Search Results (1,730)

With the rapid development of the social economy, island ecosystem services (ESs) are facing increasingly severe disruptions from human activities. This study constructs an integrated analytical framework of spatiotemporal changes–driving mechanisms–trade-offs/synergies. It aims to support regional sustainability by assessing the spatiotemporal patterns of ESs in the Zhoushan Archipelago, identifying key ecological functional zones and areas with high trade-offs and synergies, in order to formulate management strategies for long-term ecological balance. The results indicate that all four ESs in the Zhoushan Archipelago exhibited declining trends from 2000 to 2020. Spatially, these four ESs collectively exhibit a distribution pattern characterized by higher values in the south and lower values in the north. The cold spot and hot spot analysis results indicate that both the significant cold spot areas and significant hot spot areas have expanded, with noticeable changes occurring on Zhoushan Island, Daishan Island, and Liuheng Island. Based on these spatiotemporal variation characteristics, ecological functional zoning was conducted. The results show that the area of ecologically vulnerable zones has significantly increased, while the area of other functional zones has decreased. Driving factor analysis reveals that the land use/land cover, annual average precipitation, digital elevation model, slope, and normalized difference vegetation index have the most significant impact on the spatial heterogeneity of ESs. Furthermore, trade-off/synergy analysis among ESs was conducted. Spatially, high-trade-off areas are primarily located in central Zhoushan Island, Liuheng Island, Jintang Island, Daishan Island, and Sijiao Island. High-synergy areas are mainly distributed in northern Zhoushan Island, Qushan Island, Taohua Island, and the Ma’an Archipelago. These findings provide a scientific basis for the ecological conservation and restoration of the Zhoushan Archipelago, offering significant reference value for promoting sustainable development in island regions. Full article

Morchella is a nutritious and artificially cultivable rare ascomycete, and its growth and development regulation mechanisms are a current research hotspot. High-temperature stress severely limits the annual yield of Morchella, and this challenge is intensifying with global warming. However, previous studies have lacked systematic screening for heat-tolerant Morchella strains, and their molecular response mechanisms to heat stress remain unclear. In this study, we conducted a comprehensive analysis of phenotypic characteristics, physiological metabolism, and transcriptomics on 19 Morchella strains under normal (25 °C) and high-temperature (30 °C) conditions. The heat-tolerant strain HLM exhibited superior performance in mycelial growth, morphology, and field cultivation. It maintained cell homeostasis under heat stress through mild osmotic regulation (elevated levels of proline, soluble sugars, and proteins), a robust antioxidant system (increased activities of CAT, POD, and SOD), and reduced malondialdehyde accumulation. Transcriptomic analysis identified a novel regulatory model of “stress perception—metabolic preparation—terminal detoxification” in the heat-tolerant strain HLM under heat stress. The rapid upregulation of the SMPD1 gene may mediate ceramide signal generation, promoting G6PDH expression to drive carbon flow into the pentose phosphate pathway, thereby increasing NADPH output. As the detoxification terminal, AKR4C uses this reducing power to eliminate toxic carbonyl end products like malondialdehyde, completing the defense loop. These findings offer new insights into the heat-tolerance mechanisms of large ascomycetes, provide a theoretical foundation for stress-resistant Morchella breeding and cultivation in high-temperature areas, and serve as valuable resources for exploring heat-tolerance mechanisms and molecular breeding in other edible fungi. Full article

This study quantifies the effect of air and fuel filter restriction on fuel consumption, regulated pollutants (CO and HC), and CO₂ greenhouse gas emissions under real driving conditions in a hilly high-altitude environment. Four filter configurations were evaluated: clean air filter–clean fuel filter (CAF–CFF, reference), dirty air filter–clean fuel filter (DAF–CFF), clean air filter–dirty fuel filter (CAF–DFF), and dirty air filter–dirty fuel filter (DAF–DFF). Each test was repeated three times over the same RDE route in Quito (≈2100–2900 m). Fuel consumption was estimated from ECU-based signals, and CO₂ emission factors and regulated pollutant (CO and HC) emission factors were computed from measured exhaust concentrations and distance normalization. Results were analyzed by RDE section (urban, rural, motorway) and expressed as percent changes relative to the reference configuration to directly isolate filter restriction effects. Relative to CAF–CFF, DAF–CFF produced the largest increase in average fuel consumption (+7.2%) and the largest urban CO₂ penalty (+22.7%), indicating a strong efficiency sensitivity to intake restriction under transient operation. CAF–DFF increased average fuel consumption by 6% and produced the strongest motorway penalties for CO (+77.3%) and HC (+44.4%), suggesting that fuel delivery restriction has a stronger influence on incomplete oxidation products under sustained higher load. The combined restriction (DAF–DFF) showed non-additive responses depending on the operating regime. Random Forest models were trained to estimate CO₂, CO, and HC, achieving R² values of 0.8571, 0.8229, and 0.7690, respectively, while multiple linear regression achieved an R² of 0.852 for fuel consumption. The proposed approach supports data-driven monitoring of filter restriction effects under real driving operation, while acknowledging that fuel consumption and CO₂ are obtained through different measurement and conversion paths and may not yield identical percent changes. Full article

