Search Results (21,679)

Background: Due to chronic venous insufficiency, venous leg ulcers (VLUs) develop as chronic wounds characterized by impaired healing, persistent inflammation, and endothelial dysfunction. Nitrosative stress, mitochondrial damage, and tissue apoptosis caused by excess nitric oxide (NO) produced by iNOS in macrophages and fibroblasts are contributing factors in the chronic wound environment; therefore, pharmacological modulation of iNOS presents an attractive mechanistic target in chronic wound pathophysiology. Methods: Herein, we present the use of a structure-based computational strategy to assess the inhibition of tavaborole, a boron-based antifungal agent, against iNOS using human iNOS crystal structure (PDB ID: iNOS) by molecular docking using AutoDock 4.2, 500 ns simulation of molecular dynamics (MD), with equilibration within ~50 ns and analyses over full trajectory and binding free energy calculations through the MM-PBSA approach. Results: Docking studies showed favorable binding of tavaborole (–6.1 kcal/mol) in the catalytic domain, which stabilizes contacts with several key residues (CYS200, PRO350, PHE369, GLY371, TRP372, TYR373, and GLU377). MD trajectories for 1 ns showed stable structural configurations with negligible deviations (RMSD ≈ 0.44 ± 0.10 nm) and hydrogen bonding, and MM-PBSA analysis confirmed energetically favorable complex formation (ΔG_binding ≈ 18.38 ± 63.24 kJ/mol) similar to the control systems (L-arginine and 1400W). Conclusions: Taken together, these computational findings indicate that tavaborole can stably occupy the iNOS active site and interact with key catalytic residues, providing a mechanistic basis for further in vitro and ex vivo validation of its potential as an iNOS inhibitor to reduce nitrosative stress and restore endothelial homeostasis in venous leg ulcers, rather than direct therapeutic proof. Full article

Glycolysis-derived pyruvate is the almost exclusive source of acetyl-CoA for energy production in mitochondrial compartments of all types of neuronal and glial cells. Neurons utilize several times more glucose than glial cells due to their neurotransmitter functions. Cholinergic neurons that are responsible for cognitive functions require additional amounts of acetyl-CoA for acetylcholine-transmitter synthesis in their cytoplasmic compartment. It may be assured by preferential localization of ATP-citrate lyase (ACLY) in the cytoplasm of cholinergic neurons’ perikaryons and axonal terminals. This thesis is supported by the existence of strong regional and developmental correlations of ATP-citrate lyase and choline acetyltransferase (ChAT) activities and ACh levels in the brain. Electrolytic or chemical lesions of cholinergic nuclei cause proportional loss of the above parameters in the respective cortical target areas. On the other hand, the regional activity of mitochondrial pyruvate dehydrogenase complex (PDHC), which synthesizes nearly the whole pool of neuronal acetyl-CoA, displays no correlation with cholinergic innervation. It makes cholinergic neurons highly susceptible to brain pathologies impairing energy metabolism. Therefore, the ACLY pathway, which provides acetyl units directly to the site of acetylcholine synthesis in cholinergic nerve terminals, plays a key role in the maintenance of cholinergic neurotransmission. On the other hand, in cholinergic motor neurons, various ACLY–protein complexes are involved not only in neurotransmission but also in axonal transport of cholinergic elements from the perikaryon to cholinergic neuro-muscular junctions. This review presents findings supporting this thesis. Full article

The aggregation of tau protein is a central pathological event in Alzheimer’s disease, and this pathology is hypothesized to spread via a prion-like mechanism driven by tau “seeds”. While aggregated tau from Alzheimer’s disease brains is known to contain age-related d-isomerized aspartic acid (d-Asp) residues, it remains unknown how this modification affects the seeding activity that drives disease propagation. Here, we investigated the impact of site-specific d-isomerization within R2 and R3 tau repeat-domain peptides, which form the core of tau fibrils. We demonstrate that the stereochemical integrity of these peptides is critical for their seeding function. d-isomerization at Asp314 within the R3 peptide seed severely impaired its ability to template the fibrillization of full-length tau in vitro. This finding was validated in a cellular model, where R3 seeds containing d-Asp314 were significantly less potent at inducing the formation of phosphorylated tau aggregates compared to wild-type seeds. Our results establish that Asp d-isomerization within tau seeds acts as a potent attenuator of their pathological seeding activity, suggesting this spontaneous modification may intrinsically modulate the progression of Alzheimer’s disease. Full article

