Search Results (8,479)

Background: The rapid growth of e-commerce has intensified the need for last-mile delivery systems that can navigate urban congestion while minimizing environmental impact. Hybrid truck–drone networks offer a promising solution by combining heavy-duty ground transport with aerial flexibility; however, their deployment faces significant challenges in jointly managing operational risks, energy limits, and regulatory compliance. Methods: This study proposes a hybrid matheuristic framework to solve this multi-objective problem, simultaneously minimizing transportation cost, service time, energy consumption, and operational risk. A two-phase approach combines a metaheuristic for initial truck routing with a Mixed-Integer Linear Programming (MILP) formulation for optimal drone assignment and scheduling. This decomposition strikes a balance between exact optimization and computational scalability. Results: Experiments across various instance sizes (up to 100 customers) and fleet configurations demonstrate that integrating MILP enhances solution diversity and convergence compared to standalone strategies. Sensitivity analyses reveal significant impacts of drone speed and endurance on system efficiency. Conclusions: The proposed framework provides a practical decision-support tool for balancing complex trade-offs in time-sensitive, risk-constrained delivery environments, thereby contributing to more informed urban logistics planning. Full article

Walnut peptide Lys-Gly-His-Leu-Phe-Pro-Asn (KG-7) is a food-derived bioactive peptide with a high antioxidant capacity. We systematically evaluated the ameliorative effects of KG-7 on scopolamine-induced memory deficits in mice and its intestinal absorption mechanisms through integrating motion behavior analysis, molecular biochemistry research, and fluorescence imaging technology. Morris water maze tests revealed that KG-7 significantly improved the behavioral performance of these mice. Further mechanistic investigations demonstrated that KG-7 restored cholinergic function by reducing acetylcholinesterase activity and increasing acetylcholine levels. Hematoxylin-eosin staining and hippocampal immunohistochemistry confirmed that KG-7 alleviated neuronal damage by downregulating Hes1 overexpression, clarifying its behavioral improvement mechanism. In vitro fluorescence imaging showed that KG-7 reached peak accumulation in brain tissue 8 h post-administration, confirming its brain delivery. To elucidate the absorption mechanism, immunohistochemistry and immunofluorescence revealed that KG-7 markedly reduced the expression of efflux transporter P-gp in the small intestine, thereby diminishing efflux activity, while weakened tight junction (Occludin, ZO-1) fluorescence indicated activation of the paracellular pathway. Western blot analysis confirmed that KG-7 enhanced paracellular absorption efficiency and reduced intestinal efflux by downregulating ZO-1, Occludin, and efflux transporters (P-gp, BCRP, and LRP1) alongside upregulating Claudin-2 expression. These findings provide a foundation for exploring walnut peptides that enhance memory and optimize absorption. Full article

Marine bioactive substances exhibit structural diversity and function-specific properties, attracting considerable interest in their potential applications in targeted nutritional delivery to the gut and microbiota regulation. These bioactive components, sourced from seaweed, marine crustaceans, and microorganisms, including polysaccharides, polyphenols, and lipids, demonstrate exceptional biocompatibility and specific recognition capabilities. They serve as an optimal carrier matrix and functional core for developing an efficient, precision-targeted intestinal nutrition delivery system. Research findings demonstrate that optimization via innovative delivery technologies, including nanoencapsulation and polymer microsphere encapsulation, enables marine bioactive substances to navigate various physiological barriers in the gastrointestinal tract effectively. This facilitates targeted, sustained release of nutritional components and enhances bioavailability. Simultaneously, these substances may relieve dysbiosis by modulating the composition of the gut microbiota and the quantity and activity of specific metabolic products, thereby reinforcing intestinal barrier integrity. This narrative review systematically examines the sources and functional attributes of marine bioactive compounds, emphasizing their application strategies in developing targeted delivery systems for the gut and their regulatory effects on gut microbiota. It concludes by delineating future research directions in this field, particularly in optimizing carrier functionalities and clarifying action mechanisms. Full article

