Phagocytosis is one of the earliest cellular functions, developing approximately 2 billion years ago. Although FcR-based phagocytic signaling is well-studied, how it originated from ancient phagocytosis is unknown. Lipid redistribution upregulates a phagocytic program recapitulating FcR-based phagocytosis with complete dependence on Src family kinases, Syk, and phosphoinositide 3-kinases (PI3K). Here we show that in phagocytes, an atypical ITAM sequence in the ancient membrane anchor protein Moesin transduces signal without receptor activation. Plasma membrane deformation created by solid structure binding generates phosphatidylinositol 4,5-bisphosphate (PIP2) accumulation at the contact site, which binds the Moesin FERM domain and relocalizes Syk to the membrane via the ITAM motif. Phylogenic analysis traces this signaling using PI3K and Syk to 0.8 billion years ago, earlier than immune receptor signaling. The proposed general model of solid structure phagocytosis implies a preexisting lipid redistribution-based activation platform collecting intracellular signaling components for the emergence of immune receptors.

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Chitosan nanospheres have great potential in drug controlled release systems, because they show excellent degradability, biocompatibility, and nontoxicity. The particle size control and size distribution of nanospheres are necessary in order to improve reproducibility, bioavailability, and repeatable release behavior. In order to prepare uniformly sized and size-controllable chitosan nanospheres, in this study, a premix membrane emulsification technique was developed on the basis of direct membrane emulsification, and the uniformly sized chitosan naonospheres were successfully prepared by optimizing preparation conditions. The detail preparation process is as follows: The chitosan aqueous solution was used as a dispersed phase, and the mixture of liquid paraffin and petroleum ether containing emulsifier was used as a continuous phase. The coarse emulsions were first prepared by low-speed stator homogenization and then poured into the premix reservoir. Nanodroplets were achieved by extruding the coarse emulsions through the SPG (Shirasu porous glass) membrane with a high pressure. The nanodroplets were further cross-linked to obtain chitosan nanospheres. In this process, several factors played key roles in obtaining chitosan nanoparticles with narrow size distribution, including the amounts of emulsifier in oil phase, the composition of oil phase, the concentration of chitosan, the ratio of water to oil phase, the transmembrane pressure and number of passes, and so on. The results showed that the chitosan nanospheres from 300 nm to 1.85 µm were successfully prepared by premix membrane emulsification by changing the pore size of the membrane and the polydispersity index could be as low as 0.027 under optimized conditions, and it is a potential technique to prepare size-controllable uniform chitosan nanospheres with fast production.

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