Search Results (1,798)

The composition of low-polarity extracts obtained by sequential extraction of the aerial parts of Rhododendron adamsii Rehd. with hexane and methyl tert-butyl ether (MTBE) was investigated using GC-MS. The hexane extract was dominated by non-polar components: squalene, n-alkanes (nonacosane, hentriacontane), sesquiterpenes (trans-nerolidol, spathulenol, β-farnesene), and β-sitosterol. The subsequent MTBE extract was enriched in more polar lipids, primarily free triterpenic acids (ursolic and oleanolic acids). A critical finding was the complete absence of diterpene grayanotoxins in all tested extracts, confirming the safety of the non-polar extraction approach. In bioactivity assays, the total hexane extract demonstrated potent inhibitory activity against the SARS-CoV-2 main protease (3CLpro) with IC₅₀ values of 0.0125–0.025 mg/mL, only one order of magnitude higher than the reference inhibitor disulfiram. Fractionation revealed that the activity was distributed among free acids, bound acids, and the unsaponifiable residue, indicating a multicomponent mechanism. Importantly, none of the samples inhibited HIV-1 protease (IC₅₀ > 0.1 mg/mL), demonstrating selectivity for the cysteine protease 3CLpro over the aspartyl protease of HIV-1. These results highlight that sequential non-polar extraction of R. adamsii provides a grayanotoxin-free lipophilic complex with selective anti-SARS-CoV-2 protease activity, paving the way for bioactivity-guided identification of individual inhibitors. Full article

Clear cell renal cell carcinoma (ccRCC) is notorious for its clinical unpredictability. While Aquaporin-1 (AQP1) is a major water channel in healthy kidneys, its specific role and regulatory mechanisms in ccRCC remain unclear. Using bioinformatics analysis of 610 TCGA-KIRC patients (RNA sequencing and DNA methylation), single-cell transcriptomics of 27,402 cells, and experimental validation (CCK-8, scratch, Transwell, and xenograft assays, with Western blotting, HE staining, and immunohistochemistry), we systematically characterized AQP1 expression, regulation, and function. AQP1 was significantly downregulated in ccRCC via promoter hypermethylation, with single-cell analysis confirming tumor cell-specific loss. Low AQP1 correlated with worse prognosis; multivariate Cox regression identified AQP1 as an independent protective factor (HR = 0.510, p < 0.001), and a prognostic nomogram showed good predictive accuracy for 1-, 3-, and 5-year survival. AQP1 overexpression suppressed proliferation, migration, invasion, and xenograft growth, accompanied by upregulation of TNF-α, TNFRSF1A, Bax, and Cleaved Caspase-3 and reduced Vimentin, suggesting activation of TNF-related pro-apoptotic signaling. AQP1 is epigenetically silenced in ccRCC and suppresses tumor growth via TNF-mediated apoptosis, establishing it as an independent prognostic biomarker and candidate therapeutic target. Full article

Halitosis is caused by volatile sulfur compounds (VSCs) produced by periodontopathogens. The aim of this study is to examine the mechanism by which Ligilactobacillus salivarius WB21 inhibits halitosis. A susceptibility assay for Porphyromonas gingivalis was conducted using spent culture media (SCM) from L. salivarius WB21, and VSCs from the suspension of P. gingivalis were analyzed in the presence or absence of the SCM. After co-cultivating P. gingivalis and L. salivarius, P. gingivalis growth and VSC levels were measured using a spectrophotometer and a gas chromatograph, respectively. Additionally, levels of methyl mercaptan in the suspension and in the mgl gene of P. gingivalis were investigated. The SCM from L. salivarius WB21 significantly inhibited growth of P. gingivalis (p < 0.05) and significantly reduced emission of VSCs from the suspension of P. gingivalis (p < 0.05). When L. salivarius WB21 was present in a co-culture condition, P. gingivalis growth was significantly inhibited, and levels of methyl mercaptan in the culture medium were also reduced (p < 0.05). Finally, expression of the mgl gene of P. gingivalis was significantly reduced under co-cultivation with L. salivarius WB21 (p < 0.05). L. salivarius WB21 may inhibit colonization of periodontopathogens in the oral cavity and suppress production and emission of VSCs. Therefore, L. salivarius WB21 may be effective in treating halitosis when applied to the oral cavity. Full article

