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      • KCI등재

        Clusterin negatively modulates mechanical stress-mediated ligamentum flavum hypertrophy through TGF-β1 signaling

        Liu Chunlei,Li Peng,Ao Xiang,Lian Zhengnan,Liu Jie,Li Chenglong,Huang Minjun,Wang Liang,Zhang Zhongmin 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

        Ligamentum flavum hypertrophy (LFH) is a major cause of lumbar spinal canal stenosis (LSCS). The pathomechanisms for LFH have not been fully elucidated. Isobaric tags for relative and absolute quantitation (iTRAQ) technology, proteomics assessments of human ligamentum flavum (LF), and successive assays were performed to explore the effect of clusterin (CLU) upregulation on LFH pathogenesis. LFH samples exhibited higher cell positive rates of the CLU, TGF-β1, α-SMA, ALK5 and p-SMAD3 proteins than non-LFH samples. Mechanical stress and TGF-β1 initiated CLU expression in LF cells. Notably, CLU inhibited the expression of mechanical stress-stimulated and TGF-β1-stimulated COL1A2 and α-SMA. Mechanistic studies showed that CLU inhibited mechanical stress-stimulated and TGF-β1-induced SMAD3 activities through suppression of the phosphorylation of SMAD3 and by inhibiting its nuclear translocation by competitively binding to ALK5. PRKD3 stabilized CLU protein by inhibiting lysosomal distribution and degradation of CLU. CLU attenuated mechanical stress-induced LFH in vivo. In summary, the findings showed that CLU attenuates mechanical stress-induced LFH by modulating the TGF-β1 pathways in vitro and in vivo. These findings imply that CLU is induced by mechanical stress and TGF-β1 and inhibits LF fibrotic responses via negative feedback regulation of the TGF-β1 pathway. These findings indicate that CLU is a potential treatment target for LFH.

      • Polyol Reduction: A Low-Temperature Eco-Friendly Solution Process for p-Channel Copper Oxide-Based Transistors and Inverter Circuits

        Liu, Ao,Zhu, Huihui,Noh, Yong-Young American Chemical Society 2019 ACS APPLIED MATERIALS & INTERFACES Vol.11 No.36

        <P>An optimized polyol reduction method was proposed for p-type Cu<SUB><I>x</I></SUB>O deposition using a spin-coating method at low temperatures. The film characterizations and the electrical properties of integrated thin-film transistors (TFTs) were investigated as a function of annealing temperature and polyol type. The Cu<SUB><I>x</I></SUB>O TFTs derived from propylene glycol showed the optimal performance with an average field-effect hole mobility of 0.15 cm<SUP>2</SUP> V<SUP>-1</SUP> s<SUP>-1</SUP>, an on/off current ratio of ∼10<SUP>4</SUP>, and a threshold voltage of −7 V at a low temperature of 220 °C. Considering few investigations on the operational/air stability of solution-processed p-type oxide TFTs, we carried out systematical studies and revealed different roles of O<SUB>2</SUB> and H<SUB>2</SUB>O on the device performance. The low activation energy (0.16 eV) for hole transport and high voltage gain (37) of the composed complementary inverter highlight great potential for the construction of all oxide-based transparent flexible electronics and circuits.</P> [FIG OMISSION]</BR>

      • Kinetic Resolution of Allylic Alcohol with Chiral BINOL-Based Alkoxides: A Combination of Experimental and Theoretical Studies

        Liu, Yidong,Liu, Song,Li, Dongmei,Zhang, Nan,Peng, Lei,Ao, Jun,Song, Choong Eui,Lan, Yu,Yan, Hailong American Chemical Society 2019 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.141 No.2

        <P>The development and characterization of enantioselective catalytic kinetic resolution of allylic alcohols through asymmetric isomerization with chiral BINOL derivatives-based alkoxides as bifunctional Brønsted base catalysts were described in the study. A number of chiral BINOL derivatives-based alkoxides were synthesized, and their structure-enantioselectivity correlation study in asymmetric isomerization identified a promising chiral Brønsted base catalyst, which afforded various chiral secondary allylic alcohols (ee up to 99%, <I>S</I> factor up to >200). In the mechanistic study, alkoxide species were identified as active species and the phenol group of BINOL largely affected the high reactivity and enantioselectivity via hydrogen bonding between the chiral Brønsted base catalyst and substrates. The strategy is the first successful synthesis strategy of various chiral secondary allylic alcohols through enantioselective transition-metal-free base-catalyzed isomerization. The applicability of the strategy had been demonstrated by the synthesis of the bioactive natural product (+)-veraguensin.</P> [FIG OMISSION]</BR>

