Search Results (765)

Background: Breast cancer, the most prevalent malignancy among women worldwide, exhibits significant heterogeneity, particularly in the tumor microenvironment (TME), which poses challenges for treatment. Spatial transcriptomics (ST) has emerged as a transformative technology, enabling gene expression analysis while preserving tissue spatial architecture. This provides unprecedented insights into tumor heterogeneity, cellular interactions, and disease mechanisms, offering a powerful tool for advancing breast cancer research and therapy. This review aims to synthesize the applications of ST in breast cancer research, focusing on its role in decoding tumor heterogeneity, characterizing the TME, elucidating progression and metastasis dynamics, and predicting therapeutic responses. We also explore how ST can bridge molecular profiling with clinical translation to enhance precision therapy. The key scientific concepts of review included the following: We summarize the technological advancements in ST, including imaging-based and sequencing-based methods, and their applications in breast cancer. Key findings highlight how ST resolves spatial heterogeneity across molecular subtypes and histological variants. ST reveals the dynamic interplay between tumor cells, immune cells, and stromal components, uncovering mechanisms of immune evasion, metabolic reprogramming, and therapeutic resistance. Additionally, ST identifies spatial prognostic markers and predicts responses to chemotherapy, targeted therapy, and immunotherapy. We propose that ST serves as a hub for integrating multi-omics data, offering a roadmap for precision oncology and personalized treatment strategies in breast cancer. Full article

Cholesterol stress profoundly modulates cellular processes, but its underlying mechanisms remain incompletely understood. To investigate cholesterol-responsive networks, we performed integrated transcriptome (RNA-seq) and metabolome (LC-MS) analyses on HeLa cells treated with cholesterol for 6 and 24 h. Through transcriptomic analysis of cholesterol-stressed HeLa cells, we identified stage-specific responses characterized by early-phase stress responses and late-phase immune-metabolic coordination. This revealed 1340 upregulated and 976 downregulated genes after a 6 h cholesterol treatment, including induction and suppression of genes involved in cholesterol efflux and sterol biosynthesis, respectively, transitioning to Nuclear Factor kappa-B (NF-κB) activation and Peroxisome Proliferator-Activated Receptor (PPAR) pathway modulation by 24 h. Co-expression network analysis prioritized functional modules intersecting with differentially expressed genes. We also performed untargeted metabolomics using cells treated with cholesterol for 6 h, which demonstrated extensive remodeling of lipid species. Interestingly, integrated transcriptomic and metabolic analysis uncovered GFPT1-driven Uridine Diphosphate-N-Acetylglucosamine (UDP-GlcNAc) accumulation and increased taurine levels. Validation experiments confirmed GFPT1 upregulation and ANGPTL4 downregulation through RT-qPCR and increased O-GlcNAcylation via Western blot. Importantly, clinical datasets further supported the correlations between GFPT1/ANGPTL4 expression and cholesterol levels in Non-Alcoholic Steatohepatitis (NASH) liver cancer patients. This work establishes a chronological paradigm of cholesterol sensing and identifies GFPT1 and ANGPTL4 as key regulators bridging glycosylation and lipid pathways, providing mechanistic insights into cholesterol-associated metabolic disorders. Full article

Nature-based solutions (NbS) are increasingly recognized as strategic alternatives and complements to grey infrastructure for addressing water-related challenges in the context of climate change, urbanization, and biodiversity decline. This article presents a critical, theory-informed review of the state of NbS implementation in European water management, drawing on a structured synthesis of empirical evidence from regional case studies and policy frameworks. The analysis found that while NbS are effective in reducing surface runoff, mitigating floods, and improving water quality under low- to moderate-intensity events, their performance remains uncertain under extreme climate scenarios. Key gaps identified include the lack of long-term monitoring data, limited assessment of NbS under future climate conditions, and weak integration into mainstream planning and financing systems. Existing evaluation frameworks are critiqued for treating NbS as static interventions, overlooking their ecological dynamics and temporal variability. In response, a dynamic, climate-resilient assessment model is proposed—grounded in systems thinking, backcasting, and participatory scenario planning—to evaluate NbS adaptively. Emerging innovations, such as hybrid green–grey infrastructure, adaptive governance models, and novel financing mechanisms, are highlighted as key enablers for scaling NbS. The article contributes to the scientific literature by bridging theoretical and empirical insights, offering region-specific findings and recommendations based on a comparative analysis across diverse European contexts. These findings provide conceptual and methodological tools to better design, evaluate, and scale NbS for transformative, equitable, and climate-resilient water governance. Full article

