Search Results (150)

Background/Objective: Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β plaques, derived from the amyloid precursor protein through sequential cleavage by β-secretase 1 (BACE-1) and γ-secretase. BACE-1 is therefore a key drug target for designing of selective inhibitors to avoid off-target effects associated with BACE-2 inhibition. The objective of this study was to design novel BACE-1 inhibitors using a structure-based drug design approach. Methods: A focused compound library was designed based on the SAR of N-(4-fluorophenyl)formamide derivatives. In silico ADME predictions were performed to assess pharmacokinetic suitability. Compounds showing favorable ADME profiles were subjected to molecular docking against the BACE-1 enzyme. The top-scoring hit, compound 9.7 (−5.48 (kcal/mol), was further evaluated using a 200 ns MD simulation to assess the stability of its binding interactions with BACE-1. Results: Designed compounds indicated acceptable physicochemical and ADME characteristics. Molecular docking identified compound 9.7 as exhibiting favorable binding interactions with binding pocket residues of BACE-1. The 200 ns MD simulation further confirmed the stability of the docked complex. MD simulations confirmed that 9.7 forms stable interactions with the catalytic residue ASP32 and key hydrophobic residues TRP115 and PHE108 of BACE-1. These important interactions are absent in the reference compound verubecestat. Conclusions: The multi-step computational analysis suggests that compound 9.7 is a promising and selective BACE-1 inhibitor. Its favorable ADME profile, favorable docking interactions, and stable MD simulation behavior highlight its potential as a hit compound for further optimization in the development of anti-Alzheimer’s agents. Full article

An innovative approach to improving the quality of meat products is to change their recipe composition. The aim of the study was to improve the quality of poultry products with different proportions of plant components. The test groups consisted of paste products: P₁—with 50% slaughter turkey meat and 40% plant additives; P₂—with 30%, respectively. The control group consisted of classic poultry pâté in paste form. The assessment of paste quality considered the physical characteristics (pH, color), nutritional value (basic chemical composition, fatty acid profile, fiber content, vitamin E, cholesterol, minerals), microbiological quality (total number of aerobic bacteria, Pseudomonas) and sensory quality of the samples. It was found that poultry products containing plant components had increased nutritional value, including reduced fat and cholesterol content, while maintaining a favorable fatty acid profile, increased fiber, vitamin E and mineral content (Mg, Mn, K, Na, Ca, Fe) as well as microbiological safety and acceptable sensory characteristics compared to the control group. Within the research groups, the product from group P2, with a 60% share of plant components, received a higher recommendation with regard to health-promoting properties (higher fiber, Mn, Mg, Na, Ca, Zn content, optimal ratio of omega 6 to omega 3 fatty acids) and sensory characteristics (tastiness, spreadability). Full article

Background: In phenylketonuria (PKU) patients, dried blood spot (DBS) sampling remains the standard method for monitoring phenylalanine (Phe) levels. However, delays in reporting results can hinder timely dietary adjustments. Patients and caregivers have expressed a preference for point-of-care testing (POCT) devices that enable home-based monitoring. Objectives: Our aim was to compare blood Phe measurements in PKU patients and caregiver usability of a POCT system with DBS, which is the standard practice monitoring method. Methods: Twenty participants (eighteen children with PKU and two healthy controls) were recruited. Caregivers of children with PKU were asked to perform blood Phe measurements at home under the supervision of a researcher, using both the POCT device (Egoo Phe system) and DBS sampling. Healthy controls collected the same number of samples using both methods in a hospital setting. The POCT system required 40 µL of blood and used an enzymatic, bioluminescent detection system. DBS samples were analyzed by tandem mass spectrometry (TMS) and required two blood spots (approximately 100 µL of blood). The Egoo Connect App, linked via Bluetooth to the POCT device, displayed results after 29 min. Caregiver usability of the POCT system was assessed using questionnaires at each visit. Results: A total of 100 paired samples were collected. Median values were 274 μmol/L (range: 30–1039) for POCT and 270 μmol/L (range: 20–1190) for DBS. POCT readings were a mean of 4.6% higher than DBS with a noticeable strong correlation observed (y = 1.017x; R² = 0.8450; p < 0.0001). The usability of the POCT system improved with caregiver practice, and all caregivers expressed a preference for POCT over DBS. Conclusions: The POCT system for blood Phe demonstrated strong concordance with DBS and high caregiver acceptance, highlighting its potential to transform PKU care through faster, patient-driven monitoring and more timely clinical decision-making. Full article

