Recent studies on sphingolipids suggest that acid sphingomyelinase (ASM), which plays a central role in the pathogenesis of major depression, is emerging to be a novel target for developing antidepressants. Herein we first described the design, synthesis, and biological evaluation of hydroxamic acid-based direct inhibitors of ASM with the effort of validating their antidepressant effects in vivo. As a result, a series of novel ASM inhibitors were developed using a structure-based approach. Our studies demonstrated that the administration of 21b improved depression-like behaviors of rats. Importantly, this positive result was relevant to the inhibition of ASM and the increasing neurogenesis in hippocampus. To the best of our knowledge, this is the first time that direct inhibitors of ASM were developed to support the possibility of ASM as a potential therapeutic target for depression.
To fulfill the requirement of fields such as robotics, aviation, and special machining, motors with quill shafts or outer rotors have been used. For these special motors, the photoelectric encoder’s volume is normally too big and easy to be polluted by oil or dust; magnetic encoder normally has poor accuracy, and alnico piece may not provide enough magnetic field coverage area. The aim of this essay is to find a new structure of magnetic encoder to improve the precision and magnetic field coverage area. By using two multi-pole alnico rings with a different number of pole pairs to provide a magnetic field, the coverage area could be improved. The position differences between two alnicos pole positions are used to calculate absolute angle value, so the accuracy of the encoder could be absolute and no less than that of a combined magnetic encoder with the same number of pole pairs. A special algorithm is proposed for decoding. This new kind of magnetic encoder could be used on special motors with quill shafts or outer rotors. Its volume and weight are less than the photoelectric encoder and have better performance on antipollution. The alnico ring is easy to modify to suit the structure of the motor.
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