Search Results (191)

Background/Objectives: Inclusion complexes among drugs and cyclodextrin-modified polymers are a topic of recent interest in pharmaceutical research and industry as they might expand the solubility, bioavailability, and stability of the guest molecules. Polyurethanes derived from cyclodextrins show some biomedical applications. In this study, two cross-linked polyurethane networks based on hydroxypropyl-β-cyclodextrin (HPβCD) and polyethylene glycols (PEG 2000 or PEG 6000) were synthesized with NCO/OH molar ratio 4.3 and 6.3 by the typical two-step polymerization method. Methods: Inclusion complexes of clotrimazole (CLOT) with two HPβCD-modified polyurethane networks and their corresponding physical mixtures were prepared using kneading methods and physical mixing in a 1:6 weight ratio of CLOT:HPβCD. Results: Obtained prepolymers, previously end-capped with isocyanate groups forming urethane links with HPβCD, which were confirmed by FTIR analysis. TGA results indicate a slight increase in thermal stability of the prepared complexes. The characteristic endothermic peak of the CLOT at around 145.90 °C did not appear in the DSC curve of the drug-loaded inclusion complexes. The XRD patterns of physical mixtures showed specific peaks corresponding to pure clotrimazole. SEM micrographs confirmed an elliptical/spherical- and plate-shaped particles without phase segregation, indirectly confirming that CLOT is not separately present due to inclusion into HPβCD and entrapment into polyurethane networks. Novel complexes PUR2/HPβCD-CLOT-IC and PUR3/HPβCD-CLOT-IC were applied as drug carriers, and diffusion-controlled kinetics of CLOT release were best described using Higuchi model. Conclusions: The obtained in vitro results showed surprisingly slow/prolonged clotrimazole release from modified polyurethane networks due to the significant influence of NCO/OH molar ratio and the chosen polyol soft segments chain length with potential in vivo applications. Full article

Background: Silver nanoparticles (AgNPs) trigger apoptosis in cancer cells, while albumin nanoparticles enable effective drug delivery. This study compares the antitumor and cytotoxic effects of albumin-coated AgNPs (AgNPs-Alb) versus AgNPs on human prostate cancer cell lines. Method: AgNPs-Alb were synthesized and tested against PC3 and LNCaP prostate cancer cell lines. Characterization via Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), and Ultraviolet-Visible (UV-Vis) spectroscopy confirmed their properties. IC50 values were determined using MTT assay, with apoptosis assessed by Annexin-V/PI staining. DNA cell cycle was analyzed by PI staining. Migration, proliferation, and nuclear morphology were evaluated through scratch-wound, colony-forming, and Hoechst staining assays. Gene expression of Snail, E-cadherin, VEGF-C, VEGF-A, Bcl2, Bax, and P53 was analyzed using real-time PCR. Results: The IC50 values for AgNPs and AgNPs-Alb were 48 μM and 32 μM in PC3 cells, and 110 μM and 95 μM in LNCaP cells, respectively. AgNPs-Alb significantly inhibited PC3 cell migration compared to AgNPs (p < 0.001) and Bicalutamide (p < 0.0001). In both cell lines, AgNPs-Alb significantly reduced colony formation compared to AgNPs and Bicalutamide (p < 0.05). Flow cytometry revealed a higher percentage of apoptotic cells in PC3 with AgNPs-Alb treatment compared to AgNPs and Bicalutamide. In LNCaP cells, AgNPs-Alb induced a significantly higher percentage of Sub-G1 cells. AgNPs-Alb treatment caused greater mRNA suppression of VEGF-A and a higher Bax/Bcl2 ratio in PC3 and LNCaP cells (p < 0.05). Additionally, a significant increase in P53 and E-cadherin, alongside a decrease in VEGF-C expression in LnCAP cells, was observed (p < 0.05). Conclusions: This study suggests that AgNPs-Alb have stronger anticancer and cytotoxic effects compared to AgNPs alone against PCa cell lines and higher effects were observed on PC3 cells compared to LnCAP cells. Full article

