Tetrahydrohyperforin(IDN5706) targets the endoplasmic reticulum for autophagy activation： potential mechanism for Alzheimer＇s disease therapy

Alzheimer’s disease（AD）is the most common form of dementia worldwide among the older population.To date,there is no therapy to stop the destruction of brain cells and all the available treatments only compensate for the loss of synaptic transmission,thus resulting in marginal benefits to patients.

Study on the Potential Mechanism of Drug Pair "Honeysuckle-Astragalus" on COVID-19 based on Network Pharmacology

Objective:To explore the potential mechanism of drug pair "Honeysuckle-Astragalus" on 2019-nCoV using network pharmacology.Methods:The active compounds of Honeysuckle-Astragalus were searched by TCMSP database platform and BATMAN-TCM platform, and the targets related to the active compounds were searched and screened out through the database. The targets related to 2019-nCoV were screened out through OMIM and GeneCards databases. The network diagram of "drug-component-disease-target" was constructed by using the Cytoscape software, and the PPI network diagram of target protein interaction was constructed by using the STRING database. DAVID database was used for gene ontology(GO) analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.Results:23 active components of Honeysuckle, 20 active components of Astragalus and 10 targets of intersection of active components and 2019-nCoV were screened, mainly including NOS3, DPP4, TN, FIL6, etc. Using DAVID database analysis and taking P<0.05 as the screening criteria, 85 biological processes were obtained, of which the first 20 were related to processes such as response to antibiotic, lipopolysaccharide-mediated signaling pathway, negative regulation of cell proliferation, etc. Twenty-six signal pathways were screened, among which the first 20 were related to Malaria, Herpes simplex infection, TNF signaling pathway, etc. Conclusion: Honeysuckle-Astragalus may have the characteristic of multiple components, multiple targets and multiple pathways in the treatment of 2019-nCoV,and its mechanism of action may be to treat 2019-nCoV through antiviral infection and repair of lung injury, which provides a theoretical basis for the treatment of 2019-nCoV with honeysuckle-Astragalus in clinic.

Dimethylacetamide-induced Hepatic Injury in Vitro: Mechanism and Potential Preventive Strategy

N,N-Dimethylacetamide （DMAc） is a widely used organic solvent in modern chemical industry with low to moderate hepatotoxicity to occupational health of employees. But so far, there are fewer and less conclusive data concerning its pathogenic mechanism in detail. In current study, the toxicity of DMAc was firstly investigated on human normal hepatocytes （LO-2）, using a series of molecular biology measurements to ananlyze the effect and mechanism of DMAc-induced hepatic cell injury and explore effective prophylactic measures. We found that DMAc triggered LO-2 apoptosis in a obviously dose-dependent manner, caused by increased ROS generation and activation of Bcl-2 pathway. Significantly, glutathione （GSH） rather than vitamin C （Vit C） could partially inhibit DMAc-induced apoptosis thus showing potential as a effective precaution for workers.

Differential Proteomics Reveals the Potential Injury Mechanism Induced by Heavy Ion Radiation in Mice Ovaries

In the present study, we used a proteomics approach based on a two-dimensional electrophoresis （2-DE） reference map to investigate protein expression in the ovarian tissues of pubertal Swiss-Webster mice subjected to carbon ion radiation （CIR）. Among the identified proteins, ubiquitin carboxy-terminal hydrolase L1 （UCH-L1） is associated with the cell cycle[1] and that it influences proliferation in ovarian tissues. We analyzed the expression of UCH-L1 and the proliferation marker proliferation cell nuclear antigen （PCNA） following CIR using immunoblotting and immunofluorescence. The proteomics and biochemical results provide insight into the underlying mechanisms of CIR toxicity in ovarian tissues.

Prediction of the mechanism of prostate prescription Ⅰ in the treatment of chronic prostatitis based on integrative pharmacology of traditional Chinese medicine

Objective:To investigate potential mechanism of Prostate prescriptionⅠin the treatment of chronic prostatitis based on integrated pharmacology.Methods:with the help of TCMIP,the effective compounds of Prostate prescriptionⅠwere screened,and the potential target database of Prostate prescriptionⅠwas established by using the target prediction function of TCMIP.Based on the Human Phenotype Ontology database and protein interaction network(PPI)database,the disease target of CP was identified and the target interaction network was constructed;Through the GO function analysis and KEGG pathway enrichment analysis of the candidate targets,combined with Chinese and foreign literature studies to predict the potential Signaling pathway of Prostate prescriptionⅠin the treatment of CP.Results:79 effective compounds of Prostate prescriptionⅠexerted its effect on 33 targets through 11 pathways.Conclusion:Clinical efficacy of Prostate prescriptionⅠon CP may be reflected in antiinflammation and anti-tumor,cell metabolism,immune regulation,neuroregulation and so on.

