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Background Dysbiosis or imbalance of gut microbiota in Alzheimer's disease (AD) affects the production of short-chain fatty acids (SCFAs), whereas exogenous SCFAs supplementation exacerbates brain Aβ burden in APP/PS1 mice. Bifidobacterium is the main producer of SCFAs in the gut flora, but oral administration of Bifidobacterium is ineffective due to strong acids and bile salts in the gastrointestinal tract. Therefore, regulating the levels of SCFAs in the gut is of great significance for AD treatment. Methods We investigated the feasibility of intranasal delivery of MSNs- Bifidobacterium (MSNs-Bi) to the gut and their effect on behavior and brain pathology in APP/PS1 mice. Results Mesoporous silica nanospheres (MSNs) were efficiently immobilized on the surface of Bifidobacterium . After intranasal administration, fluorescence imaging of MSNs-Bi in the abdominal cavity and gastrointestinal tract revealed that intranasally delivered MSNs-Bi could be transported through the brain to the peripheral intestine. Intranasal administration of MSNs-Bi not only inhibited intestinal inflammation and reduced brain Aβ burden but also improved olfactory sensitivity in APP/PS1 mice. Conclusions These findings suggested that restoring the balance of the gut microbiome contributes to ameliorating cognitive impairment in AD, and that intranasal administration of MSNs-Bi may be an effective therapeutic strategy for the prevention of AD and intestinal disease.

Amine-functionalized mesoporous silica nanospheres (~80 nm) (NH 2 -MSNS) were prepared by a co-condensation method using tetraethyl orthosilicate and aminopropyltrimethoxysilane. The catalytic activities of the NH 2 -MSNS catalysts were investigated in water-medium Knoevenagel condensation. Under microwave irradiation, the NH 2 -MSNS catalysts showed higher efficiency than the common amine-functionalized mesoporous silicas (NH 2 -MCM-41) with long channels synthesized by traditional method. Moreover, the NH 2 -MSNS displayed comparable catalytic efficiencies with the homogeneous propylamine base-catalyst, and could also be easily recovered and reused up to eight times. Obviously, the easy diffusion and rapid mass transfer of substrate into the short channel mesopores played important roles in the significant improvement in the catalytic activities. Graphical Abstract Amine functionalized mesoporous silica nanoparticles organocatalyst was synthesized by surfactant directed co-concentration, which exhibited comparable efficiencies with the propylamine homogeneous catalyst in water-medium under microwave, and could be easily recycled and used repetitively.