Search Results (1,459)

Petit-spot volcanism is a type of intraplate volcanism that commonly occurs near the outer rise in subducting plates. Although deformation of the incoming plate is considered important for its development, the deeper mantle processes contributing to this volcanism remain poorly understood. Here, we use more than 1500 broadband seismograms containing long-period SS precursors to investigate the mantle transition zone (MTZ) beneath the Sunda–Java subduction system. Beneath the northern Sunda–Java region, the 660 km discontinuity (d660) reaches ~690 km depth, resulting in an MTZ thicker than 270 km, consistent with the thermal influence of the subducted Indo-Australian slab. The associated weakening of S660S amplitudes may reflect hydration or other factors affecting the lower MTZ. South of the trench, the MTZ beneath most of the Christmas Island Seamount Province is relatively uniform, with a thickness of ~251 km. Beneath Christmas Island, however, the 410 km discontinuity (d410) is depressed to ~420–425 km, whereas d660 remains near 670–675 km, producing a localized thinner MTZ of ~245–250 km. This structure is compatible with localized slab-related mantle processes and may reflect thermal or compositional heterogeneity near the top of the MTZ. Although our observations do not directly resolve volatile transport or melt generation, they provide new constraints on the deep-mantle environment associated with rejuvenated petit-spot volcanism at Christmas Island. Full article

Cerebrovascular computational fluid dynamics (CFD) models often rely on generic boundary conditions, which may limit their ability to represent subject-specific hemodynamics and cerebral autoregulation (CA). We propose a multimodal data-driven boundary calibration (MDBC) framework integrating transcranial color-coded Doppler and continuous blood pressure monitoring to optimize individualized outlet resistances. As a proof-of-concept, we evaluated the MDBC framework in a single healthy volunteer at resting baseline and enhanced external counterpulsation (EECP)—a hemodynamic perturbation potentially triggering CA. Compared with conventional open boundary (OB) and static Murray allocation boundary (SMAB) strategies, MDBC achieved closer agreement with in vivo middle cerebral artery (MCA) velocity waveforms under both states. At rest, MDBC’s left MCA relative root mean square error (rRMSE) was 7.19%, versus 22.85% (OB) and 30.89% (SMAB). During EECP, conventional models yielded rRMSEs > 32%, whereas MDBC maintained 11.24%. Meanwhile, MDBC reproduced inter-hemispheric perfusion imbalance, an EECP-induced flow surge in the right MCA, and pronounced wall shear stress increases that were masked by generic boundary strategies. Moreover, MDBC estimated a 25.8% increase in global cerebrovascular resistance during EECP, suggesting the capability of the framework to characterize subject-specific impedance adaptations potentially associated with CA during intervention. These single-subject findings support the technical feasibility of integrating multimodal physiological measurements into cerebrovascular CFD boundary calibration and warrant further validation in larger cohorts and patient populations. Full article

This study evaluated the reliability of artificial intelligence (AI)-based cephalometric measurements of overjet (OJ) and overbite (OB) and their agreement with manual assessment and investigated factors that may influence measurement outcomes. This retrospective cross-sectional study included 200 orthodontic patients (125 females, 75 males; mean age 20.12 years) selected from 440 records. Manual OJ and OB measurements were obtained twice from dental models using digital calipers and served as the reference standard. AI-based measurements were generated from lateral cephalometric radiographs using WebCeph™. Reliability was assessed using intraclass correlation coefficients (ICCs), while agreement between methods was evaluated using paired t-tests and Bland–Altman analysis. AI-based measurements showed significantly higher OJ and slightly lower OB values than manual measurements, with mean differences of 0.89 mm for OJ and −0.44 mm for OB (p < 0.05). Intra- and inter-examiner reliability were excellent (ICCs > 0.90). Bland–Altman analysis demonstrated that most measurement differences were within the 95% limits of agreement despite a small systematic bias. These findings suggest that AI-assisted cephalometric analysis provides a rapid and reliable approach for routine orthodontic assessment; however, individual discrepancies may be clinically relevant when high measurement precision is required. Therefore, AI should be considered a useful adjunct to conventional assessment, whereas manual measurements remain the reference standard when maximum measurement accuracy is essential. Full article

