Search Results (151,930)

Despite numerous research efforts and several effective vaccines and therapies developed against coronavirus disease 2019 (COVID-19), drug repurposing remains an attractive alternative approach for treatment of SARS-CoV-2 variants and other viral infections that may emerge in the future. Cellular polyamines support viral propagation and tumor growth. Here we tested the antiviral activity of two polyamine metabolism-targeting drugs, an irreversible inhibitor of polyamine biosynthesis, α-difluoromethylornithine (DFMO), and a non-steroidal anti-inflammatory drug (NSAID), Sulindac, which have been previously evaluated for colon cancer chemoprevention. The drugs were tested as single agents and in combination in the human Calu-3 lung adenocarcinoma and Caco-2 colon adenocarcinoma cell lines and the K18-hACE2 transgenic mouse model of severe COVID-19. In the infected human cell lines, the DFMO/Sulindac combination significantly suppressed SARS-CoV-2 N1 Nucleocapsid mRNA by interacting synergistically when cells were pretreated with drugs and additively when treatment was applied to the infected cells. The Sulindac alone and DFMO/Sulindac combination treatments also suppressed the expression of the viral Spike protein and the host angiotensin-converting enzyme 2 (ACE2). In K18-hACE2 mice, the antiviral activity of DFMO and Sulindac as single agents and in combination was tested as prophylaxis (drug supplementation started 7 days before infection) or as treatment (drug supplementation started 24 h post-infection) at the doses equivalent to patient chemoprevention trials (835 ppm DFMO and 167 ppm Sulindac). The drugs’ antiviral activity in vivo was evaluated by measuring the clinical (survival rates and clinical scores), viral (viral load and virus infectivity), and biochemical (plasma polyamine, Sulindac, and Sulindac metabolite levels) endpoints. Prophylaxis with DFMO and Sulindac as single agents significantly increased survival rates in the young male mice (p = 0.01 and p = 0.027, respectively), and the combination was effective in the aged male mice (p = 0.042). Young female mice benefited the most from the prophylaxis with Sulindac alone (p = 0.001) and the DFMO/Sulindac combination (p = 0.018), while aged female mice did not benefit significantly from any intervention. Treatment of SARS-CoV-2-infected animals with DFMO or/and Sulindac did not significantly improve their survival rates. Overall, our studies demonstrated that DFMO and Sulindac administration as the prophylaxis regimen provided strong protection against the lethal outcome of SARS-CoV-2 infection and that male mice benefited more from the polyamine-targeted antiviral treatment than female mice. Our findings underscore the importance of evaluation of the antiviral activity of the drugs in the context of sex and age. Full article

Alzheimer’s disease (AD) is the most common cause of dementia worldwide, and there are still no strategies to slow or prevent its clinical progression. Significant financial and research resources have been invested into studying the pathology of AD. However, its pathogenesis is not fully understood. This review provides a comprehensive analysis of current understanding of AD pathogenesis, including classical hypotheses (amyloid cascade, tau pathology, neuroinflammation, oxidative stress), emerging mechanisms (cellular senescence, endoplasmic reticulum stress, ubiquitin-proteasome system dysfunction), and alternative mechanisms (cholinergic dysfunction, glutamate excitotoxicity, disruption of the microbiota–gut–brain axis, and autophagy). Schematic illustrations summarize the relationships between the hypotheses and their role in the pathogenesis of AD. Particular attention is paid to the systematization of promising biological targets and the analysis of modern ligands of various nature, including small molecules, peptides, antibodies and their fragments, natural compounds, as well as innovative hybrid and multifunctional structures. A separate section is devoted to radiopharmaceuticals for PET imaging (Florbetaben, Flortaucipir, etc.) and promising therapeutic agents. Thus, in this review we (1) systematize modern concepts of AD pathogenesis, including classical, emerging mechanisms and alternative hypotheses; (2) conduct a comparative analysis of ligand classes (small molecules, peptides, antibodies, etc.) and their therapeutic potential; and (3) discuss the clinical prospects of radiopharmaceuticals for PET imaging and targeted therapy. The work provides a comprehensive analysis of modern approaches, which can help in the development of more effective drugs against AD. Full article

