No abstract

Recently, increasing evidence has suggested the association between gut dysbiosis and Alzheimer's disease (AD) progression, yet the role of gut microbiota in AD pathogenesis remains obscure. Herein, we provide a potential mechanistic link between gut microbiota dysbiosis and neuroinflammation in AD progression. Using AD mouse models, we discovered that, during AD progression, the alteration of gut microbiota composition leads to the peripheral accumulation of phenylalanine and isoleucine, which stimulates the differentiation and proliferation of pro-inflammatory T helper 1 (Th1) cells. The brain-infiltrated peripheral Th1 immune cells are associated with the M1 microglia activation, contributing to AD-associated neuroinflammation. Importantly, the elevation of phenylalanine and isoleucine concentrations and the increase of Th1 cell frequency in the blood were also observed in two small independent cohorts of patients with mild cognitive impairment (MCI) due to AD. Furthermore, GV-971, a sodium oligomannate that has demonstrated solid and consistent cognition improvement in a phase 3 clinical trial in China, suppresses gut dysbiosis and the associated phenylalanine/isoleucine accumulation, harnesses neuroinflammation and reverses the cognition impairment. Together, our findings highlight the role of gut dysbiosis-promoted neuroinflammation in AD progression and suggest a novel strategy for AD therapy by remodelling the gut microbiota.

Five-hundred-meter Aperture Spherical radio Telescope (FAST) is a Chinese mega-science project to build the largest single dish radio telescope in the world. Its innovative engineering concept and design pave a new road to realize a huge single dish in the most effective way. FAST also represents Chinese contribution in the international efforts to build the square kilometer array (SKA). Being the most sensitive single dish radio telescope, FAST will enable astronomers to jump-start many science goals, such as surveying the neutral hydrogen in the Milky Way and other galaxies, detecting faint pulsars, looking for the first shining stars, hearing the possible signals from other civilizations, etc. The idea of sitting a large spherical dish in a karst depression is rooted in Arecibo telescope. FAST is an Arecibo-type antenna with three outstanding aspects: the karst depression used as the site, which is large to host the 500-meter telescope and deep to allow a zenith angle of 40 degrees; the active main reflector correcting for spherical aberration on the ground to achieve a full polarization and a wide band without involving complex feed systems; and the light-weight feed cabin driven by cables and servomechanism plus a parallel robot as a secondary adjustable system to move with high precision. The feasibility studies for FAST have been carried out for 14 years, supported by Chinese and world astronomical communities. Funding for FAST has been approved by the National Development and Reform Commission in July of 2007 with a capital budget ~ 700 million RMB. The project time is 5.5 years from the commencement of work in March of 2011 and the first light is expected to be in 2016. This review intends to introduce the project of FAST with emphasis on the recent progress since 2006. In this paper, the subsystems of FAST are described in modest details followed by discussions of the fundamental science goals and examples of early science projects.