Publications by authors named "Hyun Suk Jung"

191 Publications

Load and Display: Engineering Encapsulin as a Modular Nanoplatform for Protein-Cargo Encapsulation and Protein-Ligand Decoration Using Split Intein and SpyTag/SpyCatcher.

Biomacromolecules 2021 Jun 18. Epub 2021 Jun 18.

Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea.

Protein cage nanoparticles have a unique spherical hollow structure that provides a modifiable interior space and an exterior surface. For full application, it is desirable to utilize both the interior space and the exterior surface simultaneously with two different functionalities in a well-combined way. Here, we genetically engineered encapsulin protein cage nanoparticles (Encap) as modular nanoplatforms by introducing a split-C-intein (Int) fragment and SpyTag into the interior and exterior surfaces, respectively. A complementary split-N-intein (Int) was fused to various protein cargoes, such as NanoLuc luciferase (Nluc), enhanced green fluorescent protein (eGFP), and Nluc-miniSOG, individually, which led to their successful encapsulation into Encaps to form [email protected] through split intein-mediated protein ligation during protein coexpression and cage assembly in bacteria. Conversely, the SpyCatcher protein was fused to various protein ligands, such as a glutathione binder (GST-SC), dimerizing ligands (FKBP12-SC and FRB-SC), and a cancer-targeting affibody (SC-EGFRAfb); subsequently, they were displayed on [email protected] through SpyTag/SpyCatcher ligation to form [email protected]/Ligands in a mix-and-match manner. [email protected]/glutathione--transferase (GST) was effectively immobilized on glutathione (GSH)-coated solid supports exhibiting repetitive and long-term usage of the encapsulated luciferases. We also established luciferase-embedded layer-by-layer (LbL) nanostructures by alternately depositing [email protected]/FKBP12 and [email protected]/FRB in the presence of rapamycin and applied enhanced green fluorescent protein (eGFP)@Encap/EGFRAfb as a target-specific fluorescent imaging probe to visualize specific cancer cells selectively. Modular functionalization of the interior space and the exterior surface of a protein cage nanoparticle may offer the opportunity to develop new protein-based nanostructured devices and nanomedical tools.
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http://dx.doi.org/10.1021/acs.biomac.1c00481DOI Listing
June 2021

MiR-154-5p-MCP1 Axis Regulates Allergic Inflammation by Mediating Cellular Interactions.

Front Immunol 2021 31;12:663726. Epub 2021 May 31.

Department of Biochemistry, Kangwon National University, Chuncheon, South Korea.

In a previous study, we have demonstrated that p62, a selective receptor of autophagy, can regulate allergic inflammation. In the present study, microRNA array analysis showed that miR-154-5p was increased by antigen (DNP-HSA) in a p62-dependent manner in rat basophilic leukemia cells (RBL2H3). NF-kB directly increased the expression of miR-154-5p. miR-154-5p mediated allergic reactions, including passive cutaneous anaphylaxis and passive systemic anaphylaxis. Cytokine array analysis showed that antigen stimulation increased the expression of MCP1 in RBL2H3 cells in an miR-154-5p-dependent manner. Reactive oxygen species (ROS)-ERK-NF-kB signaling increased the expression of MCP1 in antigen-stimulated RBL2H3 cells. Recombinant MCP1 protein induced molecular features of allergic reactions both and . Anaphylaxis-promoted tumorigenic potential has been known to be accompanied by cellular interactions involving mast cells, and macrophages, and cancer cells. Our experiments employing culture medium, co-cultures, and recombinant MCP1 protein showed that miR-154 and MCP1 mediated these cellular interactions. MiR-154-5p and MCP1 were found to be present in exosomes of RBL2H3 cells. Exosomes from PSA-activated BALB/C mouse induced molecular features of passive cutaneous anaphylaxis in an miR-154-5p-dependent manner. Exosomes from antigen-stimulated RBL2H3 cells enhanced both tumorigenic and metastatic potentials of B16F1 melanoma cells in an miR-154-5p-dependent manner. Exosomes regulated both ROS level and ROS mediated cellular interactions during allergic inflammation. Our results indicate that the miR-154-5p-MCP1 axis might serve as a valuable target for the development of anti-allergy therapeutics.
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http://dx.doi.org/10.3389/fimmu.2021.663726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201518PMC
May 2021

The CAGE-MiR-181b-5p-S1PR1 Axis Regulates Anticancer Drug Resistance and Autophagy in Gastric Cancer Cells.

Front Cell Dev Biol 2021 25;9:666387. Epub 2021 May 25.

Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, South Korea.

Cancer-associated gene (CAGE), a cancer/testis antigen, has been known to promote anticancer drug resistance. Since the underlying mechanisms of CAGE-promoted anticancer drug resistance are poorly understood, we established Anticancer drug-resistant gastric cancer cells (AGS ) to better elucidate possible mechanisms. AGS showed an increased expression level of CAGE and autophagic flux compared with anticancer drug-sensitive parental gastric cancer cells (AGS cells). AGS cells showed higher invasion potential, growth rate, tumor spheroid formation, and angiogenic potential than AGS cells. CAGE exerted effects on the response to anticancer drugs and autophagic flux. CAGE was shown to bind to Beclin1, a mediator of autophagy. Overexpression of CAGE increased autophagic flux and invasion potential but inhibited the cleavage of PARP in response to anticancer drugs in CAGE CRISPR-Cas9 cell lines. TargetScan analysis was utilized to predict the binding of miR-302b-5p to the promoter sequences of CAGE, and the results show that miR-302b-5p directly regulated CAGE expression as illustrated by luciferase activity. MiR-302b-5p regulated autophagic flux and the response to anticancer drugs. CAGE was shown to bind the promoter sequences of miR-302b-5p. The culture medium of AGS cells increased CAGE expression and autophagic flux in AGS cells. ImmunoEM showed CAGE was present in the exosomes of AGS cells; exosomes of AGS cells and human recombinant CAGE protein increased CAGE expression, autophagic flux, and resistance to anticancer drugs in AGS cells. MicroRNA array revealed miR-181b-5p as a potential negative regulator of CAGE. MiR-181b-5p inhibitor increased the expression of CAGE and autophagic flux in addition to preventing anticancer drugs from cleaving poly(ADP-ribose) polymerase (PARP) in AGS cells. TargetScan analysis predicted sphingosine 1-phosphate receptor 1 (SIPR1) as a potential target for miR-181b-5p. CAGE showed binding to the promoter sequences of S1PR1. The downregulation or inhibition of S1PR1 led to decreased autophagic flux but enhanced the sensitivity to anticancer drugs in AGS cells. This study presents a novel role of the CAGE-miR-181b-5p-S1PR1 axis in anticancer drug resistance and autophagy.
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http://dx.doi.org/10.3389/fcell.2021.666387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185229PMC
May 2021

