Blocking the PD-1 signal transduction by occupying the phosphorylated ITSM recognition site of SHP-2.

Targeting the PD-1/PD-L1 axis with small-molecular inhibitors is a promising approach for immunotherapy. Here, we identify a natural pentacyclic triterpenoid, Pygenic Acid A (PA), as a PD-1 signaling inhibitor. PA exerts anti-tumor activity in hPD-1 knock-in C57BL/6 mice and enhances effector functions of T cells to promote immune responses by disrupting the PD-1 signaling transduction. Furthermore, we identify SHP-2 as the direct molecular target of PA for inhibiting the PD-1 signaling transduction. Subsequently, mechanistic studies suggest that PA binds to a new druggable site in the phosphorylated PD-1 ITSM recognition site of SHP-2, inhibiting the recruitment of SHP-2 by PD-1. Taken together, our findings demonstrate that PA has a potential application in cancer immunotherapy and occupying the phosphorylated ITSM recognition site of SHP-2 may serve as an alternative strategy to develop PD-1 signaling inhibitors. In addition, our success in target recognition provides a paradigm of target identification and confirmation for natural products.

Breaking the Gender Imbalance: Female Presence in the Computational Chemistry Group at Viva Biotech.

The growing field of computational chemistry and artificial intelligence is drawing unprecedented attention in drug discovery. However, the underrepresentation of female scientists persists in the field. While the gender disparity is acknowledged in academic settings, the issue is less addressed and intensifies in the pharmaceutical and biotech industry both at the entry-level and leadership positions. At Viva Biotech, we challenge this norm: over 60% of the full-time employees in our computational chemistry group are women, a testament of our commitment to the pursuit of gender equality. We share our vision of the evolving role of computational chemistry in drug discovery and where women stand and rise in the field. In this article, we discuss how we engage female empowerment with tactical approaches and from personal experiences. The intention is to offer actionable guidance for female computational chemists at early career stages to bring visibility to their impacts, and ascent to senior positions.

Experimental study on the atomization characteristics and dust removal efficiency of a fan-shaped nozzle for purifying working environment.

The inadequacy of the existing research in characterizing the atomization performance of the whole atomization field by the local region at nozzle axis hinders the improvement of dust removal performance of a spray system, especially for fan-shaped nozzles with large atomization angle. To solve this inadequacy, 88 measuring points were designed in this study to reveal the spatial distribution characteristics of atomization parameters of a fan-shaped pressure atomization nozzle using a 3D Fiber Phase-Doppler Anemometer. Moreover, the atomization performance and dust removal performance of the whole atomization field under different spray pressures were characterized. The results showed that the spatial distribution of atomization parameters in the axis and radial direction of the nozzle was inhomogeneous. As the axial distance from the nozzle outlet increased, the average droplet size showed a trend of first decreasing and then increasing, the proportion of the droplet of 15-70 µm showed a trend of first increasing and then decreasing, while the average droplet velocity and droplet flux showed a decreasing trend. In addition, the spray orientation was perpendicular to gravity, and the atomization field was parallel to gravity, resulting in a significant difference in the average droplet size between the upper region and the axis. Compared with the upper and lower regions, the atomization effect at the axis was superior, manifested by higher average droplet velocity and droplet flux, indicating that characterizing nozzle atomization performance with atomization parameters at the axis will lead to overestimation. The increase of spray pressure can improve atomization performance and dust removal efficiency to a certain extent, but the improvement effect had a limit. The atomization field can be divided into atomization region, expansion region and contraction region, and the expansion region was considered as an effective dust removal region. These findings provide reference for the design and operation of a spray system.