Hashing has been widely used for large-scale search due to its low storage cost and fast query speed. By using supervised information, supervised hashing can significantly outperform unsupervised hashing. Recently, discrete supervised hashing and feature learning based deep hashing are two representative progresses in supervised hashing. On one hand, hashing is essentially a discrete optimization problem. Hence, utilizing supervised information to directly guide discrete (binary) coding procedure can avoid sub-optimal solution and improve the accuracy. On the other hand, feature learning based deep hashing, which integrates deep feature learning and hash-code learning into an end-to-end architecture, can enhance the feedback between feature learning and hash-code learning. The key in discrete supervised hashing is to adopt supervised information to directly guide the discrete coding procedure in hashing. The key in deep hashing is to adopt the supervised information to directly guide the deep feature learning procedure. However, most deep supervised hashing methods cannot use the supervised information to directly guide both discrete (binary) coding procedure and deep feature learning procedure in the same framework. In this paper, we propose a novel deep hashing method, called deep discrete supervised hashing (DDSH). DDSH is the first deep hashing method which can utilize pairwise supervised information to directly guide both discrete coding procedure and deep feature learning procedure and thus enhance the feedback between these two important procedures. Experiments on four real datasets show that DDSH can outperform other state-of-the-art baselines, including both discrete hashing and deep hashing baselines, for image retrieval.

Oligodendrocyte‐formed myelin sheaths play important roles in the neuronal functions in the central nervous system. In demyelinating diseases, such as Multiple Sclerosis, the myelin sheaths are damaged and the remyelinating process is somehow hindered. Restoration of the myelin sheaths requires the differentiation of the oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs). To discover small molecule compounds that might promote the OPC to OL differentiation, a high‐throughput screening system is established and L‐ascorbyl‐2‐phosphate (As‐2P), a stable form of Vitamin C (Vc), is found to greatly enhance the OPC to OL differentiation. As‐2P promotes gradual expression of OL lineage markers, including O4, CNPase and MBP, in a dose‐ and time‐dependent manner. It also facilitates the formation of myelin sheaths in OPC‐neuron co‐culture. As‐2P also promotes the repair of the myelin sheaths in vivo and provides significant therapeutic effect in a cuprizone‐mediated demyelination animal model. Interestingly, As‐2P's function in promoting OPC differentiation is not related to its antioxidant activity. And an intracellular rather than an extracellular mechanism might be involved. Considering the safe use of Vc as a dietary supplement for many years, it might also be used as an alternative medicine for CNS demyelinating diseases.

Myelin sheaths play important roles in neuronal functions. In the central nervous system (CNS), the myelin is formed by oligodendrocytes (OLs), which are differentiated from oligodendrocyte precursor cells (OPCs). In CNS demyelinating disorders such as multiple sclerosis (MS), the myelin sheaths are damaged and the remyelination process is hindered. Small molecule drugs that promote OPC to OL differentiation and remyelination may provide a new way to treat these demyelinating diseases. Here we report that donepezil, an acetylcholinesterase inhibitor (AChEI) developed for the treatment of Alzheimer's disease (AD), significantly promotes OPC to OL differentiation. Interestingly, other AChEIs, including huperzine A, rivastigmine, and tacrine, have no such effect, indicating that donepezil's effect in promoting OPC differentiation is not dependent on the inhibition of AChE. Donepezil also facilitates the formation of myelin sheaths in OPC-DRG neuron co-culture. More interestingly, donepezil also promotes the repair of the myelin sheaths in vivo and provides significant therapeutic effect in a cuprizone-mediated demyelination animal model. Donepezil is a drug that has been used to treat AD safely for many years; our findings suggest that it might be repurposed to treat CNS demyelinating diseases such as MS by promoting OPC to OL differentiation and remyelination.

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