Search Results (8,224)

Liver cancer remains a significant global health burden, requiring the development of precise nucleic acid delivery systems. Lipid nanoparticles (LNPs) are leading candidates; however, their efficiency is governed by the pK_a of ionizable lipids, which dictates nanoparticle stability and endosomal escape. In this study, we employed a machine learning–driven quantitative structure–activity relationship framework to predict the pK_a of ionizable lipids derived from the DLin–KC2–DMA scaffold. Utilizing a dataset of 56 compounds, we compared Random Forest, Artificial Neural Network, and Extreme Gradient Boosting (XGB) models integrated with Permutation Importance (PI) for feature selection. The optimized PI–XGB model exhibited exceptional predictive accuracy (R² = 0.970, R²_CV = 0.901, RMSE_test = 0.115) and robust generalization confirmed via external validation (RMSE_ext. = 0.313). Mechanistic insights derived from SHapley Additive exPlanation analysis identified charge distribution, molecular topology, and polarity as critical determinants of lipid ionization. These results demonstrate the power of interpretable machine learning in elucidating molecular structure–property relationships, offering a robust computational strategy for the rational design of next–generation ionizable lipids to optimize LNP–mediated gene therapy for liver cancer. Full article

The cathodic oxygen reduction reaction (ORR) remains a major kinetic barrier to high-efficiency proton exchange membrane fuel cells (PEMFCs), motivating the search for electrocatalysts that combine high activity, low metal usage, and long-term durability. This review examines single-atom catalysts (SACs) as an emerging platform for fuel-cell cathodes with particular emphasis on how atomic-level design, ORR mechanism, and practical deployment barriers are interrelated. The review discusses the key ORR pathways, intermediate binding principles, and scaling constraints that govern cathodic performance, and examines how metal-center selection, coordination-environment engineering, support regulation, synergistic multi-site construction, and morphology-controlled synthesis can be used to tune intrinsic activity and stabilize isolated active sites. It further highlights mechanistic insights from theoretical and operando studies, with emphasis on structure–activity relationships, dynamic active-site evolution, and approaches to mitigate scaling limitations. Major barriers to practical deployment, including carbon corrosion, demetalization, agglomeration, peroxide/reactive oxygen species attack, and the persistent gap between half-cell metrics and membrane electrode assembly performance, are also critically assessed. Rather than treating these topics separately, this review discusses them as connected factors that together determine the viability of SAC-based fuel-cell cathodes. Full article

Background: Osteopathy’s integration into contemporary healthcare requires clear articulation of its theoretical and practical foundations and active engagement in interprofessional practice. Despite growing institutional recognition, conceptual ambiguity remains regarding foundational principles and their operationalization. Osteopathy is broadly described as a person-centered, evidence-informed discipline promoting health through manual and educational strategies within systemic and biopsychosocial contexts. Objectives: This Perspective critically examines osteopathic principles, proposes a shared conceptual model for interdisciplinary care, and outlines a structured research agenda for empirical validation, aiming to enhance person-centered, preventive, and sustainable practice. Methods: A narrative review synthesized historical, theoretical, and contemporary evidence. Records were thematically analyzed through expert collaborative brainstorming to achieve consensus, ensuring both conceptual and empirical rigor. Results: Twenty-two studies were included, forming two thematic areas: (1) historical evolution of osteopathic principles, encompassing foundational definitions, early interpretive divergences, codifications, and adaptations; and (2) contemporary reconceptualization for interdisciplinary care, integrating systems-oriented and biopsychosocial frameworks. Emphasis was placed on self-regulation, structure–function relationships, and holistic care. This synthesis bridges historical and modern insights, highlighting osteopathy’s relevance in integrative, pediatric, and preventive healthcare. Conclusions: Reconceptualizing osteopathic principles strengthens professional identity and supports sustainable, evidence-informed, person-centered practice. The proposed framework informs interprofessional collaboration and guides a research roadmap to validate and integrate osteopathy globally within contemporary healthcare systems. Full article

