Inhibition of APE1/Ref-1 Redox Activity with APX3330 Blocks Retinal Angiogenesis in vitro and in vivo

This study examines the role of APE1/Ref-1 in the retina and its potential as a therapeutic target for inhibiting retinal angiogenesis. APE1/Ref-1 expression was quantified by Western blot. The role of APE1/Ref-1 redox function in endothelial cell in vitro angiogenesis was examined by treating retinal vascular endothelial cells (RVECs) with APX3330, a small molecule inhibitor of APE1/Ref-1 redox activity. In vitro methods included a proliferation assay, a transwell migration assay, a Matrigel tube formation assay, and a Real-Time Cell Analysis (RTCA) using the xCELLigence System. In vivo functional studies of APE1/Ref-1 were carried out by treating very low density lipoprotein (VLDL) receptor knockout mice (Vldlr−/−) with intravitreal injection of APX3330, and subsequent measurement of retinal angiomatous proliferation (RAP)-like neovascularization for one week. APE1/Ref-1 was highly expressed in the retina and in RVECs and pericytes in mice. APX3330 (1–10 μM) inhibited proliferation, migration and tube formation of RVECs in vitro in a dose-dependent manner. Vldlr−/− RVECs were more sensitive to APX3330 than wild-type RVECs. In Vldlr−/− mice, a single intravitreal injection of APX3330 at the onset of RAP-like neovascularization significantly reduced RAP-like neovascularization development. APE1/Ref-1 is expressed in retinal vascular cells. APX3330 inhibits RVEC angiogenesis in vitro and significantly reduces RAP-like neovascularization in Vldlr−/− mice. These data support the conclusion that APE1/Ref-1 redox function is required for retinal angiogenesis. Thus, APE1/Ref-1 may have potential as a therapeutic target for treating neovascular age-related macular degeneration and other neovascular diseases

MiR-101-3p targets KPNA2 to inhibit the progression of lung squamous cell carcinoma cell lines

We herein discuss the impacts of miR-101-3p on the tumorigenesis-related cell behaviors in lung squamous cell carcinoma (LUSC) by repressing KPNA2. TCGA database was utilized to measure miR101-3p and KPNA2 levels in LUSC tissues and cells. The interaction of miR-101-3p and KPNA2-3’UTR was determined by dual luciferase assay. Western blot evaluated the protein level of KPNA2. MiR-101-3p was under-expressed in LUSC cells while KPNA2 was overexpressed. Western blot confirmed the impact of KPNA2 expression on cancer cell progression. The negative regulatory impact of miR-101-3p on KPNA2 was also verified. In vitro cell function assays revealed the suppressing effect of high miR-101-3p expression on cell invasion, migration and viability, as well as its promoting effect on apoptosis. Up-regulated miR-101-3p weakened the promoting effect of overexpressed KPNA2 on LUSC malignant progression. To conclude, miR-101-3p repressed viability, invasion, and migration, and facilitated cell apoptosis in LUSC by suppressing KPNA2

Response Properties of Interneurons and Pyramidal Neurons in Macaque MSTd and VPS Areas During Self-Motion

To perceive self-motion perception, the brain needs to integrate multi-modal sensory signals such as visual, vestibular and proprioceptive cues. Self-motion perception is very complex and involves multi candidate areas. Previous studies related to self-motion perception during passive motion have revealed that some of the areas show selective response to different directions for both visual (optic flow) and vestibular stimuli, such as the dorsal subdivision of the medial superior temporal area (MSTd) and the visual posterior sylvian fissure (VPS), although MSTd is dominated by visual signals and VPS is dominated by vestibular signals. However, none of studies related to self-motion perception have distinguished the different neuron types with distinct neuronal properties in cortical microcircuitry, which limited our understanding of the local circuits for self-motion perception. In the current study, we classified the recorded MSTd and VPS neurons into putative pyramidal neurons and putative interneurons based on the extracellular action potential waveforms and spontaneous firing rates. We found that: (1) the putative interneurons exhibited obviously broader direction tuning than putative pyramidal neurons in response to their dominant (visual for MSTd; vestibular for VPS) stimulation type; (2) either in visual or vestibular condition, the putative interneurons were more responsive but with larger variability than the putative pyramidal neurons for both MSTd and VPS areas; and (3) the timing of vestibular and visual peak directional tuning was earlier in the putative interneurons than that of the putative pyramidal neurons for both MSTd and VPS areas. Based on these findings we speculated that, within the microcircuitry, several adjacent putative interneurons with broad direction tuning receive earlier strong but variable signals, which might act feedforward input to shape the direction tuning of the target putative pyramidal neuron, but each interneuron may participate in several microcircuitries, targeting different output neurons