      • KCI등재

        A Dual Functional Ti-Ga Alloy: Inhibiting Biofilm Formation and Osteoclastogenesis Differentiation via Disturbing Iron Metabolism

        Fupeng Li,Kai Huang,Jinbing Wang,Kai Yuan,Yiqi Yang,Yihao Liu,Xianhao Zhou,Keyu Kong,Tao Yang,Jian He,Chunjie Liu,Haiyong Ao,Fengxiang Liu,Qian Liu,Tingting Tang,Shengbing Yang 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

        Background Although biomedical implants have been widely used in orthopedic treatments, two major clinical challenges remain to be solved, one is the bacterial infection resulting in biofilm formation, and the other is aseptic loosening during implantation due to over-activated osteoclastogenesis. These factors can cause many clinical issues and even lead to implant failure. Thus, it is necessary to endow implants with antibiofilm and aseptic looseningprevention properties, to facilitate the integration between implants and bone tissues for successful implantation. To achieve this goal, this study aimed to develop a biocompatible titanium alloy with antibiofilm and anti-aseptic loosening dual function by utilizing gallium (Ga) as a component. Methods A series of Ti-Ga alloys were prepared. We examined the Ga content, Ga distribution, hardness, tensile strength, biocompatibility, and anti-biofilm performance in vitro and in vivo. We also explored how Ga3+ ions inhibited the biofilm formation of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) and osteoclast differentiation. Results The alloy exhibited outstanding antibiofilm properties against both S. aureus and E. coli in vitro and decent antibiofilm performance against S. aureus in vivo. The proteomics results demonstrated that Ga3+ ions could disturb the bacterial Fe metabolism of both S. aureus and E. coli, inhibiting bacterial biofilm formation. In addition, Ti-Ga alloys could inhibit receptor activator of nuclear factor-κB ligand (RANKL)-dependent osteoclast differentiation and function by targeting iron metabolism, then suppressing the activation of the NF-κB signaling pathway, thus, showing their potential to prevent aseptic loosening. Conclusion This study provides an advanced Ti-Ga alloy that can be used as a promising orthopedic implant raw material for various clinical scenarios. This work also revealed that iron metabolism is the common target of Ga3+ ions to inhibit biofilm formation and osteoclast differentiation.

      • KCI등재

        Exosomes derived from regulatory T cells attenuates MPP+-induced inflammatory response and oxidative stress in BV-2 cells by inhibiting the TLR4/NF-κB signaling

        Liu Jun,Zhang Junqing,Ao Yuanyuan 대한독성 유전단백체 학회 2023 Molecular & cellular toxicology Vol.19 No.2

        Background Parkinson’s disease (PD) is a common neurodegenerative disorder associated with microglia-mediated neuroinfl ammation in pathogenesis. Regulatory T cells (Treg cells) are involved in the regulation of microglia activation and neuroinfl ammation. However, it is yet to be established whether exosomes derived from Treg cells (Treg-Exos) possess protective eff ect against MPP + -induced infl ammation and oxidative stress in microglia. Objective In our study, we examined the function of Treg cells in the in vitro PD model. MTT assay was used to assess the viability of BV2 cells. ROS, MDA, and SOD activity were detected, and ELISA was performed to estimate the infl ammatory response and oxidative stress of BV-2 cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were applied to detect the level changes of genes involved in the TLR4/NF-κB signaling pathway. Results The results showed that Treg-Exos improved the cell viability of MPP + -treated BV2 cells. MPP + -induced increase in ROS and MDA production, as well as decrease in SOD activity in BV2 cells were attenuated by Treg-Exos. The increased levels of infl ammatory cytokines IL-β, IL-6, and TNF-α in MPP + -induced BV2 cells were also prevented by the treatment of Treg-Exos. Treg-Exos inhibited MPP + -induced activation of the TLR4/NF-κB signaling, indicated by decreased protein level of TLR4 and p-p65/p65 ratio in BV2 cells. Further, we also found that upregulation of TLR4 blocks the protective eff ect of Treg-Exos on MPP + -treated BV2 cells. Conclusions Collectively, Treg-Exos attenuated MPP + -induced oxidative stress and infl ammatory injury in BV-2 cells by inhibiting the TLR4/NF-κB signaling.

