PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons

PANoptosis is a newly identified type of regulated cell death that consists of pyroptosis,apoptosis,and nec roptosis,which simultaneously occur during the pathophysiological process of infectious and inflammatory diseases.Although our previous lite rature mining study suggested that PANoptosis might occur in neuronal ischemia/repe rfusion injury,little experimental research has been reported on the existence of PANoptosis.In this study,we used in vivo and in vitro retinal neuronal models of ischemia/repe rfusion injury to investigate whether PAN optosis-like cell death(simultaneous occurrence of pyroptosis,apo ptosis,and necroptosis)exists in retinal neuronal ischemia/repe rfusion injury.Our results showed that ischemia/repe rfusion injury induced changes in morphological features and protein levels that indicate PANoptosis-like cell death in retinal neurons both in vitro and in vivo.Ischemia/repe rfusion inju ry also significantly upregulated caspase-1,caspase-8,and NLRP3 expression,which are important components of the PANoptosome.These results indicate the existence of PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons and provide preliminary experimental evidence for future study of this new type of regulated cell death.

Complex roles of necroptosis in cancer

Necroptosis is a tightly regulated form of necrosis that requires the activation of receptor-interacting protein(RIP)kinases RIPK1 and RIPK3,as well as the RIPK3 substrate mixed lineage kinase domain-like protein(MLKL).Because of membrane rupture,necroptotic cells release damage-associated molecular patterns(DAMPs)that evoke immune responses.Necroptosis is emerging as an important cellular response in the modulation of cancer initiation,progression,and metastasis.Necroptosis of cancer cells is considered to be an immunogenic cell death capable of activating anti-tumor immunity.Necroptosis also participates in the promotion of myeloid cell-induced adaptive immune suppression and thus contributes to oncogenesis.In addition,necroptosis of endothelial cells and tumor cells is conducive to tumor metastasis.In this review,we summarize the current knowledge of the complex role of necroptosis in cancer and discuss the potential of targeting necroptosis components for cancer therapies.

Effect of protein molecular weight on the mass transfer in protein mixing

The mixing of protein solutions with that of precipitating agents is very important in protein crystallization experiments. In this work, the interferometry images were recorded during the mixing of two proteins with different molecular weights： lysozyme of -14.6 kDa, trypsin of -23.3 kDa and pepsin of -34.8 kDa were placed in a Mach-Zehnder interferometer. The protein mo- lecular weight dependence on the competition of the transport process and kinetics at the interface was studied. The concentra- tion profiles of protein solutions were calculated to analyze the mass transfer during the mixing process. It was observed that the mass transfer process is more efficient during the mixing of proteins with higher molecular weights. In addition, the more rapid concentration changes above the interface suggest that convection may dominate the diffusion. The phenomenon of con- vection is higher in the protein solutions with higher molecular weight.