DC Emergency Power Control Strategy for AC/DC Multi-Channel Interconnected System

Inter-regional transmission line fault often results in power flow transferring, tie-line overloading and system islanding. Traditional control methods such asgenerator tripping and load shedding are costly, and also have undesirable impacts on theloadside. In this paper, a new emergency power control strategy is proposed for multi-channel interconnected system by using the overload capacity of non-fault DC lines. First of all, the capacity of emergency power control can be acquired by critical transmission power of a certain tie-line for stability. Secondly, the shortest electric distance can be calculated by Dijkstra algorithm, and then the priority of emergency control of the DC lines can be obtained by the entropy weight method. When the inter-regional transmission power decreases and the effect of single DC line emergency control is poor, the multi-channel cooperative emergency control strategy is proposed to ensure the system stability. Simulation results verify the effectiveness of the method proposed.

SIRT1 activation synergizes with FXR agonism in hepatoprotection via governing nucleocytoplasmic shuttling and degradation of FXR

Farnesoid X receptor(FXR)is widely accepted as a promising target for various liver diseases;however,panels of ligands in drug development show limited clinical benefits,without a clear mechanism.Here,we reveal that acetylation initiates and orchestrates FXR nucleocytoplasmic shuttling and then enhances degradation by the cytosolic E3 ligase CHIP under conditions of liver injury,which represents the major culprit that limits the clinical benefits of FXR agonists against liver diseases.Upon inflammatory and apoptotic stimulation,enhanced FXR acetylation at K217,closed to the nuclear location signal,blocks its recognition by importin KPNA3,thereby preventing its nuclear import.Concomitantly,reduced phosphorylation at T442 within the nuclear export signals promotes its recognition by exportin CRM1,and thereby facilitating FXR export to the cytosol.Acetylation governs nucleocytoplasmic shuttling of FXR,resulting in enhanced cytosolic retention of FXR that is amenable to degradation by CHIP.SIRT1 activators reduce FXR acetylation and prevent its cytosolic degradation.More importantly,SIRT1 activators synergize with FXR agonists in combating acute and chronic liver injuries.In conclusion,these findings innovate a promising strategy to develop therapeutics against liver diseases by combining SIRT1 activators and FXR agonists.

Combined obeticholic acid and apoptosis inhibitor treatment alleviates liver fibrosis

Obeticholic acid(OCA), the first FXR-targeting drug, has been claimed effective in the therapy of liver fibrosis. However, recent clinical trials indicated that OCA might not be effective against liver fibrosis, possibly due to the lower dosage to reduce the incidence of the side-effect of pruritus. Here we propose a combinatory therapeutic strategy of OCA and apoptosis inhibitor for combating against liver fibrosis. CCl4-injured mice, D-galactosamine/LPS(GalN/LPS)-treated mice and cycloheximide/TNFα(CHX/TNFα)-treated HepG2 cells were employed to assess the effects of OCA, or together with IDN-6556, an apoptosis inhibitor. OCA treatment significantly inhibited hepatic stellate cell(HSC)activation/proliferation and prevented fibrosis. Elevated bile acid(BA) levels and hepatocyte apoptosis triggered the activation and proliferation of HSCs. OCA treatment reduced BA levels but could not inhibit hepatocellular apoptosis. An enhanced anti-fibrotic effect was observed when OCA was co-administrated with IDN-6556. Our study demonstrated that OCA inhibits HSCs activation/proliferation partially by regulating BA homeostasis and thereby inhibiting activation of HSCs. The findings in this study suggest that combined use of apoptosis inhibitor and OCA at lower dosage represents a novel therapeutic strategy for liver fibrosis.