Search Results (12,389)

Walkability for non-motorized users is crucial for fostering inclusive, healthy, and sustainable communities. By prioritizing modern human-centered design principles, social equality is promoted for all categories of users, regardless of physical abilities or socio-economic status. Despite the importance of this indicator, a series of inconsistencies that produce inadequate and inaccessible urban space can still be observed in cities. The aim of this paper is to present the methodology for the calculation of the walkability index at the local level. This new methodological procedure considers walkability for pedestrians, with a special focus on people with reduced mobility. Based on specifically defined criteria, initial calculations were performed and integrated into the dynamic walkability index (DWI). One of the main advantages of this index is that it includes the dynamic component of the share of different categories of users in the total sample, which enables simple time modification without repeating the entire procedure. The developed methodology can be used as a tool for ranking existing street segments according to the urgency of reconstruction, while on the other hand promoting equality and inclusion of all categories of users in decision-making processes, thus creating more comfortable and safer environments. Full article

Burkholderia pseudomallei complex and B. cepacia complex are two evolutionary distinct clades of pathogens causing human disease. Most vaccine efforts have focused on the former group largely due to their biothreat status and global disease burden. It has been proposed that a vaccine could be developed that simultaneously protects against both groups of Burkholderia by specifically targeting conserved antigens. Only a few studies have set out to identify which antigens may be optimal targets for such a vaccine. We have previously assessed the ability of three highly conserved B. pseudomallei antigens, namely OmpA1, OmpA2, and Pal, coupled to gold nanoparticle vaccines, to protect mice against a homotypic B. pseudomallei challenge. Here, we have expanded our study by demonstrating that antibodies to each of these proteins show varying levels of reactivity to homologues in B. cepacia complex, with OmpA2 antibodies exhibiting the highest cross-reactivity. Remarkably, some nanovaccine immunized mice, particularly those that received OmpA2, produced antibodies that bind Pseudomonas aeruginosa, which harbors distantly related homologous proteins. T cells elicited to Pal and OmpA2 responded to stimulation with B. cepacia complex-derived homologues. Our study supports incorporation of these antigens, particularly OmpA2, for the development of a pan-Burkholderia vaccine. Full article

In recent years, with the rapid advancement of science and technology, generative artificial intelligence has increasingly entered the public eye. Primarily through intelligent algorithms that simulate human logic and integrate vast amounts of network data, it provides designers with solutions that transcend traditional thinking, enhancing both design efficiency and quality. Compared to traditional design methods reliant on human experience, generative design possesses robust data processing capabilities and the ability to refine design proposals, significantly reducing preliminary design time. This study employs the CiteSpace visualization tool to systematically organize and conduct knowledge map analysis of research literature related to generative AI in architectural design within the Web of Science database from 2005 to 2025. Findings reveal the following: (1) International research exhibits a trend toward interdisciplinary convergence. In recent years, research in this field has grown rapidly across nations, with continuously increasing academic influence; (2) Research primarily focuses on technological applications within architectural design, aiming to drive innovation and development by providing superior, more efficient technical support; (3) Generative AI in architectural design has emerged as a prominent international research focus, reflecting a shift from isolated design to industry-wide integration; (4) Generative AI has become a core global architectural design topic, with future research advancing toward full-process intelligent collaboration. High-quality knowledge graphs tailored for the architecture industry should be constructed to overcome data silos. Concurrently, a multidimensional evaluation system for generative quality must be established to deepen the symbiotic design paradigm of human–machine collaboration. This significantly enhances efficiency while reducing the iterative nature of traditional methods. This study aims to provide empirical support for theoretical and practical advancements, offering crucial references for practitioners to identify business opportunities and policymakers to optimize relevant strategies. Full article