Human iPSC-derived cardiomyocytes (iPSC-CMs) exhibit fetal-like mitochondrial networks and limited oxidative metabolism, constraining their translational utility. The key bottleneck is mitochondrial immaturity, resulting from blunted PGC-1α–NRF1/2–TFAM axis activation and insufficient nuclear–mitochondrial coordination, rather than sarcomeric or electrophysiological immaturity alone. This review synthesizes genome-guided interventions (CRISPRa and mtDNA editing) and complementary environmental strategies—including metabolic substrate switching, electromechanical stimulation, and extracellular vesicle (EV)-mediated mitochondrial transfer—to drive mitochondrial biogenesis and maturation in iPSC-CMs. We systematically reviewed studies (2005–2025) targeting (1) key regulators of mitochondrial biogenesis (PGC-1α, NRF1/2, TFAM), (2) CRISPR-based transcriptional activators/repressors and mtDNA editors (DdCBE, mitoTALENs), and (3) maturation approaches such as metabolic conditioning, electromechanical stimulation, 3D tissue culture, and EV-mediated mitochondrial transfer. CRISPRa-mediated activation of PGC-1α, NRF1, and GATA4, combined with mtDNA base editors, enhances mitochondrial mass and OXPHOS function, while integration with environmental maturation strategies further promotes adult-like phenotypes. Integrative approaches that combine genome-guided interventions (CRISPRa, mtDNA editing) with environmental maturation cues yield the most adult-like iPSC-CM phenotypes reported to date. CRISPR-guided mitochondrial biogenesis thus represents a frontier for producing metabolically competent, structurally mature iPSC-CMs for disease modeling and therapy. Remaining translational challenges include efficient mitochondrial delivery, metabolic homeostasis, and multi-omics validation. We propose standardized workflows to couple nuclear and mitochondrial editing with maturation strategies. Full article

To enhance the bioavailability of hydrophobic nobiletin (NOB), this study constructed nanoparticles (LT-NOB) via self-assembly of lysozyme and tannic acid (TA). The multivalent weak interaction network between TA and lysozyme effectively encapsulated amorphous NOB, inhibiting crystallization. The optimized LT-NOB exhibited a size of 212 nm, high encapsulation efficiency (89.5%), and drug loading (47.25%). Cellular uptake was significantly improved, primarily through macropinocytosis, followed by lysosomal escape and endoplasmic reticulum targeting. In Caco-2 and co-culture models, LT-NOB enhanced mucosal permeation by 75% and 50%, respectively, compared to free NOB. This work elucidates a robust strategy for stabilizing amorphous drugs and promoting their intestinal absorption, providing a foundation for advanced nanodrug delivery. Full article

This work examines the results of research into internal combustion engine malfunction using the example of a vehicle control group of a specific transport company during the warranty and post-warranty periods. Studies have established that the most frequently encountered distribution laws for random variables during vehicle operation are normal, Weibull, log-normal, and exponential, and research has determined the patterns of units’ malfunctions and the internal combustion engine parts. The reliable operation of vehicles is achieved by maintaining a stock of spare parts, the size and range of which play an important part in the ensuing costs. It is important to forecast the need for spare parts to improve the efficiency of vehicle operation. A common drawback of forecasting methods, from the point of view of material resource management is the limited consideration of important factors such as the spare parts’ delivery time from the moment of ordering, the time frame for performing the repair work, and the spare parts’ cost. We determined that 65.7% of spare parts are delivered within one day, and 15.7% are delivered within 2 weeks. Further, it takes up to 3 h for the replacement of 82.45% of the spare parts. To determine the need for spare parts, it is important to consider the actual operational reliability and the listed factors to enable optimizing the repair fund of the motor transport enterprise and increase the efficiency of use of rolling stock. Full article

In the field of logistics distribution, the two-echelon vehicle routing problem has long been a critical focus. Against the backdrop of global warming, enterprises conducting logistics operations must now prioritize not only delivery costs but also the environmental impact of carbon emissions. To address these challenges, this study integrates occasional drivers into the two-echelon vehicle routing framework, centering on carbon emission reduction. First, Affinity Propagation (AP) clustering is applied to assign customer points to transfer centers. Subsequently, an optimization model is formulated to minimize both vehicle routing costs and carbon emission costs through a collaborative delivery system involving specialized and crowdsourced vehicles. An enhanced Sparrow–Whale Optimization Algorithm (S-WOA) is proposed to solve the model. The algorithm is tested against traditional heuristic methods on three datasets of different scales. Experimental results demonstrate that the two-echelon logistics and distribution model combining specialized vehicles and occasional drivers achieves a significant reduction in total delivery costs compared to models relying solely on specialized vehicles. Further analysis reveals that, with a fixed crowdsourced compensation coefficient, increasing the crowdsourced detour coefficient leads to a decline in total delivery costs. Conversely, when the detour coefficient remains constant, raising the compensation coefficient results in an upward trend in total costs. These insights provide actionable strategies for optimizing cost-efficiency and sustainability in logistics operations. Full article

To address three critical challenges in traditional digital twin applications for smart manufacturing—static mirroring, localized optimization, and economic decoupling—we propose and validate a novel paradigm: the Twin-Data Mid-End (TDME) system driven by dual technological-economic mechanisms. By integrating real-time big data from production lines, equipment, supply chains, and market terminals through unified semantic frameworks, microservices-based technical modules, and deep reinforcement learning decision engines, this system generates instant reward signals based on multi-dimensional economic metrics including marginal profits, delivery cycles, and inventory turnover. This enables seamless “hot-swappable” reconfiguration of process algorithms, equipment controls, scheduling strategies, and organizational structures without production interruption. The system concurrently facilitates technological iteration and economic restructuring while dynamically optimizing efficiency-profit Pareto frontiers. Objective validation across 12 months of closed-loop industrial trials demonstrates reduced line changeover time by 37%, decreased unit comprehensive costs by 14.6%, shortened market response cycles by 42%, and increased return on investment by 11%, highlighting the paradigm’s practical applicability and broad adaptability. Full article