Synthesis and adsorption properties of gelatin-conjugated hematite (α-FeO) nanoparticles for lead removal from wastewater.

J Hazard Mater 2021 Mar 20;416:125696. Epub 2021 Mar 20.

School of Advanced Materials Science and Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address:

Gelatin-conjugated hematite nanoparticles (HT NPs) are prepared through the solid-state phase transformation in the presence of phosphate. Their adsorption capacity and kinetics are investigated for Pb removal in wastewater. The gelatin-conjugated HT NPs with a size of 4-6 nm exhibit an excellent Pb removal performance, with a high adsorption capacity of 169.49 mg g and a fast equilibrium adsorption kinetics, attributed to the large number of active sites and highly negative charge on the surface of HT NPs. Moreover, the magnetic property of HT NPs enables to selectively collect NPs in the wastewater by using a permanent magnet, leading to its high reusability.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125696DOI Listing
March 2021

Extracellular vesicles derived from macrophages display glycyl-tRNA synthetase 1 and exhibit anti-cancer activity.

J Extracell Vesicles 2020 Nov 1;10(1):e12029. Epub 2020 Dec 1.

Institute for Artificial Intelligence and Biomedical Research Medicinal Bioconvergence Research Center College of Pharmacy & College of Medicine Gangnam Severance Hospital Yonsei University Incheon Korea.

Glycyl-tRNA synthetase 1 (GARS1), a cytosolic enzyme secreted from macrophages, promotes apoptosis in cancer cells. However, the mechanism underlying GARS1 secretion has not been elucidated. Here, we report that GARS1 is secreted through unique extracellular vesicles (EVs) with a hydrodynamic diameter of 20-58 nm (mean diameter: 36.9 nm) and a buoyant density of 1.13-1.17 g/ml. GARS1 was anchored to the surface of these EVs through palmitoylated C390 residue. Proteomic analysis identified 164 proteins that were uniquely enriched in the GARS1-containing EVs (GARS1-EVs). Among the identified factors, insulin-like growth factor II receptor, and vimentin also contributed to the anti-cancer activity of GARS1-EVs. This study identified the unique secretory vesicles containing GARS1 and various intracellular factors that are involved in the immunological defence response against tumorigenesis.
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http://dx.doi.org/10.1002/jev2.12029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890555PMC
November 2020

Dynamic structural property of organic-inorganic metal halide perovskite.

iScience 2021 Jan 24;24(1):101959. Epub 2020 Dec 24.

Department of Energy Science and Nature Inspired Materials Processing Research Center, Sungkyunkwan University, Suwon 16419, Republic of Korea.

Unique organic-inorganic hybrid semiconducting materials have made a remarkable breakthrough in new class of photovoltaics (PVs). Organic-inorganic metal (Pb and/or Sn) halides (-I, -Br, and -Cl) are the semiconducting absorber with the crystal structure of the famous "Perovskite". It is widely called "perovskite solar cells (PSCs)" in PV society. Now, the power conversion efficiency (PCE) of PSCs is recorded in 25.5%. Prototypical composition of the absorbers is (A = methylammonium [MA], formamidinium [FA], and Cs), (M = Pb and/or Sn), and (X = I, Br, and Cl) in the form of perovskite AMX. Since the report on the stable all solid-state PSCs in 2012, the average annual growth rate of PCE is well over ∼10%. Such an outstanding PV performance attracts huge number of scientists in our research society. Their chemical as well as physical properties are dramatically different from monocrystalline Si, GaAs, other III-IV semiconductors, and many oxides with the crystal structure of perovskite. In this review, different fundamental aspects, in particular, the dynamic properties of A site cationic molecules and PbI octahedrons linked with their corners, from other semiconducting and dielectric materials are reviewed and summarized. Upon discussing unique properties, perspectives on the promising PV applications based on the comprehension in dynamic nature of the orientation in A site molecule and PbI octahedron tilting will be given.
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http://dx.doi.org/10.1016/j.isci.2020.101959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788097PMC
January 2021

High-Efficiency Perovskite Solar Cells.

Chem Rev 2020 Aug 28;120(15):7867-7918. Epub 2020 Jul 28.

School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.

With rapid progress in a power conversion efficiency (PCE) to reach 25%, metal halide perovskite-based solar cells became a game-changer in a photovoltaic performance race. Triggered by the development of the solid-state perovskite solar cell in 2012, intense follow-up research works on structure design, materials chemistry, process engineering, and device physics have contributed to the revolutionary evolution of the solid-state perovskite solar cell to be a strong candidate for a next-generation solar energy harvester. The high efficiency in combination with the low cost of materials and processes are the selling points of this cell over commercial silicon or other organic and inorganic solar cells. The characteristic features of perovskite materials may enable further advancement of the PCE beyond those afforded by the silicon solar cells, toward the Shockley-Queisser limit. This review summarizes the fundamentals behind the optoelectronic properties of perovskite materials, as well as the important approaches to fabricating high-efficiency perovskite solar cells. Furthermore, possible next-generation strategies for enhancing the PCE over the Shockley-Queisser limit are discussed.
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http://dx.doi.org/10.1021/acs.chemrev.0c00107DOI Listing
August 2020

Homoharringtonine Inhibits Allergic Inflammations by Regulating NF-κB-miR-183-5p-BTG1 Axis.