The spatial distribution patterns and temporal evolution of ancient designed gardens provide critical insights into the interactive dynamics among regional human–environment relationships, institutional structures, and cultural transmission. Taking 420 ancient garden sites on Hainan Island from the Tang to Qing dynasties (618–1911 AD) as the study objects, this research constructs a spatial database based on historical documents and local gazetteers. It further applies kernel density analysis, spatial overlay, and administrative hierarchy normalization to investigate their spatiotemporal distribution patterns and evolution mechanisms. The results reveal that: (1) natural geographical constraints serve as the fundamental boundaries defining the spatial differentiation; (2) transport corridors serve as the structural curve directing the spatial expansion; (3) the administrative hierarchy serves as institutions shaping the distribution of garden types and the spatial stratification; (4) social and cultural factors serve as the endogenous driving force for the continuous evolution of the spatial distribution. The evolution mechanism implies an analytical framework, i.e., “natural geographical constraints, the organization of transportation corridors, the influence of administrative hierarchies, and the dynamics of socio-cultural diffusion”, offering a transferable approach for studying historical cultural landscapes in island and peripheral regions. Full article

Iron ore tailings have been shown to promote the formation of soil aggregate cementing agents through weathering, thereby influencing soil aggregate formation in reclaimed land. However, their mechanism of action under different reclamation methods remains unclear. This study established a field station in the semi-arid region of Northern China to investigate three typical iron ore tailing reclamation methods, including topsoil blending type (DT), sublayer moisture conservation type (JT), and thick-layer tailings type (FT), with adjacent farmland as the control (CK). The analysis of soil organic carbon (SOC) components, soil inorganic carbon (SIC), iron/aluminum oxides, and aggregate composition and stability in the reclaimed soils revealed the evolution patterns of cementing materials and the potential mechanisms driving aggregate formation. The results indicate that the reclamation process promotes the weathering of tailings, with a significant increase in free iron oxide (Fed) content ranging from 19.09% to 41.93%. Iron oxides released from iron ore tailings influenced the reclaimed topsoil through plant litter return processes, resulting in a significantly higher amorphous iron oxide (Feo) content compared to CK. Additionally, the content of crystalline aluminum oxide (Alc) in the DT topsoil showed a significant increase, reaching 2.82 g/kg. The variation in organic and inorganic cementing agents significantly influences aggregate composition and stability, with soil particulate organic carbon (POC), crystalline iron oxide (Fec), Alc, and amorphous aluminum oxide (Alo) identified as the primary agents affecting aggregate formation (p < 0.05). After five years of reclamation, the proportion of DT macroaggregates (>0.25 mm) increased to 42.10%, and both the mean weight diameter (MWD) and the geometric mean diameter (GMD) increased significantly to 2.21 mm and 0.43 mm, respectively. In contrast, JT macroaggregates and microaggregates (0.053–0.25 mm) decreased to 26.88% and 29.01%, respectively, and aggregate stability significantly declined. FT macroaggregates and their stability showed no significant difference compared to CK. The study shows that after years of reclamation, both DT and FT reclamation methods have reached normal farmland levels in terms of aggregate formation and stability, making them practical and valuable reclamation solutions. Full article

