• The Korean Journal of Physiology and Pharmacology
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• v.26 no.3
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• pp.145-155
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• 2022

Multidrug resistance of tumors has been a severe obstacle to the success of cancer chemotherapy. The study wants to investigate the reversal effects of imperatorin (IMP) on doxorubicin (DOX) resistance in K562/DOX leukemia cells, A2780/Taxol cells and in NOD/SCID mice, to explore the possible molecular mechanisms. K562/DOX and A2780/Taxol cells were treated with various concentrations of DOX and Taol with or without different concentrations of IMP, respectively. K562/DOX xenograft model was used to assess anti-tumor effect of IMP combined with DOX. MTT assay, Rhodamine 123 efflux assay, RT-PCR, and Western blot analysis were determined in vivo and in vitro. Results showed that IMP significantly enhanced the cytotoxicity of DOX and Taxol toward corresponding resistance cells. In vivo results illustrated both the tumor volume and tumor weight were significantly decreased after 2-week treatment with IMP combined with DOX compared to the DOX alone group. Western blotting and RT-PCR analyses indicated that IMP downregulated the expression of P-gp in K562/DOX xenograft tumors in NOD/SCID mice. We also evaluated glycolysis and glutamine metabolism in K562/DOX cells by measuring glucose consumption and lactate production. The results revealed that IMP could significantly reduce the glucose consumption and lactate production of K562/DOX cells. Furthermore, IMP could also remarkably repress the glutamine consumption, α-KG and ATP production of K562/DOX cells. Thus, IMP may sensitize K562/DOX cells to DOX and enhance the antitumor effect of DOX in K562/DOX xenograft tumors in NOD/SCID mice. IMP may be an adjuvant therapy to mitigate the multidrug resistance in leukemia chemotherapy.

• Biomolecules & Therapeutics
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• v.31 no.3
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• pp.319-329
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• 2023

Resistance to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is a concerning problem. Polo-like kinase 1 (PLK1) is a key cell cycle modulator and is known to be associated with an activation of the PI3K pathway, which is related to the stabilization of DNA methyltransferase 1 (DNMT1), a target of HMAs. We investigated the effects of volasertib on HMA-resistant cell lines (MOLM/AZA-1 and MOLM/DEC-5) derived from MOLM-13, and bone marrow (BM) samples obtained from patients with MDS (BM blasts >5%) or AML evolved from MDS (MDS/AML). Volasertib effectively inhibited the proliferation of HMA-resistant cells with suppression of DNMTs and PI3K/AKT/mTOR and ERK pathways. Volasertib also showed significant inhibitory effects against primary BM cells from patients with MDS or MDS/AML, and the effects of volasertib inversely correlated with DNMT3B expression. The DNMT3B-overexpressed AML cells showed primary resistance to volasertib treatment. Our data suggest that volasertib has a potential role in overcoming HMA resistance in patients with MDS and MDS/AML by suppressing the expression of DNMT3 enzymes and PI3K/AKT/mTOR and ERK pathways. We also found that DNMT3B overexpression might be associated with resistance to volasertib.

• BMB Reports
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• v.56 no.3
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• pp.184-189
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• 2023

Ovarian cancer (OC) is the most common gynecological malignancy worldwide, and chemoresistance occurs in most patients, resulting in treatment failure. A better understanding of the molecular processes underlying drug resistance is crucial for development of efficient therapies to improve OC patient outcomes. Circular RNAs (circRNAs) and ferroptosis play crucial roles in tumorigenesis and resistance to chemotherapy. However, little is known about the role(s) of circRNAs in regulating ferroptosis in OC. To gain insights into cisplatin resistance in OC, we studied the ferroptosis-associated circRNA circSnx12. We evaluated circSnx12 expression in OC cell lines and tissues that were susceptible or resistant to cisplatin using quantitative real-time PCR. We also conducted in vitro and in vivo assays examining the function and mechanism of lnc-LBCSs. Knockdown of circSnx12 rendered cisplatin-resistant OC cells more sensitive to cisplatin in vitro and in vivo by activating ferroptosis, which was at least partially abolished by downregulation of miR-194-5p. Molecular mechanics studies indicate that circSnx12 can be a molecular sponge of miR-194-5p, which targets SLC7A11. According to our findings, circSnx12 ameliorates cisplatin resistance by blocking ferroptosis via a miR-194-5p/SLC7A11 pathway. CircARNT2 may thus serve as an effective therapeutic target for overcoming cisplatin resistance in OC.

