Publications by authors named "Ji-Hoon Lee"

280 Publications

Effects of Annealing Temperature on the Oxygen Evolution Reaction Activity of Copper-Cobalt Oxide Nanosheets.

Nanomaterials (Basel) 2021 Mar 8;11(3). Epub 2021 Mar 8.

Department of Energy & Electronic Materials, Surface Materials Division, Korea Institute of Materials Science, Changwon 642831, Korea.

Developing high performance, highly stable, and low-cost electrodes for the oxygen evolution reaction (OER) is challenging in water electrolysis technology. However, Ir- and Ru-based OER catalysts with high OER efficiency are difficult to commercialize as precious metal-based catalysts. Therefore, the study of OER catalysts, which are replaced by non-precious metals and have high activity and stability, are necessary. In this study, a copper-cobalt oxide nanosheet (CCO) electrode was synthesized by the electrodeposition of copper-cobalt hydroxide (CCOH) on Ni foam followed by annealing. The CCOH was annealed at various temperatures, and the structure changed to that of CCO at temperatures above 250 °C. In addition, it was observed that the nanosheets agglomerated when annealed at 300 °C. The CCO electrode annealed at 250 °C had a high surface area and efficient electron conduction pathways as a result of the direct growth on the Ni foam. Thus, the prepared CCO electrode exhibited enhanced OER activity (1.6 V at 261 mA/cm) compared to those of CCOH (1.6 V at 144 mA/cm), CoO (1.6 V at 39 mA/cm), and commercial IrO (1.6 V at 14 mA/cm) electrodes. The optimized catalyst also showed high activity and stability under high pH conditions, demonstrating its potential as a low cost, highly efficient OER electrode material.
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http://dx.doi.org/10.3390/nano11030657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998886PMC
March 2021

Complete Genome Sequence of Shigella sonnei Strain SE6-1, Capable of Selenate Reduction.

Microbiol Resour Announc 2021 Apr 1;10(13). Epub 2021 Apr 1.

Department of Bioenvironmental Chemistry, Jeonbuk National University, Jeonju, Jeollabuk-do, Republic of Korea

We report the complete genome sequence of selenate [Se(VI)]-reducing SE6-1, which was isolated from stream sediment from an industrial complex in Jeonju, South Korea. The genome sequence is 4,762,774 bp long, with a G+C content of 50.7% and 4,548 genes, including 4,440 coding sequences, 22 rRNA genes, and 86 tRNA genes.
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http://dx.doi.org/10.1128/MRA.00135-21DOI Listing
April 2021

Homology-directed repair protects the replicating genome from metabolic assaults.

Dev Cell 2021 Feb;56(4):461-477.e7

Protein Signaling Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark. Electronic address:

Homology-directed repair (HDR) safeguards DNA integrity under various forms of stress, but how HDR protects replicating genomes under extensive metabolic alterations remains unclear. Here, we report that besides stalling replication forks, inhibition of ribonucleotide reductase (RNR) triggers metabolic imbalance manifested by the accumulation of increased reactive oxygen species (ROS) in cell nuclei. This leads to a redox-sensitive activation of the ATM kinase followed by phosphorylation of the MRE11 nuclease, which in HDR-deficient settings degrades stalled replication forks. Intriguingly, nascent DNA degradation by the ROS-ATM-MRE11 cascade is also triggered by hypoxia, which elevates signaling-competent ROS and attenuates functional HDR without arresting replication forks. Under these conditions, MRE11 degrades daughter-strand DNA gaps, which accumulate behind active replisomes and attract error-prone DNA polymerases to escalate mutation rates. Thus, HDR safeguards replicating genomes against metabolic assaults by restraining mutagenic repair at aberrantly processed nascent DNA. These findings have implications for cancer evolution and tumor therapy.
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http://dx.doi.org/10.1016/j.devcel.2021.01.011DOI Listing
February 2021

Poly-ADP-ribosylation drives loss of protein homeostasis in ATM and Mre11 deficiency.

Mol Cell 2021 04 10;81(7):1515-1533.e5. Epub 2021 Feb 10.

The University of Texas at Austin, Department of Molecular Biosciences, Austin, TX 78712, USA. Electronic address:

Loss of the ataxia-telangiectasia mutated (ATM) kinase causes cerebellum-specific neurodegeneration in humans. We previously demonstrated that deficiency in ATM activation via oxidative stress generates insoluble protein aggregates in human cells, reminiscent of protein dysfunction in common neurodegenerative disorders. Here, we show that this process is driven by poly-ADP-ribose polymerases (PARPs) and that the insoluble protein species arise from intrinsically disordered proteins associating with PAR-associated genomic sites in ATM-deficient cells. The lesions implicated in this process are single-strand DNA breaks dependent on reactive oxygen species, transcription, and R-loops. Human cells expressing Mre11 A-T-like disorder mutants also show PARP-dependent aggregation identical to ATM deficiency. Lastly, analysis of A-T patient cerebellum samples shows widespread protein aggregation as well as loss of proteins known to be critical in human spinocerebellar ataxias that is not observed in neocortex tissues. These results provide a hypothesis accounting for loss of protein integrity and cerebellum function in A-T.
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http://dx.doi.org/10.1016/j.molcel.2021.01.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026623PMC
April 2021

Anti-contamination SMART (Spectrum Monitoring Apparatus with Roll-to-roll Transparent film) window for optical diagnostics of plasma systems.

Rev Sci Instrum 2021 Jan;92(1):013507

Institute of Plasma Technology, Korea Institute of Fusion Energy (KFE), Gunsan 54004, Korea.