Dynamic Wireless Power Transfer (DWPT) is emerging as critical smart city infrastructure for sustainable urban mobility, enabling electric vehicle charging while driving. However, DWPT introduces complex fault scenarios requiring intelligent monitoring. Existing fault diagnosis approaches for wireless power transfer systems face three key complexities: (1) they are limited to static charging with only 2–4 fault categories, failing to address the time-varying coupling dynamics and segmented coil handover transients inherent in dynamic charging; (2) they lack integration with the host distribution grid, ignoring grid-side disturbances that propagate to charging stations; and (3) they offer only reactive detection without predictive capability for incipient fault management. This paper presents a deep neural network (DNN)-based fault diagnosis framework utilizing multi-station sensor fusion for DWPT systems integrated with the IEEE 13-bus distribution network to address these limitations. The system monitors 36 sensor features across three charging stations, employing feature-level concatenation with station-specific normalization for multi-station fusion, achieving 97.85% classification accuracy across eight fault types. Unlike static charging, the framework explicitly models time-varying coupling dynamics due to vehicle motion, including segmented coil handover effects. A digital twin provides dual-horizon prediction: long-term forecasting (24–72 h) for incipient faults and real-time detection under 50 ms for critical protection, with fault probability outputs and ranked fault lists enabling actionable maintenance decisions. The DNN outperforms SVM (92.45%), Random Forest (94.82%), and LSTM (96.54%) with statistical significance ($p<0.001$), while maintaining model inference latency of 4.2 ms, suitable for edge deployment. Circuit-based analysis provides analytical justification for fault signatures, and practical parameter acquisition methods enable real-world implementation. Five case studies validate robustness across highway, urban, and grid disturbance scenarios with detection accuracies exceeding 95%. Full article

Insulin resistance in type 2 diabetes is associated with cardiovascular disease. Nutritional overload, hyperinsulinemia, and physical inactivity are the major etiological factors driving the development of insulin resistance. In an obesogenic environment, insulin resistance has been proposed to protect the body against toxic fuel overload, hyperinsulinemia-induced injury, and metabolic stress. Insulin resistance has been further hypothesized to defend the heart and blood vessels against fuel overload when an individual is chronically overeating. Recent landmark cardiovascular outcome trials in type 2 diabetes show major improvements in cardiovascular disease outcomes after treatment with GLP-1 receptor agonists or SGLT2 inhibitors. Bariatric surgery achieves even greater improvements in cardiovascular disease outcomes than treatments with these newer pharmacological agents. It had been previously predicted that glucose-lowering approaches that normalize whole-body energy balance have the greatest potential to improve cardiovascular outcomes in type 2 diabetes. This review hypothesizes that treatment with bariatric surgery, GLP-1 receptor agonists, or SGLT2 inhibitors lowers glucose and nutritional off-loading, normalizes whole-body energy balance, and reduces ectopic fat depositions. This plays a central role in the dramatic reduction in cardiovascular disease and the reversal of insulin resistance in type 2 diabetes, which are observed after these three treatments. Full article

Histones, normally confined to nucleosomes, are released into the bloodstream during sepsis due to cell damage and NETosis, contributing to organ dysfunction. In sepsis-associated encephalopathy (SAE), histones may worsen neurological outcomes. Using a cecal ligation and puncture (CLP)-induced polymicrobial sepsis model, we evaluated histone release, blood–brain barrier (BBB) disruption, complement activation, and glial responses in the brain. Immunofluorescence revealed histone accumulation and increased soluble histone levels in the brain 8–24 h post-CLP. BBB permeability increased, confirmed by FITC-inulin and Texas Red-dextran clearance assays. Complement activation, along with increased GFAP-positive astrocytes and Iba1-positive microglia, occurred post-CLP. Histones were detected in astrocytes and microglia. In vitro, stimulated astrocytes released histones upon activation and also demonstrated the ability to uptake extracellular FITC-labeled histones. Histone exposure elevated intracellular calcium levels and triggered cytokine secretion in astrocytes. Notably, histone stimulation activated the NLRP3 inflammasome, amplifying inflammation. These findings suggest that histone release during sepsis drives neuroinflammation, BBB disruption, and glial activation, positioning extracellular histones as potential therapeutic targets for sepsis-related brain manifestations like SAE. Full article

