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        TIP60 contributes to porcine embryonic development by regulating DNA damage response

        Guo, Jing,Zhou, Wenjun,Niu, Ying-Jie,Shin, Kyung-Tae,Heo, Young Tae,Kim, Nam-Hyung,Cui, Xiang-Shun Elsevier 2018 Theriogenology Vol.108 No.-

        <P><B>Abstract</B></P> <P>The acetyltransferase TIP60 (also known as Kat5) is a member of the MYST family of histone acetyltransferases and was initially identified as a cellular protein. TIP60 acetylates histone and non-histone proteins and is involved in diverse biological processes, including apoptosis, cell cycle, and DNA damage responses. In this study, a specific inhibitor of TIP60 was used to detect the function of TIP60 in porcine parthenogenetic embryos. The results showed that TIP60 inhibition impaired porcine parthenogenetic embryonic development. The mechanism of TIP60 was also determined. We found that the TIP60 inhibition impaired embryonic development by ROS induced DNA damage, as demonstrated by the number of γH2A in the nuclei. TIP60 inhibition triggered DNA damage through the regulation of p53-p21 pathway and TIP60 played a role in DNA repair. TIP60 inhibition decreased the efficiency of DNA repair by regulating 53BP1-dependent repair after DNA damage. Inhibition of TIP60 also increased the adaptive response, autophagy, by modulating LC3. Therefore, TIP60 plays a role in early porcine parthenogenetic embryonic development by regulating DNA damage and repair.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TIP60 inhibition disrupted the embryonic development. </LI> <LI> TIP60 inhibition triggered the DNA damage and incomplete DNA repair due to the excessive generation of ROS. </LI> <LI> TIP60 inhibition induced the apoptosis and autophagy. </LI> </UL> </P>

      • The Role of TIP60 in Early Porcine Embryonic Development

        Wenjun Zhou,Jing Guo,Nam-Hyung Kim,Xiang-Shun Cui 한국동물생명공학회(구 한국동물번식학회) 2017 발생공학 국제심포지엄 및 학술대회 Vol.2017 No.10

        The acetyltransferase TIP60 (also known as Kat5) is a member of the MYST family of histone acetyltransferases and was initially identified as a cellular protein. TIP60 acetylates histone and nonhistone proteins and is involved in diverse biological processes, including apoptosis, cell cycle, and DNA damage responses. In this study, a specific inhibitor of TIP60 was used to detect the function of TIP60 in porcine parthenogenetic embryos. The results showed that TIP60 inhibition impaired porcine parthenogenetic embryonic development. The mechanism of TIP60 was also determined. We found that the TIP60 inhibition impaired embryonic development by ROS induced DNA damage, as demonstrated by the number of γH2A in the nuclei. TIP60 inhibition triggered DNA damage through the regualetion of p53-p21 pathway and TIP60 played a role in DNA repair. TIP60 inhibition decreased the efficiency of DNA repair by regulating 53BP1-dependent repair after DNA damage. Inhibition of TIP60 also increased the adaptive response, autophagy, by modulating LC3. Therefore, TIP60 plays a role in early porcine parthenogenetic embryonic development by regulating DNA damage and repair.

      • KCI등재

        Phosphodiesterase 4D contributes to angiotensin II-induced abdominal aortic aneurysm through smooth muscle cell apoptosis

        Gao Ran,Guo Wenjun,Fan Tianfei,Pang Junling,Hou Yangfeng,Feng Xiaohang,Li Bolun,Ge Weipeng,Fan Tianhui,Zhang Tiantian,Lu Jiakai,Jing He,Jin Mu,Yan Chen,Wang Jing 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

        Abdominal aortic aneurysm (AAA) is a permanent expansion of the abdominal aorta that has a high mortality but limited treatment options. Phosphodiesterase (PDE) 4 family members are cAMP-specific hydrolyzing enzymes and have four isoforms (PDE4A-PDE4D). Several pan-PDE4 inhibitors are used clinically. However, the regulation and function of PDE4 in AAA remain largely unknown. Herein, we showed that PDE4D expression is upregulated in human and angiotensin II-induced mouse AAA tissues using RT-PCR, western blotting, and immunohistochemical staining. Furthermore, smooth muscle cell (SMC)-specific Pde4d knockout mice showed significantly reduced vascular destabilization and AAA development in an experimental AAA model. The PDE4 inhibitor rolipram also suppressed vascular pathogenesis and AAA formation in mice. In addition, PDE4D deficiency inhibited caspase 3 cleavage and SMC apoptosis in vivo and in vitro, as shown by bulk RNA-seq, western blotting, flow cytometry and TUNEL staining. Mechanistic studies revealed that PDE4D promotes apoptosis by suppressing the activation of cAMP-activated protein kinase A (PKA) instead of the exchange protein directly activated by cAMP (Epac). Additionally, the phosphorylation of BCL2-antagonist of cell death (Bad) was reversed by PDE4D siRNA in vitro, which indicates that PDE4D regulates SMC apoptosis via the cAMP-PKA-pBad axis. Overall, these findings indicate that PDE4D upregulation in SMCs plays a causative role in AAA development and suggest that pharmacological inhibition of PDE4 may represent a potential therapeutic strategy.