Optical emission spectroscopy is widely used in semiconductor and display manufacturing for plasma process monitoring. However, because of the contamination of the viewport, quantitative analysis is extremely difficult; therefore, qualitative analysis is used to detect species in the process. To extend plasma monitoring in advanced precise processes, the contamination problem of the viewport must be solved. We propose a new spectrum monitoring apparatus with a roll-to-roll transparent film window for optical diagnostics of a plasma system. By moving a transparent film in front of the viewport, contamination in the emission light path becomes negligible. However, the speed of the film should be optimized to reduce the maintenance period and to minimize measurement errors. We calculated the maximum thickness of SiO, SiN, ITO, and the Ar/CHF plasma contaminant to suppress the electron temperature error measured by the line-intensity-ratio within 2% at 2 eV. The thickness of the SiN, ITO, and Ar/CHF plasma contaminant should be thinner than 12.5 nm, 7.5 nm, and 100 nm, respectively.
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http://dx.doi.org/10.1063/5.0031869DOI Listing
January 2021

Identification and characterization of GAL4 drivers that mark distinct cell types and regions in the adult gut.

J Neurogenet 2020 Dec 16:1-11. Epub 2020 Dec 16.

Department of Biological Science, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.

The gastrointestinal tract in the adult serves as a model system for exploring the mechanisms underlying digestion, absorption and excretion, stem cell plasticity, and inter-organ communication, particularly through the gut-brain axis. It is also useful for studying the cellular and adaptive responses to dietary changes, alterations in microbiota and immunity, and systematic and endocrine signals. Despite the various cell types and distinct regions in the gastrointestinal tract, few tools are available to target and manipulate the activity of each cell type and region, and their gene expression. Here, we report 353 GAL4 lines and several split-GAL4 lines that are expressed in enteric neurons (ENs), progenitors (ISCs and EBs), enterocytes (ECs), enteroendocrine cells (EEs), or/and other cell types that are yet to be identified in distinct regions of the gut. We had initially collected approximately 600 GAL4 lines that may be expressed in the gut based on RNA sequencing data, and then crossed them to to perform immunohistochemistry to identify those that are expressed selectively in the gut. The cell types and regional expression patterns that are associated with the entire set of GAL4 drivers and split-GAL4 combinations are annotated online at http://kdrc.kr/index.php (K-Gut Project). This GAL4 resource can be used to target specific populations of distinct cell types in the fly gut, and therefore, should permit a more precise investigation of gut cells that regulate important biological processes.
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http://dx.doi.org/10.1080/01677063.2020.1853722DOI Listing
December 2020

Redox activation of ATM enhances GSNOR translation to sustain mitophagy and tolerance to oxidative stress.

EMBO Rep 2021 Jan 27;22(1):e50500. Epub 2020 Nov 27.

Department of Biology, Tor Vergata University, Rome, Italy.

The denitrosylase S-nitrosoglutathione reductase (GSNOR) has been suggested to sustain mitochondrial removal by autophagy (mitophagy), functionally linking S-nitrosylation to cell senescence and aging. In this study, we provide evidence that GSNOR is induced at the translational level in response to hydrogen peroxide and mitochondrial ROS. The use of selective pharmacological inhibitors and siRNA demonstrates that GSNOR induction is an event downstream of the redox-mediated activation of ATM, which in turn phosphorylates and activates CHK2 and p53 as intermediate players of this signaling cascade. The modulation of ATM/GSNOR axis, or the expression of a redox-insensitive ATM mutant influences cell sensitivity to nitrosative and oxidative stress, impairs mitophagy and affects cell survival. Remarkably, this interplay modulates T-cell activation, supporting the conclusion that GSNOR is a key molecular effector of the antioxidant function of ATM and providing new clues to comprehend the pleiotropic effects of ATM in the context of immune function.
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http://dx.doi.org/10.15252/embr.202050500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788447PMC
January 2021

The cancer-associated ATM R3008H mutation reveals the link between ATM activation and its exchange.

Cancer Res 2020 Nov 25. Epub 2020 Nov 25.

Pathology and Pediatrics, Columbia University

ATM kinase is a tumor suppressor and a master regulator of the DNA damage response. Most cancer-associated alterations to ATM are missense mutations at the PI3-kinase regulatory domain (PRD) or the kinase domain. Expression of kinase-dead ATM protein solely accelerates lymphomagenesis beyond ATM loss. To understand how PRD suppresses lymphomagenesis, we introduced the cancer-associated PRD mutation-R3008H (R3016 in mouse) into mice. R3008H abrogated DNA damage- and oxidative stress-induced activation of ATM without consistently affecting ATM protein stability and recruitment. In contrast to the early embryonic lethality of AtmKD/KD mice, AtmR3016H (AtmR/R) mice were viable, immunodeficient, and displayed spontaneous craniofacial abnormalities and delayed lymphomagenesis compared to Atm-/- controls. Mechanistically, R3008H rescued the tardy exchange of ATM-KD at DNA damage foci, indicating that PRD coordinates ATM activation with its exchange at DNA-breaks. Taken together, our results reveal a unique tumorigenesis profile for PRD mutations that is distinct from null or kinase-dead mutations.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-2447DOI Listing
November 2020

Boosting Activity and Selectivity of CO Electroreduction by Pre-Hydridizing Pd Nanocubes.

Small 2020 12 17;16(49):e2005305. Epub 2020 Nov 17.

Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA.

