Search Results (4,825)

A Group A Streptococcus (GAS, Streptococcus pyogenes) is an exclusively human pathogen whose virulence is driven by a diverse array of surface structures, secreted toxins, and immune evasion mechanisms. Central to its pathogenicity is the M protein, a surface-anchored molecule that inhibits phagocytosis by interfering with complement deposition and binding host factors such as fibrinogen. GAS also secretes a wide range of toxins and enzymes that damage tissues and disrupt host defences. Streptolysin O and streptolysin S are potent cytolysins that lyse immune cells and contribute to tissue necrosis. Pyrogenic exotoxins (such as SpeA and SpeC) act as superantigens, triggering massive, dysregulated T cell activation and cytokine release, an underlying mechanism in streptococcal toxic shock syndrome. Additional factors like DNases and streptokinase facilitate bacterial spread by breaking down host tissue and counteracting neutrophil extracellular traps (NETs). Immune evasion is further supported by the production of enzymes that interfere with complement functions, like the cleavage of chemokines and the targeting of antibodies. Together, these virulence determinants allow GAS to cause a wide spectrum of diseases, ranging from uncomplicated pharyngitis and impetigo to invasive conditions like necrotising fasciitis and sepsis. This review provides a timely overview of the important GAS virulence factors and an update on the current vaccine landscape. Full article

Forest cover condition is a key determinant of ecosystem functioning and ecological resilience, yet its spatial variability across large and environmentally heterogeneous regions remains insufficiently understood. Leaf area index (LAI) provides a continuous and physically meaningful indicator of forest canopy condition, reflecting variations in canopy density associated with climate and landscape structure. Here, we develop a spatially explicit and interpretable analytical framework to diagnose the dominant climatic and landscape controls on forest cover condition across mainland China during 2000–2020. By integrating machine-learning modelling with SHapley Additive exPlanations, GeoDetector interaction analysis, and nonlinear dependence diagnostics, we quantify the relative contributions and interactions of precipitation, temperature, topography, and forest landscape structure to spatial patterns in forest LAI. The results reveal pronounced spatial heterogeneity in forest cover control regimes. Precipitation dominates forest cover condition in humid regions but exhibits nonlinear saturation, whereas forest fragmentation strongly constrains canopy development and moderates climate-LAI relationships in arid and semi-arid forested landscapes. In high-elevation regions, topographic and thermal factors exert primary control. Overall, the findings demonstrate that forest cover condition reflects climate-conditioned and landscape-dependent control regimes, providing a transparent basis for large-scale forest cover assessment and ecological monitoring. Full article

As one of China’s “New Four Furnaces”, the city of Hangzhou faces significant heat challenges exacerbated by rapid urbanization. Urban parks offer effective nature-based solutions, but optimizing their multi-dimensional cooling performance—encompassing cooling area (PCA), efficiency (PCE), intensity (PCI), and gradient (PCG)—remains a key challenge. This study quantitatively analyzed the internal and external landscape features of 18 parks in Hangzhou, revealing that park cooling performance is not simply a case of “bigger is better.” We found that parks with more complex shapes and irregular boundaries exhibited higher cooling efficiency per unit area (PCE) compared to larger parks with smooth, simple shapes, though sometimes at the expense of peak PCI. Furthermore, the surrounding built environment is critical: high building density within a 300 m buffer zone was found to significantly impede the spatial extent of the cooling effect (PCA). Based on these findings, we propose that to effectively mitigate urban heat, cities should (1) shift focus away from creating large, isolated parks with smooth boundaries; (2) prioritize a network of smaller, morphologically diverse parks with irregular edges that extend into the community; and (3) enhance each park’s cooling reach through strategies like green streets and tree-lined paths. These approaches offer tangible, actionable guidance for designing high-performance cooling green infrastructure in dense urban environments. Full article

