Search Results (11,801)

Alzheimer’s disease (AD) is a prevalent neurodegenerative condition that progressively impairs cognitive processes, particularly learning and memory. A key pathological feature of AD involves senile plaques mainly composed of β-amyloid (Aβ) peptides, generated via the amyloidogenic pathway from amyloid precursor protein (APP) through sequential β-secretase (BACE1) and γ-secretase cleavage, positioning BACE1 inhibition as a prime therapeutic target. In this study, we applied bioassay-guided fractionation of the butanol-soluble fraction from Dryopteris crassirhizoma rhizomes, previously reported to inhibit Aβ production, to isolate and characterize Aβ-lowering constituents. Through successive chromatographic steps, nine compounds were isolated and structurally classified into flavonoids, chromones, and phloroglucinols, including epicatechin (1), β-carboxymethyl-(-)-epicatechin (2), 7-methoxy-isobiflorin (3), biflorin (4), eriodictyol (5), noreugenin (6), phloroglucinols (butyrylphloroglucinol (7), 2-propionyl-4-methylphloroglucinol (8), and 2-butyryl-4-methylphloroglucinol (9) by comprehensive spectroscopic analysis (NMR, MS, UV, IR). These compounds were assessed for effects on sAPPβ and BACE1 (β-secretase) levels by Western blot, with Aβ production quantified via ELISA in a cellular AD model (APP-CHO cells). Compounds 5–9 significantly reduced sAPPβ and BACE1 expression while potently suppressing Aβ generation. These results demonstrate that diverse constituents from D. crassirhizoma rhizomes inhibited Aβ production through BACE1 suppression, highlighting their potential as natural lead compounds for AD prevention or therapy. Full article

Empirical approaches alone have significant limitations for accurate estimation of the fracture toughness of welds in gas line pipes being considered for repurposing to hydrogen service. These problems arise because most samples machined from ex-service welds contain a range of microstructures. The different microstructural zones have different properties and even when compact tension samples with side grooves are utilized, it is unlikely that plane strain conditions are achieved during laboratory testing. Thus, the measured toughness may not be directly relevant to assessing in-service performance. The present research has been undertaken as part of an integrated series of projects seeking to define a robust protocol for assessing the damage tolerance of piping used for the transmission of hydrogen, especially when considering repurposing existing infrastructure. The key work described in this paper involved establishing heat treatments which produced microstructures relevant to the constituents found in ex-service welds of X46 type steel. Following comprehensive microstructural characterization, these heat treatments were applied to steel sections which allowed for the fabrication of standard compact tension specimens, which were subsequently tested in hydrogen to measure fracture toughness. The results obtained showed that the fracture behavior varied for different microstructures. To identify the influence that hydrogen gas has on the performance of pipeline steels, it is important to assess microstructures relevant to the welds present, as testing only on base metal may not provide conservative information. However, the results from well-planned and carefully executed programs can be used to identify the relative performance in hydrogen. The data can also be used as critical input to models which form part of an integrated approach to structural integrity assessment. Full article

Siraitia grosvenorii fruit, a traditional medicinal and edible plant, undergoes significant alterations in quality and bioactive composition during the dehydration process. This study investigated the effects of hot-air drying at various temperatures on the physicochemical properties, antioxidant activity, and drying kinetics of S. grosvenorii fruit. The drying process was terminated when fruit moisture content reached 15%, with corresponding drying durations of 420, 225, 144, 96, and 51 h at 40 °C, 50 °C, 60 °C, 70 °C and 80 °C, respectively. Among the ten mathematical models evaluated, the Midilli–Kucuk model provided the most accurate description of the drying kinetics of S. grosvenorii fruit. Quality analysis revealed that drying reduced the sugar/acid ratio, contents of mogrosides and ascorbic acid, while increasing total phenolic and flavonoid levels. Microstructural analysis revealed that higher temperatures increased drying rates by expanding the porosity of the pulp. Based on the retention of bioactive components and antioxidant capacity, 70 °C was identified as the optimal drying temperature. Overall, these findings suggest that oven-drying optimizes drying efficiency and ensures the retention of essential bioactive constituents in S. grosvenorii. Full article