The electrochemical CO reduction reaction (CO RR) to syngas represents a promising solution to mitigate CO emissions and manufacture value-added chemicals. Palladium (Pd) has been identified as a potential candidate for syngas production via CO RR due to its transformation to Pd hydride under CO RR conditions, however, the pre-hydridized effect on the catalytic properties of Pd-based electrocatalysts has not been investigated. Herein, pre-hydridized Pd nanocubes (PdH ) supported on carbon black (PdH NCs/C) are directly prepared from a chemical reduction method. Compared with Pd nanocubes (Pd NCs/C), PdH NCs/C presented an enhanced CO RR performance due to its less cathodic phase transformation revealed by the in situ X-ray absorption spectroscopy. Density functional theory calculations revealed different binding energies of key reaction intermediates on PdH NCs/C and Pd NCs/C. Study of the size effect further suggests that NCs of smaller sizes show higher activity due to their more abundant active sites (edge and corner sites) for CO RR. The pre-hydridization and reduced NC size together lead to significantly improved activity and selectivity of CO RR.
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http://dx.doi.org/10.1002/smll.202005305DOI Listing
December 2020

Engineered Microsystems for Spheroid and Organoid Studies.

Adv Healthc Mater 2021 01 13;10(2):e2001284. Epub 2020 Nov 13.

Department of Mechanical Engineering, Chung-Ang University, Seoul, 06974, Republic of Korea.

3D in vitro model systems such as spheroids and organoids provide an opportunity to extend the physiological understanding using recapitulated tissues that mimic physiological characteristics of in vivo microenvironments. Unlike 2D systems, 3D in vitro systems can bridge the gap between inadequate 2D cultures and the in vivo environments, providing novel insights on complex physiological mechanisms at various scales of organization, ranging from the cellular, tissue-, to organ-levels. To satisfy the ever-increasing need for highly complex and sophisticated systems, many 3D in vitro models with advanced microengineering techniques have been developed to answer diverse physiological questions. This review summarizes recent advances in engineered microsystems for the development of 3D in vitro model systems. The relationship between the underlying physics behind the microengineering techniques, and their ability to recapitulate distinct 3D cellular structures and functions of diverse types of tissues and organs are highlighted and discussed in detail. A number of 3D in vitro models and their engineering principles are also introduced. Finally, current limitations are summarized, and perspectives for future directions in guiding the development of 3D in vitro model systems using microengineering techniques are provided.
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http://dx.doi.org/10.1002/adhm.202001284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855453PMC
January 2021

Effect of Binding Affinity of Crystal Water on the Electrochemical Performance of Layered Double Hydroxides.

ChemSusChem 2020 Dec 6;13(24):6546-6551. Epub 2020 Nov 6.

School of Chemical and Biological Engineering and Institute of Chemical Process, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826 (Republic of, Korea.

The ever-increasing demand for safe batteries has driven research efforts to develop aqueous rechargeable batteries. In this regard, Ni-based layered double hydroxides (LDHs) have received marked attention owing to their adequate operating potential, high specific capacity, and decent cycling performance. Nevertheless, the effect of immobile intercalants (e. g., crystal water and anions) that are inherently present in the interlayer galleries is barely understood. In this paper, we report that the electrochemical performance of LDH largely depends on the extent to which the crystallinity is affected by the binding strength of crystal water to the transition metal slabs. A series of infrared spectroscopy and in-situ X-ray absorption analyses reveal that the lattice disordering in LDHs is beneficial for accommodating the stress during the (de)intercalation of carrier ions, which serves as the origin of their superior specific capacities and cycle life. This study presents a useful structure-property relationship of the way in which the binding affinity of crystal water affects the key electrochemical properties of the host electrode materials.
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http://dx.doi.org/10.1002/cssc.202002306DOI Listing
December 2020

Drosophila as a model system for deciphering the 'host physiology-nutrition-microbiome' axis.

Curr Opin Insect Sci 2020 10 23;41:112-119. Epub 2020 Sep 23.

School of Biological Science, Seoul National University and National Creative Research Initiative Center for Hologenomics, Seoul 151-742, South Korea. Electronic address:

For metazoans, nutritional stressors, such as undernutrition during growth and development, results in serious outcomes, including growth impairments and organ wasting. When undernutrition is accompanied by other complications, including chronic inflammation, a more complex pathophysiology may emerge, such as environmental enteropathy. Although nutrition is one of the most important environmental factors that influences host physiology, the mechanism by which undernutrition induces host pathophysiology is not fully understood. Recently, gut microbiome was found to alleviate undernutrition-induced pathophysiology in an insect model, revealing the importance of nutrition-microbiome interactions. Here, we discussed how nutrition-microbiome interactions influence host physiology, including growth, tissue homeostasis, immunity, and behavior, by regulating the central metabolic signaling pathways with an emphasis on findings made through Drosophila, an insect model.
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http://dx.doi.org/10.1016/j.cois.2020.09.005DOI Listing
October 2020

Open-to-Air RAFT Polymerization on a Surface under Ambient Conditions.

Langmuir 2020 Oct 24;36(39):11538-11545. Epub 2020 Sep 24.

Department of Chemistry, Chungnam National University, Daejeon 34134, Republic of Korea.

