Search Results (1,372)

Background/Objectives: The development of specific inhibitors for cyclooxygenase-2 (COX-2) is a challenge for public health. A series of 17 N-phthalimide hybrids was evaluated using a functional M06 meta-GGA hybrid in combination with a polarized 6-311G (d, p) basis set. The top three candidates (6, 10, and 17) were synthesized and evaluated as selective COX-2 inhibitors of PGE-2 using an integrated in silico–in vitro approach. Methods: Molecular docking against COX-2 (PDB 5KIR) and COX-1 (PDB 6Y3C), supported by homology modeling and DFT geometry optimization (B3LYP/6-31G*), revealed that the phthalimide carbonyl groups and the 3,4,5-trimethoxyphenyl or geranyl-derived moieties establish key hydrogen bonds and hydrophobic contacts with Arg120, Tyr355, Tyr385, and Ser530 in the COX-2 active site, conferring predicted selectivity ΔGCOX−2 vs. COX−1 = −1.4 to −2.8 kcal/mol. Results: The compounds complied with Lipinski’s and Veber’s rules and displayed favorable ADMET profiles. In vitro assessment in LPS-stimulated J774A.1 murine macrophages confirmed potent inhibition of PGE₂ production, 3.05 µg/mL, with compound 17 exhibiting the highest efficacy, 97.79 ± 5.02% inhibition at 50 µg/mL, and 10 showing 95.22 ± 6.03% inhibition at 50 µg/mL. Notably, all derivatives maintained >90% cell viability up to 250 µg/mL by resazurin assay and showed no evidence of cytotoxicity or mitosis potential in the tests at 24 h. Conclusions: These results demonstrate that strategic hybridization of phthalimide with natural and synthetic product-derived fragments yields highly potential PGE2 inhibitors. Therefore, compounds 6, 10, and 17 are promising lead candidates for the development of safer anti-inflammatory agents. Full article

This paper proposes a large-scale, self-healing multipoint fiber Bragg grating (FBG) sensor network that employs reinforcement learning (RL) techniques to enhance the resilience and efficiency of optical wireless communication networks. The system features a mesh-structured, self-healing ring-mesh architecture employing 2 × 2 optical switches, enabling robust multipoint sensing and fault tolerance in the event of one or more link failures. To further extend network coverage and support distributed deployment scenarios, free-space optical (FSO) links are integrated as wireless optical backhaul between central offices and remote monitoring sites, including structural health, renewable energy, and transportation systems. These FSO links offer high-speed, line-of-sight connections that complement physical fiber infrastructure, particularly in locations where cable deployment is impractical. Additionally, RL-based artificial intelligence (AI) techniques are employed to enable intelligent path selection, optimize routing, and enhance network reliability. Experimental results confirm that the RL-based approach effectively identifies optimal sensing paths among multiple routing options, both wired and wireless, resulting in reduced energy consumption, extended sensor network lifespan, and improved transmission delay. The proposed hybrid FSO–fiber self-healing sensor system demonstrates high survivability, scalability, and low routing path loss, making it a strong candidate for future services and mission-critical applications. Full article

Glioblastoma (GB) is one of the most aggressive and invasive cancers. Current treatment protocols for GB include surgical resection, radiotherapy, and chemotherapy with temozolomide. However, despite these treatments, physicians still struggle to effectively image, diagnose, and treat GB. As such, patients frequently experience recurrence of GB, demanding innovative strategies for early detection and effective therapy. Bioconjugated quantum dots (QDs) have emerged as powerful nanoplatforms for precision imaging and targeted drug delivery due to their unique optical properties, tunable size, and surface versatility. Due to their extremely small size, QDs can cross the blood–brain barrier and be used for precision imaging of GB. This review explores the integration of QDs with click chemistry for robust bioconjugation, focusing on artificial intelligence (AI) to advance GB therapy, mechanistic insights into cellular uptake and signaling, and strategies for mitigating toxicity. Click chemistry enables site-specific and stable conjugation of targeting ligands, peptides, and therapeutic agents to QDs, enhancing selectivity and functionalization. Algorithms driven by AI may facilitate predictive modeling, image reconstruction, and personalized treatment planning, optimizing QD design and therapeutic outcomes. We discuss molecular mechanisms underlying interactions of QDs with GB, including receptor-mediated endocytosis and intracellular trafficking, which influence biodistribution and therapeutic efficacy. Use of QDs in photodynamic therapy, which uses reactive oxygen species to induce apoptotic cell death in GB cells, is an innovative therapy that is covered in this review. Finally, this review addresses concerns associated with the toxicity of metal-based QDs and highlights how QDs can be coupled with AI to develop new methods for precision imaging for detecting and treating GB for induction of apoptosis. By converging nanotechnology and computational intelligence, bioconjugated QDs represent a transformative platform for paving a safer path to smarter and more effective clinical interventions of GB. Full article

