Search Results (20,446)

Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide despite substantial advances in surgery, chemotherapy, targeted therapies, and immunotherapy. The limited efficacy of current treatment strategies in advanced disease and the emergence of therapeutic resistance highlight the urgent need for novel adjunctive therapeutic approaches. Increasing evidence indicates that chronic stress and sustained activation of β-adrenergic signaling promote colorectal tumor initiation, progression, angiogenesis, metastatic dissemination, and immune evasion, thereby identifying this pathway as a potential therapeutic target. Drug repurposing has emerged as an attractive strategy for accelerating the development of new anticancer therapies by identifying novel applications for clinically approved drugs with well-established safety profiles. Among these, β-blockers have gained considerable attention because of their ability to inhibit β-adrenergic signaling and modulate multiple oncogenic pathways implicated in CRC progression. Although accumulating preclinical and observational clinical evidence suggests that β-blockers may possess anticancer potential, the underlying molecular mechanisms and their translational relevance have not yet been comprehensively integrated. This review provides a critical overview of the current evidence regarding the therapeutic potential of β-blockers in CRC by integrating findings from preclinical and clinical studies. Particular emphasis is placed on the regulation of key signaling pathways, including cAMP/PKA/CREB, PI3K/AKT/mTOR, and RAS/RAF/MEK/ERK, as well as on the effects of β-blockers on tumor cell proliferation, apoptosis, angiogenesis, epithelial–mesenchymal transition, metastasis, and modulation of the tumor microenvironment and antitumor immune responses. However, significant barriers limit the translation of these findings into routine clinical practice, including the limited representativeness of preclinical models, potential hemodynamic adverse effects, and the inherent limitations of observational studies. Importantly, owing to the lack of prospective randomized clinical trials, the current evidence remains insufficient to establish the clinical efficacy of β-blockers in colorectal cancer. Although β-blockers possess several characteristics that make them attractive candidates for drug repurposing, including a well-established safety profile, widespread availability, and low cost, further mechanistic studies, prospective randomized clinical trials, and biomarker-based patient stratification are essential to determine their clinical efficacy and define their role in personalized CRC therapy. Full article

Renewable energy plays a vital role in global sustainability goals, yet investment in this sector remains exposed to numerous uncertainties that may hinder project success. While the subject has attracted greater attention from scholars and policymakers, the lack of specific structures for prioritizing investment risks in renewable energy in Saudi Arabia persists. This study investigates and prioritizes the risks associated with renewable energy investments in Saudi Arabia. A three-stage methodological approach was used: risks were first identified through a comprehensive literature review and organized into eight categories; experts from academia, the private sector, and the government assessed these risks using the Fuzzy Group Decision-Making (FGDM) method to incorporate both probability and impact; and response strategies were developed for the most significant risks. Among the 23 risk factors analyzed, 11 were categorized as high-level. The top risks include insufficient supporting policy frameworks and incentives (0.6025), complex approval systems (0.5873), and environmental impact on solar panel efficiency (0.5738). The findings emphasize the importance of streamlining regulatory frameworks and enhancing technical and infrastructural readiness. This study provides a new evidence-based framework for informed decision-making and improving the planning of investments in renewable energy in Saudi Arabia. Full article

