Intracellular trafficking of TREM2 is regulated by presenilin 1

Yingjun Zhao,Xiaoguang Li,Timothy Huang,Lu-lin Jiang,Zhenqiu Tan,Muxian Zhang,Irene Han-Juo Cheng,Xin Wang,Guojun Bu,Yun-wu Zhang,Qi Wang,Huaxi Xu 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Genetic mutations in triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to a variety of neurodegenerative diseases including Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia and Parkinson’s disease. In the brain, TREM2 is highly expressed on the cell surface of microglia, where it can transduce signals to regulate microglial functions such as phagocytosis. To date, mechanisms underlying intracellular trafficking of TREM2 remain elusive. Mutations in the presenilin 1 (PS1) catalytic subunit of the γ-secretase complex have been associated with increased generation of the amyloidogenic Aβ (amyloid-β) 42 peptide through cleavage of the Aβ precursor amyloid precursor protein. Here we found that TREM2 interacts with PS1 in a manner independent of γ-secretase activity. Mutations in TREM2 alter its subcellular localization and affects its interaction with PS1. Upregulation of PS1 reduces, whereas downregulation of PS1 increases, steady-state levels of cell surface TREM2. Furthermore, PS1 overexpression results in attenuated phagocytic uptake of Aβ by microglia, which is reversed by TREM2 overexpression. Our data indicate a novel role for PS1 in regulating TREM2 intracellular trafficking and pathophysiological function.

Dynamic performance of 6.5 kV SiC MOSFET body diodes and anti‑parallel Schottky barrier diodes

Yujie Du,Xinling Tang,Xiaoguang Wei,Shuai Sun,Fei Yang,Zhibin Zhao 전력전자학회 2023 JOURNAL OF POWER ELECTRONICS Vol.23 No.6

For a silicon carbide (SiC) metal–oxide–semiconductor fi eld-eff ect transistor (MOSFET), both the body diode of the MOSFET and an anti-parallel diode can function as a freewheeling diode that carries reverse current. Selecting a suitable freewheeling method is particularly important to fully exploit the performance of high-voltage SiC MOSFET devices. In this study, based on the 6.5 kV SiC MOSFET and the Schottky barrier diode (SBD) developed by our research group, the dynamic characteristics of the MOSFET body diode, the SBD, and the parallel connection of the two are investigated. In addition, the influence of capacitive current on the dynamic characteristics is analyzed by establishing an equivalent circuit model. Test results show that when compared with the body diode, the SBD has an extremely low reverse recovery current, a lower capacitive current, and better reverse recovery temperature stability. Thus, the SBD is regarded as the most suitable freewheeling diode for the 6.5 kV SiC MOSFET. Finally, a package solution for the 6.5 kV SiC MOSFET and SBD is proposed.

Suppression of synuclein gamma inhibits the movability of endometrial carcinoma cells by PI3K/AKT/ERK signaling pathway

Man Ni,Yue Zhao,Xiaoguang Wang 한국유전학회 2021 Genes & Genomics Vol.43 No.6

Background Although overexpression of synuclein gamma (SNCG) has been reported in several cancers, few studies have been performed onSNCG in endometrial carcinomas. Objective This study aimed to investigate the role of SNCG in the progression of endometrial carcinoma. Methods The expression pattern and function ofSNCG gene were analyzed using the Gene Expression Omnibus (GEO) and Gene Set Enrichment Analysis (GSEA) datasets. Two vector types, containing either SNCG or negative control shRNAs, were used to evaluate cell proliferation, apoptosis, and metastasis using Cell Counting Kit 8, colony formation, fow cytometry, wound-healing, transwell, and invasion assays. The relative protein levels of N-cadherin, E-cadherin, vimentin, p-PI3K, PI3K, p-AKT, AKT, p-ERK, and ERK were determined by western bloting. Results Our results revealed thatSNCG mRNA expression and SNCG protein levels in shRNA-treated SPEC2 cells were lower than in the negative control cells. Furthermore, cell proliferation, migration, and invasion were signifcantly inhibited in SNCG shRNA-treated cells, but apoptosis was increased. The results of western blot analysis indicated that SNCG silencing reduced the protein levels of N-cadherin, vimentin, p-PI3K, p-AKT, and p-ERK, but not those of total PI3K, AKT, and ERK. Conclusions Therefore, shRNA-mediated suppression of SNCG inhibited SPEC2 cell proliferation, migration, and invasion, and promoted SPEC2 cell apoptosis, which was presumably accomplished via regulation of the PI3K/AKT/ERK signaling pathway.

