Activation of Phosphatidylinositol 3-Kinase/AKT/Snail Sig-nalling Pathway Contributes to Epithelial-Mesenchymal Transition-Induced Multi-Drug Resistance to Sorafenib in Hepatocellular Carcinoma Cells

( Jiejie Dong ),( Bo Zhai ),( Weihua Sun ),( Fengli Hu ),( Hao Cheng ),( Lishan Xu ),( Jun Xu ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Sorafenib, an orally available kinase inhibitor, is the standard first-line systemic drug for advanced hepatocellular carcinoma (HCC), and it exerts potent inhibitory activity against epithelial-mesenchymal transition (EMT) and multidrug resistance (MDR) by inhibiting mitogen- activated protein kinase (MAPK) signalling in HCC. However, after long-term exposure to sorafenib, HCC cells exhibit EMT and resistance to sorafenib. The activation of AKT by sorafenib is thought to be responsible for the development of these characteristics. The present study aims to examine the underlying mechanism and seek potential strategies to reverse this resistance and the progression to EMT. Methods: Cell viability assay; Transfection of siRNA; Construction of the pCDNA3.1-Snail eukaryotic expression vector and transfection; Cell migration and invasion assays; Western blot analysis; Real-time reverse transcription PCR. Results: Sorafenib-resistant cells showed increased metastatic and invasive ability, with a higher expression of P-glycoprotein (P-gp), compared with the parental cells. This phenomenon was at least partially due to EMT and the appearance of MDR in sorafenib-resistant HCC cells. Moreover, MDR was a downstream molecular event of EMT. Silencing Snail with siRNA blocked EMT and partially reversed the MDR, thereby markedly abolishing invasion and metastasis in sorafenib- resistant HCC cells, but silencing of MDR1 had no effect on the EMT phenotype. Additionally, HCC parental cells that were stably transfected with pCDNA3.1-Snail exhibited EMT and MDR. Two sorafenib- resistant HCC cell lines, established from human HCC HepG2 and Huh7 cells, were refractory to sorafenib-induced growth inhibition but were sensitive to MK-2206, a novel allosteric AKT inhibitor. Thus, the combination of sorafenib and MK-2206 led to significant reversion of the EMT phenotype and P-gp-mediated MDR by downregulating phosphorylated AKT. Conclusions: These findings underscore the significance of EMT, MDR and enhanced PI3K/AKT signalling in sorafenib-resistant HCC cells.

Setup and Performance of a Combined Hardware-in-loop and Software-in-loop Test for MMC-HVDC Control and Protection System

Chang Lin,Dong Liu,Xueguang Wu,ZhiyuanHe,Weihua Wang,Wei Li 전력전자학회 2015 ICPE(ISPE)논문집 Vol.2015 No.6

Despite the rapid development of VSC-HVDC technology, the practical experience to operate modular multi-level converter (MMC) has not yet been sufficiently accumulated. Real-time simulation is one of the most efficient approaches to verify the control and protection (C & P) scheme under various contingencies. With the increasing number of sub-modules, the accurate simulation of the MMC-HVDC becomes more difficult, as it requires larger computing resources and more complex interface between the test platform and the C&P system hardware devices. This paper proposes an application of real-time simulation, which combines the hardware-in--loop (HIL) and software-in-loop (SIL) approach to test a control and protection system for MMC-based HVDC links. In the proposed system, a pole control and protection (PCP) will be tested using the HIL approach, while the valve base controller (VBC) is tested using the SIL method. The setup of the test rig and performance is demonstrated in this paper.

Study of microstructure evolution and mechanical behaviour changes of PAN-based carbon fibers after high-temperature heat treatment (up to 2950 °C)

Lichao Song,Weihua Xie,Dong Yu,Songhe Meng,Fan Yang,Fengliang Liu,Ying Zhang 한국공업화학회 2023 Journal of Industrial and Engineering Chemistry Vol.124 No.-

The quantitative relationship between the microstructure behaviour and mechanical properties of polyacrylonitrile(PAN) carbon fibers (CF) after being heat treated in the range of 2000–2950 C was studied. The surface morphology, elemental composition, orientation of graphite microcrystallites (P), carboninterlayer spacing distances (d002), crystallite dimension (Lc and La), skin-core structure, pore structureand mechanical properties were characterised and evaluated after high-temperature heat treatment(HHT). The study found that increasing temperature resulted in an increase in the orientation of graphitecrystals and the stress component of microcrystalline strong bonding direction along the fiber axial direction,leading to Young’s modulus of T300 and M40J increases of 18.7% and 7.7%, respectively. Meanwhile,the decrease in tensile strength by 53.9% and 29.4%, respectively, can be attributed to the deterioration ofthe homogeneity of the CF radial structure and a reduction in the stress dissipation path inside the CF. Finally, we have developed a theoretical model to predict the CF tensile strength and Young’s modulusbased on Griffith’s fracture theory and uniform stress model, and it was verified with a relative errorbetween the calculated and measured values less than 10%.