Front Pharmacol 2020 7;11:1032. Epub 2020 Jul 7.

Department of Biochemistry, Kangwon National University, Chunchon, South Korea.

Homoharringtonine (HHT) is a drug for treatment of chronic myeloid leukemia. However, the role of HHT in allergic inflammations remains unknown. Mouse model of atopic dermatitis (AD) induced by 2, 4,-dinitroflurobenzene (DNFB) and anaphylaxis employing 2,4-dinitropheny-human serum albumin (DNP-HSA) were used to examine the role of HHT in allergic inflammations. HHT inhibited allergic reactions and attenuated clinical symptoms associated with AD. DNFB induced features of allergic reactions in rat basophilic leukemia (RBL2H3) cells. HHT suppressed effect of AD on the expression of Th1/Th2 cytokines. HHT inhibited passive cutaneous anaphylaxis and passive systemic anaphylaxis. MiR-183-5p, increased by antigen stimulation, was downregulated by HHT in RBL2H3 cells. MiR-183-5p inhibitor suppressed anaphylaxis and AD. B cell translocation gene 1 (BTG1) was shown to be a direct target of miR-183-5p. BTG1 prevented antigen from inducing molecular features of allergic reactions. AD increased the expression of NF-κB, and NF-κB showed binding to the promoter sequences of miR-183-5p. NF-κB and miR-183 formed positive feedback to mediate allergic reactions. Thus, HHT can be an anti-allergy drug. We present evidence that NF-κB-miR-183-5p-BTG1 axis can serve as target for development of anti-allergy drug.
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http://dx.doi.org/10.3389/fphar.2020.01032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358642PMC
July 2020

Histone Deacetylase Inhibitors to Overcome Resistance to Targeted and Immuno Therapy in Metastatic Melanoma.

Front Cell Dev Biol 2020 17;8:486. Epub 2020 Jun 17.

Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chunchon, South Korea.

Therapies that target oncogenes and immune checkpoint molecules constitute a major group of treatments for metastatic melanoma. A mutation in (BRAF V600E) affects various signaling pathways, including mitogen activated protein kinase (MAPK) and PI3K/AKT/mammalian target of rapamycin (mTOR) in melanoma. Target-specific agents, such as MAPK inhibitors improve progression-free survival. However, BRAF mutant melanomas treated with BRAF kinase inhibitors develop resistance. Immune checkpoint molecules, such as programmed death-1 (PD-1) and programmed death ligand-1(PD-L1), induce immune evasion of cancer cells. MAPK inhibitor resistance results from the increased expression of PD-L1. Immune checkpoint inhibitors, such as anti-PD-L1 or anti-PD-1, are main players in immune therapies designed to target metastatic melanoma. However, melanoma patients show low response rate and resistance to these inhibitors develops within 6-8 months of treatment. Epigenetic reprogramming, such as DNA methylaion and histone modification, regulates the expression of genes involved in cellular proliferation, immune checkpoints and the response to anti-cancer drugs. Histone deacetylases (HDACs) remove acetyl groups from histone and non-histone proteins and act as transcriptional repressors. HDACs are often dysregulated in melanomas, and regulate MAPK signaling, cancer progression, and responses to various anti-cancer drugs. HDACs have been shown to regulate the expression of PD-1/PD-L1 and genes involved in immune evasion. These reports make HDACs ideal targets for the development of anti-melanoma therapeutics. We review the mechanisms of resistance to anti-melanoma therapies, including MAPK inhibitors and immune checkpoint inhibitors. We address the effects of HDAC inhibitors on the response to MAPK inhibitors and immune checkpoint inhibitors in melanoma. In addition, we discuss current progress in anti-melanoma therapies involving a combination of HDAC inhibitors, immune checkpoint inhibitors, and MAPK inhibitors.
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http://dx.doi.org/10.3389/fcell.2020.00486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311641PMC
June 2020

Exosomal MicroRNAs as Mediators of Cellular Interactions Between Cancer Cells and Macrophages.

Front Immunol 2020 11;11:1167. Epub 2020 Jun 11.

Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, South Korea.

Tumor microenvironment consists of cancer cells and various stromal cells such as endothelial cells, cancer-associated fibroblasts (CAFs), myeloid-derived suppressor cells (MDSCs), neutrophils, macrophages, and other innate and adaptive immune cells. Of these innate immune cells, macrophages are an extremely heterogeneous population, and display both pro-inflammatory and anti-inflammatory functions. While M1 macrophages (classically activated macrophages) display anti-tumoral and pro-inflammatory functions, M2 macrophages display pro-tumoral and anti-inflammatory functions. Cellular interactions and molecular factors in the tumor microenvironment affect the polarization of macrophages. We review molecules and immune cells that influence the polarization status of macrophages. Tumor-associated macrophages (TAMs) generally express M2 phenotype, and mediate many processes that include tumor initiation, angiogenesis, and metastasis. A high number of TAMs has been associated with the poor prognosis of cancers. MicroRNAs (miRNAs) have been known to regulate cellular interactions that involve cancer cells and macrophages. Tumor-derived exosomes play critical roles in inducing the M1 or M2-like polarization of macrophages. The roles of exosomal miRNAs from tumor cells in the polarization of macrophages are also discussed and the targets of these miRNAs are presented. We review the effects of exosomal miRNAs from TAMs on cancer cell invasion, growth, and anti-cancer drug resistance. The relevance of exosomal microRNAs (miRNAs) as targets for the development of anti-cancer drugs is discussed. We review recent progress in the development of miRNA therapeutics aimed at elevating or decreasing levels of miRNAs.
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http://dx.doi.org/10.3389/fimmu.2020.01167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300210PMC
April 2021

Glycemic Status, Insulin Resistance, and the Risk of Nephrolithiasis: A Cohort Study.

