Search Results (5,048)

Perlecan, a major heparan sulfate proteoglycan in the vascular basement membrane, plays an essential role in maintaining endothelial barrier integrity, regulating fibroblast growth factor-2 signaling, and exerting anticoagulant activity. Although alterations in perlecan expression are implicated in the initiation and progression of atherosclerosis, the upstream regulatory mechanisms remain unclear. In this study, we investigated the effects of extracellular ATP on perlecan expression in vascular endothelial cells. ATP, but not ADP or adenosine, suppressed perlecan expression at both mRNA and protein levels in a time- and concentration-dependent manner. This suppression was recovered by knockdown of P2Y2 receptor (P2Y2R), but not by P2X4 receptor, P2X7 receptor, or P2Y1 receptor knockdown, indicating the selective involvement of P2Y2R. Mechanistically, ATP reduced Akt phosphorylation mediated by P2Y2R, and inhibition of Akt by inhibitors decreased perlecan expression, whereas inhibitors of phosphoinositide 3-kinase, mammalian target of rapamycin complex 1, extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, c-Jun N-terminal kinases did not exhibit this recovery effect. These results suggest that ATP downregulates perlecan synthesis via the P2Y2R-mediated inhibition of Akt signaling. Given that ATP is markedly elevated under pathological conditions, such as inflammation and platelet activation, suppression of perlecan synthesis is an important mechanism by which ATP promotes vascular disease progression. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder whose primary manifestation is motor dysfunction. Previous research showed that (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol (Prottremine) exhibits potent antiparkinsonian activity in animal models of PD, with an efficacy comparable to levodopa. Herein, we report the synthesis of a new Prottremine derivative, (1R,2R,6S)-3-methyl-6-(3-(4-phenylpiperidin-1-yl)prop-1-en-2-yl)cyclohex-3-ene-1,2-diol. The compound was fully characterized and its structure was confirmed through single-crystal X-ray diffraction analysis. Full article

Eco-friendly silver nanoparticle systems are highly effective due to their large surface area and strong adsorption capacity. In this study, a novel silver (diethyldithiocarbamate)-decorated reduced graphene oxide nanocomposite (Ag(DDTC)@rGO) was synthesized via a simple green method, yielding a stable and monodispersed material. SEM and HRTEM analyses revealed uniform anchoring of the Ag(DDTC) complex on rGO, producing a coherent nanocomposite with strong physicochemical coupling. The Ag(DDTC)@rGO nanocomposite exhibited a high Brunauer–Emmett–Teller (BET) surface area (289 m² g⁻¹) with an average pore diameter of 45 nm, confirming the mesoporous nature of the composite. FTIR spectra showed characteristic bands of rGO and DDTC ligands, with new peaks at 620–640 cm⁻¹ confirming the successful anchoring of silver–diethyldithiocarbamate species onto rGO via Ag–S and Ag–O bond formation. Raman spectroscopy further confirmed the multilayered rGO structure after Ag(DDTC) incorporation. X-ray diffraction (XRD) identified a broad hybrid amorphous–crystalline pattern, favorable for catalytic and sensing functions. The superior malachite green adsorption capacity of Ag(DDTC)@rGO was attributed to synergistic electrostatic, π–π stacking, hydrogen bonding, and silver-mediated interactions. Furthermore, antibacterial assays demonstrated significant inhibition of P. aeruginosa ATCC 9027 and S. enterica ATCC 14028, further enhanced by mild heat activation (40–50 °C) that significantly improved the surface activation of silver nanoparticles. The multifunctional Ag(DDTC)@rGO nanocomposite exhibits strong adsorption and antibacterial properties, highlighting its potential for sustainable wastewater treatment and environmental remediation applications. Full article

