Browsing by Author "Huang, Chih-Yang"

Now showing 1 - 15 of 15

Apicidin-resistant HA22T hepatocellular carcinoma cells massively promote pro-survival capability via IGF-IR/PI3K/Akt signaling pathway activation
(2014-01-01)
Hsu, Hsi-Hsien
;
Cheng, Li-Hao
;
Ho, Tsung-Jung
;
Kuo, Wei-Wen
;
Lin, Yueh-Min
Despite rapid advances in the diagnostic and surgical procedures, hepatocellular carcinoma (HCC) remains one of the most difficult human malignancies to treat. This may be due to the chemoresistant behaviors of HCC. It is believed that acquired resistance could be overcome and improve the overall survival of HCC patients by understanding the mechanisms of chemoresistance in HCC. A stable HA22T cancer line, which is chronically resistant to a histone deacetylase inhibitor, was established. After comparing the molecular mechanism of apicidin-R HA22T cells to parental ones by Western blotting, cell cycle-regulated proteins did not change in apicidin-R cells, but apicidin-R cells were more proliferative and had higher tumor growth (wound-healing assay and nude mice xenograft model). Moreover, apicidin-R cells displayed increased levels of p-IGF-IR, p-PI3K, p-Akt, Bcl-xL, and Bcl-2 but also significantly inhibited the tumor suppressor PTEN protein and apoptotic pathways when compared to the parental strain. Therefore, the highly proliferative effect of apicidin-R HA22T cells was blocked by Akt knockdown. For all these findings, we believe that novel strategies to attenuate IGF-IR/PI3K/Akt signaling could overcome chemoresistance toward the improvement of overall survival of HCC patients.
Atomic-Scale Localized Thinning and Reconstruction of Two-Dimensional WS2 Layers through In Situ Transmission Electron Microscopy/Scanning Transmission Electron Microscopy
(2020-07-09)
Tseng, Yi-Tang
;
Tai, Kuo-Lun
;
Huang, Chun-Wei
;
Huang, Chih-Yang
;
Wu, Wen-Wei
Subnanometer nanofabrication has been investigated, and electron beam processing has been found to be a suitable strategy to control nanoparticle organization over large areas. Organized nanostructures have demonstrated their potential for technological applications. Here, we focus on the processing of tungsten disulfide (WS2) due to its novelty and promising electronic properties for further development of functional devices. First, we summarize the theory of electron beam irradiation by surveying the dynamic behaviors observed during in situ experiments. In particular, the diverse structures with various numbers of layers derived from localized thinning produce considerable lateral heterointerfaces. The generation of the intriguing tungsten-rich cluster is also consistent with the mechanism of our atomic engineering experiments. These findings suggest a method for the electron beam processing of 2D materials and demonstrate the viability of atomic engineering using electron irradiation.
Dung-shen (Codonopsis pilosula) attenuated the cardiac-impaired insulin-like growth factor II receptor pathway on myocardial cells
(2013-05-15)
Tsai, Kun-Hsi
;
Lee, Nien-Hung
;
Chen, Guei-Ying
;
Hu, Wei-Syun
;
Tsai, Chen-Yen
Previous studies from our lab showed that increase in AngIl in H9c2 cells causes elevated IGFII and IGFIIR through MEK and JNK, leading to rise in intracellular calcium, calcineurin activation by PLC-beta 3 via G alpha q, insertion into mitochondrial membranes of Bad, and apoptosis via caspases 9 and 3. Codonopsis pilosula is traditionally used to lower blood pressure. The purpose of our study is to investigate if C. pilosula attenuates AngII plus Leu(27)-IGFII-induced calcium influx and apoptosis in H9c2 cardiomyoblasts. C pilosula significantly attenuated AngII induced IGFIIR promoter activity. Leu(27)-IGFII was applied to enhance the Angll effect. C pilosula also reversed Ca2+ influx, MOMP and apoptosis increased by AngIl plus Leu(27)-IGFIL Molecular markers in IGFIIR apoptotic pathway (IGFIIR, calcineurin, etc.) and IGFIIR-G alpha q association were downregulated by C pilosula. However, p-Bad(Ser136) and BcI-2 were increased. Therefore, C pilosula suppresses Angll plus Leu(27)-IGFII-induced IGFII/IGFIIR pathway in myocardial cells. (C) 2012 Elsevier Ltd. All rights reserved.