Municipal solid waste (MSW) disposal is one of the areas of sustainability development of modern countries including the Republic of Kazakhstan. Annually, more than 4 million tons of MSW are generated, and this amount continues to grow. Additionally, approximately 120 million tons of waste have already accumulated in landfills across the country. It is essential to select an MSW disposal technology that is environmentally friendly, minimizes the generation of more hazardous waste, and maximizes energy efficiency. Ideally, the technology should not only reduce energy consumption but also generate energy and valuable by-products that have market demand. The aim of this study is to conduct experimental research to evaluate the efficiency and environmental impact of incinerating both unsorted and sorted municipal solid waste. As a result of the experiment, the volumes of flue gases and the concentrations of harmful substances produced by the combustion of both unsorted and sorted waste were determined. Additionally, an analysis of the slag and ash generated from the combustion of sorted MSW was conducted. The obtained results enable the development of a waste-free technological scheme for a plant designed for the complete utilization of municipal solid waste. Full article

Rare earth elements (REEs) have significant application value in the quality control of nuclear materials and in traceability research in nuclear forensics. Methods were developed for the determination of REEs in uranium-bearing nuclear materials. The digestion parameters for uranium oxides and uranium ores, such as the digestion acid, digestion temperature, and digestion time, were optimized and reported. The optimized digestion parameters for uranium oxides were 2 mL HNO₃ at 160 °C for 3 h, and those for uranium ores were 7 mL mixed acid (HNO₃–HClO₄–HF = 5:5:3) at 180 °C for 36 h. Two digestion methods were demonstrated to be effective for the quantitative recovery of REEs. The suitable system and specifications for different resin columns were investigated to achieve a high decontamination factor of U (10⁵) by UTEVA resin. The corresponding loading system was 10 mL 4 M HNO₃, and the elution system was 6 mL 4 M HNO₃. Additionally, the analysis of ultra-trace REEs in high-uranium matrices was accomplished using two UTEVA resins. The developed methods were subjected to the Cochran test and the Grubbs test, and the relative standard deviation (RSD) for all REEs was below 6%. In uranium oxide samples with different spiked amounts, the recovery of REEs exceeded 80% in all cases, and the RSDs were all less than 10%. The method’s detection limits were below 10 ppt for all REEs (except for Ce), ensuring the accurate measurement of REEs in uranium-bearing nuclear materials. Full article

Real estate plays a pivotal role in fostering national economic growth and ensuring social stability. In China, housing constitutes the largest fixed asset for the majority of households. Given the extensive network of upstream and downstream industries associated with real estate, the government places significant emphasis on its regulation and development, employing a variety of policy instruments to maintain market stability. This study adopts a quantitative approach to conduct a text analysis of China’s real estate policies through the lens of knowledge mapping and LDA topic modeling, while also comparing policy content across 21 different cities. The findings indicate that real estate policy in China transcends mere market regulation. It also encompasses governance within the construction industry as well as provisions for housing security. Furthermore, due to the diverse roles that real estate plays in economic development and urban construction, there is notable regional heterogeneity in policy priorities. By text analysis of real estate policies, this study provides a systematic overview of policy content, thereby laying a foundation for more nuanced and regionally differentiated research within the realm of real estate policy. Full article

Background/Objectives: The execution of clinical trials is increasingly constrained by operational complexity, regulatory requirements, and variability in site performance. These challenges have direct implications for the reliability of trial outcomes. However, standardized methods to evaluate site-level performance remain underdeveloped. This study introduces the Clinical Trial Site Performance Measure (CT-SPM), a novel framework designed to systematically capture site-level operational quality and to provide a scalable short form for routine monitoring. Methods: We conducted a multicenter study across six Italian academic hospitals (January–June 2025). Candidate performance indicators were identified through a systematic review and expert consultation, followed by validation and reduction using advanced statistical approaches, including factor modeling, ROC curve analysis, and nonparametric scaling methods. The CT-SPM was assessed for structural validity, discriminative capacity, and feasibility for use in real-world settings. Results: From 126 potential indicators, 18 were retained and organized into four domains: Participant Retention and Consent, Data Completeness and Timeliness, Adverse Event Reporting, and Protocol Compliance. A bifactor model revealed two higher-order dimensions (participant-facing and data-facing performance), highlighting the multidimensional nature of site operations. A short form comprising four items demonstrated good scalability and sufficient accuracy to identify underperforming sites. Conclusions: The CT-SPM represents an innovative, evidence-based instrument for monitoring trial execution at the site level. By linking methodological rigor with real-world applicability, it offers a practical solution for benchmarking, resource allocation, and regulatory compliance. This approach contributes to advancing clinical research by providing a standardized, data-driven method to evaluate and improve performance across networks. Full article

