Search Results (139,489)

Sprouty-related proteins with enabled/vasodilator-stimulated phosphoprotein homology 1 (EVH1) domain (SPREDs) are negative regulators of the Ras/MAPK signaling pathway and are known to modulate developmental and endocrine processes. While the roles of SPRED1 and SPRED2 are increasingly understood, the physiological relevance of SPRED3 remains elusive. To elucidate its function, we generated SPRED3 knockout (KO) mice and performed phenotypic, molecular, and hormonal analyses. SPRED3-deficient mice exhibited growth retardation and a non-Mendelian genotype distribution. X-Gal staining revealed Spred3 promoter activity in the thyroid, adrenal gland, pituitary, cerebral cortex, and kidney. Hormonal profiling identified elevated thyroid-stimulating hormone (TSH) and reduced thyroxine (T₄) levels, indicating primary hypothyroidism. Thyroidal extracellular signal-regulated kinase (ERK) signaling was mildly reduced in SPRED3 KO mice, and immunoblotting revealed altered expression of autophagy regulators, including reduced sequestosome 1 (p62), increased autophagy-related gene 5 (ATG5), as well as an elevated microtubule-associated protein 1 light chain 3 (LC3) II/I ratio and a decreased pBeclin/Beclin ratio in SPRED3 KO mice. Our findings indicate that SPRED3 is involved in thyroidal homeostasis and plays a regulatory role in autophagy processes within the thyroid gland. Full article

Calcium ameliorates salt-related growth defects in plants. The objective of this study was to determine whether supplying calcium through a seed enrichment technique enhances the germinability and early growth of timothy (Phleum pratense L.) under saline conditions. For seed enrichment, timothy seeds were soaked in CaCl₂ solutions at concentrations of 50 mM or 100 mM for 24 h at room temperature. Seeds treated with distilled water served as the control. Under distilled water conditions, germination rates among the seeds showed minimal variation, approximately 95% on average. However, in a 200 mM NaCl environment, the germination rate of the control seeds significantly decreased to 25%, while the germination rates of the Ca-enriched seeds remained high, exceeding 86%. Additionally, the Ca-enriched seeds germinated more quickly than the control seeds. When plants were grown with distilled water, the total dry matter weights did not differ significantly among the treatment types. However, under salt stress with 100 mM NaCl, the plants derived from Ca-enriched seeds thrived and exhibited higher dry matter weights compared to the control plants. The Ca-enriched seeds contained more soluble sugars and demonstrated higher catalase activity than the control seeds, and their corresponding plants accumulated less sodium under salt stress compared to the control plants. Seed enrichment is an effective technique for supplying calcium to timothy, and a concentration of 50 mM of CaCl₂ in the treatment solution is sufficient to achieve salt tolerance. Full article

Inonotus obliquus, a medicinal mushroom valued for its bioactive compounds, has not been previously characterized from Romanian sources. This study presents the first comprehensive chemical and biological screening of I. obliquus, introducing novel polymer-based encapsulation systems to enhance the stability and bioavailability of its bioactive constituents. Two distinct delivery systems were designed to enhance the functionality of I. obliquus extracts: (i) microencapsulation in maltodextrin (MIO) and (ii) a sequential approach involving preparation of silver nanoparticle-loaded I. obliquus (IO–AgNPs), followed by microencapsulation to yield the hybrid MIO–AgNP system. Comprehensive metabolite profiling using GC–MS and ESI–QTOF–MS revealed 142 bioactive constituents, including terpenoids, flavonoids, phenolic acids, amino acids, coumarins, styrylpyrones, fatty acids, and phytosterols. Structural integrity and successful encapsulation were confirmed by XRD, FTIR, and SEM analyses. Both IO–AgNPs and MIO–AgNPs demonstrated potent antioxidant activity, significant acetylcholinesterase inhibition, and robust antimicrobial effects against Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Escherichia coli. Cytotoxicity assays revealed pronounced activity against MCF-7, HCT116, and HeLa cell lines, with MIO–AgNPs exhibiting superior efficacy. The synergistic integration of maltodextrin and AgNPs enhanced compound stability and bioactivity. As the first report on Romanian I. obliquus, this study highlights its therapeutic potential and establishes polymer-based nanoencapsulation as an effective strategy for optimizing its applications in combating microbial resistance and cancer. Full article