Oxygen (O)-mediated controlled radical polymerization was performed on surfaces under ambient conditions, enabling on-surface polymer brush growth under open-to-air conditions at room temperature in the absence of metal components. Polymerization of zwitterionic monomers using this O-mediated surface-initiated reversible addition fragmentation chain-transfer (O-SI-RAFT) method yielded hydrophilic surfaces that exhibited anti-biofouling effects. O-SI-RAFT polymerization can be performed on large surfaces under open-to-air conditions. Various monomers including (meth)acrylates and acrylamides were employed for O-SI-RAFT polymerization; the method is thus versatile in terms of the polymers used for coating and functionalization. A wide range of hydrophilic and hydrophobic monomers can be employed. In addition, the end-group functionality of the polymer grown by O-SI-RAFT polymerization allowed chain extension to form block copolymer brushes on a surface.
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http://dx.doi.org/10.1021/acs.langmuir.0c01947DOI Listing
October 2020

Proteome-wide identification of HSP70/HSC70 chaperone clients in human cells.

PLoS Biol 2020 07 20;18(7):e3000606. Epub 2020 Jul 20.

The Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, United States of America.

The 70 kDa heat shock protein (HSP70) family of chaperones are the front line of protection from stress-induced misfolding and aggregation of polypeptides in most organisms and are responsible for promoting the stability, folding, and degradation of clients to maintain cellular protein homeostasis. Here, we demonstrate quantitative identification of HSP70 and 71 kDa heat shock cognate (HSC70) clients using a ubiquitin-mediated proximity tagging strategy and show that, despite their high degree of similarity, these enzymes have largely nonoverlapping specificities. Both proteins show a preference for association with newly synthesized polypeptides, but each responds differently to changes in the stoichiometry of proteins in obligate multi-subunit complexes. In addition, expression of an amyotrophic lateral sclerosis (ALS)-associated superoxide dismutase 1 (SOD1) mutant protein induces changes in HSP70 and HSC70 client association and aggregation toward polypeptides with predicted disorder, indicating that there are global effects from a single misfolded protein that extend to many clients within chaperone networks. Together these findings show that the ubiquitin-activated interaction trap (UBAIT) fusion system can efficiently isolate the complex interactome of HSP chaperone family proteins under normal and stress conditions.
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http://dx.doi.org/10.1371/journal.pbio.3000606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392334PMC
July 2020

Electrochemical Conversion of CO to Syngas with Palladium-Based Electrocatalysts.

Acc Chem Res 2020 Aug 14;53(8):1535-1544. Epub 2020 Jul 14.

Department of Chemical Engineering, Columbia University, New York, New York 10027, United States.

ConspectusElectrocatalytic reduction of CO is a desirable method to produce valuable products from CO. One of the main research challenges for electrocatalysis that produces carbon-containing products from CO is avoiding unwanted hydrogen production. Instead of totally eliminating hydrogen, our approach makes use of the readily available protons in aqueous electrolyte to coproduce CO and H, making synthesis gas (syngas) with a tunable CO:H ratio; the resulting syngas can then be used as feedstock for existing thermocatalytic processes such as Fischer-Tropsch and methanol synthesis reactions. We discovered that palladium hydride (PdH), formed under electrocatalytic reaction conditions, is an effective electrocatalyst that enables this unique product distribution. We employed in situ synchrotron techniques to determine the formation of the PdH phase during electrocatalytic reduction of CO. We also performed density functional theory (DFT) calculations to determine the binding energies of key intermediates on PdH to identify descriptors to correlate experimentally observed trends in activity and selectivity.Since first reporting on the potential application of PdH to produce syngas, our research group has refined control over the syngas product selectivity, improved the activity, and reduced the loading of Pd in electrocatalysts. We achieved this by the following approaches: understanding the structure-function relationship with shape-controlled Pd nanoparticles, determining the cation and isotopic effects of electrolyte, alloying Pd with inexpensive secondary metals, supporting Pd on transition metal carbides and nitrides, and utilizing single atom Pd catalysts. At each step, we monitored the phase transition from Pd to PdH under reaction conditions with in situ synchrotron-based X-ray absorption and X-ray diffraction techniques by identifying the onset potential for the appearance of the characteristic Pd-Pd bond length and diffraction patterns associated with PdH formation. We also identified descriptors for syngas production on PdH, bimetallic PdH, and supported PdH catalysts by correlating DFT calculations of PdH stability in different catalytic systems as well as the effect of PdH formation on the binding strength of reaction intermediates. The research methodology established here is useful not only for continued optimization of Pd-based syngas-producing electrocatalysts but also for enhancing activity while reducing the loading of precious metals for other electrocatalytic applications. Moreover, we feel the advances in electrocatalytic syngas production described here represent a critical step toward sustainable CO utilization that should inspire continued efforts.
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http://dx.doi.org/10.1021/acs.accounts.0c00277DOI Listing
August 2020

Two short antimicrobial peptides derived from prosaposin-like proteins in the starry flounder (Platichthys stellatus).

Fish Shellfish Immunol 2020 Oct 30;105:95-103. Epub 2020 Jun 30.