Background: Inhibition of histone deacetylase is a highly sought-after objective in the fight against cancer. Thus, the development of innovative HDAC inhibitors with significantly higher potency than SAHA against specific cancer cell types represents complex and demanding work. Method: The utilization of the underexplored and privileged scaffold 4-chlorothieno[2,3-b]pyridine as a cap tethering diverse aliphatic and aromatic linkers, followed by the screening of both cellular and enzymatic activities, is undertaken in this study. Results: Compounds 7a and 9a demonstrated impressive mean GI₅₀ values of 2.15 µM and 1.89 µM, respectively. Both compounds reduced caspase-3 levels in RPMI-8226 cells, suggesting induction of apoptosis. Compound 7a showed remarkable IC₅₀ values of 0.37 µM, 0.58 µM, and 0.70 µM against HDACs 1, 4, and 6, respectively, consistent with the cellular assay. Additionally, compound 7a exhibited a selectivity index of 11 for RPMI-8226 cells over PBMCs, reflecting its high selectivity and potential safety. Moreover, ADMET prediction tools indicated that compounds 7a and 9b may have more favorable pharmacokinetic properties than the gold-standard HDAC inhibitor, SAHA. Conclusions: Further study and exploration of the derivatives of compounds 7a and 9a can lead to further advancement in the development of potent HDAC inhibitor anticancer drugs. Full article

This study presents an efficient, environmentally benign approach for synthesizing chitosan-entrapped titanium dioxide (TiO₂) nanocomposites utilizing aqueous orange peel extract playing its role in reduction and stabilization of the nanoparticles and exploring its anticancer activity in vitro. TiO₂ nanoparticles were initially synthesized via a modified sol-gel method incorporating the orange peel extract. Subsequently, these nanoparticles were entrapped within a chitosan matrix. The orange peel extract was thoroughly characterized using analysis of phytochemicals present, and Gas Chromatography–Mass Spectrometry (GC–MS) analysis of a reconstructed methanolic extract to identify potential biomolecules responsible for the reduction and capping processes. The synthesized chitosan-entrapped TiO₂ nanoparticles were subjected to comprehensive characterization using various analytical techniques, like UV–visible spectroscopy, Dynamic Light Scattering (DLS) and Zeta Potential analysis, X-ray Diffraction (XRD), FTIR, High-Resolution Scanning Electron Microscopy (HR-SEM) and Energy-Dispersive X-ray Spectroscopy (EDAX). An absorption peak was observed at 296 nm, a hydrodynamic diameter of 400 nm, a+ 35.88 mV zeta potential, and an SEM image showing a diameter in the range of 300–645 nm, indicating polymer entrapment with enhanced size. Brine shrimp assay, MTT assay using normal fibroblasts, 3T3-L1, and zebrafish embryo assay were done to observe the biocompatibility of the synthesized nanostructure. The concentration of 50 μg/mL was found to be inert in both in vitro and in vivo. Furthermore, cervical cancer cells, SiHa, were treated with the nanoparticles to exhibit their cancer-killing capability with an IC₅₀ value of 30.74 μg/mL. The results demonstrate the effectiveness of orange peel extract as a sustainable agent for TiO₂ nanoparticle synthesis and the successful formation of a stable chitosan-entrapped nanocomposite. This approach offers a promising pathway for producing functional metal oxide nanomaterials with reduced environmental impact and enhanced properties for diverse biomedical applications. Future studies using other types of cancer cells and animal models for cancerous tumors need to be explored. Full article