Environmental contaminants exhibit heterogeneous neurotoxicity profiles, yet systematic comparisons between legacy neurotoxicants and emerging pollutants remain scarce. To address this gap, we implemented an integrative transcriptome meta-analysis framework that harmonized eight transcriptomic datasets spanning in vivo and in vitro neural models exposed to two legacy neurotoxicants (bisphenol A [BPA], 2, 2′, 4, 4′-tetrabromodiphenyl ether [BDE-47]) and polystyrene nanoplastics (PSNPs) as an emerging contaminant. Our analysis revealed a substantial overlap (68% consistency) in differentially expressed genes (DEGs) between BPA and PSNPs, with shared enrichment in extracellular matrix disruption pathways (e.g., “fibronectin binding” and “collagen binding”, p < 0.05). Network-based toxicogenomic mapping linked all three contaminants to six neurological disorders, with BPA showing the strongest associations with Hepatolenticular Degeneration. Crucially, a sex-stratified analysis uncovered male-specific transcriptional responses to BPA (e.g., lipid metabolism and immune response dysregulation), whereas female models showed no equivalent enrichment. This highlights the sex-specific transcriptional characteristics of BPA exposure. This study establishes a novel computational toxicology workflow that bridges legacy and emerging contaminant research, providing mechanistic insights for chemical prioritization and gender-specific risk assessment. Full article

Authorities responsible for critical infrastructure, particularly bridges, face significant challenges. Many bridges, constructed in the 1960s and 1970s, are now approaching or have surpassed their intended service life. A report from the German Federal Ministry for Digital and Transport (BMVI) indicates that about 12% of the 40,000 federal trunk road bridges in Germany are in “inadequate or unsatisfactory” condition. Similar issues are observed in other countries worldwide. Economic constraints prevent ad hoc replacements, necessitating continued operation with frequent and costly inspections. This situation creates an urgent need for cost-effective, permanent monitoring solutions. This study explores the potential use of low-cost acceleration sensors for monitoring infrastructure structures. Inclination is calculated from the acceleration data of the sensor, using gravitational acceleration as a reference point. Long-term changes in inclination may indicate a change in the geometry of the structure, thereby triggering alarm thresholds. It is particularly important to consider specific challenges associated with low measurement accuracy and the susceptibility of sensors to environmental influences in a low-cost setting. The results of laboratory tests allow for an estimation of measurement accuracy and an analysis of the various error characteristics of the sensors. The article outlines the methodology for developing low-cost inclination sensor systems, the laboratory tests conducted, and the evaluation of different measures to enhance sensor accuracy. Full article

Thermal sensors are widely used in medical, industrial and other fields, where the requirements for high sensitivity and portability continues to increase. Here we propose a suspended bridge structure fabricated using MEMS, which effectively shrinks the size and reduces heat loss. This study reviews current sensor-related theories of heat conduction, convective heat transfer and thermal radiation. Heat loss models for suspended and non-suspended bridge structures are established, and finite element analysis is conducted to evaluate their thermal performance. The thermal performance of the suspended bridge structure is further validated through infrared temperature measurements on the manufactured sensor device. Theoretical calculations demonstrate that the proposed suspension bridge structure reduces heat loss by 88.64% compared with traditional designs. Benefiting from this improved heat retention, which was also confirmed by infrared thermography, the thermal sensor fabricated based on the suspension bridge structure achieves an ultra-high sensitivity of 0.38 V/W and a fast response time of less than 200 ms, indicating a high accuracy in thermal characterization. The correlation coefficient obtained for the sensor output voltage and input power of the sensor is approximately 1.0. Based on this design, multiple microfluidic channels with suspended bridge structures can be integrated to realize multi-component detection, which is important for the development of multifunctional biomedical detection. Full article