Autonomous robotic systems designed for extraterrestrial in situ resource utilization (ISRU) will play a central role in enabling a sustained human presence on the Moon and Mars. These robots are expected to perform tasks such as regolith excavation, water extraction, oxygen production, and propellant generation under extremely harsh environmental conditions, including large temperature variations, abrasive dust, high radiation levels, and significant communication delays with Earth. Consequently, their onboard electrical systems must operate with high reliability, autonomy, and fault tolerance. A critical enabling technology for these systems is the isolated power conversion architecture, which distributes energy from primary power sources to multiple robotic subsystems, including mobility actuators, drilling systems, sensors, computing units, and thermal management modules. Future lunar and Martian missions are expected to rely on a combination of alternative energy sources, including solar photovoltaic arrays with energy storage, fuel cells, radioisotope power systems, and nuclear surface power reactors, which can provide continuous and high-density energy independent of sunlight availability. These diverse power sources require flexible and highly efficient isolated DC–DC power conversion architectures capable of managing wide input voltage ranges while ensuring electrical isolation, safety, and system stability across distributed robotic platforms. This literature review surveys recent developments in autonomous isolated power conversion architectures suitable for lunar and Martian resource extraction robots. The review examines advanced converter topologies such as resonant converters, phase-shifted full-bridge converters, dual-active bridge converters, and modular multiport power converters designed for high efficiency, high power density, and scalable power distribution. Emphasis is placed on converter architectures capable of interfacing with nuclear-powered systems and other high-energy-density sources while supporting distributed loads in robotic mining and processing systems. In addition, the paper reviews emerging autonomous control strategies, including adaptive digital control, intelligent power management, fault detection and self-recovery mechanisms, and distributed power architectures capable of maintaining stable operation under dynamic load conditions. The role of wide-bandgap semiconductor technologies, including silicon carbide (SiC) and gallium nitride (GaN), is also examined, highlighting their potential to enable higher switching frequencies, improved efficiency, reduced system mass, and enhanced thermal performance in vacuum environments. Finally, system-level considerations for integrating isolated power conversion within robotic ISRU platforms are discussed, including redundancy strategies, power bus architectures, electromagnetic compatibility, thermal management, and long-duration reliability requirements. By consolidating advances across power electronics, autonomous control, and space power systems, this review identifies key research gaps and outlines design directions for next-generation autonomous power conversion systems capable of supporting scalable lunar and Martian resource extraction infrastructures powered by both renewable and nuclear energy sources. Full article

Background/Objectives: Healthcare delivery systems are inherently complex, and efforts to improve quality and safety often fail to achieve sustained, system-wide impact because of misalignment between work system design, care processes, and clinical practice. This article presents a practical, theory-informed framework that integrates human factors and systems thinking to guide the design and implementation of clinical pathways for reliable care delivery and system-level transformation. Methods: A conceptual framework was developed through synthesis of literature from human factors engineering, sociotechnical systems theory, and healthcare quality improvement. The framework organizes healthcare delivery into three interconnected domains—the work system, care processes, and outcomes—while positioning clinical pathways as the operational mechanism linking system design to care execution. Pediatric immunization was used as an illustrative case example. Results: The framework illustrates how misalignment in system design may contribute to variability in care processes and outcomes. Clinical pathways integrated into routine workflows and supported by human factors strategies—including decision-support heuristics, workflow simulation, and structured debriefing—may promote more reliable care delivery. Sustained implementation across teams and clinical settings is expected to reduce missed opportunities, improve consistency of care, and support progression toward system-level transformation. Conclusions: Clinical pathways can serve as practical tools for translating system design principles into reliable healthcare delivery when implemented using human factors and systems-based approaches. This framework provides healthcare leaders and quality improvement teams with a structured approach for designing, implementing, and scaling pathways to support safer, more reliable, and more consistent care delivery. Full article

The mutualistic association between plants and their seed-associated microbiota has emerged as a key determinant of crop productivity, influencing plant nutrition, immunity, and tolerance to abiotic stress. Seed biopriming, the controlled application of beneficial microorganisms to seeds before sowing, exploits this interaction to enhance germination, seedling establishment, and stress resilience. Unlike conventional chemical priming, seed biopriming induces coordinated molecular reprogramming through changes in the seed metabolome, proteome, and epigenome. This review synthesizes current evidence demonstrating that seed biopriming promotes the accumulation of osmoprotectants, strengthens antioxidant defenses, enhances secondary metabolism, and generates priming-specific proteomic responses. We further examine how these changes interact with phytohormonal signaling networks and epigenetic mechanisms, including DNA methylation, histone modification, and small RNA-mediated regulation, to establish stress memory and improve plant adaptation. The review also discusses recent advances in synthetic microbial communities and nanobiotechnology for improving inoculant stability and efficacy. Despite promising progress, large-scale application remains constrained by inconsistent field performance, formulation stability, and regulatory challenges. Finally, we highlight the integration of multi-omics and artificial intelligence as promising approaches to improve mechanistic understanding, optimize microbial selection, and accelerate the development of reliable seed biopriming strategies for sustainable agriculture under climate change. Full article