This study investigates the spatial and economic differentiation of organic farming across the European Union by analyzing regional specialization patterns using Location Quotients (LQ). The results reveal a highly heterogeneous landscape shaped by the interaction of agro-ecological conditions, production traditions, market development, and structural characteristics of national agricultural systems. Six distinct regional models of organic farming are identified: the Nordic–Baltic cereal–forage model, the Alpine–Central European grassland model, the Mediterranean permanent-crop model, the Central–Eastern European raw-material model, the Western European intensive horticultural model, and the island-based niche-specialization model. Regression analyses show that overall organic specialization is strongly associated with market development, whereas the structure of organic crop production is primarily determined by agro-ecological and structural factors rather than consumer demand or purchasing power. These findings highlight the strong embeddedness of organic farming within long-term regional development pathways and underscore the need for regionally differentiated policy instruments within the Common Agricultural Policy. Effective support measures should be tailored to dominant crop types, production systems, and comparative advantages across Member States. Full article

Sheep’s meat production and quality are influenced by genetic and physiological factors that affect muscle development, growth, and fat deposition metabolism. However, the breed-specific transcriptional landscapes driving these traits in Indian sheep breeds, especially in Nellore (meat-type) and Deccani (wool-meat type) breeds are remain unexplored. Therefore, this study aimed to investigate the differences in muscle growth and fat deposition between Nellore and Deccani breeds by integrating transcriptomic profiling, carcass characteristics, and histological analysis of longissimus dorsi muscle and liver tissues. Carcass assessment revealed higher Hot Carcass Weight (HCW), Cold Carcass Weight (CCW), Hot Carcass Yield (HCY) and Cold Carcass Yield (CCY), and larger myofibrillar cross-sectional area (p < 0.05), indicating enhanced musculature, which was observed in Nellore. Deccani showed elevated Intramuscular Fat (IMF) deposition (p < 0.05), indicating improved meat flavour/juiciness. Transcriptomic profiling revealed several Differentially Expressed Genes (DEGs) associated with meat quality and quantity traits. In Nellore, the genes WFIKKN2, FGFRL1, FKBP4, and IRF1 were upregulated, while the gene TAS1R2 was downregulated, leading to enhanced muscle development, superior carcass traits, thermotolerance, and immunity. While Deccani showed higher expression of lipid metabolism genes PLA2G4F, ACSL1, ACOX1, CPT1A, and PLIN1, which are linked to higher IMF content. Functional enrichment analysis revealed 46 significantly enriched GO terms for the DEGs (p < 0.05), including oxidoreductase activity, muscle development, etc. These outcomes demonstrate novel genetic markers and key biological insights into the regulation of muscle development, thermotolerance, immunity, and IMF for future validation in Indian sheep breeds. Full article

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, classically characterized by right ventricular outflow tract obstruction, ventricular septal defect, overriding aorta, and right ventricular hypertrophy. Recent advances in molecular and genomic research indicate that TOF is part of a phenotypic continuum encompassing Trilogy, Tetralogy, and Pentalogy of Fallot, in which the variability of anatomical presentation reflects shared genetic and epigenetic mechanisms with highly variable penetrance and expressivity. Variants in NOTCH1, FLT4, KDR, GATA6, and TBX1 highlight key pathways in conotruncal development and endothelial–mesenchymal transition, yet these well-known genes explain only a fraction of the genetic landscape. Emerging studies have identified additional candidate genes and networks involved in cardiac morphogenesis, including transcriptional regulators, signaling mediators, chromatin-remodeling factors, and splicing-associated genes such as PUF60 and DVL3. Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNA expression, further modulate phenotypic expressivity and contribute to variability along the Trilogy–Tetralogy–Pentalogy spectrum. This review integrates current genomic and clinical evidence to provide a comprehensive overview of the molecular architecture of Fallot-type conotruncal malformations, emphasizing the interplay between genetic and epigenetic mechanisms, genotype–phenotype correlations, and implications for diagnosis, risk stratification, counseling, and personalized management in the era of precision cardiology. Full article

