Search Results (426)

Alzheimer’s disease is driven by multiple molecular drivers, including the pathological behavior of two intrinsically disordered proteins, amyloid-β (Aβ) and tau, whose aggregation is regulated by sequence-encoded ensembles and liquid–liquid phase separation (LLPS). This review integrates recent advances in biophysics, structural biology, and computational modeling to provide a multiscale perspective on how sequence determinants, post-translational modifications, and protein dynamics regulate the conformational landscapes of Aβ and tau. We discuss sequence-to-ensemble principles, from charge patterning and aromatic binders to familial mutations that reprogram structural ensembles and modulate LLPS. Structural studies, including NMR, SAXS, cryo-EM, and cryo-electron tomography, trace transitions from disordered monomers to fibrils and tissue-level structures. We highlight experimental challenges in LLPS assays, emerging standards for reproducibility, e.g., LLPSDB, PhaSePro, and FUS benchmarks, and computational strategies to refine and condensate modeling. Finally, we explore the therapeutic implications, including condensate-aware medicinal chemistry, ensemble-driven docking, and novel insights from clinical trials of anti-Aβ antibodies. Together, these perspectives underscore a paradigm shift toward environment- and ensemble-aware therapeutic design for Alzheimer’s and related protein condensation disorders. Full article

Liposomal systems are advanced carriers of active substances which, thanks to their ability to encapsulate these substances, significantly improve their pharmacokinetics, bioavailability, and selectivity. This article presents the results of spectroscopic studies for a selected compound from the 1,3,4-thiadiazole group, namely 4-[5-(naphthalen-1-ylmethyl)-1,3,4-thiadiazol-2-yl]benzene-1,3-diol (NTBD, see below in the text), in selected liposomal systems formed from the phospholipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). Detailed spectroscopic analyses were carried out using electronic absorption and fluorescence spectroscopy; resonance light scattering (RLS) spectra measurements; dynamic light scattering (DLS); as well as time-resolved methods—fluorescence lifetime measurements using the TCSPC technique. Subsequently, based on the interpretation of spectra obtained by FTIR infrared spectroscopy, the preliminary molecular organization of the above-mentioned compounds within lipid multilayers was determined. It was found that NTBD preferentially occupies the region of polar lipid headgroups in the lipid multilayer, although it also noticeably interacts with the hydrocarbon chains of the lipids. Furthermore, X-ray diffraction (XRD) techniques were used to study the effect of NTBD on the molecular organization of DPPC lipid multilayers. Monomeric structures and aggregated forms of the above-mentioned 1,3,4-thiadiazole analogue were characterized using X-ray crystallography. Interesting dual fluorescence effects observed in steady-state fluorescence measurements were linked to the excited-state intramolecular proton transfer (ESIPT) effect (based on our earlier studies), which, in the obtained biophysical systems—liposomal systems with strong hydrophobicity—is greatly enhanced by aggregation-induced emission (AIE) effects. In summary, the research presented in this study, concerning the novel 1,3,4-thiadiazole derivative NTBD, is highly relevant to drug delivery systems, such as various model liposomal systems, as it demonstrates that depending on the concentration of the selected fluorophore, different forms may be present, allowing for appropriate modulation of its biological activity. Full article

Rubberized concrete is a novel green building material that enhances many features when rubber particles are incorporated into cement mortar, simultaneously yielding economic benefits through the recycling of waste tires. This study applies styrene–butadiene latex (SBL) for toughening treatment. The investigation delves into the mechanism by which SBL improves the interface between rubber and cement, encompassing macroscopic mechanical properties, microscopic structural characteristics, and nano-scale interfacial interactions. Macroscopic mechanical tests reveal a significant increase in flexural strength, shear strength, and compressive strength of the composite concrete upon the introduction of SBL and rubber. Specifically, the compressive strength improved by 8.8%, shear strength by 13.7%, and flexural strength by 18.9% at 28 days. Through electron microscopy observation of corresponding polymer cement concrete sections, observations reveal that SBL reinforces both interfaces and elucidates its bonding impact at the micro-level interface. Molecular dynamics (MD) modeling of SBL/rubber/CSH is employed at the nanoscale to compute and examine the local structure, dynamic behavior, and binding energy of the interface. The findings indicate that SBL mitigates interface impacts, enhances interface hydrogen bonds, van der Waals interactions, $\mathrm{C}\mathrm{a}-\mathrm{H}$ coordination bonds, and stability, consequently improving interfacial adhesion and fortifying the feeble interface bonding between organic polymers (rubber) and inorganic silicates (CSH). Full article