Soil strengthening with hydraulic binders has gained popularity in recent years and provides an alternative to traditional methods, both for foundation reinforcement and for retaining walls. In many cases, columns, walls, or soil-cement mix blocks require reinforcement with steel sections. Correctly assessing the load-bearing capacity of a reinforced element requires an understanding of the bonding forces between the steel and the soil-cement mix. This article presents the results of pull-out tests conducted on steel flat bars embedded in a soil-cement mix. A soil-cement mix containing sand, silt, and clay fractions was prepared. The surfaces of the flat bars were treated in three different ways, and their roughness was subsequently measured. The pull-out strength of steel flat bars embedded in a soil-cement mix with compressive strength in the range of 1–2 MPa was determined. The tests revealed a correlation between surface roughness and bond strength. The conducted tests provided the basis for developing new research directions and for formulating a new bonding model for the interaction between steel profiles and soil-cement. Full article

Among the many nanomaterials studied for biomedical uses, silica and gold nanoparticles have gained significant attention because of their unique physical and chemical properties and their compatibility with living tissues. Mesoporous silica nanoparticles (MSNs) have great stability and a large surface area, while gold nanoparticles (AuNPs) display remarkable optical features. Both types of nanoparticles have been widely researched for their individual roles in drug delivery, imaging, biosensing, and therapy. When combined with gadolinium (Gd), a common contrast agent, these nanostructures provide improved imaging due to gadolinium’s strong paramagnetic properties. This study focuses on incorporating gold nanoparticles and gadolinium into a silica matrix to develop a theranostic system. Various analytical techniques were used to characterize the nanocomposites, including infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-Vis), thermogravimetric analysis (TGA), nitrogen adsorption, scanning electron microscopy (SEM), dynamic light scattering (DLS), X-ray fluorescence (XRF), X-ray diffraction (XRD), vibrating sample magnetometry (VSM), and neutron activation analysis (NAA). Techniques like XRF mapping, XANES, nitrogen adsorption, SEM, and VSM were crucial in confirming the presence of gadolinium and gold within the silica network. VSM and EPR analyses confirmed the attenuation of the saturation magnetization for all nanocomposites. This validates their potential for biomedical applications in diagnostics. Moreover, activating gold nanoparticles in a nuclear reactor generated a promising radioisotope for cancer treatment. These results indicate the potential of using a theranostic nanoplatform that employs mesoporous silica as a carrier, gold nanoparticles for radioisotopes, and gadolinium for imaging purposes. Full article

This study examines occupational accident rates in the construction sector through a case study conducted in the Balearic Islands (Spain) between 2009 and 2018. The analysis is structured around three key dimensions: macroeconomic trends, changes in occupational accident reporting systems, and legislative reforms enacted during the study period. The research evaluates the influence of business, economic, and regulatory factors on two distinct construction typologies: private residential buildings (single-family and multi-family dwellings) and public-use residential buildings (hotels, aparthotels, and tourist apartments). The objective is to determine how business characteristics and construction environments influence occupational accident prevalence, establishing a causal framework informed by economic indicators and regulatory shifts. Using local data, the study analyzes variations in accident rates by construction type, accident form, and company size. The results indicate that accident rates are structurally shaped by economic and regulatory factors, with notable differences across construction typologies and company sizes. These findings highlight the need for evidence-based, targeted prevention strategies. This study enhances understanding of how structural conditions influence occupational risk in construction and offers a foundation for developing more effective safety policies. Full article