SA-ConvLSTM is a recently proposed spatiotemporal model for total electron content (TEC) prediction, which effectively catches long-term temporal evolution and global-scale spatial correlations in TEC. However, its reliance on standard convolution limits spatial feature extraction to fixed regular regions, reducing the flexibility for irregular TEC variations. To address this limitation, we enhance SA-ConvLSTM by incorporating deformable convolution, proposing SA-DConvLSTM. This achieves adaptive spatial feature extraction through learnable offsets in convolutional kernels. Building on this improvement, we design ED-SA-DConvLSTM, a TEC spatiotemporal prediction model based on an encoder–decoder architecture with SA-DConvLSTM as its fundamental block. Firstly, the effectiveness of the model improvement was verified through an ablation experiment. Subsequently, a comprehensive quantitative comparison was conducted between ED-SA-DConvLSTM and baseline models (C1PG, ConvLSTM, and ConvGRU) in the region of 12.5° S–87.5° N and 25° E–180° E. The experimental results showed that the ED-SA-DConvLSTM exhibited superior performance compared to C1PG, ConvGRU, and ConvLSTM, with prediction accuracy improvements of 10.27%, 7.65%, and 7.16% during high solar activity and 11.46%, 4.75%, and 4.06% during low solar activity, respectively. To further evaluate model performance under extreme conditions, we tested the ED-SA-DConvLSTM during four geomagnetic storms. The results showed that the proportion of its superiority over the baseline models exceeded 58%. Full article

The Dual-frequency Precipitation Radar (DPR) aboard the Global Precipitation Measurement (GPM) mission provides valuable three-dimensional precipitation structure data on a global scale and has been widely used in hydrometeorological research. However, due to its spatial resolution limitations and inherent algorithmic assumptions, the accuracy of GPM precipitation estimates can exhibit systematic biases, especially under complex terrain conditions or in the presence of variable precipitation structures, such as light stratiform rain or intense convective storms. In this study, we evaluated the near-surface precipitation rate estimates from the GPM-DPR Level 2A product using over 1440 min of disdrometer observations collected across China from 2021 to 2023. Based on three years of stable stratiform precipitation data from the Jinghe station, we developed a least squares linear correction model for radar reflectivity. Independent validation using national disdrometer data from 2023 demonstrated that the corrected reflectivity significantly improved rainfall estimates under light precipitation conditions, although improvements were limited for convective events or in complex terrain. To further enhance retrieval accuracy, we introduced a regionally adaptive R–Z relationship scheme stratified by precipitation type and terrain category. Applying these localized relationships to the corrected reflectivity yielded more consistent rainfall estimates across diverse conditions, highlighting the importance of incorporating regional microphysical characteristics into satellite retrieval algorithms. The results indicate that the accuracy of GPM precipitation retrievals is more significantly influenced by precipitation type than by terrain complexity. Under stratiform precipitation conditions, the GPM-estimated precipitation data demonstrate the highest reliability. The correction framework proposed in this study is grounded on ground-based observations and integrates regional precipitation types with terrain characteristics. It effectively enhances the applicability of GPM-DPR products across diverse environmental conditions in China and offers a methodological reference for correcting satellite precipitation biases in other regions. Full article

As people spend extended periods of time indoors, stress and negative emotions caused by work have become increasingly difficult to ignore. Observing window views is widely considered an effective method to alleviate stress and promote mental health. However, the specific visual elements within these views that contribute to stress reduction and the differential restorative benefits across varying compositions remain insufficiently understood. This study focuses on four major visual elements commonly seen through windows: sky, buildings, greenery, and roads. Using a horizontal layering approach, nine window views were created based on different proportions of these elements. Participants were exposed to these views, and their responses were evaluated through the positive and negative affect scale (PANAS), as well as electroencephalographic (EEG) data acquisition. The findings indicate that greenery exhibits the most pronounced positive effect on stress mitigation and the enhancement of positive affect, while the presence of roads is more likely to elicit negative emotional responses. Additionally, the visual richness and structural completeness of the window scenes are found to significantly impact restorative outcomes. These findings provide empirical insights for landscape and architectural design aimed at improving psychological well-being. Full article