Robust Security Control Under Denial-of-service Jamming Attacks: An Event-triggered Sliding-mode Control Approach

Bo-Chao Zheng,Lina Guo,Yangyang Zhao,Xiaoguang Liu,Zhou Gu 제어·로봇·시스템학회 2022 International Journal of Control, Automation, and Vol.20 No.12

Robust security problem for uncertain cyber-physical systems (CPSs) subject to periodic denial-ofservice (DoS) jamming attacks is investigated based on event-triggered (ET) sliding-mode control (SMC) approach in this paper. First, a new type of SMC approach driven by ET mechanism is constructed using the property of the period DoS jamming attacks. Then, sufficient conditions for robust stabilization of dynamical systems constrained by system parameters and attacks period are proposed. Further, it is proved that the execution time interval of the proposed ET-based SMC strategy has a positive lower bound, and thus Zeno-free behavior occurs during system evolution. Finally, comparisons results show the effectiveness and superiority of this methodology.

Fatigue study on additional cutout between U shaped rib and floorbeam in orthotropic bridge deck

Xiaochen Ju,Zhibin Zeng,Xinxin Zhao,Xiaoguang Liu 국제구조공학회 2018 Steel and Composite Structures, An International J Vol.28 No.3

The field around additional cutout of the floor beam web in orthotropic bridge deck was subjected to high stress concentration, especially the weld toe between floor beam and U shaped rib and the free edge of the additional cutout. Based on different considerations, different geometrical parameters of additional cutout were proposed in European, American and Japanese specifications, and there remained remarkable differences among them. In this study, considering influence of out-ofplane deformation of floor beam web and U shaped rib, parameter analysis for additional cutout under typical load cases was performed by fine finite element method. The influence of additional cutout shape and height to the stress distribution around the additional cutout were investigated and analyzed. Meanwhile, the static and fatigue test on this structure details was carried out. The stress distribution was consistent with the finite element analysis results. The fatigue property for additional cutout height of 95mm was slightly better than that of 61.5 mm.

Weight reduction does not induce an undesirable decrease in muscle mass, muscle strength, or physical performance in men with obesity: a pilot study

( Bokun Kim ),( Takehiko Tsujimoto ),( Rina So ),( Xiaoguang Zhao ),( Sechang Oh ),( Kiyoji Tanaka ) 한국운동영양학회 2017 Physical Activity and Nutrition (Phys Act Nutr) Vol.21 No.4

[Purpose] To date, there have been no reports on whether weight reduction causes decreases in muscle mass, muscle strength, or physical performance that could lead to health problems. Thus, in this pilot study, we investigated the appropriateness of the changes in muscle mass, muscle strength and physical performance after weight reduction. [Methods] Obese men who completed a weight reduction program to decrease and maintain a body mass index (BMI) of less than 25 kg/m2 for one year were recruited for the study. One year after the completion of a weight reduction program, the participants’ muscle mass, muscle strength, and physical performance were compared with those in a reference group composed of individuals whose BMI was less than 25 kg/m2. Whole-body scanning was performed using dual-energy X-ray absorptiometry to analyze muscle mass. Handgrip strength and knee extensor strength were measured to evaluate arm and leg muscle strength, respectively. For physical performance, a jump test was employed. [Results] The results showed that the biceps, triceps, subscapular, and suprailiac areas of professional fashion models were significantly thinner than those of women in general (p<.001), and that their waist size was also significantly smaller (p<.001). However, hip circumference showed no significant difference. Body mass index, waist-to-hip ratio, and body fat (%) in professional fashion models were significantly lower than those in women in general (p<.001), while the body density in professional fashion models was significantly greater (p<0.001). [Conclusion] Weight reduction participants showed an average reduction in body weight of -16.47%. Normalized arm muscle mass and handgrip strength were significantly greater in the weight reduction group than in the reference group; however, no significant differences were detected between the two groups with respect to the other variables. After one year, there were no significant differences between the two groups.

