Bushen Yizhi Formula regulates the IRE1αpathway to alleviate endoplasmic reticulum stress in an Alzheimer’s disease rat model

While the Bushen Yizhi Formula can treat Alzheimer’s disease(AD),the yet to be ascertained specific mechanism of action was explored in this work.Methods:Different concentrations of the Bushen Yizhi Formula and amyloid-beta peptide(Aβ)were used to treat rat pheochromocytoma cells(P12)and human neuroblastoma cells(SH-SY5Y).Cell morphological changes were observed to determine the in vitro cell damage.Cell Counting Kit(CCK)-8 assay and flow cytometry were employed to identify cell viability and apoptosis/cell cycle,respectively.Western blotting and immunohistochemistry were employed to measure the expressions of endoplasmic reticulum stress(ERS)-related proteins(GRP78 and CHOP),p-IRE1α,IRE1α,ASK1,p-JNK,JNK,Bax,Bcl-2,XBP-1,and Bim.Fura 2-acetoxymethyl ester(Fura-2/AM)was used to determine the intracellular calcium(Ca^(2+))concentration.Also,an AD model was constructed by injecting Aβinto the CA1 area of the hippocampus in Sprague Dawley rats.AD model rats were gavaged with different concentrations of Bushen Yizhi Formula for 14 consecutive days.The Morris water maze experiment was conducted to test the learning and memory of rats.Hematoxylin&Eosin(H&E)and Terminal-deoxynucleotidyl Transferase(TdT)-mediated dUTP Nick-End Labeling(TUNEL)staining were done to determine histopathological changes in the brain.Results:Bushen Yizhi Formula relieved the Aβ-induced effects including cell injury,decreased viability,increased apoptosis,G0/G1 phase cell cycle arrest,upregulation of GRP78,CHOP,p-IRE1α,p-JNK,Bax,XBP-1 and Bim,as well as down-regulation of Bcl-2.These results were also seen with IRE1αsilencing.While Aβsuppressed the learning and memory abilities of rats,the Bushen Yizhi Formula alleviated these effects of Aβ.Brain nerve cell injury induced by Aβcould also be treated with Bushen Yizhi Formula.Conclusion:Bushen Yizhi Formula could influence ERS through the IRE1αsignaling pathway to achieve its therapeutic effects on AD.

High cycle fatigue failure with radial cracks in gears of aero-engines

The gears in aero-engines perform energy and motion transfer between the HighPressure Rotor(HPR)and accessories.Firstly,an occurred fault with radial cracks in the driven gear disk was diagnosed as High Cycle Fatigue(HCF)failure through necessary examinations.Analysis of fault tree and test signals indicated that the fracture was relevant to the swing vibration of the driven gear excited by the unbalance excitation on HPR.Secondly,a corresponding mechanism model was established,in which the gear meshing effect was considered,with lateral and swing vibration mode.The Governing Equations(GEs)and the Finite Element Model(FEM)were established and verified.Then,the modal shapes,harmonic response,and transient response were analyzed,indicating that the swing vibration of the driven gear could be significantly excited by the unbalance on HPR,which induced the cracks in the driven gear disk to extend radially.Furthermore,influences of factors on the unbalance response were obtained,in which the unbalance response appeared local minimum points and maximum points.Meanwhile,1#and 2#bearing stiffness had rather significant influences on the response.Thus it is efficient to modify them to achieve vibration control.