The western corn rootworm (Diabrotica virgifera virgifera) relies on odorant-binding proteins (OBPs) to locate maize hosts and mates via volatile organic compounds (VOCs). However, the molecular recognition mechanisms of specific attractants, such as (E)-β-caryophyllene, 6-methoxy−2-benzoxazolinone (6-MBOA), and the sex pheromone 8R-methyl−2R-decyl propanoate (2R,8R-MDP), remain elusive. Here, we integrated phylogenetic analysis, AlphaFold2 structural prediction, molecular docking, molecular dynamics (MD) simulations, and in vitro fluorescence competitive binding assays to characterize the binding specificity of DvirOBPs toward these key ligands. Pan-family screening identified DvirOBP54b as possessing the highest ligand-binding specificity, resolving its evolutionary divergence from its tandem duplicative paralog DvirOBP54a. Structural and dynamic analyses revealed that DvirOBP54b binding to (E)-β-caryophyllene and 2R,8R-MDP is predominantly driven by hydrophobic interactions within a core pocket (Phe7, Phe69, Ile70, Ala121). Conversely, its interaction with 6-MBOA is further stabilized by a specific hydrogen bond at Thr66. Dynamic trajectories confirmed the high stability of the DvirOBP54b complexes, while in vitro assays validated the strong binding affinities toward the core host-derived volatiles. These findings elucidate the structural basis of VOC-mediated olfactory recognition in D. v. virgifera, providing critical molecular targets for developing high-efficiency attractants and novel pest management strategies. Full article

Essential oils from aromatic plants are gaining traction as naturally derived preservative and antioxidant ingredients, yet the quantitative relationships between field climate conditions and both oil yield and food relevant bioactivity remain poorly characterised. Here, we characterised the leaf essential oil of Melaleuca bracteata F. Muell. “Revolution Gold” across a complete annual cycle using a fixed plant, multiscale spatio temporal sampling framework. Leaf samples were collected at four seasonal time points (March, June, September, and December) and four diurnal time points (06:00, 12:00, 16:00, and 21:00) from a single field individual in Meizhou, Guangdong, China. Gas chromatography–mass spectrometry (GC-MS) profiling identified 51 volatile constituents, with methyl eugenol dominating the composition (up to 93.67% in summer). Oil yield peaked in summer (2.43 mL kg⁻¹ dry weight) and was lowest in spring (1.28 mL kg⁻¹ dry weight). DPPH radical scavenging and ABTS radical cation decolorisation assays revealed that antioxidant activity was highest in summer harvested oils, with IC₅₀ values of 7.68 mg mL⁻¹ (DPPH) and 8.85 mg mL⁻¹ (ABTS), consistent with peak methyl eugenol accumulation. Permutation-based multiple regression (999 permutations; R² = 0.947) identified seasonal precipitation as the strongest positive predictor of oil yield (β = 11.22, p < 0.05), while temperature exerted a significant negative influence (β = −11.21, p < 0.05). Non-metric multidimensional scaling (NMDS) and permutational multivariate analysis of variance (PERMANOVA) confirmed highly significant seasonal clustering of compositional profiles (F = 15.258, p = 0.001) against negligible diurnal structuring (F = 0.178, p =0.991). Redundancy analysis (RDA) attributed 71.03% of total compositional variance to the climatic predictor set. Pearson correlation analysis established significant positive associations between methyl eugenol content and antioxidant capacity (r > 0.80, p < 0.05). These findings provide an integrated, climate resolved basis for harvest timing optimisation of M. bracteata and identify summer as the strategically optimal harvest window for yield and bioactive functionality. Full article

The Senegal tree (Sengalia senegal) is the primary plant source of Gum Arabic (GA), a natural secretion rich in soluble fiber and bioactive polysaccharides. It has longstanding uses in traditional medicine, nutrition, and pharmaceuticals. The present study aimed to evaluate the phytochemical profile, antimicrobial, anti-inflammatory, and anticancer activities of GA methanolic extract (GAME), supported by molecular docking analysis of its key compounds. The gas chromatography–mass spectrometry (GCMS) analysis of the GAME identified many compounds, such as 9-octadecenoic acid (38.29%), methyl ester (15.52), 1,2-benzenedicarboxylic acid, 3-nitro (9.8%), hexadecadienoic acid, methyl ester (8.5), and á-d-mannofuranoside, methyl (7.38). The molecular docking analysis showed that 9-octadecenoic acid had strong binding affinity with target proteins, which included xanthine oxidase (XO), lipoxygenase (LOX), and cyclooxygenase-2 (COX-2), with the highest affinity to XO (−137.03 kcal/mol) and lipoxygenase (−135.09 kcal/mol). GAME possessed broad-spectrum antibacterial activity against Salmonella typhimurium (S. typhimurium), Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), and Staphylococcus aureus (S. aureus), with a zone of inhibition from 16.28 to 16.93 mm. B. subtilis was resistant to the tested extract. The extract also showed good membrane stability and potent inhibition of albumin, XO, LOX, and COX-2, with IC₅₀ values of 31.62, 13.02, 27.6, and 28.99 μg/mL, respectively. The cytotoxic assessment demonstrated moderate, dose-dependent effects on the Caco-2 (colorectal adenocarcinoma) and HeLa (cervical carcinoma) cell lines. These findings highlight the therapeutic potential of GA as a natural plant source of antibacterial, anti-inflammatory and anticancer agents. The combination of molecular docking with in vitro assays provides strong evidence supporting its application in the development of plant-based pharmaceuticals. This research suggests that GA could be a useful ingredient in the creation of anti-inflammatory and antibacterial drugs derived from plants. Full article

