Search Results (113,476)

To address the challenges of homogenization and unclear functional hierarchy in pet water fountain design, as well as to meet diverse user needs, reduce costs, and improve efficiency, this study undertakes product design based on comprehensive research and analysis of key design elements that fulfill the practical requirements of both humans and pets. Furthermore, to evaluate and optimize the proposed design scheme, an integrated AHP-improved CRITIC-TOPSIS comprehensive design evaluation model is introduced within the framework of multi-criteria decision theory to assess and refine pet water fountain design solutions. The methodology commences with the application of the AHP to construct a multi-level evaluation index system and determine subjective weights for each index. Subsequently, the improved CRITIC method is integrated to calculate the comprehensive weights of each indicator. The TOPSIS method is then employed to rank and optimize the design schemes. Strategies for further improvement are proposed based on key indicators that are assigned higher weights. The results of the simulation verification experiment and sensitivity analysis indicate that the proposed method achieves high accuracy and reliability in the evaluation of pet water fountain designs. This methodology establishes a rigorous evaluation framework that can be extended to other pet product designs. Full article

Throughout the long history of human development, a large number of activity relics have been left on the earth, among which settlements are important carriers for studying human construction activities. In the era without modern active environmental control technology, humans used their experience to create the miracle of harmonious coexistence between humans and nature. Especially in the construction of settlements under complex environmental stress, it is the crystallization of human wisdom. For China, the settlements of ethnic minorities, due to their unique culture and harsh living environment, are undoubtedly key objects for studying the wisdom of human settlement construction. Therefore, this study takes the Tujia rural settlements in the mountainous environment of northeastern Sichuan as the research object and uses the spatial analysis function of ArcGIS to construct a complete “culture-space” environmental adaptation wisdom research system. The research results show that there is a close relationship between the cultural wisdom and spatial construction wisdom of the Tujia people in northeastern Sichuan. Cultural wisdom plays a key role in guiding settlements to adapt to terrain, water resources, and climate, etc., thus presenting a highly coordinated mechanism between the overall distribution of Tujia rural settlements in northeastern Sichuan and the construction of settlement space and the environment. The “culture-space” environmental adaptation research framework proposed in this study can provide a reference for the study of rural settlement space worldwide, and the clear settlement environmental adaptation strategies in the research can provide guidance for the construction of modern mountainous town spaces. Full article

Alpha-1 antitrypsin deficiency (AATD) is an inherited disorder characterized by intracellular retention of mutant Z (Pi*Z) alpha-1 antitrypsin (AAT) within hepatocytes, resulting in progressive liver disease. Currently, no approved pharmacological therapies exist for AATD-associated hepatic injury. Emerging preclinical evidence indicates that inhibition of mammalian target of rapamycin (mTOR) ameliorates liver pathology in AATD; however, the status of mTOR activity and its regulatory mechanisms under Pi*Z AAT-induced cellular stress remains incompletely understood. In this study, we investigated alterations in mTOR signaling and its upstream regulatory pathways using a gene-edited human hepatocyte model harboring the Pi*Z mutation (Huh7.5Z cells) and a Pi*Z AAT transgenic mouse model. Attenuation of mTORC1 activity was observed in both cellular and murine Pi*Z models. In vitro analyses demonstrated activation of AMP-activated protein kinase (AMPKα), a key inhibitory regulator of mTORC1, accompanied by paradoxical activation of Akt and the unfolded protein response (UPR) branch ATF6α. Pharmacological inhibition of mTOR significantly reduced intracellular Pi*Z AAT accumulation, alleviated ER stress, and suppressed apoptotic signaling through enhancement of autophagy. These findings reveal that hepatocytes adapt to Pi*Z AAT-induced stress through coordinated regulation of mTOR by AMPK, Akt, and ATF6α pathways. This study provides mechanistic insight into metabolic and stress-response signaling in AATD and identifies mTOR modulation as a promising therapeutic strategy for AATD-associated liver disease. Full article