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage loss, extracellular matrix degradation, chondrocyte apoptosis, and elevated inflammatory mediators. Chondrocytes respond to IL-1β and other inflammatory signals by secreting cytokines and activating transcriptional pathways that perpetuate inflammation. Because current therapies do not prevent OA progression, bioactive compounds with cytoprotective and immunomodulatory activity are of considerable interest. Lonomia obliqua bristle extract (LOCBE) and its recombinant proteins rLOPAP and rLOSAC exhibit cytoprotective, proliferative, and antioxidant effects in mammalian cells, as well as the ability to influence cytoskeletal dynamics. Given the importance of Rac-1, RhoA, Rab9, and β-catenin in chondrocyte function and cartilage homeostasis, we evaluated LOCBE, rLOPAP, and rLOSAC in human chondrocytes stimulated or not with IL-1β. LOCBE and rLOPAP induced IL-6 and IL-8 secretion, although at lower levels than IL-1β. LOCBE exerts a cytoprotective effect in IL-1β-treated chondrocytes and reduces β-catenin, RhoA, and Rab9 expression without affecting NF-κB p65 translocation. rLOPAP increased mitochondrial activity, cytokine secretion, Rab9 expression, and membrane-associated β-catenin, and under inflammatory conditions, enhanced Rac-1 levels. In contrast, rLOSAC did not induce inflammatory cytokines and decreased RhoA and Rac-1 expression while increasing membrane-associated β-catenin. These findings suggest that L. obliqua extract and its derived-proteins rLOPAP and rLOSAC modulate cytoskeletal regulatory pathways and inflammatory responses in chondrocytes, supporting their potential as therapeutic leads for targeting mechanisms relevant to OA progression. Full article

Lignans are naturally occurring compounds found in a wide variety of plant species, including flaxseed, soybean, pumpkin seed, broccoli, sesame seed, and some berries. Lignans have been used for centuries in both food and traditional herbal medicine. Recently, numerous new lignans and lignan derivatives with diverse biological properties have been identified. Lignans are considered promising for human health due to their hydrogen-donating antioxidant activity together with their ability to complex divalent transition metal cations. They have demonstrated beneficial effects for cardiovascular disease, as well as in maintaining blood glucose levels, supporting cardiac health, promoting anti-obesity effects, decreasing the risk of renal diseases, enhancing brain function, improving skin and gut health, among others. This review explores the biosynthesis and biological effects of lignans, with a particular focus on their antihypertensive and anti-obesity properties, as well as the molecular mechanisms involved. It also highlights recent advances in sustainable lignan extraction techniques that are suitable for human use. The mechanisms underlying these bioactivities are thought to involve hormonal metabolism and availability, antioxidant action, modulation of angiogenesis, and more. However, further research is needed to fully elucidate the molecular pathways through which lignans exert their therapeutic effects. Overall, lignans from various plant sources hold significant potential for application in functional foods, dietary supplements, and pharmaceutical products aimed at preventing and managing a range of health conditions, including hypertension and obesity. Full article

The post-implantation phase of mammalian development is crucial yet challenging to study due to ethical and technical constraints, particularly in humans. Recent revolutionary advances in extended in vitro culture systems for mammalian embryos now offer unprecedented windows into this developmental “black box”. This review synthesizes how these platforms, alongside stem cell-derived embryo models, are transforming our ability to model early human development in a dish. We detail the technological evolution from two-dimensional (2D) to three-dimensional (3D) cultures that support mouse, non-human primate, and human embryos through key stages of implantation and gastrulation, recapitulating events like lineage specification and axial patterning. Furthermore, we explore how these models serve as powerful tools for investigating the etiology of early pregnancy failure, screening for developmental toxicity of pharmaceuticals, and deciphering the molecular pathogenesis of birth defects. By bridging fundamental embryology with clinical and pharmacological applications, these innovative models herald a new era in biomedical research, holding significant promise for advancing reproductive medicine and regenerative strategies. Full article

The application of social cognitive theory has expanded to the boundaries of human-computer interaction research. However, existing research has scarcely addressed mutual cognitive facilitation between humans and personalized educational large language model (LLM) agents. This study explored how educational LLM agents influence teachers’ curriculum design and content creation, based on a sample of 464 teachers from coastal regions of China, along with semi-structured interviews with 23 participants. Quantitative analysis of the survey data revealed that the involvement of educational LLM agents positively predicts teachers’ ability to create content in curriculum design. Additionally, teachers’ self-efficacy mediated this relationship, while both school support and self-efficacy together created a chain mediation effect. Qualitative findings from the interviews supported the quantitative results and further highlighted individual differences and contextual nuances in teachers’ use of educational LLM agents. In summary, the findings indicated that educational LLM agents positively impact teachers’ curriculum design and content creation, with school support and teachers’ self-efficacy acting as a chain mediator in this process. Full article

