Histone deacetylase inhibitors VPA and WT161 ameliorate the pathological features and cognitive impairments of the APP/PS1 Alzheimer's disease mouse model by regulating the expression of APP secretases.

BACKGROUND: Alzheimer's disease (AD) is a degenerative neurological disorder. Recent studies have indicated that histone deacetylases (HDACs) are among the most prominent epigenetic therapy targets and that HDAC inhibitors have therapeutic effects on AD. Here, we identified sodium valproate (VPA), a pan-HDAC inhibitor, and WT161, a novel HDAC6 selective inhibitor, as potential therapeutic agents for AD. Underlying molecular mechanisms were investigated. METHODS: A cellular model, N2a-APPswe, was established via lentiviral infection, and the APPswe/PSEN1dE9 transgenic mouse model was employed in the study. LC-MS/MS was applied to quantify the concentration of WT161 in the mouse brain. Western blotting, immunohistochemical staining, thioflavin-S staining and ELISA were applied to detect protein expression in cells, tissues, or serum. RNA interference was utilized to knockdown the expression of specific genes in cells. The cognitive function of mice was assessed via the nest-building test, novel object recognition test and Morris water maze test. RESULTS: Previous studies have focused mainly on the impact of HDAC inhibitors on histone deacetylase activity. Our study discovered that VPA and WT161 can downregulate the expression of multiple HDACs, such as HDAC1 and HDAC6, in both AD cell and mouse models. Moreover, they also affect the expression of APP and APP secretases (BACE1, PSEN1, ADAM10). RNA interference and subsequent vitamin C induction further confirmed that the expression of APP and APP secretases is indeed regulated by HDAC1 and HDAC6, with the JNK pathway being the intermediate link in this regulatory process. Through the above pathways, VPA and WT161 effectively reduced Aß deposition in both AD cell and mouse models and significantly improved cognitive function in AD mice. CONCLUSIONS: In general, we have discovered that the HDAC6-JNK-APP secretases cascade is an important pathway for VPA and WT161 to exert their therapeutic effects on AD. Investigations into the safety and efficacy of VPA and WT161 were also conducted, providing essential preclinical evidence for assessing these two epigenetic drugs for the treatment of AD.

Experimental study on the shear performance of an anchor cable with a C-shaped tube anchored flat structural plane.

To analyse the influence of normal stress (σn) and steel tube strength on an anchor cable with a C-shaped tube (ACC), we selected Q235 steel tubes and Q345 steel tubes as representative ACCs and carried out double shear tests of ACC-reinforced jointed rock masses. Based on the test results, the influence of the steel tube strength on the ACC axial force and shear force under different normal stresses, the characteristics of the shear force-shear displacement curve of the anchored flat structural plane (FSP) in the rock mass, and the ACC failure mode and contribution to the anchored concrete surface shear strength were studied. The test results show that under 2 ~ 10 MPa of σn, the failure angle varies between 28° and 40° due to the bending of the ACC near the structural plane and increases with increasing σn. Compared with Q235-ACC, Q345-ACC contributes more to the shear strength of the structural plane and can better exert its axial force when resisting the lateral shearing action of the structural plane. Additionally, we proved that σn is a main factor affecting the shear stiffness of the structural plane and that the Q345 C-shaped tube effectively improves the shear stiffness of an ACC-reinforced jointed rock mass and can more fully mobilize the anchor cable during shearing ductility in the tangential direction compared to the performance of the Q235 C-shaped tube. The research results can provide a reference for the further application of ACCs to roadways.

Forecasts for the concentration of petroleum gas leakage diffusion under different liquid level heights of a sealing ring of sizeable floating roof tank.

The sealing ring of the external floating roof tank is prone to petroleum gas leakage due to material aging and oil corrosion. Petroleum gas leakage and diffusion easily accumulate above the floating deck. When it is within the explosion limit range, there will be the risk of explosion and fire. To deal with the explosion accident of storage tank caused by the concentration distribution of petroleum gas leakage for the sealing ring, and to study the influence of petroleum gas diffusion and concentration distribution after sealing ring leakage on the control area above the floating deck in the tank farm environment, this paper established numerical models of sealing ring leakage under different liquid level heights for 10 × 104 m3 external floating roof tank. Through numerical calculation, it is found that the diffusion concentration of petroleum gas is related to the wind speed, the range of the control area above the floating deck, and leakage when sealing rings leak at different liquid levels. Through dimensionless analysis, the functional relationship of gas leakage diffusion concentration distribution under different liquid level heights of external floating roof tank sealing rings is verified by numerical calculation results. The results show that the numerical results are consistent with those predicted by the formula.

Research on Intelligent Embedded Fan System Based on YOLOv2 Lightweight Algorithm.

With the development of artificial intelligence, the application of intelligent algorithms to low-power embedded chips has become a new research topic today. Based on this, this study optimizes the YOLOv2 algorithm by tailoring and successfully deploys it on the K210 chip to train the face object detection algorithm model separately. The intelligent fan with YOLOv2 model deployed in K210 chip can detect the target of the character and obtain the position and size of the character in the machine coordinates. Based on the obtained information of character coordinate position and size, the fan's turning Angle and the size of air supply are intelligently perceived. The experimental results show that the intelligent fan design method proposed here is a new embedded chip intelligent method of cutting and improving the YOLOv2 algorithm. It innovatively designed solo tracking, crowd tracking, and intelligent ranging algorithms, which perform well in human perception of solo tracking and crowd tracking and automatic air volume adjustment, improve the accuracy of air delivery and user comfort, and also provide good theoretical and practical support for the combination of AI and embedded in other fields.

[Density functional theory studies on structure and spectrum of Cu3 Ti cluster].

Bulk intermetallic Ti-Cu compounds have been found to possess special properties, including increased hardness, as well as displaying enhanced sound absorption and e shape memory. Since only one Raman progression is observed, there is not sufficient information to determine the structure of TiCu3. The different structures and vibrational frequencies of the Cu3 Ti cluster were studied by means of the density functional theory with SVWN5, B3LYP and BPW91 methods at basis sets of lanl2dz, 6-31g, 6-311g, 6-311g(d), 6-311 +/- g(2df) and 6-311 +/- g(3d2f). The calculated results show that the ground state of the Cu3 Ti cluster is a e-type structure with the C2v point group symmetry, and the bond lengths and vibrational frequencies of Cu3 T are considerably dependent on the variation of basis sets. We observed only a single Raman progression in approximately 300 cm(-1). This progression is most likely the totally symmetric stretch. The computed and observed Raman spectra were also compared with each other.