Publications by authors named "Jin-Hong Kim"

234 Publications

Suppression of Osteoarthritis progression by post-natal Induction of Nkx3.2.

Biochem Biophys Res Commun 2021 Jul 27;571:188-194. Epub 2021 Jul 27.

Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea. Electronic address:

Osteoarthritis (OA) is an incurable joint disease affecting 240 million elderly population, and major unmet medical needs exist for better therapeutic options for OA. During skeletal development, Nkx3.2 has been shown to promote chondrocyte differentiation and survival, but to suppress cartilage hypertrophy and blood vessel invasion. Here we show that Nkx3.2 plays a key role in osteoarthritis (OA) pathogenesis. Marked reduction of Nkx3.2 expression was observed in three different murine OA models. Consistent with these findings, analyses of surgery-induced and age-driven OA models revealed that cartilage-specific post-natal induction of Nkx3.2 can suppress OA progression in mice. These results suggest that Nkx3.2 may serve as a promising target for OA drug development.
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http://dx.doi.org/10.1016/j.bbrc.2021.07.074DOI Listing
July 2021

Double J-Coupling Strategy for Near Infrared Emitters.

J Am Chem Soc 2021 Jul 29. Epub 2021 Jul 29.

Institut für Organische Chemie, Universität Würzburg, 97074 Würzburg, Germany.

Fluorophores emitting in the near-infrared (NIR) are highly desired for various applications, but increasing nonradiative rates cause severe fluorescence quenching for wavelengths beyond 800 nm. Here, a bis(squaraine) dye is reported that bears two NIR dyes in a head-to-tail chromophore arrangement. This arrangement leads to molecular J-type exciton coupling, resulting in an absorption maximum at 961 nm and a fluorescence peak at 971 nm with a quantum yield of 0.33% in chloroform. In less polar toluene, the bis(squaraine) self-assembles into nanofibers, affording another bathochromic shift with an absorption maximum at 1095 nm and a fluorescence peak at 1116 nm originating from molecular J-type coupling.
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http://dx.doi.org/10.1021/jacs.1c05934DOI Listing
July 2021

BL-11C Micro-MX: a high-flux microfocus macromolecular-crystallography beamline for micrometre-sized protein crystals at Pohang Light Source II.

J Synchrotron Radiat 2021 Jul 1;28(Pt 4):1210-1215. Epub 2021 Jun 1.

Pohang Accelerator Laboratory, Pohang University of Science and Technology, 80 Jigokro-127-Beongil, Pohang, Nam-gu, Gyeongbuk 37673, Republic of Korea.

BL-11C, a new protein crystallography beamline, is an in-vacuum undulator-based microfocus beamline used for macromolecular crystallography at the Pohang Accelerator Laboratory and it was made available to users in June 2017. The beamline is energy tunable in the range 5.0-20 keV to support conventional single- and multi-wavelength anomalous-dispersion experiments against a wide range of heavy metals. At the standard working energy of 12.659 keV, the monochromated beam is focused to 4.1 µm (V) × 8.5 µm (H) full width at half-maximum at the sample position and the measured photon flux is 1.3 × 10 photons s. The experimental station is equipped with a Pilatus3 6M detector, a micro-diffractometer (MD2S) incorporating a multi-axis goniometer, and a robotic sample exchanger (CATS) with a dewar capacity of 90 samples. This beamline is suitable for structural determination of weakly diffracting crystalline substances, such as biomaterials, including protein, nucleic acids and their complexes. In addition, serial crystallography experiments for determining crystal structures at room temperature are possible. Herein, the current beamline characteristics, technical information for users and some recent scientific highlights are described.
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http://dx.doi.org/10.1107/S1600577521004355DOI Listing
July 2021

Regulation of Dual Activity of Ascorbate Peroxidase 1 From by Conformational Changes and Posttranslational Modifications.

Front Plant Sci 2021 14;12:678111. Epub 2021 Jun 14.

Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, South Korea.

Ascorbate peroxidase (APX) is an important reactive oxygen species (ROS)-scavenging enzyme, which catalyzes the removal of hydrogen peroxide (HO) to prevent oxidative damage. The peroxidase activity of APX is regulated by posttranslational modifications (PTMs), such as S-nitrosylation, tyrosine nitration, and S-sulfhydration. In addition, it has been recently reported that APX functions as a molecular chaperone, protecting rice against heat stress. In this study, we attempted to identify the various functions of APX in and the effects of PTMs on these functions. Cytosol type APX1 from (AtAPX1) exists in multimeric forms ranging from dimeric to high-molecular-weight (HMW) complexes. Similar to the rice APX2, AtAPX1 plays a dual role behaving both as a regular peroxidase and a chaperone molecule. The dual activity of AtAPX1 was strongly related to its structural status. The main dimeric form of the AtAPX1 protein showed the highest peroxidase activity, whereas the HMW form exhibited the highest chaperone activity. Moreover, studies indicated that the structure of AtAPX1 was regulated by heat and salt stresses, with both involved in the association and dissociation of complexes, respectively. Additionally, we investigated the effects of S-nitrosylation, S-sulfhydration, and tyrosine nitration on the protein structure and functions using gel analysis and enzymatic activity assays. S-nitrosylation and S-sulfhydration positively regulated the peroxidase activity, whereas tyrosine nitration had a negative impact. However, no effects were observed on the chaperone function and the oligomeric status of AtAPX1. Our results will facilitate the understanding of the role and regulation of APX under abiotic stress and posttranslational modifications.
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http://dx.doi.org/10.3389/fpls.2021.678111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236860PMC
June 2021