Background/Objectives: Despite clonal expansion during a primary immune response, or after subsequent antigen encounters, the frequency of memory B cells (B_mem) specific for an antigen remains low, making their detection difficult. However, unlike serum antibodies, which have a short half-life in vivo and thus require continuous replenishment to maintain stable titers, circulating B_mem are long-lived; they preserve immunological preparedness through their ability to rapidly engage in recall responses and differentiate into antibody-secreting cells (ASCs) upon antigen encounter. To this end, development of assays suited for the reliable detection of rare antigen-specific B_mem is critical and can provide insights into an individual’s antigen exposure history and immune status beyond that offered by traditional serum antibody measurements alone. Methods: ImmunoSpot^® has emerged as a suitable technique for the detection of individual antigen-specific B cells through visualizing their antibody-derived secretory footprints. Here, we report the theoretical and practical foundations for detecting rare antigen-specific B_mem in human peripheral blood mononuclear cells (PBMC). Leveraging the unique availability of verifiably naïve vs. antigen-experienced human samples, we used SARS-CoV-2 Spike (S-) and Nucleocapsid (NCAP) antigens to interrogate the presence of B_mem with these respective specificities. Results: While 100% diagnostic accuracy was achieved for both antigens, detection of NCAP-specific B_mem required reducing the lower detection limit of the standard assay. Specifically, this was achieved by testing a total of 2 million PBMC across multiple replicate assay wells and assessing the cumulative number of secretory footprints detected. Conclusion: The protocols described here should facilitate the reliable detection of ASCs present at varying precursor frequencies and serve as guidance for routine immune monitoring of rare B_mem with specificity for any antigen. Full article

Global climate change has emerged as a critical challenge for human society in the 21st century. As hubs of population and economic activity, urban and rural areas are increasingly exposed to complex and compounded disaster risks. To systematically evaluate the role of educational intervention in climate adaptability capacity building, this study employs a case study approach, focusing on the “Climate Change Adaptation Education and Teaching Alliance Program” launched in Taiwan in 2014. Through a comprehensive analysis of its institutional structure, curriculum, alliance network, and practical activities, the study explores the effectiveness of educational innovation in cultivating climate resilience talent. The study found that the program, through interdisciplinary collaboration and a practice-oriented teaching model, successfully integrated climate adaptability content into 57 courses, training a total of 2487 students. Project-based learning (PBL) and workshops significantly improved students’ systems thinking and practical abilities, and many of its findings were adopted by local governments. Based on these empirical results, the study proposes that urban and rural planning education should be promoted in the following ways: first, updating teaching materials to reflect regional climate characteristics and local needs; second, enhancing curriculum design by introducing core courses such as climate-resilient planning and promoting interdisciplinary collaboration; third, enriching hands-on learning through real project cases and participatory workshops; and fourth, deepening integration between education and practice by establishing multi-stakeholder partnerships supported by dedicated funding and digital platforms. Through such an innovative educational framework, we can prepare a new generation of professionals capable of supporting global sustainable development in the face of climate change. This study provides a replicable model of practice for education policymakers worldwide, particularly in promoting the integration of climate resilience education in developing countries, which can help accelerate the achievement of UN Sustainable Development Goals (SDG11) and foster interdisciplinary collaboration to address the global climate crisis. Full article

