Network Pharmacology-Based Dissection of the Bioactive Compounds and Pharmacological Mechanisms of Yiqi Fumai Lyophilized Injection for the Treatment of Heart Failure

Objective:Yiqi Fumai Lyophilized Injection(YQFM),a Chinese medicine injection,has been widely used for the treatment of cardiovascular diseases,especially heart failure(HF).However,bioactive compounds and underlying mechanisms of YQFM in treating HF remain poorly understood.Materials and Methods:Network pharmacology was employed to investigate the bioactive compounds and mechanisms of YQFM.A compound-target network was constructed to screen bioactive compounds based on contribution index calculation.Then,an adriamycin-induced HF rat model was established to evaluate the cardio-protective effects of YQFM by hematoxylin and eosin staining and enzyme-linked immunosorbent assays.Results:Network pharmacology indicated that YQFM may alleviate HF through 36 compounds and 109 targets.Particularly,ginsenosides Rb1,Rg1,Re,Rf,Rb2,Rh1,schisandrin,and ginsenoside Rc were indicated as the top contributors of YQFM in treating HF.YQFM was predicted to act on multiple targets such as vascular endothelial growth factor A,interleukin-2(IL-2),IL-6,and IL-1β,as well as to regulate signaling pathways such as hypoxia-inducible factor 1,tumor necrosis factor,VEGF,and PI3K-Akt.The pharmacological study suggested that YQFM could attenuate cardiac injury and up-regulate plasma concentrations of VEGFR-1 and NO in HF rats.Ginsenoside Rb1,as the major contributor from network pharmacology analysis,also showed a cardioprotective effect and up-regulation of VEGFR-1 in plasma.Conclusions:Ginsenosides and schisandrin were predicted as the most important contributors to the cardioprotective effect of YQMF.Ginsenoside Rb1 was proved to alleviate HF and increase the plasma concentration of VEGFR-1.

Simultaneous determination of 35 constituents and elucidation of effective constituents in a multi-herb Chinese medicine formula Xiaoer-Feire-Kechuan

Xiaoer-Feire-Kechuan(XFK) is an 11-herb Chinese medicine formula to treat cough and pulmonary inflammation.The complicated composition rendered its chemical analysis and effective-component elucidation.In this study,we combined quantitative analysis and bioactivity test to reveal the antiinflammatory constituents of XFK.First,UPLC-DAD and UHPLC/Q-Orbitrap-MS methods were established and validated to quantify 35 analytes(covering 9 out of 11 herbs) in different XFK formulations.Parallel reaction monitoring mode built in Q-Orbitrap-MS was used to improve the sensitivity and selectivity.Then,anti-inflammatory activities of the 35 analytes were analyzed using in vitro COX-2 inhibition assay.Finally,major analytes forsythosides H,I,A(8-10),and baicalin(15)(total contents varied from 21.79 to 91.20 mg/dose in different formulations) with significant activities(inhibitory rate ≥ 80%) were proposed as the anti-inflammatory constituents of XFK.The present study provided an effective strategy to discover effective constituents of multi-herb formulas.

Model-free Demand Response Scheduling Strategy for Virtual Power Plants Considering Risk Attitude of Consumers

Driven by modern advanced information and communication technologies,distributed energy resources have great potential for energy supply within the framework of the virtual power plant(VPP).Meanwhile,demand response(DR)is becoming increasingly important for enhancing the VPP operation and mitigating the risks associated with the fluctuation of renewable energy resources(RESs).In this paper,we propose an incentivebased DR program for the VPP to minimize the deviation penalty from participating in the power market.The Markov decision process(MDP)with unknown transition probability is constructed from the VPP’s prospective to formulate an incentivebased DR program,in which the randomness of consumer behavior and RES generation are taken into consideration.Furthermore,a value function of prospect theory(PT)is developed to characterize consumer’s risk attitude and describe the psychological factors.A model-free deep reinforcement learning(DRL)-based approach is proposed to deal with the randomness existing in the model and adaptively determine the optimal DR pricing strategy for the VPP,without requiring any system model information.Finally,the results of cases tested demonstrate the effectiveness of the proposed approach.