Although neoadjuvant chemotherapy is widely used after osteosarcoma (OS) surgery, suboptimal chemotherapy accelerates OS recurrence, and postoperative bone repair remains challenging. Here, we report a selenium-loaded biomimetic calcium phosphate (Se@BioCaP) to provide a long-term therapeutic-dose release for postoperative OS treatment. Sodium selenite was incorporated into a biomimetic calcium phosphate (BioCaP) via a wet biomimetic mineralization protocol. The release kinetics of Se@BioCaP achieved a transition from non-Fickian transport to Fickian diffusion, delivering sustained cytotoxic concentrations under acidic, tumor-like conditions while maintaining biocompatibility with osteoblasts (OBs) under physiological conditions. The reduction in OS cell viability was associated with the disruption of redox homeostasis, including the downregulation of key antioxidant enzymes (SOD2 and GPx1), increased reactive oxygen species (ROS), and acidic vesicular organelle (AVO) formation. Notably, Se@BioCaP200 extracts maintained in vitro anticancer and pro-osteogenic activity at day 42, while antibacterial activity was maintained through day 42. These findings suggest that Se@BioCaP may be a promising candidate for postoperative OS management. Full article

This study evaluated the effects of breeder age (BA) and in ovo (IO) administration of vitamin D₃ metabolites on hatchability, body weight, bone traits, and leg health in broiler chickens. A total of 640 eggs obtained from young (YB; 29 wk) and old (OB; 52 wk) Ross 308 broiler breeder flocks were assigned on day 18 of incubation to four treatments: 25(OH)D₃, 1,25(OH)₂D₃, diluent, or non-injected. Chicks were reared under standard conditions until market age. Hatchability was not affected by BA or IO treatments. Birds derived from OBs exhibited greater hatch weight and final body weight than those derived from YBs. At market age, BA effects on bone traits were limited to greater femur length in OB birds. In contrast, IO administration of vitamin D₃ metabolites significantly enhanced bone mineralization and mechanical competence, as evidenced by higher tibial Ca, P, and Mg concentrations; increased bone ash content; a higher Seedor index; and greater breaking strength. Treated birds also exhibited shorter, narrower, and heavier long bones, indicating altered bone geometry. Furthermore, the incidence of gait abnormalities and tibial dyschondroplasia was markedly reduced, whereas femoral head necrosis remained unaffected. Among the metabolites evaluated, 25(OH)D₃ produced the most consistent improvements in final body weight, bone traits, and leg health. Overall, IO administration of vitamin D₃ metabolites, particularly 25(OH)D₃, improved bone traits and leg health at market age and may represent a practical strategy to enhance broiler welfare and production performance. Full article

Background: Physiologically based pharmacokinetic (PBPK) modeling is a mechanistic tool used to predict how a drug moves through the body by incorporating real human physiology, including organ sizes, blood flows, tissue compositions, and enzyme activities. It has been widely employed to estimate drug exposure in different populations with organ impairment, genotype variabilities, and physiological variations. Metoclopramide is an antiemetic and prokinetic agent that is subject to CYP2D6 polymorphism. The study aims to develop PBPK models for several CYP2D6 variants to predict changes in the pharmacokinetic (PK) behavior of metoclopramide. Methods: To conduct this study, a literature review was conducted, and the retrieved physicochemical, biochemical, and PK data were integrated into PK-Sim to develop a PBPK model. Initially, a non-genotype-specific model was developed and extrapolated to genotype-based models. The models were verified using a Visual Predicted Check (VPC), mean predicted-to-observed ratio (R_pre/obs) values, and mean relative deviation (MRD). Results: The simulated profiles were aligned with the reported data, and all the predicted and observed PK parameters were comparable, as the R_pre/obs values were within the 0.5–2 range and MRD values were <2. Moreover, an increasing trend in AUC_0–∞ was observed across CYP2D6*wt/*wt, CYP2D6*wt/*10, CYP2D6*10/*10, and CYP2D6*5/*10, with approximately 1.63-, 2.64-, and 2.88-fold increases compared with the CYP2D6*wt/*wt genotype. Conclusions: The models have adequately estimated the PK behavior of metoclopramide across different CYP2D6 variants. These models might be helpful for populations with diverse CYP2D6 genotypes in dose optimization. Full article