Triangular mesh surface representation is widely adopted in geometric design and reverse engineering applications. However, in high-precision Computer Numerical Control (CNC) machining, significant limitations persist in automated Computer-Aided Manufacturing (CAM) tool path generation for such representations. Conventional CAM workflows heavily rely on manual engineering interventions, such as creating drive surfaces or tuning extensive parameters—a dependency that becomes particularly acute for generic free-form models. To address this critical challenge, this paper proposes a novel end-to-end single-step end-milling tool path generation methodology for triangular mesh surfaces in high-precision five-axis CNC machining. The framework includes clustering analysis for optimal workpiece orientation, normal vector distribution analysis to identify shallow and steep regions, Graphics Processing Unit (GPU)-accelerated collision detection for feasible tool orientation domains, and iso-planar tool path generation with Traveling Salesman Problem (TSP) optimization for efficient tool lifting and movement. Experimental validation confirms the framework ensures machining quality and algorithmic robustness. Full article

T-cell lymphoblastic lymphoma (T-LBL) is an aggressive malignancy of immature T-cells accounting for a substantial proportion of pediatric non-Hodgkin lymphoma cases. Current chemotherapeutic regimens achieve five-year event-free survival rates of 80–90%, yet relapse occurs in approximately 20% of patients and remains a major therapeutic challenge. This underscores the need for improved, molecularly informed treatment strategies. Recent genomic profiling has highlighted the central role of NOTCH1 signaling in T-LBL pathogenesis. NOTCH1, a transmembrane receptor critical for T-cell differentiation and maturation, requires tightly regulated activation during normal thymocyte development. Dysregulated signaling disrupts this balance, driving aberrant proliferation and impaired differentiation, characteristics of malignant transformation. While activating mutations have long been recognized as key oncogenic events, the recent identification of recurrent NOTCH1 translocations, associated with adverse outcomes, reveals an additional mechanism of pathway activation. These findings reinforce NOTCH1 as a pivotal oncogenic hub in T-cell malignancies and a compelling target for therapeutic intervention. This review synthesizes current insights into the molecular landscape of pediatric T-LBL, with a focus on the biological and clinical implications of NOTCH1 mutations and translocations. Furthermore, we examine emerging approaches to therapeutically exploit aberrant NOTCH1 signaling for the more precise and effective treatment of this disease and formulate outstanding research questions. Full article

Decarbonization has emerged as a crucial objective in the optimization of port collection and distribution networks. To investigate the synergistic effects of carbon trading mechanisms and the implementation of electric autonomous container trucks (EACTs), this study develops a multi-objective bi-level programming model that simultaneously minimizes transportation cost, carbon trading cost, and transportation time. The model is solved using the Non-dominated Sorting Genetic Algorithm II (NSGA-II), generating a Pareto-optimal solution set, from which the optimal solution is selected using a normalized ideal point method. Simulation-based case studies validate the feasibility and practical applicability of the proposed model. The results show that the optimized network significantly outperforms the traditional road-dominant mode. Under the baseline carbon price of 70 CNY/ton, the optimal deployment rate of EACTs reaches 25.03% and 33.87%. Sensitivity analysis reveals a distinct non-linear threshold effect: increasing the carbon price to 90 CNY/ton drives the EACT adoption rate to 32.76% and 45.38%, resulting in a 6.98% reduction in carbon emissions and a 12.75% decrease in total operational costs compared to the baseline scenario. Additionally, strict carbon quotas (e.g., 3000 tons) are found to further compel a modal shift, peaking EACT usage at 35.08% and 46.71%. These quantitative findings offer actionable insights for optimizing multimodal transport structures and refining carbon trading policies. Full article