The development of next-generation HIV-1 therapeutics, including ultralong-acting antivirals, novel mechanistic classes, and curative immunotherapies, promises to overcome the limitations of lifelong, daily antiretroviral therapy (ART). However, the real-world efficacy of these treatments depends on the complex epidemiological landscapes in which they are used. In South America, HIV-1 epidemics intersect hyperendemic arboviruses, including dengue, Zika, chikungunya, and yellow fever, and regionally isolated pathogens, such as mammarenaviruses. These co-infections cause profound episodic immune activation and organ dysfunction that alter drug pharmacokinetics, disrupting healthcare access and adherence. These factors can compromise ART efficacy, promote resistance, and influence latent reservoir dynamics. This review synthesizes clinical and translational evidence of this intersection. We evaluate how emergent agents, such as capsid inhibitors (lenacapavir), long-acting injectables (cabotegravir/rilpivirine), maturation inhibitors (GSK3640254), and broadly neutralizing antibodies (bNAbs), perform in the context of co-endemic viral challenges. Specifically, we argue that therapeutic development must become “co-infection-aware” to progress toward a cure and achieve durable HIV-1 control. We provide a translational roadmap that explicitly incorporates co-infection endpoints into clinical trials, develops preclinical models that better reflect real-world viral exposures, and prioritizes implementation strategies that remain effective in the case of recurrent outbreaks. Integrating regional viral ecology into HIV-1 therapeutic research is therefore a necessary step toward developing interventions that are durable and effective on a global scale. Full article

Since land use considerably affects the spatial variation of PM_2.5 levels, it is crucial to predict PM_2.5 concentrations under future land use changes. However, prior research has primarily concentrated on meteorological factors influencing PM_2.5 predictions, while neglecting the effect of land use configurations. Consequently, in our study, a novel Patch-generating Land Use Simulation–Land Use Regression (PLUS-LUR) method was developed by integrating the PLUS model’s dynamic prediction capability with the LUR model’s spatial interpretation strength. The incorporation of landscape indices as key variables was essential for predicting PM_2.5 concentrations. First, the random forest-optimized LUR method was trained with PM_2.5 datasets from the Pearl River Delta (PRD) monitoring stations and multi-source spatial datasets. We assessed the modeling accuracy with and without considering landscape indices using the test dataset. Subsequently, the PLUS approach was applied to forecast land use as well as associated landscape indices in 2028. Based on these projections, grid-scale influencing factors were input into the previously constructed LUR model to forecast future PM_2.5 distributions at a grid scale. The results reveal a spatial pattern with higher PM_2.5 levels in central areas and lower levels in peripheral regions. Furthermore, the PM_2.5 concentrations in the PRD are all below the Grade II threshold of the China Ambient Air Quality Benchmark in 2028. Notably, the predictions incorporating landscape indices demonstrate higher accuracy and reliability compared to those excluding them. These results provide methodological support for future PM_2.5 assessment and land use management. Full article

Limitations associated with traditional automation approaches within manufacturing have driven the pursuit of more flexible and intelligent robot guidance methods. One promising development in this area is the integration of external multitarget six degrees of freedom (6 DoF) distributed large-volume metrology (DLVM) into the control loop. Although multiple standards exist across dimensional metrology, motion tracking, indoor positioning, robot guidance, and machine tool accuracy, there is no harmonised, technology-agnostic standard that fully encompasses the unique challenges of 6 DoF DLVM systems for dynamic applications. This work identifies key gaps in the current standards’ landscape and presents a technology-agnostic candidate test methodology intended to support future standardisation of dynamic DLVM performance evaluation. The method provides a metrologically grounded spatial reference path and a temporal alignment strategy so that position and orientation errors can be reported in the intrinsic coordinates of the path. The paper covers the basic principle of the test, artefact construction, synchronisation strategies, preliminary error modelling, and a baseline uncertainty approach, and reports representative results from initial prototype trials on a multi-nodal distance-camera DLVM system. The prototype results demonstrate feasibility and highlight temporal sampling and traceable timing as current limiting factors for fully deconvolving latency and pose error; these aspects are therefore positioned as instrumentation requirements and the focus of ongoing work. Full article

