Neural stem cell-derived exosomes promote mitochondrial biogenesis and restore abnormal protein distribution in a mouse model of Alzheimer's disease

Mitochondrial dysfunction is a hallmark of Alzheimer’s disease.We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 mice.Because Alzheimer’s disease affects the entire brain,further research is needed to elucidate alterations in mitochondrial metabolism in the brain as a whole.Here,we investigated the expression of several important mitochondrial biogenesis-related cytokines in multiple brain regions after treatment with neural stem cell-derived exosomes and used a combination of whole brain clearing,immunostaining,and lightsheet imaging to clarify their spatial distribution.Additionally,to clarify whether the sirtuin 1(SIRT1)-related pathway plays a regulatory role in neural stem cell-de rived exosomes interfering with mitochondrial functional changes,we generated a novel nervous system-SIRT1 conditional knoc kout AP P/PS1mouse model.Our findings demonstrate that neural stem cell-de rived exosomes significantly increase SIRT1 levels,enhance the production of mitochondrial biogenesis-related fa ctors,and inhibit astrocyte activation,but do not suppress amyloid-βproduction.Thus,neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer’s disease that activates the SIRT1-PGC1αsignaling pathway and increases NRF1 and COXIV synthesis to improve mitochondrial biogenesis.In addition,we showed that the spatial distribution of mitochondrial biogenesis-related factors is disrupted in Alzheimer’s disease,and that neural stem cell-derived exosome treatment can reverse this effect,indicating that neural stem cell-derived exosomes promote mitochondrial biogenesis.

Numerical Study of the Influences of a Monsoon Gyre on Intensity Changes of Typhoon Chan-Hom(2015)

Typhoon Chan-Hom （2015） underwent a weakening in the tropical western North Pacific （WNP） when it interacted with a monsoon gyre, but all operational forecasts failed to predict this intensity change. A recent observational study indicated that it resulted from its interaction with a monsoon gyre on the 15-30-day timescale. In this study, the results of two numerical experiments are presented to investigate the influence of the monsoon gyre on the intensity changes of Typhoon Chan-Hom （2015）. The control experiment captures the main observed features of the weakening process of Chan-Hom （2015） during a sharp northward turn in the Philippine Sea, including the enlargement of the eye size, the development of strong convection on the eastern side of the monsoon gyre, and the corresponding strong outer inflow. The sensitivity experiment suggests that intensity changes of Chan-Hom （2015） were mainly associated with its interaction with the monsoon gyre. When Chan-Horn （2015） initially moved westward in the eastern part of the monsoon gyre, the monsoon gyre enhanced the inertial stability for the intensification of the typhoon. With its coalescence with the monsoon gyre, the development of the strong convection on the eastern side of the monsoon gyre prevented moisture and mass entering the inner core of Chan-Hom （2015）, resulting in the collapse of the eyewall. Thus, the weakening happened in the deep tropical WNP region. The numerical simulations confirm the important effects of the interaction between tropical cyclones and monsoon gyres on tropical cyclone intensity.