Functional CRISPR screens in T cells reveal new opportunities for cancer immunotherapies.

T cells are fundamental components in tumour immunity and cancer immunotherapies, which have made immense strides and revolutionized cancer treatment paradigm. However, recent studies delineate the predicament of T cell dysregulation in tumour microenvironment and the compromised efficacy of cancer immunotherapies. CRISPR screens enable unbiased interrogation of gene function in T cells and have revealed functional determinators, genetic regulatory networks, and intercellular interactions in T cell life cycle, thereby providing opportunities to revamp cancer immunotherapies. In this review, we briefly described the central roles of T cells in successful cancer immunotherapies, comprehensively summarised the studies of CRISPR screens in T cells, elaborated resultant master genes that control T cell activation, proliferation, fate determination, effector function, and exhaustion, and highlighted genes (BATF, PRDM1, and TOX) and signalling cascades (JAK-STAT and NF-κB pathways) that extensively engage in multiple branches of T cell responses. In conclusion, this review bridged the gap between discovering element genes to a specific process of T cell activities and apprehending these genes in the global T cell life cycle, deepened the understanding of T cell biology in tumour immunity, and outlined CRISPR screens resources that might facilitate the development and implementation of cancer immunotherapies in the clinic.

Numerical Simulation of Flow Characteristics for Supercritical CO2-Sprayed Polyurethane Resin.

Conventional paint spraying processes often use small molecule organic solvents and emit a large amount of volatile organic compounds (VOCs) that are highly toxic, flammable, and explosive. Alternatively, the spraying technology using supercritical CO2 (scCO2) as a solvent has attracted attention because of its ability to reduce VOC emissions, but the flow characteristics of coatings have not been thoroughly studied. Therefore, we numerically simulate the spraying process based on the actual process of scCO2 spraying polyurethane coatings by computational fluid dynamics (CFD). The effects of inlet pressure and volume fraction of scCO2 on the fluid motion parameters inside the nozzle as well as the atomization effect of droplets outside the nozzle are investigated. The simulated results show that a fluid with a large volume fraction of scCO2 will obtain a smaller density, resulting in a larger velocity and a larger distance for the spray to effectively spray. Higher coating content and bigger inlet pressures will result in higher discrete phase model (DPM) concentrations, and thus a bigger inlet pressure should be used to make the droplets more uniform across the 30° spray range. This study can provide theoretical guidance for the process of scCO2-sprayed polyurethane resin.

Analysis and Characterization on Dynamic Recrystallization in Casting AZ31 Mg Alloys Under Plane Strain Compression.

Studies on twinning, twin-induced dynamic recrystallization (TDRX), and their temperature and strain rate dependences are of considerable significance to the ultimate strength and plastic formability of the coarse-grained Mg alloys during severe plastic deformation. Plane strain compression tests were conducted on the parallelepiped samples of casting AZ31 Mg alloys. The twinning and recrystallization behaviors close to and away from the crack boundaries were characterized using electron backscatter diffraction. The results show: (1) with increasing strain rate for tests, the extension twin proliferates significantly. Due to the local stress concentration, the TDRX is more active in the area close to the crack tip and exhibits the positive strain-rate sensitivity as twinning; (2) the TDRX is not only stress-favored but also closely links to the temperature. However, the TDRX is not utterly proportional to the temperature. Compared to 400 °C, 300 °C is more beneficial to the TDRX, achieving the higher strength and plastic deformability. The main reason is that the higher strain-hardening rate and flow stress at the higher strain rate and lower temperature motivates the transformation from twinning to the fine twin-walled grains more efficiently, and the stress-favored TDRX is crucial to refine grains and continue plastic deformation for the casting Mg alloys with coarse grains.