Institute of Marine Industry, College of Marine Science, Gyeongsang National University, 455, Tongyeong, 650-160, Republic of Korea. Electronic address:

Prosaposin (PSAP) is a precursor of saposin (SAP), which is present in lysosomal and secreted proteins. PSAP is a member of the SAP-like protein families, which comprise multifunctional proteins. In particular, their antimicrobial activity has been reported. We identified PSAP-like (PsPSAPL) sequences from starry flounder and analysed their expression and antimicrobial activity based on cDNA and amino acid sequences. PsPSAPL showed conservation of three saposin B type domains at high levels, and PsPSAPL mRNA was relatively abundantly distributed in the brain and gills of healthy starry founders. PsPSAPL mRNA showed significant expression changes in response to viral haemorrhagic septicaemia virus and Streptococcus parauberis. Synthetic peptides (PsPSAPL-1 and -2), prepared based on amino acid sequences, were used to confirm as well as analyse the antimicrobial activity against bacteria and parasites. Consequently, PsPSAPL-1 and -2 were found to significantly inhibit the growth of various bacteria and kill the Miamiensis avidus. In addition, bacterial biofilm formation was significantly inhibited. Safety was also confirmed by analysing cell haemolysis. These results indicate the immunological function of PsPSAP and the potential antimicrobial activity of the AMPs PsPSAPL-1 and -2.
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http://dx.doi.org/10.1016/j.fsi.2020.05.075DOI Listing
October 2020

Development of pyrazolo[3,4-d]pyrimidine-6-amine-based TRAP1 inhibitors that demonstrate in vivo anticancer activity in mouse xenograft models.

Bioorg Chem 2020 08 15;101:103901. Epub 2020 Jun 15.

College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, South Korea; Western Seoul Center, Korea Basic Science Institute, Seoul 03760, South Korea. Electronic address:

TNF Receptor Associated Protein 1 (TRAP1) is a mitochondrial paralog of Hsp90 related to the promotion of tumorigenesis in various cancers via maintaining mitochondrial integrity, reducing the production of reactive oxygen species, and reprogramming cellular metabolism. Consequently, Hsp90 and TRAP1 have been targeted to develop cancer therapeutics. Herein, we report a series of pyrazolo[3,4-d]pyrimidine derivatives that are mitochondria-permeable TRAP1 inhibitors. Structure-based drug design guided the optimization of potency, leading to the identification of compounds 47 and 48 as potent TRAP1 and Hsp90 inhibitors with good metabolic and plasma stability as well as acceptable CYP and hERG inhibition. X-ray co-crystallization studies confirmed both 47 and 48 interact with the ATP binding pocket in the TRAP1 protein. Compounds 47 and 48 demonstrated excellent anticancer efficiency in various cancer cells, with limited toxicity over normal hepatocyte and prostate cells. Mouse PC3 xenograft studies showed 47 and 48 significantly reduced tumor growth.
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http://dx.doi.org/10.1016/j.bioorg.2020.103901DOI Listing
August 2020

Enhancer RNAs Mediate Estrogen-Induced Decommissioning of Selective Enhancers by Recruiting ERα and Its Cofactor.

Cell Rep 2020 06;31(12):107803

Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. Electronic address:

The function of enhancer RNAs (eRNAs) in transcriptional regulation remains obscure. By analyzing the genome-wide nascent transcript profiles in breast cancer cells, we identify a special group of eRNAs that are essential for estrogen-induced transcriptional repression. Using eRNAs of TM4SF1 and EFEMP1 as the paradigms, we find that these RNA molecules not only stabilize promoter-enhancer interactions but also recruit liganded estrogen receptor α (ERα) to particular enhancer regions, facilitate the formation of a functional transcriptional complex, and cause gene silencing. Interestingly, ERα is shown to directly bind with eRNAs by its DNA-binding domain. These eRNAs help with the formation of a specific ERα-centered transcriptional complex and promote the association of the histone demethylase KDM2A, which dismisses RNA polymerase II from designated enhancers and suppresses the transcription of target genes. Our work demonstrates a complete mechanism underlying the action of eRNAs in modulating and refining the locus-specific transcriptional program.
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http://dx.doi.org/10.1016/j.celrep.2020.107803DOI Listing
June 2020

Relationship between Decreased Estimated Glomerular Filtration Rate and Sarcopenic Obesity among Postmenopausal Women: Korea National Health and Nutrition Examination Survey (2008-2011).

Korean J Fam Med 2020 Sep 21;41(5):332-338. Epub 2020 May 21.

Department of Family Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Korea.

Background: Previous studies have shown that body composition is associated with chronic kidney disease (CKD), and perimenopause is associated with increased fat mass and decreased lean body mass. Muscle wasting is common among patients with CKD. Sarcopenic obesity (SO) refers to excess adiposity with decreased muscle mass. However, little is known about the relationship between SO and renal function decline. Here, we identified the relationship between SO and decreased estimated glomerular filtration rate (eGFR) in postmenopausal women.

Methods: We conducted a cross-sectional study based on the data from the Korea National Health and Nutrition Examination Survey (2008-2011). We analyzed 4,560 postmenopausal women who underwent dual energy X-ray absorptiometry. Sarcopenia was defined based on weight-adjusted appendicular skeletal muscle mass. Obesity was defined based on body mass index. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Subjects were classified into four groups: normal, obese, sarcopenic, and sarcopenic obese. Logistic regression analysis was performed to examine the association between SO and decreased eGFR. The results were adjusted for variable confounders.

Results: In the unadjusted model, the odds ratio (OR) of decreased eGFR for SO was 1.67 (95% confidence interval [CI], 1.23-2.26). The obese and sarcopenic groups had ORs of 0.67 (95% CI, 0.44-1.03) and 0.70 (95% CI, 0.44-1.10), respectively. After controlling for confounding variables, there was also a significant association between SO and decreased eGFR (adjusted OR, 1.48; 95% Cl, 1.05-2.07).

Conclusion: SO was independently associated with decreased eGFR in postmenopausal Korean women.
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http://dx.doi.org/10.4082/kjfm.19.0032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509127PMC
September 2020

Comparison of the Prognostic Factors of Fetuses With Congenital Pulmonary Airway Malformations According to Type.

