Search Results (17,985)

Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are systemic inflammatory diseases deeply rooted in age-related immunosenescence and inflammaging. Conventional long-term glucocorticoid (GC) therapy poses significant metabolic and infectious risks for older adults, necessitating safer alternatives. This review critically evaluates the pathophysiological rationale and clinical efficacy of small-molecule drugs, including Janus kinase inhibitors (JAKi) and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), as steroid-sparing treatments for PMR and GCA. By selectively inhibiting intracellular networks like the JAK-STAT pathway and nucleotide biosynthesis, these agents aim to attenuate maladaptive inflammation. Clinical evidence highlights that JAK inhibitors, particularly upadacitinib for GCA and tofacitinib or baricitinib for PMR, demonstrate the potential to induce remission and significantly reduce the required GC burden in a subset of patients. Although methotrexate remains the primary csDMARD, its modest overall efficacy suggests it should be reserved for patients with definitive contraindications or restricted access to JAK inhibitors. Furthermore, novel therapies like clofutriben demonstrate potential in reversing GC-induced morbidities without compromising disease control. Ultimately, integrating targeted small-molecule immunomodulators establishes a crucial therapeutic paradigm that attempts to maximize clinical remission while safeguarding the physiological integrity of geriatric patients against severe GC toxicities. Full article

The fascinating features of nanomaterials have attracted immense interest across various fields, including nanoelectronics, magnetite-aided nanocatalysis, and nanomedicine. Herein, a 10% SiO₂/g-C₃N₄/Bi₂SiO₅@Bi₂O₃ triple nanohybrid was formulated via a simple protocol employing acacia powder as a capping/fuel agent. The XRD confirmed the presence of g-C₃N₄, Bi₂SiO₅, Bi₂O₃, and SiO₅ phases, and the TEM image shows densely packed, almost spherical nanoparticles of an average size of 9.2 nm. There was activity of the SiO₂/g-C₃N₄/Bi₂SiO₅@Bi₂O₃ in the field of hydrogen generation via NaBH₄ hydrolysis, and antitumor antiproliferation activity against HepG-2 and MCF-7 cells. The graphitized Bi₂O₃/SiO₂ exhibited HGRs of 303, 615, 785, and 1740 mL min⁻¹ g⁻¹ at 20, 30, 40, and 50 °C, respectively. Hydrolyzing NaBH₄ doses of 0.3, 0.5, 0.7, and 1.0 at 40 °C resulted in a dramatic evolution at HGRs of 526, 785, 1786, and 4000 mL min⁻¹ g⁻¹, respectively. Furthermore, the g-C₃N₄/Bi₂O₃/SiO₂ antiproliferative effect against HepG-2 and MCF-7 cells showed a positive impact at 3.9 and 7.9 µg/mL, with IC₅₀ values of 82.4 and 59.6 µg/mL, respectively. Moreover, the maximum dose of 500 μg/mL of SiO₂/g-C₃N₄/Bi₂SiO₅@Bi₂O₃ resulted in 93.8% inhibition of MCF-7 cells, whereas the same dose yielded 91.7% inhibition of HepG-2 cells. It is significant to note that, given the lower cost of SiO₂/g-C₃N₄/Bi₂SiO₅@Bi₂O₃ relative to currently prescribed antitumor medications, these outcomes can be considered ideal for practical use as antitumor agents. Full article

