Search Results (3,333)

Fyn is a Src-family tyrosine kinase implicated in synaptic dysfunction and neuroinflammation across multiple neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Saracatinib (AZD0530) is a potent Src-family inhibitor that has been explored as a repurposed therapeutic; however, its clinical utility is limited by poor kinase selectivity caused by high sequence conservation within Src-family ATP-binding sites. Here, we combine surface plasmon resonance (SPR) and X-ray crystallography to define saracatinib recognition by the Fyn kinase domain (KD). SPR single-cycle kinetics shows that saracatinib binds the isolated Fyn KD and full-length Fyn with low-nanomolar affinity, whereas dasatinib binds with subnanomolar affinity and markedly slower dissociation. We determined the crystal structure of the Fyn KD-saracatinib complex at 2.22 Å resolution. The kinase adopts an active-like conformation with the DFG motif and αC-helix in the ‘in’ state and a conserved β3 αC Lys-Glu salt bridge. Saracatinib occupies the adenine and ribose pockets, and engages the hinge through direct and water-mediated hydrogen bonding while complementing a hydrophobic back pocket by van der Waals contacts. Comparison with reported saracatinib-bound structures of other kinases suggests that the active-state geometry observed for Fyn creates a pocket not observed in inactive-like complexes, providing a structural handle for designing Fyn-selective inhibitors. Comparison with all saracatinib-bound kinase co-structures currently available in the PDB (ALK2 and PKMYT1) indicates a conserved monodentate hinge binding mode but kinase-dependent αC-helix conformations, providing a structural rationale for designing Fyn-selective analogues. Full article

Background: Human noroviruses are the leading cause of foodborne gastroenteritis worldwide. Accumulating evidence suggests that food matrices containing fucosylated or histo-blood group antigen (HBGA)-like glycans may facilitate viral attachment and persistence, yet the molecular mechanisms underlying these interactions remain unclear. Methods: In this study, we performed a comparative computational analysis of norovirus–glycan interactions by integrating AlphaFold3-based structure prediction, molecular docking, and molecular dynamics simulations. A total of 182 P-domain models representing all genotypes across five human norovirus genogroups (GI, GII, GIV, GVIII, and GIX) were predicted and docked with a lettuce-derived core-fucosylated hexasaccharide (H₂N₂F₂) previously identified by our group. The three complexes exhibiting the most favorable docking energies were further examined using 40 ns molecular dynamics simulations, followed by MM/GBSA binding free energy calculations and per-residue decomposition analyses. Results: Docking results indicated that the majority of modeled P proteins were able to adopt energetically favorable interaction poses with H₂N₂F₂, with predicted binding energies ranging from −3.7 to −7.2 kcal·mol⁻¹. The most favorable docking energies were observed for GII.6_S9c_KC576910 (−7.2 kcal·mol⁻¹), GII.3_MX_U22498 (−7.1 kcal·mol⁻¹), and GII.4_CARGDS11182_OR700741 (−6.8 kcal·mol⁻¹). Molecular dynamics simulations suggested stable ligand engagement within canonical HBGA-binding pockets, with recurrent residues such as Asp374, Gln393, and Arg345 contributing to electrostatic and hydrophobic interactions, consistent with previously reported HBGA-binding motifs. MM/GBSA analyses revealed comparatively favorable binding tendencies among these complexes, particularly for globally prevalent genotypes including GII.3, GII.4, and GII.6. Conclusions: This work provides a large-scale structural and energetic assessment of the potential interactions between a naturally occurring lettuce-derived fucosylated hexasaccharide and human norovirus P domains. The results support the notion that core-fucosylated food-associated glycans can serve as interaction partners for diverse norovirus genotypes and offer comparative molecular insights into glycan recognition patterns relevant to foodborne transmission. The integrative AlphaFold3–docking–dynamics framework presented here may facilitate future investigations of virus–glycan interactions within food matrices. Full article