The green synthesis of nanomaterials using biological resources has emerged as a sustainable alternative to conventional chemical routes. In this study, the wild ectomycorrhizal mushroom Russula sanguinea (Rs) was employed as a natural reducing and stabilizing agent for the biosynthesis of silver-decorated zinc-based nanostructures (Ag–ZnNSs/Rs). The formation and physicochemical properties of the nanostructures were systematically characterized using UV–Vis spectroscopy, FT-IR spectroscopy, SEM, TEM, and EDX analysis. Transmission electron microscopy revealed predominantly spherical nanoparticles with good dispersion, and quantitative analysis of 227 individual particles demonstrated an average diameter of 19.36 ± 7.89 nm (range: 10.92–61.00 nm). FT-IR analysis confirmed the involvement of fungal biomolecules in metal ion reduction and surface stabilization, indicating effective bio-capping of the nanostructures. The biofunctional performance of the biosynthesized Ag–ZnNSs/Rs was evaluated through antioxidant and antimicrobial assays. Compared to the crude mushroom extract, the nanostructures exhibited significantly enhanced 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity with an IC₅₀ value of 7.29 ± 0.10 mg mL⁻¹ compared to 13.66 ± 0.15 mg mL⁻¹ for the crude extract. In addition, notable antimicrobial activity was observed against representative Gram-positive and Gram-negative bacteria (Bacillus cereus, Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) as well as the yeast Candida albicans. Overall, this study demonstrates that Russula sanguinea is an effective biological platform for the green synthesis of silver-decorated zinc-based nanostructures with improved biofunctional properties, highlighting the potential of wild mushrooms as underexplored resources in sustainable nanomaterial development. Full article

The anticipated transition from 5G to 6G is driven not by incremental performance demands but by a widening mismatch between emerging application requirements and the capabilities of existing cellular systems. Despite rapid progress across 3GPP Releases 15–20, the current literature lacks a unified analysis that connects these standardization milestones to the concrete technical gaps that 6G must resolve. This study addresses this omission through a cross-release, application-driven review that traces how the evolution from enhanced mobile broadband to intelligent, sensing integrated networks lays the foundation for three core 6G service pillars: immersive communication (IC), everything connected (EC), and high-precision positioning. By examining use cases such as holographic telepresence, cooperative drone swarms, and large-scale Extended Reality (XR) ecosystems, this study exposes the limitations of today’s spectrum strategies, network architectures, and device capabilities and identifies the performance thresholds of Tbps-level throughput, sub-10 cm localization, sub-ms latency, and 10 M/km² device density that next-generation systems must achieve. The novelty of this review lies in its synthesis of 3GPP advancements in XR, the non-terrestrial network (NTN), RedCap, ambient Internet of Things (IoT), and consideration of sustainability into a cohesive key performance indicator (KPI) framework that links future services to the required architectural and protocol innovations, including AI-native design and sub-THz operation. Positioned against global initiatives such as Hexa-X and the Next G Alliance, this paper argues that 6G represents a fundamental redesign of wireless communication advancement in 5G, driven by intelligence, adaptability, and long-term energy efficiency to satisfy diverse uses cases and requirements. Full article

Celtis africana, a rare plant native to southwestern Saudi Arabia, was explored for the first time as a source for the green synthesis of silver nanoparticles (AgNPs). Catechol-bearing phenolic amides in the aqueous leaf extract acted as both reducing and capping agents, enabling eco-friendly AgNP fabrication. The synthesized AgNPs were characterized using SEM, TEM, XRD, UV-Vis, and FTIR, revealing predominantly spherical nanoparticles with an average size of 9.28 ± 0.11 nm, a face-centered cubic crystalline structure, and a pronounced surface plasmon resonance at 424 nm. HPLC analysis confirmed the presence of caffeoyltryamine in the extract, while UV-Vis and FTIR indicated its attachment to the AgNP surface. The AgNPs exhibited broad-spectrum antimicrobial activity against Gram-positive bacteria (S. aureus, MRSA and E. faecalis) and Gram-negative bacteria (E. coli, K. pneumoniae, S. typhimurium, and P. aeruginosa), as well as pathogenic fungi such as C. albicans, C. glabrata, C. parapsilosis, and C. krusei with performance comparable to or exceeding that of AgNPs from Artemisia vulgaris, Moringa oleifera, and Nigella sativa. The MIC and MBC values for S. aureus, MRSA, E. coli, and S. typhimurium were consistently 6.25 µg/mL and 25 µg/mL, respectively, reflecting strong inhibitory and bactericidal effects at low concentrations. MTT assays demonstrated selective cytotoxicity, showing higher viability in normal human skin fibroblasts (HSF) than in MCF-7 breast cancer cells. The AgNPs also displayed strong antioxidant activity (IC₅₀ = 5.41 µg/mL, DPPH assay) and efficient catalytic reduction of 4-nitrophenol (4-NP) and methylene blue (MB), with rate constants of 0.0165 s⁻¹ and 0.0047 s⁻¹, respectively, exceeding most reported values. These findings identify Celtis africana as a promising source for eco-friendly AgNPs with strong antimicrobial, antioxidant, and catalytic properties for broad biological and environmental applications. Full article