Isodonis Excisoidis Herba (IEH) is a newly discovered herbal medicine used to treat esophageal cancer, chronic pharyngitis, and hepatitis, and ent-kaurane diterpenoids are its main active components. However, systematic studies on the chemical profile of ent-kaurane diterpenoids are lacking. In this study, UHPLC-LTQ-Orbitrap-MS was performed to investigate the fragmentation behaviors of three different types of ent-kaurane diterpenoids from IEH. Bridgehead-unsubstituted 7,20-epoxy-ent-kaurane diterpenoids yielded ions with typical losses of R₇H, R₁H, R₁₄H, CH₂O, CO, and R₆H. The [M + NH₄ − NH₃ − R₂₀]⁺ precursor ions at 331.1895 and the characteristic ions at m/z 313.1792, 295.1686, 285.1842, 277.1581, 267.1737, and 249.1632 were the most possible fragmentation pathways for bridgehead-substituted 7,20-epoxy-ent-kaurane diterpenoids. Fragmentation with the successive loss of multiple 18, 42, or 60 Da occurring in the OH groups and OAc groups is characteristic of 7,20-non-epoxy-kaurane diterpenoids. Using accurate mass measurements for each precursor ion and the subsequent fragmented ions, a total of 94 ent-kaurane diterpenoids were identified or tentatively characterized in IEH, including 48 potentially new ent-kaurane diterpenoids. Full article

Maintaining color constancy in polymer extrusion processes is a key difficulty in manufacturing applications, as fluctuations in processing parameters greatly influence pigment dispersion and the quality of the finished product. Preliminary historical data mining analysis was conducted in 2009. This work concentrates on Opaque PC Grade 5, which constituted 2.43% of the pigment; it contained 10 PPH of resin2 with a Melt Flow Index (MFI) of 6.5 g/10 min and 90 PPH of resin1. It also employs a fixed resin composition with an MFI of 25 g/10 min. This research identified the significant processing parameters (PPs) contributing to the lowest color deviation. Interactions between processing parameters, for the same color formulation, were analyzed using statistical methods under various processing conditions. A principle-driven General Trends (GT) diagnostic procedure was applied, wherein each parameter was individually varied across five levels while holding others constant. Particle size distribution (PSD) and colorimetric data (CIE Lab*) were systematically measured and analyzed. To complete this, correlations for the impact of temperature (Temp) on viscosity, particle characteristics, and color quality were studied by characterizing viscosity, Digital Optical Microscopy (DOM), and particle size distribution at various speeds. The samples were characterized for viscosity at three temperatures (230, 255, 280 °C) and particle size distribution at three speeds: 700, 750, 800 rpm. This study investigates particle processing features, such as screw speed and pigment size distribution. The average pigment diameter and the fraction of small particles were influenced by the speed of 700–775 rpm. At 700 rpm, the mean particle size was 2.4 µm, with 61.3% constituting particle numbers. The mean particle size diminished to 2 µm at 775 rpm; however, the particle count proportion escalated to 66% at 800 rpm. This research ultimately quantifies the relative influence of particle size on the reaction, resulting in a color value of 1.36. The mean particle size and particle counts are positively correlated; thus, reduced pigment size at increased speed influences color response and quality. The weighted contributions of the particles, 51.4% at 700 rpm and 48.6% at 800 rpm, substantiate the hypothesis. Further studies will broaden the GT analysis to encompass multi-parameter interactions through design experiments and will test the diagnostic assessment procedure across various polymer grades and colorants to create robust models of prediction for industrial growth. The global quality of mixing polycarbonate compounding constituents ensured consistent and smooth pigment dispersion, minimizing color streaks and resulting in a significant improvement in color matching for opaque grades. Full article

Contrast-induced acute kidney injury (CIAKI) has emerged as the third most prevalent etiology of clinically acquired acute kidney injury, with a lack of specific preventive and therapeutic strategies. Rubia Cordifolia L. (madder root), a medicinal herb with a long-standing history and extensive clinical application, exhibits multiple pharmacological activities. This study aimed to clarify the renal protective effect of Rubia cordifolia L. dichloromethane extract (RCDE) on CIAKI modeling rats and investigate potential anti-apoptotic and autophagy-inducing effects molecular mechanisms. In this study, RCDE constituents were identified by UPLC-Q-TOF-MS. A CIAKI rat model was established to evaluate the nephroprotective effect of RCDE. The results showed that RCDE high-dose group significantly decreased serum SCr and BUN levels, attenuated renal histopathological damage, and modulated oxidative stress markers by decreasing MDA and CAT while increasing SOD, compared with the model group. It downregulated the expressions of Bcl-2, caspase-3 and p62, upregulated the expressions of Bax, Beclin1 and reduced the LC3B-II/LC3B-I ratio in renal tissues. Molecular docking indicates that anthraquinone compounds are probably the principal active constituents of RCDE. This study provides experimental evidence for the intervention efficacy of RCDE against CIAKI. Full article