Application of Gamma Ray-Responsive Genes for Transcriptome-Based Phytodosimetry in Rice.

Plants (Basel) 2021 May 13;10(5). Epub 2021 May 13.

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

Transcriptome-based dose-response curves were recently applied to the phytodosimetry of gamma radiation in a dicot plant, , as an alternative biological assessment of genotoxicity using DNA damage response (DDR) genes. In the present study, we characterized gamma ray-responsive marker genes for transcriptome-based phytodosimetry in a monocot plant, rice ( L.), and compared different phytodosimetry models between rice and using gamma-H2AX, comet, and quantitative transcriptomic assays. The transcriptome-based dose-response curves of four marker genes (, , and ) were reliably fitted to quadratic or exponential decay equations ( > 0.99). However, the single or integrated dose-response curves of these genes were distinctive from the conventional models obtained by the gamma-H2AX or comet assays. In comparison, rice displayed a higher dose-dependency in the comet signal and transcription, while the gamma-H2AX induction was more dose-dependent in . The dose-dependent transcriptions of the selected gamma-ray-inducible marker genes, including , , , and in rice and , , , and in , were maintained similarly at different vegetative stages. These results suggested that the transcriptome-based phytodosimetry model should be further corrected with conventional genotoxicity- or DDR-based models despite the high reliability or dose-dependency of the model. In addition, the relative weighting of each gene in the integrated transcriptome-based dose-response model using multiple genes needs to be considered based on the trend and amplitude of the transcriptional change.
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http://dx.doi.org/10.3390/plants10050968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152246PMC
May 2021

Outcomes and Loop Pattern Analysis of a Road-Map Technique for ERCP with Side-Viewing Duodenoscope in Patients with Billroth II Gastrectomy (with Video).

J Pers Med 2021 May 12;11(5). Epub 2021 May 12.

Department of Gastroenterology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Korea.

Endoscopic retrograde cholangiopancreatography (ERCP) in patients who have undergone a Billroth II gastrectomy is a major challenge. This study aimed to evaluate the outcomes of the road-map technique for duodenal intubation using a side-viewing duodenoscope for ERCP in Billroth II gastrectomy patients with naïve papilla, and to analyze the formation and release patterns of common bowel loops that occur when the duodenoscope navigates the afferent limb. The duodenoscopy approach success rate was 85.8% (97/113). In successful duodenoscopy approach patients, there were five bowel looping patterns that occurred when the preceding catheter-connected duodenoscope was advanced into the duodenum: (1) reverse ɣ-loop (29.9%), (2) fixed reverse ɣ-loop (5.2%), (3) simple U-loop (22.7%), (4) N-loop (28.9%), and (5) reverse alpha loop (13.4%). The duodenoscopy cannulation and duodenoscopy therapeutic success rates were 81.4% (92/113) and 80.5% (91/113), respectively, while the overall cannulation and therapeutic success rates were 92.0% (104/113) and 87.6% (99/113), respectively. Bowel perforation occurred in three patients (2.7%). The road-map technique may benefit duodenoscope-based ERCP in Billroth II gastrectomy patients by minimizing the tangential axis alignment between the duodenoscopic tip and driving of the afferent limb, and by predicting and counteracting bowel loops that occur when the duodenoscope navigates the afferent limb.
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http://dx.doi.org/10.3390/jpm11050404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150314PMC
May 2021

An Efficient Narrowband Near-Infrared at 1040 nm Organic Photodetector Realized by Intermolecular Charge Transfer Mediated Coupling Based on a Squaraine Dye.

Adv Mater 2021 Jul 31;33(26):e2100582. Epub 2021 May 31.

Universität Würzburg, Center for Nanosystems Chemistry (CNC) and Bavarian Polymer Institute (BPI), Theodor-Boveri-Weg, 97074, Würzburg, Germany.