Spatiotemporal heterogeneity of land-use multifunction (LUMF) is crucial for the preservation and management of large-scale national cultural parks in alleviating potential human-land conflicts. Using 28 multidimensional indicators across economic, social, and environmental dimensions, this study established an LUMF index system for the Long March National Cultural Park of China (CLMNCP). LUMF values for 77 prefecture-level cities were quantified from 2008 to 2023, and their spatiotemporal heterogeneity was examined using a spatial autocorrelation model. Subsequently, the Optimal Parameters-based GeoDetector (OPGD) model was applied to identify key driving factors. The main findings are as follows: (1) From 2008 to 2023, the total, economic (EF), social (SF), and environmental (EnF) functions in the CLMNCP exhibited a consistent upward trend. (2) Significant spatial heterogeneity characterized the trade-offs and synergies among these functions. The EF-EnF interaction displayed a concave synergistic relationship, while the EF-SF and SF-EnF interactions showed convex, fluctuating patterns during their transitions between trade-off and synergy. (3) The primary drivers varied across function pairs. The EF-SF synergy was predominantly influenced by agricultural production, resource supply, and cultural service factors. The EF-EnF interaction was mainly shaped by natural conditions and environmental improvement factors. In contrast, the SF-EnF interaction was primarily driven by economic development, cultural services, and resource supply. These findings support functional zoning and targeted management of large-scale national cultural park to balance development and conservation while reducing human-land conflicts. Full article

Objective: The integration of artificial intelligence (AI) into computer-aided detection (CAD) is a major innovation in lung cancer diagnosis. However, its reliability in detecting the earliest radiographic sign—faint ground-glass opacities (GGOs) indicating pre-invasive adenocarcinoma—remains a critical, unquantified gap. This study aimed to perform a rigorous failure analysis to define the specific conditions under which commercial AI/CAD systems fail in a low-dose CT (LDCT) screening setting. Methods: In this retrospective diagnostic accuracy study, a primary cohort of 100 patients and an external validation cohort of 50 patients with moderate/low-risk nodules on LDCT were included. An expert reference standard was established by a consensus panel of three thoracic radiologists. Two independent, commercially deployed AI/CAD systems from different vendors (Vendor A & Vendor B) processed all cases. Nodules confirmed by experts but missed by AI were analyzed. Their morphology was categorized, and their mean CT attenuation (HU) was measured via manual region-of-interest placement. Results: The AI systems demonstrated significant and comparable false negative rates in the combined cohort: 12.7% for Vendor A and 14.7% for Vendor B. The vast majority of missed nodules were GGOs (92.3% and 78.6%, respectively, in the primary cohort). Crucially, quantitative analysis revealed a consistent density threshold for AI failure: the mean CT value of missed GGOs was −737 ± 51.50 HU for Vendor A and −727 ± 70.07 HU for Vendor B. This algorithmic blind spot was fully corroborated by the external validation cohort (−741 ± 48.2 HU and −733 ± 62.5 HU, respectively). Anatomical complexity (juxta-pleural/endobronchial location) was a secondary failure factor. Conclusions: This study identifies a quantifiable “−730 HU blind spot” as a common limitation of current commercial AI/CAD systems in diagnosing early lung adenocarcinoma. This finding represents a pivotal advancement in understanding AI’s role in diagnostics: it is not infallible. To innovate and safeguard screening efficacy, radiologists must adopt a human–AI collaborative model with mandated manual verification targeting low-attenuation opacities, ensuring this diagnostic innovation fulfills its promise while mitigating the risks of overdiagnosis. Full article

Human respiratory syncytial virus (RSV) is the predominant etiological agent responsible for lower respiratory tract infections in young children. Recurrent infections throughout an individual’s lifespan can lead to significant morbidity, particularly in the elderly and in adults, influencing the trends of hospitalization rates. Consequently, it is imperative to develop technologies that can sanitize environments from this pathogen while being compatible with human presence. Structure Resonant Energy Transfer (SRET) is the scientific principle underlying a sanitization technology that has demonstrated efficacy against several enveloped viruses, including SARS-CoV-2 and Influenza A viruses. SRET employs specific frequencies of electromagnetic waves to effectively disrupt the structural integrity of viral envelopes through dipole coupling. This disruption leads to the inactivation of the virus, rendering it non-infectious. The objective of this study is to analyse the effect of a specific SRET sanitization method on RSV. The sanitization test was conducted in aerosol form within a BSL-3 laboratory, exploring the frequency band from 8 to 16 GHz. An optimal sub-band was identified, giving an inactivation efficiency up to 99.5%. In conclusion, it has been demonstrated that the microwave non-thermal sanitization method is effective against RSV. These results confirm its potential as a viable approach for environmental decontamination. Full article