Background: In nuclear medicine, numerous cancer types are treated via internal irradiation with radiopharmaceuticals, including low-LET (linear energy transfer) beta-emitting radionuclides like Lu-177. In most cases, such treatments lead to low-dose exposure of organ systems with β-irradiation, which induces only few isolated DSBs (double-strand breaks) in the nuclei of hit cells, the most threatening DNA damage type. That damaging effect contrasts with the clustering of DNA damage and DSBs in nuclei traversed by high-LET particles (α particles, ions, etc.). Methods: After in-solution β-irradiation for 1 h with Lu-177 leading to an absorbed dose of about 100 mGy, we investigated the spatial nano-organization of chromatin at DSB damage sites, of repair proteins and of heterochromatin marks via single-molecule localization microscopy (SMLM) in PBMCs. For evaluation, mathematical approaches were used (Ripley distance frequency statistics, DBScan clustering, persistent homology and similarity measurements). Results: We analyzed, at the nanoscale, the distribution of the DNA damage response (DDR) proteins γH2AX, 53BP1, MRE11 and pATM in the chromatin regions surrounding a DSB. Furthermore, local changes in spatial H3K9me3 heterochromatin organization were analyzed relative to γH2AX distribution. SMLM measurements of the different fluorescent molecule tags revealed characteristic clustering of the DDR markers around one or two damage foci per PBMC cell nucleus. Ripley distance histograms suggested the concentration of MRE11 molecules inside γH2AX-clusters, while 53BP1 was present throughout the entire γH2AX clusters. Persistent homology comparisons for 53BP1, MRE11 and γH2AX by Jaccard index calculation revealed significant topological similarities for each of these markers. Since the heterochromatin organization of cell nuclei determines the identity of cell nuclei and correlates to genome activity, it also influences DNA repair. Therefore, the histone H3 tri methyl mark H3K9me3 was analyzed for its topology. In contrast to typical results obtained through photon irradiation, where γH2AX and H3K9me3 markers were well separated, the results obtained here also showed a close spatial proximity (“co-localization”) in many cases (minimum distance of markers = marker size), even with the strictest co-localization distance threshold (20 nm) for γH2AX and H3K9me3. The data support the results from the literature where only one DSB induced by low-dose low LET irradiation (<100 mGy) can remain without heterochromatin relaxation for subsequent repair. Full article

Overexpression of protein phosphatase 5 (PP5) is implicated in tumor cell growth, establishing PP5 as a compelling target for small-molecule anticancer therapy. Building on prior success in achieving selectivity within the PP2A domain through scaffold functionalization that maximizes active-site interactions, we propose a parallel strategy for PP5 inhibition. Norcantharidin, the demethylated cousin of cantharidin, is a potent yet unselective phosphatase inhibitor, making its bicyclic framework an attractive platform for systematic derivatization. The approach reported herein exploits anhydride reactivity to generate a carboxylic acid derivative that is transformed into a chloromethyl ester. Chloromethyl ester functionality serves as a strategically activated intermediate enabling downstream functional-group diversification under mild, neutral conditions while preserving scaffold integrity. This modular synthetic strategy establishes a foundation for the development of PP5-selective norcantharidin derivatives with improved tumor selectivity, potency, and synthetic feasibility. Full article

