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•A randomized, double-blind, placebo-controlled trial was conducted in healthy Chinese infants.•Efficacy and safety of a pentavalent rotavirus vaccine (RV5) were assessed.•Efficacy against rotavirus gastroenteritis of any-severity caused by any serotype was 69.3%.•Efficacy against severe rotavirus gastroenteritis caused by any serotype was 78.9%.•RV5 was efficacious and generally well-tolerated in Chinese infants. A randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RotaTeq™, RV5) against rotavirus gastroenteritis (RVGE). 4040 participants aged 6–12weeks were enrolled and randomly assigned to either 3 oral doses of RV5 (n=2020) or placebo (n=2020), administered ∼4weeks apart. The participants also received OPV and DTaP in a concomitant or staggered fashion. The primary objective was to evaluate vaccine efficacy (VE) against naturally-occurring RVGE at least 14days following the third dose. Key secondary objectives included: VE against naturally-occurring severe RVGE and VE against severe and any-severity RVGE caused by rotavirus serotypes contained in the vaccine, occurring at least 14days after the third dose. All adverse events (AEs) were collected for 30days following each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. (ClinicalTrials.gov registry: NCT02062385). VE against RVGE of any-severity caused by any serotype was 69.3% (95% CI: 54.5, 79.7). The secondary efficacy analysis showed an efficacy of: 78.9% (95% CI: 59.1, 90.1) against severe RVGE caused by any serotype; 69.9% (95% CI: 55.2, 80.3) and 78.9% (95% CI: 59.1, 90.1) against any-severity and severe RVGE caused by serotypes contained in the vaccine, respectively. Within 30days following any vaccination, 53.5% (1079/2015) and 53.3% (1077/2019) of participants reported at least one AE, and 5.8% (116/2015) and 5.7% (116/2019) reported SAEs in the vaccine and placebo groups, respectively. No SAEs were considered vaccine-related in recipients of RV5. Two intussusception cases were reported in recipients of RV5 who recovered after receiving treatment. Neither was considered vaccine-related. In Chinese infants, RV5 was efficacious against any-severity and severe RVGE caused by any serotype and generally well-tolerated with respect to AEs.

Agricultural drought poses a severe threat to food security in the North China Plain, necessitating accurate and timely monitoring approaches. This study presents a novel drought assessment framework that innovatively integrates multiple remote sensing indices through an optimized random forest algorithm, achieving unprecedented accuracy in regional drought monitoring. The framework introduces three key innovations: (1) a systematic integration of six drought-related factors including vegetation condition index (VCI), temperature condition index (TCI), precipitation condition index (PCI), land cover type (LC), aspect (ASPECT), and available water capacity (AWC); (2) an optimized random forest algorithm configuration with 100 decision trees and enhanced feature extraction capability; and (3) a robust triple-validation strategy combining standardized precipitation evapotranspiration index (SPEI), comprehensive meteorological drought index (CI), and soil moisture verification. The framework demonstrates exceptional performance with R2 values consistently above 0.80 for monthly assessments, reaching 0.86 during autumn and 0.73 during summer seasons. Particularly, it achieves 87% accuracy in mild drought (−1.0 < SPEI ≤ −0.5) and 85% in moderate drought (−1.5 < SPEI ≤ −1.0) detection. The 20-year (2000–2019) spatiotemporal analysis reveals that moderate drought events dominated the region (23.7% of total occurrences), with significant intensification during the 2010–2012 and 2014–2016 periods. Summer drought frequency peaked at 12–15 months in south-central Shandong (37°N, 117°E) and eastern Henan (34°N, 114°E). The framework’s high spatial resolution (1 km) and comprehensive validation protocol establish a reliable foundation for agricultural drought monitoring and water resource management, offering a transferable methodology for regional drought assessment worldwide.

Tamoxifen resistance is accountable for relapse in many ER-positive breast cancer patients. Most of these recurrent patients receive chemotherapy, but their chemosensitivity is unknown. Here, we report that tamoxifen-resistant breast cancer cells express significantly more BARD1 and BRCA1, leading to resistance to DNA-damaging chemotherapy including cisplatin and adriamycin, but not to paclitaxel. Silencing BARD1 or BRCA1 expression or inhibition of BRCA1 phosphorylation by Dinaciclib restores the sensitivity to cisplatin in tamoxifen-resistant cells. Furthermore, we show that activated PI3K/AKT pathway is responsible for the upregulation of BARD1 and BRCA1. PI3K inhibitors decrease the expression of BARD1 and BRCA1 in tamoxifen-resistant cells and re-sensitize them to cisplatin both in vitro and in vivo. Higher BARD1 and BRCA1 expression is associated with worse prognosis of early breast cancer patients, especially the ones that received radiotherapy, indicating the potential use of PI3K inhibitors to reverse chemoresistance and radioresistance in ER-positive breast cancer patients. Most breast cancer patients are estrogen receptor positive and thus benefit from treatments that inhibit estrogen production; however, one third of tamoxifen-treated patients develops resistance and relapse. Here the authors show that tamoxifen resistant cells are resistant to chemotherapy because of BARD1 and BRCA1 upregulation.