Background: Neutrophil dysregulation drives inflammatory pathologies through mechanisms such as matrix metalloproteinase-9 (MMP-9) release. High-value bioprospecting of agro-industrial residues offers a sustainable strategy to identify novel bioactive compounds. In this study, the immunomodulatory effects of seed oils (SOs) obtained via supercritical fluid extraction from Passiflora edulis and Rubus glaucus byproducts on human neutrophil responses was evaluated. Methods: SO lipid profiles were characterized via GC-MS. Human neutrophils were isolated using Percoll gradients and treated with the SOs (10–50 µg/mL). Cytocompatibility was assessed via MTT and trypan blue assays. MMP-9 activity and ERK1/2/p38 phosphorylation were determined via zymography and Western blotting, respectively. Results of GC-MS revealed matrices rich in unsaturated lipids: R. glaucus SO was dominated by linoleic (50.02%) and α-linolenic (29.84%) acids, whereas P. edulis SO contained linoleic (58.91%) and oleic (19.75%) acids. Both oils were highly biocompatible up to 50 µg/mL. Both SOs significantly increased MMP-9 release; notably, R. glaucus induced a dose-dependent response and a potential priming effect at 10 µg/mL. Interestingly, neither oil induced the phosphorylation of ERK1/2 or p38. Conclusions: Supercritical fluid-extracted SOs from P. edulis and R. glaucus byproducts modulate early neutrophil responses by increasing MMP-9 release through pathways independent of classical MAPK phosphorylation. Further functional and in vivo validation is needed to clarify the precise regulatory roles of these specialized lipid matrices in human inflammation resolution and their potential as bioactive ingredients for nutraceutical or pharmaceutical applications. Full article

The genus Aegilops comprises important wild relatives of cultivated wheat and represents a valuable genetic resource for wheat improvement. In this study, the complete chloroplast genomes of five Aegilops species (Ae. crassa, Ae. cylindrica, Ae. juvenalis, Ae. tauschii, and Ae. triuncialis) collected from Kazakhstan and Uzbekistan were sequenced, assembled, and comparatively analyzed. The chloroplast genomes exhibited a conserved quadripartite structure consisting of a large single-copy (LSC), a small single-copy (SSC), and two inverted repeat (IR) regions. Genome sizes ranged from 135,612 to 136,840 bp, with an identical GC content of 38% across all species. Comparative analyses revealed high structural conservation among chloroplast genomes, particularly within IR regions, whereas greater sequence divergence was observed in the non-coding regions of the LSC and SSC. Sliding-window analysis identified several highly polymorphic regions, including rpl32-trnL(UAG), ndhF-rpl32, trnC(GCA)-rpoA, psbA, and ndhD, which may serve as potential DNA barcodes and informative markers for phylogenetic studies. A total of 850 chloroplast simple sequence repeats (SSRs) were detected, predominantly A/T-rich mononucleotide repeats. Codon usage analysis demonstrated a conserved preference for A/U-ending codons across all species. Ka/Ks analysis indicated that most chloroplast protein-coding genes are under strong purifying selection, although relatively elevated evolutionary rates were detected in rpoA and ycf4. Phylogenetic analyses based on complete chloroplast genomes strongly supported sectional relationships within Aegilops and confirmed close maternal relationships among several species. Overall, this study provides chloroplast genome resources for Aegilops and contributes to understanding chloroplast genome evolution, phylogeny, and molecular marker development. Full article

Alzheimer’s disease (AD) lacks effective disease-modifying therapeutics. Probiotics, promising neuroprotective candidates, exert benefits mainly by modulating gut-brain-axis (GBA) signaling. This study explored the anti-AD effects and mechanisms of Rhodopseudomonas pseudopalustris (R. pse). Using Caenorhabditis elegans (C. elegans) AD models, we evaluated AD-related phenotypes (learning deficits, paralysis) after R. pse administration, and performed genetic analysis and metabolomic profiling to clarify its regulatory pathways and metabolites. Mechanistically, R. pse significantly alleviated AD-related phenotype in C. elegans. It upregulated γ-glutamylcysteine synthetase (GCS-1) to enhance the glutathione (GSH)-dependent antioxidant defense. Knockout of the oxidation repair enzyme methionine sulfoxide reductase A-1 (MSRA-1) abolished the neuroprotective effects of R. pse, which was rescued by methionine. R. pse also activated activating transcription factor 7 (ATF-7)-mediated innate immunity and transforming growth factor β (TGF-β) signaling, with pantothenic acid as its functional metabolite. Collectively, R. pse is a potential anti-AD bacterium that mitigates AD model pathogenesis by enhancing the cellular antioxidant capacity, providing experimental evidence for bacteria-based AD interventions. Full article