This article examines the significant contributions of Helga de Alvear as a gallerist, collector, and patron, a pivotal figure in the evolution of the Spanish and international contemporary art market. Her legacy is particularly notable through the establishment of the Helga de Alvear Museum in the city of Cáceres, intended to share her vast collection of over 3000 works and foster exhibition, research, conservation, and education. The study analyzes her art collection, highlighting its substantial international minimalist art component, contextualizing its development with her personal and professional journey. Furthermore, it explores the institutionalization of her legacy, from the Helga de Alvear Foundation to the creation and evolution of the museum, its innovative architecture and museography, and its impact on Cáceres’s urban landscape. Full article

The reinforcement effect of single-reinforced soil support under external loading has limitations, and it is difficult for it to meet engineering stability requirements. Therefore, the stability analysis of slopes supported by a combination of anti-slip piles and reinforced soil under the seismic loading effect needs an in-depth study. Based on the upper-bound theorem of limit analysis and the strength-reduction technique, this study establishes an upper-bound stability model for high–steep slopes that simultaneously considers seismic action and the combined reinforcement of anti-slide piles and reinforced soil. A closed-form safety factor is derived. The theoretical results are validated against published data, demonstrating satisfactory agreement. Finally, the MATLAB R2022a sequential quadratic programming method is used to optimize the objective function, and the Optum G2 2023 software is employed to analyze the factors influencing slope stability due to the interaction between anti-slide piles and geogrids. The research indicates that the horizontal seismic acceleration coefficient k_h exhibits a significant negative correlation with the safety factor F_s. Increases in the tensile strength T of the reinforcing materials, the number of layers n, and the length l all significantly improve the safety factor F_s of the reinforced-soil slope. Additionally, as l increases, the potential slip plane of the slope shifts backward. For slope support systems combining anti-slide piles and reinforced soil, when the length of the geogrid is the same, adding anti-slide piles can significantly improve the slope’s safety factor. As anti-slide piles move from the toe to the crest of the slope, the safety factor first decreases and then increases, indicating that the optimal reinforcement position for anti-slide piles should be in the middle to lower part of the slope body. The length of the anti-slip piles should exceed the lowest layer of the geogrid to more effectively utilize the blocking effect of the pile ends on the slip surface. The research findings can provide a theoretical basis and practical guidance for parameter optimization in high–steep slope support engineering. Full article

Lost circulation, a prevalent challenge in drilling engineering, poses significant risks including drilling fluid loss, wellbore instability, and environmental contamination. Conventional plugging materials often exhibit an inadequate performance under high-temperature, high-pressure (HTHP), and complex formation conditions. To address that, this study developed a high-performance gel–resin composite plugging material resistant to HTHP environments. By optimizing the formulation of bisphenol-A epoxy resin (20%), hexamethylenetetramine (3%), and hydroxyethyl cellulose (1%), and incorporating fillers such as nano-silica and walnut shell particles, a controllable high-strength plugging system was constructed. Fourier-transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA) confirmed the structural stability of the resin, with an initial decomposition temperature of 220 °C and a compressive strength retention of 14.4 MPa after 45 days of aging at 140 °C. Rheological tests revealed shear-thinning behavior (initial viscosity: 300–350 mPa·s), with viscosity increasing marginally to 51 mPa·s after 10 h of stirring at ambient temperature, demonstrating superior pumpability. Experimental results indicated excellent adaptability of the system to drilling fluid contamination (compressive strength: 5.04 MPa at 20% dosage), high salinity (formation water salinity: 166.5 g/L), and elevated temperatures (140 °C). In pressure-bearing plugging tests, the resin achieved a breakthrough pressure of 15.19 MPa in wedge-shaped fractures (inlet: 7 mm/outlet: 5 mm) and a sand-packed tube sealing pressure of 11.25 MPa. Acid solubility tests further demonstrated outstanding degradability, with a 97.69% degradation rate after 24 h in 15% hydrochloric acid at 140 °C. This study provides an efficient, stable, and environmentally friendly solution for mitigating drilling fluid loss in complex formations, exhibiting significant potential for engineering applications. Full article