Dung-Shen Downregulates the Synergistic Apoptotic Effects of Angiotensin II Plus Leu 27-IGF II on Cardiomyoblasts
(2014-01-01)
Chang, Ko-Shih
;
Lee, Nien-Hung
;
Kuo, Wei-Wen
;
Hu, Wei-Syun
;
Chang, Mu-Hsin
Background: Insulin growth factor II (IGFII) is expressed after ischemic stress in pig hearts and after myocardial infarction in humans. However, its receptor (IGFIIR) cannot be found in normal adult hearts. Moreover, a mouse IGFII overexpression model showed a heart and kidney hypertrophy phenomenon similar to Beckwith-Wiedemann syndrome in humans. The previous studies from our lab showed that an increase in AngII in H9c2 cells causes an elevation in IGFII and IGFIIR through MEK and JNK activation, leading to a rise in intracellular Ca2+ ions, activation of calcineurin by PLC-beta 3 via Gaq, insertion into mitochondrial membranes of BAD, and apoptosis via activation of caspases 9 and 3. Codonopsis pilosula (Dung-shen) has various uses in traditional Chinese medicine, including lowering blood pressure, and increasing red and white blood cell counts. Methods: The purpose of our study is to investigate whether the addition of C. pilosula will attenuate the Angl I plus Leu27-IGF11-induced apoptosis in H9c2 cardiomyoblast cells. Results: From MTT [3-(4, 5-dimethy1-2-thiazolyI)-2, 5-dipheny1-2-tetrazolium bromide] results, it was revealed that Angll plus Leu27-IGFII significantly reduced cell viability, which was reversed by C. pilosula. Additionally, C. pilosula also reversed apoptosis (TUNEL staining) increased by Angll plus Leu27-IGFII. Up-regulation of caspase 3 by Angl I plus Leu27-IGFII was attenuated by C. pilosula treatment, as shown in western blotting assay and immunofluorescence microscopy results. Conclusions: C. pilosula is able to suppress the apoptotic pathway enhanced by Angl I plus Leu27-IGFII in myocardial cells.
Dynamic observation on the functional metal oxide conversion behaviors in Fe3O4/ZnO heterostructures
(2020-03-01)
Huang, Chih-Yang
;
Tai, Kuo-Lun
;
Huang, Chun-Wei
;
Tseng, Yi-Tang
;
Lo, Hung-Yang
We directly observed the atomic diffusion process of bilayered Fe/ZnO transforming into a Fe3O4/ZnO heterostructure. Significantly, we suggested a unique two-step route in which Fe diffused along [0001](znO) via boundaries of ZnO and then reacted along [(1) over bar2 (1) over bar0](ZnO). The specific orientation relationship of [0001(]ZnO)//[11 (1) over bar ]Fe3O4 could be precisely controlled. In addition, the formation of a ZnO/Fe3O4 heterostructure can be tuned in terms of reaction depth by controlling the annealing time. This study provided a novel nanofabricated method to produce oriented metal oxide heterostructures while visualizing the atomic mechanism of metal oxide formation, which allows for further investigation of promising devices. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Electron Beam Irradiation-Induced Deoxidation and Atomic Flattening on the Copper Surface
(2019-10-30)
Lin, Ting-Yi
;
Lee, Shih-Kuang
;
Huang, Guan-Min
;
Huang, Chun-Wei
;
Tai, Kuo-Lun
Electron beam (e-beam) has been developed for nanomaterial observation and moreover to induce structural evolutions in atomic scale. In this work, we demonstrate the deoxidation of cuprous oxide (Cu2O) and the formation of an atomically flat surface on a Cu nanowire by e-beam irradiation. To develop e-beam irradiation applications, the relation between e-beam radiation and the atomic surface is significant. Through the density functional theory simulation of atomic sputtering, an obvious disparity in the sputtering threshold has been found under different structural conditions, which leads to different structural evolutions. Both surface deoxidation and atomic surface flattening reactions have been identified as self-limiting and irreversible processes via in situ transmission electron microscope observation. Under e-beam irradiation, the dynamic mechanism of atomic surface flattening is driven by the convergence of total surface energy and confirmed by climbing-image nudged elastic band (ci-NEB) calculations. With precise control, e-beam irradiation reveals enormous potentials in atomic surface engineering.