      • SCOPUS
      • KCI등재

        EFFECT OF THIOPHENE IN BITHIAZOLE-BRIDGED SENSITIZERS ON THE PERFORMANCE OF DYE-SENSITIZED SOLAR CELLS

        XIAOYU ZHANG,JIANLI HUA,JINXIANG HE,WENJUN WU,HANS AGREN,XIN LI,FULING GUO 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2014 NANO Vol.9 No.5

        In this paper, we have designed and synthesized four bithiazole-bridged sensitizers (BT-T2,TBT-T2, BT-T3 and TBT-T3) with triphenylamine and indoline as the donor segment andapplied them to dye-sensitized solar cells (DSSCs). For triphenylamine-based sensitizers as BT-T2 and TBT-T2, adding one thiophene unit between triphenylamine donor and bithiazolemoiety not only led to bathochromic shift of the maximum absorption and increase of molarextinction coe±cient, but also enhanced the photovoltaic conversion e±ciency from 7.12% ofBT-T2 to 7.51% of TBT-T2. But for indoline-based sensitizers as BT-T3 and TBT-T3,adding one thiophene unit between indoline donor and bithiazole moiety resulted in hypochro-matic shift instead of bathochromic shift. We employed the density functional theory (DFT)calculations to further investigate the in°uence of the thiophene unit on their optical and elec-tronic properties and photovoltaic performance of corresponding DSSC devices. Given theresults, a reasonable explanation is the introduction of thiophene unit suppressed the intramo-lecular charge transfer and charge separation in the conjugation system of indoline-based sen-sitizer, which led to the hypochromatic shift of the maximum absorption wavelength and ¯nallythe low Jsc . Since the Jsc dropped sharply from 15.26 mAcm? 2 to 4.52 mAcm? 2 , the photovoltaicconversion e±ciency decreased dramatically from 7.86% to 1.93%.

      • KCI등재

        Effect of curing condition on mechanical properties of scarf-repaired composite laminates

        Xiaoquan Cheng,Jie Zhang,Yujia Cheng,Xin Guo,Wenjun Huang 국제구조공학회 2020 Steel and Composite Structures, An International J Vol.37 No.4

        Composite structures are generally pressurized at both sides when repaired by the scarf repair method. But single-face vacuum bag curing (SVC) may be used in some practical scarf repair of penetration damage due to the low accessibility of composite structures, which can decrease bonding quality and may reduce structural mechanical properties. In this paper, experimental investigations were conducted on tensile and compressive properties of scarf-repaired composite laminates using SVC and double-face vacuum bag curing (DVC) in four hygrothermal environments. Finite element models of composite scarf joints with voids were established to further explore the failure mechanism of scarf-repaired laminates. Results show that the curing condition hardly affects tensile and compressive properties of the repaired laminates though it significantly affects the bonding quality with adhesive inner voids. Failure loads of scarf joints almost keep unchanged with adhesive voids increasing.

      • KCI등재

        Strength and Mechanism of Carbonated Solidified Clay with Steel Slag Curing Agent

        Man Li,Qiang Wang,Jingdong Yang,Xiaoliang Guo,Wenjun Zhou 대한토목학회 2021 KSCE JOURNAL OF CIVIL ENGINEERING Vol.25 No.3

        Industrial wastes, such as steel slag and desulfurized gypsum, are piled up in large quantities and only a very small portion is recycled, adversely impacting natural ecosystems. Meanwhile, environmental problems caused by CO2 have increasingly received attention. Hence, this study introduces a novel environmentally friendly composite, formed by sodium hydroxide (used as an activator), desulfurized gypsum and steel slag (S-GS). The main objective of this study is to evaluate the potential use of S-GS for solidifying clay under the condition of carbonation curing. Besides, the samples’ characteristics are investigated according to the tests of unconfined compressive strength (UCS), pH, carbonation depth, quality loss and scanning electron microscope (SEM). It is found that the UCS of solidified clay decreases with the increasing water content while it increases first and then decreases with the increasing desulfurized gypsum content, reaching the maximum when the water content is 0.5 times the liquid limit and the content of desulfurized gypsum is 8%. Moreover, compared with the standard curing, carbonation curing can stimulate the activity of S-GS to improve the UCS of samples more effectively. With the increasing carbonation curing time, the mass loss rate and carbonation depth of samples increase while the pH value decreases. Additionally, based on the normalized analysis, the carbonation time has the most significant effect on the UCS. Furthermore, the SEM results indicate that formation of Calcium carbonate and Magnesium carbonate are primary reasons for improving the UCS of the stabilised clay during carbonization. This research promotes steel slag and desulfurized gypsum as green stabilisers for soil stabilization, and the method of carbonation curing contributes to the higher UCS, which also greatly shortens the curing time.

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