Background/Objectives: Vitamin D deficiency is a global health concern, yet circulating 25-hydroxyvitamin D (25OHD) concentrations vary substantially across geographical regions and ancestral groups. Genetic predisposition may contribute to these differences. This systematic review aimed to synthesize evidence from genome-wide association studies (GWAS) on genetic variation associated with circulating 25OHD across populations from different ancestral backgrounds and to evaluate linkage disequilibrium (LD) between reported variants. Methods: A systematic review was conducted according to PRISMA 2020 guidelines. PubMed and the GWAS Catalog were searched to identify genome-wide association studies (GWAS) on circulating 25-hydroxyvitamin D (25OHD) concentrations. Studies were screened against predefined eligibility criteria, and data were extracted using a standardized framework. Methodological quality was assessed using a standardized tool, and study power adequacy was assessed formally. Genome-wide significant SNPs were extracted, and unique variants between studies were grouped by ancestry. Among these, dbSNP-indexed variants were grouped into genomic cluster windows and evaluated for LD structure. Results: Fifteen GWAS were included. Across these studies, 349 genome-wide significant SNP associations were identified, corresponding to 294 unique variants, of which 283 were indexed in dbSNP and retained for genomic and LD analyses. Variant discovery was dominated by large-scale European-ancestry studies, although African, Middle Eastern, East Asian, Hispanic/Latino, South Asian, and trans-ethnic studies also contributed signals. Some evidence of ancestry-specific variation was apparent, yet not conclusive due to lower study power in non-European cohorts. Variant aggregation was strongest at biologically relevant vitamin D loci, including GC, CYP2R1, DHCR7/NADSYN1, and FLG. Fifteen variants were replicated in at least two independent cohorts. LD-based clustering identified several high LD groups comprising variants identified across studies, with the strongest LD appearing between variants within established vitamin D-related loci, particularly GC, CYP2R1, DHCR7/NADSYN1, and FLG. Conclusions: Circulating 25OHD appears to be influenced by shared core loci involved in vitamin D metabolism, across ancestries. Although some evidence of ancestry-specific variation was identified, findings should be interpreted with caution, in light of the predominance of European-ancestry GWAS and scarcity of sufficiently powered GWAS for other ancestral populations. Larger GWAS in non-European populations are essential for improving ancestry-specific variant discovery and interpretation. Full article

Aconitum soongaricum, a medicinal plant endemic to the Tianshan Mountains in Xinjiang, China, produces numerous natural compounds with potential medicinal value. Mitochondria function as energy hubs and play critical roles in plant development and stress adaptation; thus, their genomic composition underpins biological functions. Here, we assembled the complete mitochondrial genome of A. soongaricum using next- and third-generation sequencing data and performed comparative analyses with related species. The mitochondrial genome exhibited a typical circular structure of 487,849 bp with a GC content of 46.80%. A total of 77 genes were annotated, including 41 protein-coding genes (PCGs), three rRNAs, 31 tRNAs, and two pseudogenes. The genome showed a strong A/U bias at the third codon position and displayed C-to-U RNA editing transitions, whereas no U-to-C transitions were estimated. Maximum-likelihood phylogenetic analysis supported a close relationship among A. soongaricum, A. carmichaelii, and A. kusnezoffii, confirming the utility of mitochondrial genomes for genetic relationship inference in genus Aconitum. Divergence time estimation placed the differentiation of A. soongaricum from the other two species at approximately 4.19 million years ago (Mya). Additionally, we evaluated the expression levels of NADH dehydrogenase (nad) genes across different tissues and under drought stress using real-time PCR, revealing diverse expression patterns. Collectively, this study provides a foundation for future investigations into the genetic mechanisms underlying evolution, energy metabolism, and environmental adaptation in A. soongaricum. Full article