Exploring the causes of the concave curved form of the roofs in traditional Chinese architecture is key to understanding its unique esthetics and structural logic. Regarding its causes, the academic community offers various explanations, including esthetics and function, but research that delves deeply into specific construction techniques and material limitations and systematically explains how they lead to the precise roof forms is relatively insufficient, which limits our comprehensive understanding of the deep generative logic of this unique form. This study aimed to bridge this gap by systematically exploring the causes of the concave curved form of roofs in traditional Chinese architecture (such as flying eaves, upturned corners, and Ju zhe) from the perspective of construction technology. Through a systematic review of historical literature (especially Yingzao fashi (Treatise on Architectural Methods)); the empirical investigation and analysis of typical architectural examples; detailed research on the structural practices, material properties (especially the creep behavior of timber), and construction techniques of key timber components such as flying rafters, hip rafters, and rafters; and mechanical principles and computational simulation, this study found that the concave curved forms of different parts of the roof, such as the eaves (flying rafters), corners (corner upturn), and main body (Ju zhe), are not purely esthetic choices but are, to a large extent, technical responses or inevitable results stemming from objective construction constraints of the time, including limitations on timber length, component connection methods, structural load distribution, and long-term deformation. Based on these findings, this study proposes the concept of “Passive Form” to summarize this form-generation mechanism, emphasizing that architectural forms are not solely determined by subjective will but are rooted in the adaptation and transformation of real constraints in construction, providing a technical perspective rooted in practice for understanding the forms of Chinese traditional architecture. Full article

This study explores English language teachers’ beliefs and practices regarding assessment and associated training needs in two diverse European educational contexts: Norway and Cyprus. Using a quantitative approach, the research employed survey questionnaires completed by 134 Norwegian and 396 Cypriot teachers. Analysis, including chi-square and Mann–Whitney tests, revealed important foundational beliefs and practices of language assessment literacy (LAL), alongside distinct practices influenced by contrasting educational systems and socio-cultural landscapes. Context emerged as a critical factor shaping teachers’ confidence, knowledge, and professional development needs in assessment. Findings highlight the importance of integrating culturally responsive frameworks into LAL development programs to better address diverse educator needs. Recommendations are also provided for designing localized, context-sensitive teacher training initiatives and fostering collaborative practices to bridge gaps in LAL. The study concludes by highlighting future research directions to expand understanding of LAL in multicultural settings. Full article

Urban green spaces (UGSs) and forests play a vital role in shaping sustainable and livable cities, offering not only ecological benefits but also spaces that are essential for human well-being, social interactions, and everyday life. Understanding the landscape features that resonate most with public preferences is essential for enhancing the appeal, accessibility, and functionality of these environments. However, traditional approaches—such as surveys or single-data analyses—often lack the nuance needed to capture the complex and multisensory nature of human responses to green spaces. This study explores a cross-modal methodology that integrates natural language processing (NLP) and deep learning techniques to analyze text and image data collected from public reviews of 19 urban parks in Nanjing. By capturing both subjective emotional expressions and objective visual impressions, this study reveals a consistent public preference for natural landscapes, particularly those featuring evergreen trees, shrubs, and floral elements. Text-based data reflect users’ lived experiences and nuanced perceptions, while image data offers insights into visual appeal and spatial composition. By bridging human-centered insights with data-driven analysis, this research provides a robust framework for evaluating landscape preferences. It also underscores the importance of designing green spaces that are not only ecologically sound but also emotionally resonant and socially inclusive. The findings offer valuable guidance for the planning, design, and adaptive management of urban green infrastructure in ways that support healthier, more responsive, and smarter urban environments. Full article

This study compares complaints in Korean and Chinese, focusing on how they are expressed explicitly or implicitly. Complaints are potentially face-threatening, yet they frequently appear in conversations among native Korean and Chinese speakers who are characterized as upholding Neo-Confucian values and emphasizing social harmony. Although some contrastive studies have examined complaints across languages, none have specifically investigated the explicit and implicit strategies employed in Korean and Chinese complaint discourse. Given the growing intercultural contact between Korean and Chinese speakers, this gap calls for closer attention. To address this, the present study explores how native Korean and Chinese speakers articulate complaints in the Korean and Chinese versions of the travel reality show Sisters Over Flowers. Sixteen episodes were analyzed using interactional sociolinguistic methods, incorporating both qualitative and quantitative approaches. The analysis uncovered both explicit and implicit strategies (e.g., expressions of annoyance or disapproval, overt grievances, questions, advice, teasing, and hints). Notably, the Korean participants produced significantly fewer complaints than their Chinese counterparts. These findings offer theoretical and practical insights. Theoretically, the results challenge overly broad notions of East–West pragmatic distinctions by demonstrating meaningful variation within East Asian cultures. Practically, a better understanding of explicit and implicit complaint strategies in Korean and Chinese can enhance intercultural communication, promote culturally sensitive responses, and bridge misunderstandings in increasingly globalized settings. Full article

