NEDD8-activating enzyme inhibitor, MLN4924 (Pevonedistat) induces NOXA-dependent apoptosis through up-regulation of ATF-4

Liu, Xiaojun,Jiang, Yanan,Wu, Jianfu,Zhang, Wenjuan,Liang, Yupei,Jia, Lijun,Yu, Jinha,Jeong, L.S.,Li, Lihui Elsevier 2017 Biochemical and biophysical research communication Vol. No.

<P><B>Abstract</B></P> <P>It has been reported that MLN4924 can inhibit cell growth and metastasis in various kinds of cancer. We have reported that MLN4924 is able to inhibit angiogenesis through the induction of cell apoptosis both in vitro and in vivo models. Moreover, Neddylation inhibition using MLN4924 triggered the accumulation of pro-apoptotic protein NOXA in Human umbilical vein endothelial cells (HUVECs). However, the mechanism of MLN4924-induced NOXA up-regulation has not been addressed in HUVECs yet. In this study, we investigated how MLN4924 induced NOXA expression and cellular apoptosis in HUVECs treated with MLN4924 at indicated concentrations. MLN4924-induced apoptosis was evaluated by Annexin V-FITC/PI analysis and expression of genes associated with apoptosis was assessed by Quantitative RT-PCR and western blotting. As a result, MLN4924 triggered NOXA-dependent apoptosis in a dose-dependent manner in HUVECs. Mechanistically, inactivation of Neddylation pathway caused up-regulation of activating transcription factor 4 (ATF-4), a substrate of Cullin-Ring E3 ubiquitin ligases (CRL). NOXA was subsequently transactivated by ATF-4 and further induced apoptosis. More importantly, knockdown of ATF-4 by siRNA significantly decreased NOXA expression and apoptotic induction in HUVECs. In summary, our study reveals a new mechanism underlying MLN4924-induced NOXA accumulation in HUVECs, which may help extend further study of MLN4924 for angiogenesis inhibition treatment.</P> <P><B>Highlights</B></P> <P> <UL> <LI> MLN4924 triggered NOXA-dependent apoptosis in a dose-dependent manner in HUVECs. </LI> <LI> Inactivation of neddylation caused up-regulation of ATF4, a substrate of CRL. </LI> <LI> NOXA was transactivated by ATF4 and further induced apoptosis. </LI> <LI> Knockdown of ATF-4 significantly decreased NOXA expression and apoptotic induction. </LI> <LI> We revealed a new mechanism underlying MLN4924-induced NOXA accumulation in HUVECs. </LI> </UL> </P>

An improved design of power-cycling hydrodynamic mechanical transmission

Xiaojun Liu,Dongye Sun 대한기계학회 2020 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.34 No.8

Recent studies have demonstrated that the power-cycling hydrodynamic mechanical (PCHM) transmission has excellent performance in improving power performance and fuel economy of a wheel loader. However, these results have been obtained by assuming that its speed ratio can always change continuously. Hence, this study first investigated the speed ratio of the transmission how to change when shifting from one gear to another. It was found that the concept of the PCHM transmission suggested in the literature is ineffective, even for a configuration with two gears in the gearbox. Then, the configuration of the PCHM transmission was developed as a different one to increase the torque multiplication capacity and efficiency of the transmission. A design method for this transmission is proposed to quantify its performances. The design method is based on a multi-objective optimization problem which is comprised of two objectives, seven design variables and eleven constraints. The relationships between average efficiency of the transmission and maximum tractive force of the vehicle and the seven transmission parameters are qualitatively examined. Results show that the performance of the transmission depends mainly on the number of transmission gears instead of on three parameters of the torque converter. The average efficiency is not sensitive to the maximum tractive force on a globally optimal Pareto front. The PCHM transmission with the new configuration can enable the average efficiency and the maximum tractive force to increase by 2.1 % and by 6.6 %, compared to that of the traditional hydrodynamic mechanical transmission, respectively.

Research on the Flame Simulation Method Based on the Particle System

Xumin Liu,Zilong Duan,Dawei Qian,Xiaojun Wang 보안공학연구지원센터 2014 International Journal of Control and Automation Vol.7 No.12

In reality, flame is a common fluid scene. In this paper, we simulated flame by using improved particle system and detail the properties and changes of particles in the model. We realized a realistic color change and dynamic flickering flame characteristics. We used texture mapping method to render the flame and used the hierarchical programming structure to provide a simple and practical interactive flame simulation. We also designed and implemented demonstration system of flame simulation. Experiments show that using the flame image generated in this paper can not only satisfy the visual effect but also meet the real-time requirements.

A Low Power Consumption Frequency Adaptation Mechanism Based on the Traffic and Implementation on NetFPGA

Lei Zhou,Lianghua Li,Xiaoju Liu,Xiaojun Wang 보안공학연구지원센터 2014 International Journal of Future Generation Communi Vol.7 No.6

Both in academic and industrial research, building a green energy-saving network has become a hot topic. Combined with hardware division and adaptive algorithm, this paper proposes an adaptive frequency control mechanism based on traffic to reduce power consumption. By calculating real-time traffic, the network device can adjust its operating frequency. On the premise of maintaining network performance, this mechanism could reduce the power consumption significantly. Besides, the adaptive frequency mechanism has been verified and realized in the NetFPGA Reference Router. Experimental data show that under different ranges of traffic loads and without affect its performance, the Router embedded this mechanism can reduce power consumption by more than 20%.