Am J Kidney Dis 2020 11 10;76(5):658-668.e1. Epub 2020 Jun 10.

Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea. Electronic address:

Rationale & Objective: The effect of glycemic status on nephrolithiasis risk remains controversial. This study sought to examine the association of glycemic status and insulin resistance with incident nephrolithiasis.

Study Design: A retrospective cohort study.

Setting & Participants: 278,628 Korean adults without nephrolithiasis who underwent a comprehensive health examination between 2011 and 2017.

Exposures: Glucose level, glycated hemoglobin level, and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR).

Outcome: Nephrolithiasis ascertained using abdominal ultrasound.

Analytical Approach: A parametric proportional hazard model was used to estimate adjusted HRs and 95% CIs. We explored prespecified potential sex differences in the association of glycemic status and incident nephrolithiasis.

Results: During a median follow-up of 4.2 years, 6,904 participants developed nephrolithiasis. Associations between levels of glycemic status and incident nephrolithiasis were examined separately in men and women (P for interaction = 0.003). Among men, multivariable-adjusted HRs for incident nephrolithiasis comparing glucose levels of 90-99, 100-125, and ≥ 126 mg/dL were 1.10 (95% CI, 1.01-1.19), 1.11 (95% CI, 1.02-1.21), and 1.27 (95% CI, 1.10-1.46), respectively, while HRs for incident nephrolithiasis comparing glycated hemoglobin levels of 5.7%-5.9%, 6.0%-6.4%, and 6.5%-<5.7% were 1.03 (95% CI, 0.96-1.10), 1.18 (95% CI, 1.07-1.31), and 1.20 (95% CI, 1.06-1.37), respectively. The HR for incident nephrolithiasis comparing the highest HOMA-IR quintile to the lowest quintile was 1.18 (95% CI, 1.06-1.31). Among women, no apparent association was found between glycemic status and nephrolithiasis risk.

Limitations: Glucose tolerance testing and computed tomography assessment for nephrolithiasis were not available.

Conclusions: Higher glycemic values, even within the normoglycemic range, and HOMA-IR were positively associated with increased risk for nephrolithiasis, associations that were only observed among men. Insulin resistance and hyperglycemia may contribute to the development of nephrolithiasis, particularly among men.
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http://dx.doi.org/10.1053/j.ajkd.2020.03.013DOI Listing
November 2020

Exosomes derived from chemically induced human hepatic progenitors inhibit oxidative stress induced cell death.

Biotechnol Bioeng 2020 09 30;117(9):2658-2667. Epub 2020 Jun 30.

Center for Exosome & Bioparticulate Research, Hanyang University, Gyeonggi-do, Korea.

The emerging field of regenerative medicine has revealed that the exosome contributes to many aspects of development and disease through intercellular communication between donor and recipient cells. However, the biological functions of exosomes secreted from cells have remained largely unexplored. Here, we report that the human hepatic progenitor cells (CdHs)-derived exosome (EXO ) plays a crucial role in maintaining cell viability. The inhibition of exosome secretion treatment with GW4869 results in the acceleration of reactive oxygen species (ROS) production, thereby causing a decrease of cell viability. This event provokes inhibition of caspase dependent cell death signaling, leading to a ROS-dependent cell damage response and thus induces promotion of antioxidant gene expression or repair of cell death of hypoxia-exposed cells. Together, these findings show the effect of exosomes in regeneration of liver cells, and offer valuable new insights into liver regeneration.
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http://dx.doi.org/10.1002/bit.27447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496643PMC
September 2020

Measurement of Quantum Yields of Monolayer TMDs Using Dye-Dispersed PMMA Thin Films.

Nanomaterials (Basel) 2020 May 28;10(6). Epub 2020 May 28.

Department of Energy Science, Sungkyunkwan University, Suwon 16419, Korea.

In general, the quantum yields (QYs) of monolayer transition metal dichalcogenides (1L-TMDs) are low, typically less than 1% in their pristine state, significantly limiting their photonic applications. Many methods have been reported to increase the QYs of 1L-TMDs; however, the technical difficulties involved in the reliable estimation of these QYs have prevented the general assessment of these methods. Herein, we demonstrate the estimation of the QYs of 1L-TMDs using a poly methyl methacrylate (PMMA) thin film embedded with rhodamine 6G (R6G) as a reference specimen for measuring the QYs of 1L-TMDs. The PMMA/R6G composite films with thicknesses of 80 and 300 nm demonstrated spatially homogeneous emissions with the incorporation of well-dispersed R6G molecules, and may, therefore, be used as ideal reference specimens for the QY measurement of 1L-TMDs. Using our reference specimens, for which the QY ranged from 5.4% to 22.2% depending on the film thickness and R6G concentrations, we measured the QYs of the exfoliated or chemical vapor deposition (CVD)-grown 1L-WS, -MoSe, -MoS, and -WSe TMDs. The convenient procedure proposed in this study for preparing the thin reference films and the simple protocol for the QY estimation of 1L-TMDs may enable accurate comparisons of the absolute QYs between the 1L-TMD samples, thereby enabling the development of a method to improve the QY of 1L-TMDs.
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http://dx.doi.org/10.3390/nano10061032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353022PMC
May 2020

Highly Efficient Photo-Induced Charge Separation Enabled by Metal-Chalcogenide Interfaces in Quantum-Dot/Metal-Oxide Hybrid Phototransistors.

ACS Appl Mater Interfaces 2020 Apr 25;12(14):16620-16629. Epub 2020 Mar 25.

Displays and Devices Research Laboratory School of Electrical and Electronics Engineering, Chung-Ang University, Seoul 06974, Korea.