This study evaluates the feasibility of developing sustainable gypsum composites incorporating silica fume waste and fiber reinforcement for construction applications. The experimental program was divided into two phases. First, silica fume was incorporated into the gypsum matrix at addition levels ranging from 10% to 35% by weight of gypsum using water-to-gypsum ratios of 0.7 and 0.8. Dry bulk density, Shore C hardness, flexural strength, and compressive strength were determined according to standards. Subsequently, the most promising formulations were reinforced with polypropylene and glass fibers at dosages of 2% and 4% by weight of gypsum. Selected specimens were also analyzed by scanning electron microscopy (SEM). The results showed that silica fume can be successfully incorporated at levels of up to 35% while complying with the requirements established by UNE-EN 13279. Silica fume addition increased bulk density by up to 9.64% and improved surface hardness. Fiber reinforcement further enhanced mechanical performance, with the best formulation reaching compressive strength values close to 14 MPa, representing an increase of 27.14% compared with the corresponding silica-fume matrix. SEM observations confirmed matrix densification and satisfactory fiber–matrix adhesion. These findings demonstrate that the combined use of silica fume waste and fiber reinforcement is a viable strategy for producing gypsum composites with improved performance while promoting industrial waste valorization. Full article

Aphids are among the most economically important pests affecting agricultural productivity worldwide. Despite various control strategies, managing aphid populations remains a challenge due to their rapid reproduction, ability to transmit pathogenic plant viruses, and their resistance to insecticides. The present article presents the current major difficulties experienced in the control of aphid pests, detailing various case studies, whilst recent scientific findings from Europe, the United States of America, and other global regions are described in order to clarify the challenges and the possibilities in sustainable pest management. Overall, we conclude that the complexity of aphid pest control demands integrated management strategies supported by robust policy frameworks. Enhanced collaboration between researchers, policymakers, farmers, and industry stakeholders is essential to develop sustainable solutions that address both immediate pest control needs and long-term agroecosystem resilience. Furthermore, studies are necessary, which especially include molecular genetics and ecological assessments, in order to understand the life history and rapid evolution of aphids, and hence, formulate the most rational means to combat them, both in the greenhouse and field. Full article

Project-Based Learning (PBL) has become an important pedagogical strategy for developing technical and professional competencies in engineering education through authentic, multidisciplinary experiences. This paper presents a PBL case study conducted in an undergraduate Computer Engineering course in which students designed and implemented Smart Fisio Borregos, an Internet of Things (IoT) and Artificial Intelligence (AI) system designed as both a learning vehicle for students and a prototype tool intended to support rehabilitation training through real-time exercise guidance and monitoring; the educational effectiveness of the rehabilitation-support function has not yet been formally validated. The project followed a prototype-driven methodology that integrated low-cost sensors, embedded systems, cloud databases, computer vision, and AI services into a unified platform. The resulting prototype incorporated equipment occupancy monitoring, environmental control, RFID-based access management, a web dashboard for data visualization, and a computer-vision module based on MediaPipe Pose Landmarker for exercise analysis and feedback. The project provided students with opportunities to apply knowledge from programming, embedded systems, databases, networking, and AI while developing collaboration, problem-solving, and project-management skills. The paper describes the pedagogical framework, system architecture, implementation process, and project outcomes, illustrating how multidisciplinary engineering projects can be used to create authentic learning experiences connected to real-world challenges. The proposed approach offers a replicable model for integrating IoT and AI technologies into engineering curricula while contributing to educational innovation related to health and well-being. The study aligns with Sustainable Development Goal 3 (Good Health and Well-Being) and Sustainable Development Goal 9 (Industry, Innovation, and Infrastructure). Full article

The rapid growth of artificial intelligence (AI) data centers introduces highly variable and mission-critical load profiles that challenge conventional power supply strategies. This paper proposes an islanded microgrid gas turbine generator (GTG) and long-duration energy storage (LDES) hybrid architecture to provide both short-term load balancing and extended energy support under prolonged outage conditions. A probabilistic multi-phase workload model is developed to capture the temporal characteristics of training, fine-tuning, and inference processes, incorporating both high-frequency fluctuations and multi-day workload variations. Based on reliability requirements, an LDES sizing methodology is formulated to ensure long-duration autonomy for mission-critical operation in a 12 MW power-block AI data center system, with the storage capacity determined based on a 12-h autonomy criterion. The GTG operating point is then evaluated using four storage performance metrics: charge/discharge transition frequency, charging time ratio, state-of-charge (SoC) deviation, and cumulative energy movement. The results indicate that the optimal GTG operating point ranges from approximately 40–73.3% of the initially selected rating, closely tracking the time-varying average load and significantly reducing LDES utilization and storage stress. While GTG fixed-output operation may induce SoC drift under sustained workload variations, applying the identified optimal operating point maintains SoC within the desired range, demonstrating stable LDES operation without dynamic adjustment. The proposed framework provides quantitative design and operational guidelines for GTG–LDES hybrid systems in next-generation AI data centers. Full article