Bovine mastitis remains a major challenge in dairy production despite extensive antimicrobial use, with therapeutic failure increasingly attributed to factors beyond classical antimicrobial resistance (AMR). Growing evidence indicates that treatment inefficacy arises from the combined effects of pharmacokinetic/pharmacodynamic (PK/PD) constraints, biofilm-mediated tolerance, intracellular persistence, and the adaptive capacity of mastitis pathogens. Intramammary therapy is particularly limited by poor tissue penetration, episodic drug elimination via milk flow, and inactivation by milk components, frequently resulting in subtherapeutic exposure at the site of infection. These limitations are amplified in chronic and subclinical mastitis, where biofilms and intracellular reservoirs reduce antimicrobial susceptibility and promote relapse and resistance selection. This narrative review integrates current knowledge on pharmacokinetic and pharmacodynamic (PK/PD) barriers, microbial survival strategies, and antimicrobial resistance (AMR) mechanisms that underlie treatment failure in bovine mastitis. It critically evaluates conventional antimicrobial therapies alongside emerging approaches, including antimicrobial peptides, bacteriophages and endolysins, nanoparticle-based delivery systems, immunomodulators, CRISPR-guided antimicrobials, and drug repurposing strategies. Overall, available evidence highlights the potential of these approaches to enhance therapeutic durability, particularly in settings where biofilm formation, intracellular persistence, and resistance limit conventional treatment efficacy. By mapping research coverage across mastitis phenotypes and therapeutic outcomes, this review identifies key gaps in long-term efficacy and resistance mitigation and underscores the need for PK/PD-guided, biofilm-aware, and resistance-conscious strategies to support durable next-generation mastitis management. Full article

The fish liver, as the main detoxification organ, is highly susceptible to xenobiotic exposure, often resulting in various hepatopathies. The cytochrome P450 system plays a central role in xenobiotic metabolism, with cytochrome P450 reductase (CYPOR) supplying the electrons required for CYP enzyme activity. This study aimed to evaluate the relationship between the ecological state of a reservoir and fish health, including CYPOR levels, through hematological, bacteriological, and histological analyses. Samples of water and fish were collected from 12 littoral sites of Lake Ladoga. A total of 1360 specimens of fish from carp (Cyprinidae) and perch (Percidae) families were examined. For histological examination and CYPOR level determination, we selected 40 specimens using a blind randomization method. This sample size was sufficient for statistical analyses. Hematological smears were stained with azure eosin; bacteriological cultures were grown on multiple media; liver samples were stained with hematoxylin and eosin and Sudan III. CYPOR levels in liver homogenates were measured by ELISA-test. Physical and hydrochemical analyses indicated a high pollution level in the littoral zones. Isolated bacterial species were non-pathogenic but exhibited broad antibiotic resistance. Hematological evaluation revealed erythrocyte vacuolization and anisocytosis. Histological analysis showed marked fatty degeneration in hepatocytes, indicating toxic damage. CYPOR concentrations ranged from 0.3–0.4 ng/mL in healthy fish to 5–6 ng/mL in exposed specimens, showing strong correlation between environmental influence and enzyme activity. These findings demonstrate the potential of CYPOR as a sensitive biomarker for biomonitoring programs. The integrated methodological approach provides a model for assessing aquatic ecosystem health and identifying zones requiring priority remediation. Full article