Most risk assessment and source apportionment studies of the heavy metals in the surface soils in China have focused primarily on East China, whereas studies focused on Northwest China, particularly regarding heavy metals in surface soils in the central and western areas, remain limited. In this study, surface soils in the central–western Ali region were investigated, and the concentrations of nine heavy metals were determined. Moreover, the distribution patterns and ecological risks of these heavy metals were elucidated via a combination of the geoaccumulation index, pollution load index ($PLI$), comprehensive potential ecological risk index ($RI$), and integrated X-ray diffraction (XRD)–multivariate statistical techniques. Additionally, the pollution characteristics and sources were analyzed. The results indicated the following: (1) The spatial distribution of heavy metal pollution is closely linked to the geological background, and high–pollution zones (e.g., Cr, Ni, Co, Cu, As, and Cd) conform well with the distributions of ultramafic rocks and iron/chromite ore beds. The geoaccumulation index revealed that Cd caused slight and moderate contamination at 29.1% and 5.5% of the sites, respectively, whereas As affected 14.6% of the sites. The pollution load index indicated moderate pollution in 20% of the sites, and the potential ecological risk index indicated that 41.8% of the sites posed moderate risks, which was largely driven by Cd (mean $E_r^i$ = 43.1). The comprehensive ecological risk index ($RI$ = 115) confirmed a moderate risk level overall. Principal component analysis revealed three primary sources: natural weathering (Cr–Ni–Co–Cu, 39.1%); a mixed source influenced by nonagricultural anthropogenic activities such as transport and regional deposition, combined with natural processes such as arid climate and alkaline soil conditions that influence Cd mobility (Cd–Mo–Pb, 20.8%); and industrial/mining activities (As–Sb, 14.2%). Mineralogical analyses further indicated that heavy metals are present via lattice substitution, adsorption, and precipitation. This study systematically clarifies the composite pollution pattern and sources of heavy metals in the alpine Ali region, supporting targeted contamination control. Full article

In this work, samples of reduced graphene oxide (rGO) were prepared by treating graphite oxide (GrO) with thiourea (TU) and ascorbic acid (AA). Aerogels rGO-TU and rGO-AA were prepared using the freeze-drying method and were analyzed using X-ray diffraction, FTIR and Raman spectroscopy, ¹H and ¹³C NMR, TEM, and SEM-EDS. Based on the NMR, FTIR, SEM-EDS, and TEM data, GO with TU is reduced with simultaneous functionalization of its oxygen-containing groups. According to ¹H and ¹³C NMR data, the reduction of GO occurred simultaneously with an interaction of the amino groups of thiourea with carbonyl groups on the graphene sheets, forming an imine bond. This is evidenced by the appearance of additional signals in the ¹³C spectrum of GO-TU samples in the region of 140–230 ppm. The Boehm titration method showed that the number of oxygen-containing groups in rGO-TU aerogels decreased by about five times compared to GO. However, thiourea interacts with the GO surface, most likely due to electrostatic interaction and hydrogen bonds. The adsorption capacity of rGO-TU aerogel with respect to methylene blue (MB) after 1440 min was 60.2 mg/g, while for rGO-AA it was 71.4 mg/g. This fact indicates the importance of optimizing GO reduction to increase the number of active sites. Full article

Pulmonary arterial hypertension (PAH) is a devastating cardiovascular disorder caused by right heart failure leading to premature death. The TGFBR2 and BMPR-II receptors, which are members of the TGF-β receptor family, are considered promising targets for developing novel drugs in PAH. Lupeol and ψ-taraxasterol, naturally occurring triterpene molecules with proven anti-inflammatory, anti-cancer, and cardioprotective activities, hold considerable potential in the treatment of PAH. Hence, the present study aimed to evaluate the impacts of lupeol and ψ-taraxasterol isolated from Cirsium sintenisii Freyn on the TGF-β and BMP pathways, aiming to determine their therapeutic values in PAH. The effects of the compounds were extensively investigated using both in silico and wet lab experiments, including reporter assays, RT-PCR/QPCR, Western blots, and cell proliferations assays. Both lupeol and ψ-taraxasterol demonstrated interactions with the majority of components of these signaling pathways, including the TGFBR2 and BMPR-II receptors, suggesting that both compounds were capable of modulating the BMP and TGF-β pathways. Data derived from reporter assays, RT-PCR/QPCR, and Western blots demonstrated that lupeol and ψ-taraxasterol inhibited the TGF-β signaling pathway by reducing the phosphorylation of the SMAD3 protein and the expression of pai-1 transcripts. Additionally, ψ-taraxasterol enhanced BMP signaling via regulating the phosphorylation of SMAD1/5 proteins and upregulated the expression of id-1 transcripts. Finally, lupeol and ψ-taraxasterol inhibited abnormal proliferation of mutant-type (bmpr2^R899X+/-) PAMSCs stimulated with the TGF-β1 ligand with no discernible effects on wild-type cells. This is the first comprehensive report outlining the potential therapeutic effects of lupeol and ψ-taraxasterol in PAH, which may have immediate experimental and clinical applications not only in PAH but also other BMP- and TGF-β-associated disorders. Full article

