SNAREs are the core machinery mediating membrane fusion. In this review, we provide an update on the recent progress on SNAREs regulating membrane fusion events, especially the more detailed fusion processes dissected by well-developed biophysical methods and in vitro single molecule analysis approaches. We also briefly summarize the relevant research from Chinese laboratories and highlight the significant contributions on our understanding of SNARE-mediated membrane trafficking from scientists in China.
Dendritic cells (DCs) have the potential to activate or tolerize T cells in an Ag-specific manner. Although the precise mechanism that determines whether DCs exhibit tolerogenic or immunogenic functions has not been precisely elucidated, growing evidence suggests that DC function is largely dependent on differentiation status, which can be manipulated using various growth factors. In this study, we investigated the effects of mobilization of specific DC subsets—using GM-CSF and fms-like tyrosine kinase receptor 3-ligand (Flt3-L)—on the susceptibility to induction of experimental autoimmune myasthenia gravis (EAMG). We administered GM-CSF or Flt3-L to C57BL/6 mice before immunization with acetylcholine receptor (AChR) and observed the effect on the frequency and severity of EAMG development. Compared with AChR-immunized controls, mice treated with Flt3-L before immunization developed EAMG at an accelerated pace initially, but disease frequency and severity was comparable at the end of the observation period. In contrast, GM-CSF administered before immunization exerted a sustained suppressive effect against the induction of EAMG. This suppression was associated with lowered serum autoantibody levels, reduced T cell proliferative responses to AChR, and an expansion in the population of FoxP3+ regulatory T cells. These results highlight the potential of manipulating DCs to expand regulatory T cells for the control of autoimmune diseases such as MG.
The development of highly efficient and economical materials for the oxygen reduction reaction (ORR) plays a key role in practical energy conversion technologies. However, the intrinsic scaling relations exert thermodynamic inhibition on realizing highly active ORR electrocatalysts. Herein, a novel and feasible gradient orbital coupling strategy for tuning the ORR performance through the construction of Co 3d‐O 2p‐Eu 4f unit sites on the Eu2O3–Co model is proposed. Through the gradient orbital coupling, the pristine ionic property between Eu and O atoms is assigned with increased covalency, which optimizes the eg occupancy of Co sites, and weakens the OO bond, thus ultimately breaking the scaling relation between *OOH and *OH at Co–O–Eu unit sites. The optimized model catalyst displays onset and half‐wave potential of 1.007 and 0.887 V versus reversible hydrogen electrode, respectively, which are higher than those of commercial Pt/C and most Co‐based catalysts ever reported. In addition, the catalyst is found to possess superior selectivity and durability. It also reveals better cell performance than commercial noble‐metal catalysts in Zn–air batteries in terms of high power/energy densities and long cycle life. This study provides a new perspective for electronic modulation strategy by the construction of gradient 3d–2p–4f orbital coupling.
Author Contributions. Y.Zho. conducted most of the experiments and analyzed the results. Z.L. and S.Z. conducted the animal experiments. R.Z., H.L., X.L., X.Q., and Y.Zhe. provided technical support. M.Z. carried out work on Rab26-RILP interaction. L.L. provided technical support for the pancreas sectioning. W.H. was involved with the ideas and writing the paper. T.W. conceived the idea for the project, designed the experiments, and wrote the paper. T.W. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
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