Background: Gastroesophageal reflux disease (GERD) exposes restorative materials to gastric acid, which may compromise their esthetic and optical properties. Limited evidence exists regarding the performance of different CAD/CAM ceramics under acidic challenges. Methods: Forty CAD/CAM ceramic discs were prepared (n = 10 per group): high-translucency zirconia (Z; Ceramill Zolid Gen-X), lithium disilicate (E; IPS e.max CAD), zirconia-reinforced lithium silicate (S; VITA Suprinity), and hybrid ceramic (C; Cerasmart 270). Specimens were immersed in simulated gastric acid (0.06 M HCl, pH 1.2) at 37 °C for 96 h. Color difference (ΔE) and translucency parameter (ΔTP) were recorded before and after immersion using a spectrophotometer. Data were analyzed using one-way ANOVA with Tukey’s post hoc test (α = 0.05). Results: All materials exhibited changes in color and translucency after acidic immersion. Group Z demonstrated the lowest ΔE values, indicating the best color stability, whereas group C showed the highest ΔE and a significant reduction in ΔTP. Groups E and S revealed moderate but clinically acceptable changes. Intergroup differences were statistically significant (p < 0.05). Conclusions: Exposure to simulated gastric acid as in (GERD) resulted in measurable alterations in the optical properties of CAD/CAM ceramic materials. The extent of color change and translucency loss differed among the materials tested. High-translucency zirconia (Z) exhibited the greatest stability, while hybrid ceramic (C) showed the most pronounced changes. Zirconia-reinforced lithium silicate (S) and lithium disilicate (E) demonstrated moderate alterations, falling between these two extremes. Full article

The development of bioactive food packaging is an important issue, given its potential to preserve food quality and safety without the use of synthetic preservatives. This study aimed to develop new polystyrene foam (PS) films with hydroxytyrosol (HOxTYR) and eugenol (EUG), alone or in combination, as bioactive molecules to preserve sliced sponge cake during long-term storage. The cake samples were analyzed periodically during storage at 15 °C in terms of quality attributes (pH, water activity, height, volume and weight loss, firmness, CIE Lab color, lipid peroxidation products, microbial spoilage, and overall acceptability) and shelf life. The active film containing the combination of 0.6% HOxTYR and 0.6% EUG showed the strongest antioxidant activity, which was attributed to a potential synergism between the compounds, resulting in lower lipid oxidation rates (TBARS). The combination of HOxTYR and EUG also offered the greatest reduction in bacterial load (62% for S. aureus and 58% for E. coli), suggesting a synergistic effect on microbial inhibition. Likewise, samples packaged in a modified atmosphere (MAP) with the active film containing the combination of HOxTYR and EUG showed the best performance, including a smoother texture and greater volume, more stable color, lower microbial counts, and greater overall acceptability, and, consequently, a longer shelf life of up to 70 days at room temperature. Furthermore, the results of this study could contribute to environmental protection by reducing food waste, and suggest that the developed active packaging technique represents a promising and innovative approach to the preservation of bakery products. Full article