Background: This study evaluates an additive manufacturing (AM) network designed to balance economic performance, lead time, and environmental impact within the healthcare logistics and supply chain. Methods: An integrated framework is proposed that identifies optimal AM facility locations using spatial K-means clustering and optimizes delivery routes through a multi-objective vehicle routing problem with time windows (MOVRPTW). This framework was applied to a case study in Phra Nakhon Si Ayutthaya, Thailand, utilizing hospital geocoordinates, demand profiles, and CO₂ emission factors to evaluate centralized versus decentralized network configurations. Results: Findings demonstrate that hub structures derived from K-means clustering achieve the highest economic efficiency, reducing the AM part cost per unit to 698.51 Baht. In contrast, a fully centralized network resulted in a significantly higher unit cost of 4759.79 Baht, while clustering based on hospital types yielded a unit cost of 959.34 Baht. Quantitative results indicate that the multi-objective approach provides a superior trade-off, achieving lead time requirements while maintaining operational costs and emissions. Conclusions: The results indicate that the proposed framework, particularly through spatial clustering, offers a practical decision-support tool for designing AM networks that achieve a balance between operational efficiency and sustainability objectives in healthcare logistics. Full article

Mitochondria serve as an essential component in the maintenance of cardiac function, and targeting them may represent a promising approach to handling heart failure (HF). HF in this review refers to various etiologies, including ischemic cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy, unless otherwise specified. Mitochondrial dysfunction, a distinctive feature of HF, leads to a progressive decrease in bioenergetic reserves due to switching of energy production from oxidation of fatty acids in mitochondria to glycolytic pathways. The main problem in developing methods to improve mitochondrial function lies in the fact that protein preparations injected through the bloodstream cannot enter cells through the plasma membrane. Modern gene therapy involving the delivery of missing genes to cells using adeno-associated virus (AAV) vectors has the potential to improve the function of cardiomyocytes (CMCs). This type of therapy aims to target proteins that have been lost, damaged, or altered due to pathological conditions in the myocardium. This review summarizes pathophysiological mechanisms associated with mitochondrial dysfunction, which is mainly caused by increased oxidative stress and impaired mitochondrial biodynamics under HF progression. It also addresses possible ways to modulate these processes using gene therapy. Special attention is paid to modern characteristics of AAVs that can be used as vectors for the efficient delivery of desired genes to CMCs. Full article

Polymer-based drug delivery systems offer robust opportunities to improve chemotherapy performance while mitigating systemic toxicity, a critical challenge in leukemia treatment. In this study, poly(ε-caprolactone) (PCL) microparticles were developed as carriers for the co-delivery of cytarabine (ARA-C), a frontline antileukemic agent, and a pecan-derived polyphenolic extract (PRE) as a complementary bioactive component. Microparticles were prepared by a double emulsion solvent evaporation method and formulated with varying drug and extract loadings. The systems were characterized in terms of morphology, particle size, colloidal properties, encapsulation efficiency, and chemical composition using optical microscopy, scanning electron microscopy, dynamic light scattering, zeta potential analysis, UV–Vis spectroscopy, Folin–Ciocalteu assay, and FTIR spectroscopy. In vitro release studies revealed sustained and formulation-dependent release profiles for both ARA-C and PRE, which were successfully fitted to kinetic models, indicating diffusion- and matrix-controlled release mechanisms. Additionally, preliminary cell viability assays using fibroblasts supported the cytocompatibility of the formulations. The results support the use of PCL-based microparticles as reproducible polymeric systems for the co-encapsulation and controlled release of cytarabine and polyphenol-rich extracts, contributing to the development of combination delivery approaches relevant to leukemia treatment. Full article

