c-Met-targeted chimeric antigen receptor T cells inhibit hepatocellular carcinoma cells in vitro and in vivo

c-Met is a hepatocyte growth factor receptor overexpressed in many tumors such as hepatocellular carcinoma(HCC).Therefore,c-Met may serve as a promising target for HCC immunotherapy.Modifying T cells to express c-Met-specific chimeric antigen receptor(CAR)is an attractive strategy in treating c-Met-positive HCC.This study aimed to systematically evaluate the inhibitory effects of 2^(nd)-and 3^(rd)-generation c-Met CAR-T cells on hepatocellular carcinoma(HCC)cells.Here,2^(nd)-and 3^(rd)-generation c-Met CARs containing an anti-c-Met singlechain variable fragment(scFv)as well as the CD28 signaling domain and CD3ζ(c-Met-28-3ζ),the CD137 signaling domain and CD3ζ(c-Met-137-3ζ),or the CD28 and CD137 signaling domains and CD3ζ(c-Met-28-137-3ζ)were constructed,and their abilities to target c-Met-positive HCC cells were evaluated in vitro and in vivo.All c-Met CARs were stably expressed on T cell membrane,and c-Met CAR-T cells aggregated around c-Met-positive HCC cells and specifically killed them in vitro.c-Met-28-137-3ζCAR-T cells secreted more interferon-gamma(IFN-γ)and interleukin 2(IL-2)than c-Met-28-3ζCAR-T cells and c-Met-137-3ζCAR-T cells.Compared with c-Met low-expressed cells,c-Met CAR-T cells secreted more cytokines when co-cultured with c-Met high-expressed cells.Moreover,c-Met-28-137-3ζCAR-T cells eradicated HCC more effectively in xenograft tumor models compared with the control groups.This study suggests that 3^(rd)-generation c-Met CAR-T cells are more effective in inhibiting c-Met-positive HCC cells than 2^(nd)-generation c-Met CAR-T cells,thereby providing a promising therapeutic intervention for c-Met-positive HCC.

Analysis on the Influence of Computer Technology on Agricultural Development in China

Wide application of the computer-leading information technology is promoting tremendous changes in agricultural management,production,sales and agricultural science and technology,and education,showing broad application prospects,bringing unprecedented development opportunities to the information technology industry,greatly driving agricultural modernization,but also bringing challenges to agricultural science and technology workers to meet the agricultural information technology revolution. Information technology,as a kind of resource,is manifesting its functions in agricultural production and operation of agricultural products,and farmers are also paying more attention to the use of information technology to guide production and sales. China should take full advantage of the computer-centered information resources,and take the road of agricultural modernization and information to develop agriculture.

Performance optimization for high speed axial piston pump considering cylinder block tilt

Increasing the rotating speed is considered as an efficient approach to upgrade the power-to-weight ratio in an axial piston pump,but penalized by more leakage and more severe wear resulting from the adverse cylinder block tilt.Previous studies mainly focused on the bearing characteristic of the valve plate/cylinder block pair,but the spline coupling also plays a key role in the undesired cylinder block tilt,which has been little studied.A theoretical model for the rotating assembly is presented to investigate the effect of the spline coupling length on the cylinder block tilt and the performance of the valve plate/cylinder block pair.A typical high-speed axial piston pump with the displacement of 5.2 mL/r at 10000 r/min was studied by simulation and experiment.It shows that the optimal spline coupling length is one value increased by 2 mm from the original,bringing a remarkable leakage reduction under the high-speed condition by decreasing the cylinder block tilting angle.The experiment result matches well with the simulation.The influences of the spline coupling on the cylinder block tilt and the leakage were demonstrated.

Coupled evolution of piston asperity and cylinder bore contour of piston/cylinder pair in axial piston pump

The wear condition of the piston/cylinder pair is crucial to the performance and reliability of the axial piston pump.The hard piston surface,the soft cylinder bore surface,and the interface oil film affects each other during the wear process.Specifically,in the mixed lubrication region,the geometry of the hard piston surface asperity directly affects the wear of soft cylinder bore surface,while the asperities may deform or even degrade when penetrating and sliding against the cylinder bore.So far,there is no suitable method to simulate their coupled evolution.This paper proposed a wear process simulation model considering the real-time interaction between the elasto-plastic deformation of the piston surface asperity,the wear contour of the cylinder bore,and the lubrication condition of the interface.An offline library of the elasto-plastic constitutive behavior of the asperity based on the finite element method(FEM)is established as a part of the simulation model to precisely analyze the deformation and degradation of the asperity and quickly invoke them in the numerical wear process simulation.The simulation and experimental results show that the piston asperity and the cylinder bore contour converge to a steady state after running-in for about 0.5 h.The distribution of the simulated asperity degradation and wear depth is also verified by the experiment.