Immune checkpoint inhibitors (ICIs) for cancer therapy may induce immune-related adverse events including myocarditis, which occurs infrequently but carries a high mortality rate. Crocins are the active constituents derived from Crocus sativus L. (saffron), and have demonstrated various bioactivities including anti-tumor, anti-inflammation, antioxidation, anti-ischemia, anti-aging, and neuroprotective effects. This study established a subcutaneous xenotransplanted tumor model of human liver cancer in nude mice to better mimic ICI-related myocarditis. Animal experimental results revealed that crocins improved cardiac function, relieved myocardial damage and autoimmune response, and suppressed oxidative stress and inflammatory reaction. Quantitative proteomics and Western blotting verification confirmed that crocins ameliorated experimental ICI-related myocarditis by targeting the Hpx/Nrf2/HO-1 pathway. Molecular docking revealed that the best docking activities were demonstrated by crocin I–HO-1, crocin II–Hpx, and crocin III–Nrf2. These findings shed new light on the development of therapeutic strategies for treating ICI-related myocarditis and provided the fundamental basis for expanding the clinical application of crocins. Full article

Utilizing forestry and agricultural byproducts like wood and hemp residues advance sustainable additive manufacturing (AM), while reducing material costs. This study investigated the development and characterization of wood–sodium silicate composites incorporating hemp hurd and hemp fibers for AM applications. Formulations varied by wood fiber type (unsifted, 40 mesh, and pellet), sodium silicate concentration (50–60 wt%), and hemp hurd content (0–15 wt%). Properties evaluated include particle size and bulk density of the constituent materials, rheological behavior, extrusion performance, composite bulk density, and flexural and compressive strengths. Rheology and extrusion were largely influenced by the liquid content. Mixtures with low liquid content (50 wt% sodium silicate) had high motor power and low viscosity. As liquid content increased, motor power decreased, while viscosity increased up to 55 wt% and then decreased at 60 wt%. Mechanical properties correlated with particle size, where finer particles enhanced strength. A cost analysis was conducted using raw material prices to determine the economic feasibility of each formulation. Finally, the formulations were evaluated based on strength-to-cost ratios, extrudability and processability. The formulation with pellet wood fibers, 55 wt% sodium silicate, and 10 wt% hemp hurd achieved a high ratio of 73.0 MPa/$ while maintaining low motor power. This formulation offered additional benefits which are discussed qualitatively. Full article

An integrated field–analytical framework was applied to quantify the impact of two small-settlement treatment facilities (TF1 and TF2) on the Irtysh River (East Kazakhstan). The main objective of this study is to quantify effluent-driven dilution and non-conservative changes in key water-quality indicators downstream of TF1 and TF2 and to evaluate parsimonious models for predicting effluent-outlet BOD and COD from upstream measurements. Paired upstream–downstream control sections are sampled in 2024–2025 for 22 indicators, and plant influent–effluent records are compiled for key wastewater variables. Chloride-based conservative mixing indicated very strong dilution (approximately $D\approx 2.0\times {10}^3$ for TF1 and $D\approx 4.2\times {10}^2$ for TF2). Deviations from the mixing line were summarized using a transformation diagnostic $\theta$. At TF1, several constituents exceeded mixing expectations ($\theta \approx 13$ for COD, $\theta \approx 42$ for ammonium, and $\theta \approx 6$ for phosphates), while nitrate shows net attenuation $\theta <0$. At TF2, $\theta$ values cluster near unity, indicating modest deviations. Under a small-sample regime $\left(\mathrm{N}=10\right)$ and leave-one-out validation, regularized regression provided accurate forecasts of effluent-outlet BOD and COD. Lasso under LOOCV performed best (BOD_after: RMSE = 0.626, MAE = 0.459, and $R^2=0.976$; COD_after: RMSE = 0.795, MAE = 0.634, and $R^2=0.997$). The results reconcile strong reach-scale dilution with constituent-specific local departures and support targeted modernization and operational forecasting for water-quality management in small facilities. Full article