Cold-ripened fish marinades, produced mainly from Atlantic herring, represent one of the major seafood products in Northern and Central Europe. Because the shelf-life of these mildly acidified, salty products rarely surpasses 4 weeks, more than half of the commercial lots contain the preservatives sodium benzoate (E211) and potassium sorbate (E202). However, the broader technological consequences of such additives remain poorly documented. This study evaluated the impact of 0.25 (w/w) benzoate + 0.10 g/100 g sorbate on the quality of industrial-scale marinades (200 kg fish; 7 d, 4 ± 1 °C). Physicochemical traits (mass loss, pH, proximate composition, salt content, colour, and texture), enzymatic indices of ripening (cathepsins, amino-peptidases, and TCA soluble nitrogen fractions), lipid oxidation, microbial growth, and sensory attributes were analyzed. Preservatives caused only marginal changes in pH and proximate composition (0.3–3.4% w/w differences) but markedly suppressed proteolysis. Free amino acid and peptide fractions in muscle decreased by 6.0% and 8.8%, in parallel to 45% and 22% reductions in leucine- and alanine-amino-peptidase activities in muscle. In the marinating brine, the levels of total nitrogen, peptides, and free amino acids were also lower in the samples with preservatives, confirming that sodium benzoate and potassium sorbate slowed down the enzymatic ripening of the marinades. Concomitantly, peroxide, p-anisidine, and TOTOXs increased by up to 9.4, 71.3, and 33.7%, respectively, indicating accelerated lipid oxidation despite the chelating capacity of benzoate/sorbate acids. Overall sensory acceptability declined slightly (−0.15 points on a five-point scale), mainly owing to chemical off-flavours and lower juiciness. Microbial counts remained <1.0 log CFU/g in the preservative batch versus 2.1 log in the control. Benzoate–sorbate combinations effectively stabilized the microbiota of marinated herring without appreciably altering basic physicochemical traits, but they retard enzymatic ripening, diminish antioxidant peptide pools, and thereby promote lipid oxidation—collectively lowering the nutritional value. The data supports a cautious, minimal-use approach to application of chemical preservatives in cold-ripened fish products. Full article

This study investigated the interaction between cannabidiol (CBD) derivatives and the GPR55 receptor using a bioinformatics-driven molecular docking approach. GPR55, implicated in central nervous system (CNS) pathologies, represents a promising target for novel therapeutics. Drug-likeness evaluation via SwissADME confirmed that all selected derivatives complied with Lipinski′s Rule of Five, exhibiting favorable physicochemical properties with molecular weights below 500 Da and acceptable logP values. Molecular docking simulations, performed using AutoDock Vina through PyRx, revealed strong binding affinities, with docking scores ranging from −9.2 to −7.2 kcal/mol, indicating thermodynamically feasible interactions. Visualization and interaction analysis identified a conserved binding pocket involving key residues, including TYR101, PHE102, TYR106, ILE156, PHE169, MET172, TRP177, PRO184, LEU185, LEU270 and MET274. Ligand clustering in this region further supports the presence of a structurally defined binding site. Molecular dynamics simulations of GPR55 in complex with the three top-scoring ligands (3″-HOCBD, THC, and CBL) revealed that all ligands remained stably bound within the cavity over 100 ns, with ligand-specific rearrangements. Predicted oral bioavailability was moderate (0.55), consistent with the need for optimized formulations to enhance systemic absorption. These findings suggest that CBD derivatives may act as potential modulators of GPR55, offering a basis for the development of novel CNS-targeted therapeutics. Full article

This study examined how perceptions of artificial intelligence (AI) relate to technostress in healthcare professionals, testing whether AI acceptance mediates this relationship and whether self-efficacy moderates the formation of acceptance. Seventy-one participants completed measures of Perceptions of AI (Shinners), AI Acceptance (UTAUT), Self-Efficacy, and four technostress outcomes: Technostress Overall, Techno-Overload, Techno-Complexity/Insecurity, and Techno-Uncertainty. Conditional process analyses (PROCESS Model 7; 5000 bootstrap samples) were performed controlling for sex, age (years), and professional role (radiology residents, attending radiologists, PhD researchers). Perceptions of AI were directly and positively associated with Technostress Overall (b = 0.57, p = 0.003), Techno-Overload (b = 0.58, p = 0.008), and Techno-Complexity/Insecurity (b = 0.83, p < 0.001), but not with Techno-Uncertainty (b = −0.02, p = 0.930). AI Acceptance negatively predicted the same three outcomes (e.g., Technostress Overall b = −0.55, p = 0.004), and conditional indirect effects indicated significant negative mediation at low, mean, and high self-efficacy for these three outcomes. Self-efficacy moderated the Perceptions → Acceptance path (interaction b = −0.165, p = 0.028), with a stronger X→M effect at lower self-efficacy, but indices of moderated mediation were not significant for any outcome. The results suggest that perceptions of AI exert both demand-like direct effects and buffering indirect effects via acceptance; implementation should therefore foster acceptance, build competence, and address workload and organizational clarity. Full article