With the increasing complexity of cyber threats and the inefficiency of traditional vulnerability management, artificial intelligence has been increasingly integrated into cybersecurity. This review provides a comprehensive evaluation of AI-powered strategies including machine learning, deep learning, and large language models for identifying cybersecurity vulnerabilities and supporting automated patching. In this review, we conducted a synthesis and appraisal of 29 peer-reviewed studies published between 2019 and 2024. Our results indicate that AI methods substantially improve the precision of detection, scalability, and response speed compared with human-driven and rule-based approaches. We detail the transition from conventional ML categorization to using deep learning for source code analysis and dynamic network detection. Moreover, we identify advanced mitigation strategies such as AI-powered prioritization, neuro-symbolic AI, deep reinforcement learning and the generative abilities of LLMs which are used for automated patch suggestions. To strengthen methodological rigor, this review followed a registered protocol and PRISMA-based study selection, and it reports reproducible database searches (exact queries and search dates) and transparent screening decisions. We additionally assessed the quality and risk of bias of included studies using criteria tailored to AI-driven vulnerability research (dataset transparency, leakage control, evaluation rigor, reproducibility, and external validation), and we used these quality results to contextualize the synthesis. Our critical evaluation indicates that this area remains at an early stage and is characterized by significant gaps. The absence of standard benchmarks, limited generalizability of the models to various domains, and lack of adversarial testing are the obstacles that prevent adoption of these methods in real-world scenarios. Furthermore, the research suggests that the black-box nature of most models poses a serious problem in terms of trust. Thus, XAI is quite pertinent in this context. This paper serves as a thorough guide for the evolution of AI-driven vulnerability management and indicates that next-generation AI systems should not only be more accurate but also transparent, robust, and generalizable. Full article

Allomelanin is a natural class of melanin found mainly in fungi and derived from nitrogen-free precursors such as 1,8-dihydroxynaphthalene (1,8-DHN). Despite its biological relevance, allomelanin remains significantly less explored than other synthetic melanin analogs, particularly compared to polydopamine, a synthetic analog of eumelanin. In this review, we provide a comprehensive overview of current knowledge on allomelanin, summarizing the main methods used to characterize its molecular structure, morphology, and chemical functionalities. We also present its emerging applications, ranging from human health to materials science, highlighting how its optical characteristics, ability to modulate redox processes, and antioxidant properties support its growing technological interest. Finally, we describe the natural presence and biological role of allomelanin, highlighting how knowledge of its biosynthetic processes and functions in nature can guide more effective strategies for the design and optimization of new allomelanin materials. Full article

Reactive oxygen species (ROS) are a major cause of skin aging, leading to oxidation and cleavage of collagen that supports skin structure. Previous studies have demonstrated that Magnolia officinalis var. officinalis (M. officinalis) dry extract reduces mitochondria-enriched ROS production and improves senescence-related phenotypes in vitro. However, its effects on human skin aging have not been investigated. In this study, we conducted both in vitro and clinical trials using an M. officinalis liquid extract, which can be directly applied to cosmetic formulations. The M. officinalis liquid extract restored mitochondrial function and reduced mitochondria-enriched ROS production. Furthermore, M. officinalis liquid extract activated mitophagy, which removes defective mitochondria, a major source of ROS production. In clinical trials, the M. officinalis liquid extract reduced the mean depth of neck wrinkles by 12.73% and the maximum depth by 17.44%. It also reduced the mean roughness (Ra), root mean square roughness (Rq), and maximum depth of roughness (Rmax) by 12.73%, 10.16%, and 10.81%, respectively. Furthermore, the key to the skin-improving effects of M. officinalis liquid extract lies in its ability to increase skin elasticity by 3.76% and brighten skin tone by 0.76%. In conclusion, this study identified a novel mechanism by which M. officinalis liquid extract rejuvenates skin aging. M. officinalis can be utilized as a cosmetic ingredient to improve skin aging and therapeutic candidate for the development of anti-aging treatments. Full article