Artistic gymnastics is one of the most physically demanding sports, characterized by a high incidence of both acute and chronic injuries. Although previous research has primarily focused on biomechanical and training-related factors, the multifactorial etiology of injuries—including molecular and genetic aspects—remains insufficiently explored. This systematic review aimed to synthesize current evidence on the causes, mechanisms, and prevention of injuries in artistic gymnastics, with particular emphasis on biomechanical, molecular, and genetic determinants of injury risk and athletic performance. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and was registered in the PROSPERO database (Registration No: CRD420251167521). Electronic databases (PubMed, KoBSON, and Google Scholar) were searched for studies published between 2015 and 2025 using the keywords “gymnastics injuries,” “overuse injuries,” “injury prevention,” “biomechanics,” “IL-6,” “TNF-α,” and “miRNA biomarkers.” Nineteen studies met the inclusion criteria and were analyzed based on injury incidence, localization, mechanisms, and molecular and genetic associations. The majority of injuries were localized in the joints of both upper and lower extremities, particularly during puberty and at higher competitive levels. Repetitive loading, improper technique, and insufficient recovery were identified as the main etiological factors. Molecular biomarkers such as IL-6, TNF-α, and miRNAs (miR-155, miR-146a) were found to play key roles in inflammatory responses, while genetic polymorphisms including ACTN3 R577X, ESR1 rs2234693, and CYP19A1 rs936306 were associated with flexibility, explosive strength, and susceptibility to injury. Injury prevention in artistic gymnastics requires a personalized and multidisciplinary approach that integrates biomechanical, clinical, molecular, and genetic data. Incorporating molecular and genetic profiling into training and rehabilitation programs may enhance early detection of overuse conditions and optimize both health and performance outcomes in gymnasts. Full article

The year 2024 marked the 80th anniversary of Woodward’s total synthesis of quinine. Quinine is a natural alkaloid from the bark of the cinchona tree that has been used for years as an antimalarial drug. The antibacterial effect of quinine salts has also been regarded. With this in mind, a series of original 9-deoxycinchone alkaloid derivatives bearing a dialkylamino- or heterocyclic moiety at the 4 position of the 9-(((4-X-but-2-ynyloxy)methyl)-1,2,3-triazolyl)-substituent was synthesized. The copper-catalyzed three-component A³-coupling reaction of 9-(((4-prop-2-ynyloxy)methyl)-1,2,3-triazolyl)- substituted cinchona alkaloid derivatives with secondary amines and formaldehyde was the main route of synthesis. The present study attempted to examine the antibacterial properties of 9-substituted 9-desoxyquinine-derived compounds and their antibacterial activity against pathogenic bacterial strains, e.g., Staphylococcus aureus, Bacillus subtillis, Bacillus cereus, and Escherichia coli. The difference in the antibacterial activity profile of diastereoisomeric 9-(((4-X-but-2-ynyloxy)methyl)-1,2,3-triazolyl)-substituted derivatives of cinchona alkaloids indicated the importance of the nature of nitrogen substituents in the molecules. In a concentration-dependent pattern, (9R)- and (9S)- (((4-asocan-1yl)-but-2-ynyl-oxy)methyl)-1,2,3-triazolyl)-substituted compounds demonstrated considerable biofilm-inhibitory efficacy against the S. aureus bacterial strain. A detailed study of the molecular interactions with the targeted protein MurB was performed using docking simulations, and the obtained results are quite promising. Full article