Anime pilgrimage refers to the act of fans visiting real-world locations featured in anime works, offering visual familiarity alongside cultural depth. However, existing studies on anime tourism provide limited computational support for selecting pilgrimage sites based on contextual and experiential factors. This study proposes an intelligent recommendation framework based on multi-source data fusion that integrates three key elements: transportation accessibility, seasonal alignment between the current environment and the anime’s depicted scene, and a Cross-Platform Popularity Index (CPPI) derived from major global platforms. We evaluate each pilgrimage location using route-based accessibility analysis, season-scene discrepancy scoring, and robustly normalized popularity metrics. These factors are combined into a weighted Multi-Criteria Decision Making (MCDM) model to generate context-aware recommendations. To rigorously validate the proposed approach, a user study was conducted using a ranking task involving popular destinations in Tokyo. Participants were presented with travel conditions, spatial relationships, and popularity scores and then asked to rank their preferences. We used standard ranking-based metrics to compare system-generated rankings with participant choices. Furthermore, we conducted an ablation study to quantify the individual contribution of accessibility, seasonality, and popularity. The results demonstrate strong alignment between the model and user preferences, confirming that incorporating these three dimensions significantly enhances the reliability and satisfaction of real-world anime pilgrimage planning. Full article

This article presents a case study from a Social and Health Care School in Denmark, where a rooftop garden was designed to promote student health and support nature-based teaching across subject areas. A novel aspect of the project is the formal integration of the garden into teaching, implying that its long-term impact may extend beyond the students to the end-users they will later encounter in nursing homes and hospitals nationwide. This study applies the Evidence-Based Health Design in Landscape Architecture (EBHDL) process model, encompassing evidence collection, programming, and concept design, with the University of Copenhagen acting in a consultancy role. A co-design process with students and teachers was included as a novel source of case-specific evidence. Methodologically, this is a participatory practice-based case study focusing on the full design and construction processes, combining continuous documentation with reflective analysis of ‘process insights,’ generating lessons learned from the application of the EBHDL process model. This study identifies two categories of lessons learned. First, general insights emerged concerning governance, stakeholder roles, and the critical importance of site selection, procurement, and continuity of design responsibility. Second, specific insights were gained regarding the application of the EBHDL model, including its alignment with Danish and international standardised construction phases. These insights are particularly relevant for project managers in nature-based initiatives. The results also show how the EBHDL model aligns with Danish and international standardised construction phases, offering a bridge between health design methods and established building practice. The case focuses on the EBHDL process rather than verified outcomes and demonstrates how evidence-based and participatory approaches can help structure complex design processes, facilitate stakeholder engagement, and support decision-making in institutional projects. Full article

Developing sustainable and molecularly selective adsorbents for heavy-metal removal remains a critical challenge in water purification. Herein, we report a green molecular-engineering approach for fabricating aza-crown ether functionalized sodium alginate aerogels (ACSA) capable of highly selective Cu²⁺ capture. The aerogels were synthesized via saccharide-ring oxidation, Cu²⁺-templated self-assembly, and reductive amination, enabling the covalent integration of aza-crown ether motifs within a hierarchically porous biopolymer matrix. Structural analyses (FTIR, ¹³C NMR, XPS, SEM, TGA) confirmed the in situ formation of macrocyclic N/O coordination sites. Owing to their interconnected porosity and chemically stable framework, ACSA exhibited rapid sorption kinetics following a pseudo-second-order model (R² = 0.999) and a Langmuir maximum adsorption capacity of 150.82 mg·g⁻¹. The material displayed remarkable Cu²⁺ selectivity over Zn²⁺, Cd²⁺, and Ni²⁺, arising from the precise alignment between Cu²⁺ ionic radius (0.73 Å) and crown-cavity dimensions, synergistic N/O chelation, and Jahn-Teller stabilization. Over four regeneration cycles, ACSA retained more than 80% of its original adsorption capacity, confirming excellent durability and reusability. This saccharide-ring modification strategy eliminates crown-ether leaching and weak anchoring, offering a scalable and environmentally benign route to bio-based adsorbents that combine molecular recognition with structural stability for efficient Cu²⁺ remediation and beyond. Full article

