• Molecules and Cells
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• v.41 no.12
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• pp.1008-1015
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• 2018

$I{\kappa}B$, a cytoplasmic inhibitor of nuclear factor-${\kappa}B$ ($NF-{\kappa}B$), is reportedly degraded via the proteasome. However, we recently found that long-term incubation with proteasome inhibitors (PIs) such as PS-341 or MG132 induces $I{\kappa}B{\alpha}$ degradation via an alternative pathway, lysosome, which results in $NF-{\kappa}B$ activation and confers resistance to PI-induced lung cancer cell death. To enhance the anti-cancer efficacy of PIs, elucidation of the regulatory mechanism of PI-induced $I{\kappa}B{\alpha}$ degradation is necessary. Here, we demonstrated that PI up-regulates nuclear factor (erythroid-derived 2)-like 2 (Nrf2) via both de novo protein synthesis and Kelch-like ECH-associated protein 1 (KEAP1) degradation, which is responsible for $I{\kappa}B{\alpha}$ degradation via macroautophagy activation. PIs increased the protein level of light chain 3B (LC3B, macroautophagy marker), but not lysosome-associated membrane protein 2a (Lamp2a, the receptor for chaperone-mediated autophagy) in NCI-H157 and A549 lung cancer cells. Pretreatment with macroautophagy inhibitor or knock-down of LC3B blocked PI-induced $I{\kappa}B{\alpha}$ degradation. PIs up-regulated Nrf2 by increasing its transcription and mediating degradation of KEAP1 (cytoplasmic inhibitor of Nrf2). Overexpression of dominant-negative Nrf2, which lacks an N-terminal transactivating domain, or knock-down of Nrf2 suppressed PI-induced LC3B protein expression and subsequent $I{\kappa}B{\alpha}$ degradation. Thus, blocking of the Nrf2 pathway enhanced PI-induced cell death. These findings suggest that Nrf2-driven induction of LC3B plays an essential role in PI-induced activation of the $I{\kappa}B$/$NF-{\kappa}B$ pathway, which attenuates the anti-tumor efficacy of PIs.

• Journal of Korean Tunnelling and Underground Space Association
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• v.21 no.1
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• pp.1-29
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• 2019

Related to the previous paper on the typical crack pattern of tunnel lining with NATM, the characteristic defects in reinforced cement concrete lining of NATM tunnel have analyzed with the precise inspection with safety and diagnosis (PISD) by KISTEC. Depending on the reinforcing materials, steel rebar, steel fiber, and glass fiber have been implemented to reinforcing lining in various NATM tunnel constructions. Reinforcing lining with rebar are prevailed on NATM tunnel to countermeasure the weak geological circumstances, to pursuit the economical tunnel sections, and to resist the risk of tunnel deterioration. By the special act on the safety control of public facilities, the reinforced NATM tunnels for more than 1 km length are scrutinized closely to characterize defects; crack, reinforcement exposure, and lack of lining. Crack resistance by reinforcing is shown in comparison with the normalized crack to the length of tunnel. Typical exposed reinforcements in lining have exemplified with various sections. The lack of lining due to the mal-construction, spalling, fire, earthquake and leaching has been analyzed. The cause and mechanism with the field inspections and other studies has also been verified. Detailed cases are selected by the above concerns as well as the basic information from FMS (Facilities Management System). Likewise the previous paper, this study provides specialized defects in reinforced lining of NATM and it can be widely used in spreading the essential technics and reporting skills. Furthermore, it would be advised and amended for the detail guideline of Safety Diagnosis and PISD (tunnel).

• Korean Journal of Clinical Laboratory Science
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• v.51 no.2
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• pp.221-234
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• 2019

Cancer is genetically, metabolically and infectiously induced life threatening disorder showing aggressive growing pattern with invasive tendency. In order to prevent this global menace from jeopardizing human life, enormous studies on carcinogenesis and treatment for chemotherapy resistance have been intensively researched. Hinokitiol (${\beta}$-thujaplicin) extracted from heart wood of cupressaceous is a well-known bioactive compound demonstrating anti-inflammation, anti-bacteria and anti-cancer effects on several cancer types via apoptosis and autophagy. This study proposed that hinokitiol activates transcription factor EB (TFEB) nuclear translocation for autophagy and lysosomal biogenesis regardless of nutrient condition in cancer cells. Mitophagy and ${\beta}$-catenin translocation into the nucleus under treatment of hinokitiol on non-small cell lung cancer (NSCLC) cells and HeLa cells were investigated. Hinokitiol exerted cytotoxicity on HeLa and HCC827 cells; moreover, artificially induced autophagy by overexpression of TFEB granted imperfect sustainability onto HeLa cells. Taken together, hinokitiol is the prominent autophagy inducer and activator of TFEB nuclear translocation. Alternative cancer therapy via autophagy is pros and cons since the autophagy in cancer cells is related to prevention and survival mechanism depending on nutrition. To avoid paradox of autophagy in cancer therapy, fine-tuned regulation and application of hinokitiol in due course for successful suppressing cancer cells are recommended.