乌拉尔甘草地上部分的化学成分及其PTP1B与α-葡萄糖苷酶抑制活性研究

从乌拉尔甘草地上部分分离得到11个化合物,分别是glycyuralin Q(1),glycyuralin R(2),licoriphenone(3),奥洛波尔(4),trifoliol(5),7,2′,4′-三羟基-5-甲氧基-3-香豆素(6),11-羰基-9(Z),12(Z)-十八碳二烯酸(7),11-羰基-9(E),12(E)-十八碳二烯酸(8),甘草利酮(9),格里西轮(10),2′-羟基刺芒柄花素(11)。其中1和2为新化合物,其结构采用1D、2D NMR及HR-MS等技术进行鉴定。分别筛选11个化合物对PTP1B及α-葡萄糖苷酶的抑制活性,发现化合物1、2和10对PTP1B酶有较好的抑制活性,其IC50值分别是1.43、4.71和3.79μM;化合物2、4和10抑制α-葡萄糖苷酶的IC50值分别是13.61、11.13和17.48μM。

Packaging and Temperature Compensation of Fiber Bragg Grating for Strain Sensing： A Survey

During last decades, sensor elements based on the fiber Bragg grating （FBG） have been widely studied and developed due to the advantages of immunity to electromagnetic interference, compact size, high precision, and so on. The FBG itself is sensitive to axial strain and temperature variation directly and can indirectly measure these complex physical parameters, such as pressure, displacement, and vibration, by using some specially designed elastic structures to convert them into the axial strain of the FBG. Whether the FBG is fixed on the measured object to measure the strain directly or fixed on an elastic structure body to measure other physical quantities, these types of FBGs could be collectively called as strain sensing FBGs. The packaging of the FBG has important influence on FBG characteristics that directly affect the measurement accuracy, such as strain transfer, temperature characteristic, and spectral shape. This paper summarizes the packaging methods and corresponding temperature compensation methods of the currently reported strain sensing FBGs, focusing especially on fully pasted FBG, pre-stretched FBG with double-end fixed, and metallic packaging. Furthermore, the advantages and drawbacks of different packaging methods have been analyzed, which can provide a reference for future researches.

Hybrid Energy Sharing Mechanism for Integrated Energy Systems Based on the Stackelberg Game

Integrating the sharing economy and the power industry is of positive significance for the development of the energy market.With the energy market transforming from a traditional vertical structure to an interactive and competitive structure,users'roles need to change,along with supply and demand interacting more frequently.Thus,the traditional centralized optimization method for a single energy source can hardly reveal the complex multi-entity behavior of multi-energy coupling.Therefore,this paper establishes a distributed electrical-gas-thermal energy sharing mechanism centered on an energy hub that can converse energy,and build a more applicable integrated energy system body.First,the supply-demand interaction and the energy conversion process is constructed with reference to the operationa丨mode of’a sharing economy and the dual role of prosumers.A Stackelberg model is established with the integrated energy system operator as the leader and prosumers as the followers,to simultaneously optimize the profit of the leader in the upper level and the comfort of the fo!lowers,energy use and utility in the lower level.Furthermore,for protecting the participants’privacy,a distributed algorithm is used to find the optimal solution to equilibrate the model,and the existence and uniqueness of the solution is proved.Finally,a case study validates the effectiveness of the hybrid energy sharing mechanism and provides a reference for the integration of the energy sharing economy with the integrated energy system.

Schaftoside inhibits 3CL^(pro)and PL^(pro)of SARS-CoV-2 virus and regulates immune response and inflammation of host cells for the treatment of COVID-19

It is an urgent demand worldwide to control the coronavirus disease 2019(COVID-19)pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The 3-chymotrypsin-like protease(3CL^(pro))and papain-like protease(PL^(pro))are key targets to discover SARS-CoV-2 inhibitors.After screening 12 Chinese herbal medicines and 125 compounds from licorice,we found that a popular natural product schaftoside inhibited 3CL^(pro)and PL^(pro)with IC_(50)values of 1.73±0.22 and 3.91±0.19μmol/L,respectively,and inhibited SARS CoV-2 virus in Vero E6 cells with EC_(50)of 11.83±3. 23μmol/L. Hydrogen-deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of3CLpro, and K157, E167 and A246 of PLpro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The antiinflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.

Network-Constrained Energy Consumption Game for Dynamic Pricing Markets

The electricity distribution network is experiencing a profound transformation with the concept of the smart grid,providing possibilities for selfish consumers to interact with the distribution system operator(DSO)and to maximize their individual energy consumption utilities.However,this profitseeking behavior among consumers may violate the network constraints,such as line flows,transformer capacity and bus voltage magnitude limits.Therefore,a network-constrained energy consumption(NCEC)game among active load aggregators(ALAs)is proposed to guarantee the safety of the distribution network.The temporal and spatial constraints of an ALA are both considered,which leads the formulated model to a generalized Nash equilibrium problem(GNEP).By resorting to a well-developed variational inequality(VI)theory,we study the existence of solutions to the NCEC game problem.Subsequently,a two-level distributed algorithm is proposed to find the variational equilibrium(VE),a fair and stable solution to the formulated game model.Finally,the effectiveness of the proposed game model and the efficiency of the distributed algorithm are tested on an IEEE-33 bus system.