In this work we investigate the integration possibility of a thermistor paste from ESL (ElectroScience Laboratory, now Vibrantz) to see if it is adapted for Vibrantz Low Temperature Cofired Ceramics (LTCC) L8 and A6M-E materials. An alumina-based sample is used as a reference circuit throughout this study. Square, two-squares-in-parallel and two-squares-in-series thermistors are tested, placed internally and externally. Resistive values are measured in a range from 25 °C to 300 °C. The variation in the resistive values among similar thermistors is significant, with a maximum standard deviation of 67%. However, in all cases, there is a positive linear relationship between resistance and temperature. The Temperature Coefficient of Resistance (TCR) value is calculated before and after annealing. In general, the L8 and Al₂O₃ samples exhibit higher TCR values than the A6M-E sample. Additionally, when placed internally, the TCR value decreases approximately 30% for both tested LTCC materials. An Energy-Dispersive X-ray Spectroscopy (EDX) material analysis has also been conducted on the samples, revealing that the main chemical components are oxide, silicon, calcium, and ruthenium but also some barium and titanium, which indicates SiO₂, TiO₂, BaTiO₃ and RuO₂ oxides in the thermistor paste. The possibility to implement thermistors internally and externally on Vibrantz LTCC without delamination problems is endorsed by this study. Full article

Non-synchronous vibration (NSV), flutter, or rotating stall can cause severe blade vibrations and limit the operating range of compressors and fans. To enhance the understanding of these phenomena, this study investigated the corresponding mechanisms in modern composite ultra-high-bypass-ratio (UHBR) fans based on the ECL5/CATANA test campaign. Extensive steady and unsteady instrumentation such as stereo-PIV, fast-response pressure probes, and rotor strain gauges were used to derive the aerodynamic and structural characteristics of the rotor at throttled operating conditions. The study focused on the analysis of the transition region from transonic to subsonic speeds where two distinct phenomena were observed. At transonic design speed, rotating stall was encountered, while NSV was observed at 90 speed. At the intermediate 95 speedline, a peculiar behavior involving a single stalled blade was observed. The results emphasize that rotating stall and NSV exhibit different wave characteristics: rotating stall comprises lower wave numbers and higher propagation speeds at around 78 rotor speed, while small-scale disturbances propagate at 57 rotor speed and lock-in with blade eigenmodes, causing NSV. Both phenomena were observed in a narrow range of operation and even simultaneously at specific conditions. The presented results contribute to the understanding of different types of operating range-limiting phenomena in modern UHBR fans and serve as a basis for the validation of numerical simulations. Full article

A remarkably well-preserved skeleton of a male Mammuthus meridionalis, approximately 60 years old, from the Early Pleistocene that is housed at the Castle of L’Aquila (Italy) exhibits a fractured left tusk with severe bone erosion of the alveolus and premaxillary bone, as well as marked spinal deformities. The cranial region underwent ultrasonographic, radiological, and histological examinations, while morphological and biomechanical analyses were conducted on the vertebral column. Microscopic analysis revealed intra vitam lesions, including woven bone fibers indicative of early bone remodeling and lamellar bone with expanded and remodeled Haversian systems. These findings are consistent with osteomyelitis and bone sequestration, likely resulting from chronic pulpitis following the tusk fracture, possibly due to an accident or interspecific combat. The vertebral column shows cervical scoliosis, compensatory curves, fusion between the first cervical vertebrae, and asymmetric articular facets, suggesting postural adaptations. Evidence of altered molar wear and masticatory function also support long-term survival post-trauma. Additionally, lesions compatible with spondyloarthropathy, an inflammatory spinal condition not previously documented in Mammuthus meridionalis, were identified. These findings provide new insights into the pathology and adaptive responses of extinct proboscideans, demonstrating the critical role of (paleo)histological methods in reconstructing trauma, disease, and aspects of life history in fossil vertebrates. Full article

