- Research Article
- 10.1016/j.ejmech.2026.118708
Discovery of HDM2004, a potent, selective and orally bioavailable HPK1 inhibitor for tumor immunotherapy.
- Apr 01, 2026
- European journal of medicinal chemistry
- Zhimin Zhang + 10 more +10
Publications from 2021 to 2026
Showing 10 of 405 papers
Discovery of HDM2004, a potent, selective and orally bioavailable HPK1 inhibitor for tumor immunotherapy.
Experimental and microstructural investigation on the strength and frost resistance of basalt fiber reinforced steel slag foamed concrete.
Aiming to facilitate the high-value repurposing of industrial steel slag, this investigation synthesized basalt fiber-reinforced steel-slag foamed concrete (BFSFC) incorporating fiber volume fractions of 0%, 0.15%, 0.30%, and 0.45%. The experimental study assessed compressive and flexural capacities alongside resistance to freeze-thaw cycling, while micro-void was reconstructed via X-ray CT and corroborated by SEM imaging. Grey Relational Analysis (GRA) was subsequently utilized to correlate pore metrics with strength degradation under freezing conditions. Empirical findings identify 0.30% as the critical fiber volume fraction; this optimal mix yielded a 28-day compressive strength of 1.322MPa (a 12.03% increment over the reference) and elevated flexural strength to 0.517MPa (an increase of approximately 64%). Following 15 freeze-thaw iterations, the BFSFC2 specimen maintained a mass loss below 5% and restricted strength deterioration to 8.69%, a sharp contrast to the 31.14% decay observed in the control group. Microscopic analysis attributes this stability to a fiber-induced reduction in pore network complexity and morphological refinement. Furthermore, GRA confirms that fiber dosage exhibits the strongest correlation with fractal dimension (0.991), whereas frost-induced strength decline is primarily governed by fractal dimension (0.805) and large pore size (> 200μm, 0.743), highlighting the dominance of pore network complexity and large pore-defects in freezing behavior. Conclusively, BFSFC2 provides a balanced improvement in mechanical performance and freeze-thaw resistance, supporting a microstructure-based optimization route for producing lightweight foamed concrete using steel slag for cold regions.
Read moreLong-Term Hydrodynamic Evolution and Extreme Parameter Estimation in the Mekong River Estuary
Tropical estuarine hydrodynamic processes are governed by complex interactions between tides, monsoons, and fluvial runoff. To obtain long-term (≥30 years) hydrodynamic conditions of the Mekong River Estuary, this study established a Finite Volume Coastal Ocean Model (FVCOM) coupled with validated Weather Research and Forecast (WRF) wind forcing for a 32-year (1988–2019) high-resolution simulation. Validation against in situ observations confirms the model’s robustness. Temporal–spatial patterns of water level and current were analyzed, and extreme parameters for 1–100 year return periods were derived via the Pearson-III probability distribution. Results indicate the study area is a mesotidal environment (tidal range = 3.58 m) dominated by SSE-NNW reciprocating tidal currents. Relative to Vietnam’s national elevation datum, 100-year return period extreme high/low water levels are 2.15 m and −2.03 m, with a maximum storm surge setup of 2.09 m. The 100-year return period maximum current velocity reaches 4.58 m/s (A21 station), and Mekong River runoff exerts a negligible influence (<5% velocity change). This study provides high-precision baseline data for offshore wind farm engineering and disaster risk assessment, offering a methodological reference for tropical estuarine hydrodynamic simulations.
Read moreROV deployment onboard a small OSV coupled with a floating wind turbine by a single point mooring system
Enhancing 1O2 pathway via ultrasound-coupled iron-carbon activated persulfate for improving sludge dehydration and reducing antibiotics mutagenicity.
Experimental study of glued horizontal joints in prefabricated hybrid wind turbine towers under extreme bending-torsion ratios
Design method and numerical study for determining ceramic fracture parameters based on mesoscopic grains
Improving Daily Precipitation Estimates through Machine Learning-Based Downscaling, Precipitation Event Classification, and Categorical Merging
Soil structural controls on soil retention in karst grasslands with different levels of rocky desertification
Introduction Grassland degradation in karst regions is typically characterized by increased bedrock exposure, vegetation fragmentation, and soil structural instability. However, the mechanisms by which these changes affect hillslope erosion resistance remain poorly quantified. Methods In this study, natural grassland plots under four levels of degradation, defined by bedrock exposure rates (RER) of 0%, 20%, 40%, and 55%, were selected in representative limestone and dolomite areas in Guizhou Province, China. Undisturbed soil samples from the 0∼20 cm layer were collected for aggregate stability tests and undisturbed soil scouring experiment. Using 9 diagnostic indicators of soil structural function, the effects of degradation on soil retention capacity were quantitatively assessed. Results The results showed that with increasing RER, the proportion of macroaggregates (&gt;2 mm) decreased by 31.6%, and mean weight diameter (MWD) declined by 58.3%. Relative dispersion index (RSI) and relative mechanical Breakdown index (RMI) increased to 1.96 and 2.21, respectively, with the most severe structural breakdown occurring under fast wetting conditions. In the scouring experiments, sediment concentration peaked at 1.8 g/min within the first minute in the 55% RER plots, significantly higher than in the 0% RER plots. Meanwhile, the soil resistance coefficient declined by more than 50%. Composite functional evaluation revealed that MWD, RSI, Anti-scourability coefficient (AS), and root surface area were the most sensitive indicators across degradation levels. Limestone grassland (LG) demonstrated stronger performance in maintaining structural integrity and erosion resistance compared to Dolomite grassland (DG). Discussion These findings provide a scientific basis for identifying early warning signs of erosion resistance loss and offer theoretical support for ecological restoration and degradation threshold identification in karst grassland ecosystems.
Read moreEntropy Production Analysis and Fluid–Structure Refinement of a Stepless Stratified Intake
Thermal stratification in deep reservoirs can cause ecologically problematic cold-water releases, and many existing selective-withdrawal phenomena rely on a limited set of fixed intake levels, which constrains their ability to follow seasonal shifts in the thermocline. Stepless stratified intakes with continuously adjustable flap gates offer quasi-continuous control of withdrawal depth, but their multi-gate, multi-brace layouts generate complex internal hydraulics whose energy-loss mechanisms are not well captured by conventional head-loss and resistance-coefficient metrics. In this study, physical-model measurements are combined with a validated three-dimensional numerical model, and entropy-production theory is used as a diagnostic to resolve where and by which mechanisms mechanical energy is irreversibly degraded inside a single-unit stepless stratified intake. The analysis shows that turbulent entropy production accounts for more than 98% of total dissipation, concentrated mainly in the flow channel and gate shaft, while the reservoir and outlet pipe contribute only weakly. Local entropy-production-rate fields indicate that dominant irreversibilities are associated with flow turning at the active gate leaves and with separation and wake development around horizontal and vertical braces, which generate low-velocity bands across gate levels and a low-velocity corridor in the shaft. Five geometric modification schemes targeting gate-entrance shaping and brace layout are evaluated; a combined brace-alignment and edge-rounding configuration most effectively weakens dissipation hotspots, improves discharge sharing among gate levels and reduces total entropy production. These findings show that entropy-based diagnostics can complement traditional hydraulic indicators and provide effective guidance for the design and refinement of stepless stratified intake structures.
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