This study develops a theoretical framework to evaluate the equivalent bulk and shear moduli of nanoporous materials, incorporating nanoscale surface effects through the Steigmann–Ogden surface mechanics model. By decomposing the spatial gradient into in-plane and out-of-plane components, stress boundary conditions at a spherical nanovoid/matrix interface are derived with improved computational efficiency. A representative volume element (RVE) is modeled as an infinite spherical matrix embedding a concentric nanoinhomogeneity or nanovoid. Generalized displacement solutions, rooted in elasticity theory, are formulated for both domains, with unknown coefficients determined using macroscopic strain conditions, Steigmann–Ogden interface constraints, and displacement finiteness at the nanoinhomogeneity’s center. The Mori–Tanaka homogenization approach is employed to compute the equivalent moduli, with nanovoid-specific results derived by setting the nanoinhomogeneity’s elastic moduli to zero. Numerical experiments, conducted on nanoporous aluminum, investigate the influence of surface bulk modulus, shear modulus, bending modulus, porosity, and nanovoid radius. The results demonstrate that surface effects are pronounced for smaller nanovoids ( nm) and higher porosity, significantly deviating from classical predictions due to increased surface-to-volume ratios. The equivalent bulk modulus remains independent of surface bending modulus under hydrostatic loading, while the shear modulus exhibits strong sensitivity to bending stiffness, modulated by surface moduli.

Host survival depends on the elimination of virus and mitigation of tissue damage. Herein, we report the modulation of D-mannose flux rewires the virus-triggered immunometabolic response cascade and reduces tissue damage. Safe and inexpensive D-mannose can compete with glucose for the same transporter and hexokinase. Such competitions suppress glycolysis, reduce mitochondrial reactive-oxygen-species and succinate-mediated hypoxia-inducible factor-1α, and thus reduce virus-induced proinflammatory cytokine production. The combinatorial treatment by D-mannose and antiviral monotherapy exhibits in vivo synergy despite delayed antiviral treatment in mouse model of virus infections. Phosphomannose isomerase ( PMI ) knockout cells are viable, whereas addition of D-mannose to the PMI knockout cells blocks cell proliferation, indicating that PMI activity determines the beneficial effect of D-mannose. PMI inhibition suppress a panel of virus replication via affecting host and viral surface protein glycosylation. However, D-mannose does not suppress PMI activity or virus fitness. Taken together, PMI-centered therapeutic strategy clears virus infection while D-mannose treatment reprograms glycolysis for control of collateral damage. Glucose metabolism is crucial for cellular energy regulation and affects the immune response. Here the authors show that nutritional supplementation of mannose may be beneficial during virus infections by rewiring glucose metabolic dysregulation and alleviating inflammatory tissue damage.

Dust aerosols significantly influence climate by modulating radiative balance and cloud processes. This study integrates MERRA-2 reanalysis data and the CMIP6 multi-model ensemble to assess the spatiotemporal evolution of dust emissions, deposition, and associated radiative effects in Central Asia from 1980 to 2100. Four SSP scenarios project that dust emissions in Central Asia exhibit a high-emission, high-deposition pattern with primary sources exceeding 15 µg m−2 s−1. The deposition area substantially exceeds the source area (maximum > 8 µg m−2 s−1). Cross-scenario analysis demonstrates that dust emissions are highly sensitive to climate policy, with end-of-century emissions in the SSP5-8.5 high-emission scenario increasing by 94.9 % relative to the baseline period. In contrast, emissions under the SSP1-2.6 low-carbon pathway vary by only 4.5 %. Simulations using the SBDART model show that aerosol direct radiative forcing (ADRF) from dust in Central Asia under clear-sky conditions exhibits a vertical gradient, with cooling at the top of the atmosphere (TOA) and heating within the atmosphere, yielding a net negative forcing at the TOA, with a minimum of < −10 W m−2 near the Caspian Sea. Peak positive forcing within the atmosphere, observed in spring, reaches 10.0 W m−2. Increased dust emissions reduce shortwave radiation at the surface by up to −20 W m−2. Ground-based observations indicate seasonal variations in the dust-induced heating rate, with peak radiative forcing in spring at Kashgar (93.0 W m−2) and a maximum near-surface heating rate of 2.6 K d−1. In contrast, the near-surface heating rate at Issyk-Kul Lake in autumn (0.34 K d−1) is approximately four times higher than in spring (0.08 K d−1).