Quantum dot (QD)-based optoelectronics have received great interest for versatile applications because of their excellent photosensitivity, facile solution processability, and the wide range of band gap tunability. In addition, QD-based hybrid devices, which are combined with various high-mobility semiconductors, have been actively researched to enhance the optoelectronic characteristics and maximize the zero-dimensional structural advantages, such as tunable band gap and high light absorption. However, the difficulty of highly efficient charge transfer between QDs and the semiconductors and the lack of systematic analysis for the interfaces have impeded the fidelity of this platform, resulting in complex device architectures and unsatisfactory device performance. Here, we report ultrahigh detective phototransistors with highly efficient photo-induced charge separation using a SnS-capped CdSe QD/amorphous oxide semiconductor (AOS) hybrid structure. The photo-induced electron transfer characteristics at the interface of the two materials were comprehensively investigated with an array of electrochemical and spectroscopic analyses. In particular, photocurrent imaging microscopy revealed that interface engineering in QD/AOS with chelating chalcometallate ligands causes efficient charge transfer, resulting in photovoltaic-dominated responses over the whole channel area. On the other hand, monodentate ligand-incorporated QD/AOS-based devices typically exhibit limited charge transfer with atomic vibration, showing photo-thermoelectric-dominated responses in the drain electrode area.
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http://dx.doi.org/10.1021/acsami.0c01176DOI Listing
April 2020

Tailored 2D/3D Halide Perovskite Heterointerface for Substantially Enhanced Endurance in Conducting Bridge Resistive Switching Memory.

ACS Appl Mater Interfaces 2020 Apr 24;12(14):17039-17045. Epub 2020 Mar 24.

School of Advanced Materials Science and Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.

Hybrid organic-inorganic halide perovskites (HPs) have garnered significant attention for use in resistive switching (RS) memory devices due to their low cost, low operation voltage, high on/off ratio, and excellent mechanical properties. However, the HP-based RS memory devices continue to face several challenges owing to the short endurance and stability of the HP film. Herein, two-dimensional/three-dimensional (2D/3D) perovskite heterojunction films were prepared via a low-temperature all-solution process and their RS behavior was investigated for the first time. The 2D/3D perovskite RS devices exhibited excellent performance with an endurance of 2700 cycles, a high on/off ratio of 10, and an operation speed of 640 μs. The calculated thermally assisted ion hopping activation energy and the results of the time-of-flight secondary ion mass spectroscopy demonstrated that the 2D perovskite layer could efficiently prevent the Ag ion migration into the 3D perovskite film. Moreover, we found that owing to its high thermal conductivity, the 2D perovskite can control the rupture of the Ag conductive filament. Thus, the 2D perovskite layer enhances endurance by controlling both Ag migration and filament rupture. Hence, this study provides an alternate strategy for improving endurance of HP-based RS memory devices.
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http://dx.doi.org/10.1021/acsami.9b22918DOI Listing
April 2020

Dual Binding to Orthosteric and Allosteric Sites Enhances the Anticancer Activity of a TRAP1-Targeting Drug.

J Med Chem 2020 03 2;63(6):2930-2940. Epub 2020 Mar 2.

Department of Biological Sciences, Ulsan National Institutes of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.

The molecular chaperone TRAP1 is the mitochondrial paralog of Hsp90 and is overexpressed in many cancer cells. The orthosteric ATP-binding site of TRAP1 has been considered the primary inhibitor binding location, but TRAP1 allosteric modulators have not yet been investigated. Here, we generated and characterized the Hsp90 inhibitor PU-H71, conjugated to the mitochondrial delivery vehicle triphenylphosphonium (TPP) with a C carbon spacer, named SMTIN-C10, to enable dual binding to orthosteric and allosteric sites. In addition to tight binding with the ATP-binding site through the PU-H71 moiety, SMTIN-C10 interacts with the E115 residue in the N-terminal domain through the TPP moiety and subsequently induces structural transition of TRAP1 to a tightly packed closed form. The data indicate the existence of a druggable allosteric site neighboring the orthosteric ATP pocket that can be exploited to develop potent TRAP1 modulators.
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http://dx.doi.org/10.1021/acs.jmedchem.9b01420DOI Listing
March 2020

High-Efficiency Flexible Perovskite Solar Cells Enabled by an Ultrafast Room-Temperature Reactive Ion Etching Process.

ACS Appl Mater Interfaces 2020 Feb 30;12(6):7125-7134. Epub 2020 Jan 30.

School of Advanced Materials Science & Engineering , Sungkyunkwan University , Suwon 16419 , Republic of Korea.

Perovskite solar cells (PSCs), which have surprisingly emerged in recent years, are now aiming at commercialization. Rapid, low-temperature, and continuous fabrication processes that can produce high-efficiency PSCs with a reduced fabrication cost and shortened energy payback time are important challenges on the way to commercialization. Herein, we report a reactive ion etching (RIE) method, which is an ultrafast room-temperature technique, to fabricate mesoporous TiO (mp-TiO) as an electron transport layer for high-efficiency PSCs. Replacing the conventional high-temperature annealing process by RIE reduces the total processing time for fabricating 20 PSCs by 40%. Additionally, the RIE-processed mp-TiO exhibits enhanced electron extraction, whereupon the optimized RIE-mp-TiO-based PSC exhibits a power conversion efficiency (PCE) of 19.60% without - hysteresis, when the devices were optimized with a TiCl surface treatment process. Finally, a flexible PSC employing RIE-mp-TiO is demonstrated with 17.29% PCE. Considering that the RIE process has been actively used in the semiconductor industry, including for the fabrication of silicon photovoltaic modules, the process developed in this work could be easily applied toward faster, simpler, and cheaper manufacturing of PSC modules.
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http://dx.doi.org/10.1021/acsami.9b19030DOI Listing
February 2020

Structural and kinetic insights into flavin-containing monooxygenase and calponin-homology domains in human MICAL3.

IUCrJ 2020 Jan 1;7(Pt 1):90-99. Epub 2020 Jan 1.

College of Life Sciences and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.