A highly sensitive short-wave infrared (SWIR, λ > 1000 nm) organic photodiode (OPD) is described based on a well-organized nanocrystalline bulk-heterojunction (BHJ) active layer composed of a dicyanovinyl-functionalized squaraine dye (SQ-H) donor material in combination with PC BM. Through thermal annealing, dipolar SQ-H chromophores self-assemble in a nanoscale structure with intermolecular charge transfer mediated coupling, resulting in a redshifted and narrow absorption band at 1040 nm as well as enhanced charge carrier mobility. The optimized OPD exhibits an external quantum efficiency (EQE) of 12.3% and a full-width at half-maximum of only 85 nm (815 cm ) at 1050 nm under 0 V, which is the first efficient SWIR OPD based on J-type aggregates. Photoplethysmography application for heart-rate monitoring is successfully demonstrated on flexible substrates without applying reverse bias, indicating the potential of OPDs based on short-range coupled dye aggregates for low-power operating wearable applications.
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http://dx.doi.org/10.1002/adma.202100582DOI Listing
July 2021

Long-type double-balloon enteroscopy-assisted ERCP using hand-made accessories in Roux-en-Y hepaticojejunostomy.

Hepatobiliary Pancreat Dis Int 2021 Apr 27. Epub 2021 Apr 27.

Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea. Electronic address:

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http://dx.doi.org/10.1016/j.hbpd.2021.04.012DOI Listing
April 2021

Coordinate regulation of the senescent state by selective autophagy.

Dev Cell 2021 May 28;56(10):1512-1525.e7. Epub 2021 Apr 28.

School of Biological Sciences, Seoul National University, Seoul 08826, South Korea. Electronic address:

Cellular senescence is a complex stress response implicated in aging. Autophagy can suppress senescence but is counterintuitively necessary for full senescence. Although its anti-senescence role is well described, to what extent autophagy contributes to senescence establishment and the underlying mechanisms is poorly understood. Here, we show that selective autophagy of multiple regulatory components coordinates the homeostatic state of senescence. We combined a proteomic analysis of autophagy components with protein stability profiling, identifying autophagy substrate proteins involved in several senescence-related processes. Selective autophagy of KEAP1 promoted redox homeostasis during senescence. Furthermore, selective autophagy limited translational machinery components to ameliorate senescence-associated proteotoxic stress. Lastly, selective autophagy of TNIP1 enhanced senescence-associated inflammation. These selective autophagy networks appear to operate in vivo senescence during human osteoarthritis. Our data highlight a caretaker role of autophagy in the stress support network of senescence through regulated protein stability and unravel the intertwined relationship between two important age-related processes.
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http://dx.doi.org/10.1016/j.devcel.2021.04.008DOI Listing
May 2021

Factors affecting the diagnostic yield of endoscopic transpapillary forceps biopsy in patients with malignant biliary strictures.

J Gastroenterol Hepatol 2021 Mar 17. Epub 2021 Mar 17.

Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.

Background And Aim: Transpapillary biliary forceps biopsy (TBFB) is a common method to obtain histological evidence for the differential diagnosis of biliary stricture. This study aimed to evaluate the factors associated with a positive cancer diagnosis from TBFB and the number of tissue samples required to increase the diagnostic yield in patients with malignant biliary strictures.

Methods: A total of 376 patients who underwent TBFB for investigation of biliary stricture were included. Factors affecting the diagnostic yield of TBFB were determined using univariate analysis and multivariate logistic regression analyses.

Results: Bile duct cancer (odds ratio [OR] = 3.50, P = 0.002), intraductal growing type (OR = 9.01, P = 0.001), and number of tissue samples (n < 5 vs 5 ≤ n < 10, OR = 4.13, P = 0.01; n < 5 vs n ≥ 10, OR = 12.25, P < 0.001; 5 ≤ n < 10 vs n ≥ 10, OR = 2.97, P = 0.046) were significant factors associated with positive results for malignancy. In patients with periductal infiltrating-type bile duct cancer, the number of tissue samples was a significant factor for diagnostic sensitivity (54.3% in the n < 5 group, 83.3% in the 5 ≤ n < 10 group and 98.2% in the n ≥ 10 group) (P < 0.001).

Conclusions: Bile duct cancer, intraductal growing type, and five or more tissue samples were significant predictors of positive TBFB results in patients with malignant biliary stricture. Increasing the number of tissue samples by five or more led to higher sensitivity in bile duct cancer patients with the periductal infiltrating type.
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http://dx.doi.org/10.1111/jgh.15497DOI Listing
March 2021

Multifaceted Chromatin Structure and Transcription Changes in Plant Stress Response.

Authors:
Jin-Hong Kim

Int J Mol Sci 2021 Feb 18;22(4). Epub 2021 Feb 18.

