Molecular Mechanism of Ginseng in Treating Nephrotic Syndrome Based on Network Pharmacology and Experimental Verification

[Objectives]To study the potential molecular mechanism of ginseng in treating nephrotic syndrome(NS)by using network pharmacology,molecular docking and experimental verification methods.[Methods]The active components and targets of ginseng were obtained through the network pharmacology database,and the potential targets for the treatment of NS were predicted.The STRING data platform and Cytoscape software were used to construct protein interaction network,and carry out GO and KEGG enrichment analysis.Molecular docking of active components of ginseng and core targets was performed.The in vitro experiment verified the improvement effect of kaempferol,a key active ingredient of ginseng,on podocyte injury.[Results]After screening,17 active components of ginseng and 38 key targets for treating NS were obtained.GO and KEGG enrichment analysis showed that NF-κB,MAPK and other inflammatory pathways were involved.Molecular docking results show that the core components had good binding activity to key targets.The results of in vitro experiments show that kaempferol can reduce the phosphorylation level of AKT1,down-regulate the expression levels of NF-κB p65 and p-NF-κB p65,play an anti-inflammatory effect by inhibiting the activation of NF-κB pathway,and improve podocyte injury.[Conclusions]Ginseng may play a role in the treatment of NS by regulating multiple targets and pathways such as inflammatory response,substance metabolism,and signal transduction.

Heat and power load dispatching considering energy storage of district heating system and electric boilers

As one of promising clean and low-emission energy, wind power is being rapidly developed in China.However, it faces serious problem of wind curtailment,particularly in northeast China, where combined heat and power(CHP) units cover a large proportion of the district heat supply. Due to the inherent strong coupling between the power and the heat load, the operational flexibility of CHP units is severely restricted in winter to meet the heat supply demand, which imparts considerable stress on the wind power connection to the grid. To promote the integration of wind power and enhance the flexibility of CHP units, this paper presented a method of heat and power load dispatching by exploring the energy storage ability of electric heating boilers and district heating systems. The optimization results indicate that the proposed method can integrate additional wind power into the grid and reduce the coal consumption of CHP units over the optimized period. Furthermore, the thermal inertia of a district heating system is found to contribute more to the reduction of coal consumption, whereas the electric heating boilers contribute to lower wind curtailment.

Alopecuroidines A-C, three matrine-derived alkaloids from the seeds of Sophora alopecuroides

Three matrine-derived alkaloids, alopecuroidine A(1), alopecuroidine B(2 a) and alopecuroidine C(2 b)were isolated from the seeds of Sophora alopecuroides. Their structures were elucidated by extensive spectroscopic analyses and X-ray diffraction. Three compounds possess an unprecedented rearranged fused7/6/5/6 tetracyclic skeleton with a diazacycloheptane structure. Their plausible biosynthetic pathway was also proposed. The anti-proliferative activities of compounds 1 and 2 a were examined by the MTT assay.Compound 1 inhibited the viability of human lung cancer A549 cells, having a half maximal inhibitory concentration(IC50) of 7.58 ± 2.47 μmol/L at 72 h. The flow cytometric analysis suggested that 1 inhibited A549 cell growth by inducing apoptosis and cell-cycle arrest. Additionally, 1 induced the loss of mitochondrial membrane potential, elevated intracellular reactive oxygen species, increased the Bax/Bcl-2 ratio, stimulated cleaved-caspase-3 and P53 protein levels, and suppressed the pro-caspase-3 level. Thus,1 appeared to induce A549 cells apoptosis through a mitochondria-mediated apoptotic pathway.

Generic,efficient,and effective deobfuscation and semantic-aware attack detection for Power Shell scripts

In recent years,Power Shell has increasingly been reported as appearing in a variety of cyber attacks.However,because the PowerShell language is dynamic by design and can construct script fragments at different levels,state-of-the-art static analysis based Power Shell attack detection approaches are inherently vulnerable to obfuscations.In this paper,we design the first generic,effective,and lightweight deobfuscation approach for PowerShell scripts.To precisely identify the obfuscated script fragments,we define obfuscation based on the differences in the impacts on the abstract syntax trees of PowerShell scripts and propose a novel emulation-based recovery technology.Furthermore,we design the first semantic-aware PowerShell attack detection system that leverages the classic objective-oriented association mining algorithm and newly identifies 31 semantic signatures.The experimental results on 2342 benign samples and 4141 malicious samples show that our deobfuscation method takes less than 0.5 s on average and increases the similarity between the obfuscated and original scripts from 0.5%to 93.2%.By deploying our deobfuscation method,the attack detection rates for Windows Defender and VirusTotal increase substantially from 0.33%and 2.65%to 78.9%and 94.0%,respectively.Moreover,our detection system outperforms both existing tools with a 96.7%true positive rate and a 0%false positive rate on average.