MICAL is an oxidoreductase that participates in cytoskeleton reorganization via actin disassembly in the presence of NADPH. Although three MICALs (MICAL1, MICAL2 and MICAL3) have been identified in mammals, only the structure of mouse MICAL1 has been reported. Here, the first crystal structure of human MICAL3, which contains the flavin-containing monooxygenase (FMO) and calponin-homology (CH) domains, is reported. MICAL3 has an FAD/NADP-binding Rossmann-fold domain for mono-oxygenase activity like MICAL1. The FMO and CH domains of both MICAL3 and MICAL1 are highly similar in structure, but superimposition of the two structures shows a different relative position of the CH domain in the asymmetric unit. Based on kinetic analyses, the catalytic efficiency of MICAL3 dramatically increased on adding F-actin only when the CH domain was available. However, this did not occur when two residues, Glu213 and Arg530, were mutated in the FMO and CH domains, respectively. Overall, MICAL3 is structurally highly similar to MICAL1, which suggests that they may adopt the same catalytic mechanism, but the difference in the relative position of the CH domain produces a difference in F-actin substrate specificity.
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http://dx.doi.org/10.1107/S2052252519015409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949599PMC
January 2020

Functional properties and the oligomeric state of alkyl hydroperoxide reductase subunit F (AhpF) in Pseudomonas aeruginosa.

Protoplasma 2020 May 7;257(3):807-817. Epub 2020 Jan 7.

Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, 29 Geumgu-gil, Jeongeup, 56212, South Korea.

Alkyl hydroperoxide reductase subunit F (AhpF) is a well-known flavoprotein that transfers electrons from pyridine nucleotides to the peroxidase protein AhpC via redox-active disulfide centers to detoxify hydrogen peroxide. However, study of AhpF has historically been limited to particular eubacteria, and the connection between the functional and structural properties of AhpF remains unknown. The present study demonstrates the dual function of Pseudomonas aeruginosa AhpF (PaAhpF) as a reductase and a molecular chaperone. It was observed that the functions of PaAhpF are closely linked with its structural status. The reductase and foldase chaperone function of PaAhpF predominated for its low-molecular-weight (LMW) form, whereas the holdase chaperone function of PaAhpF was found associated with its high-molecular-weight (HMW) complex. Further, the present study also demonstrates the multiple function of PaAhpF in controlling oxidative and heat stresses in P. aeruginosa resistance to oxidative and heat stress.
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http://dx.doi.org/10.1007/s00709-019-01465-0DOI Listing
May 2020

Effect of Metal Electrodes on Aging-Induced Performance Recovery in Perovskite Solar Cells.

ACS Appl Mater Interfaces 2019 Dec 16;11(51):48497-48504. Epub 2019 Dec 16.

School of Advanced Materials Science & Engineering , Sungkyunkwan University , Suwon 16419 , Republic of Korea.

For commercialization of perovskite solar cells (PSCs), it is important to substitute the alternative electrode for Au to decrease the unit cost. From the early stage, Ag exhibits a potential to be a good counter electrode in PSCs; however, there is an abnormal s-shaped - curve with the Ag electrode, and it is recovered as time passes. The perception of the aging-induced recovery process and refutation of the raised stability issues are required for commercial application of Ag electrodes. Herein, we compared the aging effect of PSCs with Ag and Au electrodes and found that only devices with Ag electrodes have a dramatical aging-induced recovery process. We observed the change of photoelectronic properties only in the devices with Ag electrodes as time passes, which mainly contributes to recovery of the s-shaped - curve. We verified the work function change of an aged Ag electrode and its mechanism by photoelectron spectroscopy analysis. By comparing the light stability under 1 sun intensity illumination, we can assure the practical stability of Ag electrodes in case of being encapsulated. This work suggests the profound understanding of the aging-induced recovery process of PSCs and the possibility of commercial application of Ag electrodes.
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http://dx.doi.org/10.1021/acsami.9b14619DOI Listing
December 2019

CAGE-miR-140-5p-Wnt1 Axis Regulates Autophagic Flux, Tumorigenic Potential of Mouse Colon Cancer Cells and Cellular Interactions Mediated by Exosomes.

Front Oncol 2019 14;9:1240. Epub 2019 Nov 14.

Department of Biochemistry, Kangwon National University, Chuncheon-si, South Korea.

Although the cancer/testis antigen CAGE has been implicated in tumorigenesis, the molecular mechanisms of CAGE-promoted tumorigenesis remain largely unknown. CT26 cells, CT26 (mouse colon cancer cells) cells stably expressing CAGE, were established to investigate CAGE-promoted tumorigenesis. Down-regulation of CAGE led to decreased autophagic flux in CT26 cells. CAGE interacted with Beclin1, a mediator of autophagy. The CT26 cells showed enhanced autophagosome formation and displayed greater tumor spheroid-forming potential than CT26 cells. MicroRNA array analysis revealed that CAGE decreased the expression of various microRNAs, including miR-140-5p, in CT26 cells. CAGE was shown to bind to the promoter sequences of miR-140-5p. MiR-140-5p inhibition increased the tumorigenic potential of and autophagic flux in CT26 cells. A miR-140-5p mimic exerted negative effects on the tumorigenic potential of CT26 cells and autophagic flux in CT26 cells. MiR-140-5p was predicted to bind to the 3'-UTR of Wnt1. CT26 cells showed higher expression of Wnt1 than CT26 cells. Down-regulation of Wnt1 decreased autophagic flux. Luciferase activity assays showed the direct regulation of wnt1 by miR-140-5p. Tumor tissue derived from the CT26 cells revealed higher expressions of factors associated with activated mast cells and tumor-associated macrophages than tumor tissue derived from CT26 cells. Culture medium from the CT26 cells increased autophagic flux in CT26 cells, mast cells and macrophages. Culture medium from the CT26 cells increased CD163 and autophagic flux in CT26 cells, mast cells, and macrophages in a Wnt1-dependent manner. Exosomes from CT26 cells increased autophagc flux in CT26 cells, mast cells, and macrophages. Exosomes from CT26 cells increased the tumorigenic potential of CT26 cells. Wnt1 was shown to be present within the exosomes. Recombinant Wnt1 protein increased autophagic flux in CT26, mast cells, and macrophages. Recombinant wnt1 protein mediated interactions between the CT26 cells, mast cells, and macrophages. Our results showed novel roles for the CAGE-miR-140-5p-Wnt1 axis in autophagic flux and cellular interactions mediated by exosomes.
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http://dx.doi.org/10.3389/fonc.2019.01240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868029PMC
November 2019

Liquid electron microscopy: then, now and future.