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

Sessile plants are exposed throughout their existence to environmental abiotic and biotic stress factors, such as cold, heat, salinity, drought, dehydration, submergence, waterlogging, and pathogen infection. Chromatin organization affects genome stability, and its dynamics are crucial in plant stress responses. Chromatin dynamics are epigenetically regulated and are required for stress-induced transcriptional regulation or reprogramming. Epigenetic regulators facilitate the phenotypic plasticity of development and the survival and reproduction of plants in unfavorable environments, and they are highly diversified, including histone and DNA modifiers, histone variants, chromatin remodelers, and regulatory non-coding RNAs. They contribute to chromatin modifications, remodeling and dynamics, and constitute a multilayered and multifaceted circuitry for sophisticated and robust epigenetic regulation of plant stress responses. However, this complicated epigenetic regulatory circuitry creates challenges for elucidating the common or differential roles of chromatin modifications for transcriptional regulation or reprogramming in different plant stress responses. Particularly, interacting chromatin modifications and heritable stress memories are difficult to identify in the aspect of chromatin-based epigenetic regulation of transcriptional reprogramming and memory. Therefore, this review discusses the recent updates from the three perspectives-stress specificity or dependence of transcriptional reprogramming, the interplay of chromatin modifications, and transcriptional stress memory in plants. This helps solidify our knowledge on chromatin-based transcriptional reprogramming for plant stress response and memory.
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http://dx.doi.org/10.3390/ijms22042013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922328PMC
February 2021

Upgrade of BL-5C as a highly automated macromolecular crystallography beamline at Pohang Light Source II.

J Synchrotron Radiat 2021 Mar 5;28(Pt 2):602-608. Epub 2021 Feb 5.

Beamline Science, Pohang Accelerator Laboratory, 80 Jigokro-127-beongil, Pohang, Kyungbuk 37673, Republic of Korea.

BL-5C is an in-vacuum undulator beamline dedicated to macromolecular crystallography (MX) at the 3 GeV Pohang Light Source II in Korea. The beamline delivers X-ray beams with a focal spot size of 200 µm × 40 µm (FWHM, H × V) over the energy range 6.5-16.5 keV. The measured flux is 7 × 10 photons s at 12.659 keV through an aperture size of 50 µm. The experimental station is newly equipped with the photon-counting detector EIGER 9M, the multi-axis micro-diffractometer MD2, and a robotic sample changer with a high-capacity dewar. These instruments enable the operation of this beamline as an automated MX beamline specialized in X-ray fragment screening. This beamline can collect more than 400 data sets a day without human intervention, and a difference map can be automatically calculated by using the data processing pipeline for ligand or fragment identification.
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http://dx.doi.org/10.1107/S1600577521000588DOI Listing
March 2021

Linked N-Acetylglucosamine Modification of Mitochondrial Antiviral Signaling Protein Regulates Antiviral Signaling by Modulating Its Activity.

Front Immunol 2020 2;11:589259. Epub 2021 Feb 2.

Glycosylation Network Research Center, Yonsei University, Seoul, South Korea.

Post-translational modifications, including -GlcNAcylation, play fundamental roles in modulating cellular events, including transcription, signal transduction, and immune signaling. Several molecular targets of -GlcNAcylation associated with pathogen-induced innate immune responses have been identified; however, the direct regulatory mechanisms linking -GlcNAcylation with antiviral RIG-I-like receptor signaling are not fully understood. In this study, we found that cellular levels of -GlcNAcylation decline in response to infection with Sendai virus. We identified a heavily -GlcNAcylated serine-rich region between amino acids 249-257 of the mitochondrial antiviral signaling protein (MAVS); modification at this site disrupts MAVS aggregation and prevents MAVS-mediated activation and signaling. -GlcNAcylation of the serine-rich region of MAVS also suppresses its interaction with TRAF3; this prevents IRF3 activation and production of interferon-β. Taken together, these results suggest that -GlcNAcylation of MAVS may be a master regulatory event that promotes host defense against RNA viruses.
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http://dx.doi.org/10.3389/fimmu.2020.589259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884448PMC
July 2021

Glucose deprivation-induced endoplasmic reticulum stress response plays a pivotal role in enhancement of TRAIL cytotoxicity.

J Cell Physiol 2021 Sep 15;236(9):6666-6677. Epub 2021 Feb 15.

Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Abnormalities of the tumor vasculature result in insufficient blood supply and development of a tumor microenvironment that is characterized by low glucose concentrations, low extracellular pH, and low oxygen tensions. We previously reported that glucose-deprived conditions induce metabolic stress and promote tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cytotoxicity. In this study, we examined whether the metabolic stress-associated endoplasmic reticulum (ER) stress response pathway plays a pivotal role in the enhancement of TRAIL cytotoxicity. We observed no significant cytotoxicity when human colorectal cancer SW48 cells were treated with various doses of TRAIL (2-100 ng/ml) for 4 h or glucose (0-25 mM) for 24 h. However, a combination of TRAIL and low glucose-induced dose-dependent apoptosis through activation of caspases (-8, -9, and -3). Studies with activating transcription factor 4 (ATF4), C/EBP-homologous protein (CHOP), p53 upregulated modulator of apoptosis (PUMA), or death receptor 5 (DR5)-deficient mouse embryonic fibroblasts or HCT116 cells suggest that the ATF4-CHOP-PUMA axis and the ATF4-CHOP-DR5 axis are involved in the combined treatment-induced apoptosis. Moreover, the combined treatment-induced apoptosis was completely suppressed in BH3 interacting-domain death agonist (Bid)- or Bcl-2-associated X protein (Bax)-deficient HCT116 cells, but not Bak-deficient HCT116 cells. Interestingly, the combined treatment-induced Bax oligomerization was suppressed in PUMA-deficient HCT116 cells. These results suggest that glucose deprivation enhances TRAIL-induced apoptosis by integrating the ATF4-CHOP-PUMA axis and the ATF4-CHOP-DR5 axis, consequently amplifying the Bid-Bax-associated mitochondria-dependent pathway.
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http://dx.doi.org/10.1002/jcp.30329DOI Listing
September 2021

Development of a novel fluorescent biosensor for dynamic monitoring of metabolic methionine redox status in cells and tissues.