Under global climate change, analyzing carbon storage dynamics and their drivers is essential for understanding regional carbon sink capacity. Human activities and land-use change have substantially affected regional carbon storage. However, in China, most existing studies emphasize specific driving pathways, and integrated analyses of the combined effects of climate, natural, human, and landscape factors remain limited. This study aims at clarifying the integrated mechanisms by which multiple driving factors influence regional carbon storage. The InVEST model was used to analyze the carbon storage spatiotemporal changes. OPGD was then applied to evaluate the explanatory power of driving factors and their interactions, quantifying their contributions to carbon storage spatial patterns. Based on PLS-SEM, the direct and indirect effects of LULC, climate, natural, human, and landscape factors were quantified to elucidate the driving pathways of carbon storage. This study focuses on Shaanxi Province, which is a key ecological restoration region in the core area of the Loess Plateau. The main results are as follows: (1) From 2000 to 2020, carbon storage in Shaanxi Province showed a continuous increasing trend, rising from 2.97 × 10¹⁰ Mg C to 3.03 × 10¹⁰ Mg C. (2) LULC was identified as the most important direct and predominantly negative driving factor of carbon storage. (3) Natural factors had a strong positive influence on carbon storage, among which slope and NDVI exhibited the highest explanatory power; in contrast, climate factors showed weaker but still positive effects. (4) Human activities affected carbon storage through both direct and indirect pathways associated with LULC, with positive effects driven by landscape factors and negative effects driven by natural factors, while climate factors exhibited mixed but weak effects. Overall, carbon storage dynamics in Shaanxi Province reflect a hierarchical and path-dependent process shaped by the combined effects of natural constraints, human activities, and policy guidance through LULC pathways, providing important evidence for systematically understanding the driving structure and pathways of regional carbon storage. These findings highlight the importance of aligning land-use policies with regional biophysical constraints to enhance carbon sequestration efficiency. Full article

Wildfires are a major natural hazard causing extensive ecological damage and endangering human survival. Previous studies on wildfires in China have mostly focused on specific regions or individual drivers, with limited systematic assessments at the long-term and national scales. The spatiotemporal patterns of wildfires and their multiple driving mechanisms under China’s diverse climatic regimes remain insufficiently understood. To bridge this gap, we combined MCD64A1 burned area data (2001–2023) with multi-source natural (meteorological, vegetation, and topographic) and anthropogenic factors, using random forest models at both the national and regional scales to examine the spatiotemporal patterns, dominant drivers, and response mechanisms of wildfires in China. The results revealed that: (1) Spatially, wildfires were concentrated in northeastern and southern China, which accounted for 86.20% of the total burned area. Temporally, northern wildfires were primarily a spring-dominated fire regime, with peak activity in March and April, whereas southern wildfires were winter-dominated, peaking in February. (2) At the national scale, elevation was the key topographic factor influencing wildfire occurrence (relative importance = 0.49), with low-elevation and gentle-slope areas being more fire-prone. At the regional scale, the driving factors exhibit spatial differentiation, forming a spatial pattern of topography-dominated and climate-dominated. (3) Partial dependence plot analysis revealed nonlinear and threshold responses. Fire probability increases rapidly when the soil moisture is below 20 mm, while extremely high land surface temperatures in arid regions suppress fire occurrence due to fuel limitations. This study enhances the understanding of spatially heterogeneous wildfire drivers in China and provides a scientific basis for region-specific wildfire prevention and management strategies. Full article