Reconstructing long-term continuous precipitation series is essential for characterising rainfall variability, detecting hydroclimatic trends, and supporting water resource management in semi-arid Mediterranean regions. This study analyses rainfall variability in the Sebou watershed (northern Morocco, ~40,000 km²) over 1980–2024, using eleven stations spanning an altitudinal gradient from 5 m (Kénitra) to 1478 m (Aït Khebbach). To reconstruct continuous monthly series over 44 hydrological years, ERA5 reanalyses were bias-corrected using seasonal Quantile Mapping (QM) versus station data, available only until 2001. Raw ERA5 data show a generalised positive bias increasing with altitude (from +8.9% at Kénitra to +112.9% at Pont du Mdez), with severe NSE degradation in complex relief areas (NSE = −3.834 at Pont du Sker). After QM correction, the mean bias drops to −0.1% and mean NSE improves from −0.32 to +0.68. Cross-validation (100 random-splitting iterations) confirms correction robustness, yielding a mean NSE of 0.594 ± 0.076. The stationarity hypothesis at the 2001/2002 boundary is validated for all eleven stations through the Pettitt test applied directly to the ERA5–OBS bias series (p = 1.000). Mann–Kendall trend analysis reveals no significant trend for most stations, reflecting strong natural decadal variability of the semi-arid Mediterranean regime, which may limit trend detection over the study period. SPI-12 analysis identifies four major drought episodes (1981–1985, 1991–1995, 1999–2002, 2018–2022) and notable wet surpluses (1995–1996, 2008–2010). Aïn Timédrine (650 m) shows notable chronic drought vulnerability (9 years with SPI-12 < −1.0). This study provides the first continuous 44-year monthly precipitation series for the Sebou basin, quantifies the ERA5 elevation mismatch (Δz) as the dominant bias predictor (r = −0.828, p = 0.002), and delivers a multi-scale drought characterisation (SPI-3, SPI-6, SPI-12), constituting a valuable dataset for long-term hydrological modelling. Full article

Oenothera biennis L. is an economically important oil and ornamental crop. However, the regulatory mechanisms underlying its flower bud differentiation remain poorly understood. To elucidate the interactions between the environmental cues and molecular networks governing this process, this study investigated natural populations from the Lesser Khingan Mountains. The results demonstrate that exposure to 0–10 °C for at least 15 d and long-day (LD) conditions correlated strongly with floral induction. Notably, 200 mg·L⁻¹ of exogenous GA₃ effectively substituted for vernalization, significantly promoting bolting and advancing flower development. Expression profiling revealed an antagonistic expression pattern between floral activators such as ObFT and ObAP2 and repressors such as ObFLC. Both vernalization and GA₃ upregulated floral activators while suppressing the repressors, and these processes were coincident with the transition to flowering. Flower bud differentiation goes through six continuous stages, spanning from inflorescence primordia to gynoecium primordia formation. Hybrid fruit setting, the pollen–ovule ratio (98) and the outcrossing index (OCI = 3) confirmed that O. biennisis is a facultative selfer, with reproduction predominantly relying on self-pollination. This study provides a systematic characterization of the integrated regulatory network coordinating vernalization, photoperiod, and gibberellin in Oenothera flowering, proposing a framework for the putative FT-FLC antagonism. These findings establish a molecular foundation for the precision management of flowering time and informed breeding strategies. Full article

While global climate change is fundamentally reshaping thermal regimes, capturing these shifts in topographically diverse regions remains a significant hurdle for standard gridded datasets. This study provides a comprehensive spatiotemporal analysis of 16 extreme temperature indices across Northern Carpathians from 1980 to 2024 using the E-OBS dataset. The QDM framework proved highly effective in neutralizing elevation-induced temperature biases, which reached up to 5.1 °C in raw E-OBS data. Beyond simple bias removal, the correction significantly improved the daily accuracy of the dataset, with RMSE values at high-altitude stations, such as the Chopok summit (1995 m), decreasing from 5.1 °C to 2.3 °C. Both Warm Days (TX90p) and Summer Days (SU) show near-perfect Field Coherence ($C_f$ = 100% and 98%, respectively). A prominent feature of this temporal national average trend is its inherent asymmetry; the Annual Minimum (TNn) is climbing nearly twice as fast (+1.1 °C/decade) as the Annual Maximum (TXx) (+0.6 °C/decade), though the warming of these coldest nights is more localized (74.5% coherence). We also identified a clear signal of Elevation-Dependent Warming (EDW), with absolute maximums surging most aggressively in the Northern Carpathians at +1.6 °C/decade. Conversely, cold-tail indices like Ice Days are in a concurrent nationwide retreat ($C_f$ = 97%), a shift that significantly reduces the physical window for winter tourism and alters the climatic envelope for fragile mountain ecosystems. Ultimately, these results position Slovakia as a high-sensitivity climate region where observed trends often outpace broader Central European averages, highlighting the urgent need for localized, nature-based adaptation strategies. Full article