Rice bran oil (RBO) is increasingly valued for its bioactive constituents and associated health benefits. This study presents a comprehensive comparative analysis of RBOs derived from purple (PRBO), red (RRBO), and white (WRBO) rice bran, focusing on their physicochemical properties, fatty-acid profiles, bioactive components, antioxidant activity, oxidative stability, and lipidomics. Our results demonstrate that PRBO consistently exhibited a more favorable fatty-acid composition, characterized by a higher proportion of unsaturated fatty acids and significantly greater concentrations of bioactive compounds (including tocopherols/tocotrienols, γ-oryzanol, phytosterols, and squalene). Accordingly, PRBO showed the highest radical-scavenging activity and storage oxidative stability, followed by RRBO and WRBO. Additionally, untargeted lipidomics using UPLC–MS–MS identified 2908 lipid species spanning 57 subclasses and revealed distinct variety-specific lipid signatures. PRBO was uniquely enriched in lipid species such as ceramide phosphate (CerP) and monogalactosyldiacylglycerol (MGDG). RRBO was characterized by a distinct abundance of sitosteryl esters (SiE), phosphatidic acid (PA), and cardiolipin (CL), while WRBO was distinguished by phosphatidylethanol (PEt), lysodimethylphosphatidylethanolamine (LdMePE), and sphingomyelin (SM). Overall, PRBO possessed not only a broader repertoire of lipid species but also higher relative abundances of nutritionally significant lipids. These results enable quality evaluation and varietal authentication of colored RBOs and guide their targeted use in health-oriented foods and nutritional interventions. Full article

In the context of climate change and the general trend toward a healthy lifestyle, reducing the alcoholic strength of wines poses a major challenge for producers. In order to obtain quality low-alcohol wines (LAWs), Muscat Ottonel conventional wine was subjected to reverse osmosis followed by vacuum concentration of the hydroalcoholic permeate (ROVC) or to two-step vacuum concentration (TSVC), with the recovery of aromas as the first alcoholic fraction (F1). Beverages with alcoholic concentrations of 3.50, 5.50, and 8.50% vol. were obtained, with compositional characteristics and sensory properties varying significantly with alcoholic strength and dealcoholization technique applied. ROVC produced wines with organic acids, volatile constituents, extract, and color intensity decreasing progressively with the reduction in alcohol concentration. At similar alcohol concentration, TSVC LAW showed a significantly higher phenolic content, antioxidant activity, volatile compounds (including esters and terpenes), and overall structural balance, maintaining better the typicity of wines. In both processes, reducing alcohol below 5.50% vol. significantly affected the quality and acceptability of the final product. Hierarchical cluster analysis indicated that TSVC LAWs were statistically closer to the conventional wine (control). These findings improve the understanding of how dealcoholization technologies affect the composition of wine, improving product quality, sustainability, and operational efficiency. Full article

The emergence of SARS-CoV-2, the etiological agent of COVID-19, has resulted in widespread global infection and millions of deaths. Viral entry is initiated by the interaction between the viral spike (S) protein and the host cell receptor ACE2, followed by TMPRSS2-mediated proteolytic activation that facilitates membrane fusion. Bitter melon (Momordica charantia L., MC), a traditional medicinal and edible plant widely used in tropical Asia, possesses notable anti-inflammatory, antioxidant, antitumor, and hypoglycemic properties. In this study, the ethanol extract of bitter melon (EMC) markedly downregulated ACE2 and TMPRSS2 expression in both in vitro and in vivo models without inducing cytotoxicity. Furthermore, phytochemicals isolated from EMC—including p-coumaric acid, rutin, and quercetin—exhibited comparable inhibitory effects. These results indicate that EMC and its bioactive constituents may interfere with SARS-CoV-2 entry by modulating the ACE2/TMPRSS2 axis, highlighting their potential as natural adjuncts for COVID-19 prevention or management. Full article