J Ultrasound Med 2020 Nov 18;39(11):2243-2252. Epub 2020 May 18.

Departments of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

Objectives: To compare the prognostic factors of fetuses with microcystic and macrocystic congenital pulmonary airway malformations (CPAMs).

Methods: We retrospectively evaluated fetuses with CPAMs at Asan Medical Center. The CPAM size, mass effect, and maximum cyst size in macrocystic CPAMs were evaluated prenatally. The adverse postnatal outcomes, including respiratory symptoms, mechanical ventilation, and surgery, were evaluated.

Results: In 118 cases, 2 fetal deaths and 1 neonatal death occurred. All cases of fetal hydrops and complete regression after birth were in the macrocystic and microcystic CPAM groups, respectively. Twenty-four neonates (20.7%) had respiratory symptoms, and 18 (15.5%) required mechanical ventilation. Sixty-three neonates (54.3%) underwent surgery, of whom 21 (33.3%) required surgery in the neonatal period. The maximum congenital pulmonary airway malformation volume ratio was significantly associated with all postnatal outcomes (P < .05), and the optimal cutoff values were lower for respiratory symptoms, mechanical ventilation, and neonatal surgery in the macrocystic CPAMs. The maximum cyst size was also associated with all postnatal outcomes in macrocystic CPAMs (P < .05).

Conclusions: Different cutoff values for the maximum congenital pulmonary airway malformation volume ratio should be applied according to the CPAM type for the prediction of postnatal outcomes. The maximum cyst size can also be a useful prognostic factor in macrocystic CPAMs.
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http://dx.doi.org/10.1002/jum.15335DOI Listing
November 2020

Hierarchically Designed Cathodes Composed of Vanadium Hexacyanoferrate@Copper Hexacyanoferrate with Enhanced Cycling Stability.

ACS Appl Mater Interfaces 2020 Jun 13;12(22):24817-24826. Epub 2020 May 13.

Materials Center for Energy Convergence, Surface Technology Division, Korea Institute of Materials Science, 797 Changwondae-ro, Seongsan-gu, Changwon, Gyeongnam 51508, Republic of Korea.

Prussian blue analogues (PBAs) have been highlighted as electrode materials for aqueous rechargeable batteries (ARBs) because of their favorable crystal structure and electrochemical activity. However, dissolution of the transition-metal ions during cycling degrades the materials and hinders the development of long-life-span batteries. To overcome this limitation, a strategy to revive the capacity degradation of PBA-based cathodes was developed herein based on designing all-PBA-based core@shell materials, while specific reduction upon introducing the shell layers was minimized. The core@shell materials were constructed using a V/Fe PBA (high capacity) core and a Cu/Fe PBA (high cycling stability) shell via a two-step co-precipitation method. The electrochemical performances including specific capacity, cycling stability, and rate capability as a function of the Cu/Fe PBA shell thickness were explored. At the optimal Cu/Fe PBA thickness, improved capacity retention after 200 cycles of >90% (72% for the core only) was attained with negligible capacity reductions from 94 (core only) to 90 (core@shell) mA h g, arising from the high electrochemical activity and stability of the Cu/Fe PBA shell and stabilized interfaces due to the crystallographic coherence between the core and shell materials. In addition, the power performance of the core@shell materials was significantly improved, e.g., C/C for a core@shell of 80% and core only of 62%, arising from the unique chemical coordination and facile ion diffusion kinetics of the Cu/Fe PBA shell. The newly developed V/Fe@Cu/Fe PBA-based cathodes offer an effective strategy for fabricating sustainable and low-cost ARBs.
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http://dx.doi.org/10.1021/acsami.0c05458DOI Listing
June 2020

Promoting HO production via 2-electron oxygen reduction by coordinating partially oxidized Pd with defect carbon.

Nat Commun 2020 May 1;11(1):2178. Epub 2020 May 1.

Department of NanoEngineering, University of California San Diego, La Jolla, California, 92093, USA.

Electrochemical synthesis of HO through a selective two-electron (2e) oxygen reduction reaction (ORR) is an attractive alternative to the industrial anthraquinone oxidation method, as it allows decentralized HO production. Herein, we report that the synergistic interaction between partially oxidized palladium (Pd) and oxygen-functionalized carbon can promote 2e ORR in acidic electrolytes. An electrocatalyst synthesized by solution deposition of amorphous Pd clusters (Pd and Pd) onto mildly oxidized carbon nanotubes (Pd-OCNT) shows nearly 100% selectivity toward HO and a positive shift of ORR onset potential by ~320 mV compared with the OCNT substrate. A high mass activity (1.946 A mg at 0.45 V) of Pd-OCNT is achieved. Extended X-ray absorption fine structure characterization and density functional theory calculations suggest that the interaction between Pd clusters and the nearby oxygen-containing functional groups is key for the high selectivity and activity for 2e ORR.
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http://dx.doi.org/10.1038/s41467-020-15843-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195490PMC
May 2020

Reactions of CO and ethane enable CO bond insertion for production of C3 oxygenates.

Nat Commun 2020 Apr 20;11(1):1887. Epub 2020 Apr 20.

Chemistry Division, Brookhaven National Laboratory, Upton, NY, 11973, USA.