The relationship between species richness and evenness across communities remains an unsettled issue in ecology from both theoretical and empirical perspectives. As a result, we do not know the mechanisms that could generate a relationship between species richness and evenness, and how this responds to spatial scale. Here we examine the relationship between species richness(S) and evenness (Pielou's J' evenness) using a chronosequence of successional sub-alpine meadow communities in the eastern Qinghai-Tibetan Plateau. These meadows range from natural community (never farmed), to those that have been protected from agricultural exploitation for periods ranging from 1 to 10 years. A total of 30 sampling quadrats with size of 0.5 m×0.5 m were laid out along two transects at each meadow. Using correlation analyses we found a consistent negative correlation between S and J' in these communities along the successional gradient at the sampling scale of 0.5 m×0.5 m. We also explored the relationship between S and J' at different sampling scales (from 0.5 m×0.5 m to10 m×10 m) using properly measured ramet-mapped data of a10 m×10 m quadrat in the natural community. We found that S was negatively corrected with J' at the scales of 0.5 m×0.5 m to 2 m×2 m, but such a relationships disappeared at relative larger scales (≥2 m×4 m). When fitting different species abundance models combined with trait-specific methods, we found that niche preemption may be the determining mechanism of species evenness along the succession gradient. Considering all results together, we can conclude that such niche differentiation and spatial scale effects may help to explain the maintenance of high species richness in sub-alpine meadow communities.

Background The human brain is a dynamic neural system with time-varying functional connectivity (FC) strengths between brain regions. Evidence indicates that adolescents with major depressive disorder (MDD) exhibit decreased average FC strength in cognitive tasks. Nevertheless, research focused on dynamic FC analysis in this population remains limited. This study aims to identify cognitive task-related dynamic FC features as valuable biomarkers to characterize clinical symptoms in adolescents with MDD. Methods A total of 83 adolescents with MDD and 78 age/sex-matched healthy controls (HCs) were recruited. We utilized functional near-infrared spectroscopy (fNIRS) to record brain functional data from participants while they performed the verbal fluency task (VFT). An analytical framework for fNIRS data was proposed, in which the average FC strength values over the entire VFT duration and the principal components (PCs) of dynamic (time-varying) FC strength values were extracted as static and dynamic FC features, respectively. A random forest model was built to distinguish adolescents with MDD from HCs. Statistical analyses of the FC features were conducted to identify between-group differences, as well as their relationships with clinical symptoms in adolescents with MDD. Results The random forest model achieved an accuracy of 86.32% (95% confidence interval: 83.75%-89.38%) for distinguishing adolescents with MDD from HCs. Significant between-group differences emerged in several FC features (false discovery rate-corrected q  < 0.05). For adolescents with MDD, the average FC strength value in the right dorsolateral prefrontal cortex (DLPFC) ~ right medial prefrontal cortex (mPFC) pathway was a significant predictor of depressive and anxious symptoms; the 3rd PC of dynamic FC strength values in the left DLPFC ~ left temporal lobe (TL) pathway and the 5th PC of dynamic FC strength values in the right mPFC ~ right TL pathway were significant predictors of anhedonic symptoms. Conclusions VFT-related static and dynamic FC features in specific brain pathways are potential biomarkers for characterizing clinical symptoms in adolescents with MDD. The developed random forest model holds promise as a diagnostic tool for MDD in adolescents. Clinical trial number Not applicable.

Fast radio bursts (FRBs) are extremely bright, millisecond-duration cosmic transients of unknown origin. The growing number of wide-field and high-time-resolution radio surveys, particularly with next-generation facilities such as the Square Kilometre Array and MeerKAT, will dramatically increase FRB discovery rates, but will also produce data volumes that overwhelm conventional search pipelines. Real-time detection thus demands software that is both algorithmically robust and computationally efficient. We present Astroflow, an end-to-end, GPU-accelerated pipeline for single-pulse detection in radio time–frequency data. Built on a unified C++/CUDA core with a Python interface, Astroflow integrates radio-frequency interference excision, incoherent dedispersion, dynamic-spectrum tiling, and a YOLO-based deep detector. Through vectorized memory access, shared-memory tiling, and OpenMP parallelism, it achieves >10× faster-than-real-time processing on consumer GPUs for a typical 150 s, 2048-channel observation—while preserving high sensitivity across a wide range of pulse widths and dispersion measures. These results establish the feasibility of a fully integrated, GPU-accelerated single-pulse search stack, capable of scaling to the data volumes expected from upcoming large-scale surveys. Astroflow offers a reusable and deployable solution for real-time transient discovery, and provides a framework that can be continuously refined with new data and models.