We investigate the profitability of systematic sector rotation strategies in the Canadian equity market using TSX 60 constituents (2000–2025). Testing 72 distinct strategies across three theoretical frameworks—momentum, mean-reversion, and balanced approaches—with varying rebalancing frequencies, we identify that median-performer selection combined with quarterly rebalancing generates statistically significant risk-adjusted returns (Sharpe ratio 0.922 versus 0.624 for equal-weighted buy-and-hold). Our primary contributions include rigorous out-of-sample validation, demonstrating performance persistence from 2020 to 2025, machine learning regime classification with 72.7% accuracy, and a comprehensive transaction cost analysis. Results support intermediate-horizon mean reversion in sector returns and challenge strict efficient market hypothesis interpretations in concentrated markets. Findings inform tactical asset allocation practices and contribute to the momentum-reversal literature by documenting conditions under which rotation strategies generate economically meaningful alpha. Full article

Curcumin is a polyphenolic compound isolated from Curcuma longa, which is widely recognized for its therapeutic properties: particularly its strong anti-inflammatory and antioxidant activities. However, its practical incorporation into functional foods, especially aqueous dairy beverages, is severely hindered by its extremely low water solubility, poor chemical stability (notably at the near-neutral pH of milk), and very limited oral bioavailability. This review provides a critical synthesis of the literature published in the last two decades, with a focus on the development and application of food-grade oil-in-water (O/W) nanoemulsions to advanced colloidal delivery systems. It covers the fundamental principles of nanoemulsion formulation, including the selection of the oil phase, surfactants, and stabilizers, as well as both high-energy and low-energy fabrication techniques. It further examines the integration of these nano-delivery systems into dairy matrices (milk, yogurt, cheese), highlighting key interactions between nanoemulsion droplets and native dairy constituents such as casein micelles and whey proteins. Critically, findings indicate that nanoencapsulation not only enhances curcumin’s solubility but also protects it from chemical degradation during industrial processes, including pasteurization and sterilization. Moreover, the dairy matrix structure plays a key role in modulating curcumin bioaccessibility, with fortified products frequently exhibiting enhanced stability, shelf life, and sensory attributes. Finally, key technological challenges addressed the heterogeneous global regulatory landscape surrounding biopolymers and future trends: most notably, the growing shift toward “clean-label” biopolymer-based delivery systems. Full article

Background: Chronic nonbacterial prostatitis (CNP), the major subset of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), imposes a substantial global burden yet lacks satisfactory therapies. Maizibizi Wan (MZBZ) has long been used clinically for prostatitis, but its pharmacodynamic substance basis and mechanisms remain unclear. Methods: Ultra-high-performance liquid chromatography–Q-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS) coupled with Global Natural Products Social Molecular Networking (GNPS) molecular networking profiled MZBZ constituents and rat plasma–exposed prototype components and metabolites was used. Based on blood-absorbable components, network pharmacology predicted core targets/pathways; representative interactions were validated by molecular docking. A λ-carrageenan–induced CNBP rat model underwent histopathology (H&E), serum cytokine assays (TNF-α, IL-1β, IL-6/IL-17), immunohistochemistry (COX-2, TNF-α, MMP-9), and Western blotting (P-p65/p65, p-AKT/AKT, COX-2, TGF-β1, BCL2). Results: A total of 188 chemical constituents were identified in MZBZ (79 flavonoids, 38 organic acids, 30 alkaloids, 15 phenylpropanoids, 7 steroids, 4 phenylethanoid glycosides, 15 others). A total of 35 blood-absorbable components (18 prototype components, 17 metabolites) were identified, mainly involving Phase I oxidation and Phase II glucuronidation/sulfation. Network analysis yielded 54 core targets enriched in NF-κB and PI3K/AKT signaling and apoptosis. Docking indicated stable binding of key flavonoids to COX-2, NFKB1, TNF, IL-6, and BCL2. In vivo, MZBZ ameliorated prostatic inflammation, reduced serum TNF-α/IL-1β/IL-6/IL-17 (p < 0.05 or p < 0.01); decreased P-p65/p65, p-AKT/AKT, COX-2, and TGF-β1; and increased BCL2 in prostate tissue. Conclusions: MZBZ exerts anti-CNBP effects via multi-component synergy (prototypes + metabolites) that suppresses inflammatory cytokines, modulates apoptosis, and inhibits NF-κB and PI3K/AKT pathways. These findings provide a mechanistic basis and quality control cues for the rational clinical use of MZBZ. Full article