Despite the growing acceptance of the varieties of English, standard language ideology continues to cause some to be valorized and denigrated. This paper examines the attitudes of Filipino-Americans within an inner-circle English variety zone towards Philippine English (PhE), focusing on its status, development, lexicon, intelligibility, and acceptability. The study surveyed 113 Filipino-American speakers of American English (AmE) who were familiar with Philippine culture and PhE. Studies show that some first-language English speakers exhibit negative attitudes towards new English varieties. Contrary to this trend, our findings reveal positive attitudes among AmE speakers towards PhE. However, although it is commonly understood, these positive attitudes do not guarantee the full acceptability of PhE. Notably, there is a growing trend towards the acceptability of PhE neologisms, especially in formal and scientific contexts, indicating a shift in previous perceptions. Additionally, the findings of the study highlight that word-formation processes significantly influence the acceptability of new terms across different speech domains, a novel finding that merits further investigation. Acceptability plays a vital role in the dissemination of local expressions and in shaping the status of a language variety. This research may contribute to understanding the evolving dynamics of the acceptability of PhE and its status in local and international contexts. The positive attitudes towards PhE among American English speakers indicate a shift in perceptions. Language teaching can build on this trend by fostering an environment where students are encouraged to appreciate and respect different English varieties. This can be achieved through exposure to diverse linguistic inputs and discussions on language attitudes. Full article

Breast cancer is a prevalent malignancy worldwide. Human MutT homolog 1 (MTH1) is over expressed in breast tumors, and cancer cells rely on MTH1 for survival. This protein ensures the integrity of the nucleotide pool by preventing the integration of oxidized 2′-deoxynucleoside triphosphates (dNTPs) during DNA replication. Therefore, inhibiting MTH1 pharmacologically emerged as a valid target in treating breast cancer. In the present study, we screened biologically active phytochemicals from the NPACT database to discover potential inhibitors of MTH1. Molecular docking analysis was employed to identify the binding conformation and the interaction pattern. The top five compounds were selected for detailed analysis based on their superior binding affinity and interactions with crucial residues (Asn33, Gly36, Tyr7, Phe72, Trp117, Lys23, and Phe27, Glu100) of MTH1. Additionally, the ADMET profile of selected compounds highlighted the high intestinal absorption, low toxicity, and acceptable metabolic stability, exhibiting their potential as drug candidates. Furthermore, in silico validation of selected compounds was performed through molecular dynamics (MD) simulation, which revealed that the resultant complexes are appreciably stable. Compounds revealed RMSD values ranging between 1.0 and 1.5 Å, indicating strong and stable binding conformations. PCA analysis revealed restricted conformational sampling, highlighting stabilization, particularly with ZINC14727630, ZINC14819291, ZINC14781695, and ZINC95099417. MM-GBSA confirmed the stability of the ligand–protein complexes, with ZINC14819291, ZINC14727630, and ZINC95099417 demonstrating the most stable interactions with MTH1, with total binding free energies of −32.46, −45.06, and −33.44 kcal/mol, respectively. Our results support that these natural compounds could act as potential anti-MTH1 for ameliorating the breast cancer. However, experimental validation is required to validate the efficacy of these molecules and robustness of this anticancer approach. Full article