Biophilic design has emerged as a multidimensional response to growing concerns about health, well-being, and ecological balance in the built environment. Despite its rising prominence, research on the topic remains fragmented across building typologies, user groups, and geographic contexts. This study presents a comprehensive review of the biophilic design literature, employing a hybrid methodology combining structured content analysis and bibliometric mapping. All peer-reviewed studies indexed in the Web of Science and Scopus were manually screened for architectural relevance and systematically coded. A total of 435 studies were analysed to identify key trends, thematic patterns, and research gaps in the biophilic design discipline. This review categorises the literature by methodological strategies, building typologies, spatial scales, population groups, and specific biophilic design parameters. It also examines geographic and cultural dimensions, including climate responsiveness, heritage buildings, policy frameworks, theory development, pedagogy, and COVID-19-related research. The findings show a strong emphasis on institutional contexts, particularly workplaces, schools, and healthcare, and a reliance on perception-based methods such as surveys and experiments. In contrast, advanced tools like artificial intelligence, simulation, and VR are notably underused. Few studies engage with neuroarchitecture or neuroscience-informed approaches, despite growing recognition of how spatial design can influence cognitive and emotional responses. Experimental and biometric methods remain scarce among the few relevant contributions, revealing a missed opportunity to connect biophilic strategies with empirical evidence. Regarding biophilic parameters, greenery, daylight, and sensory experience are the most studied parameters, while psychological parameters remain underexplored. Cultural and climate-specific considerations appear in relatively few studies, and many fail to define a user group or building typology. This review highlights the need for more inclusive, context-responsive, and methodologically diverse research. By bridging macro-scale bibliometric patterns with fine-grained thematic insights, this study provides a replicable review model and valuable reference for advancing biophilic design as an evidence-based, adaptable, and human-centred approach to sustainable architecture. Full article

This research presents a comprehensive methodology for calibrating Discrete Element Method (DEM) parameters governing rice grain interactions with biodegradable Polylactic Acid (PLA) components in agricultural bucket elevator systems. Rice grains, a critical global food staple requiring efficient post-harvest handling, were modeled as three-sphere clusters to accurately represent their physical dimensions (6.5 mm length), while the Hertz–Mindlin contact model provided the theoretical framework for particle interactions. The calibration process employed a multi-phase experimental design integrating Plackett–Burmann screening, steepest ascent method, and Face Central Composite Design to systematically identify and optimize critical micro-mechanical parameters for agricultural material handling. Statistical analysis revealed the coefficient of static friction between rice and PLA as the dominant factor, contributing 96.49% to system performance—significantly higher than previously recognized in conventional agricultural processing designs. Response Surface Methodology generated predictive models achieving over 90% correlation with experimental results from 3D-printed PLA shear box tests. Validation through comparative velocity profile analysis during bucket elevator discharge operations confirmed excellent agreement between simulated and experimental behavior despite a 20% discharge velocity variance that warrants further investigation into agricultural material-specific phenomena. The established parameter set enables accurate virtual prototyping of sustainable agricultural handling equipment, offering post-harvest processing engineers a powerful tool for optimizing bulk material handling systems with reduced environmental impact. This integrated approach bridges fundamental agricultural material properties with sustainable engineering design principles, providing a scalable framework applicable across multiple agricultural processing operations using biodegradable components. Full article