Programmable electromagnetic environments, including reconfigurable intelligent surface (RIS)-assisted systems, are often described in terms of physical or controllable degrees of freedom. Such counts, however, do not determine which channel or operator directions can actually be distinguished by a finite measurement architecture. This paper develops an operator-space formulation of observable degrees of freedom for programmable propagation systems. We distinguish three nested layers: the physical operator space generated by the family of physically admissible propagation operators, the effective operator space selected by architectural constraints, and the observable subspace induced by a finite probing architecture. Once the effective space is fixed, observability is characterized by the spectrum of the associated measurement Gram operator. To remove arbitrary amplitude scaling, we introduce a common probe-energy normalization and define the resolution-dependent observable dimension $N_{\mathrm{obs}}\left(\eta \right)$ from the normalized Gram spectrum. The same spectrum also yields an observability condition number, which quantifies the stability of the visible subspace. We then extend the construction to symmetry-resolved operator spaces, showing how invariant probing can create sectorial blind subspaces and how controlled symmetry breaking produces second-order restricted visibility inside the original blind subspace. The mathematical ingredients are standard finite-dimensional tools from operator theory, frame theory, representation theory, and matrix concentration; the contribution is their integration into a measurement-oriented degrees-of-freedom framework for programmable electromagnetic environments. Numerical experiments with normalized probing families, sectorial decompositions, controlled symmetry breaking, and a canonical narrowband RIS-inspired model illustrate that architectures with the same effective dimension and probing budget can exhibit substantially different observable dimensions and conditioning. The results support the view that practical electromagnetic design should optimize not only the number of accessible modes or control states, but also the Gram geometry through which those directions are measured. Full article

Background: Childhood dyslipidemia often tracks into adulthood and contributes to early atherosclerotic changes. Although serum 25-Hydroxyvitamin D (25(OH)D) has been implicated in lipid metabolism, findings in children remain inconsistent, and whether these associations differ by overweight/obesity (ow/ob) status is unclear. We therefore aimed to investigate the associations of serum 25(OH)D concentrations and lipid profiles stratified by ow/ob status among children and adolescents aged 9–17 years. Methods: This cross-sectional study included 3067 children and adolescents from Guangzhou, southern China. Anthropometric measurements were obtained by trained staff, and ow/ob status was classified according to WHO criteria. Fasting blood samples were collected to measure serum 25(OH)D and lipid parameters. Multivariable regression analyses were adopted to determine the associations between serum 25(OH)D and lipid profiles. Stratified analysis and interaction tests were further applied according to ow/ob status. Results: Higher 25(OH)D concentrations were most consistently associated with lower TG (β = −0.026; 95% CI, −0.040 to −0.011), higher HDL-C (β = 0.025; 95% CI, 0.014 to 0.035), and lower TG/HDL-C ratios (β = −0.044; 95% CI, −0.061 to −0.027). Positive associations were also observed for TC, LDL-C, and non-HDL-C with serum 25(OH)D, but these were attenuated after further adjustment for HDL-C. No significant association was observed for the TC/HDL-C ratio. In stratified analyses, associations with several lipid parameters were observed mainly among children and adolescents without ow/ob, whereas significant inverse associations among those with ow/ob were largely limited to TG and the TG/HDL-C ratio. Significant interactions between vitamin D and ow/ob status were observed for TC and non-HDL-C, but were attenuated after further adjustment for HDL-C. Conclusions: In this cross-sectional study, serum 25(OH)D was associated with several lipid parameters among children and adolescents, most consistently with TG, HDL-C, and the TG/HDL-C ratios. Stratified analyses showed different vitamin D–lipid association patterns across ow/ob status, with statistically significant interactions observed only for TC and non-HDL-C. The attenuation of several associations after adjustment for HDL-C suggests that HDL-C may be involved in these observed patterns. Future longitudinal studies are needed to examine causality of vitamin D–lipid associations and the potential role of HDL-C in these associations. Full article

High-temporal-resolution vertical total electron content (VTEC) inversion is important for ionospheric delay correction in maritime GNSS applications, but offshore single-station observations often suffer from limited satellite geometry, clustered ionospheric pierce points, and noise-sensitive least-squares (LSs) solutions. This study proposes a Virtual-Observation-Based Tikhonov Regularization (TVO) method for stabilizing ill-conditioned least-square VTEC inversion. TVO links the regularization factor to the condition number of the normal-equation matrix and selectively constrains higher-order spatial-gradient parameters while preserving background VTEC and receiver-bias terms. Experiments using the European mid-latitude station OBE4 and 17 surrounding stations on 1 July 2021 show that short epoch intervals and increased model complexity aggravate ill-conditioning, especially for the full quadratic model at 30 s. Compared with LS, TVO reduces the average RMS difference relative to the GIM-interpolated VTEC reference by 56.30% across the four VTEC models for the 17 stations. Maritime validation using South China Sea buoy data collected from 19 to 25 May 2025 further shows that TVO suppresses local discontinuities and amplitude anomalies, reducing the overall RMS difference relative to the GIM-interpolated VTEC reference from 26.07 TECU to 14.74 TECU. These results suggest that TVO can improve the numerical stability of maritime single-station VTEC inversion under constrained observation geometry. Full article

