Search Results (4,235)

Pine wilt disease (PWD), caused by Bursaphelenchus xylophilus, is driven by a tri-component system involving the pinewood nematode, Monochamus spp. beetle vectors, and susceptible pine hosts. Chemical control remains a scenario-dependent option for emergency suppression and high-value protection, but its deployment is constrained by strong regional regulatory and practical differences. In Europe (e.g., Portugal and Spain), field chemical control is generally not practiced; post-harvest phytosanitary treatments for wood and wood packaging rely mainly on heat treatment, and among ISPMs only sulfuryl fluoride is listed for wood treatment with limited use. This review focuses on recent progress in PWD chemical control, summarizing advances in nematicide discovery and modes of action, greener formulations and delivery technologies, and evidence-based, scenario-oriented applications (standing-tree protection, vector suppression, and infested-wood/inoculum management). Recent studies highlight accelerated development of target-oriented nematicides acting on key pathways such as neural transmission and mitochondrial energy metabolism, with structure–activity relationship (SAR) efforts enabling lead optimization. Formulation innovations (water-based and low-solvent products, microemulsions and suspensions) improve stability and operational safety, while controlled-release delivery systems (e.g., micro/nanocapsules) enhance penetration and persistence. Application technologies such as trunk injection, aerial/UAV operations, and fumigation/treatment approaches further strengthen scenario compatibility and operational efficiency. Future research should prioritize robust target–mechanism evidence, resistance risk management and rotation strategies, greener formulations with smart delivery, and scenario-based exposure and compliance evaluation to support precise, green, and sustainable integrated control together with biological and other sustainable approaches. Full article

Cancer stem cells (CSCs) represent a small but highly resilient tumor subpopulation responsible for sustained growth, metastasis, therapeutic resistance, and recurrence. Their survival is supported by aberrant activation of developmental and inflammatory pathways, including Wnt/β-catenin, Notch, Hedgehog, PI3K/Akt/mTOR, STAT3, and NF-κB, as well as epithelial–mesenchymal transition (EMT) programs and niche-driven cues. Increasing evidence shows that phytochemicals, naturally occurring bioactive compounds from medicinal plants, can disrupt these networks through multi-targeted mechanisms. This review synthesizes current findings on prominent phytochemicals such as curcumin, sulforaphane, resveratrol, EGCG, genistein, quercetin, parthenolide, berberine, and withaferin A. Collectively, these compounds suppress CSC self-renewal, reduce sphere-forming capacity, diminish ALDH⁺ and CD44⁺/CD24⁻ fractions, reverse EMT features, and interfere with key transcriptional regulators that maintain stemness. Many phytochemicals also sensitize CSCs to chemotherapeutic agents by downregulating drug-efflux transporters (e.g., ABCB1, ABCG2) and lowering survival thresholds, resulting in enhanced apoptosis and reduced tumor-initiating potential. This review further highlights the translational challenges associated with poor solubility, rapid metabolism, and limited bioavailability of free phytochemicals. Emerging nanotechnology-based delivery systems, including polymeric nanoparticles, lipid carriers, hybrid nanocapsules, and ligand-targeted formulations, show promise in improving stability, tumor accumulation, and CSC-specific targeting. These nanoformulations consistently enhance intracellular uptake and amplify anti-CSC effects in preclinical models. Overall, the consolidated evidence supports phytochemicals as potent modulators of CSC biology and underscores the need for optimized delivery strategies and evidence-based combination regimens to achieve meaningful clinical benefit. Full article

Monogenean parasite infestation in fish leads to economic losses in aquaculture, representing a veterinary challenge and an environmental concern. The common administration procedures of anthelmintics to treat monogeneans in fish have low efficiency and diverse drawbacks. In this study, we produced a nanoparticle using chitosan and alginate, biodegradable and biocompatible polysaccharides, as an oral drug delivery material of albendazole anthelmintic for parasite-infected fingerlings of Nile tilapia. The molecular interaction between the biopolymers was optimized and characterized by titration calorimetry. Freeze-drying of nanoparticles resulted in a fine powder with a particle size in the order of 400 nm. The nanoparticles provided 98% encapsulation of albendazole and sustained delivery with predominantly Fickian diffusion. The palatability of the nanoparticle formulation facilitated the oral administration of albendazole. The treatment of 100% prevalence of monogeneans was effective with a six-day dosage providing a total of 915 mg/kg b.w. of drug, resulting in total parasite clearance after 10 days from the treatment beginning, evidenced by microscopy analysis, and no mortality occurred. Therefore, molecular interactions between biofriendly polyelectrolytes yielded albendazole-carrying nanoparticles for high-efficiency parasite treatment in fish farming. Full article