Can the digital economy promote the development of the energy economy? Evidence from China

In this paper, 22 indexes are selected at three levels, including the informatization development level, the Internet development level, and the digital transaction development level, based on China’s provincial panel data from 2011 to 2020, so as to build a digital economy development index system. Moreover, 28 basic indexes are selected from three aspects, including energy construction, energy production and energy consumption, so as to develop an energy economy development evaluation index system. The development index of China’s digital economy and energy economy are measured by using the entropy weight method. The effect of the digital economy on the energy economy and its mechanism are tested by the static panel, the dynamic panel, and the mediating effect and regulating effect models. The results indicate that the digital economy has pronouncedly promoted the development of China’s energy economy, and the development of the digital economy can have an effect on the rationalization of the industrial structure and then affect the development of the energy economy, and there is an intermediary effect. Moreover, the upgrading of the industrial structure is conducive to regulating the digital economy and facilitates the development of the energy economy. The development of the energy economy can be better promoted by focusing on the coordinated regional layout of the digital economy development, building a reliable energy commodity trading platform, and expediting the optimization and upgrading of the industrial structure

Preliminarily Static Analysis of CFETR Central Solenoid Magnet System

Conceptual design of China Fusion Engineering Test Reactor (CFETR) Central Solenoid (CS) coil had been started in Institute of Plasma Physics, Chinese Academy of Sciences. The highest field of CS coil is 17.2 T when the running current is 60 kA. CS magnet system mainly consists of 8 Nb3Sn coils compressed with 8 sets of preload structure. The functions of the preload structure are to apply an enough axial compression to the CS coils and to have a mechanical rigidity against the repulsive force between 8 Nb3Sn coils. This paper describes structural design of CFETR CS magnet system. A global finite element model is created based on the design geometry data to investigate the mechanical property of CFETR CS preload structure and support structure under the different operating conditions. 2D finite element model under electromagnetic is created to calculate the stress on the conductor jacket and turn insulation.</p

Impact of hypertension and smoking on the rupture of intracranial aneurysms and their joint effect

Background In general population, the prevalence of intracranial aneurysm reaches as high as three percent. The goal of the study was to analyze retrospectively the independent risk factors for the rupture of intracranial aneurysms and their joint effect. Methods The records and angiographies of continuous 519 intracranial aneurysm patients treated at our center between February 2013 and July 2014 were retrospectively analyzed. Ruptured group and unruptured group were included in the study according to their clinical and imaging information. Univariate analysis and multivariate logistic regression analysis was used to identified independent risk factors for the rupture of intracranial aneurysms. We assessed the joint effect of independent risk factors for the rupture of intracranial aneurysms with an additional logistic regression analysis. Results The results of multivariate analysis show that hypertension (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.05–2.18) and smoking (odds ratio [OR], 1.57; 95% confidence interval [CI], 1.06–2.33) were independent risk factors for rupture of intracranial aneurysms. The joint risk of hypertension and smoking was higher (OR, 2.28; 95% CI, 1.29–4.02) than the risks of hypertension (OR, 1.74; 95% CI, 1.11–2.72) and smoking (OR, 1.86; 95% CI, 1.05–3.29) independently. Conclusions Hypertension and smoking increase of the rupture risk of intracranial aneurysms. And the joint risk of hypertension and smoking was higher than the risks of hypertension and smoking independently