Methylated flavonoids are abundant phytochemicals in Eucalyptus and are of interest because methylation can alter flavonoid diversity, bioactivity, and stability. However, the enzymes responsible for flavonoid methylation in eucalypts remain largely uncharacterised. We used comparative leaf transcriptomics of two species with contrasting flavanone profiles, together with protein-structure-guided candidate selection, to identify prospective O-methyltransferases involved in methylated flavonoid biosynthesis. Five candidate methyltransferases from E. eugenioides were cloned, heterologously expressed, and assayed against a panel of flavonoids and a chalcone precursor. The enzymes showed distinct substrate preferences and regioselectivities. EeOMT1 acted as a broad 7-O-methyltransferase, whereas EeOMT3–EeOMT5 preferentially methylated B- and C-ring hydroxyl groups, with differing capacities for sequential methylations at different sites. EeOMT2 was of particular interest because it methylated pinocembrin chalcone to alpinetin chalcone more efficiently than it converted the flavanone pinocembrin to alpinetin. Expression–metabolite analyses across E. eugenioides genotypes were consistent with roles for EeOMT2 and EeOMT1 in the in planta accumulation of 5-O- and 7-O-methylated flavanones, respectively. These findings support a revised model in which alpinetin biosynthesis proceeds, at least in part, through methylation of a chalcone precursor before flavanone formation. This work provides a foundation for elucidating flavonoid methylation pathways in plants and for engineering the production of tailored methylated flavonoids. Full article

Relapse remains the leading cause of treatment failure following hematopoietic cell transplantation (HCT) for hematologic malignancies. Circulating tumor DNA (ctDNA) has emerged as a promising minimally invasive biomarker for measurable residual disease (MRD) assessment and early relapse detection; however, the prognostic significance of ctDNA in the post-transplant setting has not been comprehensively synthesized. We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines and registered the protocol in PROSPERO (CRD420261392100). PubMed, Embase, Web of Science, EBSCO, Cochrane CENTRAL, and supplementary sources were searched through November 2025. Eligible studies evaluated tumor-specific ctDNA or tumor-informed/tumor-associated cfDNA in patients undergoing allogeneic or autologous HCT for hematologic malignancies. Random-effects meta-analyses were performed for relapse/progression, overall survival (OS), and relapse-free/progression-free survival (RFS/PFS). Studies evaluating total cfDNA quantity, methylation-based cfDNA profiling, cfRNA, or chimerism-only monitoring were synthesized narratively. Ten observational cohort studies comprising 883 patients met inclusion criteria. Across acute leukemias, lymphomas, multiple myeloma, and myelodysplastic syndromes, ctDNA/cfDNA positivity was consistently associated with adverse outcomes. The pooled hazard ratio (HR) for relapse or disease progression was 12.57 (95% CI: 4.59–34.46; p < 0.001), while pooled HRs were 7.45 (95% CI: 4.11–13.48; p < 0.001) for OS and 4.46 (95% CI: 2.22–8.97; p < 0.001) for RFS/PFS. Although statistical heterogeneity was low, interpretation was limited by the relatively small number of studies contributing to each pooled endpoint. Narrative evidence additionally suggested that broader circulating nucleic acid approaches may provide complementary information regarding graft-versus-host disease, infection, and other post-transplant complications. Tumor-specific ctDNA positivity is consistently associated with increased relapse risk and inferior survival outcomes following HCT. These findings support further investigation of ctDNA-based MRD monitoring as a promising non-invasive biomarker for post-transplant molecular surveillance and risk stratification. However, prospective multicenter validation studies, assay standardization, and ctDNA-guided interventional trials remain necessary before routine clinical implementation can be recommended. Full article