Dextrin-based nanosponges (D-NS) are promising candidates for oral drug delivery due to their biocompatibility, mucoadhesive properties, and tunable swelling behavior. In this study, pH-sensitive nanosponges were synthesized using β-cyclodextrin (β-CD), GluciDex^®2 (GLU2), and KLEPTOSE^® Linecaps (LC) as building blocks, crosslinked with pyromellitic dianhydride (PMDA) and citric acid (CA). The nanosponges were mechanically size-reduced via homogenization and ball milling, and characterized by FTIR, TGA, dynamic light scattering (DLS), and zeta potential measurements. Swelling kinetics, cross-linking density (determined using Flory–Rehner theory), rheological behavior, and mucoadhesion were evaluated under simulated gastric and intestinal conditions. The β-CD:PMDA 1:4 NS was selected for drug studies due to its optimal balance of structural stability, swelling capacity (~863% at pH 6.8), and highest apomorphine (APO) loading (8.23%) with 90.58% encapsulation efficiency. All nanosuspensions showed favorable polydispersity index values (0.11–0.30), homogeneous size distribution, and stable zeta potentials, confirming suspension stability. Storage at 4 °C for six months revealed no changes in physicochemical properties or apomorphine (APO) degradation, indicating protection by the nanosponge matrix. D-NS exhibited tunable swelling, pH-responsive behavior, and mucoadhesive properties, with nanoparticle–mucin interactions quantified by the rheological synergism parameter (∆G′ = 53.45, ∆G″ = −36.26 at pH 6.8). In vitro release studies demonstrated slow, sustained release of APO from D-NS in simulated intestinal fluid compared to free drug diffusion, highlighting the potential of D-NS as pH-responsive, mucoadhesive carriers with controlled drug release and defined nanoparticle–mucin interactions. Full article

Achieving sustainable delivery is a critical goal in international engineering projects, which involve interdependent actors—such as contractors, suppliers, and designers—engaged in simultaneous cooperation and competition. This study investigates how coopetition, conceptualized as intensity and balance, affects sustainable delivery performance through dynamic capabilities. Specifically, we introduce exploitation and exploration as mediating capabilities and examine their effects under coopetition structures (horizontal vs. vertical). We use hierarchical regression analyses, relationship critical tests, and the fuzzy set qualitative comparative analysis (fsQCA) approach. Using survey data from 172 global projects, the results show that exploitation and exploration partially mediate the relationship between coopetition intensity and sustainable delivery performance, and fully mediate the effect of coopetition balance. The analysis uncovers a structural differentiation in capability efficacy, showing that exploitation yields stronger effects within horizontal structures, whereas exploration exerts greater influence under vertical structures. fsQCA reveals three complex configurational pathways to sustainable delivery performance, demonstrating the compensatory configurational pathways in which structural characteristics can, under certain conditions, substitute for dynamic capabilities. This study extends the application of coopetition and dynamic capability theories to the context of international engineering projects and underscores the crucial role of governance structures in shaping capability development and sustainable delivery outcomes. Full article

With rapid urbanization and population growth, efficient transportation systems are increasingly crucial, particularly in sectors like healthcare and pharmaceutical logistics, which face unique challenges. In Morocco, there is a lack of studies on pharmaceutical transport, especially regarding costs and delivery conditions, creating a need for a specialized model. This research presents the development and validation of a predictive model for optimizing urban transport in Morocco. Tested across key sectors—pharmaceuticals, agri-food, electronics, and manufactured goods—the model demonstrated strong performance, though variations emerged based on product complexity. Notably, the agri-food sector presented greater logistical challenges, while the manufacturing and electronics sectors yielded higher prediction accuracy. By integrating statistical process control (SPC) and Lean Six Sigma principles, the model ensures ongoing performance monitoring and continuous improvement. It supports cost reduction, time optimization, and lower environmental impact through enhanced route planning and delivery efficiency. The pharmaceutical sector was selected as a case study due to its critical logistical constraints, such as cold chain requirements and the need for high reliability. Python was used for model development, enabling rapid iteration and collaborative validation. The results confirm the model’s adaptability and generalizability to similar urban environments across North and Sub-Saharan Africa. The study offers a robust and scalable framework for improving transport efficiency while aligning with sustainability and smart mobility goals. Full article