Biosens Bioelectron 2021 Apr 29;178:113031. Epub 2021 Jan 29.

Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea. Electronic address:

Aberrant production of reactive oxygen species (ROS) leads to tissue damage accumulation, which is associated with a myriad of human pathologies. Although several sensors have been developed for ROS quantification, their applications for ROS-related human physiologies and pathologies still remain problematic due to the unstable nature of ROS. Herein, we developed Trx1-cpYFP-fRMsr (TYfR), a genetically-encoded fluorescent biosensor with the remarkable specificity and sensitivity toward fMetRO (free Methionine-R-sulfoxide), allowing for dynamic quantification of physiological levels of fMetRO, a novel indicator of ROS and methionine redox status in vitro and in vivo. Moreover, using the sensor, we observed a significant fMetRO enrichment in serum from patients with acute coronary syndrome, one of the most severe cardiovascular diseases, which becomes more evident following percutaneous coronary intervention. Collectively, this study proposes that fMetRO is a novel biomarker of tissue damage accumulation in ROS-associated human pathologies, and that TYfR is a promising tool for quantifying fMetRO with potentials in versatile applications.
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http://dx.doi.org/10.1016/j.bios.2021.113031DOI Listing
April 2021

Association of Intensive Endoscopic Screening Burden With Gastric Cancer Detection.

JAMA Netw Open 2021 01 4;4(1):e2032542. Epub 2021 Jan 4.

Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.

Importance: The rapidly increasing number of gastric cancer examinations performed over a short period might influence screening performance. Accessing the association between calendar month and gastric cancer detection rates might improve policy and guide institutional support.

Objective: To evaluate the association between the increased number of examinations over a certain period and gastric cancer detection rates among a large population included in the Korean National Cancer Screening Program (KNCSP).

Design, Setting, And Participants: This retrospective, population-based cohort study used data from the KNCSP comprising 26 765 665 men and women aged 40 years or older who participated in the screening program between January 1, 2013, and December 31, 2016. Data were analyzed from November 1, 2019, to March 31, 2020.

Exposures: Gastric cancer screening with endoscopy.

Main Outcomes And Measures: The primary outcome was monthly gastric cancer detection rates in the KNCSP. A negative binomial regression model was used to evaluate the association between the screening month and detection rates.

Results: In total, 21 535 222 individuals underwent endoscopy (mean [SD] age, 55.61 [10.61] years; 11 761 709 women [54.62%]). The quarterly number of participants was the highest in the last quarter of the study period (2013-2014: 4 094 951 [41.39%], 2015-2016: 4 911 629 [42.19%]); this proportion was 2.48 to 2.84 times greater than that of the first quarter. Cancer detection rates were the lowest in December (2013-2014: 0.22; 95% CI, 0.22-0.23; 2015-2016: 0.21; 95% CI, 0.21-0.22); this was approximately a 40.0% to 45.0% reduction compared with the rates in January. The age group was the significant factor for monthly detection rates. After adjustment for the age group and taking account of the number of screenings, the estimated coefficient range for the screening month was negative and the detection rate in December was significantly different than in January for both the consequent cycles (2013-2014: -0.05 to -0.18; P < .001; and 2015-2016: -0.06 to -0.19; P < .001). In the multivariable logistic model, the association of calendar month with detected cancer remained after adjusting for other confounding factors (December, 2013-2014: odds ratio, 0.82; 95% CI, 0.76-0.87; P < .001; 2015-2016: odds ratio, 0.83; 95% CI, 0.79-0.89; P < .001).

Conclusions And Relevance: The findings of this cohort study suggest that the workload of endoscopists increased with the increasing number of examinations toward the end of the year, as demonstrated by the decreased cancer detection rates. These findings may help to improve gastric cancer detection rates of screening programs by controlling the monthly screening number and policy modifications.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.32542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791358PMC
January 2021

Nanofibrous Conductive Binders Based on DNA-Wrapped Carbon Nanotubes for Lithium Battery Electrodes.

iScience 2020 Nov 28;23(11):101739. Epub 2020 Oct 28.

Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, South Korea.