This study investigates the electronic and photocatalytic properties of greenly fabricated rutile-phase titanium dioxide (bTiO₂) modified with iron vanadate (Fe/bTiO₂/VO₄) and vanadium-substituted goethite (Fe/bTiO₂/VOOH) by detailed experimental assay and density functional theory (DFT) calculations. Our analysis of the density of states (DOS), band structure, and work function reveals that both dopant systems significantly modify the electronic structure of pure rutile bTiO₂. The dye methyl orange (MO) was used as the model pollutant. During photodegradation tests, parameters such as the reaction time, solid-to-liquid ratio, initial concentrations of the photocatalyst and dye, as well as distance of the lamp from the reactor and pH were varied. Degradation kinetics follows the equation of the pseudo-first order law for both photocatalysts (k_VO4 = 0.058 min⁻¹ and k_VOOH = 0.065 min⁻¹), while degradation efficiencies of 92% and 99% were observed after 120 min at pH 3, respectively. Specifically, the DOS analysis highlights the contribution of Fe 3d and V 3d orbitals, which create new electronic states within the bandgap, facilitating charge transfer. These insights provide a strong foundation for the rational design of novel, highly efficient Fe/bTiO₂-based photocatalysts for the degradation of organic pollutants in water. Full article

Chronic inhalation exposure to nanoplastics, specifically polyethylene terephthalate (PET) nanoplastics (PET-NPLs) is an emerging health concern, yet the long-term consequences for genomic stability and DNA damage response (DDR) capacity in bronchial epithelial cells remain poorly characterized. For this study, human bronchial epithelial BEAS-2B cells were continuously exposed to PET-NPLs for over 20 weeks, after which elevated basal DNA genotoxic damage was observed, as assessed by the alkaline comet assay. In addition, a broad transcriptional suppression of the DDR, with 27 of 84 profiled genes involved in DDR showing reduced expression relative to passage-matched control was observed. The suppressed genes span ATM/ATR checkpoint signaling, homologous recombination (HR), base excision repair (BER), nucleotide excision repair (NER), and apoptotic pathways. To determine whether chronic PET-NPL exposure altered susceptibility to acute genotoxic challenge in a damage-type-specific manner, cells were treated with methyl methanesulfonate (MMS), ultraviolet-C (UV-C) radiation, or bleomycin. While MMS and UV-C induced comparable levels of DNA damage in control and PET-exposed cells, bleomycin produced significantly greater damage in PET-exposed cells, indicating selective sensitization to doble-strand breaks (DSB)-type and oxidative genotoxic insults. Transcriptional profiling during bleomycin challenge identified 18 DDR genes with relatively higher expression in PET-exposed cells compared to passage-matched controls, encompassing HR, BER, ATM/ATR signaling, the Fanconi anemia pathway, and apoptosis. Furthermore, PET-exposed cells retained significantly higher residual DNA damage after 3 h of bleomycin challenge, indicating a persistent early repair deficit. Together, these findings suggest that chronic PET-NPL exposure specifically compromises the bronchial epithelial DDR, with potential implications for long-term genomic stability in respiratory epithelia subjected to nanoplastic inhalation. Full article

Pediatric brain and other central nervous system (CNS) tumors remain a leading cause of cancer-related death in children, while contemporary management increasingly depends on molecular classification, risk stratification, and longitudinal disease assessment. Yet tissue-based profiling has major limitations in pediatric neuro-oncology, particularly for deep-seated, eloquent, or surgically hazardous tumors and when repeat sampling is impractical. For primary CNS tumors, cerebrospinal fluid is generally more informative than plasma because it is anatomically closer to the tumor and more enriched for tumor-derived material. This narrative review summarizes current and emerging applications of cerebrospinal fluid in pediatric neuro-oncology, from conventional staging to molecular diagnosis, methylation-based classification, measurable residual disease detection, pharmacodynamic monitoring, and relapse surveillance. We discuss the biological rationale for cerebrospinal fluid analysis, major pre-analytical and technical determinants of assay performance, and the strengths and limitations of key analyte classes, including cytology, circulating tumor cells, cell-free DNA, RNA, extracellular vesicles, proteins, and metabolites. We also summarize how these approaches are being applied across major pediatric central nervous system tumor entities. Cerebrospinal fluid liquid biopsy is unlikely to replace tissue or imaging, but is increasingly positioned to complement both in precision pediatric neuro-oncology. Full article