• Korean Journal of Medicinal Crop Science
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• v.28 no.6
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• pp.395-411
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• 2020

Background: This study investigated the anti-obesity effect of the flavonoid rich fraction (FRF) and its constituent, rutin obtained from the leaf of Morus alba L., on the lipid accumulation mechanism in 3T3-L1 adipocyte and C57BL/6 mouse models. Methods and Results: In Oil Red O staining, FRF (1,000 ㎍/㎖) treatments showed inhibition rate of 35.39% in lipid accumulation compared to that in the control. AdipoRedTM assay indicated that the triglyceride content in 3T3-L1 adipocytes treated with FRF (1,000 ㎍/㎖) was reduced to 23.22%, and free glycerol content was increased to 106.04% that of the control. FRF and its major constituent, rutin affected mRNA gene expression. Rutin contributed to the inhibition of Sterol regulatory element binding protein-1c (SREBP-1c) gene expression, and inhibited the transcription factors SREBP-1c, peroxisome proliferator-activated receptor gamma (PPAR-γ), CCAAT/enhancer binding protein α (C/EBPα), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC). In addition, the effect of FRF administration on obesity development in C57BL/6 mice fed high-fat diet (HFD) was investigated. FRF suppressed weight gain, and reduced liver triglyceride and leptin secretion. FRF exerted potential anti-inflammatory effects by improving insulin resistance and adiponectin levels, and could thus be used to help counteract obesity. The mRNA expressions of PPAR-γ, FAS, ACC, and CPT-1 were determined in liver tissue. Quantitative real-time PCR analysis was also performed to evaluate the expression of IL-1β, IL-6, and TNF-α in epididymal adipose tissue. Compared to the control group, mice fed the HFD showed the up-regulation in PPAR-γ, FAS, IL-6, and TNF-α genes, and down-regulation in CPT1 gene expression. FRF treatement markedly reduced the expression of PPAR-γ, FAS, IL-6, and TNF-α compared to those in HFD control, whereas increased the expression level of CPT1. Conclusions: These results suggest that the FRF and its major active constituent, rutin, can be used as effective anti-obesity agents.

• Journal of Life Science
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• v.31 no.1
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• pp.1-9
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• 2021

Brown seaweeds have been shown to decrease blood glucose levels and improve insulin sensitivity previously. In this study, we investigated the effect of fucoidan, a complex polysaccharide derived from brown seaweeds, on glucose uptake to improve insulin resistance, and examined its mechanism of action in 3T3-L1 adipocytes. We observed that fucoidan significantly increased glucose uptake and it was related to an increased expression of plasma membrane-glucose transporter 4 (PM-GLUT4) in 3T3-L1 adipocytes. Fucoidan treatment increased the activation of phosphatidylinositol-3-kinase (PI3K) and the phosphorylation of insulin receptor substrate 1 (IRS1tyr) compared with that of the control cells. Fucoidan also promoted the phosphorylation of Akt and protein kinase C (PKC)-λ/ζ compared to that of the control cells. Moreover, fucoidan significantly upregulated acetyl-CoA-carboxylase (ACC) and adenosine monophosphate - activated protein kinase (AMPK) phosphorylation. As a result, translocation of GLUT4 was significantly enhanced in 3T3-L1 adipocytes, which significantly promoted glucose uptake via the PI3K/AMPK pathways. The elevation of glucose uptake by fucoidan was blocked by inhibitor of PI3K and inhibitor of AMPK in 3T3-L1 adipocytes. These findings indicate that fucoidan might ameliorate glucose uptake through GLUT4 translocation to the plasma membrane by activating the PI3K/Akt and AMPK pathways in 3T3-L1 adipocytes. Fucoidan is thought to be of high material value to diabetes treatments and functional foods.

• Animal Bioscience
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• v.34 no.8
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• pp.1403-1414
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• 2021

Objective: This study explored the mechanism of the Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway under conditions of zearalenone (ZEA)-induced oxidative stress in the duodenum of post-weaning gilts. Methods: Forty post-weaning gilts were randomly allocated to four groups and fed diets supplemented with 0, 0.5, 1.0, or 1.5 mg/kg ZEA. Results: The results showed significant reductions in the activity of the antioxidant enzymes total superoxide dismutase and glutathione peroxidase and increases the malondialdehyde content with increasing concentrations of dietary ZEA. Immunohistochemical analysis supported these findings by showing a significantly increased expression of Nrf2 and glutathione peroxidase 1 (GPX1) with increasing concentrations of ZEA. The relative mRNA and protein expression of Nrf2, GPX1 increased linearly (p<0.05) and quadratically (p<0.05), which was consistent with the immunohistochemical results. The relative mRNA expression of Keap1 decreased linearly (p<0.05) and quadratically (p<0.05) in the duodenum as the ZEA concentration increased in the diet. The relative mRNA expression of modifier subunit of glutamate-cysteine ligase (GCLM) increased quadratically (p<0.05) in all ZEA treatment groups and the relative mRNA expression of quinone oxidoreductase 1 (NQO1) catalytic subunit of glutamate-cysteine ligase decreased linearly (p<0.05) and quadratically (p<0.05) in the ZEA1.0 group and ZEA1.5 group. The relative protein expression of Keap1 and GCLM decreased quadratically (p<0.05) in the duodenum as the ZEA concentration increased in the diet, respectively. The relative protein expression of NQO1 increased linearly (p<0.05) and quadratically (p<0.05) in all ZEA treatment groups in the duodenum. Conclusion: These findings suggest that ZEA regulates the expression of key factors of the Keap1-Nrf2 signaling pathway in the duodenum, which enables resistance to ZEA-induced oxidative stress. Further studies are needed to examine the effects of ZEA induced oxidative stress on other tissues and organs in post-weaning gilts.

