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Qian Kun,Xu Wei,Xia Xiaoyao,Ding Jinhuo 한국유전학회 2022 Genes & Genomics Vol.44 No.12
Background: Methyltransferase-like 3 (METTL3) is an RNA N6-methyladenosine (m6A) methyltransferase, which plays a critical role in micorRNA (miRNAs) processing and maturation, but it is still unclear whether METTL3 regulated miRNAs participates in the regulation of cancer aggressiveness in gastrointestinal stromal tumors (GISTs). Objectives: This study was designed to investigate this issue, and uncover the potential underlying mechanisms. Methods: the expression of METTL3 in GISTs tissues and cell lines were determined by RT-qPCR and Western blot. Cell proliferation and migration were assessed by colony formation, CCK-8 and Transwell. The mRNA expression of all proteins was detected by RT-qPCR, and tumor xenograft study was applied to confirm the effect of METTL3 on GISTs development in vivo. Results: In our study, we showed that METTL3 was significantly upregulated in GISTs tissues and cell lines. Functional experiments demonstrated that overexpression of METTL3 promoted GISTs cell malignant biological behavior and tumor growth in vitro and in vivo, and conversely, silencing of METTL3 had opposite effects and suppressed GISTs progression. Further mechanistical experiments verified that METTL3 promoted the maturation of miR-25-3p in an m6A-dependent manner. Similar to METTL3, miR-25-3p was also validated as an oncogene to promote cancer development in GISTs. Finally, our rescuing experiments hinted that silencing of miR-25-3p abrogated the tumor-initiating effects of METTL3 overexpression on GISTs. Conclusion: Collectively, those results indicated that METTL3 played an oncogenic role in GISTs through positively modulating the miR-25-3p in an m6A-dependent manner, and we firstly discussed how the METTL3/m6A/miR-25-3p axis affected GISTs development.
Qiankun Zhu,Mengli Zhu,Gaotao Fan,Jiaxin Zou,Peichun Feng,Zubi Liu,Wanjun Wang 대한화학회 2014 Bulletin of the Korean Chemical Society Vol.35 No.1
Coptis chinensis 3'-hydroxy-N-methylcoclaurine 4'-O-methyltransferase (HOMT), an essential enzyme in the berberine biosynthetic pathway, catalyzes the methylation of 3'-hydroxy-N-methylcoclaurine (HMC) producing reticuline. A 3D model of HOMT was constructed by homology modeling and further subjected to docking with its ligands and molecular dynamics simulations. The 3D structure of HOMT revealed unique structural features which permitted the methylation of HMC. The methylation of HMC was proposed to proceed by deprotonation of the 4'-hydroxyl group via His257 and Asp258 of HOMT, followed by a nucleophilic attack on the SAM-methyl group resulting in reticuline. HOMT showed high substrate specificity for methylation of HMC. The study evidenced that Gly117, Thr312 and Asp258 in HOMT might be the key residues for orienting substrate for specific catalysis.
Studies on the Small Body Size Mouse Developed by Mutagen N-Ethyl-N-nitrosourea
QianKun Zhang,Kyu-Hyuk Cho,Jae-Woo Cho,Dal-Sun Cha,Han-Jin Park,Seokjoo Yoon,ShouFa Zhang,Chang-Woo Song 한국독성학회 2008 Toxicological Research Vol.24 No.1
Mutant mouse which show dwarfism has been developed by N-ethyl-N-nitrosourea (ENU) mutagenesis using BALB/c mice. The mutant mouse was inherited as autosomal recessive trait and named Small Body Size (SBS) mouse. The phenotype of SBS mouse was not apparent at birth, but it was possible to distinguish mutant phenotype from normal mice 1 week after birth. In this study, we examined body weight changes and bone mineral density (BMD), and we also carried out genetic linkage analysis to map the causative gene(s) of SBS mouse. Body weight changes were observed from birth to 14 weeks of age in both affected (n = 30) and normal mice (n = 24). BMD was examined in each five SBS and normal mice between 3 and 6 weeks of age, respectively. For the linkage analysis, we produced backcross progeny [(SBS × C57BL/6J) F₁× SBS] N₂mice (n = 142), and seventy-four microsatellite markers were used for primary linkage analysis. Body weight of affected mice was consistently lower than that of the normal mice, and was 43.7% less than that of normal mice at 3 weeks of age (P < 0.001). As compared with normal mice at 3 and 6 weeks of age, BMD of the SBS mice was significantly low. The results showed 15.5% and 14.1% lower in total body BMD, 15.3% and 8.7% lower in forearm BMD, and 29.7% and 20.1% lower in femur BMD, respectively. The causative gene was mapped on chromosome 10. The map order and the distance between markers were D10Mit248 - 2.1 cM - D10Mit51 - 4.2 cM - sbs - 0.7 cM - D10Mit283 - 1.4 cM - D10Mit106 - 11.2 cM - D10Mit170.