A series of morpholine-appended 1,8-naphthalimide probes (S1–S5) was developed to investigate the influence of the morpholine moiety on H₂S detection. All probes exhibited characteristic absorption and emission features and responded to H₂S with fluorescence enhancement, although the intensity varied markedly across the series. S2 displayed the highest signal enhancement, while S5 showed minimal response, highlighting the critical role of a two-carbon spacer between the morpholine group and the fluorophore for optimal sensing. Kinetic analysis revealed that S1–S4 followed similar reaction profiles, whereas S5 reacted faster but produced a weaker signal. S2 maintained reliable performance across pH 4–9 and in DMSO-containing media and demonstrated excellent selectivity over common biothiols and other potentially interfering species. These findings provide a clear structure–activity relationship for morpholine-based fluorescent probes and inform the rational design of highly selective H₂S sensors. Full article

Urban density is a central concept in sustainable urban development, yet its measurement and interpretation remain fragmented and often limited to single indicators. This paper develops a multidimensional framework for measuring urban density and linking it to selected dimensions of liveability relevant to spatial planning and sustainable urban development. The approach conceptualises urban density as the interaction between morphological, functional, and structural dimensions within a common spatial unit defined as the urban footprint. The framework is operationalised through indicators capturing built form, population and activity intensity, and land-use composition, while selected liveability components—such as accessibility, green infrastructure, and environmental conditions—are incorporated as an interpretative layer. The methodology is demonstrated through its application to three Slovenian cities (Izola, Kranj, and Gornja Radgona), representing different urban typologies. The results show that similar aggregate density values may correspond to different spatial configurations, revealing patterns not captured by conventional indicators. The analysis identifies mismatches between density dimensions and a “density dilution effect” related to the use of heterogeneous spatial units. The findings confirm that the relationship between density and liveability is context-dependent, shaped by the interaction between built form, functional structure, and green space provision. The study contributes a transferable methodological framework that supports a more nuanced interpretation of urban density and provides a tool for informed and context-sensitive spatial planning, contributing to more efficient land use, improved environmental quality, and more sustainable urban development outcomes. Full article

Ammonia decomposition represents a promising route for CO₂-free hydrogen production; however, the development of efficient and stable catalysts remains a critical challenge. In this work, a series of Al-based mixed-oxide catalysts (AlM, where M = Ni, Co, Ce) were synthesized via co-precipitation and systematically investigated to elucidate the relationship between physicochemical properties and catalytic performance in ammonia decomposition. Comprehensive characterization by X-ray diffraction (XRD), N₂ physisorption (BET), scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM–EDX), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), and pyridine-adsorbed Fourier transform infrared spectroscopy (FTIR-Py) revealed significant variations in surface area, morphology, dispersion, and acidity as a function of the incorporated metal. Among the investigated catalysts, the AlNi system exhibited superior activity, achieving the highest ammonia conversion over the studied temperature range. This enhanced performance is attributed to its high specific surface area, homogeneous mesoporous structure, and a balanced distribution of Lewis/Brønsted acid sites, which promote effective ammonia adsorption, activation and decomposition. Kinetic analysis further confirmed the favorable reaction pathway on AlNi, as evidenced by its lower apparent activation energy and higher pre-exponential factor compared to the other materials. The results demonstrate a clear correlation between surface acidity, textural properties, and catalytic performance, highlighting the pivotal role of AlM interactions in governing ammonia decomposition. These findings provide valuable insights for the rational design of efficient catalysts for hydrogen production from ammonia. Full article