Special-shaped concrete-filled steel tube (CFST) columns are increasingly adopted as efficient vertical load-carrying members in integrated residential structural systems. However, their intrinsically nonuniform confinement promotes early local buckling and bulging of tube plates and limits deformation stability under axial compression. This study presents an experimental assessment of an L-shaped CFST column enhanced by a fully bolted threaded-rod transverse tie (RT) system, which is intended to strengthen confinement delivery and delay tube instability. Two 1500 mm-high specimens with identical cross-sectional dimensions (400 mm × 200 mm legs; 6 mm wall thickness) were fabricated using Q235 steel and C30 concrete: one conventional baseline (L1) and one RT-improved column (L2) with pre-drilled bolt holes at 150 mm spacing and installed threaded rods (10 mm nominal diameter) to provide a distributed transverse restraint. Monotonic axial compression tests were conducted under staged load control while recording the axial shortening, mid-height lateral deflection, and longitudinal and transverse steel strains. The RT detailing postponed the onset of visible local buckling, tightened the lateral deflection envelope, and increased the measured peak axial resistance from 4354 kN (L1) to 5354 kN (L2), corresponding to an increase of approximately 23%. The combined deformation and strain evidence indicates that the RT system improves the confinement effectiveness by stabilizing the tube dilation and promoting a more controlled instability evolution. Overall, the fully bolted RT approach offers a practical and fabrication-compatible pathway for enhancing the axial strength and deformation performance of L-shaped CFST columns. Full article

Recent advancements in nanotechnology have led to the development of multifunctional nanoplatforms that significantly enhance both cancer diagnosis and treatment. Gold-based nanoparticles, such as peptide-functionalized nanostructures and PEG-coated nanorods, offer improved tumor targeting, multimodal imaging (including photoacoustic and fluorescence), and effective photothermal therapy. Similarly, ultrafine iron oxide nanoprobes provide superior tumor imaging, while silver-based nanoparticles exhibit rapid systemic circulation, near-infrared fluorescence, and powerful photothermal properties. Titanium-based nanoplatforms enable a combination of therapies and advanced imaging methods. On the therapeutic side, polymeric nanoparticles (PNPs), silica-based platforms, PEG-based nanoparticles, and graphene oxide-based systems each offer unique advantages for targeted drug delivery and theranostics. PNPs, with tunable size, shape, and surface chemistry, enable controlled drug release and reduced side effects, while silica-based nanoplatforms improve tumor targeting and imaging. PEG-based nanoparticles enhance drug release and tumor penetration, and graphene oxide-based systems facilitate subcellular targeting and synergistic therapies. Collectively, these innovations are paving the way for more efficient, precise, and safer cancer therapies, leading to improved clinical outcomes. Full article

Carbon dots (CDs), a class of fluorescent nanomaterials, have emerged as powerful tools for biological applications, particularly in the targeting, imaging, and therapeutic modulation of mitochondria. Due to their small size, simplicity of synthesis, biocompatibility, and tunable optical properties, CDs can be engineered to selectively accumulate in mitochondria, enabling real-time imaging of mitochondrial function and dynamics in live cells. Moreover, their ability to carry therapeutic agents, such as antioxidants, drugs, and gene delivery vectors, offers potential in treating mitochondrial dysfunction, which is central to various diseases, including neurodegenerative disorders, cancer, and metabolic diseases. Recent advancements in surface functionalization have enhanced mitochondrial targeting and specificity, while ongoing research aims to optimize the safety, efficiency, and clinical translation of CDs for therapeutic applications. This review highlights the latest developments in the use of carbon dots for mitochondrial imaging, therapeutic delivery, and disease intervention, offering promising avenues for future research and clinical applications. Full article

The incorporation of artificial intelligence (AI) and digital technology in healthcare has revolutionized service delivery, improving diagnostic precision, patient outcomes, and operational efficacy. Nonetheless, despite considerable progress, numerous problems persist that impede the realization of full potential. Current reviews predominantly emphasize the advantages of AI in disease detection and health guidance, neglecting significant concerns such as social opposition, regulatory frameworks, and geographical discrepancies. This SLR, executed in accordance with PRISMA principles, examined 21 publications from 2020 to 2025 to assess the present condition of AI and digital technologies inside Saudi Arabia’s healthcare industry. Initially, 863 publications were obtained, from which 21 were chosen for comprehensive examination. Significant discoveries encompass the extensive utilization of telemedicine, data analytics, mobile health applications, Internet of Things, electronic health records, blockchain technology, online platforms, cloud computing, and encryption methods. These technologies augment diagnostic precision, boost patient outcomes, optimize administrative procedures, and foster preventative medicine, contributing to cost-effectiveness, environmental sustainability, and enduring service provision. Nonetheless, issues include data privacy concerns, elevated implementation expenses, opposition to change, interoperability challenge, and regulatory issues persist as substantial barriers. Subsequent investigations must concentrate on the development of culturally relevant AI algorithms, the enhancement of Arabic natural language processing, and the establishment of AI-driven mental health systems. By confronting these challenges and utilizing emerging technologies, Saudi Arabia has the potential to establish its status as a leading nation in medical services innovation, guaranteeing patient-centered, efficient, and accessible healthcare delivery. Recommendations must include augmenting data privacy and security, minimizing implementation expenses, surmounting resistance to change, enhancing interoperability, fortifying regulatory frameworks, addressing regional inequities, and investing in nascent technologies. Full article