Qiankun Ma,Xuyong Wang,Fan Yuan,Liangshen Chen,Jianfeng Tao,Zhonghua Miao 대한기계학회 2016 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.30 No.8
The friction coefficient between the vane and the slot is one of the most critical factors that affects the performance of a continuous rotary hydraulic cam-rotor vane motor. To study the effects of this coefficient on the torque characteristics of the motor, the mathematical model for the normal force and the disturbing torque between the cam rotors and the vanes of the motor was established by analyzing the forces exerted on the vanes. The mathematical model was simulated with MATLAB, and simulation results show that an increase in the friction coefficient would simultaneously decrease the normal force and increase the disturbing torque, which would negatively affect the performance of the motor. Further experimental research indicated that the low-speed performance of the hydraulic cam-rotor motor was significantly improved when the friction coefficient was reduced by controlling the parallelism tolerance, flatness and roughness between the vanes and the slots.
Common Correlated Effects Estimation of Unbalanced Panel Data Models with Cross-Sectional Dependence
Qiankun Zhou,Yonghui Zhang 한국계량경제학회 2016 계량경제학보 Vol.27 No.4
We consider the estimation and inference of unbalanced panel data models with cross-sectional dependence with a large number of individual units in a relatively short time period. By following the common correlated effects (CCE) approach of Pesaran (2006), we propose a CCE estimator for unbalanced panels (CCE-UB). The asymptotics of the CCE-UB estimator is developed in the paper. Small scale Monte Carlo simulation is conducted to examine the finite sample properties of the proposed estimator.
A full path assessment approach for vibration serviceability and vibration control of footbridges
Qiankun Zhu,Xiaoli Hui,Yongfeng Du,Qiong Zhang 국제구조공학회 2019 Structural Engineering and Mechanics, An Int'l Jou Vol.70 No.6
Most of the existing evaluation criteria of vibration serviceability rely on the peak acceleration of the structure rather than that of the people keeping their own body unmoved on the structure who is the real receiver of structural vibrations. In order to accurately assess the vibration serviceability, therefore, a full path assessment approach of vibration serviceability based on vibration source, path and receiver is not only tentatively proposed in this paper, taking the peak acceleration of receiver into account, but also introduce a probability procedure to provide more instructive information instead of a single value. In fact, semi-rigid supported on both sides of the structure is more consistent with the actual situation than simply supported or clamped due to the application of the prefabricated footbridge structures. So, the footbridge is regarded as a beam with semi-rigid supported on both sides in this paper. The differential quadrature-integral quadrature coupled method is not only to handle different type of boundary conditions, but also after being further modified via the introduction of an approximation procedure in this work, the time-varying system problem caused by human-structure interaction can be solved well. The analytical results of numerical simulations demonstrate that the modified differential quadrature-integral quadrature coupled method has higher reliability and accuracy compared with the mode superposition method. What’s more, both of the two different passive control measures, the tuned mass damper and semi-rigid supported, have good performance for reducing vibrations. Most importantly, semi-rigid supported is easier to achieve the objective of reducing vibration compared with tuned mass damper in design stage of structure.
Qiankun Zhu,Xiaoli Hui,Nana Nan,Yongfeng Du 대한토목학회 2019 KSCE JOURNAL OF CIVIL ENGINEERING Vol.23 No.5
Due to the complexity and randomness of the crowd motion, it is not easy to establish the crowd-structure coupled governing equation. Therefore, the idea of the solution procedure for the coupled system of the single pedestrian and structure is extended to carry out the research of crowd-structure coupled system. Then based on the social force model and the deceleration mechanism aswell as the self-stopped mechanism, the one-way pedestrian flow is simulated. The modified Differential Quadrature-Integral Quadrature (DQ-IQ) mixed method is used to solve the dynamic response of the structure under the moving stiffness-mass-damping model, which can demonstrate this method enjoys higher accuracy than the mode superposition method and can take enough higher modes into consideration. Additionally, the fact that the DQ-IQ mixed method can be used to solve the dynamic response of the structure subjected to the crowd is verified. The final results under random crowd show that the varying tendencies of structural modal parameters respectively changed with the the number of pedestrian acting on the structure, In order to more comprehensively and more scientifically measure the vibration function of the structure, the 1 s-RMS acceleration is introduced to weaken the interference effect of random fluctuation.