Numerous research works have tried to evaluate the correlation between inflammation and the onset of prostate cancer. Given the in vitro antioxidant power and the anti-proliferative effects on human prostate cancer cells shown by a Juglans regia L. fresh fruit extract, the aim of this work was the evaluation of its potential in the acute and chronic inflammatory states in vivo, revealing a strong anti-inflammatory activity. In the zymosan-induced edema formation assay, a light and non-significant edema reduction was shown. On the contrary, in the zymosan-induced thermal hyperalgesia assay, the reversion of hyperalgesia after the extract administration was determined. Moreover, in the formalin test, the extract caused a significant decrease in the licking time caused by the aldehyde, especially in the late phase. In silico, quercetin showed the best fit into the enzymatic pocket of AChE (docking score: −11.306 Kcal/mol). Neochlorogenic acid and ellagic acid gave the best docking scores on BChE (−10.292 Kcal/mol and −10.054 Kcal/mol, respectively). Abscisic acid showed a high binding affinity for the glucocorticoid receptor. Finally, quercetin and abscisic acid were quantified to complete the data by HPLC-DAD, giving 0.246 ± 0.003 mg/g of dried extract and 0.036 ± 0.004 mg/g of dried extract, respectively. Full article

Developing an advanced simulation to control a swarm of 20 PocketQube nanosatellites using a linear quadratic regulator (LQR) involves several crucial steps that go beyond the initial scheme. A comprehensive approach requires a deep understanding of orbital mechanics and, in particular, the challenges presented by the nanosatellite platform. The inherent limitations in terms of nanosatellite power, propulsion, and communications systems necessitate careful orbital selection and maneuver planning to achieve mission objectives efficiently and reliably. This includes optimizing launch windows, understanding atmospheric drag effects in low Earth orbits (LEOs), and designing robust attitude control systems to maintain the desired pointing for scientific instruments or communications links. Our work focused on simulating the attitude control of PocketQube nanosatellites in a swarm using the R2022a release of the Matlab/Simulink environment. First, we provided a mathematical model for the relative coordinates of a nanosatellite swarm. Second, we developed a mathematical model of the linear quadratic regulator implementation in the relative navigation. Third, we simulated the attitude control of 20 PocketQube nanosatellites using the Matlab/Simulink environment. Finally, we provided the swarm scenario and attitude control system data. The simulation of an attitude control system for 20 PocketQube nanosatellites using an LQR controller in a swarm successfully demonstrated the stabilization capabilities essential for swarm operations in the space environment. A link to a video of the simulation is provided in the Results section. Full article

The clinical durability of SARS-CoV-2 main protease (M^pro) inhibitors depends on their resilience to emerging resistance mutations. Recent genomic surveillance and functional reports have highlighted substitutions at positions 49, 165, and 301, raising questions about the robustness of the noncovalent inhibitor WU-04 in variant backgrounds. Here, we combined μs-scale, triplicate molecular dynamics simulations with end-state binding free energy estimates and a network-rewiring inference (NRI) framework that maps long-range dynamical communication across the full protease dimer. We evaluated wild type (WT), single mutants M49K, M165V, S301P, and selected double mutants (M49K & M165V, M49K & S301P). Relative to WT, single substitutions produced reductions in computed binding affinity of up to ~12kcal/mol, accompanied by loss or reshaping of the S2 subsite and altered ligand burial. Notably, the M49K/S301P double mutant partially restored WU-04 engagement, narrowing the ΔΔG_restore gap to within ΔΔG_restore of WT and re-establishing key hydrophobic and hydrogen-bond contacts. NRI analysis revealed that distal residue 301 participates in a communication corridor linking the C-terminal helical domain to the active-site cleft; its substitution rewires inter-domain coupling that can compensate for local disruptions at residue 49. Together, these results identify structural hotspots and network pathways that may inform the design of next-generation M^pro inhibitors with improved mutation tolerance—specifically by strengthening interactions that do not rely solely on the mutable S2 pocket and by engaging conserved backbone features near the 165–166 region. Full article

Intrinsically disordered regions enable transcription factors (TFs) to undergo structural changes upon ligand binding, facilitating the transduction of environmental signals into gene expression. In this study, we applied molecular modeling methods to explore the hypothesis that unstructured inter-domain and subdomain linkers in bacterial TFs can function as sensors for carbohydrate signaling molecules. We combined molecular dynamics simulations and carbohydrate docking to analyze six repressors with GntR-type DNA-binding domains, including UxuR, GntR and FarR from Escherichia coli, as well as AraR, NagR and YydK from Bacillus subtilis. Protein models obtained from different time points of the dynamic simulations were subjected to sequential carbohydrate docking. We found that the inter-domain linker of the UxuR monomer binds D-fructuronate, D-galacturonate, D-glucose, and D-glucuronate with an affinity comparable to nonspecific interactions. However, these ligands formed multimolecular clusters, a feature absent in the UxuR dimer, suggesting that protein dimerization may depend on linker occupancy by cellular carbohydrates. D-glucose interacted with linkers connecting subdomains of the LacI/GalR-type E-domains in GntR and AraR, forming hydrogen bonds that connected distant structural modules of the proteins, while in NagR, FarR and YydK, it bridged the inter-domain linkers and a β-sheet within the HutC-type E-domains. Hence, our results establish flexible linkers as pivotal metabolic sensors that directly integrate nutritional cues to alter gene expression in bacteria. Full article