Alopecia profoundly impacts psychological well-being and quality of life, yet current therapeutic options such as minoxidil and finasteride exhibit limited efficacy. Fibroblast growth factor 7 (FGF-7), also known as keratinocyte growth factor (KGF), is a paracrine growth factor secreted by dermal papilla cells that specifically activates the epithelial receptor FGFR2b. Receptor engagement triggers multiple downstream signaling cascades, including the MAPK/ERK, PI3K/Akt, and Wnt/β-catenin pathways, promoting keratinocyte proliferation, stem cell activation, and the transition of hair follicles into the anagen phase. Both in vitro and in vivo animal studies consistently demonstrate that FGF-7 accelerates telogen-to-anagen transition and enhances follicular regeneration. FGF-7 acts synergistically with insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF) to sustain nutrient delivery and cell proliferation. Human scalp studies further reveal a strong association between the FGF-7/FGFR2b signaling and follicular activity; however, clinical trials remain scarce. Topical application of FGF-7 has demonstrated an excellent safety profile, whereas systemic administration necessitates careful monitoring. Future directions include the development of engineering to extend the systemic half-life, advanced delivery systems, and gene or mRNA-based therapeutic approaches. Thus, the FGF-7/FGFR2b axis is a highly compelling molecular target for next-generation hair regeneration therapies. Full article

Simultaneous optimization of vehicle routing and cargo loading is essential for reducing operational costs and improving the environmental performance of logistics systems. To overcome the limitations of traditional sequential approaches to the one-to-many pickup and delivery vehicle routing problem with three-dimensional loading constraints (3L-PDVRP), this paper proposes a deeply coupled hybrid genetic algorithm (HGA). The algorithm adopts a grouping-based genetic encoding strategy to accommodate variable fleet sizes and incorporates a tree-search-based loading module. A dynamic three-dimensional loading feasibility verification mechanism is embedded directly into the evolutionary search so that routing decisions are continuously guided by fragility, stacking stability, support constraints, and other loading constraints. In addition, an adaptive hybrid insertion strategy is employed to balance global exploration and local exploitation during route construction and repair. Extensive computational experiments on extended benchmark instances derived from standard datasets show that the proposed method consistently outperforms a large neighborhood search (LNS)-based baseline from the literature, reducing the average total travel distance by 10.60% and increasing the average vehicle loading rate by 2.76%. These results indicate that the proposed HGA provides an effective approach to the synergistic optimization of routing and loading in one-to-many distribution settings, offering practical value for lowering transportation costs and supporting more sustainable logistics operations. This methodology provides decision support for logistics enterprises, reducing travel distances while ensuring three-dimensional loading feasibility, thereby enabling greener and safer transportation operations. Full article

Background: Self-amplifying mRNA (sa-mRNA) represents a promising platform for vaccines and gene therapies, offering sustained protein expression at low doses through self-replication. For vaccines targeting respiratory pathogens, pulmonary delivery of sa-mRNA lipid nanoparticles (LNPs) is particularly advantageous, enabling direct delivery to the infection site and induction of mucosal immunity. Objective: In this study, we evaluated the stability of sa-mRNA–LNPs under refrigerated and frozen conditions and developed a dry powder formulation suitable for inhalation, produced by freeze-drying followed by cryomilling with leucine. Methods: sa-mRNA–LNPs formulated in HEPES buffer with 20% (w/v) sucrose were stored for up to 8 weeks as liquid or freeze-dried samples at various temperatures (−80 °C, −20 °C, 4 °C, and 20 °C). Biological stability was assessed by transfection efficiency in HeLa cells, while physical stability was characterized by encapsulation efficiency, zeta potential, particle size, and polydispersity index. Results: Liquid formulations remained stable for at least 8 weeks at −80 °C and −20 °C but rapidly lost stability at 4 °C and 20 °C. Freeze-drying effectively preserved sa-mRNA–LNP functionality and structural integrity for up to 8 weeks at 4 °C, with only minor structural changes. Subsequent cryomilling in the presence of 4 wt-% leucine produced a respirable dry powder while retaining approximately 60% of the original sa-mRNA–LNP functionality. Although cryomilling induced some structural alterations, the remaining functional fraction remained stable during storage. The resulting powders displayed favorable aerosol performance for deep lung delivery, as demonstrated by cascade impaction (MMAD = 4.13 ± 0.26 µm). Conclusions: In conclusion, freeze-drying effectively preserved sa-mRNA–LNP integrity at 4 °C, whereas cryomilling with leucine produced a respirable dry powder suitable for pulmonary delivery, providing a foundation for globally accessible, needle-free sa-mRNA vaccines against respiratory diseases. Full article