Mitigating climate change through the reduction of atmospheric CO₂ emissions remains a critical global priority. Solid adsorbents, particularly shales, have become promising options for CO₂ storage due to their favorable structural and chemical properties. In this study, a solid sorbent was developed by pyrolyzing shale at 800 °C under a nitrogen (N₂) atmospheric condition, yielding spent shale. The key physicochemical properties influencing CO₂ sorption were characterized using X-ray diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM), Brunauer–Emmett–Teller (BET) surface area analysis, and Temperature-Programmed Desorption (TPD). Mineralogical analysis revealed the presence of quartz, feldspars, clays, and carbonate minerals. The spent shale exhibited surface areas of 30–34 m²/g and pore diameters ranging from 3 to 10 nm. TPD results confirmed the presence of active adsorption sites, with a maximum CO₂ sorption capacity of about 1.62 mmol/g—surpassing several commercial sorbents. Adsorption behavior was best described by the Sips and Toth isotherm models (R² > 0.99), indicating multilayer and heterogeneous adsorption processes. Kinetic modeling using both pseudo-first-order and pseudo-second-order equations revealed that CO₂ uptake was governed by both diffusion and chemisorption mechanisms. These findings positioned spent shale as a low-cost, efficient sorbent for CO₂ storage, promoting circular resource utilization and advancing sustainable carbon management strategies. This novel shale-derived material offers a competitive pathway for carbon capture, storage, and sequestration applications. Full article

The development of advanced drug delivery systems is essential for improving therapeutic efficacy, particularly in the treatment of neurodegenerative disorders such as Alzheimer’s disease. This study investigates zinc-modified mordenite zeolite (MR-ZN) as a novel platform for the controlled delivery of donepezil (DPZ), a cholinesterase inhibitor. Natural mordenite was modified with zinc, enhancing its surface area from 62.1 to 85.4 m²/g and improving its adsorption properties. Donepezil was successfully loaded at two doses (10 mg and 23 mg), achieving high loading efficiencies of 95% and 94%, respectively. Adsorption kinetics followed a pseudo-second-order model (R² > 0.99), indicating that chemisorption predominates through coordination between DPZ functional groups and Zn²⁺ sites, while complementary physisorption via hydrogen bonding and van der Waals interactions also contributes to molecular stabilization within the zeolite framework. In vitro release studies under simulated gastrointestinal conditions demonstrated sustained and pH-responsive release profile with 80% and 82% of donepezil released after 24 h for 10 mg and 23 mg formulations, respectively. Density Functional Theory (DFT) calculations revealed favorable adsorption energy (−26.4 kJ/mol), while Bader and Electron Localization Function (ELF) analyses confirmed hydrogen bonding and electrostatic interactions without compromising the zeolite framework. These findings validate MR-ZN as structurally stable, efficient, cost-effective and biocompatible matrix for oral drug delivery. The combination of experimental data and theoretical modeling supports its potential to improve bioavailability and therapeutic performance in neurodegenerative treatment. Full article

Background: In this research work, novel pyrazolone-derived oxadiazole-based benzamide derivatives (1–10) were synthesized through unique and facile synthetic routes. Introduction: These scaffolds were designed to be therapeutically more effective and have fewer side effects. Methods: To confirm the structure of analogs in detail, we employed ¹HNMR, ¹³CNMR, and HREI-MS spectroscopy. The potential of all derivatives was tested by screening them against alpha-amylase and alpha-glucosidase in comparison with reference anti-diabetic drug acarbose (4.50 ± 0.20 µM and 4.90 ± 0.30 µM). Results & Discussion: Among all tested analogs and standard drugs, derivative 3 proved to be the most promising candidate. It exhibited the most powerful inhibitory effect (IC₅₀ = 3.20 ± 0.20 µM and 3.60 ± 0.10 µM). To further investigate its activity, the experimental results were supported by in silico investigations. Molecular docking demonstrated strong and viable interactions between enzymes and the most potent compound. DFT calculations validated the electronic configuration, stability, and reactivity of lead molecules. Furthermore, the ADMET profile predicted the favorable drug likeness properties and low toxicity. The results of docking were further confirmed via molecular dynamics analysis, whereas the pharmacophore model of analog 3 supports the formation of a stable hydrogen bond network of derivatives with the receptor site of the enzyme. Conclusions: Collectively in silico and in vitro results underscore the therapeutic potential of these derivatives for the effective treatment of diabetes in the future. Full article