Reacting CO and ethane to synthesize value-added oxygenate molecules represents opportunities to simultaneously reduce CO emissions and upgrade underutilized ethane in shale gas. Herein, we propose a strategy to produce C3 oxygenates using a tandem reactor. This strategy is achieved with a FeNi/CeO catalyst (first reactor at 600-800 °C) for CO-assisted dehydrogenation and reforming of ethane to produce ethylene, CO, and H, and a RhCo/MCM-41 catalyst (second reactor at 200 °C) enabling CO insertion for the production of C3 oxygenates (propanal and 1-propanol) via the heterogeneous hydroformylation reaction at ambient pressure. In-situ characterization using synchrotron spectroscopies and density functional theory (DFT) calculations reveal the effect of Rh-Co bimetallic formation in facilitating the production of C3 oxygenates. The proposed strategy provides an opportunity for upgrading light alkanes in shale gas by reacting with CO to produce aldehydes and alcohols.
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http://dx.doi.org/10.1038/s41467-020-15849-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170877PMC
April 2020

Transition Metal Nitrides as Promising Catalyst Supports for Tuning CO/H Syngas Production from Electrochemical CO Reduction.

Angew Chem Int Ed Engl 2020 Jul 11;59(28):11345-11348. Epub 2020 May 11.

Department of Chemical Engineering, Columbia University, 821 Mudd Building, New York, NY, 10027, USA.

The electrochemical carbon dioxide reduction reaction (CO RR) to produce synthesis gas (syngas) with tunable CO/H ratios has been studied by supporting Pd catalysts on transition metal nitride (TMN) substrates. Combining experimental measurements and density functional theory (DFT) calculations, Pd-modified niobium nitride (Pd/NbN) is found to generate much higher CO and H partial current densities and greater CO Faradaic efficiency than Pd-modified vanadium nitride (Pd/VN) and commercial Pd/C catalysts. In-situ X-ray diffraction identifies the formation of PdH in Pd/NbN and Pd/C under CO RR conditions, whereas the Pd in Pd/VN is not fully transformed into the active PdH phase. DFT calculations show that the stabilized *HOCO and weakened *CO intermediates on PdH/NbN are critical to achieving higher CO RR activity. This work suggests that NbN is a promising substrate to modify Pd, resulting in an enhanced electrochemical conversion of CO to syngas with a potential reduction in precious metal loading.
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http://dx.doi.org/10.1002/anie.202003625DOI Listing
July 2020

High-flow nasal cannula oxygen therapy in idiopathic pulmonary fibrosis patients with respiratory failure.

J Thorac Dis 2020 Mar;12(3):966-972

Department of Pulmonary and Critical Care Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.

Background: High-flow nasal cannula (HFNC) oxygen therapy is widely applied in idiopathic pulmonary fibrosis (IPF) patients with acute respiratory failure (ARF); however, its advantages over mechanical ventilation (MV) remain unclear. We aimed to compare the clinical outcomes of HFNC oxygen therapy and MV in IPF patients with respiratory failure.

Methods: A retrospective descriptive study of patients with IPF admitted between January 2015 and December 2017 who underwent HFNC oxygen therapy or MV during hospitalization was conducted. The primary outcome was the comparison of in-hospital mortality among HFNC only group, MV with prior HFNC group, and MV only group.

Results: A total of 61 patients with IPF and ARF were included in the current study. Forty-five patients received HFNC oxygen therapy without endotracheal intubation and 16 received MV. The overall hospital mortality rate was 59.0%, of which 53.3% was for HFNC oxygen therapy and 55.6% (5/9) for MV only group (P=1.000). Although no significant difference in the mortality rate was observed among three groups, that of MV with prior HFNC oxygen therapy (n=7) was 100% (P=0.064). Additionally, the HFNC oxygen therapy group showed shorter length of hospital and ICU stay than the MV group (P<0.001).

Conclusions: Patients with IPF and ARF who received MV with prior HFNC oxygen therapy showed increased mortality rate than those who received HFNC only oxygen therapy or MV. Considering the complication rate of MV, need for lung transplantation, and the will to undergo end-of-life care, a proper transition from HFNC oxygen therapy to MV should be planned cautiously.
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http://dx.doi.org/10.21037/jtd.2019.12.48DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138991PMC
March 2020

Current use and management of commercial fish vaccines in Korea.

Fish Shellfish Immunol 2020 Jul 6;102:20-27. Epub 2020 Apr 6.

Aquatic Disease Control Division, National Institute of Fisheries Science (NIFS), 216 Gijanghaean-ro, Gijang-eup, Gijang-gun, Busan, 46083, Republic of Korea.

The aquaculture industry in Korea has grown rapidly since the 1960s, and it is a major food source. However, the expansion of aquaculture systems has increased the chances of infectious disease outbreaks, and vaccination plays an important role in commercial fish farming. This is the first comprehensive review of commercial fish vaccines in Korea. It not only provides an overview of commercially available fish vaccines and their associated approval processes and laws, but also some perspectives on research advances regarding fish vaccines in Korea. In Korea, fish vaccines are approved only after their safety and effectiveness have been verified according to the Pharmaceutical Affairs Act, and after approval, each vaccine lot must pass the national evaluation criteria. As of the end of 2019, 29 vaccines were approved for 10 fish pathogens, including both single and combination vaccines containing more than two inactivated pathogens. The approved fish vaccines consist of 2 immersion vaccines, as well as 1 intramuscular and 26 intraperitoneal vaccines, which require syringe injection. All the 29 vaccines are manufactured as formalin-inactivated vaccines; 1 is an adjuvant vaccine and 28 are non-adjuvant vaccines; 25 are bacterial vaccines, 2 are viral vaccines, 1 is a parasite vaccine, and 1 is a parasite and bacterial vaccine. In terms of the target fish species, 27 vaccines are used in the olive flounder (Paralichthys olivaceus), 1 in the starry flounder (Platichthys stellatus), and 1 in the red seabream (Pagrus major), striped beakfish (Oplegnathus fasciatus), and amberjack (Seriola quinqueradiata). This imbalance exists mostly because the olive flounder is the main farmed fish species in Korea. In 2018, 67.71 million vaccine doses were distributed following satisfactory performance in the national evaluation. They were used to vaccinate approximately 80.6% of farmed olive flounders.
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http://dx.doi.org/10.1016/j.fsi.2020.04.004DOI Listing
July 2020

Mitochondria at the crossroads of ATM-mediated stress signaling and regulation of reactive oxygen species.