The mechanical response and failure behavior of high-pressure frozen ice are essential to the technological progress in drilling thick polar ice sheets, but current research primarily focuses on non-pressure-frozen ice. In this paper, ice specimens with a cylindrical geometry were fabricated at −20 °C, applying freezing pressures across a range of 10 to 40 MPa with a 10 MPa interval. Their mechanical properties were investigated through triaxial compression tests under axial loading conditions and were compared with the results obtained at −10 °C. The results indicate that, with increasing freezing pressure, the samples transitioned from a failure state of interlaced cracking to a highly transparent state. The failure behavior observed in the specimens was characterized as ductile, as evidenced by the deviatoric stress–axial strain relationships. Moreover, the peak deviatoric stress exhibited a non-monotonic dependence on freezing pressure, with an initial rise from 9.59 MPa at 10 MPa to a peak of 14.37 MPa at 30 MPa and a subsequent decline to 10.12 MPa at 40 MPa. All specimens reached a relatively stable residual state at 5% axial strain, with residual deviatoric stresses ranging from 4.13 to 5.71 MPa. A reduction in freezing temperature from −10 °C to −20 °C can effectively enhance both the peak deviatoric stress and the residual stress of high-pressure frozen ice under triaxial shear conditions. All peak tangent modulus values, ranging from 1.61 to 2.93 GPa with an average of 2.2 GPa, were observed within 0.7% axial strain and exhibited mild fluctuations with increasing freezing pressure. These findings provide a more robust mechanical foundation for drilling research and operations in extremely thick polar ice caps. Full article

Antarctica, largely free from geopolitical borders, serves as a critical site for scientific research, environmental monitoring and climate studies. The continent’s ice cap holds over 60% of the Earth’s freshwater and provides a stable climatological record spanning 800,000 years. In this study, the relationship between changes in atmospheric CO₂ levels over the past century and the microstructural characteristics of Antarctic ice was investigated. While it is well-documented that CO₂ fluctuations have driven the periodic expansion and retreat of ice sheets, no research to this day has explored how variations in CO₂ concentrations influence the physical integrity of ice at the microscopic scale. To address this, grain size, anisotropy, irregularity, and solidity of surface and near-surface ice samples collected over the past 70 years were analyzed. These microstructural features were compared against historical atmospheric greenhouse gas data from multiple Antarctic research stations, including records from the Scripps Institution of Oceanography, the Japanese Antarctic Research Expedition, and the NOAA Global Monitoring Laboratory. Results reveal a correlation between rising CO₂ levels and changes in ice microstructure, particularly an increase in the grain size as well as the reduction in the grain aspect ratio and in the morphological solidity. The study remains limited by significant sources of variability, including differences in sampling depths, geographical locations, seasonal effects, and inconsistencies in analytical tools and methodologies reported across the literature. Despite these limitations, this proof-of-concept study elicits the need for continued meta-analyses of existing climate datasets. Such efforts could provide deeper insights into the role of greenhouse gas concentrations in defining the microstructural stability of Antarctic ice, which is critical for predicting ice sheet integrity and its contribution to sea level rise. Full article

