Ensemble Numerical Simulations of Realistic SEP Events and the Inspiration for Space Weather Awareness

The solar energetic particle(SEP)event is a kind of hazardous space weather phenomena,so its quantitative forecast is of great importance from the aspect of space environmental situation awareness.We present here a set of SEP forecast tools,which consists of three components:(1)a simple polytropic solar wind model to estimate the background solar wind conditions at the inner boundary of 0.1 AU(about 20 R⊙);(2)an ice-cream-cone model to estimate the erupted coronal mass ejection(CME)parameters;and(3)the improved Particle Acceleration and Transport in the Heliosphere(i PATH)model to calculate particle fluxes and energy spectra.By utilizing the above models,we have simulated six realistic SEP events from 2010 August 14 to 2014 September 10,and compared the simulated results to the Geostationary Operational Environmental Satellites(GOES)spacecraft observations.The results show that the simulated fluxes of>10 Me V particles agree with the observations while the simulated fluxes of>100 Me V particles are higher than the observed data.One of the possible reasons is that we have adopted a simple method in the model to calculate the injection rate of energetic particles.Furthermore,we have conducted the ensemble numerical simulations over these events and investigated the effects of different background solar wind conditions at the inner boundary on SEP events.The results imply that the initial CME density plays an important role in determining the power spectrum,while the effect of varying background solar wind temperature is not significant.Naturally,we have examined the influence of CME initial density on the numerical prediction results for virtual SEP cases with different CME ejection speeds.The result shows that the effect of initial CME density variation is inversely associated with CME speed.

Therapeutic strategies of glioblastoma (GBM):The current advances in the molecular targets and bioactive small molecule compounds

Glioblastoma(GBM)is the most common aggressive malignant tumor in brain neuroepithelial tumors and remains incurable.A variety of treatment options are currently being explored to improve patient survival,including small molecule inhibitors,viral therapies,cancer vaccines,and monoclonal antibodies.Among them,the unique advantages of small molecule inhibitors have made them a focus of attention in the drug discovery of glioblastoma.Currently,the most used chemotherapeutic agents are small molecule inhibitors that target key dysregulated signaling pathways in glioblastoma,including receptor tyrosine kinase,PI3K/AKT/mTOR pathway,DNA damage response,TP53 and cell cycle inhibitors.This review analyzes the therapeutic benefit and clinical development of novel small molecule inhibitors discovered as promising anti-glioblastoma agents by the related targets of these major pathways.Meanwhile,the recent advances in temozolomide resistance and drug combination are also reviewed.In the last part,due to the constant clinical failure of targeted therapies,this paper reviewed the research progress of other therapeutic methods for glioblastoma,to provide patients and readers with a more comprehensive understanding of the treatment landscape of glioblastoma.

Discovery of Tryptophan-tetrahydroisoquinoline Derivatives as Multifunctional Agents for Treatment of Alzheimer's Disease

Comprehensive Summary The cholinesterases are essential targets implicated in the pathogenesis of Alzheimer's disease(AD).We have identified tryptophan-tetrahydroisoquinoline derivatives as selective micro-nanomolar butyrylcholinesterase(BChE)inhibitors.Molecular docking was applied for the rational design and binding mode analysis.They were defined according to their target inhibitory activity,low cytotoxicity,predicted permeability through the blood-brain barrier(BBB),and in vivo cognitive improvement.Additionally,the preferred compound showed ability to decrease self-induced Aβ1-42 aggregation and Aβ1-42 induced SH-SY5Y cell injury.Altogether,these factors indicated their potential as unique lead compounds for AD treatment.

A Practical and High-Affinity Fluorescent Probe for Butyrylcholinesterase:A Good Strategy for Binding Affinity Characterization

Butyrylcholinesterase(BChE)is regarded as a promising target for the treatment of Alzheimer's disease(AD),as its level significantly increases along with the progress of this disease.Therefore,the development of potent and high-affinity small-molecule BChE inhibi-tors may be a new strategy for the discovery of anti-AD drugs.However,the current Ellman's method is unable to evaluate the affinity of compounds with BChE,and has a few deficiencies in drug development.Herein,the first small-molecule fluorescence polarization(FP)probes for BChE were rationally designed based on a high affinity inhibitor.Studies indicated that probe F6 exhibited satisfactory fluorescence intensity and suitable fluorescent properties that were compatible with the filters in the FP system.Meanwhile,probe F6 exhibited potent binding affinity to BChE.It is feasible to be applied in detecting the affinity of non-fluorescent compounds to BChE,which lays a solid foundation for the development of small-molecule BChE inhibitors.At the same time,it also can be applied as a val-uable chemical tool for better understanding the molecular biological mechanism of BChE.