Successful escapes depend on many factors, including predator type and habitat characteristics. Examining escape usually entails directly pursuing an individual and then measuring flight initiation distance (FID), but the effect of prolonged pursuit has not been well studied. We examined escape sequences by blanched adult lesser earless lizards (Holbrookia maculata) in the Salt Basin Dunes (SBDs), testing the hypothesis that escape success and sequences would vary with sex and vegetation use. Their coloration is an adaptation to their sparsely vegetated white sand habitat. To evaluate escape behavior, we followed an individual directly until it disappeared (=successful escape), stopped moving, or 2 min elapsed. We recorded trial habitat (at the start and throughout), time to trial end, FID, length of moves, and total distance moved. FID varied with starting habitat—lizards beginning trials on exposed wood had the longest FID. The sexes differed in their move lengths: females made more short moves, while males made more long moves. The most important plant was sage (Artemisia filifolia), which was occupied at the start of 39% of trials, while 71% of trials ended in sage, and larger sage bushes supported longer escape sequences. Our study highlights the importance of vegetation for refuge and emphasizes the crucial role of the dune-plant landscape to lesser earless lizards. Full article

Hemostasis and thrombosis reflect a delicate balance, regulated by the interplay between procoagulant and anticoagulant mechanisms. Hemophilia is traditionally viewed as a bleeding disorder, but emerging evidence highlights the paradoxical risks of thrombosis in hemophilia patients. We explore the landscape of hemophilia management, emphasizing challenges of balancing hemostasis in the context of aging, novel non-factor replacement therapies (NRTs), and comorbidity-driven thrombotic complications. Therapeutic approaches, including innovative NRTs, such as emicizumab, or rebalancing agents (e.g., concizumab, marstacimab, fitusiran), offer promising advancements in bleeding prophylaxis but may increase thrombotic risks. Conversely, novel anticoagulants, such as FXI inhibitors, offer potential thrombosis protection with minimal bleeding risk. Our review examines the impact of aging-related comorbidities, including cardiovascular disease, atrial fibrillation, HIV-associated complications, and acute coronary syndromes, on thrombotic risk in hemophilia patients. Evidence-based strategies for balancing hemostasis and thrombosis are outlined alongside experimental models, thrombin generation assays, and advancements in rebalancing coagulation through natural anticoagulant modulation. FXI inhibition emerges as a paradigm shift in thrombosis management, offering reduced bleeding risks while preserving vascular health. Finally, this review highlights the need for global laboratory assays to personalize treatments, emphasizing strategies to optimize safety and efficacy, particularly as hemophilia patients live longer with complex comorbidity profiles. Full article

Metastatic urothelial carcinoma (mUC) is a lethal cancer with limited therapeutic options. Advances in genomic and transcriptomic research have deepened the understanding of mUC biology, leading to the identification of clinically relevant molecular alterations that represent potential actionable targets. This has broadened the treatment landscape of the disease to include novel agents, such as antibody–drug conjugates (e.g., enfortumab vedotin) and targeted therapies, including the pan-fibroblast growth factor receptor (FGFR) inhibitor erdafitinib. Genomic alterations in FGFR3 are well-established oncogenic drivers in bladder cancer and represent predictive biomarkers of response to FGFR-targeted therapies. The phase III THOR trial demonstrated the clinical benefit of erdafitinib in previously treated mUC patients harboring FGFR3 alterations and supported its subsequent approval by the European Medicines Agency. In this context, accurate molecular profiling is essential to guide patient selection for FGFR inhibitor therapy. Equally important is the standardization and timely implementation of FGFR3 testing in clinical practice to optimize treatment planning. This review addresses key considerations in FGFR3 testing in mUC and discusses how it can be routinely incorporated into clinical practice. Full article