Aromatic ring systems appear ubiquitously in active pharmaceutical substances, such as FDA-approved histone deacetylase inhibitors. However, these rings reduce the water solubility of the molecules, which is a disadvantage during application. To address this problem, azaborine rings may be substituted for conventional aromatic ring systems. These are obtained by replacing two adjacent carbon atoms with boron and nitrogen. Incorporating B–N analogs in place of aromatic rings not only enhances structural diversity but also provides a strategy to navigate around patent-protected scaffolds. We synthesized azaborines, which are isosteric to naphthalene and indole, and utilized them as capping units for HDAC inhibitors. These molecules were attached to various aliphatic and aromatic linkers with different zinc-binding units, used in established active compounds. Nearly half of the twenty-four molecules tested exhibited inhibitory activity against at least one of the enzymes HDAC1, HDAC4, or HDAC8, with three compounds displaying IC₅₀ values in the nanomolar range. We have therefore demonstrated that azaborine building blocks can be successfully incorporated into HDACis, resulting in a highly active profile. Consequently, it should be feasible to develop active substances containing azaborine rings against other targets. Full article

At the international level, new measures, policies, and technologies are being developed to reduce greenhouse gas emissions and, more broadly, air pollutants. Road transportation is one of the main contributors to such emissions, as vehicles are extensively used in logistics operations, and many fleet owners of fossil-fueled trucks are adopting new technologies such as electric, hybrid, and hydrogen-based vehicles. This paper addresses the Hybrid Fleet Capacitated Vehicle Routing Problem with Time Windows (HF-CVRPTW), with the objectives of minimizing costs and mitigating environmental impacts. A mixed-integer linear programming model is developed, incorporating split deliveries, scheduled arrival times at stores, and a carbon cap-and-trade mechanism. The model is tested on a real case study provided by Decathlon, evaluating the performance of internal combustion engine (ICE), electric (EV), and hydrogen fuel cell (HV) vehicles. Results show that when considering economic and emission trading costs, the optimal fleet deployment priority is to use ICE vehicles first, followed by EVs and then HVs, but considering only total emissions, the result is the reverse. Further analysis explores the conditions under which alternative fuel, electricity, or hydrogen prices can achieve competitiveness, and a further analysis investigates the impact of different electricity generation and hydrogen production pathways on overall indirect emissions. Full article

Since the 1990s, glaciers in the Ányêmaqên Mountains of the Qinghai–Tibet Plateau have exhibited anomalous retreat and thinning. This persistent deglaciation has triggered secondary disasters including glacial debris flows, ice collapses, and glacial lake outburst floods, posing significant threats to regional ecological security and sustainable socioeconomic development. To address this issue, we conducted a comprehensive analysis of glacial morphological characteristics using multi-source time-series high-resolution remote sensing imagery spanning 2013–2024. Glacier boundaries were extracted through integrated methodologies combining manual visual interpretation, band ratio thresholding, three-dimensional geomorphic analysis, and an optimized DeepLabV3+ convolutional neural network with adaptive activation thresholds. Extraction accuracy was rigorously validated using quantitative metrics (Accuracy, Precision, Recall, Loss, and F1-score). Key findings reveal the following: dominant glacier types include ice caps, valley glaciers, and hanging glaciers distributed at mean elevations of 5200–5600 m; total glacial area decreased from 102.71 km² to 81.10 km², yielding an average annual decrease rate of −1.93%; glacier count increased from 74 to 86, corresponding to a mean relative change rate of 1.18% per annum; and thirty-eight geohazard sites were identified predominantly on upper slopes (30–50°) of north-facing terrain, with elevations ranging from 4500–5400 m (base) to 5120–6050 m (crest). These results provide critical data support for enhancing ecological resilience, strengthening disaster mitigation capabilities, and safeguarding public safety and infrastructure against climate change impacts in the region. Full article