In contrast to enormous progresses in electrode active materials, little attention has been paid to electrode sheets despite their crucial influence on practical battery performances. Here, as a facile strategy to address this issue, we demonstrate nanofibrous conductive electrode binders based on deoxyribonucleic acid (DNA)-wrapped single-walled carbon nanotubes (SWCNT) (denoted as [email protected]). [email protected] binder allows the removal of conventional polymeric binders and carbon powder additives in electrodes. As a proof of concept, high-capacity overlithiated layered oxide (OLO) is chosen as a model electrode active material. Driven by nanofibrous structure and DNA-mediated chemical functionalities, the [email protected] binder enables improvements in the redox reaction kinetics, adhesion with metallic foil current collectors, and chelation of heavy metal ions dissolved from OLO. The resulting OLO cathode exhibits a fast charging capability (relative capacity ratio after 15 min [versus 10 h] of charging = 83%), long cyclability (capacity retention = 98% after 700 cycles), and thermal stability.
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http://dx.doi.org/10.1016/j.isci.2020.101739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670196PMC
November 2020

Diagnostic accuracy of "sweeping" method compared to conventional sampling in rapid urease test for Helicobacter pylori detection in atrophic mucosa.

Sci Rep 2020 10 28;10(1):18483. Epub 2020 Oct 28.

Department of Gastroenterology, Ajou University School of Medicine, 164, World Cup-ro, Yeongtong-gu, Suwon, 16499, Republic of Korea.

Although the rapid urease test (RUT) is a simple method for detecting Helicobacter pylori (H. pylori) infection, it requires sufficient biopsy samples and its sensitivity varies depending on the site and condition of H. pylori infection. We compared the diagnostic performance of a "sweeping method" for H. pylori detection with the conventional biopsy sampling method in atrophic gastric conditions which can reduce RUT accuracy. This prospective study included 279 patients who underwent upper endoscopy to determine the presence of H. pylori infection. Gastric mucosa of both the antrum and the corpus were swabbed, and we named this method the "sweeping method". Biopsy sampling for the conventional method, histologic evaluation, and polymerase chain reaction were performed at the same time. The sensitivity, specificity, and accuracy of the sweeping method were 0.941, 0.826, and 0.903, respectively, compared to 0.685, 0.859, and 0.742, respectively, for the conventional biopsy method. The area under the receiver operating curve for the sweeping method was 0.884 versus 0.772 for the conventional method (P < 0.001). The sweeping method had a faster detection time than the conventional method. Compared to conventional biopsy sampling, the sweeping method with the RUT provided higher sensitivity and accuracy for the detection of H. pylori, with a faster detection time.
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http://dx.doi.org/10.1038/s41598-020-75528-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595103PMC
October 2020

A system-level approach identifies HIF-2α as a critical regulator of chondrosarcoma progression.

Nat Commun 2020 10 6;11(1):5023. Epub 2020 Oct 6.

Center for RNA Research, Institute for Basic Science, 08826, Seoul, South Korea.

Chondrosarcomas, malignant cartilaginous neoplasms, are capable of transitioning to highly aggressive, metastatic, and treatment-refractory states, resulting in significant patient mortality. Here, we aim to uncover the transcriptional program directing such tumor progression in chondrosarcomas. We conduct weighted correlation network analysis to extract a characteristic gene module underlying chondrosarcoma malignancy. Hypoxia-inducible factor-2α (HIF-2α, encoded by EPAS1) is identified as an upstream regulator that governs the malignancy gene module. HIF-2α is upregulated in high-grade chondrosarcoma biopsies and EPAS1 gene amplification is associated with poor prognosis in chondrosarcoma patients. Using tumor xenograft mouse models, we demonstrate that HIF-2α confers chondrosarcomas the capacities required for tumor growth, local invasion, and metastasis. Meanwhile, pharmacological inhibition of HIF-2α, in conjunction with the chemotherapy agents, synergistically enhances chondrosarcoma cell apoptosis and abolishes malignant signatures of chondrosarcoma in mice. We expect that our insights into the pathogenesis of chondrosarcoma will provide guidelines for the development of molecular targeted therapeutics for chondrosarcoma.
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http://dx.doi.org/10.1038/s41467-020-18817-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538956PMC
October 2020

Impact of previous metronidazole exposure on metronidazole-based second-line quadruple therapy for Helicobacter pylori infection.

Korean J Intern Med 2020 09 31;35(5):1094-1103. Epub 2020 Jul 31.

Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.

Background/aims: The negative effects on the eradication success of Helicobacter pylori infection after previous exposure to macrolides, including clarithromycin on clarithromycin-based first-line therapy have been demonstrated. However, whether this is true for metronidazole-based second-line quadruple therapy remains unclear. We investigated the relationship between past administration of metronidazole and the failure of metronidazole-based second-line quadruple therapy in patients with H. pylori infection.

Methods: Patients over 20 years of age who were diagnosed with H. pylori infection between January 1998 and March 2016 were enrolled in this study. The relationship between the clinical parameters and the results of a C13-urea breath test after metronidazole-based second-line quadruple therapy was analyzed in patients for whom clarithromycin-based triple therapy failed to eradicate H. pylori.