Essential oils (EOs) are volatile, strongly aromatic bioactive substances extracted from plants, primarily composed of terpenes, terpenoids, phenylpropanoids, and other oxygenated compounds. Owing to their unique chemical structures, EOs exhibit a wide range of biological activities, including antimicrobial, anti-inflammatory, antioxidant, anticancer, neuroprotective, bone-protective, wound-healing, and gut microbiota-modulating effects, highlighting their potential therapeutic value. However, the composition and bioactivity of EOs are influenced by multiple factors and often compromised by improper storage conditions such as temperature and light exposure, leading to the gradual loss of their functional properties. To overcome these limitations, encapsulation technologies have been employed to enhance EO stability, enable sustained and targeted release, and preserve or even improve their bioactive functions. This review summarizes the major constituents of EOs, their physiological activities, therapeutic value, and mechanisms of action. It also discusses their limitations and suitable encapsulation technologies, materials, and carrier systems for stabilization and delivery. Full article

The conventional method of flue gas desulfurization gypsum (FGDG) application, i.e., blending with flood irrigation, is hindered by low water efficiency and significant amendment loss due to runoff and uncontrolled leaching, particularly in arid and semi-arid regions in which water scarcity is a major constraint. This study aimed to evaluate a novel integration of FGDG band application with drip irrigation to enhance targeting and resource efficiency. A laboratory-scale experiment investigated the effects of two FGDG application methods (band and blend application) and drip rates (0.3 and 0.6 L h⁻¹) on soil water movement and chemical properties. Band application significantly accelerated initial wetting front advancement by up to 44.9 cm h⁻¹ near the emitter and sustained horizontal propagation, while blend application promoted a more uniform water distribution. Chemically, band application created localized zones of reduced pH (7.57–8.62) and elevated water-soluble Ca²⁺ (up to 492.2 mmol kg⁻¹), facilitating a 79.1% reduction in exchangeable Na⁺ near the emitter. In contrast, blend application resulted in broader but shallower amendment distribution, reducing exchangeable sodium percentage uniformly to 1.99–4.16% across the soil profile. The combination of banded FGDG and drip irrigation achieves targeted amelioration, with superior Na⁺/Ca²⁺ exchange and favorable moisture dynamics resulting from the synergy between amendment placement and water delivery. This approach is a viable strategy for precision reclamation in arid regions. Full article

Introduction: Magnetic nanoparticles are widely investigated as multifunctional platforms for drug delivery and theranostic applications, yet their biomedical implementation is hindered by aggregation, limited colloidal stability, and insufficient biocompatibility. Hybrid biopolymer coatings can mitigate these issues while supporting drug incorporation. Aim: This study aimed to develop casein–pullulan-coated Fe₃O₄ nanocomposites loaded with xanthohumol, enhancing stability and enabling controlled release for potential theranostic use. Methods: Fe₃O₄ nanoparticles were synthesized through co-precipitation and incorporated into a casein–pullulan matrix formed via polymer complexation and glutaraldehyde crosslinking. A 3² full factorial design evaluated the influence of casein:pullulan ratio and crosslinker concentration on physicochemical performance. Nanocomposites were characterized for size, zeta potential, morphology, composition, and stability, while drug loading, encapsulation efficiency, and release profiles were determined spectrophotometrically. Molecular docking was performed to examine casein–pullulan interactions. Results: Uncoated Fe₃O₄ nanoparticles aggregated extensively, displaying mean sizes of ~292 nm, zeta potential of +80.95 mV and high polydispersity (PDI above 0.2). Incorporation into the biopolymer matrix improved colloidal stability, yielding particles of ~185 nm with zeta potentials near –35 mV. TEM and SEM confirmed spherical morphology and uniform magnetic core incorporation. The optimal formulation, consisting of a 1:1 casein:pullulan ratio with 1% glutaraldehyde, achieved 5.7% drug loading, 68% encapsulation efficiency, and sustained release of xanthohumol up to 84% over 120 h, fitting Fickian diffusion (Korsmeyer–Peppas R² = 0.9877, n = 0.43). Conclusions: Casein–pullulan hybrid coatings significantly enhance Fe₃O₄ nanoparticle stability and enable controlled release of xanthohumol, presenting a promising platform for future targeted drug delivery and theranostic applications. Full article