This second part extends the system-level framework established in Part I by examining advanced adhesive and sealant technologies through a performance-, circularity-, and application-oriented perspective relevant to contemporary packaging systems. While Part I focused on material classification, bonding and sealing mechanisms, regulatory aspects, and interfacial design principles, the present review analyses how advanced adhesive and sealant systems behave under realistic converting, sealing, service, recycling, and end-of-life conditions. Particular attention is devoted to bio-based and compostable adhesives, recyclable mono-material architectures, advanced multilayer sealants, debond-on-demand systems, and smart or reversible interfaces designed to support circular packaging strategies. The review critically discusses the principal adhesive and sealant performance metrics—including bond strength, seal strength, seal initiation temperature (SIT), hot-tack behaviour, cohesive durability, processing robustness, and hydrothermal resistance—in relation to packaging reliability, barrier preservation, processability, and compatibility with industrial converting operations. The analysis additionally addresses interfacial failure mechanisms, recyclability constraints associated with multilayer structures, food-contact compliance, migration and non-intentionally added substances (NIAS), and the growing role of design-for-disassembly and circularity-oriented interfacial engineering. Emerging transition strategies involving waterborne systems, low-migration formulations, recyclable sealants, dynamic covalent networks, and controlled debonding technologies are evaluated in terms of their potential to reconcile packaging performance with sustainable material management. By integrating material-specific developments with system-level packaging considerations, this review highlights how adhesive and sealant interfaces increasingly represent critical design variables governing the balance between mechanical performance, sealing reliability, processability, recyclability, compostability, and circularity in next-generation packaging systems. Full article

Porous biochar is a functional filler for fiber-based composites. However, its fine particle size, weak affinity toward lignocellulosic fibers, and highly adsorptive pore structure lead to low retention and competitive AKD adsorption, creating a retention–sizing trade-off that limits composite performance. To overcome this challenge, a hierarchical encapsulation–asymmetric bridging flocculation (EABF) strategy integrating cationic starch (CS) and cationic polyacrylamide (CPAM) through sequential interfacial assembly was developed. In this strategy, CS was first adsorbed onto biochar surfaces to form a passivating encapsulation layer that partially shielded porous adsorption sites and regulated interfacial charge characteristics. Subsequently, CPAM served as an asymmetric bridging agent, preferentially linking CS-modified biochar with straw fibers to generate enlarged flocs with enhanced biochar–fiber association. The optimized assembly pathway increased biochar retention and total retention by 84.77% and 25.70%, respectively. Simultaneously, the dry tensile index, sizing degree, and water contact angle improved by 35.14%, 35.02%, and 64.13%, respectively, demonstrating concurrent enhancement of mechanical strength, surface hydrophobicity, and air barrier properties. Mechanistically, surface passivation and asymmetric bridging synergistically suppressed competitive AKD adsorption while strengthening filler–fiber connectivity, thereby coordinating particle-scale interfacial regulation with network-scale structural assembly. This work establishes a scalable interfacial engineering strategy for overcoming performance trade-offs associated with porous fillers and advances the development of sustainable high-performance fiber-based materials. Full article

Adverse effects associated with prolonged corticosteroid therapy are strongly associated with increased intraocular pressure (IOP), which may progress to iatrogenic glaucoma and irreversible blindness if left untreated. Developing reliable animal models is essential for investigating corticosteroid-induced ocular hypertension and evaluating potential therapeutic strategies. In this study, we established a simple and non-invasive rat model of corticosteroid-induced ocular hypertension using topical application of Rinderon-A ointment. Longitudinal IOP measurements were performed weekly using a Tono-Pen in conscious rats throughout the 11-week experimental period. Rinderon-A treatment resulted in sustained bilateral IOP elevation, with an initial increase observed at week 1 (28.4 ± 1.5 mmHg) and a maximal mean IOP of 31.2 ± 0.7 mmHg at week 10. Rinderon-A-treated eyes exhibited a sustained ocular hypertensive response throughout the experimental period. Collectively, this model provides a reproducible platform for studying corticosteroid-associated ocular hypertension and may facilitate future investigations of therapeutic interventions. Full article