• Transactions of Materials Processing
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• v.31 no.3
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• pp.129-135
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• 2022

The purpose of this study was to quantitatively evaluate the influence of hardness of tool materials on wear resistance in the sheet metal forming process. Punches used in the wear test were made of STD-11 and K340 tool material, and the tempering temperature was set to 530℃ and 500℃, respectively, to control the hardness of the tool materials. The punches mimic the shape of stamping tool of automotive body component to reflect its plastic deformation, and are designed to concentrate wear on the curvature region of punches. Progressive die and coil sheet were used to save time, cost, and raw sheet materials. By quantitatively measuring the wear depth of the punches, the wear behavior and mechanism of the punches were investigated, and characteristics of hardness and wear resistance according to tool materials and tempering temperatures were evaluated. Testing results indicate that the punch made of K340 tool steel with higher hardness had better wear resistance than that of STD-11 tool steel, and the hardness and wear resistance of tool steel were significantly impacted by the tempering temperature.

• The Journal of the Korea institute of electronic communication sciences
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• v.19 no.2
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• pp.427-436
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• 2024

Recently, the importance of information security (IS) has been socially recognized, leading organizations to adopt IS policies, secure specialized personnel, and demand IS compliance from employees. However, the implementation of these policies can disrupt existing work processes, causing resistance among employees. This study aims to elucidate the mechanism linking work stress, caused by IS policies that do not consider the work system, to individual job burnout and IS policy resistance. We established a research model and hypotheses based on previous studies and utilized structural equation modeling with data collected from organization members of companies that have implemented IS policies. The results of the structural equation modeling confirmed that work ambiguity and work impediment are linked to IS policy resistance through job burnout, characterized by emotional exhaustion and disengagement. Our findings suggest that the swift implementation of IS policies can provoke a backlash from employees, with stress being the primary cause. This paradoxically indicates the need for the development of organization-specific IS policies.

• Journal of Gastric Cancer
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• v.24 no.3
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• pp.300-315
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• 2024

Purpose: Gastric cancer (GC) is among the deadliest malignancies and the third leading cause of cancer-related deaths worldwide. Galectin-1 (Gal-1) is a primary protein secreted by cancer-associated fibroblasts (CAFs); however, its role and mechanisms of action of Gal-1 in GC remain unclear. In this study, we stimulated GC cells with exogenous human recombinant galectin-1 protein (rhGal-1) to investigate its effects on the proliferation, migration, and resistance to cisplatin. Materials and Methods: We used simulated rhGal-1 protein as a paracrine factor produced by CAFs to induce GC cells and investigated its promotional effects and mechanisms in GC progression and cisplatin resistance. Immunohistochemical (IHC) assay confirmed that Gal-1 expression was associated with clinicopathological parameters and correlated with the expression of neuropilin-1 (NRP-1), c-JUN, and Wee1. Results: Our study reveals Gal-1 expression was significantly associated with poor outcomes. Gal-1 boosts the proliferation and metastasis of GC cells by activating the NRP-1/C-JUN/Wee1 pathway. Gal-1 notably increases GC cell resistance to cisplatin The NRP-1 inhibitor, EG00229, effectively counteracts these effects. Conclusions: These findings revealed a potential mechanism by which Gal-1 promotes GC growth and contributes to chemoresistance, offering new therapeutic targets for the treatment of GC.

• The Transactions of the Korean Institute of Electrical Engineers P
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• v.59 no.4
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• pp.462-466
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• 2010