Artificial intelligence (AI) is now embedded across many aspects of healthcare, yet most implementations remain fragmented, task-specific, and layered onto legacy workflows. This paper does not review AI applications in healthcare per se; instead, it examines what an AI-first healthcare system would look like, one in which AI functions as a foundational organizing principle of care delivery rather than an adjunct technology. We synthesize evidence across ambulatory, inpatient, diagnostic, post-acute, and population health settings to assess where AI capabilities are sufficiently mature to support system-level integration and where critical gaps remain. Across domains, the literature demonstrates strong performance for narrowly defined tasks such as imaging interpretation, documentation support, predictive surveillance, and remote monitoring. However, evidence for longitudinal orchestration, cross-setting integration, and sustained impact on outcomes, costs, and equity remains limited. Key barriers include data fragmentation, workflow misalignment, algorithmic bias, insufficient governance, and lack of prospective, multi-site evaluations. We argue that advancing toward AI-first healthcare requires shifting evaluation from accuracy-centric metrics to system-level outcomes, emphasizing human-enabled AI, interoperability, continuous learning, and equity-aware design. Using hypertension management and patient journey exemplars, we illustrate how AI-first systems can enable proactive risk stratification, coordinated intervention, and continuous support across the care continuum. We further outline architectural and governance requirements, including cloud-enabled infrastructure, interoperability, operational machine learning practices, and accountability frameworks—necessary to operationalize AI-first care safely and at scale, subject to prospective validation, regulatory oversight, and post-deployment surveillance. This review contributes a system-level framework for understanding AI-first healthcare, identifies priority research and implementation gaps, and offers practical considerations for clinicians, health systems, researchers, and policymakers. By reframing AI as infrastructure rather than isolated tools, the AI-first approach provides a pathway toward more proactive, coordinated, and equitable healthcare delivery while preserving the central role of human judgment and trust. Full article

Recycling industrial CO₂ into agricultural systems offers a dual-purpose strategy for achieving carbon neutrality and enhancing sustainable crop production. Although elevated CO₂ is known to influence plant growth, the directed delivery of industrially sourced CO₂ via drip irrigation to modulate rhizosphere processes in arid soils remains underexplored. We conducted a two-year field experiment in a Xinjiang cotton field to evaluate the effects of five concentrations of industrial CO₂ solution (0.00–0.16 kg·m⁻³) on soil properties, nutrient dynamics, and crop performance. The optimal CO₂ treatment (0.08 kg·m⁻³) significantly reduced soil pH by up to 0.3 units and electrical conductivity by up to 27.9%, while enhancing the availability of ammonium-N (51.1%), available P (8.1%), and available K (32.65%). These improved soil conditions subsequently enhanced plant N, P, and K accumulation (56.2%, 41.9%, and 53.2%, respectively), total biomass (31.8%), and seed cotton yield (5.76–6.06%). Our findings demonstrate that CO₂-enriched irrigation enhances the rhizosphere microenvironment and nutrient availability, providing a novel pathway for carbon recycling and high-efficiency cotton production in arid regions. Full article

Quercetin’s therapeutic potential is limited by its poor water solubility and rapid degradation. Natural clay minerals such as kaolinite present sustainable platforms for drug delivery, yet the molecular mechanisms of drug encapsulation are not fully understood. Specifically, the role of kaolinite’s structural polarity, its hydrophilic aluminol (001) and hydrophobic siloxane (00-1) basal surfaces, in selective drug adsorption remains unexplored. This study combines Monte Carlo sampling and Density Functional Theory (DFT) to provide the first quantitative, atomistic comparison of quercetin adsorption on both kaolinite surfaces. The results demonstrate a pronounced polarity-driven selectivity. Strong, exothermic adsorption (−206.65 kJ mol⁻¹) occurs on the hydrophilic (001) surface, stabilized by a network of five hydrogen bonds. In contrast, the hydrophobic (00-1) surface exhibits significantly weaker sorption (−147.16 kJ mol⁻¹), dominated by van der Waals interactions. Charge-transfer analysis shows that the hydrophilic (001) surface exhibits a net charge transfer of −0.198 e, approximately 2.4 times greater than that of the hydrophobic (00-1) surface (−0.083 e), consistent with differential electron density maps and partial density of states. By linking hydrogen bonding and charge transfer to adsorption energy, these results elucidate how surface polarity dictates drug encapsulation. This work establishes a predictive framework for designing kaolinite-based nanocarriers with optimized stability, bioavailability, and controlled release, guiding the development of sustainable drug delivery systems. It is noted that this DFT study models adsorption at 0 K using periodic slab models in a vacuum. Full article