The jalapeño pepper (Capsicum annuum L.) is a crop of great economic and nutritional importance worldwide; however, increasing yield and quality under conditions of reduced synthetic inputs remains a significant challenge, mainly due to restrictions in plant nutrition and stress response capacity; in this context, plant-based biostimulants, such as Ricinus communis extracts, are of particular interest due to their potential to modulate plant metabolism, promote growth, and favor the accumulation of bioactive compounds. In this study, the effect of a foliar-applied biostimulant derived from a methanolic extract of Ricinus communis L. on the physiological, agronomic, and biochemical parameters of jalapeño peppers was evaluated under open field conditions. A randomized complete design with five treatments was established: three extract concentrations (T50: 50 mg L⁻¹, T75: 75 mg L⁻¹, and T100: 100 mg L⁻¹), a commercial biostimulant (Pepton 85/16 ^®), and an absolute control. Significant differences (α ≤ 0.05) were observed between treatments T50, T75, and T100 with the application of castor bean and the absolute control in stem diameter, fruit number, yield, and polar and equatorial fruit diameter, as well as phenols, flavonoids, and antioxidant capacity (ABTS and DPPH). The application of R. communis extract (T50, T75, and T100) significantly improved plant performance compared to the control, particularly in yield (up to 270%), fruit number (73%), shoot biomass (up to 38%), and root development (up to 32%). Furthermore, increases in chlorophyll content and in antioxidant-related compounds were observed, including phenols, flavonoids, ABTS, and DPPH (up to 17%). Spearman correlation analysis revealed strong associations between structural and metabolic variables, highlighting the relationship between stem diameter, fruit traits, and bioactive compound accumulation, as well as the link between chlorophyll content and reproductive performance. The ¹H NMR analysis indicated the presence of secondary metabolites such as ricin, unsaturated fatty acids, and phenolic compounds; however, their isolation and relationship with the biostimulant activity of the extract require further specific studies. Overall, foliar application of R. communis extract improved the growth, productivity, and biochemical attributes of jalapeño pepper, highlighting its potential as a sustainable alternative for crop management. Full article

Hidradenitis suppurativa (HS) is a chronic inflammatory dermatosis characterized by recurrent nodules, abscesses, and sinus tract formation in intertriginous skin. Although HS is increasingly recognized as an autoinflammatory condition rather than a classical infection, antimicrobial therapies remain central to disease management, implicating a potential role for the cutaneous microbiome in disease activity. Recent advances in culture-independent sequencing techniques have enabled more detailed characterization of microbial communities in HS, revealing consistent alterations in microbial composition and diversity. Compared with healthy skin, HS lesions exhibit reduced microbial diversity, depletion of commensal organisms such as Cutibacterium acnes, and enrichment of anaerobic bacteria including Prevotella, Porphyromonas, and Finegoldia. These alterations are more pronounced in chronic, tunnel-forming disease and are frequently associated with biofilm formation, which may contribute to treatment resistance and persistent inflammation. Microbiome changes have also been observed beyond overtly lesional skin, suggesting a broader field effect. Evidence regarding extracutaneous microbial compartments, particularly the gut microbiome, remains limited and heterogeneous, while methodological variability in sampling, sequencing, and treatment exposure continues to complicate cross-study comparisons. Emerging data further suggest that immune-targeted therapies, including biologic and small-molecule agents, may indirectly influence microbial community structure through modulation of the inflammatory milieu. Collectively, the available evidence supports cutaneous dysbiosis as a characteristic feature of HS that may potentially interact bidirectionally with immune dysfunction. Future longitudinal, multi-omic studies integrated with clinical phenotyping will be critical to clarify causal relationships and to determine whether microbiome modulation can be leveraged to improve therapeutic outcomes in HS. Full article

Type 1 diabetes mellitus (T1DM) is a chronic, non-preventable, and incurable disease that requires lifelong insulin administration. The principal challenge is calculating the prandial insulin bolus to avoid hypoglycemia and hyperglycemia. Traditional bolus calculators are based on limited number of variables, but there are many variables that define the complex interactions among glucose levels, like carbohydrate intake, physical activity, mood, and contextual factors. While recent artificial intelligence (AI) approaches have shown promise in glucose prediction, most remain correlational and offer limited interpretability for clinical decision support. This study evaluates a causal inference-based framework for insulin bolus calculation using Directed Acyclic Graphs (DAGs) and the Greedy Relaxation of the Sparsest Permutation (GRaSP). Historical data from individuals with T1DM were analyzed, incorporating domain knowledge constraints to guide structure learning. A bootstrap-based stability analysis was conducted to evaluate the robustness of inferred relationships. Results show that integrating prior medical knowledge reduces graph complexity and improves interpretability. However, bootstrap stability reflects robustness of the learning procedure rather than causal validity. The findings suggest that the proposed framework is useful for generating plausible causal hypotheses, but not for confirming causal relationships. Further validation using conditional independence testing, equivalence class analysis, and temporal causal methods is required. However, the proposed framework focuses on generating plausible causal hypotheses rather than establishing causal validity, which requires further refutation-based validation. Full article