Urban resilience has emerged as a critical paradigm for addressing the intertwined challenges of climate change, rapid urbanization, and social inequality, positioning green public spaces as catalysts for social, ecological, and institutional transformation. This article presents a systematic review conducted under the PRISMA 2020 guidelines, examining how collaborative and community participation influenced transformative urban resilience in green public spaces between 2021 and 2025. A total of 6179 records were initially identified across ScienceDirect and MDPI (last search: July 2025), of which 26 empirical studies met the inclusion criteria (peer-reviewed, empirical, published 2021–2025). Methodological rigor was strengthened through the application of the Mixed Methods Appraisal Tool (MMAT, 2018) and confidence in qualitative evidence was assessed using the GRADE-CERQual approach, enhancing transparency and reliability. Data extraction and synthesis followed a theoretical-methodological coding framework, allowing for the comparison of participatory strategies, typologies of green spaces, resilience dimensions, and applied instruments. The results show that multi-actor co-management, co-design, and community self-organization are the most frequent participatory strategies, while urban green infrastructure, pocket parks, and urban gardens constitute the predominant spatial contexts. Socio-ecological and social-participatory resilience emerged as dominant theoretical perspectives, with qualitative and mixed-methods designs prevailing across studies. Evidence synthesis through GRADE-CERQual identified seven key pathways—multi-actor co-management, Nature-based Solutions, community-based actions, social equity, cultural identity, institutional innovation, and planned densification—each contributing differently to resilience dimensions. Overall, the findings highlight that transformative resilience depends on deep, inclusive participatory processes, multi-level governance, and the integration of social, ecological, and cultural dimensions. Despite the heterogeneity of designs and unequal data adequacy, this review confirms that transformative urban resilience is a co-produced process grounded in community action, ecological sustainability, and collaborative governance. Strengthening underexplored areas—technological innovation, cultural resilience, and standardized methodological instruments—is essential for advancing comparative research and practice. Full article

Background: The aim of the S.A.P.O.R.E. (Sustainable And Pocket friendly Options for nutritious and Responsible Eating) initiative was to offer students attending the University of Brescia a teaching kitchen programme to develop cooking and food skills (CS and FS) and promote healthy food choices. Methods: The course was structured in four weekly lessons, and both before and after, participants were asked to anonymously complete validated questionnaires to assess CS and FS, adherence to the Mediterranean Diet (MD) and dietary fibre intake. Levels of competence and satisfaction were assessed at the end of the course. Results: Twenty-eight students completed the course. Mean CS and FS scores significantly increased, from 56.1 ± 19.8 to 68.0 ± 16.5 (score range 0–98, p < 0.001) and from 92.7 ± 22.4 to 104.3 ± 21.0 (score range 0–133; p = 0.012), respectively. The MediLite score significantly increased from 9.43 ± 2.77 to 10.9 ± 2.06 (p = 0.006). The mean daily dietary fibre intake increased slightly from 17.8 ± 8.4 to 19.2 ± 7.1 g. More than 70% of participants correctly answered the questionnaire about acquired competence. The average cost for a single meal was EUR 1.50 ± 0.60, and the mean level of students’ satisfaction was 4.4 out of 5. Conclusions: This initiative was significantly associated with improvement in CS, FS and adherence to MD, but not in fibre intake. Full article