Modulating the electronic structure and surface properties of graphitic carbon nitride (g-C₃N₄) by chemically phosphorus doping is an effective strategy for improving its photocatalytic performance. However, in order to benefit from practical applications, the cost-effectiveness, efficiency, and optimization of the doping level need to be investigated further. Herein, we report a structural doping of P into g-C₃N₄ by in situ polymerization of the mixture of dicyandiamide (DCDA) and phosphorus pentoxide (P₂O₅). As an alternative to previous studies that used complex organic phosphorus precursors or post-treatment strategies, this work proposed a one-pot thermal polycondensation method that is low-cost, scalable, and enables controlled phosphorus substitutions at carbon sites of the g-C₃N₄ heptazine structure. Most of the structural features of g-C₃N₄ were well retained after doping, but the electronic structures and light harvesting capacity had been effectively altered, which provided not only a much better charge separation but also an improvement in photocatalytic activity toward H₂ evolution under irradiation of a simulated sunlight. The optimized sample with P-doping content of 9.35 at.% (0.5PGCN) exhibited an excellent photocatalytic performance toward H₂ evolution, which is over 5 times higher than that of bulk g-C₃N₄. This work demonstrates a facile one-step in situ route for producing high-yield photocatalysts using low-cost commercial precursors, offering practical starting materials for studies in solar cells, polymer batteries, and photocatalytic applications. Full article

Electrochemical CO₂ reduction (CO₂RR) is a promising route to transform a major greenhouse gas into value-added fuels and chemicals. However, its deployment is still hindered by the sluggish activation of CO₂, poor selectivity toward multielectron products, and competition with the hydrogen evolution reaction (HER). Single-atom catalysts (SACs) have emerged as powerful materials to address these challenges because they combine maximal metal utilization with well-defined coordination environments whose electronic structure can be precisely tuned through metal–support interactions. This minireview summarizes current understanding of how structural, electronic, and chemical features of SAC supports (e.g., porosity, heteroatom doping, vacancies, and surface functionalization) govern the adsorption and conversion of key CO₂RR intermediates and thus control product distributions from CO to CH₄, CH₃OH and C₂⁺ species. Particular emphasis is placed on selectivity descriptors (e.g., coordination number, d-band position, binding energies of *COOH and *OCHO) and on rational design strategies that exploit curvature, microenvironment engineering, and electronic metal–support interactions to direct the reaction along desired pathways. Representative SAC systems based primarily on N-doped carbons, complemented by selected examples on oxides and MXenes are discussed in terms of Faradaic efficiency (FE), current density and operational stability under practically relevant conditions. Finally, the review highlights remaining bottlenecks and outlines future directions, including operando spectroscopy and data-driven analysis of dynamic single-site ensembles, machine-learning-assisted DFT screening, scalable mechanochemical synthesis, and integration of SACs into industrially viable electrolyzers for carbon-neutral chemical production. Full article

In this study, a ternary Ni/Mg/g-C₃N₄ composite was synthesized via a controlled precipitation–calcination route and evaluated for its visible-light-assisted degradation of methylene blue (MB). The structural, morphological, and optical characteristics of the composites were systematically investigated using XRD, FT-IR, FESEM, BET, and UV–Vis analyses. The results confirmed the successful construction of Ni/Mg/g-C₃N₄ heterojunctions with strong interfacial coupling and enhanced surface porosity. Among all samples, the Ni/Mg/CN20 composite exhibited the highest activity, achieving 66% MB degradation within 180 min under visible light. This superior performance was attributed to synergistic effects arising from efficient interfacial charge transfer, broadened light absorption, and abundant active sites. The composite also displayed excellent thermal stability. This work demonstrates that the rational control of g-C₃N₄ loading plays a decisive role in tuning the physicochemical and catalytic properties of Ni/Mg/g-C₃N₄ composites. The findings provide new insights into the design of cost-effective, thermally stable, and high-performance photocatalysts for visible-light-driven wastewater treatment. Full article

