CRM1 inhibitor S109 suppresses cell proliferation and induces cell cycle arrest in renal cancer cells

Liu, Xuejiao,Chong, Yulong,Liu, Huize,Han, Yan,Niu, Mingshan The Korean Society of Pharmacology 2016 The Korean Journal of Physiology & Pharmacology Vol.20 No.2

Abnormal localization of tumor suppressor proteins is a common feature of renal cancer. Nuclear export of these tumor suppressor proteins is mediated by chromosome region maintenance-1 (CRM1). Here, we investigated the antitumor effects of a novel reversible inhibitor of CRM1 on renal cancer cells. We found that S109 inhibits the CRM1-mediated nuclear export of RanBP1 and reduces protein levels of CRM1. Furthermore, the inhibitory effects of S109 on CRM1 is reversible. Our data demonstrated that S109 significantly inhibits proliferation and colony formation of renal cancer cells. Cell cycle assay showed that S109 induced G1-phase arrest, followed by the reduction of Cyclin D1 and increased expression of p53 and p21. We also found that S109 induces nuclear accumulation of tumor suppressor proteins, Foxo1 and p27. Most importantly, mutation of CRM1 at Cys528 position abolished the effects of S109. Taken together, our results indicate that CRM1 is a therapeutic target in renal cancer and the novel reversible CRM1 inhibitor S109 can act as a promising candidate for renal cancer therapy.

Interactive and Worst-Case Optimized Robust Control for Potential Application to Guaranteeing Roll Stability for Intelligent Heavy Vehicle

Liu Yulong,Ji Xuewu,Yang Kai-ming,He Xiangkun,Nakano Shirou 한국자동차공학회 2021 International journal of automotive technology Vol.22 No.5

Roll stability loss of heavy vehicle is a severe road safety problem and modern intelligent heavy vehicle (IHV) raises new requirement for advanced roll stability control technology. Two novel roll stability control frameworks, namely active steering-active anti-roll (AS-AAR) interactive control and worst-case optimized robust control, which have potential application to guaranteeing roll stability of IHV are proposed and investigated in this paper. The first control framework is implemented based on Nash dynamic game theory in which AS-AAR shared control is investigated as a dynamic difference game so that its two players, namely AS and AAR system, can interact with each other to provide satisfactory control performance. This interactive control scheme can be applied to vehicle automated driving scenario to improve vehicle tracking performance and roll stability. Based on zero-sum game theory, the second worst-case optimized robust control scheme is also developed to guarantee vehicle roll stability. This control method provides a suitable design framework to guarantee roll stability in scenario of vehicle-to-driver handover for IHV in which the steering input from human driver is regarded as uncertain disturbance. Simulation results show that both control frameworks can effectively improve roll stability as well as lateral stability while ensuing satisfied tracking performance.

Multi-objective Seamless Self-scheduling Controller Design for Heavy Commercial Vehicle Lateral Automation: An LPV/H∞ Approach

Yulong Liu,Tao Xu,Yahui Liu,Xuewu Ji 제어·로봇·시스템학회 2021 International Journal of Control, Automation, and Vol.19 No.12

Modern intelligent road transportation system raises new requirements for advanced vehicle control technology of automated heavy commercial vehicle (HCV). This paper develops a novel output feedback-based linear parameter varying (LPV)/H∞ control paradigm for automated HCV to achieve multi-objective dynamic coordinated control. The proposed control paradigm aims at keeping vehicle centered with respect to the lane boundaries while achieving better roll stability by applying appropriate steering action. The main idea is to schedule tracking performance and roll stability by adjusting steering action according to HCV rollover risk evaluated by the rollover index (RI) estimator during automatic path tracking. This novel control paradigm allows a seamless multi-objective self-scheduling control to be reached and ensures robustness and stability of the closed-loop control system. Based on Simulink & TruckSim Co-Simulation as well as hardware in loop (HIL) implementation, a comparison study between the proposed LPV/H∞ control strategy and a classical linear time-invariant (LTI)/H∞ controller is conducted, which confirms the effectiveness of the proposed control scheme.

CRM1 inhibitor S109 suppresses cell proliferation and induces cell cycle arrest in renal cancer cells

Xuejiao Liu,Yulong Chong,Huize Liu,Yan Han,Mingshan Niu 대한생리학회-대한약리학회 2016 The Korean Journal of Physiology & Pharmacology Vol.20 No.2

Abnormal localization of tumor suppressor proteins is a common feature of renal cancer. Nuclear export of these tumor suppressor proteins is mediated by chromosome region maintenance-1 (CRM1). Here, we investigated the antitumor effects of a novel reversible inhibitor of CRM1 on renal cancer cells. We found that S109 inhibits the CRM1-mediated nuclear export of RanBP1 and reduces protein levels of CRM1. Furthermore, the inhibitory effect of S109 on CRM1 is reversible. Our data demonstrated that S109 significantly inhibits proliferation and colony formation of renal cancer cells. Cell cycle assay showed that S109 induced G1-phase arrest, followed by the reduction of Cyclin D1 and increased expression of p53 and p21. We also found that S109 induces nuclear accumulation of tumor suppressor proteins, Foxo1 and p27. Most importantly, mutation of CRM1 at Cys528 position abolished the effects of S109. Taken together, our results indicate that CRM1 is a therapeutic target in renal cancer and the novel reversible CRM1 inhibitor S109 can act as a promising candidate for renal cancer therapy.