Appl Microsc 2019 Oct 25;49(1). Epub 2019 Oct 25.

Division of Chemistry and Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon-si, Gangwon-do, 24341, South Korea.

Contemporary microscopic imaging at near-atomic resolution of diverse embodiments in liquid environment has gained keen interest. In particular, Electron Microscopy (EM) can provide comprehensive framework on the structural and functional characterization of samples in liquid phase. In the past few decades, liquid based electron microscopic modalities have developed tremendously to provide insights into various backgrounds like biological, chemical, nanoparticle and material researches. It serves to be a promising analytical tool in deciphering unique insights from solvated systems. Here, the basics of liquid electron microscopy with few examples of its applications are summarized in brief. The technical developments made so far and its preference over other approaches is shortly presented. Finally, the experimental limitations and an outlook on the future technical advancement for liquid EM have been discussed.
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http://dx.doi.org/10.1186/s42649-019-0011-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809579PMC
October 2019

FcεRI-HDAC3-MCP1 Signaling Axis Promotes Passive Anaphylaxis Mediated by Cellular Interactions.

Int J Mol Sci 2019 Oct 8;20(19). Epub 2019 Oct 8.

Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chunchon 24341, Korea.

Anaphylaxis is an acute and life-threatening systemic reaction. Food, drug, aero-allergen and insect sting are known to induce anaphylaxis. Mast cells and basophils are known to mediate Immunoglobulin E (IgE)-dependent anaphylaxis, while macrophages, neutrophils and basophils mediate non IgE-dependent anaphylaxis. Histone deacetylases (HDACs) play various roles in biological processes by deacetylating histones and non-histones proteins. HDAC inhibitors can increase the acetylation of target proteins and affect various inflammatory diseases such as cancers and allergic diseases. HDAC3, a class I HDAC, is known to act as epigenetic and transcriptional regulators. It has been shown that HDAC3 can interact with the high-affinity Immunoglobulin E receptor (FcεRI), to mediate passive anaphylaxis and cellular interactions during passive anaphylaxis. Effects of HDAC3 on anaphylaxis, cellular interactions involving mast cells and macrophages during anaphylaxis, and any tumorigenic potential of cancer cells enhanced by mast cells will be discussed in this review. Roles of microRNAs that form negative feedback loops with hallmarks of anaphylaxis such as HDAC3 in anaphylaxis and cellular interactions will also be discussed. The roles of MCP1 regulated by HDAC3 in cellular interactions during anaphylaxis are discussed. Roles of exosomes in cellular interactions mediated by HDAC3 during anaphylaxis are also discussed. Thus, review might provide clues for development of drugs targeting passive anaphylaxis.
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http://dx.doi.org/10.3390/ijms20194964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801807PMC
October 2019

Structural insights into stressosome assembly.

IUCrJ 2019 Sep 21;6(Pt 5):938-947. Epub 2019 Aug 21.

College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea.

The stressosome transduces environmental stress signals to SigB to upregulate SigB-dependent transcription, which is required for bacterial viability. The stressosome core is composed of RsbS and at least one of the RsbR paralogs. A previous cryo-electron microscopy (cryo-EM) structure of the RsbRA-RsbS complex determined under a 2 symmetry restraint showed that the stressosome core forms a pseudo-icosahedron consisting of 60 STAS domains of RsbRA and RsbS. However, it is still unclear how RsbS and one of the RsbR paralogs assemble into the stressosome. Here, an assembly model of the stressosome is presented based on the crystal structure of the RsbS icosahedron and cryo-EM structures of the RsbRA-RsbS complex determined under diverse symmetry restraints (nonsymmetric 1, dihedral 2 and icosahedral envelopes). 60 monomers of the crystal structure of RsbS fitted well into the -restrained cryo-EM structure determined at 4.1 Å resolution, even though the STAS domains in the envelope were averaged. This indicates that RsbS and RsbRA share a highly conserved STAS fold. 22 protrusions observed in the 1 envelope, corresponding to dimers of the RsbRA N-domain, allowed the STAS domains of RsbRA and RsbS to be distinguished in the stressosome core. Based on these, the model of the stressosome core was reconstructed. The mutation of RsbRA residues at the binding interface in the model (R189A/Q191A) significantly reduced the interaction between RsbRA and RsbS. These results suggest that nonconserved residues in the conserved STAS folds between RsbS and RsbR paralogs determine stressosome assembly.
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http://dx.doi.org/10.1107/S205225251900945XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760441PMC
September 2019

Photo-annealed amorphous titanium oxide for perovskite solar cells.

Nanoscale 2019 Nov 25;11(41):19488-19496. Epub 2019 Sep 25.

School of Advanced Materials Science & Engineering, Sungkyunkwan University, Suwon, Republic of Korea.

Electron selective layers are important to the efficiency, stability and hysteresis of perovskite solar cells. Photo-annealing is a low-cost, roll-to-roll-compatible process that can be applied to the post-treatment fabrication of sol-gel based metal oxide layers. Here, we fabricate an amorphous titanium oxide electron selective layer at a low temperature in a dry atmosphere using a UV light annealing system and compare it with a thermal annealing process. Active oxygen species are created by using UV light to promote hydrolysis and condense the TiO precursor, which removes organic ligands effectively. The photo-annealed TiO-based perovskite solar cell has a power conversion efficiency of 19.37% without hysteresis.
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http://dx.doi.org/10.1039/c9nr05776eDOI Listing
November 2019

Targeting Autophagy for Overcoming Resistance to Anti-EGFR Treatments.