The purpose of this study is to evaluate the safety of a wire connector fabricated for the effective installation of a lighting fixture including its contact resistance, insulation resistance, withstanding voltage characteristics, etc., and to provide the basis for the analysis and judgment of PL(Product Liability) dispute by presenting a damage pattern due to a general flame and overcurrent. This study applied the Korean Standard (KS) for the incombustibility test of the connector using a general flame and performed an overcurrent characteristics test of the connector using PCITS (Primary Current Injection Test System). The contact resistance of the housing connector was measured using a high resistance meter and the insulation resistance was measured using a multimeter. In addition, a supply voltage of AC 1,500V for testing the withstanding voltage characteristics was applied to both ends of the connector. Measurement was performed on 5 specimens and the measured values were used as a basis for judgment. Since the connector is fabricated in the form of a housing, it can be connected and separated easily and has a structure that allows no foreign material to enter. In addition, since it has a structure that allows wires to be connected only when their polarity is identical, any misconnection that may occur during installation can be prevented. When the incombustibility test was performed by applying a general flame to the connector, it showed outstanding incombustibility characteristics and the blade and blade holder connected to the housing remained firmly secured even after the insulation sheath (PVC) was completely destroyed by fire. In addition, the mechanism of the damaged connecting wire showed a comparatively uniform carbonization pattern and it was found that some residual melted insulation material was attached to both ends. In the accelerated life test (ALT) to which approximately 500% of the rated current was applied, the connector damage proceeded in the order of white smoke generation, wire separation, spark occurrence and carbonization. That is, it could be seen that the connector damaged by overcurrent lost its own metallic color with traces of discoloration and carbonization. The contact resistance of the connector at a normal state was 2.164mV/A on average. The contact resistance measured after the high temperature test was 3.258mV/A. In addition, the insulation resistance after the temperature test was completed was greater than $10G\Omega$ and the withstanding voltage test result showed that no insulation breakdown occurred to all specimens showing stable withstanding voltage and insulation resistance characteristics.

• Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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• 2009.11a
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• pp.65-65
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• 2009

High temperature silicon carbide Schottky diode was fabricated with Au deposited on poly 3C-SiC thin film grown on p-type Si(100) using atmospheric pressure chemical vapor deposition. The charge transport mechanism of the diode was studied in the temperature range of 300 K to 550 K. The forward and reverse bias currents of the diode increase strongly with temperature and diode shows a non-ideal behavior due to the series resistance and the interface states associated with 3C-SiC. The charge transport mechanism is a temperature activated process, in which, the electrons passes over of the low barriers and in turn, diode has a large ideality factor. The charge transport mechanism of the diode was analyzed by a Gaussian distribution of the Schottky barrier heights due to the Schottky barrier inhomogeneities at the metal-semiconductor interface and the mean barrier height and zero-bias standard deviation values for the diode was found to be 1.82 eV and $s_0$=0.233 V, respectively. The interface state density of the diode was determined using conductance-frequency and it was of order of $9.18{\times}10^{10}eV^{-1}cm^{-2}$.

• Transactions of the Korean Society of Mechanical Engineers A
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• v.26 no.11
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• pp.2328-2335
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• 2002

A hybrid composite material has many potential usage due to the high specific strength and the resistance to fatigue, when compared to other composite materials such as fiber reinforced plastic(FRP) and metal matrix composite(MMC). However, the fracture mechanism of hybrid composite material is extremely complicated because of the bonding structure of metals and FRP. In this study, Al 7075 sheets and carbon epoxy preprags were used to fabricate the hybrid composite. Recently, nondestructive technique has been used to evaluate the fracture mechanism of these composite materials. AE technique was used to clarify the microscopic damage behavior and failure mechanism of A17075/CFRP hybrid composite. It was found that AE paralneters such as AE event, energy and amplitude were effective to evaluate the failure process of Al 7075/CFRP composite. In addition, the relationship between the AE signal and the characteristics of fracture surface using optical microscope was discussed.

• Structural Engineering and Mechanics
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• v.52 no.6
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• pp.1085-1098
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• 2014

Plastic mechanism analysis of structures subjected to large deformation has long been used in order to determine collapse mechanisms of steel structures, and the energy absorbed in plastic deformation during such collapses. In this paper the technique is applied to vehicle roof structures that undergo large plastic deformation as a result of rollover crashes. The components of such roof structures are typically steel spot-welded hat-type sections. Ten different deformation mechanisms are defined from investigations of real-world rollover crashes, and an analytical technique to determine the plastic collapse load and energy absorption of such mechanisms is determined. The procedure is presented in a generic manner, such that it may be applied to any vehicle structure undergoing a rollover induced collapse. The procedure is applied to an exemplar vehicle, in order to demonstrate its application in determining the energy absorbed in the deformation of the identified collapse mechanisms. The procedure will be useful to forensic crash reconstructionists, in order to accurately determine the initial travel velocity of a vehicle that has undergone a rollover and for which the post-crash vehicle deformation is known. It may also be used to perform analytical studies of the collapse resistance of vehicle roof structures for optimisation purposes, which is also demonstrated with an analysis of the effect of varying the geometric and material properties of the roof structure components of the exemplar vehicle.