Population-Stratified Analysis of Bone Mineral Density Distribution in Cervical and Lumbar Vertebrae of Chinese from Quantitative Computed Tomography

Yong Zhang,Zhuang Zhou,Cheng’ai Wu,Danhui Zhao,Chao Wang,Xiaoguang Cheng,Wei Cai,Ling Wang,Yangyang Duanmu,Chenxin Zhang,Wei Tian 대한영상의학회 2016 Korean Journal of Radiology Vol.17 No.5

Objective: To investigate the bone mineral density (BMD) of cervical vertebrae in a population-stratified manner and correlate with that of the lumbar vertebrae. Materials and Methods: Five hundred and ninety-eight healthy volunteers (254 males, 344 females), ranging from 20 to 64 years of age, were recruited for volumetric BMD (vBMD) measurements by quantitative computed tomography. Basic information (age, height, weight, waistline, and hipline), and vBMD of the cervical and lumbar vertebrae (C2–7 and L2–4) were recorded. Comparisons among sex, age groups and different levels of vertebrae were analyzed using analysis of variance. Linear regression was performed for relevance of different vertebral levels. Results: The vBMD of cervical and lumbar vertebrae was higher in females than males in each age group. The vBMD of the cervical and lumbar vertebrae in males and the vBMD of lumbar vertebrae in females decreased with aging. In each age group, the vBMD of the cervical vertebrae was higher than that of the lumbar vertebrae with gradual decreases from C2 to C7 except for C3; moreover, the vBMD of C6 and C7 was significantly different from that of C2–5. Correlations of vBMD among different cervical vertebrae (females: r = 0.62–0.94; males: r = 0.63–0.94) and lumbar vertebrae (males: r = 0.93–0.98; females: r = 0.82–0.97) were statistically significant at each age group. Conclusion: The present study provided normative data of cervical vertebrae in an age- and sex-stratified manner. Sex differences in vBMD prominently vary with age, which can be helpful to design a more comprehensive pre-operative surgical plan.

Melatonin prevents lung injury by regulating apelin 13 to improve mitochondrial dysfunction

Lu Zhang,Fangli Liu,Xiaomin Su,Yue Li,Yining Wang,Ruonan Fang,Yingying Guo,Tongzhu Jin,Huitong Shan,Xiaoguang Zhao,Rui Yang,Hongli Shan,Haihai Liang 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

Pulmonary fibrosis is a progressive disease characterized by epithelial cell damage, fibroblast proliferation, excessive extracellular matrix (ECM) deposition, and lung tissue scarring. Melatonin, a hormone produced by the pineal gland, plays an important role in multiple physiological and pathological responses in organisms. However, the function of melatonin in the development of bleomycin-induced pulmonary injury is poorly understood. In the present study, we found that melatonin significantly decreased mortality and restored the function of the alveolar epithelium in bleomycin-treated mice. However, pulmonary function mainly depends on type II alveolar epithelial cells (AECIIs) and is linked to mitochondrial integrity. We also found that melatonin reduced the production of reactive oxygen species (ROS) and prevented apoptosis and senescence in AECIIs. Luzindole, a nonselective melatonin receptor antagonist, blocked the protective action of melatonin. Interestingly, we found that the expression of apelin 13 was significantly downregulated in vitro and in vivo and that this downregulation was reversed by melatonin. Furthermore, ML221, an apelin inhibitor, disrupted the beneficial effects of melatonin on alveolar epithelial cells. Taken together, these results suggest that melatonin alleviates lung injury through regulating apelin 13 to improve mitochondrial dysfunction in the process of bleomycin-induced pulmonary injury.