Delphastus Casey (Coleoptera: Coccinellidae: Serangiini) comprises small predatory ladybird beetles that feed on immature whiteflies. Several Delphastus species are utilized as biological control agents. However, Delphastus pallidus (LeConte) has been understudied for the past several decades. Recent landscape surveys in South Florida revealed a marked increase in D. pallidus populations associated with multiple whitefly species. We evaluated whitefly species preferences of D. pallidus using choice and no-choice assays conducted in incubators and insectaries. Seven whitefly species were confirmed as prey and ranked in order of preference: Bemisia tabaci Gennadius > Aleurothrixus trachoides (=Aleurotrachelus trachoides) (Back) > Singhiella simplex (Singh) > Paraleyrodes bondari Peracchi > Aleurodicus rugioperculatus Martin > Asiothrixus antidesmae (Takahashi) > Aleurodicus dugesii Cockerell. Findings indicate that D. pallidus feeds on a taxonomically and morphologically diverse set of whiteflies, including both waxy and non-waxy species, which likely facilitates establishment and dispersal in ornamental and agricultural landscapes. This study is the first to document D. pallidus as a potentially native U.S. predatory beetle that attacks at least seven whitefly species. Knowledge of its prey preferences will inform mass-rearing strategies and potential deployment for whitefly biocontrol. Full article

Background & Objectives: Periodontal disease (PD) is a common oral disease that affects the supporting structures of the teeth and is a leading cause of tooth loss worldwide. This study aimed to estimate the prevalence of PD among 9th-grade teachers in the northern West Bank and examine its association with key behavioral and socioeconomic factors. Methods: A cross-sectional study was conducted among 920 teachers selected through proportional stratified random sampling from governmental and private schools. Periodontal health was assessed using the WHO Community Periodontal Index for Treatment Needs (CPITN), and oral hygiene status was measured with the Simplified Oral Hygiene Index (S-OHI). A structured questionnaire was administered to collect data on socioeconomic status, oral hygiene practices, dietary habits, and smoking behaviours. Data was analysed using descriptive statistics, bivariate and multivariate logistic regression. Results: Only 11.8% of participants exhibited completely healthy gingiva, with the mean condition ranging between calculus and shallow pockets. Oral hygiene practices were the strongest predictors of periodontal outcomes: frequent tooth brushing (Adjusted Odds Ratio: AOR = 0.015), morning brushing (AOR = 0.015), and regular toothbrush replacement (AOR = 2.514) were protective. Higher red meat intake was negatively associated with periodontal health (AOR = 0.032), while frequent nut consumption was protective (AOR = 0.227). The number of cigarettes smoked per week was positively associated with PD (AOR = 1.085). Conclusions: PD is highly prevalent among Palestinian adults, with significant behavioural and lifestyle-related determinants. Targeted oral health interventions are urgently needed to improve adults’ oral health. Full article

Respiratory syncytial virus (RSV) remains a leading cause of lower respiratory tract infections (LRTIs) and infant mortality worldwide. Despite recent advances in prophylactic interventions, effective therapeutics for active RSV infection are still lacking. Small molecule non-nucleoside inhibitors (NNIs) targeting the RSV L protein, particularly its polyribonucleotidyltransferase (PRNTase) domain, represent a promising antiviral strategy. Here, we evaluate the genetic variability of the PRNTase domain and the binding pocket of two NNIs, MRK-1 and MRK-2, to assess the potential for preexisting resistance. A comprehensive analysis of 28,140 RSV L protein sequences from NCBI Virus and GISAID EpiRSV databases revealed low overall variability within the PRNTase domain and near-complete conservation of the MRK-1/2 binding pocket. Resistance-associated mutations identified through in vitro dose-escalation studies localized to this pocket but were absent in global sequence datasets. These findings support the PRNTase domain as a genetically stable and viable target for NNI-based RSV therapeutics and suggest a low likelihood of preexisting resistance among circulating strains. Full article

Background/Objectives: Mathematical modelling provides a quantitative way to describe the fate and action of drugs in the oral cavity, where transport processes are shaped by salivary flow, pellicle formation, biofilm structure and the wash-out effect of gingival crevicular fluid (GCF). Local pharmacokinetics in the mouth differ substantially from systemic models, and therefore a dedicated framework is required. The aim of this work was to present a structured, physiologically based concept that links in vitro release testing with local pharmacokinetics and pharmacodynamics. Methods: A narrative review with elements of systematic search was conducted in PubMed, Scopus and Web of Science (1980–2025) for publications describing drug release, local PBPK, and PK/PD modelling in the oral cavity. Mathematical formulations were grouped into release kinetics, mini-PBPK transport and local PK/PD relations. Classical models (Higuchi, Korsmeyer–Peppas, Peppas–Sahlin) were integrated with a mini-PBPK structure describing saliva–mucosa–biofilm–pocket interactions. Results: The combined model captures adsorption to pellicle, diffusion within biofilm and wash-out by GCF. It allows simulation of variable clinical conditions, such as inflammation-related changes in Q_GCF, and links local exposure to pharmacodynamic outcomes. Case studies with PerioChip^®, Arestin^®, and Atridox^® demonstrate how mechanistic models explain observed therapeutic duration and low-systemic exposure. Conclusions: The proposed mini-PBPK framework bridges empirical release data and physiological transport in the oral cavity. It supports rational formulation design, optimisation of local dosage, and personalised prediction of drug retention in gingival pockets. This modelling approach can become a practical tool for the development of dental biomaterials and subgingival therapies. Full article