Transformer oil ageing alters key physicochemical properties, notably the refractive index (RI), due to physical, particulate, and chemical changes. As a result, refractometric fibre-optic sensors have gained attention for enabling real-time monitoring and overcoming the limitations of traditional offline diagnostics. This study explores the use of a Fabry–Pérot phase-modulated fibre optic sensor (FISO FRI RI Sensor) for in-situ ageing detection in four industrial transformer oils: natural ester, synthetic ester, Nytro Bio 300X (vegetable-based), and Polaris GX (mineral-based). The oils were thermally aged under controlled conditions following degassing and drying. The sensor performance was evaluated using key metrics, including repeatability, thermal response, settling time, and linearity. Results show high repeatability (with standard deviations below 7 × 10⁻⁵ RIU and repeatability coefficients under 2 × 10⁻⁴ RIU), stable thermal response (~0.0004 RIU/°C), and strong thermal linearity (R² > 0.99) across all samples. Natural ester and Nytro Bio 300X exhibited the most stable and consistent sensor responses, while synthetic ester and mineral oils showed greater variability due to temperature-induced RI shifts. These findings demonstrate the reliability and precision of this Fabry–Pérot phase-modulated sensor for online transformer oil condition monitoring, with strong potential for integration into smart grid diagnostics. Full article

The present study demonstrates encapsulation of Coriandrum sativum essential oil in chitosan nanoemulsion and its effectiveness against fungal infestation and fumonisin B₁ (FB₁)- and B₂ (FB₂)-mediated biodeterioration of stored rice samples. Mycoflora analysis of different rice varieties revealed fungal occurrence and Fusarium proliferatum-BRC-R2 as the most toxigenic strain with highest FB₁- and FB₂-producing potentiality. GC-MS analysis of Coriandrum sativum essential oil (CEO) revealed linalool as the major component. The CEO-loaded chitosan nanoemulsion (Ne-CEO) was characterized by Scanning electron microscopy, X-ray diffractometry, Dynamic light scattering, and Fourier transform infrared spectroscopy. The Ne-CEO showed better antifungal and anti-fumonisin effectiveness as compared to unencapsulated CEO. The antifungal mechanism was associated with reduced ergosterol content, efflux of ions, proteins, nucleic acids, and destruction of plasma membrane integrity. The in silico interaction of linalool with Fum 1 protein confirmed the molecular action of anti-fumonisin activity. Additionally, the Ne-CEO displayed improved antioxidant activity and promising antifungal and anti-fumonisin activity during in situ investigation in rice samples (Gobindobhog variety) along with inhibition of the deterioration of carbohydrate, protein content, and lipid peroxidation without altering organoleptic properties and seed germination potentiality. Overall, the investigation strengthens the potentiality of Ne-CEO as a novel preservative of stored food commodities. Full article

In mineral processing and metallurgy, total iron grade serves as a critical indicator guiding the entire production chain from crushing to smelting, directly influencing the quality and yield of steel products. To address the limitations of conventional matrix effect correction methods in X-ray fluorescence (XRF) analysis—such as low accuracy, high time consumption, and labor-intensive procedures—this study proposes a novel hybrid model (DSCN-LS) integrating least squares (LS) with dynamically regularized stochastic configuration networks (DSCNs) for total iron ore grade quantification. Through feature analysis, we decompose the grade modeling problem into a linear structural component and nonlinear residual terms. The linear component is resolved by means of LS, while the nonlinear terms are processed by the DSCN with a dynamic regularization strategy. This strategy implements node-specific weighted regularization: weak constraints preserve salient features in high-weight-norm nodes, while strong regularization suppresses redundant information in low-weight-norm nodes, collectively enhancing model generalizability and robustness. Notably, the model was trained and validated using datasets collected directly from industrial sites, ensuring that the results reflect real-world production scenarios. Industrial validation demonstrates that the proposed method achieves an average absolute error of 0.3092, a root mean square error of 0.5561, and a coefficient of determination (R²) of 99.91% in total iron grade estimation. All metrics surpass existing benchmarks, confirming significant improvements in accuracy and operational practicality for XRF detection under complex industrial conditions. Full article

Macroeconomic mathematical models are practical instruments structured to carry out theoretical analyses of macroeconomic developments. In this manuscript, the Caputo-like fractional operator of variable order is used to introduce and investigate the mechanism of the discrete macroeconomic model. The nature of the dynamics was established, and the emergence of chaos using a distinct variable fractional order, especially the stability of the trivial solution, is examined. The findings reveal that the variable-order discrete macroeconomic model displays chaotic dynamics employing bifurcation, the Largest Lyapunov exponent ($L{E}_{max}$), the phase portraits, and the 0–1 test. Furthermore, a complexity analysis is performed to demonstrate the existence of chaos and quantify its complexity using $C_0$ complexity and spectral entropy ($SE$). These studies show that the suggested variable-order fractional discrete macroeconomic model has more complex features than integer and constant fractional orders. Finally, MATLAB R2024b simulations are run to exemplify the outcomes of this study. Full article