Condition assessment of reinforced concrete structures presents a significant challenge worldwide as structures built in the post-war construction period (1950s–1970s) reach end of service life. The alkali-silica reaction (ASR) is one of several damage mechanisms which commonly affect infrastructure in Canada. Frequent freeze-thaw cycles and heavy use of de-icing salts in winter as well as high heat and humidity in summer are expected to have intensified ASR-induced damage. This work investigates five segments of a pier cap—PC, which had undergone encapsulation repair, and four segments of a pier shaft—PS, which represented dry and semi-submerged conditions, removed from a highway bridge constructed starting in 1957. Preliminary evaluation through visual inspection (conventional, qualitative and quantitative using the cracking index—CI) and non-destructive techniques (rebound hammer—RBH, ultrasonic pulse velocity—UPV and surface resistivity) was conducted on both internal (i.e., cut during decommissioning) and external (i.e., exposed while in service) surfaces of five PC segments and four PS segments. Differences in geometry, exposure conditions and repair history from the two members were found to have limited impact on the results of quantitative tests (i.e., CI, RBH and UPV results with average values of 1.6 mm/m, 37 MPa and 2.4 Km/s, respectively) while still exhibiting qualitative differences in visual determination (i.e., crack patterns, surface appearance and crack widths). Full article

This work develops an Updated Lagrangian Smoothed Particle Hydrodynamics (ULSPH) framework to simulate high-speed icebreaking by a hemispherically capped cylinder (HCC). Using a self-programmed C++ code with Drucker–Prager damage criteria, this work systematically analyzes how impact velocity (100–200 m/s), ice thickness (10–40 cm), and impact angle (60–90°) govern structural loads and ice failure modes. The head of the HCC is always the stress concentration area, and the peak value of the impact force increases non-linearly with increasing the initial velocity from 100 m/s to 200 m/s. The increase in ice layer thickness from 10 cm to 40 cm raises the peak value of the impact force by 18.1%. The ice layer deformation shows three-stage characteristics: collision depression, penetration perforation, and through-spray. When the impact angle α is non-vertical, the strain of the ice layer is asymmetrically distributed, and the component of the peak impact force along the y direction increases significantly with the decrease in the impact angle, reaching 129.3 kN at α = 60°. Results reveal velocity-driven nonlinear force amplification, asymmetric strain distribution at oblique angles, and critical stress concentration at the HCC head, providing design insights for polar equipment. Full article

The search for novel natural resources, such as extracts from algae and plant for use as reductants and capping agents for the synthesis of nanoparticles, may be appealing to medicine and nanotechnology. This study aimed to use Malva parviflora fruit extract as a novel source for the green synthesis of silver nanoparticles (AgNPs) and to evaluate their characterization. The results of biosynthesized AgNP characterization using multiple techniques, such as UV–Vis spectroscopy, scanning electron microscopy (SEM), FTIR analysis, and zeta potential (ZP), demonstrated that M. parviflora AgNPs exhibit a peak at 477 nm; possess needle-like and nanorod morphology with diameters ranging from 156.08 to 258.41 nm; contain –OH, C=O, C-C stretching from phenyl groups, and carbohydrates, pyranoid ring, and amide functional groups; and have a zeta potential of −21.2 mV. Moreover, the antibacterial activity of the M. parviflora AgNPs was assessed against two multidrug-resistant strains, including Staphylococcus aureus MRSA and Escherichia coli ESBL, with inhibition zones of 20.33 ± 0.88 mm and 13.33 ± 0.33 mm, respectively. The minimum bactericidal concentration (MBC) was 1.56 µg/mL for both. SEM revealed structural damage to the treated bacterial cells, and RAPD-PCR confirmed these genetic alterations. Additionally, M. parviflora AgNPs showed antioxidant activity (IC₅₀ = 0.68 mg/mL), 69% protein denaturation inhibition, and cytotoxic effects on MCF-7 breast cancer cells at concentrations above 100 µg/mL. These findings suggest that M. parviflora-based AgNPs are safe and effective for antimicrobial and biomedical applications, such as coatings for implanted medical devices, to prevent biofilm formation and facilitate drug delivery. Full article