Results: The H. pylori eradication failure rate was significantly higher in patients with a history of metronidazole use than in patients without a history of metronidazole use (p = 0.011). Multivariable analysis showed that the odds ratio of previous metronidazole use for eradication failure was 3.468 (95% confidence interval, 1.391 to 8.649; p = 0.008). In the subgroup analysis of patients with a history of metronidazole use, the duration of metronidazole use and interval between its use and eradication therapy did not significantly affect H. pylori eradication failure.

Conclusion: Previous exposure to metronidazole was a significant risk factor for treatment failure of metronidazole-based second-line quadruple therapy; therefore, this should be considered when establishing a treatment strategy for patients with H. pylori infection.
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http://dx.doi.org/10.3904/kjim.2020.174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487300PMC
September 2020

Endoscopic retrieval of a misplaced lumen-apposing metal stent alongside a nasocystic drainage tube during endoscopic ultrasound-guided cystogastrostomy.

Dig Endosc 2020 Sep 29;32(6):e142-e144. Epub 2020 Aug 29.

Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.

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http://dx.doi.org/10.1111/den.13782DOI Listing
September 2020

The role of selenium metabolism and selenoproteins in cartilage homeostasis and arthropathies.

Exp Mol Med 2020 08 13;52(8):1198-1208. Epub 2020 Aug 13.

Center for RNA Research, Institute for Basic Science, Seoul, 08826, South Korea.

As an essential nutrient and trace element, selenium is required for living organisms and its beneficial roles in human health have been well recognized. The role of selenium is mainly played through selenoproteins synthesized by the selenium metabolic system. Selenoproteins have a wide range of cellular functions including regulation of selenium transport, thyroid hormones, immunity, and redox homeostasis. Selenium deficiency contributes to various diseases, such as cardiovascular disease, cancer, liver disease, and arthropathy-Kashin-Beck disease (KBD) and osteoarthritis (OA). A skeletal developmental disorder, KBD has been reported in low-selenium areas of China, North Korea, and the Siberian region of Russia, and can be alleviated by selenium supplementation. OA, the most common form of arthritis, is a degenerative disease caused by an imbalance in matrix metabolism and is characterized by cartilage destruction. Oxidative stress serves as a major cause of the initiation of OA pathogenesis. Selenium deficiency and dysregulation of selenoproteins are associated with impairments to redox homeostasis in cartilage. We review the recently explored roles of selenium metabolism and selenoproteins in cartilage with an emphasis on two arthropathies, KBD and OA. Moreover, we discuss the potential of therapeutic strategies targeting the biological functions of selenium and selenoproteins for OA treatment.
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http://dx.doi.org/10.1038/s12276-020-0408-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423502PMC
August 2020

Doping effect in graphene-graphene oxide interlayer.

Sci Rep 2020 May 19;10(1):8258. Epub 2020 May 19.

Department of Physics, Konkuk University, Seoul, 05029, Korea.

Interlayer coupling in graphene-based van der Waals (vdW) heterostructures plays a key role in determining and modulating their physical properties. Hence, its influence on the optical and electronic properties cannot be overlooked in order to promote various next-generation applications in electronic and opto-electronic devices based on the low-dimensional materials. Herein, the optical and electrical properties of the vertically stacked large area heterostructure of the monolayer graphene transferred onto a monolayer graphene oxide film are investigated. An effective and stable p-doping property of this structure is shown by comparison to that of the graphene device fabricated on a silicon oxide substrate. Through Raman spectroscopy and density functional theory calculations of the charge transport characteristics, it is found that graphene is affected by sustainable p-doping effects induced from underneath graphene oxide even though they have weak interlayer interactions. This finding can facilitate the development of various fascinating graphene-based heterostructures and extend their practical applications in integrated devices with advanced functionalities.
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http://dx.doi.org/10.1038/s41598-020-65263-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237491PMC
May 2020

Conversion of percutaneous transhepatic biliary drainage to endoscopic ultrasonography-guided hepaticogastrostomy under balloon-targeted selective needle puncture.

Dig Endosc 2020 Jul 16;32(5):830. Epub 2020 Jun 16.

Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.

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http://dx.doi.org/10.1111/den.13715DOI Listing
July 2020

Tips for Dealing with Common Beginner's Mistakes Made during Endoscopic Ultrasound-Guided Gallbladder Drainage.

Dig Dis 2020 13;38(6):542-546. Epub 2020 Feb 13.

Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.

Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has been performed as an alternative to percutaneous drainage in surgically high-risk patients. Technical failures of EUS-GBD made by beginners are often attributed to failure of over-the-wire insertion of a fistula-dilating device or stent delivery system into the gallbladder, or stent misplacement in the final technical step. We herein report technical tips to prevent the failure of fistula dilation and provide tricks to avoid inward or outward stent misplacement.
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http://dx.doi.org/10.1159/000505644DOI Listing
November 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

Structural and biophysical properties of RIG-I bound to dsRNA with G-U wobble base pairs.