High-resolution TIR missions require sustained and well-characterized radiometric accuracy to support applications such as land surface temperature retrieval, drought monitoring, and surface energy budget analysis. To address this need, we develop an operational and automated ground-based vicarious radiometric calibration framework for TIR sensors and demonstrate its performance using the Wide-swath Thermal Infrared Imager (WTI) onboard Gaofen-5 01A (GF-5A). Three arid Gobi calibration sites were selected by integrating Moderate Resolution Imaging Spectroradiometer (MODIS) cloud products, Shuttle Radar Topography Mission (SRTM)-derived topography, and WTI-based radiometric uniformity metrics to ensure low cloud cover, flat terrain, and high spatial homogeneity. Automated ground stations deployed at Golmud, Dachaidan, and Dunhuang have continuously recorded 1 min contact surface temperature since October 2023. Field-measured emissivity spectra, Integrated Global Radiosonde Archive (IGRA) radiosonde profiles, and MODTRAN (MODerate resolution atmospheric TRANsmission) v5.2 simulations were combined to compute top-of-atmosphere (TOA) radiances, which were subsequently collocated with WTI imagery. After data screening and gain-stratified regression, linear calibration coefficients were derived for each TIR band. Based on 189 scenes from February–July 2024, all four bands exhibit strong linearity (R-squared greater than 0.979). Validation using 45 independent scenes yields a mean brightness–temperature root-mean-square error (RMSE) of 0.67 K. A full radiometric-chain uncertainty budget—including contact temperature, emissivity, atmospheric profiles, and radiative transfer modeling—results in a combined standard uncertainty of 1.41 K. The proposed framework provides a low-maintenance, traceable, and high-frequency solution for the long-term on-orbit radiometric calibration of GF-5A WTI and establishes a reproducible pathway for future TIR missions requiring sustained calibration stability. Full article

Although technologies used in non-fossil methane and fossil resources to produce blue hydrogen are relatively mature, a system-integrated approach to reference system (RS)-based purification of H₂, CO₂ capture and storage, and UHS is relatively unexplored and requires research to fill gaps in the literature regarding balanced permutations and geological viability for net-zero requirements. This research proposes a system-integrated process for H₂ production through a PSA-based purification technique coupled with amine-based CO₂ capture and underground hydrogen storage (UHS). The intellectual novelty of the research is its first quantitative treatment of synergistic effects such as heat recovery and pressure-matching across units. Additionally, a site separation technique is applied, where H₂ and CO₂ reservoirs are selected based on the permeability of rock formations and fluids. On a research methodology front, a base case of a steam methane reforming process with the production of 99.99% pure H₂ at a production rate of 5932 kg/h is modeled and simulated using Aspen Plus™ to create a balanced permutation of mass and energy across units. As per the CO₂ capture requirements of this research, a capture of 90% of CO₂ is accomplished from the production of 755 t/d CO₂ within the model. The compressed CO₂ is permanently stored at specifically identified rock strata separated from storage reservoirs of H₂ to avoid empirically identified hazards of rock–fluid interaction at high temperatures and pressures. The lean amine cooling of CO₂ to 60 °C and elimination of tail-gas recompression simultaneously provides 5.4 MW_th of recovered heat. The integrated design achieves a net primary energy penalty of 18% of hydrogen’s LHV, down from ~25% in a standalone configuration. This corresponds to an energy saving of 8–12 MW, or approximately 15–18% of the primary energy demand. The research computes a production cost of H₂ of 0.98 USD per kg of H₂ within a production atmosphere of a commercialized WGS and non-fossil methane-based production of H₂. Additionally, a sensitivity analysis of ±23% of the energy requirements of the reference system shows no marked sensitivity within a production atmosphere of a commercially available WGS process. Full article

Protecting aquatic biodiversity while ensuring reliable hydropower production and water supply remains a core challenge for both water security and biosecurity. In this PRISMA-based systematic review, we synthesize evidence from 96 studies on fish guidance and deterrence at hazardous water intakes. We examine non-physical barriers, including acoustic and light cues, electric fields, bubble curtains, and chemical stimuli, as well as physical barriers such as racks, guidance structures, and nets or screens that aim to divert fish away from intakes and toward selective passage routes. Overall, guidance and deterrence performance is strongly species- and site-specific. Multimodal systems that combine multiple cues show the highest mean guidance efficiency (~80%), followed by light-based deterrents (~77%). Acoustic, electric, and bubble barriers generally achieve intermediate efficiencies (~55–58%), whereas structural devices alone exhibit lower mean performance (~46%), with substantial variability among sites and designs. Physical screens remain effective for larger size classes but can increase head loss and debris accumulation. By contrast, non-physical systems offer more flexible, low-footprint options whose success depends critically on local hydraulics, the sensory ecology of target species, and ambient environmental conditions. We identify major knowledge gaps relating to underlying sensory and behavioral mechanisms, hydraulics-based design rules, and standardized performance metrics. We also highlight opportunities to integrate advanced monitoring and AI-based analytics into adaptive, site-specific guidance systems. Taken together, our findings show that carefully selected and tuned barrier technologies can provide practical pathways to enhance water security and biosecurity, while supporting sustainable fish passage, improving invasive-species control, and reducing ecological impacts at water infrastructure. Full article