Exploring the molecular mechanisms of OSU-03012 on vascular smooth muscle cell proliferation
(2010-11-01)
Kuo, Wei-Wen
;
Weng, Jing-Ru
;
Huang, Chih-Yang
;
Tsai, Chang-Hai
;
Liu, Wei-Hung
Restenosis is resulted from the proliferation and migration of vascular smooth muscle cells (VSMCs) from the arterial media into the intima within the vessel lumen following percutaneous transluminal coronary angioplasty (PTCA). OSU-03012, a synthetic compound (2-amino-N-{4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-phenyl} acetamide) acting as a PDK-1 inhibitor, is used as an apoptosis-promoting anticancer drug. However, whether OSU-03012 can inhibit VSMC proliferation and migration following PTCA remains unclear. In this study, we used A10 smooth muscle cells cultured in 10% FBS for stimulating proliferation and evaluated the inhibitory effects of OSU-03012 on cell proliferation and migration. The data demonstrated that OSU-03012 dose-dependently inhibited A10 cell proliferation examined by Trypan blue, MTT and morphological alteration assays, and inhibited the levels of proliferation-related proteins, proliferating cell nuclear antigen (PCNA), phosphorylated ERK examined by western blotting. Additionally, 10 mu M OSU-03012 also enhanced apoptosis examined using DAPI assay by regulating apoptosis-related proteins. Furthermore, compared with the control group, A10 cells treated with 10 mu M OSU-03012 showed a lower number of migrating cells examined by Boyden Chamber assay, and a dose-dependently reduced NFkB-dependent and interferon-stimulated response element (ISRE) promoter luciferase activities, implying the anti-migration and anti-inflammation effects of OSU03012. Taken together, this study provides insights into the pharmacological mechanisms of OSU-03012 in preventing smooth muscle cell proliferation, migration, and inflammation supporting the novel discovery of OSU-03012 as an adjuvant therapy for balloon injury-induced restenosis.
Fabrication of (111)-Oriented Nanotwinned Au Films for Au-to-Au Direct Bonding
(2018-11-01)
Wu, John A.
;
Huang, Chih-Yang
;
Wu, Wen-Wei
;
Chen, Chih
;
材料科學與工程學系
We reported that highly (111)-oriented nanotwinned gold can be fabricated by periodical-reverse electroplating. The as-deposited films are shown to have a strong (111) preferred orientation, increasing with the reverse current time. The ratios of I-(111)/I-(220) and I-(111)/I-(200) in X-ray diffraction signals indicates a strong (111) preferred orientation. Using the advantage of the fast surface diffusion of (111) plane compared to the other planes of gold, we performed direct bonding with different thicknesses. Grain growth was observed over two films' interfaces to eliminate the bonding interface, when annealed at 250 degrees C for 1 h. Shear tests were performed to gain insight on the bonding quality. All the chips failed at either the silicon substrate or substrate-adhesion layer, showing possible higher strength than the tested maximum, 40.8 MPa.
In situ atomic scale investigation of Li7La3Zr2O12-based Li+-conducting solid electrolyte during calcination growth
(2020-05-01)
Huang, Chih-Yang
;
Tseng, Yi-Tang
;
Lo, Hung-Yang
;
Chang, Jeng-Kuei
;
Wu, Wen-Wei
The development of solid-state electrolytes (SSEs) is crucial for realizing next-generation high-energy-density and high-safety lithium-ion batteries (LIBs). The chemical composition design and synthesis route are known to be the determining factors for SSE properties. One of the most promising SSEs for LIB applications is garnet-type Li+-conducting oxide synthesized via a solid-state reaction. This study performs an in situ TEM investigation of Li6.25Ga0.25La3Zr2O12 (Ga-LLZO) growth during a high-temperature calcination process. At 750 degrees C, an intermediate phase, La2Zr2O7 (LZO), is formed through epitaxial growth along the crystallographic orientations of ((1) over bar 11)(LZO)//((1) over bar 11) ZrO2 and [211](LZO)//[101]ZrO2. The incorporation of Li and Ga into LZO is found to occur at 900.C. The LZO transforms into Ga-LLZO via a layer-by-layer diffusion process that takes place along the [01 (1) over bar] direction. The Ga doping can stabilize the cubic structure of Ga-LLZO at a temperature of 900 degrees C (while a temperature of >1100 degrees C is needed to obtain cubic LLZO) and eliminate the formation of the unwanted tetragonal phase. This dynamic microstructure evolution of Ga-LLZO is examined at an atomic scale for the first time. This study opens up a new route to better characterize and understand SSE materials, providing opportunities for further tailoring SSE properties.