Background: Small airway dysfunction (SAD) plays a critical role in the management of severe asthma, particularly in patients at risk of requiring biological therapies (BTs). Short-term studies have shown that switching to single-inhaler triple therapy (SITT) with extrafine beclomethasone–formoterol–glycopyrronium improves outcomes and helps achieve quiet asthma, a state marked by symptom control, no exacerbations or oral steroids, reduced inflammation, and better small airway function. This study investigated whether, over one year, patients could maintain this state as Steady Quiet Asthma (SQA) and whether baseline measures could predict this sustained response. Methods: Twenty-six patients with severe asthma and SAD were transitioned from open triple-inhaler therapy to a closed, single-inhaler triple therapy containing extrafine beclomethasone–formoterol–glycopyrronium. Assessments at baseline (T0) and at one-year follow-up (T12) included clinical evaluations, spirometry, and impulse oscillometry, with a focus on Fres as a predictor for the need for BT. When prescribed, biologic therapies included mepolizumab, benralizumab, and dupilumab. Results: Of the 26 patients, 9 (34.6%) achieved SQA and did not require biologic therapy at the one-year follow-up, while 17 patients (65.4%) initiated biologic treatment. At T0, patients who required biologics had significantly higher median Fres (21 (19.47; 24.58) vs. 17.61 (15.82; 20.63); p = 0.049) compared to those who remained biologic-free. They also exhibited higher residual volume to total lung capacity ratio (%RV/TLC) values and lower forced expiratory volume in one second/forced vital capacity ratios (FEV₁/FVC). At T12, patients spared from BT showed significant reductions in Fres (p = 0.014) and improvements in small airway function (difference in airway resistance between 5 Hz and 20 Hz (R5–20), forced expiratory flow between 25% and 75% of FVC (%FEF25–75), and better asthma control (ACT). In contrast, patients on BT demonstrated less favorable changes in these parameters. Conclusions: Baseline Fres, FEV1/FVC ratio, and %FEV25–75 are valuable predictors of achieving Steady Quiet Asthma (SQA) and sparing biologic therapy. These findings support the use of SITT in severe asthma and highlight the importance of early functional assessments to guide personalized management. Full article

Ecological security evaluation serves as the cornerstone for ecological management decision-making and spatial optimization. This study focuses on the Dongping Lake Basin. Based on the Pressure–State–Response (PSR) model framework, it integrates ecological risk, ecosystem health, and ecosystem service indicators. Utilizing methods including Local Indicators of Spatial Association (LISA), Transition Matrix, and GeoDetector, it analyzes the spatio-temporal evolution characteristics and driving mechanisms of watershed ecological security from 2000 to 2020. The findings reveal that the Watershed Ecological Security Index (WESI) exhibited a trend of “fluctuating upward followed by periodic decline”. In 2000, the status was “relatively unsafe”. It peaked in 2015 (index 0.332, moderately safe) and experienced a slight decline by 2020. Spatially, a significantly clustered pattern of “higher in the north and lower in the south, higher in the east and lower in the west” was observed. In 2020, “High-High” clusters of ecological security aligned closely with Shandong Province’s ecological conservation red line, concentrating in core protected areas such as the foothills of the Taihang Mountains and Dongping Lake Wetland. Level transitions were characterized by “predominant continuous improvement in low levels alongside localized reverse fluctuations in middle and high levels,” with the “relatively unsafe” and “moderately safe” levels experiencing the largest transfer areas. Geographical detector analysis indicates that the Human Interference Index (HI), Ecosystem Service Value (ESV), and Annual Afforestation Area (AAA) were key drivers of watershed ecological security change, influenced by dynamic interactive effects among multiple factors. This study advances watershed-scale ecological security assessment methodologies. The revealed spatio-temporal patterns and driving mechanisms provide valuable insights for protecting the ecological barrier in the lower Yellow River and informing ecological security strategies within the Dongping Lake Watershed. Full article

In arid regions with limited water resources, improving cropland water-use efficiency (WUEc) is crucial for maintaining crop production. This study aims to investigate how changes in meteorological and vegetation factors affect WUEc in drylands and to identify its primary drivers, which are essential for understanding how cropland ecosystems respond to complex environmental changes. Using remote sensing data, we analyzed the spatiotemporal patterns of WUEc in Xinjiang from 2002 to 2022 by applying STL decomposition, Sen’s slope combined with the Mann–Kendall test, and an XGBoost–SHAP model, quantifying its key controlling factors. The results indicate that from 2002 to 2022, WUEc in Xinjiang showed an overall declining trend. Prior to 2007, WUEc increased at 0.05 gC·m⁻¹·m⁻²·a⁻¹, after which it fluctuated downward at −0.01 gC·m⁻¹·m⁻²·a⁻¹. Intra-annual peaks consistently occurred in May and during September–October. Spatially, WUEc exhibited significant heterogeneity, increasing from south to north, with 53.26% of the region showing declines. Temperature (T) and leaf area index (LAI) emerged as the primary meteorological and vegetation drivers, respectively, influencing WUEc change in 45.7% and 17.6% of the area. Both variables were negatively correlated with WUEc, with negative correlations covering 60% of the region for T and 83% for LAI. These findings provide scientific guidance for optimizing crop structure and water-resource management strategies in arid regions. Full article