Resonance mechanism of flapping wing based on fluid structure interaction simulation

Certain insect species have been observed to exploit the resonance mechanism of their wings.In order to achieve resonance and optimize aerodynamic performance,the conventional approach is to set the flapping frequency of flexible wings based on the Traditional Structural Modal(TSM)analysis.However,there exists controversy among researchers regarding the relationship between frequency and aerodynamic performance.Recognizing that the structural response of wings can be influenced by the surrounding air vibrations,an analysis known as Acoustic Structure Interaction Modal(ASIM)is introduced to calculate the resonant frequency.In this study,Fluid Structure Interaction(FSI)simulations are employed to investigate the aerodynamic performance of flapping wings at modal frequencies derived from both TSM and ASIM analyses.The performance is evaluated for various mass ratios and frequency ratios,and the findings indicate that the deformation and changes in vortex structure exhibit similarities at mass ratios that yield the highest aerodynamic performance.Notably,the flapping frequency associated with the maximum time-averaged vertical force coefficient at each mass ratio closely aligns with the ASIM frequency,as does the frequency corresponding to maximum efficiency.Thus,the ASIM analysis can provide an effective means for predicting the optimal flapping frequency for flexible wings.Furthermore,it enables the prediction that flexible wings with varying mass ratios will exhibit similar deformation and vortex structure changes.This paper offers a fresh perspective on the ongoing debate concerning the resonance mechanism of Flexible Flapping Wings(FFWs)and proposes an effective methodology for predicting their aerodynamic performance.

Discovery of TK-642 as a highly potent,selective,orally bioavailable pyrazolopyrazine-based allosteric SHP2 inhibitor

Src homology-2-containing protein tyrosine phosphatase 2(SHP2)is a promising therapeutic target for cancer therapy.In this work,we presented the structure-guided design of 5,6-fused bicyclic allosteric SHP2 inhibitors,leading to the identification of pyrazolopyrazine-based TK-642 as a highly potent,selective,orally bioavailable allosteric SHP2 inhibitor(SHP2WT IC_(50)=2.7 nmol/L)with favorable pharmacokinetic profiles(F=42.5%;t_(1/2)=2.47 h).Both dual inhibition biochemical assay and docking analysis indicated that TK-642 likely bound to the“tunnel”allosteric site of SHP2.TK-642 could effectively suppress cell proliferation(KYSE-520 cells IC_(50)=5.73μmol/L)and induce apoptosis in esophageal cancer cells by targeting the SHP2-mediated AKT and ERK signaling pathways.Additionally,oral administration of TK-642 also demonstrated effective anti-tumor effects in the KYSE-520 xenograft mouse model,with a T/C value of 83.69%.Collectively,TK-642 may warrant further investigation as a promising lead compound for the treatment of esophageal cancer.