Global warming exacerbates high-temperature stress, disturbing the growth, metabolic homeostasis and quality formation of tea plants (Camellia sinensis L.). Trehalose, a multifunctional osmolyte, can enhance abiotic stress tolerance, but its systematic metabolic mechanism against heat damage in tea remains unclear. Here, we applied integrated gas chromatography–mass spectrometry (GC-MS) and liquid chromatography–mass spectrometry (LC-MS) non-targeted metabolomics to compare control (CK), heat-stressed (T), and trehalose-treated heat-stressed (TT) tea leaves. We identified 163 differential volatile metabolites in GC-MS and 1619 differential non-volatile metabolites in LC-MS. Metabolite classification showed that organic oxygen compounds dominated differential volatile metabolites, while lipids and lipid-like molecules dominated differential non-volatile metabolites. The Kyoto Encyclopedia of Genes and Genomes enrichment showed that alanine, aspartate and glutamate metabolism, arginine biosynthesis, aminoacyl-tRNA biosynthesis, and flavone and flavonol biosynthesis were core shared pathways. Quantitatively, exogenous trehalose under heat stress significantly increased carbohydrate accumulation, restored lipid homeostasis, and elevated alanine, arginine, and related intermediates, thereby maintaining carbon–nitrogen balance. Trehalose also remodeled the amino acid substrate pool for aminoacyl-tRNA biosynthesis. In flavonoid metabolism, trehalose enhanced high-antioxidant flavonoid aglycones while reducing most glycosides and inhibiting excessive hydroxylation of flavonols. Although total flavonoid content decreased in TT relative to T, this reflected alleviated oxidative damage and reduced dependence on flavonoid-based defense. Combined with total amino acid and flavonoid quantifications, we conclude that exogenous trehalose enhances tea plant thermotolerance by coordinately regulating primary amino acid metabolism and secondary flavonoid metabolism. These findings provide a theoretical basis for using trehalose in heat-resistance cultivation and quality improvement of tea plants. Full article

Background and Objectives: Maternal nutrition during pregnancy has been associated with fetal development and long-term health trajectories through mechanisms potentially involving epigenetic and metabolic programming. However, the molecular mediators linking dietary quality to fetal biochemical profiles remain poorly characterized. This exploratory pilot study aimed to investigate associations between maternal nutritional adequacy and the amniotic-fluid metabolomic profile during the second trimester. Materials and Methods: In this prospective study, AF samples from 41 pregnant women undergoing second-trimester amniocentesis were analyzed using gas chromatography–mass spectrometry (GC-MS). Nutritional status was assessed via the FIGO Nutrition Checklist. Subjects were divided into two groups based on dietary adequacy (FIGO Score >5 vs. ≤5). Multivariate analysis (PLS-DA, VIP scores, volcano plots) and pathway enrichment were performed to identify discriminatory metabolites. Results: Exploratory metabolomic analysis suggested differences between the two nutritional groups. Several candidate metabolites, including stearic acid, lactic acid, proline, and scyllo-inositol, contributed to the observed differences between groups. These features may provide preliminary hypotheses regarding energy-, amino acid-, and lipid-related biochemical pathways. Conclusions: Maternal dietary quality was associated with differences in the amniotic-fluid metabolomic profile. These preliminary findings support further investigation of amniotic-fluid metabolomics as a potential tool for studying the fetal biochemical environment. Full article