In situ TEM investigation of electron beam-induced ultrafast chemical lithiation for charging
(2020-01-14)
Huang, Guan-Min
;
Huang, Chun-Wei
;
Kumar, Nagesh
;
Huang, Chih-Yang
;
Tseng, Tseung-Yuen
The enhancement of operational life and charging speed have been considered to be two of the major factors that will influence the development of energy storage devices in the future. Here, we utilized an electron beam (e-beam) to retrieve Li metal from LiF, the degradation product of LiPF6, and trigger the further lithiation of NiFe2O4/carbon nanotubes (CNTs) to relieve the degradation of the electrolyte and achieve ultrafast lithiation. Accordingly, in situ transmission electron microscopy (in situ TEM) was used to investigate the comprehensive mechanism of the whole process. The e-beam acting on the degradation product, i.e., LiF clusters, led to the generation of Li flakes, which served as the source for the subsequent lithiation. Then, with these Li flakes, the chemical lithiation of the NiFe2O4/CNTs was triggered, resulting in phase transformation to Ni and Fe nanograins. Compared to "electrochemical" lithiation, ultrahigh reaction speed and the ability to charge without a directly applied potential in the "chemical" lithiation are expected to extend lithiation to more diverse applications. As a result of this investigation, we have provided a new strategy for designing novel energy storage devices for the energy-harvesting field.
Observing Solid-State Formation of Oriented Porous Functional Oxide Nanowire Heterostructures by in Situ TEM
(2018-09-01)
Ho, Jo-Hsuan
;
Ting, Yi-Hsin
;
Chen, Jui-Yuan
;
Huang, Chun-Wei
;
Tsai, Tsung-Chun
Transition metal oxide nanowires have attracted extensive attention because of their physical characteristics. Among them, ZnO nanowires have great potential. Due to the multifunctional properties of ZnO, devices built using ZnO-based heterostructures always perform well. In this study, interesting diffusion behavior between ZnO nanowires and Fe metal was observed by using in situ transmission electron microscopy. ZnO nanowires and Fe metal were annealed under ultrahigh vacuum (UHV) conditions at 800 K. By controlling the annealing time for the solid-state diffusion, porous Fe3O4 and unique ZnO/porous Fe3O4 nanowire heterostructures were formed. As-formed porous Fe3O4 nanowires with voids can be divided into two types by appearance: plate-like voids and zigzag-like hollow voids. From high-resolution transmission electron microscopy (HRTEM) images and fast Fourier transform (FFT) diffraction patterns, we found that plate-like voids formed along the {111} plane, which was the close-packed plane of Fe3O4, and that zigzag-like hollow voids formed along the {111}/{022} planes. Moreover, a transition region existed during diffusion, with a parallel relationship found between the Fe3O4 crystal with plate-like voids and the ZnO crystal. A sharp interface was determined to exist between the Fe3O4 crystal with zigzag-like hollow voids and ZnO. These oriented porous Fe3O4/ZnO axial nanowire heterostructures exhibited a unique appearance and interesting formation behavior. Furthermore, the structures had a high surface-area-to-volume ratio, which is promising for sensing applications.
Observing topotactic phase transformation and resistive switching behaviors in low power SrCoOx memristor
(2020-06-01)
Lo, Hung-Yang
;
Yang, Chih-Yu
;
Huang, Guan-Ming
;
Huang, Chih-Yang
;
Chen, Jui-Yuan
Recently, complex oxides have been shown to be promising candidate in dielectric materials of resistive random access memory (RRAM). However, the detailed switching information of complex oxide RRAM is still insufficient, and direct observation of the whole switching process is required to figure out the mechanism. In this study, we deposited SrCoOx (SCO) on a niobium-doped SrTiO3 substrate as the dielectric layer via pulsed laser deposition (PLD). The novel SCO device possesses excellent RRAM properties, high cycling endurance, a long data retention time, and uniform distributions of the high resistance state (HRS) and low resistance state (LRS) resistance and Set/Reset voltage. Furthermore, the switching mechanism was investigated by using transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM), which showed that the switching behavior resulted from the topotactic phase transformation. In addition, the whole switching process was observed through in situ TEM, and the results strengthened the findings of the ex situ experiment. The discussion of this switching behavior provides support for a novel aspect of the RRAM switching mechanism and also a new option for the dielectric material in RRAM.
