TUG-891 inhibits neuronal endoplasmic reticulum stress and pyroptosis activation and protects neurons in a mouse model of intraventricular hemorrhage

Pyroptosis plays an important role in hemorrhagic stroke.Excessive endoplasmic reticulum stress can cause endoplasmic reticulum dysfunction and cellular pyroptosis by regulating the nucleotide-binding oligomerization domain and leucine-rich repeat pyrin domain-containing protein 3(NLRP3)pathway.However,the relationship between pyroptosis and endoplasmic reticulum stress after intraventricular hemorrhage is unclear.In this study,we established a mouse model of intraventricular hemorrhage and found pyroptosis and endoplasmic reticulum stress in brain tissue.Intraperitoneal injection of the selective GPR120 agonist TUG-891 inhibited endoplasmic reticulum stress,pyroptosis,and inflammation and protected neurons.The neuroprotective effect of TUG-891 appears related to inhibition of endoplasmic reticulum stress and pyroptosis activation.

Construction and Validation of a Geometry-based Mathematical Model for the Hard X-Ray Imager

Quantitative and analytical analysis of the modulation process of the collimator is a great challenge,and is also of great value to the design and development of Fourier transform imaging telescopes.The Hard X-ray Imager(HXI),as one of the three payloads onboard the Advanced Space-based Solar Observatory(ASO-S) mission,adopts modulating Fourier-Transformation imaging technique and will be used to explore the mechanism of energy release and transmission in solar flare activities.As an important step to reconstruct the images of solar flares,accurate modulation functions of HXI are needed.In this paper,a mathematical model is developed to analyze the modulation function under a simplified condition first.Then its behavior under six degrees of freedom is calculated after adding the rotation matrix and translation change to the model.In addition,unparalleled light and extended sources are also considered so that our model can be used to analyze the X-ray beam experiment.Next,applied to the practical HXI conditions,the model has been confirmed not only by Geant4 simulations but also by some verification experiments.Furthermore,how this model helps to improve the image reconstruction process after the launch of ASO-S is also presented.

Simulations and software development for the Hard X-ray Imager onboard ASO-S

China’s first solar mission,the Advanced Space-based Solar Observatory(ASO-S),is now changing from Phase B to Phase C.Its main scientific objectives are summarized as’1M2B’,namely magnetic field and two types of bursts(solar flares and coronal mass ejections).Among the three scientific payloads,Hard X-ray Imager(HXI)observes images and spectra of X-ray bursts in solar flares.In this paper,we briefly report on the progresses made by the HXI science team(data and software team)during the design phase(till May 2019).These include simulations of HXI imaging,optimization of HXI grids,development of imaging algorithms,estimation of orbital background,as well as in-orbit calibration plan.These efforts provided guidance for the engineering,improved HXI’s imaging capability and reduced the cost of the instrument.

Necrostatin-1 decreases necroptosis and inflammatory markers after intraventricular hemorrhage in mice

Necrostatin-1,an inhibitor of necroptosis,can effectively inhibit necrotic apoptosis in neurological diseases,which results in the inhibition of inflammation,endoplasmic reticulum stress,and reactive oxygen species production and substantial improvement of neurological function.However,the effects of necrostatin-1 on intraventricular hemorrhage(IVH)remain unknown.In this study,we established a mouse model of IVH by injecting autologous blood into the lateral ventricle of the brain.We also injected necrostatin-1 into the lateral ventricle one hour prior to IVH induction.We found that necrostatin-1 effectively reduced the expression levels of the necroptosis markers receptor-interacting protein kinase(RIP)1,RIP3,mixed lineage kinase domain-like protein(MLKL),phosphorylated(p)-RIP3,and p-MLKL and the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-αin the surrounding areas of the lateral ventricle.However,necrostatin-1 did not reduce ependymal ciliary injury or brain water content.These findings suggest that necrostatin-1 can prevent local inflammation and microglial activation induced by IVH but does not greatly improve prognosis.

Screening of genetic loci predisposing to herpes simplex virus infection on mouse chromosome 17

Aim:The herpes simplex virus(HSV),one of the most common viruses infecting humans,is featured by a high infection rate and usually causes complex disorders difficult to diagnose and treat.Disease progression is always combined with the specific interaction between organism and environment,but genetic factors play a decisive role in most pathogenic processes.Like most human disorders,individual difference has also been involved in the pathogenesis of HSV infection.The present study aimed to screen the potential gene loci that regulates human predisposition to HSV infection.Methods:With reference to previous studies,inbred mouse lines with significantly distinct predisposition to HSV infection were chosen for gene loci screening.Gene sites on mouse chromosome 17 associated with susceptibility to HSV infection were then identified by correlation analysis and genome-wide scanning technique.Results:Genes affecting the vulnerability of mice to HSV infection were mapped to three regions on the 17th mouse chromosome,D17MIT51.1,D17MIT39.1 and the region between D17MIT180.1 and D17MIT184.Conclusion:The results suggest that the mouse genetic background plays an important role in its susceptibility to HSV-1 infection,which might be regulated by multiple predisposing quantitative trait loci.