“Three medicines and three formulas”in COVID-19:from bench to bedside

Chinese guideline has proven effective in the fight against coronavirus disease 2019(COVID-19)during the global spread of the epidemic.Traditional Chinese medicine(TCM)is widely recognized for its effectiveness in alleviating symptoms,inhibiting disease progress,reducing mortality,and improving the cure rate of patients with COVID-19.During the pandemic,“three medicines and three formulas”(TMTFs)stood out from hundreds of others in registered clinical studies,which became highly recommended as TCM for COVID-19 treatment.The TMTFs not only effectively relieve the clinical symptoms of fever,cough,fatigue,and phlegm,but also substantially shorten the time of nucleic acid negative conversion,improve lung computed tomography imaging features and inflammation,ameliorate clinical biochemical indicators,and reduce sequelae.Their potential pharmacological mechanisms are mainly related to the crosstalk between viral toxicity,endothelial damage,cytokine storm,immune response,and microthrombus.In brief,the clinical effects and the potential mechanisms of TMTFs on COVID-19 were systematically analyzed and summarized covering the entirety of disease development,including virus invasion and replication,immune response and cytokine storm,and acute respiratory distress syndrome and multiple organ dysfunction syndrome.This review provides a theoretical basis and reference for the in-depth understanding of the positive role of TMTFs in COVID-19 treatment.

Liver injury in COVID-19:Detection,pathogenesis,and treatment

In the early December 2019,a novel coronavirus named severe acute respiratory syndrome coronavirus 2 was first reported in Wuhan,China,followed by an outbreak that spread around the world.Numerous studies have shown that liver injury is common in patients with coronavirus disease 2019(COVID-19),and may aggravate the severity of the disease.However,the exact cause and specific mechanism of COVID-associated liver injury needs to be elucidated further.In this review,we present an analysis of the clinical features,potential mechanisms,and treatment strategies for liver injury associated with COVID-19.We hope that this review would benefit clinicians in devising better strategies for management of such patients.

Sodium glucose cotransporter 2 inhibitors:New horizon of the heart failure pharmacotherapy

Sodium-glucose cotransporter 2(SGLT2)inhibitors have gained momentum as the latest class of antidiabetic agents for improving glycemic control.Large-scale clinical trials have reported that SGLT2 inhibitors reduced cardiovascular outcomes,especially hospitalization for heart failure in patients with type 2 diabetes mellitus who have high risks of cardiovascular disease.Accumulating evidence has indicated that beneficial effects can be observed regardless of the presence or absence of type 2 diabetes mellitus.Accordingly,the Food and Drug Administration approved these agents specifically for treating patients with heart failure and a reduced ejection fraction.It has been concluded that canagliflozin,dapagliflozin,empagliflozin,or ertugliflozin can be recommended for preventing hospitalization associated with heart failure in patients with type 2 diabetes and established cardiovascular disease or those at high cardiovascular risk.In the present review,we explore the available evidence on SGLT2 inhibitors in terms of the cardioprotective effects,potential mechanisms,and ongoing clinical trials that may further clarify the cardiovascular effects of the agents.

An empirical description for the hinge-like mechanism in single-layer black phosphorus:The angle–angle cross interaction

The single-layer black phosphorus is characterized by its puckered configuration that pos- sesses the hinge-like behavior, which leads to the highly anisotropic in-plane Poisson＇s ratios and the negative out-of-plane Poisson＇s ratio. We demonstrate that the hinge-like mechanism can be described by the angle-angle cross interaction, which, combined with the bond stretching and angle bending interactions, is able to provide a good description for the mechanical properties of single-layer black phosphorus. We also propose a nonlinear angle-angle cross interaction, which follows the form of Stillinger-Weber potential and can be advantageous for molecular dynamics simulations of single-layer black phosphorus under large deformation.

Traditional Chinese medicine in COVID-19

COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2(SARSCo V-2)has spread across the globe,posing an enormous threat to public health and safety.Traditional Chinese medicine(TCM),in combination with Western medicine(WM),has made important and lasting contributions in the battle against COVID-19.In this review,updated clinical effects and potential mechanisms of TCM,presented in newly recognized three distinct phases of the disease,are summarized and discussed.By integrating the available clinical and preclinical evidence,the efficacies and underlying mechanisms of TCM on COVID-19,including the highly recommended three Chinese patent medicines and three Chinese medicine formulas,are described in a panorama.We hope that this comprehensive review not only provides a reference for health care professionals and the public to recognize the significant contributions of TCM for COVID-19,but also serves as an evidence-based in-depth summary and analysis to facilitate understanding the true scientific value of TCM.

A New Resource-Saving,High Chromium and Manganese Super Duplex Stainless Steels 29Cr-12Mn-2Ni-1Mo-xN

A new family of resource saving, high chromium and manganese super duplex stainless steels （DSSs）, with a composition in mass percent, % of Cr 0.29, Mn 0.12, Ni 2.0, Mo i. 0, and N 0. 51-0. 68, has been developed by examining the effect of N on the microstructure, mechanical properties and corrosion properties. The results show that these alloys have a balanced ferrite-austenite relation. The austenite volume fraction decreases with the solution treatment temperature, but it increases with an increase in N content. The increases in nitrogen enhance the ultimate tensile strength （UTS） and reduce the ductility of the material slightly. The pitting corrosion potential increases first and then decreases with an increase in nitrogen content when the amount of N arrives to 0.68%. The yield stress and ultimate tensile strength of solution treated samples were more than 680 and 900 MPa, the elongation of experimental alloys are higher than 30%, respectively, what is more, the pitting potentials were beyond 1 100 mV.