• Journal of Navigation and Port Research
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• v.46 no.3
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• pp.168-178
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• 2022

In this study, the resistance test, the vertical static angle of the attack test and VPMM test will be conducted to estimate the maneuverability of underwater vehicles with ahead propeller. The vertical static test will be conducted within the range of -40deg to 40deg, to investigate the cross-flow drag at high incidence angles. The tests will be conducted by dividing the propeller rotation into a case in which the propeller rotates at a specific rpm, and a case in which the propeller rotates naturally, according to the towing speed. Hydrodynamic coefficients of vertical direction will be estimated by the captive model tests. Additionally, the vertical dynamic stability index based on estimated hydrodynamic coefficients will be calculated and the impact of the propeller revolution state on the index will be investigated. The results are expected to be used as reference test data for underwater vehicles with ahead propeller.

• Journal of the Microelectronics and Packaging Society
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• v.29 no.2
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• pp.81-89
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• 2022

The in-situ electromigration(EM) and annealing test were performed at 110, 130, and 150℃ with a current density of 1.3×10⁵ A/cm² conditions to investigate the effect of non-conductive film (NCF) on growth kinetics of intermetallic compound (IMC) in Cu/Ni/Sn-2.5Ag microbump. As a result, the activation energy of the Ni₃Sn₄ IMC growth in the annealing and EM conditions according to the NCF application was about 0.52 eV, and there was no significant difference. This is because the growth rate of Ni-Sn IMC is much slower than that of Cu-Sn IMC, and the growth behavior of Ni-Sn IMC increases linearly with the square root of time, so it has the same reaction mechanism dominated by diffusion. In addition, there is no difference in the activation energy of the Ni₃Sn₄ IMC growth because the EM resistance effect of the back stress according to the NCF application is not large.

• Korean journal of applied entomology
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• v.61 no.1
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• pp.197-210
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• 2022

Entomopathogenic fungi can be used to control a variety of sucking and chewing insects, with little effect on beneficial insects and natural enemies. Approximately 170 entomopathogenic fungal insecticides have been registered and used worldwide, with the recent focus being on the mode of action and mechanism of insect-fungal interactions. During the initial period of research and development, the industrialization of entomopathogenic fungi focused on the selection of strains with high virulence. However, improvement in productivity, including securing resistance to environmental stressors, is a major issue that needs to be solved. Although conidia are the primary application propagules, efforts are being made to overcome the limitations of blastospores to improve the economic feasibility of the production procedure. Fungal transformation is also being conducted to enhance insecticidal activity, and molecular biology is being used to investigate functions of various genes. In the fungi-based pest management market, global companies are setting up cooperative platforms with specialized biological companies in the form of M&As or partnerships with the aim of implementing a tank-mix strategy by combining chemical pesticides and entomopathogenic fungi. In this regard, understanding insect ecology in the field helps in providing more effective fungal applications in pest management, which can be used complementary to chemicals. In the future, when fungal applications are combined with digital farming technology, above-ground applications to control leaf-dwelling pests will be more effective. Therefore, for practical industrialization, it is necessary to secure clear research data on intellectual property rights.

• Journal of the Microelectronics and Packaging Society
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• v.29 no.3
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• pp.49-53
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• 2022

Ultra-thin glass (UTG) has been widely used in foldable display as a cover window for the protection of display and has a great potential for rollable display and various flexible electronics. The foldable display is under impact loading by bending and touch pen and exposed to other external impact loads such as drop while people are using it. These external impact loads can cause cracks or fracture to UTG because it is very thin under 100 ㎛ as well as brittle. Cracking and fracture lead to severe reliability problems for foldable smartphone. Thus, this study constructs finite element analysis (FEA) model for the pen drop test which can measure the impact resistance of UTG and conducts mechanical modeling to improve the reliability of UTG under impact loading. When a protective layer is placed to an upper layer or lower layer of UTG layer, stress mechanism which is applied to the UTG layer by pen drop is analyzed and an optimized structure is suggested for reliability improvement of UTG layer. Furthermore, maximum principal stress values applied at the UTG layer are analyzed according to pen drop height to obtain maximum pen drop height based on the strength of UTG.