Numerical simulation in time domain to study cross-flow VIV of catenary riser subject to vessel motion-induced oscillatory current

Liu, Kun,Wang, Kunpeng,Wang, Yihui,Li, Yulong The Society of Naval Architects of Korea 2020 International Journal of Naval Architecture and Oc Vol.12 No.1

The present study proposes a time domain model for the Vortex-induced Vibration (VIV) simulation of a catenary riser under the combination of the current and oscillatory flow induced by vessel motion. In this model, the hydrodynamic force of VIV comprises excitation force, hydrodynamic damping and added mass, which are taken as functions of the non-dimensional frequency and amplitude ratio. The non-dimensional frequency is related with the response frequency, natural frequency, lock-in range and the fluid velocity. The relatively oscillatory flow induced by vessel motion is taken into account in the fluid velocity. Considering that the added mass coefficient and the non-dimensional frequency can affect each other, an iterative analysis is conducted at each time step to update the added mass coefficient and the natural frequency. This model is in detail validated against the published test models. The results show that the model can reasonably reflect the effect of the added mass coefficient on the VIV, and can well predict the riser's VIV under stationary and oscillatory flow induced by vessel motion. Based on the model, this study carries out the VIV simulation of a catenary riser with harmonic vessel motion. By analyzing the bending moment near the touchdown point, it is found that under the combination of the ocean current and oscillatory flow the vessel motion may decrease the VIV response, while increase the excited frequencies. In addition, the decreasing rate of the VIV under vessel surge is larger than that under vessel heave at small vessel motion velocity, while the situation becomes opposite at large vessel motion velocity.

Numerical simulation in time domain to study cross-flow VIV of catenary riser subject to vessel motion-induced oscillatory current

Liu, Kun,Wang, Kunpeng,Wang, Yihui,Li, Yulong The Society of Naval Architects of Korea 2020 International Journal of Naval Architecture and Oc Vol.12 No.-

The present study proposes a time domain model for the Vortex-induced Vibration (VIV) simulation of a catenary riser under the combination of the current and oscillatory flow induced by vessel motion. In this model, the hydrodynamic force of VIV comprises excitation force, hydrodynamic damping and added mass, which are taken as functions of the non-dimensional frequency and amplitude ratio. The non-dimensional frequency is related with the response frequency, natural frequency, lock-in range and the fluid velocity. The relatively oscillatory flow induced by vessel motion is taken into account in the fluid velocity. Considering that the added mass coefficient and the non-dimensional frequency can affect each other, an iterative analysis is conducted at each time step to update the added mass coefficient and the natural frequency. This model is in detail validated against the published test models. The results show that the model can reasonably reflect the effect of the added mass coefficient on the VIV, and can well predict the riser's VIV under stationary and oscillatory flow induced by vessel motion. Based on the model, this study carries out the VIV simulation of a catenary riser with harmonic vessel motion. By analyzing the bending moment near the touchdown point, it is found that under the combination of the ocean current and oscillatory flow the vessel motion may decrease the VIV response, while increase the excited frequencies. In addition, the decreasing rate of the VIV under vessel surge is larger than that under vessel heave at small vessel motion velocity, while the situation becomes opposite at large vessel motion velocity.

Quad-Band Bandpass Filter Using Quad-Mode Stub-loaded Resonators

Haiwen Liu,Xiaomei Wang,YAN WANG,Shen Li,Yulong Zhao,Xuehui Guan 한국전자통신연구원 2014 ETRI Journal Vol.36 No.4

Compact multi-band bandpass filters using quad-mode stubloadedresonators are proposed in this letter. Firstly, a novelapproach about the mode-splitting characteristics of thequadruple-mode resonator is investigated, which can providedual-band behavior. Secondly, a quad-band filter is proposedand designed by cascading two quadruple-mode resonators;the upper one operates at 1.8/2.4 GHz (GSM- and WiMaxband)and the lower one at 1.57/2.1 GHz (GPS- and WCDMAband). Finally, the proposed filters have been fabricated. Respectable agreement between simulation and measurementverifies the validity of this design methodology.