RNA Biol 2020 03 18;17(3):325-334. Epub 2019 Dec 18.

Department of Chemistry, KAIST, Daejeon, Republic of Korea.

Retinoic acid-inducible gene I (RIG-I) is responsible for innate immunity via the recognition of short double-stranded RNAs in the cytosol. With the clue that G-U wobble base pairs in the influenza A virus's RNA promoter region are responsible for RIG-I activation, we determined the complex structure of RIG-I ΔCARD and a short hairpin RNA with G-U wobble base pairs by X-ray crystallography. Interestingly, the overall helical backbone trace was not affected by the presence of the wobble base pairs; however, the base pair inclination and helical axis angle changed upon RIG-I binding. NMR spectroscopy revealed that RIG-I binding renders the flexible base pair of the influenza A virus's RNA promoter region between the two G-U wobble base pairs even more flexible. Binding to RNA with wobble base pairs resulted in a more flexible RIG-I complex. This flexible complex formation correlates with the entropy-favoured binding of RIG-I and RNA, which results in tighter binding affinity and RIG-I activation. This study suggests that the structure and dynamics of RIG-I are tailored to the binding of specific RNA sequences with different flexibility.
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http://dx.doi.org/10.1080/15476286.2019.1700034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999645PMC
March 2020

Comparison of Effectiveness between Abdominal Vibration Stimulation and Walking Exercise for Bowel Cleansing before Therapeutic Colonoscopy.

Gut Liver 2020 07;14(4):468-476

Departments of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.

Background/aims: Adequate bowel preparation is important for successful colonoscopy. We aimed to evaluate the clinical feasibility and effectiveness of abdominal vibration stimulation in bowel preparation before therapeutic colonoscopy.

Methods: A single center, prospective, randomized, investigator-blinded study was performed between January 2016 and December 2016. Patients for therapeutic colonoscopy were prospectively enrolled and assigned to either the vibrator group or walking group. Patients who refused to participate in this study as part of the experimental group consented to register in the control group instead. During the preparation period, patients assigned to the walking group walked ≥3,000 steps, whereas those assigned to the vibrator group received abdominal vibrator stimulation and restricted walking. All patients received the same colon cleansing regimen: 4-L split-dose polyethylene glycol (PEG) solution.

Results: Three hundred patients who received PEG solution for therapeutic colonoscopy were finally enrolled in this study (n=100 per group). Bowel cleansing with abdominal vibration stimulation showed almost similar results to that with walking exercise (Boston Bowel Preparation Scale score for the entire colon: vibrator vs walking vs control, 7.38±1.55 vs 7.39±1.55 vs 6.17±1.15, p<0.001). There were no significant differences between the vibrator group and walking group regarding instances of diarrhea after taking PEG, time to first diarrhea after taking PEG, total procedure time, and patient satisfaction.

Conclusions: This study indicates that, compared with conventional walking exercise, abdominal vibration stimulation achieved similar rates of bowel cleansing adequacy and colonoscopy success without compromising safety or patient satisfaction.
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http://dx.doi.org/10.5009/gnl19999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366144PMC
July 2020

Tankyrase inhibition preserves osteoarthritic cartilage by coordinating cartilage matrix anabolism via effects on SOX9 PARylation.

Nat Commun 2019 10 25;10(1):4898. Epub 2019 Oct 25.

Center for RNA Research, Institute for Basic Science, 08826, Seoul, South Korea.

Osteoarthritis (OA) is a prevalent degenerative disease, which involves progressive and irreversible destruction of cartilage matrix. Despite efforts to reconstruct cartilage matrix in osteoarthritic joints, it has been a difficult task as adult cartilage exhibits marginal repair capacity. Here we report the identification of tankyrase as a regulator of the cartilage anabolism axis based on systems-level factor analysis of mouse reference populations. Tankyrase inhibition drives the expression of a cartilage-signature matrisome and elicits a transcriptomic pattern that is inversely correlated with OA progression. Furthermore, tankyrase inhibitors ameliorate surgically induced OA in mice, and stem cell transplantation coupled with tankyrase knockdown results in superior regeneration of cartilage lesions. Mechanistically, the pro-regenerative features of tankyrase inhibition are mainly triggered by uncoupling SOX9 from a poly(ADP-ribosyl)ation (PARylation)-dependent protein degradation pathway. Our findings provide insights into the development of future OA therapies aimed at reconstruction of articular cartilage.
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http://dx.doi.org/10.1038/s41467-019-12910-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814715PMC
October 2019

A Rare Case of Primary Myelofibrosis With a Solitary 1q Triplication.

Ann Lab Med 2020 Mar;40(2):174-176

Department of Laboratory Medicine, Hanyang University Seoul Hospital, Hanyang University College of Medicine, Seoul, Korea.

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http://dx.doi.org/10.3343/alm.2020.40.2.174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822012PMC
March 2020
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