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INTRODUCTION: Subtypes of the dipeptidyl peptidase (DPP) family, such as DPP4, are reportedly associated with memory impairment. DPP9 is widely distributed in cells throughout the body, including the brain. However, whether DPP9 regulates memory has not yet been elucidated. OBJECTIVES: This study aimed to elucidate the role of DPP9 in memory, as well as the underlying molecular mechanism. METHODS: We performed immunofluorescence on mouse brains to explore the distribution of DPP9 in different brain regions and used AAV vectors to construct knockdown and overexpression models. The effects of changing DPP9 expression on memory were demonstrated through behavioral experiments. Finally, we used electrophysiology, proteomics and affinity purification mass spectrometry (AP-MS) to study the molecular mechanism by which DPP9 affects memory. RESULTS: Here, we report that DPP9, which is found almost exclusively in neurons, is expressed and has enzyme activity in many brain regions, especially in the hippocampus. Hippocampal DPP9 expression increases after fear memory formation. Fear memory was impaired by DPP9 knockdown and enhanced by DPP9 protein overexpression in the hippocampus. According to subsequent hippocampal proteomics, multiple pathways, including the peptidase pathway, which can be bidirectionally regulated by DPP9. DPP9 directly interacts with its enzymatic substrate neuropeptide Y (NPY) in neurons. Hippocampal long-term potentiation (LTP) is also bidirectionally regulated by DPP9. Moreover, inhibiting DPP enzyme activity impaired both LTP and memory. In addition, AP-MS revealed that DPP9-interacting proteins are involved in the functions of dendritic spines and axons. By combining AP-MS and proteomics, DPP9 was shown to play a role in regulating actin functions. CONCLUSION: Taken together, our findings reveal that DPP9 affects the CNS not only through enzymatic activity but also through protein-protein interactions. This study provides new insights into the molecular mechanisms of memory and DPP family functions.
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We study locating propagation sources in complex networks. We proposed an multi-source location algorithm for different propagation dynamics by using sparse observations. Without knowing the propagation dynamics and any dynamic parameters, we can calculate node centrality based on the character that positive correlation between inform time of nodes and geodesic distance between nodes and sources. The algorithm is robust and have high location accuracy for any number of sources. We study locatability of the proposed source location algorithm and present a corresponding strategy to select observer nodes based on greedy algorithm. All simulations on both model and real-world networks proved the feasibility and validity of this algorithm.
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PURPOSE: This study analysed the mechanical features of the extraction space closure in clear aligners through mechanical research. METHODS: A patient with four first premolars extraction was chosen as sample, and four plans with clear aligners for space closure were designed, including anterior retraction entirely, anterior retraction dispersedly, posterior movement mesially and posterior movement dispersedly. Finite element analysis was performed separately. RESULTS: In anterior retraction, when there was no anterior space, the force acted on them more evenly, and the posteriors needed to provide more anchorage; when anterior space existed, the force acted on the central incisors first and largely, and the posteriors needed to provide less anchorage. In posterior anchorage, when the posteriors moved entirely with mesial movement, it might help to protect second premolar's anchorage while molars would receive more mesial force; when the posteriors moved separately without designed movement, the second premolar would undertake more anchorage and more tendency to incline mesially; when the posteriors moved entirely without designed movement, the anchorage would distribute more evenly. CONCLUSIONS: Selection of the way of retracting anteriors should be based on the difference of stress distribution in different ways in addition to individual discrepancy and clinical facts. Selection of the way of moving posteriors should be based on the distribution of anchorage as well as avoiding posterior open bite. Less amount of correction in each step has better axial control.