Ascochyta blight (AB), caused by the necrotrophic fungus [Ascochyta rabiei (Pass.) Labr.], is one of the most destructive diseases of chickpea (Cicer arietinum L.), causing yield losses of up to 100% under favorable conditions. The pathogen possesses a heterothallic mating system with two mating-type idiomorphs, MAT1-1 and MAT1-2, which contribute to high genetic diversity and the frequent breakdown of host resistance. This review summarizes current knowledge of AB biology, epidemiology, and management, highlighting recent advances in molecular diagnostics, host–pathogen interactions, and population dynamics. Conventional and modern detection methods, including PCR-based assays, field-deployable diagnostic tools, and high-throughput phenotyping approaches, are discussed. Resistance to AB is genetically complex and predominantly polygenic, involving multiple quantitative trait loci (QTLs), although major resistance genes have also been reported. Genomic tools such as QTL mapping, genome-wide association studies (GWAS), and genomic selection have accelerated the identification of resistance loci and improved the efficiency of chickpea breeding. The potential of wild Cicer species as sources of novel resistance alleles is also emphasized. Integrating genetic resistance with effective disease monitoring and management strategies remains essential for sustainable AB control and the development of durable resistant cultivars. Full article

Conventional vaccine adjuvants often lack cell-type specificity and readily trigger excessive systemic inflammation, limiting their clinical application. Immunometabolic signaling centered on the ARF6 (ADP-ribosylation factor 6)-SUCNR1 (Succinate receptor 1) axis governs neutrophil recruitment and subsequent B-cell activation at vaccination sites, offering a promising target to balance adjuvant potency and biosafety. Separately published single-gene data confirm two opposing functions for the two mediators: ARF6 overactivation amplifies local pathological inflammation, whereas succinate-stimulated SUCNR1 drives neutrophil infiltration and humoral immune priming. However, direct paired evidence verifying their bidirectional crosstalk within immunization microenvironments remains limited. This review systematically integrates current research on ARF6 and SUCNR1 immunometabolism to outline a hypothetical dual-regulatory adjuvant strategy: local, transient partial silencing of pathological ARF6 activity via ARF6-targeted ASOs (antisense oligonucleotides) paired with localized succinate delivery to sustain protective SUCNR1 signaling. We summarize the molecular basis of this “one inhibition, one activation” paradigm, alongside ASO chemical modification, myeloid-targeted design, and nanocarrier delivery solutions that resolve the unique ARF6 endocytosis paradox. We further dissect unresolved translational risks, including concentration-dependent succinate inflammatory effects, carrier immunogenicity, and potential impairment of baseline neutrophil migration upon ARF6 suppression. Overall, this work synthesizes fragmented mechanistic data to construct a testable neutrophil-centered adjuvant framework, and highlights outstanding technical and biosafety hurdles that require dedicated preclinical validation to support future adjuvant development. Full article

In the context of global advocacy of sustainable agriculture and urban-rural coordinated development, it is important to explore the socio-economic effects of agricultural eco-efficiency. In this study, we aim to empirically examine the impact of agricultural eco-efficiency (AEE) on the urban-rural income gap (URIG) and its mechanisms in China in order to provide policy recommendations for promoting the coordinated development of environmental sustainability and social equity. Based on Chinese provincial panel data from 2011 to 2024, a two-way fixed-effects model was employed. Robustness was tested through winsorization and variable replacement, and the lag of AEE was used as a variable to address endogenous problems. Furthermore, the adjustment effect model, the panel threshold model, and group regression were used to analyse the regulatory effect of financial support, threshold effect of urbanization levels, and heterogeneity across regions, technologies, and infrastructure. The research results show the following: (1) Improvement in AEE is significantly associated with a narrowing of the URIG, and this conclusion remains true under multiple tests. (2) Financial support plays a significant positive moderating role. (3) The impact of AEE has a double threshold effect based on the urbanization level, which is only significant in the range of medium urbanization level. (4) The effect is more obvious in the main grain-producing areas, areas with a high agricultural mechanization level, and areas with a high transportation infrastructure level. (5) AEE helps narrow the URIG in the target and neighbouring areas. Improving the ecological efficiency of agriculture has both environmental and income distribution benefits. Policy formulation should focus on strengthening the precise orientation of financial support and implementing differentiated strategies according to the urbanization stage, regional functional positioning, and technical foundation, so as to maximise its effectiveness in reducing poverty, increasing income, and promoting urban and rural equity. Full article