Electrochemical impedance spectroscopy (EIS) is widely used at the laboratory level for monitoring/diagnostics of battery cells, but the design and validation of in situ, online measurement systems based on EIS face challenges due to complex hardware–software interactions and non-idealities. This study aims to develop an integrated co-simulation framework to support the design, debugging, and validation of EIS measurement systems devoted to the online monitoring of battery cells, helping to predict experimental results and identify/correct the non-ideality effects and sources of uncertainty. The proposed framework models both the hardware and software components of an EIS-based system to simulate and analyze the impedance measurement process as a whole. It takes into consideration the effects of physical non-idealities on the hardware–software interactions and how those affect the final impedance estimate, offering a tool to refine designs and interpret test results. For validation purposes, the proposed general framework is applied to a specific EIS-based laboratory prototype, previously designed by the research group. The framework is first used to debug the prototype by uncovering hidden non-idealities, thus refining the measurement system, and then employed as a digital model of the latter for fast development of software algorithms. Finally, the results of the co-simulation framework are compared against a theoretical model, the real prototype, and a benchtop instrument to assess the global accuracy of the framework. Full article

Vision Transformers (ViTs), inspired by their success in natural language processing, have recently gained attention for heart sound classification (HSC). However, most of the existing studies on HSC rely on single-stream architectures, overlooking the advantages of multi-resolution features. While multi-stream architectures employing early or late fusion strategies have been proposed, they often fall short of effectively capturing cross-modal feature interactions. Additionally, conventional fusion methods, such as concatenation, averaging, or max pooling, frequently result in information loss. To address these limitations, this paper presents a novel attention fusion-based two-stream Vision Transformer (AFTViT) architecture for HSC that leverages two-dimensional mel-cepstral domain features. The proposed method employs a ViT-based encoder to capture long-range dependencies and diverse contextual information at multiple scales. A novel attention block is then used to integrate cross-context features at the feature level, enhancing the overall feature representation. Experiments conducted on the PhysioNet2016 and PhysioNet2022 datasets demonstrate that the AFTViT outperforms state-of-the-art CNN-based methods in terms of accuracy. These results highlight the potential of the AFTViT framework for early diagnosis of cardiovascular diseases, offering a valuable tool for cardiologists and researchers in developing advanced HSC techniques. Full article

This review focuses on five native Australian brown algae species—Cystophora torulosa, Durvillaea potatorum, Ecklonia radiata, Hormosira banksii, and Phyllospora comosa—evaluating their environmental adaptability, biochemical composition, bioactive compounds, and potential for commercial development. Species-specific differences in temperature and light tolerance influence their habitat distribution. Nutritional assessments reveal that these algae are rich in proteins, polysaccharides, polyunsaturated fatty acids, and essential trace elements. Bioactive compounds, including polyphenols and fucoidans, exhibit antioxidant, anti-inflammatory, and anti-diabetic properties. D. potatorum extracts have considerable economic value in agriculture by enhancing crop yield, improving nutritional value, and promoting root development. C. torulosa is predominantly found in cooler marine environments and is comparatively more thermally sensitive. In contrast, H. banksii has a higher heat tolerance of up to 40 °C and thrives in warmer environments. E. radiata is widely distributed, highly tolerant of environmental stresses, and exhibits notable disease-resistant activities. P. comosa, due to its high polysaccharide content, demonstrates strong potential for industrial applications. Consumer studies indicate growing acceptance of seaweed-based products in Australia, although knowledge gaps remain. This study highlights the need for continued research, optimized processing methods, and targeted education to support the sustainable development and utilization of Australia’s native brown algae resources. Full article

The presented research aims to find a data-driven formula for the compressive stress–strain behaviour of closed-cell aluminium foams with respect to the apparent density of the material. This is a continuation and new development of an earlier study by the authors. In the previous step, 500 artificial neural network models were built and trained on experimental results from compression tests and then evaluated based on, among other factors, mean absolute relative errors for training and verification stages. In this step, the evaluation of networks is amended, and criteria are introduced that are connected with the mechanical characteristics of the material, i.e., the plateau stress and quasi-elastic gradient. A weighted condition of all measures is proposed. Based on the amended conditions, a neural network model with a weighted mean absolute relative error of ≅5% is chosen and presented, together with the mathematical equation for its stress–strain–density relationship σ = f(ε, ρ) over a range of material apparent densities ρ ∈ <0.2; 0.3> g/cm³. Experimental relationships for compressive strength and plateau stress are also presented. Full article