Over the past decade, road safety research has experienced rapid development due to the rapid expansion of large crash databases, the adoption of artificial intelligence techniques, and the demand for proactive and predictive safety solutions. This study conducts a data-driven review of recent research trends in transport safety. It focuses on main domains including crash severity analysis, human factors, vulnerable road users (VRUs), spatial modeling, and artificial intelligence applications. A systematic search of the Scopus database identified 15,599 relevant scientific papers published between 2016 and 2025. After constructing this corpus, titles, abstracts, and keywords were preprocessed using a natural language pipeline. The analysis employed BERTopic, a transformer-based topic modeling framework. The analysis identified 29 distinct research topics, further synthesized into five major thematic areas: (1) crash severity and injury analysis, (2) driver behavior and human factors, (3) vulnerable road users, (4) artificial intelligence, machine learning, and computer vision in intelligent transportation systems, and (5) spatial analysis and hotspot detection. A notable increase in publications related to artificial intelligence and machine learning has been evident since 2020. The results show a transition from descriptive, post-crash studies to integrated, multimodal, predictive analysis. Overall, the findings reveal a paradigm shift in the field. This study also identifies ethical and economic issues associated with the use of artificial intelligence in intelligent transportation systems, including data management, infrastructure requirements, system security, and model transparency. The results signify a transition from intuition-based models to explainable, spatially explicit, and data-intensive models, ultimately facilitating proactive risk assessment and informed decision-making. Full article

Background/Objectives: Antimicrobial agents have revolutionized disease management in humans and animals; however, their misuse and overuse have accelerated the emergence and spread of antimicrobial resistance (AMR) and antimicrobial resistance genes (ARGs). Dairy farms are recognized as potential hotspots for ARG dissemination, particularly through Escherichia coli, which acts as a reservoir and vector of ARGs, enabling their horizontal transfer via plasmids and other mobile genetic elements. This study aimed to characterize the genomic diversity, ARG profiles, plasmid content, and phylogenetic relationships of E. coli isolated from dairy farm environments and milk using whole-genome sequencing. Methods: A total of 31 E. coli isolates recovered from soil, effluent, cow dung, and milk samples underwent deoxyribonucleic acid extraction, library preparation, and sequencing on the Illumina MiSeq platform, followed by comprehensive bioinformatic analysis. Results: The E. coli isolates exhibited 20 distinct sequence types, including one novel sequence type. Plasmids were detected in 71% of the isolates, with the IncF plasmid family being the most predominant. Furthermore, 12 ARG groups were identified, with β-lactam resistance genes detected in 67.7% of isolates. Notably, blaCTX-M genes were identified in all phenotypically confirmed extended-spectrum β-lactamase-producing isolates. Additional ARGs, including those conferring resistance to tetracyclines (tet(A), tetX4), quinolones (qnrS1), aminoglycosides (aph, aad, ant), and folate pathway inhibitors (dfr and sul), were widely distributed throughout the samples. Phylogenetic analysis revealed clustering of isolates from different sample types, particularly among ST58 isolates, suggesting cross-environmental transmission. Conclusions: This study demonstrates that E. coli from dairy farm environments harbor diverse ARGs and plasmids, confirming their role as reservoirs of AMR. These findings underscore the importance of prudent antimicrobial use, routine genomic surveillance, and enhanced biosecurity measures to limit cross-environmental transmission. Full article

