Blood–brain barrier (BBB) damage after ischemia significantly influences stroke outcome. Compound LFHP-1c was previously discovered with neuroprotective role in stroke model, but its mechanism of action on protection of BBB disruption after stroke remains unknown. Here, we show that LFHP-1c, as a direct PGAM5 inhibitor, prevented BBB disruption after transient middle cerebral artery occlusion (tMCAO) in rats. Mechanistically, LFHP-1c binding with endothelial PGAM5 not only inhibited the PGAM5 phosphatase activity, but also reduced the interaction of PGAM5 with NRF2, which facilitated nuclear translocation of NRF2 to prevent BBB disruption from ischemia. Furthermore, LFHP-1c administration by targeting PGAM5 shows a trend toward reduced infarct volume, brain edema and neurological deficits in nonhuman primate
Macaca fascicularis
model with tMCAO. Thus, our study identifies compound LFHP-1c as a firstly direct PGAM5 inhibitor showing amelioration of ischemia-induced BBB disruption
in vitro
and
in vivo
, and provides a potentially therapeutics for brain ischemic stroke.
With the development of cloud computing, task scheduling has been an important problem in cloud computing. We should consider not only the performance of resources, but also the reliability of resources and users for resource allocation and scheduling. We proposed a trusted model based on game theory to evaluate the trusted scores of cloud participants. Simulation results show cloud users and resource tend to send feedback information to agents in order to increase their scores. Also trusted score is an important factor to affect the decision of resource allocation. Results show our model improved resource utilization and load balance.
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