Background: β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors demonstrated amyloid-lowering efficacy but failed in phase II/III clinical trials due to adverse effects and limited disease-modifying outcomes. This study employed an integrated network pharmacology and molecular docking approach to quantitatively elucidate the multitarget mechanisms of 4 (phase II/III) discontinued BACE1 inhibitors (Verubecestat, Lanabecestat, Elenbecestat, and Umibecestat) and the preclinical compound AM-6494 in Alzheimer’s disease (AD). Methods: Drug-associated targets were intersected with AD-related genes to construct a protein–protein interaction (PPI) network, followed by topological analysis to identify hub proteins. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed using statistically significant thresholds (p < 0.05, FDR-adjusted). Molecular docking was conducted using AutoDock Vina to quantify binding affinities and interaction modes between the selected compounds and the identified hub proteins. Results: Network analysis identified 10 hub proteins (CASP3, STAT3, BCL2, AKT1, MTOR, BCL2L1, HSP90AA1, HSP90AB1, TNF, and MDM2). GO enrichment highlighted key biological processes, including the negative regulation of autophagy, regulation of apoptotic signalling, protein folding, and inflammatory responses. KEGG pathway analysis revealed significant enrichment in the PI3K–AKT–MTOR signalling, apoptosis, and TNF signalling pathways. Molecular docking demonstrated strong multitarget binding, with binding affinities ranging from approximately −6.6 to −11.4 kcal/mol across the hub proteins. Umibecestat exhibited the strongest binding toward AKT1 (−11.4 kcal/mol), HSP90AB1 (−9.5 kcal/mol), STAT3 (−8.9 kcal/mol), HSP90AA1 (−8.5 kcal/mol), and MTOR (−8.3 kcal/mol), while Lanabecestat showed high affinity for AKT1 (−10.6 kcal/mol), HSP90AA1 (−9.9 kcal/mol), BCL2L1 (−9.2 kcal/mol), and CASP3 (−8.5 kcal/mol), respectively. These interactions were stabilized by conserved hydrogen bonding, hydrophobic contacts, and π–alkyl interactions within key regulatory domains of the target proteins, supporting their multitarget engagement beyond BACE1 inhibition. Conclusions: This study demonstrates that clinically failed BACE1 inhibitors engage multiple non-structural regulatory proteins that are central to AD pathogenesis, particularly those governing autophagy, apoptosis, proteostasis, and neuroinflammation. The identified ligand–hub protein complexes provide a mechanistic rationale for repurposing and optimization strategies targeting network-level dysregulation in Alzheimer’s disease, warranting further in silico refinement and experimental validation. Full article

Globally, more than 60,000 abandoned open-pit mines have been identified. Most of these sites lack effective management or ecological restoration measures. As a result, they pose substantial environmental and socioeconomic challenges. Against this backdrop, the reuse of quarry wastelands has emerged as a critical strategy for improving resource efficiency and promoting sustainable development in mining regions. Current domestic research mainly concentrates on ecological restoration techniques for abandoned quarry sites. However, systematic methods for prioritizing and ranking alternative reuse models remain limited. This study investigated four quarry reuse models: agricultural production, ecological protection, recreation-based education, and new energy development. The analysis integrated site suitability (${\mathrm{U}}_1$) with residents’ demands (${\mathrm{U}}_2$). Four representative quarry sites in Jiawang District, Xuzhou City, were selected as case studies. Based on coupled matching analysis, a priority identification method for quarry site reuse models was developed. Results indicated divergent prioritization between site suitability and resident demand. Site suitability composite values ranged from 3.9548 to 6.3094. Qishan and Kanshan sites demonstrated high suitability for recreation-based education and agricultural production, while the Dongshan site showed the highest ecological protection suitability. Suitability for emerging energy applications was generally low across all sites. Resident demand composite values showed significant variation across the four models. Recreation-based education demand (${\mathrm{U}}_2$ ranging from 0.3273 to 0.3778) substantially exceeded the other three land use types, with residents generally harbouring a degree of reluctance towards new energy development models. After coupling these factors, the original site suitability rankings were restructured: Qishan and Dongshan were selected for the recreation-based education model; Kanshan for agricultural production; and Changshan for ecological protection. This study offers insights for the diversified utilization of abandoned quarries in rural areas and provides a reference for ecological restoration and transformative development in mining regions. 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

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