Regulation of the endothelial stress response is important for blood vessel homeostasis and angiogenesis, processes disrupted in common vascular diseases and ageing. Here, we discovered that the Y-box factor ZONAB (ZO-1-associated nucleic acid binding protein; YBX3), a gene associated with risk loci for severe vascular disorders, regulates endothelial homeostasis and angiogenesis. By combining cell-based assays with primary endothelial cells and genome-wide expression and methylation measurements, we found that ZONAB depletion results in mitochondrial deregulation, increased reactive oxygen species, and a defective oxidative stress response, which correlates with increased promoter methylation of cell cycle genes. ZONAB depletion triggered cellular senescence via a phosphatidylinositol 3-kinase (PI3K)/Akt-dependent pathway, which was attenuated by PIK3 inhibitors, an antioxidant, or by drugs targeting mitochondrial function or fragmentation. Thus, our results reveal that ZONAB repression in endothelial cells leads to genome-wide changes in gene expression and DNA methylation, regulating endothelial proliferation and inflammation, as well as mitochondrial deregulation to promote cellular senescence. Hence, ZONAB supports endothelial homeostasis and may play a role in vascular health. Full article

Flavonols are dietary polyphenols whose biological activity is influenced by structural modifications such as O-methylation. This study compared two quercetin derivatives, isorhamnetin (3′-O-methylquercetin) and rhamnetin (7-O-methylquercetin). Antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), cupric reducing antioxidant capacity (CUPRAC), and ferric reducing antioxidant power (FRAP) assays. Cyclooxygenase-2 (COX-2) inhibitory activity was assessed in vitro and supported by molecular docking simulations. In vivo effects included developmental toxicity, behavioral assessment, and locomotor responses in a 6-hydroxydopamine (6-OHDA) model. The results demonstrated that rhamnetin exhibited significantly stronger radical-scavenging and reducing activity in DPPH, ABTS, and FRAP assays, whereas no significant differences were observed in the CUPRAC assay. Isorhamnetin showed stronger COX-2 inhibition, with docking results suggesting a different mode of binding when analyzing possible interactions with enzyme active site. In zebrafish larvae, rhamnetin showed lower observable developmental toxicity within the tested concentration range, whereas isorhamnetin induced developmental abnormalities at higher concentrations. Both flavonols attenuated 6-OHDA-associated locomotor deficits and modulated antioxidant enzyme activity under oxidative stress conditions. In conclusion, our findings indicate that the position of O-methylation influences flavonol antioxidant properties, COX-2 interactions, and organism-level responses. Full article

Objectives: This study aimed to isolate secondary metabolites from sea cucumber-associated fungus Trichoderma koningii KMM 4751, obtain their bromine derivatives, and investigate their antimicrobial and cytotoxic activities. Results: 3-Ethyl-4-hydroxy-6-methyl-2H-pyran-2-one (EHMP) was isolated from fungal extract. It was brominated, and a previously unreported 6-(bromomethyl)-3-ethyl-4-hydroxy-2H-pyran-2-one (Br-EHMP) was obtained. EHMP inhibited the formation of Candida albicans biofilms with an IC₅₀ of 49.3 µM, but Br-EHMP was less active. Simultaneously, bromination of EHMP significantly enhanced the inhibitory effect of Br-EHMP on Staphylococcus aureus growth and biofilm formation without increasing cytotoxicity to H9c2 cells. Br-EHMP at 10 μM can inhibit sortase A activity by near 30% in a cell-free assay. In silico molecular docking predicted the interaction of Br-EHMP with Cys184 in the sortase A active site. Conclusions: Br-EHMP emerges as a promising antibiofilm agent, and its mechanism involves sortase A inhibition. Full article

Increasing environmental pollution has intensified the focus on sustainability, encouraging the development of eco-friendly materials. This study reports the synthesis of binary (ZnO–TiO₂) and ternary (SnO₂–ZnO–TiO₂) compounds and their loading with Au/Ag/Pt/P noble metals (NMs) to enhance photodegradation efficiency under visible light compared to pristine TiO₂. The compounds were synthesized in a single step via laser pyrolysis, and then noble metal deposition through chemical impregnation and reduction was performed. Structural and morphological analyses revealed TiO₂-based nanoparticles with varied morphologies decorated with noble metal nanoparticles with sizes between 2 and 6 nm (for Pt and Pd). Photocatalytic tests demonstrated a significant improvement in Methyl Orange (MO) degradation under visible light, especially for Ag-loaded samples. The degradation rate increased from 1.03 × 10⁻³ min⁻¹ (TZ) to 22.65 × 10⁻³ min⁻¹ (TZS_Ag), while it was 0.09 × 10⁻³ min⁻¹ for the commercial P25 sample. Biocompatibility assays indicated lower cytotoxicity than Degussa P25, with Au- and Pd-loaded samples showing improved compatibility with HaCaT and HEK293 cells. Overall, these findings demonstrate that the developed TiO₂-based nanocomposites, designed through a novel and sustainable strategy combining binary/ternary heterostructures with noble metal loading, are promising candidates for efficient visible light-driven photocatalytic environmental decontamination with enhanced biological compatibility. Full article