Hair Growth Promoting Effects of 650 nm Red Light Stimulation on Human Hair Follicles and Study of Its Mechanisms via RNA Sequencing Transcriptome Analysis

( Kai Yang ),( Yulong Tang ),( Yanyun Ma ),( Qingmei Liu ),( Yan Huang ),( Yuting Zhang ),( Xiangguang Shi ),( Li Zhang ),( Yue Zhang ),( Ji’an Wang ),( Yifei Zhu ),( Wei Liu ),( Yimei Tan ),( Jinran 대한피부과학회 2021 Annals of Dermatology Vol.33 No.6

Background: Androgenetic alopecia (AGA) leads to thinning of scalp hair and affects 60%~70% of the adult population worldwide. Developing more effective treatments and studying its mechanism are of great significance. Previous clinical studies have revealed that hair growth is stimulated by 650-nm red light. Objective: This study aimed to explore the effect and mechanism of 650-nm red light on the treatment of AGA by using ex vivo hair follicle culture. Methods: Human hair follicles were obtained from hair transplant patients with AGA. Hair follicles were cultured in Williams E medium and treated with or without 650-nm red light. Real-time RT-PCR and immunofluorescence staining were used to detect the expression level of genes and proteins in hair follicles, respectively. RNA-sequencing analysis was carried out to reveal the distinct gene signatures upon 650 nm treatment. Results: Low-level 650 nm red light promoted the proliferation of human hair follicles in the experimental cultured-tissue model. Consistently, 650 nm red light significantly delayed the transition of hair cycle from anagen to catagen in vitro. RNA-seq analysis and gene clustering for the differentially expressed genes suggests that leukocyte transendothelial migration, metabolism, adherens junction and other biological process maybe involved in stimulation of hair follicles by 650-nm red light treatment. Conclusion: The effect of 650-nm red light on ex vivo hair follicles and the transcriptome set which implicates the role of red light in promoting hair growth and reversing of miniaturization process of AGA were identified.

Impact of feeding regimens on the composition of gut microbiota and metabolite profiles of plasma and feces from Mongolian sheep

Bohui Wang,Yulong Luo,Rina Su,Duo Yao,Yanru Hou,Chang Liu,Rui Du,Ye Jin 한국미생물학회 2020 The journal of microbiology Vol.58 No.6

Mongolian sheep are an indigenous ruminant raised for wool and meat production in China. The gut microbial community plays an important role in animal performance and metabolism. The objective of this study was to investigate the effects of two feeding regimens on the diversity and composition of gut microbiota and metabolite profiles of feces and plasma from Mongolian sheep. A total of 20 Mongolian sheep were assigned to one of two feeding regimens: free grazing (FG) and barn confinement (BC). When samples were collected, the average live weights of the sheep were 31.28 ± 1.56 kg and 34.18 ± 1.87 kg for the FG and BC groups, respectively. At the genus level, the FG group showed higher levels of Bacteroides, RC9_gut_group, Alistipes, Phocaeicola, Barnesiella, and Oscillibacter, and lower levels of Succinivibrio, Treponema, and Prevotella, compared to the BC group. The butyric acid content in feces was lower in the FG group (P < 0.05). Higher levels of palmitic acid, oleic acid, alpha-linolenic acid, L-carnitine, L-citrulline, and L-histidine, and lower levels of L-tyrosine, L-phenylalanine, and L-kynurenine were found in the plasma of the FG sheep. Moreover, there were substantial associations between several gut microbiota genera and alterations in feces and plasma metabolites especially those involved in the metabolism of butyric acid, linolenic acid, and L-tyrosine. Feeding regimens can not only influence the composition of gut microbiota, but also alter metabolic homeostasis in sheep.

Expression profiles of microRNAs in skeletal muscle of sheep by deep sequencing

Zhi-Jin Liu,Cun-Yuan Li,Xiao-Yue Li,Yang Yao,Wei Ni,Xiang-Yu Zhang,Yang Cao,Wureli Hazi,Dawei Wang,Renzhe Quan,Shuting Yu,Yuyu Wu,Songmin Niu,Yulong Cui,Yaseen Khan,Shengwei Hu 아세아·태평양축산학회 2019 Animal Bioscience Vol.32 No.6

Objective: MicroRNAs are a class of endogenous small regulatory RNAs that regulate cell proliferation, differentiation and apoptosis. Recent studies on miRNAs are mainly focused on mice, human and pig. However, the studies on miRNAs in skeletal muscle of sheep are not comprehensive. Methods: RNA-seq technology was used to perform genomic analysis of miRNAs in prenatal and postnatal skeletal muscle of sheep. Targeted genes were predicted using miRanda software and miRNA-mRNA interactions were verified by quantitative real-time polymerase chain reaction. To further investigate the function of miRNAs, candidate targeted genes were enriched for analysis using gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment. Results: The results showed total of 1,086 known miRNAs and 40 new candidate miRNAs were detected in prenatal and postnatal skeletal muscle of sheep. In addition, 345 miRNAs (151 up-regulated, 94 down-regulated) were differentially expressed. Moreover, miRanda software was performed to predict targeted genes of miRNAs, resulting in a total of 2,833 predicted targets, especially miR-381 which targeted multiple muscle-related mRNAs. Furthermore, GO and KEGG pathway analysis confirmed that targeted genes of miRNAs were involved in development of skeletal muscles. Conclusion: This study supplements the miRNA database of sheep, which provides valuable information for further study of the biological function of miRNAs in sheep skeletal muscle.