Instantaneous frequency extraction in time-varying structures using a maximum gradient method

Liu, Jing-liang,Wei, Xiaojun,Qiu, Ren-Hui,Zheng, Jin-Yang,Zhu, Yan-Jie,Laory, Irwanda Techno-Press 2018 Smart Structures and Systems, An International Jou Vol.22 No.3

A method is proposed for the identification of instantaneous frequencies (IFs) in time-varying structures. The proposed method combines a maximum gradient algorithm and a smoothing operation. The maximum gradient algorithm is designed to extract the wavelet ridges of response signals. The smoothing operation, based on a polynomial curve fitting algorithm and a threshold method, is employed to reduce the effects of random noises. To verify the effectiveness and accuracy of the proposed method, a numerical example of a signal with two frequency modulated components is investigated and an experimental test on a steel cable with time-varying tensions is also conducted. The results demonstrate that the proposed method can extract IFs from the noisy multi-component signals and practical response signals successfully. In addition, the proposed method can provide a better IF identification results than the standard synchrosqueezing wavelet transform.

Heat Shock Protein 90 Inhibitor Decreases Collagen Synthesis of Keloid Fibroblasts and Attenuates the Extracellular Matrix on the Keloid Spheroid Model

Liu, Qingliang,Wang, Xiaojun,Jia, Yihong Williams & Wilkins 2016 Plastic and reconstructive surgery Vol.137 No.4

A Research about Adaptive Subdivision Algorithm Based On Doo-Sabin Mode

Xumin Liu,Yongxiu Xu,Xianpeng Yang,Xiaojun Wang 보안공학연구지원센터 2015 International Journal of Signal Processing, Image Vol.8 No.2

Subdivision surface method is a series of iterative operation adopts a certain subdivision formula for an initial grid, obtains the smooth limits surface finally, and can dispose any arbitrary complex topology grid. At present most of the subdivision algorithm are 1-4 subdivisions and as the number of subdivision increase, the grid grow so too-rapid in the number of patch that it is difficult for the model after subdivision to deal with other things. We proposed an adaptive Doo-Sabin Mode subdivision algorithm to solve this problem, which take the average vector of the vertex and the angle between the intersecting surfaces of the vertex as a measurement criterion. This criterion is used to divide the surface, and then make local subdivision. In this way, when the times of subdivision are fewer (the demand of smoothness is not too high), the effect of subdivision has little difference, but efficiency of the algorithm can be greatly improved. Compared with the normal Doo-Sabin subdivision model, experimental results showed that adaptive Doo-Sabin subdivision algorithm can largely slow the growth speed of the amount of model data on the premise that guarantee the quality of surface.

Image Segmentation Algorithm Based on Improved Ant Colony Algorithm

Xumin Liu,Xiaojun Wang,Na Shi,Cailing Li 보안공학연구지원센터(IJSIP) 2014 International Journal of Signal Processing, Image Vol.7 No.3

Study on Fiber Cutting Performance of Isometric Straight Bar Plate with Different Bar Angle

Huan Liu,Jixian Dong,Xiya Guo,Chong Luo,Xiaohui Tian,Xiaojun Jiang,Sha Wang,Ruifan Yang,Chuanwu Duan,Bo Wang,Kai Qi 한국펄프·종이공학회 2019 펄프.종이기술 Vol.51 No.5

The refining plate is a direct-acting component of refiners in pulping, and the bar profile of it have a major impact on fiber cutting, which affects the paper forming and strength of the formed paper. In this paper, the fiber average length, the fiber length distribution, the original fiber cutting rate and adjacent fiber cutting rate of samples collected in different refining time are used to analyze the fiber cutting mechanism of the isometric straight bar refining plates with different bar angles. The results show that the fiber cutting performance of plates gradually decreases and the limit fiber cutting length of the plate increases with the increase of the bar angle which is opposite to the conclusion predicted by specific edge load (SEL). However, the fiber cutting action of plates is gradually weakened until the average fiber length is reduced to the limit cutting length of plates. Meanwhile, the cutting mechanism of the straight bar plates with different bar angles is different. The larger bar angle of plate, the lower fiber cutting rate and the adjacent cutting rate of which is basically kept constant during refining, while the adjacent cutting rate of smaller bar angle plate on fibers gradually decreases with refining and finally remains constant. The study on the cutting performance of different bar angle plates has positive significance for the selection and design of refining plates for different pulping process.

Refining Characteristics of Hardwood Pulp Using Straight- and Curved-bar Plates: A Time Series Study

Huan Liu,Jixian Dong,Xiaojun Jiang,Chong Luo,Xiaohui Tian,Ruifang Yang,Litao Zhang,Bo Wang,Yan Yan 한국펄프·종이공학회 2019 펄프.종이기술 Vol.51 No.5

There are obvious differences in the refining characteristics of plates with straight bars compared to curved bar plates having the same bar parameters during refining. The objective of this research is to explore the difference in the refining characteristics of the straight bar and curved bar plates on experimental and theoretical studies. The bar angle of the curved bar plate is defined, and the two plates are used in the refining of bleached sulphate eucalyptus pulp (BSEP). Samples at different refining times were collected, and the properties of the fibers, pulp, and paper were detected and analyzed. It was found that the curved bar and straight bar plates have a similar influence on the pulp SR freeness. However, the curved bar plate effectively retained the fiber length, which means that its fiber cutting effect is weaker than that of the straight bar plate. Meanwhile, the fiber external fibrillation of the samples refined by the curved bar plate was better than that of the samples refined by the straight bar, which showed a higher tensile and tear index of the formed paper. Through the theoretical analysis of refining intensity via characterization of the parameter bar edge length (BEL), the specific edge load (SEL) of the curved bar plate was lower, and the refining characteristics predicted by the refining intensity were similar to the results from the experiments conducted in this paper.