No abstract

Programmed death-ligand 1/programmed cell death 1 (PD-L1/PD-1) is one of the most important immune checkpoints in humans and other mammalian species. However, the occurrence of the PD-L1/PD-1 checkpoint in evolutionarily ancient vertebrates remains elusive because of the absence of a PD-1 homolog before its appearance in tetrapods. In this article, we identified, to our knowledge, a novel PD-L1/B and T lymphocyte attenuator (BTLA) checkpoint in zebrafish by using an Edwardsiella tarda–induced bacterial infection model. Results showed that zebrafish (Danio rerio) PD-L1 (DrPD-L1) and BTLA (DrBTLA) were differentially upregulated on MHC class II+ macrophages (Mϕs) and CD8+ T cells in response to E. tarda infection. DrPD-L1 has a strong ability to interact with DrBTLA, as shown by the high affinity (KD = 5.68 nM) between DrPD-L1/DrBTLA proteins. Functionally, the breakdown of DrPD-L1/DrBTLA interaction significantly increased the cytotoxicity of CD8+BTLA+ T cells to E. tarda–infected PD-L1+ Mϕ cells and reduced the immune escape of E. tarda from the target Mϕ cells, thereby enhancing the antibacterial immunity of zebrafish against E. tarda infection. Similarly, the engagement of DrPD-L1 by soluble DrBTLA protein diminished the tolerization of CD8+ T cells to E. tarda infection. By contrast, DrBTLA engagement by a soluble DrPD-L1 protein drives aberrant CD8+ T cell responses. These results were finally corroborated in a DrPD-L1–deficient (PD-L1−/−) zebrafish model. This study highlighted a primordial PD-L1/BTLA coinhibitory axis that regulates CD8+ T cell activation in teleost fish and may act as an alternative to the PD-L1/PD-1 axis in mammals. It also revealed a previously unrecognized strategy for E. tarda immune evasion by inducing CD8+ T cell tolerance to target Mϕ cells through eliciting the PD-L1/BTLA checkpoint pathway.

Background: Peroxiredoxin (Prx) was previously known only as a Cys-dependent thioredoxin. Results: Cys-independent catalase-like activity was observed in two vertebrate Prx1 proteins. Conclusion: Prx1 possesses dual antioxidant activities with varied affinities toward H 2 O 2 . Significance: This discovery extends our knowledge on Prx1 and provides new opportunities to further study the biological roles of this family of antioxidants.

This letter proposes an on-state drain-source voltage (V ds,on ) measurement circuit for SiC MOS-FETs. The proposed circuit effectively solves the problem of inconsistent diode volt-ampere characteristics through an additional current source. The voltage difference between the two diodes is compensated by adjusting the auxiliary current under the condition of a fixed first current. This circuit does not require diode pre-selection and significantly improves measurement accuracy. The circuit is implemented in a double-pulse test (DPT) of a SiC MOSFET (900 V/23 A, 25 °C). The results show that the circuit has a fast response speed with a delay time of 0.4 μs. Even at the same current, the forward voltage difference between the two diodes reaches 3.32 mV. Compared to measurement results from a six-bit semi-digital multimeter, the measurement error of the proposed circuit is less than 1.5% at different currents and temperatures.