This study investigated the representative elementary volume (REV) for visible porosity in horticultural growing media (peat, commercial mixture, treated wood fibre/peat, pure wood fibre) using x-ray micro-computed tomography (µCT) with 2D and 3D image division, pore morphology, water retention curve (WRC), and saturated hydraulic conductivity (K_sat) via pore network modelling (PNM). Two sample sizes (10 × 10 cm, 3 × 3 cm, height × diameter) with resolutions of 46 and 15 µm were analysed. REV was assessed using deterministic (dREV) and statistical (sREV) criteria, evaluating the porosity and coefficient of variation across subvolumes. The results showed that 3D division of large samples achieved REV only for pure wood fibre (8000–10,000 µm), while 2D division met both criteria for all media. For small samples, 3D division achieved REV only for wood fibre/peat mixture, but 2D division succeeded for all media above 3000 µm. Pore analyses indicated that pure wood fibre had the largest, most connected pores, enhancing drainage, while peat showed complex, retentive structures. WRCs aligned well with lab data (R² > 0.88). PNM Ksat estimates from small images were more accurate, with discrepancies (21–172%) due to segmentation artefacts. Future studies should incorporate permeability or tortuosity and explore multiscale imaging for improved hydrophysical predictions. This study also highlights advantages unique to X-ray µCT compared to standard laboratory methods, e.g., direct three-dimensional quantification of pore structure parameters and an image-based determination of the REV. Full article

Determining the lithostratigraphic provenance of limestone artefacts is challenging. We addressed the issue by analysing Roman stone artefacts, where previously traditionalpetrological methods failed to identify the provenance of 72% of the products due to the predominance of micrite limestone. We applied statistical classification methods to 15 artefacts using linear discriminant analysis, decision trees, random forest, and support vector machines. The latter achieved the highest accuracy, with 73% of the samples classified to the same stratigraphic member as determined by the expert. We improved classification reliability and evaluated it by aggregating the results of different classifiers for each stone product. Combining aggregated results with additional evidence from paleontological data or precise optical microscopy leads to successful provenance determination. After a few samples were reassigned in this procedure, a support vector machine correctly classified 87% of the samples. Strontium isotope ratios (⁸⁷Sr/⁸⁶Sr) proved particularly effective as provenance indicators. We successfully assigned all stone products to local sources across four lithostratigraphic members, thereby confirming local patterns of stone use by Romans. We provide guidance for future use of statistical learning in provenance determination. Our integrated approach, combining geological and statistical expertise, provides a robust framework for challenging provenance determination. Full article

Purinergic P2X7 receptors (P2X7Rs) may provide cardioprotection against ischemic heart disease. Cardiac angiogenesis is an endogenous adaptive response of hypoxic cardiomyocytes, mediated by vascular endothelial growth factor (VEGF) via hypoxia-inducible factor-1α (HIF-1α). The study aimed to determine whether P2X7Rs can regulate cardiac pro-angiogenic signaling in hypoxic H9c2 cardiomyocytes by modulating the angiogenic factor VEGF through HIF-1α genes. H9c2 rat cardiomyocytes were exposed to hypoxia alone or in combination with the P2X7R antagonist A740003. Subsequently, ATP levels and LDH activity were measured. The expression of P2X7R, HIF-1α, and VEGF was detected. Intracellular ATP level was significantly lower in hypoxia cardiomyocytes, whereas extracellular ATP, HIF-1α, and LDH levels were significantly higher in hypoxic cardiomyocytes. These effects were associated with increased P2X7R and VEGF gene expressions. Pretreatment with A740003 reversed HIF-1α and VEGF expressions in hypoxic cardiomyocytes. The findings suggest that P2X7Rs regulate pro-angiogenic signaling in hypoxic cardiomyocytes through the HIF-1α/VEGF pathway. Thus, the P2X7R-mediated HIF-1α/VEGF pathway may represent a novel approach to stimulating angiogenesis and preventing heart failure in ischemic heart disease. Full article