The catalytic removal of toluene, a representative aromatic volatile organic compound (VOC), requires efficient and stable catalysts. This study systematically investigated the effect of B-site doping with transition metals (Fe, Cu, and Ni) on the catalytic performance of LaMnO₃ perovskite for toluene oxidation. The LaMn_0.5X_0.5O₃ catalysts were synthesized via a sol–gel method and evaluated. The LaMn_0.5Ni_0.5O₃ catalysts exhibited the optimal catalytic performance, achieving toluene conversion temperatures of 243 °C at 50% conversion (T₅₀) and 296 °C at 90% conversion (T₉₀). Comprehensive characterization revealed that Ni doping effectively refined the catalyst’s microstructure (grain size decreased to 19.21 nm), increased the concentration of surface-active oxygen species (142.7%), elevated the Mn⁴⁺/Mn³⁺ ratio to 0.65, and enhanced lattice oxygen mobility. These modifications collectively contributed to its outstanding catalytic activity. The findings demonstrate that targeted B-site doping, particularly with Ni, is a promising strategy for engineering efficient perovskite catalysts for VOC abatement. Full article

Parasitoids are key natural antagonists of forest insect pests and are gaining importance in integrated forest protection under increasing climate-related disturbances. This study aimed to quantify the influence of vegetation diversity and canopy structure on the abundance and diversity of the overall insect community responses to vegetation structure and to provide an ecological context. Second, detailed analyses focused on three focal parasitoid families (Braconidae, Ichneumonidae, Tachinidae), which are of particular relevance for integrated forest protection due to their central role in integrated forest protection and in pesticide-free regulation approaches for risk mitigation in forest ecosystems. Malaise traps were deployed at eight randomly selected broadleaf and coniferous sites, and insect samples from six sampling dates in summer 2024 were analyzed. The sampling period coincided with the full development of woody and vascular plants, representing the phase of highest expected activity of phytophagous insects and associated parasitoids. Vegetation surveys (Braun–Blanquet), canopy closure, and canopy cover were recorded for each site. Across all samples, five arthropod classes, 13 insect orders, and 31 hymenopteran families were identified, with pronounced site-specific differences in community composition and abundance. Our results suggest that broadleaf-dominated sites, characterized by higher plant species richness and greater structural heterogeneity, support a more diverse assemblage of phytophagous insects, thereby increasing host availability and niche diversity for parasitoids. Parasitoid communities generally showed higher diversity at broadleaf sites. Spearman correlations and multiple linear regressions revealed a strong negative relationship between canopy cover and total insect abundance ρ (Spearman’s rank correlation coefficient (Spearman ρ = −0.72, p = 0.042; p = 0.012, R² = 0.70), R² (coefficient of determination), whereas parasitoid diversity (Shannon index) and the relative proportion of Ichneumonidae were positively associated with canopy cover (ρ = 0.85, p = 0.008). In addition, canopy cover had a significant positive effect on overall insect diversity (Shannon index; p = 0.015, R² = 0.63). Time-series analyses revealed a significant seasonal decline in parasitoid abundance (p < 0.001) and parasitoid diversity (p = 0.018). Time-series analyses revealed seasonal dynamics characterized by fluctuations in parasitoid abundance and diversity and a general decrease over the course of the sampling period. The findings demonstrate that structurally diverse mixed forests, particularly those with a high proportion of broadleaf trees mixed forests with heterogeneous canopy layers can enhance the diversity of specialized natural enemies, while dense canopy cover reduces overall insect abundance. These insights provide an ecological basis for silvicultural strategies that strengthen natural regulation processes within integrated forest protection. Full article

Virtual Field Trips (VFTs) have emerged as an alternative to Traditional Field Trips (TFTs), addressing logistical, financial, and accessibility constraints in geoscience education. This study presents a comparative analysis of the educational impact of a VFT and a TFT implemented with the same 10th-grade class in a Portuguese secondary school. The VFT, focused on volcanism and its socioeconomic impacts, used Google Earth to explore the island of São Miguel in the Azores. The TFT, centred on the rock cycle, was conducted at the Lavadores Beach geological site. Both interventions followed the field-based learning model by Orion and were structured around three phases: preparation, field trip (virtual or traditional), and post-activity synthesis. Data was collected through diagnostic tests, schematization, observation grids, student reports (snapshot), group projects, and written responses to a fieldwork guide recorded on Padlet during the VFT and TFT. The results showed that both VFTs and TFTs enhance conceptual understanding and student engagement, though they foster different skills: VFTs strengthen digital literacy, improve accessibility and inclusion for students with mobility or geographic constraints, allow for content revisitation, foster collaboration among students, integrate multimedia resources, and enable virtual exploration of remote locations that would otherwise be inaccessible. They also offer reduced costs, greater scheduling flexibility, and allow for individualised pacing of student learning. In contrast, TFTs provide richer sensory and practical experiences that are essential for hands-on scientific inquiry and foster stronger connections with the natural environment. The study concludes that a complementary use of both strategies offers the most inclusive and effective approach to teaching geosciences. Full article