To examine the complex relationships among physical activity, emotion regulation, psychological stress, and mood states in college students, this study analyzed questionnaire data collected from 494 participants. Network analysis was employed to construct a global association network, compare gender differences, and characterize patterns of directed statistical dependencies via directed acyclic graph (DAG) analysis. The results showed that: (1) the network comprised 25 nodes and 94 non-zero edges, reflecting extensive conditional associations across the four domains; (2) bridge centrality analysis identified cognitive reappraisal, self-related emotions, and anger as key bridge nodes, with cognitive reappraisal exhibiting the highest bridge strength; (3) accuracy and stability analyses yielded a centrality stability coefficient (CS) of 0.749 for strength, indicating adequate network stability; (4) network comparison tests revealed no significant gender differences in overall network structure or global strength, although certain local edge weights differed; (5) DAG analysis suggested that stable directional dependencies were primarily concentrated within individual subsystems, with no marked structural differences observed between male and female groups. In conclusion, physical activity, emotion regulation, psychological stress, and mood states appear to constitute an interconnected psychological adaptation system. Cognitive reappraisal, self-related emotions, and anger likely serve as pivotal bridge nodes warranting priority in future longitudinal research and targeted interventions. Full article

Alkaloids are structurally diverse, nitrogen-containing plant secondary metabolites with well-documented insecticidal activity. This review examines alkaloid-based insecticides, focusing on their chemical diversity, biosynthetic origins, plant distribution, and physicochemical properties relevant to pest control on farms. The principal molecular targets and modes of action are discussed, including interactions with nicotinic acetylcholine receptors, acetylcholinesterase, ryanodine receptors, and GABAergic signaling. Another focus is key metabolic enzymes, together with their activity spectra against major agricultural pests. Recent advances in rational structural modification, supported by crystallographic data, computational modeling, and structure–activity relationship studies, are highlighted as strategies to enhance the potency, selectivity, and stability of these compounds. Toxicological profiles, food residue behavior, analytical challenges, and regulatory considerations are critically assessed, emphasizing that natural origin does not equate to inherent safety. The review further evaluates the role of alkaloid-based insecticides within integrated pest management systems and identifies key research gaps related to environmental safety, non-target effects, and regulatory development and harmonization. It concludes that alkaloids are positioned as potentially valuable tools for sustainable agriculture when deployed within science-based regulatory frameworks and integrated control strategies. Full article

The design of multitargeted drug candidates has recently emerged as a highly attractive area of research. Numerous heterometallic compounds have been developed to enhance both the biological efficacy and physicochemical properties of monometallic metallodrugs. Combining classical transition metals with established antitumor activity, such as Pt, Ru, and Au, with other metal-based fragments offers the potential to generate complex compounds with improved pharmacokinetic and pharmacodynamic profiles. Incorporating different bioactive metal cations within a single molecular framework may enhance anticancer activity through metal-specific interactions with distinct biological targets or through improved physicochemical characteristics of the resulting heteronuclear complexes. Recent studies have underscored the significant progress and promising impact of this multitargeted strategy, particularly in systems that combine ruthenium with other biologically active metal centers. This approach may enable selective biological targeting and help overcome drug resistance. This review compiles and analyzes reported ruthenium-based heteronuclear complexes, offering a comprehensive and critical assessment of recent advances in the rational design and synthesis of novel multinuclear compounds as potential chemotherapeutic agents. Particular emphasis is placed on understanding structure–activity relationships, mechanistic pathways, and the role of metal–metal and metal–ligand interactions in modulating biological responses. The findings summarized herein highlight the remarkable efficacy of a wide range of multinuclear ruthenium anticancer complexes and support the hypothesis that synergistic and/or cooperative interactions between distinct metal-based fragments can significantly enhance pharmacological performance, including improved selectivity, stability, and cellular uptake. Furthermore, emerging insights into their modes of action, resistance profiles, and potential for targeted delivery underscore their promise as viable alternatives to conventional therapies. Overall, this dynamic and rapidly evolving field is poised to inspire continued interdisciplinary research and drive the development of next-generation metallodrugs with improved therapeutic indices and clinical potential. Full article