      • KCI등재

        IL-17A exacerbates diabetic retinopathy by impairing Müller cell function via Act1 signaling

        Ao-Wang Qiu,Zheng Bian,Ping-An Mao,Qing-Huai Liu 생화학분자생물학회 2016 Experimental and molecular medicine Vol.48 No.-

        Diabetic retinopathy (DR), one of the most serious complications of diabetes, has been associated with inflammatory processes. We have recently reported that interleukin (IL)-17A, a proinflammatory cytokine, is increased in the plasma of diabetic patients. Further investigation is required to clarify the role of IL-17A in DR. Ins2Akita (Akita) diabetic mice and high-glucose (HG)-treated primary Müller cells were used to mimic DR-like pathology. Diabetes induced retinal expression of IL-17A and IL-17 receptor A (IL-17RA) in Müller cells in contrast to ganglion cells. Further evidence demonstrated that retinal Müller cells cultured in vitro increased IL-17A and IL-17RA expression as well as IL-17A secretion in the HG condition. In both the HG-treated Müller cells and Akita mouse retina, the Act1/TRAF6/IKK/NF-κB signaling pathway was activated. IL-17A further enhanced inflammatory signaling activation, whereas Act1 knockdown or IKK inhibition blocked the downstream signaling activation by IL-17A. HG- and diabetesinduced Müller cell activation and dysfunction, as determined by increased glial fibrillary acidic protein, vascular endothelial growth factor and glutamate levels and decreased glutamine synthetase and excitatory amino acid transporter-1 expression, were exacerbated by IL-17A; however, they were alleviated by Act1 knockdown or IKK inhibition. In addition, IL-17A intravitreal injection aggravated diabetes-induced retinal vascular leukostasis, vascular leakage and ganglion cell apoptosis, whereas Act1 silencing or anti-IL-17A monoclonal antibody ameliorated the retinal vascular damage and neuronal cell apoptosis. These findings establish that IL-17A xacerbates DR-like pathology by the promotion of Müller cell functional impairment via Act1 signaling.

      • SCIESCOPUSKCI등재

        Effect of dietary supplementation with Allium mongolicum Regel extracts on growth performance, carcass characteristics, and the fat color and flavor-related branched-chain fatty acids concentration in ram lambs

        Liu, Wangjing,Ao, Changjin Asian Australasian Association of Animal Productio 2021 Animal Bioscience Vol.34 No.7

        Objective: This study aimed to investigate the effect of dietary supplementation with Allium mongolicum Regel extracts on the growth performance, carcass characteristics, fat color, and concentrations of three branched-chain fatty acids related to flavor in ram lambs. Methods: Sixty 3-month-old, male, small-tailed Han sheep were selected and randomly allocated into four groups in a randomized block design. Four feeding treatments were used: i) a basal diet without supplementation as the control group (CK); ii) the basal diet supplemented with 10 g/lamb/d Allium mongolicum Regel powder as the AMR group; iii) the basal diet supplemented with 3.4 g/lamb/d Allium mongolicum Regel water extract as the AWE group; and iv) the basal diet supplemented with 2.8 g/lamb/d Allium mongolicum Regel ethanol extract as the AFE group. Results: The results demonstrated that the dry matter intake was lower for the AFE group than that in other groups (p = 0.001). The feed conversion ratio was greater for the AFE than that in other groups (p = 0.039). Dietary supplementation with Allium mongolicum Regel powder and its extracts decreased the concentrations of 4-methyloctanoic acid (MOA) (p<0.001), 4-ethyloctanoic acid (EOA) (p<0.001), and 4-methylnonanoic acid (MNA) (p = 0.044) in perirenal adipose tissue compared to those observed in the CK lambs. Dietary supplementation with Allium mongolicum Regel powder and its extracts decreased the concentrations of MOA (p<0.001) and EOA (p<0.001) in dorsal subcutaneous adipose tissue compared to those in the CK lambs. The concentrations of MOA (p<0.001) and EOA (p = 0.002) in omental adipose tissue were significantly affected by treatment, although there was a tendency for lower MNA (p = 0.062) in AMR, AWE, and AFE lambs than that in CK lambs. Conclusion: This study demonstrated that Allium mongolicum Regel and its extracts could significantly promote feed efficiency, although dry matter intake decreased and could decrease the MOA and EOA concentrations related to characteristic flavor and odor of body fat in lambs, except for tail adipose tissue.

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