Post-inflammatory hyperpigmentation (PIH) is a common pigmentary disorder characterized by excessive melanin production following skin inflammation. Histamine, a key inflammatory mediator, is known to stimulate melanogenesis via H₂ receptors; however, the underlying calcium (Ca²⁺) signaling mechanisms remain largely unexplored. In this study, we investigated the role of the ORAI1-STIM1 complex in histamine-induced melanogenesis using B16F10 melanoma cells and normal human epidermal melanocytes (NHEMs). Histamine (10–30 μM) significantly increased melanin content (2.5–2.8-fold), an effect specifically abolished by the H₂ antagonist famotidine. Notably, while acute histamine application failed to trigger immediate Ca²⁺ influx, chronic exposure significantly enhanced store-operated Ca²⁺ entry (SOCE) capacity by approximately 2.8-fold, providing evidence for a functional remodeling of the Ca²⁺ signaling machinery. Histamine-induced melanogenesis was significantly suppressed by intracellular Ca²⁺ chelation, pharmacological inhibition of ORAI1 (BTP-2 or Synta-66), and siRNA-mediated silencing of ORAI1 or STIM1, but not ORAI2, ORAI3, or STIM2. Our findings demonstrate that chronic histamine exposure drives hyperpigmentation through ORAI1-STIM1-mediated SOCE remodeling, establishing this complex as a promising therapeutic target for the treatment of PIH and related inflammatory pigmentary disorders. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumours, driven by late diagnosis, early metastatic dissemination, and profound resistance to systemic therapies. Increasing evidence indicates that these hallmarks are not solely tumour cell intrinsic but are critically orchestrated by a complex and highly dynamic tumour microenvironment (TME) composed of pancreatic stellate cells (PSCs), cancer-associated fibroblast (CAF) subtypes, immune cells, endothelial and neuronal elements, and a dense extracellular matrix (ECM). This review provides an integrated overview of the cellular and acellular components of the PDAC TME and delineates how their reciprocal crosstalk drives desmoplasia, immune suppression, metabolic reprogramming, epithelial–mesenchymal transition (EMT), pre-metastatic niche formation, and metastatic outgrowth. Particular emphasis is placed on the context-dependent roles of stromal and immune niches in modulating drug delivery, chemoresistance, and failure of immunotherapy, highlighting why indiscriminate stromal depletion has yielded paradoxical outcomes. Building on these mechanistic insights, the review critically examines emerging therapeutic strategies targeting PSCs, CAF subsets, ECM components, myeloid and lymphoid populations, and key signalling pathways, including approaches that normalize stroma, reprogram immunity, or exploit nanocarrier-based delivery systems. Finally, a structured framework is proposed for rational TME-targeted combination regimens that integrate cytotoxic, targeted, and immunotherapeutic agents to overcome current therapeutic barriers in PDAC. Full article

With the increasing adoption of regenerative braking technology in electric vehicles (EVs), one-pedal driving (OPD) mode has become a prevalent feature. While OPD offers technical advantages in energy efficiency, its implications for driver behavior and traffic safety remain unclear. To address the lack of human factors research in this domain, this study utilized a driving simulator to systematically compare driving performance between OPD and two-pedal driving (TPD) modes. Twenty-six participants engaged in car-following tasks under varying traffic densities (uncongested vs. congested) and cognitive load levels (normal vs. 1-back). Driving performance and safety were quantified using the absolute speed difference, distance headway, braking frequency, and Time-to-Collision at brake onset (TTC_brake). The results revealed a significant trade-off: while OPD simplified operation, it led to compromised driving performance compared to TPD in specific contexts. Specifically, OPD resulted in larger speed variations and reduced safety margins during the approach stage. Conversely, under high cognitive load, OPD demonstrated a protective effect by mitigating performance degradation. These findings suggest that while OPD can benefit drivers under mental pressure, its deployment requires adaptive safety strategies, such as the integration of Headway Monitoring Warning (HMW) and Forward Collision Warning (FCW), to compensate for performance deficits in complex traffic environments. Full article

The tumor microenvironment (TME) plays a key role in driving tumor progression, metastasis, and resistance to therapy. The TME is a highly variable ecosystem composed of both cancer and surrounding normal cells, immune survey cells and the extracellular matrix, also composed of signaling molecules that mediate interactions between them. Blood cancer cells pose a unique challenge because of their circulation and widespread distribution along with their capacity to invade various niches, interacting with a wide range of host cells such as fibroblasts, immune cells, endothelial cells, and adipocytes. Metabolism reprogramming in this tumor context, notably referring to elevated cholesterol and fatty acid metabolism, emerges as a crucial event in shaping an immune-suppressive microenvironment that promotes tumor progression. Cholesterol and fatty acids are supplied by both de novo biosynthesis and exogenous uptake from lipoproteins. Lipoproteins are pseudo-micellar structures, designed to transport essential water-insoluble metabolites, including triacylglycerols and cholesterol, in the plasma, lymph, and interstitial fluids. A number of studies have reported abnormal circulating lipoprotein levels in leukemic patients and have suggested that lipoproteins are key for cancer cells to thrive. However, the role of lipoprotein metabolism in cancer cells in the context of the TME is still incompletely discussed so far. The aim of this review is to consider the importance of lipoprotein metabolism in shaping the tumor microenvironment in the context of hematological malignancies. Full article