The Up-Regulation of miR-199b-5p in Erythroid Differentiation Is Associated with GATA-1 and NF-E2

Li, Yuxia,Bai, Hua,Zhang, Zhongzu,li, Weihua,Dong, Lei,Wei, Xueju,Ma, Yanni,Zhang, Junwu,Yu, Jia,Sun, Guotao,Wang, Fang Korean Society for Molecular and Cellular Biology 2014 Molecules and cells Vol.37 No.3

MicroRNAs (miRNAs) represent a class of small non-coding regulatory RNAs that play important roles in normal hematopoiesis, including erythropoiesis. Although studies have identified several miRNAs that regulate erythroid commitment and differentiation, we do not understand the mechanism by which the crucial erythroid transcription factors, GATA-1and NF-E2 directly regulate and control differentiation via miRNA pathways. In this study, we identified miR-199b-5p as a key regulator of human erythropoiesis, and its expression was up-regulated during the erythroid differentiation of K562 cells. Furthermore, the increase of miR-199b-5p in erythroid cells occurred in a GATA-1- and NF-E2-dependent manner during erythrocyte maturation. Both GATA-1 and NF-E2 bound upstream of the miR-199b gene locus and activated its transcription. Forced expression of miRNA-199b-5p in K562 cells affected erythroid cell proliferation and maturation. Moreover, we identified c-Kit as a direct target of miR-199b-5p in erythroid cells. Taken together, our results establish a functional link among the erythroid transcription factors GATA-1/NF-E2, miR-199b-5p and c-Kit, and provide new insights into the coupling of transcription and post-transcription regulation in erythroid differentiation.

The Up-Regulation of miR-199b-5p in Erythroid Differentiation Is Associated with GATA-1 and NF-E2

Yuxia Li,Hua Bai,Zhongzu Zhang,Weihua li,Lei Dong,Xueju Wei,Yanni Ma,Junwu Zhang,Jia Yu,Guotao Sun,Fang Wang 한국분자세포생물학회 2014 Molecules and cells Vol.37 No.3

MicroRNAs (miRNAs) represent a class of small non-co-ding regulatory RNAs that play important roles in normal hematopoiesis, including erythropoiesis. Although studies have identified several miRNAs that regulate erythroid commitment and differentiation, we do not understand the mechanism by which the crucial erythroid transcription factors, GATA-1and NF-E2 directly regulate and control differentiation via miRNA pathways. In this study, we identified miR-199b-5p as a key regulator of human erythropoiesis, and its expression was up-regulated during the erythroid differentiation of K562 cells. Furthermore, the increase of miR-199b-5p in erythroid cells occurred in a GATA-1- and NF-E2-dependent manner during erythrocyte maturation. Both GATA-1 and NF-E2 bound upstream of the miR-199b gene locus and activated its transcription. Forced expression of miRNA-199b-5p in K562 cells affected erythroid cell proliferation and maturation. Moreover, we identified c-Kit as a direct target of miR-199b-5p in erythroid cells. Taken together, our results establish a functional link among the erythroid transcription factors GATA-1/NF-E2, miR-199b-5p and c-Kit, and provide new insights into the coupling of transcription and post-transcription regulation in erythroid differentiation.

Genetic diversity and structure of the endangered species Megaleranthis saniculifolia in Korea as revealed by allozyme and ISSR markers

Jeong, Ji Hee,Kim, Eun Hye,Guo, Weihua,Yoo, Ki Oug,Jo, Dong Gwang,Kim, Zin Suh Springer-Verlag 2010 Plant systematics and evolution Vol.289 No.1

A reduced time-varying model for a long beam on elastic foundation under moving loads

Guiming Mei,Caijin Yang,Shulin Liang,Jiangwen Wang,Dong Zou,Weihua Zhang,Yunshi Zhao,Zhong Huang,Shuqi Song,Mengying Tan,Yao Cheng,Bingrong Miao 대한기계학회 2018 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.32 No.9

Dynamics of a long beam on the elastic foundation subjected to moving loads is studied in the present paper. The sliding window technique is used to dynamically truncate the long beam and a reduced time-varying beam system is obtained. The Hamilton’s principle is employed to establish the equations of motion of the reduced system. The variable separation method is adopted to solve dynamical responses of the reduced system. Examples of a long simply supported Timoshenko beam on the nonlinear foundation subjected to a single moving load and multiple loads are included. Numerical results of the reduced model compared with the ones obtained from the moving element model adapted in literature are carried out to show the validity and the good efficiency of the method proposed in the present paper.

CAWR: Buffer Replacement with Channel-Aware Write Reordering Mechanism for SSDs

Ronghui Wang,Zhiguang Chen,Nong Xiao,Minxuan Zhang,Weihua Dong 한국전자통신연구원 2015 ETRI Journal Vol.37 No.1

A typical solid-state drive contains several independent channels that can be operated in parallel. To exploit this channel-level parallelism, a variety of works proposed to split consecutive write sequences into small segments and schedule them to different channels. This scheme exploits the parallelism but breaks the spatial locality of write traffic; thus, it is able to significantly degrade the efficiency of garbage collection. This paper proposes a channel-aware write reordering (CAWR) mechanism to schedule write requests to different channels more intelligently. The novel mechanism encapsulates correlated pages into a cluster beforehand. All pages belonging to a cluster are scheduled to the same channels to exploit spatial locality, while different clusters are scheduled to different channels to exploit the parallelism. As CAWR covers both garbage collection and I/O performance, it outperforms existing schemes significantly. Trace-driven simulation results demonstrate that the CAWR mechanism reduces the average response time by 26% on average and decreases the valid page copies by 10% on average, while achieving a similar hit ratio to that of existing mechanisms.