Excessive macrophage activation is thought to be the primary cause of the cytokine storm that results in severe coronavirus disease 2019 (COVID-19) complications. The underlying mechanisms remain elusive, and more research is needed to find disease-critical genes and develop effective therapies. In this study, we used publicly accessible microarray datasets of cytokine storm in cultured human monocyte-derived macrophages challenged with cytokines, and employed bioinformatics, such as weighted gene co-expression network analysis (WGCNA) and differential expression analysis, to dissect gene expression profiles and identify putative disease-related molecules. Initially, three co-expression modules and related key genes were discovered, which highly correlated to macrophages challenged with cytokines. Then, a preliminary gene expression signature consisting of 203 upregulated and 24 downregulated genes was identified. Next, protein–protein interaction analysis and hub gene identification were used to identify 11 crucial hub genes, namely tripartite motif-containing 21 (TRIM21), interferon regulatory factor 1 (IRF1), guanylate binding protein 1 (GBP1), transporter associated with antigen processing 1 (TAP1), nuclear myosin I (NMI), interleukin 15 receptor subunit alpha (IL15RA), apolipoprotein L1 (APOL1), intercellular adhesion molecule 1 (ICAM-1), protein tyrosine phosphatase non-receptor type 1 (PTPN1), E74-like ETS transcription factor 4 (ELF4) and guanylate binding protein 2 (GBP2). Then, the LINCS L1000 characteristic direction signatures search engine (L1000CDS2) was employed for drug repurposing studies. Dasatinib was predicted to be the leading therapeutic compound to perturb the gene signature of cytokine storm in human macrophages. Connectivity Map results suggested that dasatinib may normalize ICAM-1 expression. In addition, the results of molecular docking studies and molecular dynamics simulation revealed that dasatinib may spontaneously interact with ICAM-1 via several key residues and form a relatively stable protein–ligand complex. Overall, this work, based on an analysis of co-expression correlation networks, gene expression signatures and pivotal genes in human macrophages challenged with cytokines, combined with drug repurposing studies, demonstrated that dasatinib may interact with ICAM-1 and could be a potential candidate for cytokine storm. However, due to the limitations of computational approaches, further experimental validation is necessary. Full article

This study presents a comprehensive 35-year (1990–2025) shoreline change assessment along the southeast coast of Ireland, integrating multi-decadal Landsat satellite archives with GIS-based Digital Shoreline Analysis System (DSAS) metrics to quantify both spatial and temporal coastal dynamics. Unlike previous studies that focus on shorter timeframes or localized sectors, this research provides a regional-scale, orientation-specific comparison between the eastern-facing (SE1; County Wexford) and southern-facing (SE2; County Waterford) shorelines. Shoreline evolution was quantified using four complementary DSAS indicators—Shoreline Change Envelope (SCE), Net Shoreline Movement (NSM), End Point Rate (EPR), and Linear Regression Rate (LRR), allowing robust discrimination between short-term variability and multi-decadal trends. The results reveal noticeable spatial variability in shoreline behavior with 57% accretion and 42% erosion across the eastern-facing coast (SE1) in County Wexford and the southern-facing coast (SE2) in County Waterford. SCE values ranging from 2.26 m to 663.83 m indicate considerable short-term shoreline variability, particularly within dynamic barrier and embayed systems. NSM values between −216.65 m and +663.83 m indicate erosional hotspots, particularly along soft-sediment coasts and exposed southern-facing sectors, whereas accretion is limited to embayments, sandy beaches, and zones of effective sediment trapping. Rate-based analyses show EPR values between −14.82 and +20.38 m/yr and LRR values between −5.27 and +20 m/yr, with LRR providing more reliable estimates of multi-decadal trends in highly dynamic environments. The findings highlight the strong influence of coastal orientation, sediment availability, geological controls, and human activities on shoreline change in southeastern Ireland. These findings provide valuable evidence to support coastal management, hazard mitigation, and climate adaptation planning, with the assistance of policymakers, to develop effective strategies that enhance the resilience and quality of life of coastal communities. Full article

Background: Highly pathogenic avian influenza H5N1 viruses of clade 2.3.4.4b have spread globally since 2021, causing extensive outbreaks in avian populations and repeated spillovers into diverse mammalian hosts, including humans. These cross-species transmission events highlight ongoing pandemic risks and underscore the need for vaccine strategies that reflect viral evolution at the human–animal interface. Despite the availability of licensed H5 vaccines and newly recommended World Health Organization (WHO) candidate vaccine viruses (CVVs), the extent to which these vaccines elicit cross-reactive antibody responses against contemporary clade 2.3.4.4b viruses, including mammalian spillover isolates of avian origin, remains incompletely characterized. Method: In this study, ferret antisera were generated using four WHO-recommended H5 CVVs, including a clade 1 strain (A/Vietnam/1194/2004) and three clade 2.3.4.4b strains (A/Astrakhan/3212/2020, A/American wigeon/South Carolina/22-000345-001/2021, and A/Ezo red fox/Hokkaido/1/2022), formulated with alum adjuvant to reflect licensed vaccine formulation used in national preparedness programs. Antibody responses and cross-reactive activity were evaluated using hemagglutination inhibition (HI) and microneutralization (MN) assays against homologous vaccine strains and a feline-origin clade 2.3.4.4b H5N1 field isolate from Korea, A/Feline/Korea/SNU-01/2023. Results: Antisera induced by clade 2.3.4.4b CVVs showed cross-reactive antibody responses against homologous and heterologous clade 2.3.4.4b viruses and demonstrated measurable HI and MN responses against the feline-origin field isolate. In contrast, antisera raised against the clade 1 Vietnam CVV exhibited limited cross-reactivity against clade 2.3.4.4b viruses. Overall, clade 2.3.4.4b CVVs generally showed higher antibody responses than the clade 1 vaccine strain across multiple panels. Conclusions: These findings provide descriptive insights into antigenic differences between clade 1 and clade 2.3.4.4b viruses and support the antigenic relevance of clade 2.3.4.4b CVVs for contemporary H5N1 strains. This study highlights the importance of ongoing antigenic evaluation to inform vaccine strain selection within a One Health framework. Full article