Background/Objectives: This study developed a targeted drug delivery nanoplatform for treating HER2-positive breast cancer. The nanoplatform encapsulated two hydrophobic anticancer agents, neratinib (NTB) and docetaxel (DTX), within nanoparticles (DTX+NTB−NP) functionalized for conjugation to trastuzumab to form trastuzumab-tagged nanoparticles (TRZ−NP). Trastuzumab is a HER2-specific monoclo-nal antibody that binds to HER2 receptors, blocking signal transduction and inducing an-tibody-dependent cellular cytotoxicity (ADCC). Upon receptor-mediated endocytosis, neratinib inhibits cytosolic HER2 signaling, while docetaxel disrupts mitotic cell division, collectively leading to tumor cell death. Methods: Nanoparticles were fabricated by the nanoprecipitation technique, followed by surface modification with a crosslinker and a targeting moiety. DTX+NTB−NP, TRZ−NP, and singly loaded nanoparticles (NTB−NP and DTX−NP) were characterized and their effects evaluated in HER2-positive cancer cell line and xenograft model. Results: In vitro antiproliferation assay in SKBR-3 cell line re-veals a dose and time-dependent cytotoxicity. There was no significant difference in cyto-toxicity observed between DTX+NTB−NP and its free form (DTX+NTB) [p = 0.9172], and between TRZ−NP and its free form (TRZ+DTX+NTB) [p = 0.6750]. However, TRZ−NP, at half the concentration of the singly loaded nanoparticles, significantly reduced the viabil-ity of SKBR-3 cells compared to pure trastuzumab (TRZ) [p < 0.001], NTB−NP [p = 0.0019], and DTX−NP [p = 0.0002]. In vivo evaluation in female athymic nude mice showed sig-nificant log relative tumor volume (%) reduction in groups treated with TRZ−NP and DTX+NTB−NP compared to PBS (phosphate-buffered saline) controls (p ≤ 0.001 and p ≤ 0.001), respectively. Notably, TRZ−NP demonstrated a statistically significant regression in the log relative tumor volume (%) compared to DTX+NTB−NP (p = 0.001). Conclusions: These findings underscore the therapeutic potential and suitability of these nanoplatforms for the precise and controlled targeting of HER2-positive tumors. This study is the first to synchronize the delivery of multiple agents-docetaxel, neratinib, and trastuzumab-within a nanoparticle system for treating HER2-positive tumors, offering a promising strategy to enhance treatment outcomes for HER2 positive breast cancer patients. Full article

Thermochemical energy storage (TCES) has gained significant attention as a high-capacity, long-duration solution for renewable energy integration, yet material-level challenges hinder its widespread adoption. This review for the first time systematically examines recent advancements in nano-engineered composite thermochemical materials (TCMs), focusing on their ability to overcome intrinsic limitations of conventional systems. Sorption-based TCMs, especially salt hydrates, benefit from nano-engineering through carbon-based additives like CNTs and graphene, which enhance thermal conductivity and reaction kinetics while achieving volumetric energy densities exceeding 200 kWh/m³. For reversible reaction-based systems operating at higher temperatures (250–1000 °C), the strategies include (1) nanoparticle doping (e.g., SiO₂, Al₂O₃, carbonaceous materials) for the mitigation of sintering and agglomeration; (2) flow-improving agents to enhance fluidization; and (3) nanosized structure engineering for an enlarged specific surface area. All these approaches show promising results to address the critical issues of sintering and agglomeration, slow kinetics, and poor cyclic stability for reversible reaction-based TCMs. While laboratory results are promising, challenges still persist in side reactions, scalability, cost reduction, and system integration. In general, while nano-engineered thermochemical materials (TCMs) demonstrate transformative potential for performance enhancement, significant research and development efforts remain imperative to bridge the gap between laboratory-scale achievements and industrial implementation. Full article