Low-Temperature Scanning Near-Field Optical Microscope and Spectroscopy: Application in Quantum Well Device

Gengzhao XU,Xing ZHU,Hu Liang,Kay May Lau,Weihua ZHANG,Yun-Dong Qi 한국물리학회 2005 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.47 No.1

We have constructed a versatile low-temperature scanning near-field optical microscope (LTSNOM) with the capability of near-field imaging and spectroscopy, operating at liquid nitrogen (LN) temperature. A sample is illuminated either electronically or optically by introducing a laser beam through specially designed coaxial double lenses and an optical fiber. The detected optical signal is transmitted via a fiber tip to a photoelectric multiplier tube (PMT) or a spectrometer. Shear-force detection by using a tuning-fork technique is applied to maintain the tip-sample distance. A shearforce topographic image, an optical image and a local spectrum can be obtained simultaneously. The whole scanning head is enclosed inside a container which is immersed in liquid nitrogen in a storage Dewar during the measurement. We have used this LT-SNOM to study the electroluminescence (EL) properties of InGaN/GaN multiple-quantum-well light-emitting diodes (LEDs), at both room temperature and liquid nitrogen temperature. Low-temperature experiments with the LT-SNOM show the stability of our construction and stable image acquisition at LN temperature. The results show that at room temperature the EL intensity distribution is quite inhomogeneous with islands like bright spots, and at LN temperature the EL intensity increased dramatically and the inhomogeneity reduced greatly. Furthermore, the near-field spectra show a peak at a higher photon energy at around 2.95 eV at low temperature, in addition to the 2.7 eV peak observed by far field at room temperature. The results indicate that the self-organized In rich regions play a key role in the EL properties of these LEDs, which act as radiation recombination centers. In conjunction with nearfield spectroscopy, the possible mechanism of this phenomenon is explained in terms of irradiative recombination in the MQWs, as well as the quantum-confined Starks effect.

Chelant-enhanced washing of CCA-contaminated soil: Coupled with selective dissolution or soil stabilization

Beiyuan, Jingzi,Lau, Abbe Y.T.,Tsang, Daniel C.W.,Zhang, Weihua,Kao, Chih-Ming,Baek, Kitae,Ok, Yong Sik,Li, Xiang-Dong Elsevier 2018 Science of the Total Environment Vol.612 No.-

<P><B>Abstract</B></P> <P>Remediation of CCA-contaminated soil (Cr, Cu, and As) by biodegradable chelant-enhanced washing (EDDS, <I>S,S</I>-ethylene-diamine-disuccinic-acid) needs further enhancement. This study investigated the effectiveness of coupling with pre-treatment by selective dissolution and post-treatment by soil amendments, respectively. Three groups of reagents (reductants, alkaline solvents, and organic ligands) were adopted in the pre-treatment to dissolve the oxide minerals before EDDS extraction. In the post-treatment, soil amendments (coal fly ash (CFA), acid mine drainage sludge (AMDS), green waste compost (GWC)), and their mixtures) were used for a 2-month stabilization after 2-h EDDS washing. Multi-endpoint evaluation was performed by assessing the chemical state, leachability, mobility, bioaccessibility, and plant-availability of residual metal(loid)s as well as the cytotoxicity, enzyme activities, and available nutrients of the treated soils. Pre-treatment by dithionite-citrate-bicarbonate significantly enhanced extraction efficiency, but also increased the leachability of As and Cr and bioaccessibility of Cr in the treated soils. While sodium hydroxide removed the majority of As without increasing its leachability and bioaccessibility, it increased the cytotoxicity and inhibited the acid phosphatase activity. Post-treatment with AMDS and CFA effectively controlled the mobility and leachability of residual As and Cr after EDDS washing. However, destabilized Cu was only marginally immobilized by GWC due to strong Cu-EDDS complexation. The bioaccessibility and phytoavailability of Cu was primarily reduced by EDDS washing, while those of As and Cr could be attenuated by AMDS and CFA. This study indicates that coupling chemical extraction with subsequent soil amendment plays complementary roles in mitigating effects of residual metal(loid)s and improving environmental quality.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Selective dissolution improved the removal efficiency of Cr, Cu, and As. </LI> <LI> Leachability and bioaccessibility of residual metal(loid)s were increased. </LI> <LI> NaOH washing boosted cytotoxicity and inhibited acid phosphatase activity. </LI> <LI> Mobility and leachability of residual metal(loid)s were curbed by CFA and AMDS. </LI> <LI> In contrast, bioaccessibility and plant-availability were reduced only by EDDS. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>