Cancers (Basel) 2019 Sep 16;11(9). Epub 2019 Sep 16.

Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chunchon 24341, Korea.

Epidermal growth factor receptor (EGFR) plays critical roles in cell proliferation, tumorigenesis, and anti-cancer drug resistance. Overexpression and somatic mutations of EGFR result in enhanced cancer cell survival. Therefore, EGFR can be a target for the development of anti-cancer therapy. Patients with cancers, including non-small cell lung cancers (NSCLC), have been shown to response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) and anti-EGFR antibodies. However, resistance to these anti-EGFR treatments has developed. Autophagy has emerged as a potential mechanism involved in the acquired resistance to anti-EGFR treatments. Anti-EGFR treatments can induce autophagy and result in resistance to anti-EGFR treatments. Autophagy is a programmed catabolic process stimulated by various stimuli. It promotes cellular survival under these stress conditions. Under normal conditions, EGFR-activated phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT)/mammalian target of rapamycin (mTOR) signaling inhibits autophagy while EGFR/rat sarcoma viral oncogene homolog (RAS)/mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (MAPK) signaling promotes autophagy. Thus, targeting autophagy may overcome resistance to anti-EGFR treatments. Inhibitors targeting autophagy and EGFR signaling have been under development. In this review, we discuss crosstalk between EGFR signaling and autophagy. We also assess whether autophagy inhibition, along with anti-EGFR treatments, might represent a promising approach to overcome resistance to anti-EGFR treatments in various cancers. In addition, we discuss new developments concerning anti-autophagy therapeutics for overcoming resistance to anti-EGFR treatments in various cancers.
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http://dx.doi.org/10.3390/cancers11091374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769649PMC
September 2019

Ultimate Charge Extraction of Monolayer PbS Quantum Dot for Observation of Multiple Exciton Generation.

Chemphyschem 2019 10 11;20(20):2657-2661. Epub 2019 Sep 11.

School of Advanced Materials & Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.

Multiple exciton generation (MEG) has great potential to improve the Shockley-Queisser (S-Q) efficiency limitation for colloidal quantum dot (CQD) solar cells. However, MEG has rarely been observed in CQD solar cells because of the loss of carriers through the transport mechanism between adjacent QDs. Herein, we demonstrate that excess charge carriers produced via MEG can be efficiently extracted using monolayer PbS QDs. The monolayer PbS QDs solar cells exhibit α=1 in the light intensity dependence of the short-circuit current density J (J ∝I ) and an internal quantum efficiency (IQE) value of 100 % at 2.95 eV because of their very short charge extraction path. In addition, the measured MEG threshold is 2.23 times the bandgap energy (E ), which is the lowest value in PbS QD solar cells. We believe that this approach can provide a simple method to find suitable CQD materials and design interface engineering for MEG.
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http://dx.doi.org/10.1002/cphc.201900381DOI Listing
October 2019

Attitudes of Korean smokers towards smoke-free public places: findings from the longitudinal ITC Korea Survey, 2005-2010.

BMJ Open 2019 08 10;9(8):e025298. Epub 2019 Aug 10.

Department of Psychology, University of Waterloo, Waterloo, Ontario, Canada.

Objective: Prior to December 2012, restaurants in South Korea were required to implement only partial smoking bans. This study documents the changes in Korean smokers' attitudes towards smoking bans between 2005 and 2010 and explores the effects of anti-smoking advertising as a correlate of support for total smoking bans in public places.

Design: Longitudinal cohort study of Korean adult smokers.

Setting: The data were derived from three waves (2005, 2008 and 2010) of the International Tobacco Control (ITC) Korea Survey.

Participants: The ITC Korea Survey respondents were a probability-based, nationally representative sample of Korean smokers aged 19 and older. The current analysis includes 995 smokers who participated in Wave 1 (2005), 1737 smokers who participated in Wave 2 (2008) and 1560 smokers who participated in Wave 3 (2010).

Primary And Secondary Outcome Measures: Changes in respondents' awareness of secondhand smoke (SHS) harm, attitudes towards smoking bans and personal rules for smoking in private homes and/or vehicles were analysed. Correlates of support for smoking bans in public places were examined using generalised estimating equation regression models.

Results: More than 80% of Korean smokers are aware of the harms of SHS. The proportion of smokers who support smoke-free restaurants or smoke-free bars increased twofold between 2005 and 2010. Smokers who were aware of the dangers of SHS were more likely to support a total smoking ban in workplaces. Noticing anti-smoking advertising or information was not significantly associated with support for a total smoking ban in public places.

Conclusions: Korean smokers became more supportive of smoking bans in public places between 2005 and 2008. These results show that smokers' attitudes towards smoking bans can change with the implementation of smoke-free policies, even in a country that has a high prevalence of smokers.
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http://dx.doi.org/10.1136/bmjopen-2018-025298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701818PMC
August 2019

Advances in Cryo-Correlative Light and Electron Microscopy: Applications for Studying Molecular and Cellular Events.

Protein J 2019 12;38(6):609-615

Department of Biochemistry, College of Natural Sciences, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon-Si, Gangwon-do, 200-701, South Korea.

Cryo-correlative light and electron microscopy (Cryo-CLEM) is materializing as a widespread approach amalgamating the advantages of both fluorescence light microscopy (FLM) as well as three dimensional (3D) cryo-electron tomography (cryo-ET) to reveal the ultrastructure of significant target molecules with specific cellular functions. Cryo-CLEM allows imaging of cells by means of fluorescence microscopy exhibiting the location of the destined molecule at high temporal and spatial resolution while cryo-ET is employed to analyze the 3D structure at a molecular resolution in close-to-physiological condition. Present review focuses upon the practical strategies for Cryo-CLEM and recent technical developments that will assist the broad implementation of this technique to investigate and answer questions pertaining to various biological events occurring in the cell.
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http://dx.doi.org/10.1007/s10930-019-09856-1DOI Listing
December 2019