Agricultural performance is often interpreted through agronomic inputs and technological progress; however, the translation of knowledge into production depends on the structural environments in which food systems operate. This study examined the association between food-security-related publication activity and crop production across global income settings from 2000 to 2025, while testing whether governance, health-system, and financial indicators modify that association. A longitudinal ecological panel was constructed, integrating 61,158 Scopus-indexed peer-reviewed articles on food security and related dimensions of healthy food access and availability with 23 crop production indicators grouped into staple, horticultural, and commodity domains. Income-stratified regression models were followed by hierarchical mixed-effects models and moderator screening. In exploratory stratified models, 67 of 92 income-specific associations reached nominal significance; however, only 5 of those 67 associations (7.5%) remained statistically significant after multilevel modelling and false discovery rate correction. Robust associations were concentrated in selected staple and horticultural outcomes, whereas most commodity indicators lost significance after hierarchical adjustment. Structural moderators related to territorial control, corruption, healthy life expectancy, health researcher density, healthcare access and quality, and official development assistance shifted the conditional slopes linking publication activity to crop output. These findings do not support a uniform linear relationship between publication growth and production volume. Instead, they suggest that the alignment between research ecosystems and agricultural output is structurally conditioned and likely mediated by institutional capacity, health-system resilience, and implementation environments. The ecological design, the use of publication counts as an indirect proxy, and the reliance on production volume rather than yield or efficiency should be considered when interpreting these results. Full article

With the rapid intensification of industrial and agricultural activities, water contamination by heavy metal ions has emerged as a critical global challenge, gravely imperiling ecosystem stability and public health. Among the various remediation technologies, adsorption has been widely adopted due to its high efficiency, low-cost water treatment, and simplicity of operation. However, conventional inorganic or synthetic adsorbents often exhibit poor degradability and pose a risk of secondary contamination, substantially limiting their sustainable application. Consequently, the development of environmentally benign and renewable adsorbent materials has become a central research focus in this field. Recently, cellulose-based composite hydrogels, derived from renewable resources and characterized by excellent eco-friendliness and highly tunable three-dimensional porous structures, have attracted considerable attention as promising green adsorption materials. These hydrogels demonstrate outstanding performance in the efficient sequestration of heavy metal contaminants from aqueous environments. This review systematically summarizes recent advances in cellulose-based composite hydrogels for heavy metal removal, to elucidate the structure–performance relationships linking material fabrication strategies, structural modulation, and adsorption efficiency. First, we outline the principal construction approaches, including physical crosslinking, chemical modification, and supramolecular self-assembly, and comprehensively analyze how different synthesis routes regulate pore architecture, mechanical properties, and the distribution of surface functional groups. Second, the underlying adsorption mechanisms, primarily coordination complexation, electrostatic interactions, and ion exchange, are discussed in detail. Finally, recent studies on the adsorption of cationic heavy metals (e.g., Pb(II), Cu(II), and Cd(II)) and anionic oxyanions (e.g., As(III) and Cr(VI)) are critically reviewed, with particular emphasis on the relationships between selective adsorption performance, material design principles, and specific recognition mechanisms. Overall, this review provides a theoretical foundation and practical guidance for the design and development of next-generation water treatment materials with high adsorption capacity, excellent selectivity, non-toxicity, and strong environmental compatibility, followed by future research recommendations. Full article

The hydrogen evolution reaction (HER) is a cornerstone of green hydrogen production, yet its efficiency is constrained by the sluggish kinetics of water splitting. High-entropy catalysts (HECs), single-phase materials incorporating multiple principal elements, have emerged as a transformative solution. Their unique attributes including vast compositional flexibility, tunable electronic structures, and synergistic multi-element interactions, enable them to overcome the activity, stability, and cost limitations of conventional catalysts. Despite rapid performance advancements, the rational design of HECs is fundamentally hampered by critical knowledge gaps, particularly in identifying true active sites under operando conditions and predicting long-term stability. This work critically assesses these challenges, systematically summarizing the latest progress in HECs design, synthesis, and structure–activity relationships. By bridging fundamental principles with practical applications, we provide a forward-looking perspective on key research directions. Distinct from recent progress-focused reviews, this work establishes a strategic roadmap by systematically diagnosing seven grand challenges across the science-to-technology pipeline and proposing corresponding countermeasures. This framework aims to guide future research efforts toward the rational design and practical deployments of HECs for practical and cost-effective green hydrogen production. Full article