Heavy metal contamination in water, predominantly from copper (Cu(II)) ions, poses substantial risks to human and environmental health. This study developed a novel, robust adsorbent known as a carboxylate cellulose nanocrystal–silica–graphene oxide hybrid composite porous monolith, which effectively removes Cu(II) from water in a rapid manner. Carboxylate cellulose nanocrystals with enhanced metal-binding properties were synthesized from cellulose extracted from sugarcane bagasse, a significant agricultural byproduct. The porous monolith was synthesized through the combination of carboxylate cellulose nanocrystals, tetraethyl orthosilicate (TEOS), and graphene oxide, utilizing a sol–gel method. The efficacy of the synthesis was confirmed using Fourier-Transform Infra-red (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscope (SEM), and Brunauer–Emmett–Teller (BET) analyses. The material exhibited a highly porous mesoporous structure with a surface area of 512 m²/g, signifying a significant enhancement. Batch adsorption experiments under optimal conditions (pH = 5.5, contact time = 240 min, initial concentration = 200 mg/L) demonstrated a high experimental adsorption capacity of 172 mg/g for Cu(II). The adsorption process was best described by the Langmuir isotherm model, which yielded a theoretical maximum capacity (q_m) of 172 mg/g, and the pseudo-second-order kinetic model, confirming monolayer coverage and chemisorption as the rate-limiting step. Thermodynamic analyses demonstrate that the process is both spontaneous and exothermic. The porous monolith demonstrates the capability for multiple uses, maintaining over 70% efficiency after five cycles. The findings indicate that the carboxylate cellulose nanocrystal–silica–graphene oxide hybrid composite porous monolith is an efficient and robust method for the remediation of copper-contaminated water. Full article

Background: Leishmania amazonensis, one of the causative agents of cutaneous leishmaniasis, is responsible for a neglected tropical disease affecting nearly one million individuals worldwide. Although clinical treatments are available, their effectiveness is often compromised by high toxicity and limited selectivity. Methods: From a database, 64 chalcone derivatives were studied using Comparative Molecular Similarity Indices Analysis (CoMSIA) and Hansch analysis (2D-QSAR) to construct predictive computational models. Internal and external validation criteria were applied to identify structural determinants associated with antileishmanial activity. Based on these insights, twelve novel quinoline–chalcone hybrids were designed, synthesized, and biologically evaluated against L. amazonensis. Results: The most robust CoMSIA model combined steric and hydrogen-bond acceptor fields (CoMSIA-SA), while Hansch analysis highlighted electronic descriptors—specifically LUMO energy and the global electrophilicity index—as critical for parasite growth inhibition. Guided by these computational findings, a new series of 12 hybrid quinoline–chalcone derivatives (E001–E012) was synthesized through a two-step procedure, achieving overall yields of 43–71%. Biological assays demonstrated that four compounds displayed inhibitory activity comparable to amphotericin B. Furthermore, physicochemical profiling and in silico pharmacokinetic predictions for the most active compounds (E003, E005, E006, and E011) indicated favorable biocompatibility and drug-like properties. Conclusions: These results underscore the value of an integrative computational–experimental approach in the rational design of next-generation L. amazonensis inhibitors, reinforcing chalcone-based scaffolds as promising pharmacophoric frameworks for antileishmanial drug discovery. Full article

In this study, we explored the evolution of mechanical properties in hydroxyl-terminated polybutadiene (HTPB) propellants under fatigue loading by performing fatigue tests with varying maximum stresses and cycle numbers, followed by uniaxial tensile tests on post-fatigue specimens. Residual elongation was used as a key parameter to characterize mechanical behavior, while scanning electron microscopy (SEM) provided insights into the mesostructural morphological changes that occur under different loading conditions, revealing the mechanisms responsible for variations in mechanical properties. The results show that, as the number of loading cycles increases, residual elongation decreases, with three distinct phases of decline—slow change, gradual decline, and rapid deterioration—depending on the stress levels. SEM analysis identified damage mechanisms such as “dewetting” and particle fragmentation at the mesostructural level, which compromise the material’s structural integrity, leading to reduced residual elongation. A novel aspect of this study is the application of Williams–Landel–Ferry (WLF) theory to construct a master curve describing residual elongation decay. This approach enabled the development of a generalized model to predict the material’s degradation under fatigue loading, with experimental validation of the fitted evolution model, offering a new and effective method for assessing the long-term performance of HTPB propellants. Full article