The aqueous seed extract of Ammodaucus leucotrichus Cosson & Durieu (AL-AE), a Saharan annual herb of the family Apiaceae, was evaluated for the first time as a green corrosion inhibitor for mild steel in 1.0 M hydrochloric acid. GC-MS analysis after acetylation derivatization identified ten constituents representing 99.22% of the total detected area, with 17-pentatriacontene (47.69%), 2,4-di-tert-butylphenol (13.24%), and myo-inositol (8.62%) as the dominant species. Inhibition performance was assessed by electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization (PDP) over 25–100 ppm at 298–328 K. At 100 ppm and 298 K, AL-AE achieved 96.17% by EIS and 97.10% by PDP. Adsorption obeyed the Langmuir model with a standard free energy of adsorption of −38.2 kJ mol⁻¹, consistent with a mixed physisorption–chemisorption mechanism. SEM/EDS confirmed protective film formation, with surface oxygen dropping from 34.9 to 4.1 wt%. Density functional theory (DFT) calculations at the B97-3c/CPCM (water) level in ORCA 6.1 identified 2,4-di-tert-butylphenol as the most reactive constituent, while Fukui index analysis based on Mulliken population analysis located the preferential adsorption sites on each molecule. Full article

Olfactory detection of essential oils (EOs), natural plant-derived mixtures of odorous volatile compounds, stimulates neural pathways involved in emotion, cognitive function, and memory in humans and significantly influences insect behavior (inducing attractiveness or repellency). In this study, the olfactory perception of rose (EO 1, a synthetic mixture with rose aroma), eucalyptus (EO 2), lemon (EO 3), clove (EO 4), rosemary (EO 5), and caraway (EO 6) EOs in untrained human participants was compared to the behavioral responses induced in Tenebrio molitor (adult insects) by EO exposure. Significant differences emerged in the perception of EO odor dimensions (pleasantness, intensity, and familiarity) using a Likert-type scale in untrained participants. The tested EOs elicited different behavioral responses in T. molitor insects, as assessed by repellency, escape, and choice tests. A positive correlation (r = 0.7861, p < 0.05) emerged between EO odor intensity perceived by participants and escape induction in T. molitor adults. GC–MS analysis revealed citronellol, 1,8-cineole, limonene, eugenol, α-pinene, and carvone as the most abundant volatile compounds in EO 1, EO 2, EO 3, EO 4, EO 5, and EO 6, respectively. The EO odor dimensions in participants and insect behavioral responses were also related to the in silico physicochemical/pharmacokinetic properties of the main EO components. Our results provide new insights into the chemical basis of olfactory preferences both in T. molitor adults and humans. Full article

Objectives: Limited information is available on how connector size and luting protocols influence the fracture resistance of 3D-printed resin-based fixed dental prostheses (FDPs). This in vitro study evaluated the effect of connector size and luting agent type on fracture load. Methods: Eighty 3-unit posterior FDPs were 3D-printed (GC Temp PRINT, GC Corp.) and assigned to eight groups (n = 10) by connector size (GroupA 5 × 5 mm or Group B 3 × 3 mm) and luting protocol (1: no cement; 2: TempBond temporary cement; 3: Ketac Cem glass ionomer; 4: G-Cem One self-adhesive resin cement). Specimens were seated on standardized metal abutments and loaded to failure (Instron 5567, 1 mm/min). Data analyzed by Shapiro–Wilk normality test, Mann–Whitney U (connector size), ANOVA/Kruskal–Wallis (luting within size; α = 0.05). Results: Connector size significantly affected fracture resistance (Mann–Whitney U, p < 0.001): 5 × 5 mm groups showed ~3× higher loads (1468–1638 N) than 3 × 3 mm groups (266–384 N). In 5 × 5 mm groups, luting protocol had no significant effect (ANOVA, p > 0.05). In 3 × 3 mm groups, resin cement (343 N) and temporary cement (384 N) showed higher loads than no-cement controls (266 N; Kruskal–Wallis p = 0.022, exploratory U p < 0.05); glass ionomer showed no significant difference. Conclusions: Within the limitations of this in vitro study, larger connectors substantially increased 3D-printed FDP fracture resistance. Resin-based luting agents increased loads in smaller-connector FDPs. Full article