Phosphorus contamination in water bodies is a major contributor to eutrophication, leading to algal overgrowth, oxygen depletion, and ecological imbalance. Conventional treatment methods, including chemical precipitation and synthetic adsorbents, are often limited by high operational costs, low biodegradability, and secondary pollutant generation. In this study, a cationic starch was synthesized through free radical graft polymerization of 3-methacrylamoylaminopropyl trimethyl ammonium chloride (MAPTAC) onto corn starch. The modified polymer exhibited a high degree of substitution (DS = 1.24), indicating successful functionalization with quaternary ammonium groups. Theoretical calculations using zDensity Functional Theory (DFT) at the B3LYP/6-311+G(d,p) level revealed a decrease in chemical hardness (from 0.10442 eV to 0.04386 eV) and a lower ionization potential (from 0.24911 eV to 0.15611 eV) in the modified starch, indicating enhanced electronic reactivity. HOMO-LUMO analysis and molecular electrostatic potential (MEP) maps confirmed increased electron-accepting capacity and the formation of new electrophilic sites. Experimentally, the cationic starch showed stable zeta potential values averaging +15.3 mV across pH 5.0–10.0, outperforming aluminum sulfate (Alum), which reversed its charge above pH 7.5. In coagulation-flocculation trials, the modified starch achieved 87% total suspended solids (TSS) removal at a low coagulant-to-biomass ratio of 0.0601 (w/w) using Scenedesmus obliquus, and 78% TSS removal in real wastewater at a 1.5:1 ratio. Additionally, it removed 30% of total phosphorus (TP) under environmentally benign conditions, comparable to Alum but with lower chemical input. The integration of computational and experimental approaches demonstrates that MAPTAC-modified starch is an efficient, eco-friendly, and low-cost alternative for nutrient and solids removal in wastewater treatment. Full article

Soil health is an important concept in promoting sustainable agriculture and food security, yet the absence of universally accepted benchmarks limits its utility in assessing soil function. This study explored the use of Conservation Reserve Program (CRP) soils as a potential benchmark to quantify the soil health gap (SHG) in Faribault County, Minnesota. Using the Soil Management Assessment Framework (SMAF), we evaluated physical, chemical, biological, and nutrient soil health indicators to derive a combined overall score that was used to quantify the SHG (i.e., benchmark soil minus test soil) between CRP and corn-based agricultural production (AP). Three paired farms were assessed, each consisting of CRP tall grass prairie established in 2001 and adjacent long-term AP. The results showed higher overall SMAF scores in CRP soils, with a mean SHG of 0.09. Land use had a strong influence on overall scores, largely driven by biological indicators such as soil organic carbon, microbial biomass carbon, and β-glucosidase activity. However, the SMAF demonstrated limited applicability in CRP systems, potentially under-representing their soil health status due to the SMAF’s agricultural emphasis and lack of ecosystem-specific factors such as pH. Full article

HIV/AIDS and Mycobacterial tuberculosis (Mtb) are the leading cause of deaths worldwide. Thus, better medicaments are required to manage these diseases. Quinolines have shown great potential due to their broad spectrum of biological activity. Thus, quinoline–1,2,3-triazole–aniline hybrids were synthesised in moderate to good yields. Compounds 11g (IC₅₀ = 0.388 µM), 11h (IC₅₀ = 0.01032 µM) and 11i (IC₅₀ = 0.167 µM) exhibited the most promising in vitro activities against the wild-type HIV-1 subtype B, with 11h being 9-fold more active than AZT (IC₅₀ = 0.0909 µM), the reference drug. Furthermore, compound 11h displayed moderate activity, with a MIC₉₀ of 88μM against Mtb’s H37Rv strain. Cytotoxicity studies on TZM-bl cell lines revealed that most of the tested compounds were generally non-cytotoxic; the selectivity index (SI) for 11h, the front runner, is >2472. Molecular docking studies revealed that 11h interacted with Phe112, Tyr108, Glu283 and Trp86 amino acid residues in the active site of HIV-1. DFT studies revealed that 11h has the ability to donate and accept electrons to and from available orbitals. The predicted ADMET studies showed that these compounds possess drug-likeness, and 11h has the potential for further optimisation as an anti-HIV-1 agent. Full article