The intensifying pressures of urbanization and climate change on coastal zones necessitate a holistic understanding of the interplay between human activity and ecological integrity for sustainable development. However, prevailing methods for assessing coastal vibrancy often overlook direct measures of human presence and fail to quantitatively capture its complex relationship with ecological vulnerability. To address these gaps, this study develops a novel multi-dimensional assessment framework for Coastal Landscape Vibrancy (CLV) and empirically examines its interaction with ecological vulnerability factors in Beihai, China. Moving beyond built-environment-centric approaches, our framework integrates the ‘Crowd’ dimension, directly quantified using Baidu Heat Index data, with the ‘Place’ dimension, characterized by urban features, natural attributes, and visual experience. Principal Component Analysis (PCA) was employed to objectively weight these indicators and construct a composite CLV index. We then applied multiple linear regression to analyze the influence of ecological factors constructed based on the Sensitivity-Resilience-Pressure (SRP) model. The results revealed that vibrancy was highly concentrated in urban cores and exhibited significant spatiotemporal variations. Regression analysis revealed that while ecological quality factors like green coverage (β = 0.236, p < 0.001) positively influenced vibrancy, anthropogenic stressors such as slope (β = −0.457, p < 0.001) and the impervious surface index (β = −0.092, p < 0.001) had significant negative impacts, highlighting a critical trade-off between human activity and ecological conditions. The findings provide a quantitative, evidence-based foundation for spatial planning, demonstrating that sustainable coastal vibrancy is achieved through a balanced integration of human activity and ecological conservation, rather than through unchecked development. This framework offers critical insights for formulating strategies that simultaneously enhance ecological resilience and optimize human service facilities. Full article

As a dominant typology of urban development and a critical component of public infrastructure, super high-rise buildings have transitioned from a speed-driven expansion model to one that emphasizes a balanced approach between development pace and quality. Within the context of urban stock renewal, numerous super high-rise buildings now face pressing needs for retrofitting to enhance their sustainability and urban integration. This study establishes “urbanity”—defined as the capacity of the built environment to foster vibrant, inclusive, and sustainable urban life—as a core evaluation criterion for assessing the retrofitting and renewal of super high-rise buildings. Based on a comprehensive literature review and field investigations, 21 representative indicators were identified, and the key factors influencing the upgrading of such buildings were determined. Subsequently, 20 super high-rise buildings in Shanghai were selected as case studies, and their urbanity performance was assessed using a fuzzy comprehensive evaluation model (FCEM). The findings reveal common challenges, including architectural homogenization, functional singularity, limited vitality in near-ground spaces, weak integration with surrounding infrastructure, and inefficient utilization of urban landscape resources. Furthermore, the study analyzes urbanity-oriented enhancement strategies implemented in the selected cases and proposes targeted improvement measures across five key dimensions: building morphology, functional configuration, near-ground space, infrastructure, and urban landscape. The research contributes to the body of knowledge on sustainable urban regeneration by providing a practical evaluation framework and actionable strategies for retrofitting super high-rise buildings. The findings aim to support more livable, inclusive, and resilient urban environments, with implications for both Chinese and global cities facing similar challenges in high-density urban contexts. Full article

Wildfire activity is intensifying under climate change, particularly in temperate East Asia where human-driven ignitions interact with extreme fire-weather conditions. This study examines wildfire risk during the March 2025 large wildfire event in Korea by applying explainable machine-learning models to assess ignition-prone environments and their spatial relationship with socio-environmental features relevant to exposure and management. CatBoost and LightGBM models were used to estimate wildfire susceptibility based on climatic, topographic, vegetation, and anthropogenic predictors, with SHAP analysis employed to interpret variable contributions. Both models showed strong predictive performance (CatBoost AUC = 0.910; LightGBM AUC = 0.907). Temperature, relative humidity, and wind speed emerged as the dominant climatic drivers, with ignition probability increasing under hot (>25 °C), dry (<25%), and windy (>6 m s⁻¹) conditions. Anthropogenic factors—including proximity to graves, mountain trails, forest roads, and contiguous coniferous stands (≥30 ha)—were consistently associated with elevated ignition likelihood, reflecting the role of human accessibility within pine-dominated landscapes. The socio-environmental overlay analysis further indicated that high-susceptibility zones were spatially aligned with arboreta, private commercial forests, and campsites, highlighting areas where ignition-prone environments coincide with active human use and forest management. These results suggest that wildfire risk in Korea is shaped by the spatial concurrence of climatic extremes, fuel continuity, and socio-environmental exposure. By situating explainable susceptibility modeling within an event-conditioned risk perspective, this study provides practical insights for identifying Wildfire Priority Management Areas (WPMAs) and supporting risk-informed prevention, preparedness, and spatial decision-making under ongoing climate change. Full article