This study introduces a novel photocatalyst derived from pumpkin peel bio-waste, calcined at 200 °C and incorporated with magnetite nanoparticles to form a hybrid PK-P/Fe₃O₄ catalyst. The material was characterized using X-ray diffraction (XRD), diffuse reflectance spectra (DRS), and scanning electron microscopy (SEM) with energy-dispersive X-ray spectroscopy (EDX) mapping to confirm its structure and elemental distribution. The catalyst was applied for the photo-Fenton degradation of Synozol Red KHL dye under natural solution conditions (pH 5.7). Optimal parameters were achieved with a 20 mg/L catalyst and 200 mg/L H₂O₂, resulting in complete dye removal within 25 min of irradiation. The PK-P/Fe₃O₄ catalyst exhibited excellent reusability, retaining 72% removal efficiency after 10 successive cycles. Kinetic analysis confirmed a first-order model, while thermodynamic evaluation revealed a non-spontaneous, endothermic process with a low activation energy barrier, indicating energy-efficient dye degradation. These findings highlight the potential of bio-waste-derived PK-P/Fe₃O₄ as a sustainable, low-cost, and highly effective catalyst for treating dye-polluted wastewater under photo-Fenton conditions. Full article

Ohm’s law has become ubiquitous in numerous scientific and technical disciplines. Generally, the subject is introduced to students in secondary school as fundamental technical knowledge. The present study proposes a visual model to facilitate the comprehension of Ohm’s law in electron transport in solids to pre-university and university students. The objective is to facilitate students’ comprehension of the correlation between electron movement in solids, as depicted by a current, and the energy of the system, which is introduced by the electric field and the material’s structure. The approach’s originality lies in its novel strategy for describing electron trajectory randomization. This enables the establishment of a relationship between the material’s structure and its resistivity. Moreover, the description of electron transport and scattering processes is presented regarding different types of entropy. It shows that electrons follow the maximum trajectory entropy and that thermal entropy has a quadratic relationship with configurational entropy. The determinism of Ohm’s law is inferred from statistical entropy. Full article

This paper presents a novel mechanically beam-steered antenna system for 10 GHz applications, enabled by multi-material 3D-printing technology. The proposed design eliminates the need for complex electronic circuitry by integrating a mechanically rotatable, 3D-printed hemispherical lens with a conventional rectangular patch antenna. The system comprises three main components: a 10-GHz patch antenna, a precision-fabricated hemispherical dielectric lens produced via stereolithography (SLA), and a structurally robust rotation assembly fabricated using fused deposition modeling (FDM). The mechanical rotation of the lens enables discrete beam-steering from −45° to +45° in 5° steps. Experimental results demonstrate a gain improvement from 6.21 dBi (standalone patch) to 10.47 dBi with the integrated lens, with minimal degradation across steering angles (down to 9.59 dBi). Simulations and measurements show strong agreement, with the complete system achieving 94% accuracy in beam direction. This work confirms the feasibility of integrating additive manufacturing with passive beam-steering structures to deliver a low-cost, scalable, and high-performance alternative to electronically scanned arrays. Moreover, the design is readily adaptable for motorized actuation and closed-loop control via embedded systems, enabling future development of real-time, programmable beam-steering platforms. Full article