Background: Dendritic cells (DCs) play an important role as a bridge between innate and adaptive immunity, and changes in gene expression of DCs during the immune response to Mycobacterium tuberculosis (M.tb) may affect the development of tuberculosis. Methods: Using systems biology methods, mRNA and miRNA expression profile data of DCs infected with M.tb were obtained. A total of 1398 differentially expressed mRNAs and 79 differentially expressed miRNAs were identified, and a corresponding miRNA–mRNA regulatory network was constructed using Cytoscape 3.9.1 software. The functional annotations and pathway classifications of the miRNA–mRNA network were identified using the DAVID tool. Then, the key pathway modules in the miRNA–mRNA network were screened and subjected to PPI network analysis to identify hub nodes. Subsequently the miRNA/mRNA axis was determined, validated by qRT-PCR, and evaluated through ROC curve analysis. Results: The TNF signaling pathway and the Tuberculosis pathway were key pathway modules, with miR-34a-3p/TNF and miR-190a-3p/IL1B being the greatest correlations with the two pathway modules. qRT-PCR results showed that IL1B and miR-190a-3p exhibited significant differences in both the H37Ra and BCG infection groups. The AUC of two factors (IL1B and miR-190a-3p) was 0.9561 and 0.9625, respectively, showing high sensitivity and specificity. Conclusions: Consequently, miR-190a-3p/IL1B might be a good candidate marker to characterize the immune response of DCs to M.tb and a transition signal from innate to adaptive immunity. Full article

This study investigates the relationship between sovereign credit rating transitions and domestic equity market performance, focusing on Greece from 2004 to 2024. Although credit ratings are central to sovereign risk assessment, their immediate influence on financial markets remains contested. This research adopts a multi-method analytical framework combining algebraic combinatorics and time-series econometrics. The methodology incorporates the construction of a directed credit rating transition graph, the partially ordered set representation of rating hierarchies, rolling-window correlation analysis, Granger causality testing, event study evaluation, and the formulation of a reward matrix with optimal rating path optimization. Empirical results indicate that credit rating announcements in Greece exert only modest short-term effects on the Athens Stock Exchange General Index, implying that markets often anticipate these changes. In contrast, sequential downgrade trajectories elicit more pronounced and persistent market responses. The reward matrix and path optimization approach reveal structured investor behavior that is sensitive to the cumulative pattern of rating changes. These findings offer a more nuanced interpretation of how sovereign credit risk is processed and priced in transparent and fiscally disciplined environments. By bridging network-based algebraic structures and economic data science, the study contributes a novel methodology for understanding systemic financial signals within sovereign credit systems. Full article

Background/Objectives: Cardiac aging involves the progressive structural and functional decline of the myocardium. Endurance training is a well-recognized non-pharmacological intervention that counteracts this decline, yet the molecular mechanisms driving exercise-induced cardiac rejuvenation remain inadequately elucidated. This study aimed to identify key effector genes and regulatory pathways by integrating human cardiac aging transcriptomic data with multi-omic exercise response datasets. Methods: A systems biology framework was developed to integrate age-downregulated genes (n = 243) from the GTEx human heart dataset and endurance-exercise-responsive genes (n = 634) from the MoTrPAC mouse dataset. Thirty-seven overlapping genes were identified and subjected to Enrichr for pathway enrichment, KEA3 for kinase analysis, and ChEA3 for transcription factor prediction. Candidate effector genes were ranked using ToppGene and ToppNet, with integrated prioritization via the FLAMES linear scoring algorithm. Results: Pathway enrichment revealed complementary patterns: aging-associated genes were enriched in mitochondrial dysfunction and sarcomere disassembly, while exercise-responsive genes were linked to protein synthesis and lipid metabolism. TTN, PDK family kinases, and EGFR emerged as major upstream regulators. NKX2-5, MYOG, and YBX3 were identified as shared transcription factors. SMPX ranked highest in integrated scoring, showing both functional relevance and network centrality, implying a pivotal role in mechano-metabolic coupling and cardiac stress adaptation. Conclusions: By integrating cardiac aging and exercise-responsive transcriptomes, 37 effector genes were identified as molecular bridges between aging decline and exercise-induced rejuvenation. Aging involved mitochondrial and sarcomeric deterioration, while exercise promoted metabolic and structural remodeling. SMPX ranked highest for its roles in mechano-metabolic coupling and redox balance, with X-inactivation escape suggesting sex-specific relevance. Other top genes (e.g., KLHL31, MYPN, RYR2) form a regulatory network supporting exercise-mediated cardiac protection, offering targets for future validation and therapy. Full article