Background: Among the 15 human (h) carbonic anhydrase (CA; EC 4.2.1.1) isoforms, hCA IX and XII are particularly important due to their roles in tumor cell growth and survival, identifying them as promising targets for anticancer therapy. As a result, considerable effort has been directed toward the development of novel inhibitors that are highly selective for these isoforms. Methods: A library of twelve novel N-aryl-2-(4-sulfamoylphenyl)hydrazine-1-carbothioamides 3 along with two new N-aryl-2-(4-sulfamoylphenyl)hydrazine-1-carboxamide derivatives 5 were synthesized and their inhibition abilities were tested against four human carbonic anhydrase isozymes (hCA I, II, IX and XII) related to some global diseases including glaucoma, cancer and osteoporosis. Results: All compounds exhibited potent inhibition of the tested isoforms in the nanomolar range. Compound 3i showed the highest inhibition of hCA I activity but demonstrated poor selectivity toward the other isoforms. Compound 3h displayed superior selectivity for hCA II over hCA I (hCA I/II = 37) and exhibited 2.5-fold higher inhibitory activity compared to acetazolamide (AAZ). Among the tested compounds, 3l (K_i = 32.1 nM) demonstrated markedly improved selectivity for hCA IX over hCA I, II, and XII relative to the standard drug. Notably, compound 3a showed the most potent inhibition against hCA XII (K_i = 6.8 nM), comparable to AAZ, while exhibiting significantly greater selectivity over off-target isoforms and the other tumor-associated isozyme (hCA IX/XII = 20 versus hCA IX/XII = 4.5 for AAZ). Conclusions: The present study suggests potent lead compounds as selective hCA IX and XII inhibitors with anticancer activity. Full article

A strong safety culture is essential for managing human factors in complex systems and constitutes a strategic resource for supporting the sustainable operation of organizations. However, conventional approaches remain limited by unclear conceptual boundaries and a lack of mechanisms linking safety culture with other organizational safety elements. To address these gaps, this study develops a sustainable safety culture construction method grounded in accident causation theory. Using the 24Model, we establish a concise “culture–system–ability–acts” framework that operationalizes the pathways through which safety culture shapes organizational safety performance. The method integrates four components: conceptual clarification of safety culture, quantitative assessment, factor identification based on the 24Model, and Bayesian network analysis to quantify interdependencies among culture, systems, ability, and acts. Empirical evidence from coal mining enterprises shows that safety culture influences safety performance indirectly by shaping system implementation quality, workers’ safety ability, and safety-related actions. Enhancing “demand of safety training” substantially mitigated system deficiencies related to ineffective implementation of procedures, failure in enforcing procedures, lack of qualifications, and insufficient supervision. Improved training also strengthened workers’ knowledge of accident cases, consequences of violations, and technical standards, thereby reducing competence-related gaps and promoting more consistent safety supervision behaviors. Sensitivity analysis highlights the importance of reinforcing “safety responsibilities of line departments” and improving the dissemination of safety knowledge, particularly accident case knowledge. Overall, the findings empirically validate the dynamic “culture–system–ability–acts” transmission mechanism of the 24Model and provide a structured, quantitative pathway for advancing sustainable safety culture development. Full article

The service tree (Sorbus domestica L.) fruits are rich in polyphenols, which exhibit promising therapeutic effects on bone health. This review summarizes the potential benefits of polyphenols identified in Sorbus domestica L. fruits, such as chlorogenic acid (CGA), protocatechuic acid (PCA), rutin, epicatechin, and naringin on bone biology and on bone-related diseases, including osteoporosis and diabetes mellitus. Current evidence suggests that the aforementioned polyphenols may modulate osteoblast and osteoclast activity, enhance mineralization, mitigate oxidative stress and inflammation, thereby supporting overall bone health. Specific studies highlight the anabolic and anti-resorptive effects of CGA, the osteoprotective potential of PCA, and the ability of rutin, epicatechin, and naringin to promote osteogenic differentiation and inhibit osteoclastogenesis. Although the exact mechanisms are still unclear, it is believed that these bioactive metabolites can act through a variety of signalling pathways and epigenetic mechanisms. Despite existing preclinical evidence, there is a significant gap in clinical trials evaluating the direct impact of polyphenols mentioned above on bone health in humans. Therefore, further research is needed to confirm their effectiveness in clinical settings. The therapeutic potential of the most common polyphenols from Sorbus domestica L. fruits has been evaluated by available in vitro and in vivo studies, which highlight their promising potential as dietary interventions to prevent bone loss and improve skeletal integrity in metabolic bone diseases. Based on available information, maximum health benefits may be achieved if mature Sorbus domestica L. fruits are consumed approximately two weeks after harvest or as unripe fruit-based fermented products. Full article