Background: Circulating cell-free DNA (cfDNA) enables minimally invasive tumour genomic profiling, yet simultaneous interrogation of mutations and DNA methylation remains limited by assay complexity and input constraints. Methods: Here, we evaluate the Agilent Avida Duo system, a single workflow integrating high-sensitivity mutation detection with targeted DNA methylation analysis. We analysed 21 stage III and IV melanoma patient samples. Results: The Avida Duo mutation assay detected mutant allele frequencies (MAFs) down to 0.05% and identified tumour-associated mutations in all melanoma patients, including within GC-rich regions such as the TERT promoter. Optimisation of the Avida Duo mutation workflow, using TapeStation-quantified cfDNA and reduced amplification cycles, improved library consistency without compromising sensitivity. Methylation profiling of the melanoma baseline cohort with the Avida Duo methylation panel showed high concordance with QIAseq targeted methylation results, with the mean cfDNA fraction methylation ranging from 0.051–0.079 in most patients and reaching 0.249 in the patient with the highest ctDNA burden (MAFs up to 35.4%). Conclusions: Our findings demonstrate that the Avida Duo workflow enables simultaneous, high-resolution detection of mutation and methylation profiles from a single cfDNA sample, streamlining processing and enhancing molecular insight for clinical and translational applications. Full article

This study investigates the decay-like degradation mechanisms of the matrix material in composite insulators, focusing on the pronounced influence of humid environments on partial discharge (PD) characteristics and degradation pathways. A sealed chamber discharge platform was established, integrating PD signal monitoring, surface characterization, and gas chromatography-mass spectrometry (GC-MS) with molecular network analysis to examine the synergistic effects of thermal influences from PD and active atmospheric particles at humidity levels of 0% RH, 50% RH, and 100% RH. Results show that dry conditions favor high-energy, low-repetition-rate discharges, promoting cleavage and recombination of high-bond-energy bonds (e.g., benzene rings and (α)C–O), yielding primarily long-chain carboxylic acids (C9 and above). In contrast, humid conditions shift to low-energy, high-repetition-rate discharges, with water vapor decomposition generating highly oxidizing hydroxyl radicals (·OH). These facilitate selective scission of lower-bond-energy (β)C–O bonds and deep oxidation, significantly increasing short-chain dicarboxylic acids—especially oxalic acid—whose acidity and water solubility are nearly an order of magnitude higher than in dry environments, becoming the dominant acidic products. The work demonstrates that many PD-generated organic acids act as intrinsic corrosive agents in insulating systems, independent of ambient nitric acid. This elucidates, at the reaction pathway level, how high humidity modulates PD to enhance corrosive acid production, providing a microchemical basis for understanding regional decay-like failure patterns in composite insulators. Full article

Phytochemical studies performed on the aerial parts of Teucrium davaeanum Coss. resulted in the isolation of an iridoid diglycoside, teucardoside; two phenylethanoid triglycosides, poliumoside and 3-O-methyl-poliumoside; a flavon C-diglycoside, vicenin-2 (apigenin-6,8-di-C-glycoside); and a newly described bisdesmosidic oleanane-type triterpene saponin, davaeanoside. Structure elucidations of all isolated metabolites are based on extensive spectroscopic analysis and chemical derivatizations. The extract and isolated compounds (1–5) were tested for α-amylase and α-glucosidase inhibitory activity. IC50 values were measured for all extracts and compounds and compared against acarbose. Results revealed weak or moderate α-amylase and α-glucosidase inhibitory activity at the tested concentrations of the isolated compounds, especially compound 5. However, these findings do not exclude antidiabetic activity mediated by other mechanisms such as modulation of insulin signaling, enhancement of glucose uptake, or antioxidant effects. Further studies are warranted to explore these potential pathways. In addition, the essential oils of T. davaeanum and T. zanonii were obtained by hydrodistillation and simultaneously analyzed by GC-FID and GC/MS. The major compounds of T. davaeanum essential oil were germacrene D (31.4%) and bicyclogermacrene (15.9%); the main compounds of T. zanonii were β-pinene (19.5%), α-muurolene (13.4%), oxo-7,8-dihydro-β-ionol (9.2%), and α-pinene (6.9%). Full article