Spontaneous coal combustion accounts for more than 90% of mine fires, and at the same time, the ‘dual carbon’ strategy requires fire prevention and extinguishing materials to have both low-carbon and environmentally friendly functions. To meet on-site application needs, a composite gel with fast injection, flame retardant, and CO₂ adsorption functions was developed. PVA-PEI-PAC materials were selected as the gel raw materials, and an orthogonal test with three factors and three levels was used to optimize the gelation time parameters to identify the optimal formulation. The microstructure of the gel, CO₂ adsorption performance, as well as its inhibition rate of CO, a marker gas of coal spontaneous combustion, and its effect on activation energy were systematically characterized through SEM, isothermal/temperature-programmed/cyclic adsorption experiments, and temperature-programmed gas chromatography. The results show that the optimal gel formulation is 14% PVA, 7% PEI, and 5.5% PAC. The gel microstructure is continuous, dense, and rich in pores, with a CO₂ adsorption capacity at 30 °C and atmospheric pressure of 0.86 cm³/g, maintaining over 76% efficiency after five cycles. Compared with raw coal, a 10% gel addition reduces CO release at 170 °C by 25.97%, and the temperature-programmed experiment shows an average CO inhibition rate of 25% throughout, with apparent activation energy increased by 14.96%. The gel prepared exhibited controllable gelation time, can deeply encapsulate coal, and can efficiently adsorb CO₂, significantly raising the coal–oxygen reaction energy barrier, providing an integrated technical solution for mine fire prevention and extinguishing with both safety and carbon reduction functions. Full article

This work addresses the increasing complexity of urban mobility by proposing an intelligent optimization and resource-allocation framework for Vehicle-to-Infrastructure (V2I) communications. The model integrates a macroscopic mobility analysis, an Integer Linear Programming (ILP) formulation for optimal Road-Side Unit (RSU) placement, and a Smart Generic Network Controller (SGNC) based on Q-learning for dynamic radio-resource allocation. Simulation results in a realistic georeferenced urban scenario with 380 candidate sites show that the ILP model activates only 2.9% of RSUs while guaranteeing more than 90% vehicular coverage. The reinforcement-learning-based SGNC achieves stable allocation behavior, successfully managing 10 antennas and 120 total resources, and maintaining efficient operation when the system exceeds 70% capacity by reallocating resources dynamically through the $\lambda$-based alert mechanism. Compared with static allocation, the proposed method improves resource efficiency and coverage consistency under varying traffic demand, demonstrating its potential for scalable V2I deployment in next-generation intelligent transportation systems. 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 study investigates the activation mechanism of boron-doped carbon (BMC) catalysts for the degradation of the antibiotic sulfamethoxazole (SMX) via persulfate (PMS) activation. The catalysts were synthesized using a sequential double-melting calcination method, resulting in mesoporous carbon nanosheets characterized by hierarchical macro-mesopores and atomically dispersed dual active sites. Comprehensive characterization was performed using BET, SEM, TEM, FT-IR, XPS, XRD, and Raman techniques. The optimized BMC catalyst demonstrated excellent performance, achieving complete removal of sulfamethoxazole (100%) and a high mineralization rate (~90%) within 45 min. Mechanistic analysis, including electron paramagnetic resonance (EPR), revealed that the degradation predominantly follows a singlet oxygen (1O2)-dominated pathway. The system exhibited broad applicability to various pollutants, along with notable operational stability and robust resistance to common environmental interferents. Persulfate activation was primarily attributed to boron-active sites, while the hierarchical mesoporous structure facilitated both pollutant enrichment and catalytic efficiency. Full article