Redox Biol 2020 05 21;32:101511. Epub 2020 Mar 21.

The Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, 78712, USA. Electronic address:

The Ataxia-telangiectasia mutated (ATM) kinase responds to DNA double-strand breaks and other forms of cellular stress, including reactive oxygen species (ROS). Recent work in the field has uncovered links between mitochondrial ROS and ATM activation, suggesting that ATM acts as a sensor for mitochondrial derived ROS and regulates ROS accumulation in cells through this pathway. In addition, characterization of cells from Ataxia-telangiectasia patients as well as ATM-deficient mice and cell models suggest a role for ATM in modulating mitochondrial gene expression and function. Here we review ROS responses related to ATM function, recent evidence for ATM roles in mitochondrial maintenance and turnover, and the relationship between ATM and regulation of protein homeostasis.
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http://dx.doi.org/10.1016/j.redox.2020.101511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115119PMC
May 2020

Solution-Processed Organic Light-Emitting Diodes Using a Photo-Crosslinkable Hole-Transporting Layer.

J Nanosci Nanotechnol 2020 Aug;20(8):4661-4665

Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 46241, Republic of Korea.

Photo-crosslinkable hole transporting layer (HTL) consisting of a blend of poly(bis-4-butylphenyl-N,N-bisphenyl)benzidine (poly-TPD) and bis(4-azido-2,3,5,6-tetrafluorobenzoate) (FPA) was applied to red and green organic light-emitting diodes (OLEDs) by solution processing. This photocrosslinking reaction rendered the HTL insoluble in organic solvents and enabled subsequent solution deposition of an upper emissive layer. The solvent resistance of the photo-crosslinked poly-TPD:FPA (1 wt%) film was enhanced compared to that of the non-crosslinked neat poly-TPD film. Solution-processed red and green OLEDs with the poly-TPD:FPA (1 wt%) photo-crosslinked HTL exhibited higher device performances than those with the non-crosslinked poly-TPD HTL.
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http://dx.doi.org/10.1166/jnn.2020.17832DOI Listing
August 2020

Metal-organic Framework-driven Porous Cobalt Disulfide Nanoparticles Fabricated by Gaseous Sulfurization as Bifunctional Electrocatalysts for Overall Water Splitting.

Sci Rep 2019 Dec 20;9(1):19539. Epub 2019 Dec 20.

Department of Materials Science & Engineering, Seoul National University, Seoul, 08826, Republic of Korea.

Both high activity and mass production potential are important for bifunctional electrocatalysts for overall water splitting. Catalytic activity enhancement was demonstrated through the formation of CoS nanoparticles with mono-phase and extremely porous structures. To fabricate porous structures at the nanometer scale, Co-based metal-organic frameworks (MOFs), namely a cobalt Prussian blue analogue (Co-PBA, Co[Co(CN)]), was used as a porous template for the CoS. Then, controlled sulfurization annealing converted the Co-PBA to mono-phase CoS nanoparticles with ~ 4 nm pores, resulting in a large surface area of 915.6 m g. The electrocatalysts had high activity for overall water splitting, and the overpotentials of the oxygen evolution reaction and hydrogen evolution reaction under the operating conditions were 298 mV and -196 mV, respectively, at 10 mA cm.
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http://dx.doi.org/10.1038/s41598-019-56084-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925291PMC
December 2019

Discovery of 2-((4-resorcinolyl)-5-aryl-1,2,3-triazol-1-yl)acetates as potent Hsp90 inhibitors with selectivity over TRAP1.

Bioorg Med Chem Lett 2020 01 11;30(2):126809. Epub 2019 Nov 11.

College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, South Korea; Western Seoul Center, Korea Basic Science Institute, Seoul 03760, South Korea. Electronic address:

As the most abundant heat shock protein (HSP), Hsp90 is actively involved in tumor cell growth and various responses to anti-carcinogenic stress. Hsp90 has thus emerged as a potential drug target. A structure-based drug design approach was applied to develop novel resorcinolyltriazole derivatives as Hsp90 inhibitors. Structure-activity relationships (SARs) and molecular docking were investigated to provide a rationale for binding affinity and paralog selectivity. Click chemistry between iodoethynylresorcinol and an azido derivative was used to synthesize a new family of 2-((4-resorcinolyl)-5-aryl-1,2,3-triazol-1-yl) acetates that exhibited Hsp90 binding affinities of 40-100 nM (IC). Among the synthesized molecules, the triazole alkyl acetates displayed the highest Hsp90 binding affinities. Their potency against Hsp90 was over 100-fold stronger than against TRAP1 and 1-3-fold stronger than against Grp94. In particular, compounds 18, 19, and 30 had Hsp90 inhibitory activities of ~45 nM (IC) and they displayed over 350-fold selectivity for Hsp90 over TRAP1.
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http://dx.doi.org/10.1016/j.bmcl.2019.126809DOI Listing
January 2020