To prepare and characterize low-bitter angiotensin-converting enzyme (ACE)-inhibitory peptides from sesame protein, a triple-enzyme hydrolysis system was optimized using mixture design and response surface methodology. The resulting hydrolysate was separated by ultrafiltration and medium-pressure chromatography, followed by identification through nano-liquid chromatography–electrospray ionization-tandem mass spectrometry. Finally, the mechanism of typical low-bitter ACE-inhibitory peptides was elucidated by molecular docking and molecular dynamics simulation. Results showed that the optimal enzyme activity ratio of 1:0.94:1.07 for Alcalase, trypsin, and Flavourzyme, combined with optimized hydrolysis conditions (E/S ratio of 126,793.03 nkat/g, pH 8.40, 4.82 h hydrolysis time, and 45 °C), resulted in a peptide yield of 93.19 ± 0.14%, ACE-inhibitory rate of 95.92 ± 0.23%, and bitter value of 3.15 ± 0.09. APQLGR and APWLR exhibited high ACE-inhibitory activity and minimal bitterness among the seventeen identified peptides. Although both peptides bound to the S1 pocket and Zn²⁺ catalytic site of ACE, APWLR exhibited an additional interaction with the S2 pocket. Both peptides were predicted to antagonize the bitter taste receptor T2R14 by forming stable complexes with key residues, but two complexes exhibited distinct mechanisms of stabilization. This work demonstrates a method for producing dual-functional peptides from sesame protein, paving the way for their application in functional foods. Full article

This paper examines the growing field of AI-assisted urban planning within the context of sustainable urban development, with a particular focus on spatial optimization of urban green spaces under conditions of scarcity, density, and economic pressure. While the economic, ecological, and social values of UGS are widely acknowledged, urban planners lack a cohesive, data-driven framework to quantify and spatially optimize these often-conflicting values for effective land-use optimization. To address this gap, we propose a methodology that combines Geographic Information Systems (GISs), the Analytic Hierarchy Process (AHP), and an Artificial Intelligence-Based Genetic Algorithm (AI-GA). Vračar was chosen as the case study area. Our approach evaluates (1) the economic value of UGS through housing prices; (2) the ecological value through UGS density; and (3) the social value by measuring access to urban green pockets. The integrated method simulates environmental scenarios and optimizes UGS placement for resilient urban areas. Results demonstrate that properties in mixed-use green areas proximate to urban parks have the highest economic and social value. Additionally, higher densities of UGS correlate with higher housing prices, highlighting the economic impact of green space distribution. The methodology enables planners to make decisions based on evidence that integrates statistical modeling, expert judgment, and artificial intelligence into one cohesive platform. Full article

This study focuses on the scale of wind and rainfall-induced soil erosion that is relevant to transportation infrastructure. To this end, an experimental approach was devised and carried out to assess the effectiveness of lignin, a biodegradable and non-toxic plant-derived biopolymer, in enhancing soil resistance to wind and rainfall-induced erosion. The experimental program included basic soil tests required for soil classification, wind and rainfall-induced erosion tests, pocket penetrometer tests to assess the near-surface soil strength, SEM, EDS scans, and FTIR spectroscopy to evaluate changes in the fabric and chemical composition of the soil treated with lignin. Additionally, the effect of lignin on the re-establishment of the vegetative cover after the construction completion was also investigated. It was found that an increased spraying rate of lignin solution increased both the near-surface strength and wind erosion resistance. Moreover, SEM scans showed that the presence of lignin provided abundant particle coating, which is a source of additional cohesive strength. However, the spraying rate had a minor effect on rainfall erosion resistance, which increased with an increase in lignin solution concentration. Finally, lignin treatment did not significantly affect the size of the vegetative cover and had a minor effect on soil nutrients. Full article