The Navel Orangeworm (Amyelois transitella Walker, 1863), a primary pest of nut crops native to North America, poses a significant potential threat to China’s agricultural biosecurity, yet its potential distribution dynamics under climate change remain unquantified. This study utilized the Biomod2 ensemble model platform to predict habitat suitability under current and future climate scenarios (SSP1-2.6 and SSP5-8.5). We evaluated the prediction accuracy of the ensemble model using calibration data, with TSS = 0.898 and AUC = 0.978, while spatially stratified cross-validation confirmed moderate spatial transferability to novel environments (median validation AUC = 0.60–0.75). The model identified thermal factors—Temperature Seasonality (Bio4) and the Mean Temperature of the Wettest Quarter (Bio8)—as the dominant drivers of distribution. While currently climatically suitable habitats are primarily confined to the tropical and subtropical regions of southern China, projections indicate a complex spatial shift driven by future warming: optimal southern habitats will undergo a net contraction due to heat stress, whereas low and moderately suitable areas will expand northward into key temperate agricultural areas. These results highlight that climate change will substantially alter the spatial topology of the pest’s climatic envelope, providing a critical scientific baseline of climatic suitability. These projections do not equate to realized invasion risk, which is further constrained by host availability, land use, irrigation, and human transport, offering a conservative framework for prioritizing early surveillance and optimizing quarantine measures. Full article

Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) has emerged as a biologically distinct entity, typically affecting younger, non-smoking patients and showing improved survival compared to HPV-negative tumors. Accurate HPV status determination is essential for correct staging, prognostic assessment, and treatment de-escalation. Despite advances, substantial variability persists among diagnostic methods and clinical workflows. A narrative review of PubMed, Scopus, and Web of Science databases was conducted up to July 2025. Studies addressing HPV detection techniques in OPSCC—including p16^INK4a^ immunohistochemistry (IHC), HPV DNA and RNA assays, liquid biopsy approaches, and computational surrogates—were critically analyzed regarding diagnostic accuracy, clinical applicability, and emerging innovations. Tissue-based assays remain the diagnostic reference standard. p16 IHC provides high sensitivity but limited specificity and should be confirmed with nucleic acid-based methods such as DNA PCR, in situ hybridization (ISH), or E6/E7 mRNA detection. Combined or “orthogonal” testing minimizes discordance and refines risk stratification. Liquid biopsy detection of circulating HPV DNA using droplet digital PCR or next-generation sequencing has shown high sensitivity and specificity in cohorts of patients with HPV-associated OPSCC, supporting its potential role as a complementary biomarker for treatment monitoring and surveillance. However, circulating HPV DNA alone does not unequivocally identify the anatomic source of HPV DNA and should be interpreted together with clinical, radiologic, and tissue-based findings. Oral rinse and saliva assays show moderate diagnostic performance, while artificial intelligence-based radiomic and histopathologic models are emerging as complementary tools. Reliable HPV attribution in OPSCC requires a multimodal diagnostic strategy integrating p16 IHC, molecular confirmation, and ctHPV-DNA monitoring. Methodological standardization and prospective validation are essential to implement precision-guided, cost-effective workflows in routine clinical practice. Full article