regulation, mitotic progression, epithelial–mesenchymal transition, and immune-related pathways. In addition, HNRNPLL expression was correlated with immune cell infiltration, tumor mutational burden, microsatellite instability, ferroptosis-related genes, and m6A methylation regulators. Functional experiments demonstrated that HNRNPLL knockdown suppressed proliferation, migration, and invasion of liver cancer cells and inhibited tumor growth in vivo. Conclusions: These findings suggest that HNRNPLL may act as a potential regulator of LIHC progression and is associated with tumor-related biological processes and immune features. HNRNPLL may serve as a candidate biomarker for prognosis and a potential therapeutic target in LIHC, although further mechanistic studies are required. Full article

In the present work, a novel series of eleven sulfonate derivatives with potent inhibitory activity against butyrylcholinesterase (BChE) is reported. Of these, compounds 2-[(E)-(2-Benzoylhydrazinylidene)methyl]phenyl 5-(dimethylamino)naphthalene-1-sulfonate (5c, IC₅₀ = 1.11 µM) and tert-butyl (2E)-2-[(2-{[5-(dimethylamino)naphthalene-1-sulfonyl]oxy}phenyl)methylidene]hydrazine-1-carboxylate (5b, IC₅₀ = 11.51 µM) exhibit stronger inhibitory activity than rivastigmine, the reference compound, and exhibit high selectivity for BChE over AChE (e.g., selectivity index 57 for 5c). Interestingly, compound 5c also exhibited anti-inflammatory effects, which is important for potential therapeutic applications, especially in Alzheimer’s disease. These new compounds were designed through a structure-based approach using molecular modeling techniques (docking, molecular dynamic (MD) simulations, and QTAIM (quantum theory of atoms in molecules) calculations). The most promising compounds show no detectable toxic effects and satisfy Lipinski’s rule of five, indicating that they represent attractive starting structures for the design of new derivatives acting as specific BChE inhibitors. In addition, our results indicate that relatively simple computational techniques such as docking calculations and toxicity prediction programs can be valuable when properly used in the search of new candidates for this particular target. Docking calculations show that the more active compounds of this series reach the bottom region of the gorge interacting with residues within the active site of BChE. However, our data further suggest that the use of more precise techniques, such as MD simulations and QTAIM analysis, is necessary to obtain detailed insight into ligand–enzyme interactions. Regarding QTAIM calculations, they demonstrate that such computations are very useful to evaluate the molecular interactions of the different molecular complexes. In summary, we report a new series of sulfonate derivatives as promising starting structures for the development of new selective BChE inhibitors. Full article

Hybrid nanomaterials integrating magnetic and semiconductor phases offer promising multifunctional platforms for wastewater remediation; however, their stabilization and recovery remain challenging. In this study, Fe₃O₄ and ZnTiO₃/TiO₂ nanoparticles were incorporated into a rice husk ash-based geopolymer matrix to develop hybrid nanocomposites for synergistic adsorption–photodegradation of methylene blue (MB) and methyl orange (MO). The materials were synthesized via alkaline activation followed by nanoparticle incorporation, and characterized by XRD, XRF, FTIR, SEM, EDX, BET surface area analysis, and pHPZC determination. XRD confirmed the presence of nanocrystalline Fe₃O₄ and ZnTiO₃/TiO₂ phases while preserving the amorphous aluminosilicate framework. Modified powders exhibited higher specific surface areas (up to 198 m² g⁻¹) compared to the unmodified geopolymer. Adsorption followed the Langmuir isotherm and pseudo-second-order kinetics, with spontaneous and exothermic behavior. Under UV irradiation, the ZnTiO₃/TiO₂-modified composite achieved photodegradation efficiencies up to 94% for MB and 92% for MO, whereas the Fe₃O₄-modified material combined adsorption capacity with magnetic recoverability. These results demonstrate that nanoparticle incorporation enables multifunctional performance while maintaining structural integrity of the geopolymeric matrix. Full article

Background: Cancer has emerged as the primary cause of death worldwide in recent years. Current cancer treatment strategies require improvement, creating a pressing need for the development of novel therapeutic agents. This study investigated the anticancer effects of a series of newly synthesized tri- and difluoromethylated spiro[5.5]trienone compounds and evaluated the antitumor efficacy of a lead compound, 3s. Methods: The methyl thiazolyl tetrazolium (MTT) assay was used to assess the effect of the trienone compounds on the growth of cancer cells. Cell cycle distribution and intracellular reactive oxygen species (ROS) levels were analyzed by flow cytometry. Protein expression was examined by Western blot. A mouse xenograft model was utilized to test the anticancer effects and toxicity of 3s in vivo. Results: All 21 tri- and difluoromethylated spiro[5.5]trienones exhibited inhibitory effects on the growth of cancer cells. Among them, compound 3s showed the strongest inhibitory effect. It induced cell cycle arrest at the G2/M phase and promoted apoptosis. Mechanistically, 3s activated JNK and ERK signaling and elevated intracellular ROS levels. Furthermore, in a mouse xenograft model, 3s significantly inhibited tumor growth with minimal toxicity. Conclusions: Compound 3s exhibits potent anticancer efficacy both in vitro and in vivo. The discovery of 3s offers new potential for cancer therapy. Full article