Layer chickens have dual physiological demands for rapid growth and continuous egg production. The maintenance of skeletal homeostasis in layer chickens relies on the precise coordination among OCs, osteoblasts (OBs), and osteocytes. The imbalances in the supply of nutrients such as calcium (Ca) and phosphorus (P), as well as dysfunction of the “gut–bone” axis, can disrupt normal bone development in layer chickens, leading to bone diseases such as tibial dyschondroplasia (TD) and osteoporosis (OP), seriously damaging the production performance of layer chickens. This review systematically summarizes the knowledge background of the metabolic reprogramming of OCs in layer chickens, especially mitochondria-mediated biological processes, including oxidative phosphorylation (OXPHOS), glycolysis, reactive oxygen species (ROS) signaling, mitophagy, etc. Notably, the co-culture system of OCs derived from the bone marrow cavity of embryos in vitro has been established in laying chickens. However, there are few reports on the study of mitochondrial metabolism of OCs using this model. Therefore, this review particular focuses on the bone metabolism mediated by OCs in layer chickens and proposes future research priorities, including the application of gene editing and multi-omics methods to ultimately achieve targeted nutritional or pharmacological interventions for optimizing mitochondrial function and promoting bone health. Full article

Research Infrastructures (RIs) and Observatories (Obs) are essential to the advancement of environmental and water sciences as they offer facilities, services, and data that foster innovative and high-quality research. However, their broader use is often prevented by fragmentation, limited visibility, and complex access mechanisms. Within the European Water4All Partnership, a comprehensive and continuously updated repository of water-related RIs and Obs is being developed to enhance connectivity, accessibility, and use across Europe and beyond. The repository offers a structured and well-categorized overview of water-related RIs and Obs, including information on facilities, data and services provided, highlighting their remote data access capabilities, capacity for interconnections, and policy support, thereby improving visibility, interoperability, and identification of needs and gaps within the European water sector. By linking data producers, researchers, academics, policy-decision makers and stakeholders, it supports evidence-based decision-making, fosters capacity building, and facilitates cross-domain research while contributing to European and global water initiatives aligned with EU policies, UN Sustainable Development Goals (SDGs), and key water priorities, highlighting its added value for the water Research and Innovation (R&I) sector. Full article

The southeastern Tibetan Plateau (SETP) lies at the intersection of extreme topography and the Indian summer monsoon, producing intense orographically driven precipitation. Resolving these extremes requires convection-permitting simulations (CPMs) due to the combined influence of complex terrain and vigorous convection. However, kilometer-scale simulations over SETP remain limited to short periods because of computational cost, preventing robust estimation of precipitation extremes. We analyze a decade of 1 km CPMs and apply the Simplified Metastatistical Extreme Value (SMEV) framework, which uses all wet-day precipitation rather than annual maxima, increasing the effective sample size by an order of magnitude. We apply the SMEV framework to estimate daily precipitation return levels up to 100 years. While SMEV increases the effective sample size, uncertainty remains non-negligible for long return periods when derived from a decadal record. Results show that CPMs’ estimates align with observations within 90% bootstrap confidence intervals (CIs). For instance, at a representative station (Obs: 51.6 mm/d), the 50-year return level is estimated at 57.1 mm/d (CI: 47.1–68.9 mm/d). In contrast, coarse-resolution products systematically overestimate these extremes by 50–100%, with their estimates often falling far outside the observed range beyond 20-year return periods. CPMs also reveal a model-derived, non-monotonic elevation dependence absent in coarse datasets. Instead of monotonic decline, three phrases emerge: a weak increase below 2700 m, a sharp decrease across mid-elevations, and a reversal above ~5300 m where orographic uplift enhances extremes, yielding a 2.3-fold increase. These results show that CPMs alter not only magnitude but also the spatial structure and elevation scaling of precipitation extremes, providing a physically constrained framework for extreme-value estimation in data-sparse mountains. Full article