Background: This study aims to evaluate the quality of treated wastewater flowing in the Zarqa River to determine its suitability for agricultural use. The assessment is based on physicochemical and biological parameters in accordance with Jordanian standards (JS 893:2021), the CCME water quality index, and the weighted arithmetic water quality index (WAWQI). Additionally, a microbial assessment was conducted to identify the presence of pathogens in the treated wastewater. Methods: A total of 168 water samples were collected from seven different sites along the Zarqa River over a 24-month period. This study focused on microbial assessment and selected parameters from the JS 893:2021, including total dissolved solids (TDSs), biochemical oxygen demand (BOD), dissolved oxygen (DO), chemical oxygen demand (COD), and E. coli levels. Furthermore, data were gathered on additional physicochemical parameters such as pH, mineral content (including Na, Ca, K, Mg, and Cl), salts (HCO₃, SO₄, NO₃, and PO₄), and heavy metals (Fe, Cu, Pb, Mn, and Co). The CCME water quality index and weighted arithmetic WQI scores were calculated to determine the water quality from all seven study sites. Results: In terms of Jordanian standards, Site 1 had the lowest TDS and DO values along with E. coli concentration. Further, in terms of minerals and salts, the maximum concentrations found for the sites are given herewith: Site 2 (K⁺ and NO₃), Site 3 (Cl⁻, Na⁺), Site 5 (Ca, HCO₃), and Site 7 (Mg²⁺, PO₄, and SO₄). In terms of pH, all the study sites had pH values within the acceptable range, i.e., between 6 and 9, for irrigation purposes. The concentrations of certain heavy metals, specifically lead (Pb), manganese (Mn), and cobalt (Co), were observed to be negligible. In contrast, Site 6 exhibited the highest concentration of iron (Fe) (0.0178 mg/L), while Site 5 recorded the maximum concentration of copper (Cu) (0.0210 mg/L) among the study locations. Site 1 demonstrated the most favorable water quality among the seven sites evaluated, whereas Site 6 exhibited the poorest water quality. Overall, the water quality from the majority of the sites was deemed suitable for drainage and for irrigating crops classified under the B category. However, based on the weighted arithmetic water quality index (WQI) values, none of the sites achieved a classification of good or excellent water quality, although the water quality at these sites may still be utilized for irrigation purposes. The current study is the first to report the presence of SARS-CoV-2 in Zarqa River water samples. Conclusions: The current study outcomes are promising and provide knowledgeable insights in terms of water quality parameters, while public health aspects should be considered when planning the WWTPs in parallel to reclaiming the wastewater for irrigation purposes. Full article

In this study, the total phenolic and anthocyanin contents, antioxidant activity, color, pH, serum separation, water holding capacity (WHC), rheology, texture and viscosity of cranberry (Cornus mas L.)-enriched yogurt were determined. The addition of cranberries (5–15%) to yogurt resulted in a proportional increase in antioxidant activity, total anthocyanin and phenolic contents. In yogurt samples to which cranberries were added, the WHC increased, while the serum separation values decreased. Due to the red color of the cranberry fruits, the L* (lightness) and b* (yellowness) values decreased, and the a* (redness) values increased (p < 0.05). The sensory evaluation showed that the 10% (w/w) cranberry-added yogurt had the highest general acceptability score when compared to the other samples. Also, it was found that the addition of 10% (w/w) cranberries to the yogurt samples contributed positively to the physicochemical (textural properties, rheological behavior, color and serum separation) and biochemical (antioxidant activity, phenolics and anthocyanins) properties of the samples. The addition of cranberries to yogurt influenced the growth of microbial populations. The number of starter bacteria (counts for Lactobacillus delbrueckii subsp. bulgaricus) in the yogurt samples with cranberries was slightly lower than in the control sample; but was at an acceptable level. E. coli and coliform bacteria were not detected in either the control yogurt sample or the samples with added cranberries. In conclusion, the addition of 10% (w/w) cranberries to yogurt can be recommended in order to achieve acceptable physical and sensory properties as well as the enrichment of yogurt with nutritional and functional aspects. Full article