Dental caries, a prevalent biofilm-mediated chronic disease, causes enamel demineralization, pulp infection, and systemic complications. Dental plaque biofilm is the initiating factor for the occurrence and development of caries. Streptococcus mutans is an opportunistic pathogen linked to the structure and ecology of dental plaque biofilms. The molecular mechanism of S. mutans during biofilm ontogeny in driving cariogenesis has been extensively elucidated. Here, we observed that asiatic acid is a potent biofilm disruptor that selectively dismantles S. mutans biofilm architectures, prompting us to investigate its mechanism. The minimum biofilm inhibition concentration (MBIC) of asiatic acid on S. mutans was 62.5 μM, but the MBIC level did not substantially impede planktonic growth. Using the static active-attachment model, it was demonstrated that asiatic acid significantly reduced biofilm biomass (p < 0.001) and extracellular polysaccharides (EPS) content (p < 0.001), while concurrently diminishing acid production (p = 0.017) and metabolic activity (p = 0.014). Confocal and scanning electron microscopy further confirmed structural disintegration, including bacterial detachment and reduced biofilm thickness. Transcriptome analysis of S. mutans biofilm treated with asiatic acid revealed 454 differentially expressed genes (adjusted p < 0.05, |log₂FC| ≥ 1). Notably, genes related to the CiaRH two-component system (ciaR, ciaH), a central regulatory hub for biofilm maturation and acid tolerance. This disruption initiates a downstream cascade, causing a coordinated downregulation of critical gene clusters essential for virulence and pathogenesis, including stress response (htrA, clpP, groEL, dnaK), and the glucan-binding protein gene (gbpC) essential for biofilm structural integrity. These findings provide the first mechanistic evidence linking asiatic acid to transcriptional reprogramming in S. mutans biofilm, offering a novel ecological strategy for caries prevention by targeting key regulatory pathways. Full article

The Denoising Wavelet Transform Convolutional Long Short-Term Memory Network (DWTConvLSTM) is a novel ionospheric total electron content (TEC) spatiotemporal prediction model proposed in 2025 that can simultaneously consider high-frequency and low-frequency features while suppressing noise. However, it also has flaws as it only considers unidirectional temporal features in spatiotemporal prediction. To address this issue, this paper adopts a bidirectional structure and designs a bidirectional DWTConvLSTM model that can simultaneously extract bidirectional spatiotemporal features from TEC maps. Furthermore, we integrate a lightweight attention mechanism called Convolutional Additive Self-Attention (CASA) to enhance important features and attenuate unimportant ones. The final model was named CASA-BiDWTConvLSTM. We validated the effectiveness of each improvement through ablation experiments. Then, a comprehensive comparison was performed on the 11-year Global Ionospheric Maps (GIMs) dataset, involving the proposed CASA-BiDWTConvLSTM model and several other state-of-the-art models such as C1PG, ConvGRU, ConvLSTM, and PredRNN. In this experiment, the dataset was partitioned into 7 years for training, 2 years for validation, and the final 2 years for testing. The experimental results indicate that the RMSE of CASA-BiDWTConvLSTM is lower than those of C1PG, ConvGRU, ConvLSTM, and PredRNN. Specifically, the decreases in RMSE during high solar activity years are 24.84%, 16.57%, 13.50%, and 10.29%, respectively, while the decreases during low solar activity years are 26.11%, 16.83%, 11.68%, and 7.04%, respectively. In addition, this article also verified the effectiveness of CASA-BiDWTConvLSTM from spatial and temporal perspectives, as well as on four geomagnetic storms. Full article

The construction industry in Pakistan faces persistent challenges due to uncertainties such as behavioral intention, risk identification, and stakeholder perception, which often lead to significant losses in construction activities and human resources. This study aims to quantitatively evaluate these critical factors within the theoretical framework of Building Information Modeling (BIM) and the Technology Acceptance Model (TAM). Specifically, key constructs—Behavioral Intention (BI), Hazard Identification (HI), and Stakeholder Perception (SP)—are analyzed to assess their influence on construction safety management practices. A structured questionnaire was distributed electronically to construction professionals across various ongoing projects in Pakistan. The questionnaire items were based on a five-point Likert scale, and reliability was confirmed with high Cronbach’s alpha values for BI (0.82), HI (0.92), and SP (0.91). To evaluate the relationships between constructs, descriptive statistics and multiple regression analysis were employed. The regression results showed strong model fit for BI and HI (R² = 0.945), and near-perfect fit for SP (R² = 0.998), demonstrating robust predictive power. Significant correlations were found among independent variables such as Perceived Usefulness (PU), Perceived Ease of Use (PEOU), Attitude Toward Use (ATU), and others. This study further identifies Trust (TR) and Organizational Culture (OC) as critical predictors of stakeholder perception in the BIM context. A conceptual framework was developed incorporating statistical parameters (e.g., p-values, R², t-stats) to categorize the effectiveness of BIM and TAM theoretical integration for safety risk management. This approach is novel in its use of TAM-based constructs to evaluate BIM-related safety outcomes in the Pakistani construction sector—a context where such empirical evidence is limited. The findings provide predictive insights into how behavioral, perceptual, and organizational variables influence construction safety performance, offering practical implications for BIM adoption and safety policy design. Full article