Revealing conducting filament evolution in low power and high reliability Fe3O4/Ta2O5 bilayer RRAM
(2018-11-01)
Chang, Chia-Fu
;
Chen, Jui-Yuan
;
Huang, Guan-Min
;
Lin, Ting-Yi
;
Tai, Kuo-Lun
In this work, we used the polycrystalline-Fe3O4 to improve the reliability of the Ag/Ta2O5/Pt resistive random access memory (RRAM). In both the Ag/Ta2O5/Fe3O4/Pt and Ag/Fe3O4/Ta2O5/Pt structures, the switching properties for these bilayer RRAMs were measured in atmosphere and vacuum environments. The results demonstrated that the humidity would affect the Ag filament formation in different environments, and the Ta2O5 and Fe3O4 interface in a different sequence would change the performance of the device, particularly the Forming voltage. Furthermore, the switching voltage and reliability of these bilayer RRAMs was better than single-layer RRAM device, which significantly increased endurance, especially in the Ag/Fe3O4/Ta2O5/Pt device. We also observed the conducting filament shape and evolution during Forming via in/ex-situ transmission electron microscopy (TEM) in the Ag/Fe3O4/Ta2O5/Pt system. In low humidity, the conducting filament was composed of many weak filaments in a low-resistance state (LRS), where the grain boundaries in the Fe3O4 layer limited filament size. The results of energy dispersive spectrometry (EDS) analysis demonstrated that the filament was composed of Ag metal. This study provided detailed switching knowledge of the bilayer RRAM for improving the reliability and power consumption of the device and new design viewpoints of the RRAM structure in future applications.
Rhubarb inhibits hepatocellular carcinoma cell metastasis via GSK-3-beta activation to enhance protein degradation and attenuate nuclear translocation of beta-catenin
(2013-05-01)
Tsai, Kun-Hsi
;
Hsien, Hau-Hsueh
;
Chen, Li-Mien
;
Ting, Wei-Jen
;
Yang, Yuh-Shyong
The aim of our study was to investigate the mechanisms by which rhubarb regulates beta-catenin as well as metastasis of hepatocellular carcinomas. Our results revealed that rhubarb extract inhibited HA22T cell migration ability in wound healing, migration and invasion assays in a dose-dependent manner. Rhubarb also reduced beta-catenin protein level, downregulated its downstream proteins, cyclin D, Tbx3 and c-Myc, and attenuated the expression of MMP9 and contactin-1 metastatic factors. Additionally, rhubarb inhibited beta-catenin nuclear accumulation and induced its degradation via proteasome-mediated pathway. Furthermore, we found that rhubarb suppressed the p-ser(9) GSK-3-beta protein level to inactivate Wnt signalling and reduce beta-catenin protein level. Taken together; we found that rhubarb blocked the metastatic process of HA22T hepatocellular carcinoma cells mediated through GSK-3-beta activation, and enhancement of protein degradation as well as reduction of the nuclear accumulation of beta-catenin. (C) 2012 Elsevier Ltd. All rights reserved.
Unique amorphization-mediated growth to form heterostructured silicide nanowires by solid-state reactions
(2019-05-05)
Lin, Wan-Jhen
;
Lin, Ting-Yi
;
Huang, Chun-Wei
;
Ting, Yi-Hsin
;
Tsai, Tsung-Chun
Transition metal silicide nanowires exhibit low resistivity, great thermal stability and excellent mechanical strength, contributing to their applications as interconnection and contact materials for future integrated circuits devices. In this work, we successfully fabricated two kinds of chromium silicide/silicon heterostructure nanowires through solid state reactions - bare Si/Cr3Si nanowires and Si/Cr5Si3-Al2O3 core-shell nanowires. The growth behaviors and diffusion mechanisms of the two silicide heterostructure nanowires were investigated with in-situ TEM at 700 degrees C. During the growth of chromium silicide nanowires, unique amorphous Si phase would form first in front of silicide nanowires. Also, we found that oxide-shell could control the diffusion process in silicon nanowires. With oxide-shell, compression stress would restrain the growth of chromium silicide in the radial direction but accelerate its growth rate in the axial direction. Additionally, Al2O3 shell reduced the radial expansion of chromium silicide nanowires and hindered Cr-rich phases with Cr5Si3 appearing as the first phase. The crystal structures of the nanowires have been identified to be single-crystalline A15 and D8m type structure of the intrinsic Cr3Si nanowires and Cr5Si3 nanowires, respectively. In addition to fundamental science, the significant study is beneficial for future processing techniques in nanotechnology and related applications. (C) 2019 Elsevier Ltd.