Publications by authors named "C Yong Kang"

4,671 Publications

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Primary aspergillosis of the larynx causing acute airway distress.

BMJ Case Rep 2021 Apr 9;14(4). Epub 2021 Apr 9.

Otolaryngology, Guy's and St Thomas' Hospitals NHS Trust, London, UK.

Laryngeal aspergillosis is most commonly seen as a secondary infection that spreads from the lungs and tracheobronchial tree. Primary invasive aspergillosis of the larynx is rare and most likely seen in an immunocompromised patient. We present a case of a 59-year-old woman who presented with progressive dysphonia and subsequently acute stridor. She is a non-smoker with a recent diagnosis of acute myeloid leukaemia. Fibreoptic nasendoscopy revealed a left sided vocal cord lesion ball valving into the glottic space. Histology taken during emergency debulking confirmed and the patient was successfully treated with intravenous antifungals. Although there are cases of primary laryngeal aspergillosis discussed in the literature, to the best of our knowledge this is the first reported case to have caused acute airway distress requiring emergency intervention.
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http://dx.doi.org/10.1136/bcr-2020-240434DOI Listing
April 2021

Evaluation of six anti-SARS-CoV-2 antibody test kits and practical approaches to optimize the diagnostic performance.

J Microbiol Immunol Infect 2021 Mar 26. Epub 2021 Mar 26.

Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address:

In an investigation of six anti-SARS-CoV-2 antibody kits with different target antigen and methodology, each kit showed comparable performance. As false-positive reactions occurred independently with different kits, specificity increased to 100% when pairs of kits were used. With three-kit combination, both sensitivity (99.1%) and specificity (100%) increased.
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http://dx.doi.org/10.1016/j.jmii.2021.03.008DOI Listing
March 2021

Optical Properties of the Infinite-Layer La_{1-x}Sr_{x}NiO_{2} and Hidden Hund's Physics.

Phys Rev Lett 2021 Mar;126(12):127401

Department of Physics and Astronomy, Rutgers University, Piscataway, New Jersey 08856, USA.

We investigate the optical properties of the normal state of the infinite-layer La_{1-x}Sr_{x}NiO_{2} using density functional theory plus dynamical mean-field theory. We find a correlated metal which exhibits substantial transfer of spectral weight to high energies relative to the density functional theory. The correlations are not due to Mott physics, which would suppress the charge fluctuations and the integrated optical spectral weight as we approach a putative insulating state. Instead, we find the unusual situation, that the integrated optical spectral weight decreases with doping and increases with increasing temperature. We contrast this with the coherent component of the optical conductivity, which decreases with increasing temperature as a result of a coherence-incoherence crossover. Our studies reveal that the effective crystal field splitting is dynamical and increases strongly at low frequency. This leads to a picture of a Hund's metallic state, where dynamical orbital fluctuations are visible at intermediate energies, while at low energies a Fermi surface with primarily d_{x^{2}-y^{2}} character emerges. The infinite-layer nickelates are thus in an intermediate position between the iron based high temperature superconductors where multiorbital Hund's physics dominates and a one-band system such as the cuprates. To capture this physics we propose a low-energy two-band model with atom centered e_{g} states.
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http://dx.doi.org/10.1103/PhysRevLett.126.127401DOI Listing
March 2021

Fast refocusing lens based on ferroelectric liquid crystals.

Opt Express 2021 Mar;29(6):8258-8267

Optical devices like virtual reality (VR) headsets present challenges in terms of vergence-accommodation conflict that leads to visual fatigue for the user over time. Lenses available to meet these challenges include liquid crystal (LC) lenses, which possess a response time in the millisecond range. This response time is slow, while accessing multiple focal lengths. A ferroelectric liquid crystal (FLC) has a response time in the microsecond range. In this article, we disclose a switchable lens device having a combination of the fast FLC-based polarization rotation unit and a passive polarization-dependent LC lens. A cascaded combination of three such lens units allows access to eight different focal points quite rapidly and can be a convenient device for VR applications.
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http://dx.doi.org/10.1364/OE.417112DOI Listing
March 2021

An 18.3 MJ charging and discharging pulsed power supply system for the Space Plasma Environment Research Facility (SPERF): Modular design method and component selection.

Rev Sci Instrum 2021 Mar;92(3):034709

Key Laboratory of Pulsed Power, Institute of Fluid Physics, CAEP, Mianyang 621900, Sichuan, China.

The capacitor-based pulsed power supply (PPS) system is an important subsystem of the Space Plasma Environment Research Facility being built as a user facility at Harbin Institute of Technology in China. It has been developed with a modular design to drive magnetic coils to generate magnetic fields and plasma for the physical experiments. In this paper, the modular design and component selection are proposed based on a calculation of parameter ranges of components and the number of modules followed by a simulation and an engineering test. Both the simulation and test results show the feasibility of the selected components and the number of modules to meet the designing requirements of the PPS.
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http://dx.doi.org/10.1063/5.0036923DOI Listing
March 2021

Heat-Killed Lactic Acid Bacteria Inhibit Nitric Oxide Production via Inducible Nitric Oxide Synthase and Cyclooxygenase-2 in RAW 264.7 Cells.

Probiotics Antimicrob Proteins 2021 Apr 5. Epub 2021 Apr 5.

MEDIOGEN, Co., Ltd., Jecheon, 27159, Korea.

Heat-killed lactic acid bacteria perform immunomodulatory functions and are advantageous as probiotics, considering their long product shelf-life, easy storage, and convenient transportation. In this study, we aimed to develop appropriate heat treatments for industrial preparation of probiotics with antioxidant activity. Among 75 heat-killed strains, Lactococcus lactis MG5125 revealed the highest nitric oxide inhibition (86.2%), followed by Lactobacillus acidophilus MG4559 (86.0%), Lactobacillus plantarum MG5270 (85.7%), Lactobacillus fermentum MG4510 (85.3%), L. plantarum MG5239 (83.9%), L. plantarum MG5289 (83.2%), and L. plantarum MG5203 (81.8%). Moreover, the heat-killed selected strains markedly inhibited lipopolysaccharide-induced nitric oxide synthase and cyclooxygenase-2 expression. The use of heat-killed bacteria with intact bio-functionality can elongate the shelf-life and simplify the food processing steps of probiotic foods, given their high stability. The antioxidant and immune-modulatory activities of the heat-killed strains selected in this study indicate a strong potential for their utilization probiotic products manufacturing.
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http://dx.doi.org/10.1007/s12602-021-09781-9DOI Listing
April 2021

Development of Antigen-specific Chimeric Antigen Receptor KHYG-1 Cells for Glioblastoma.

Anticancer Res 2021 Apr;41(4):1811-1819

Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea;

Background/aim: Glioblastoma is the most common cancer among primary brain tumors, however, its prognosis and treatment advances are very poor. Here, we investigated whether c-Met, FOLR1, and AXL proteins are promising targets for chimeric antigen receptor (CAR) T-cell therapy, for they are known to be over-expressed in a variety of solid tumors.

Materials And Methods: CAR constructs were prepared and CAR KHYG-1 cells targeting c-Met, FOLR1, or AXL were made by lentiviral transduction. The activity of CAR KHYG-1 cells against cancer cells was measured by cytokine secretion and cell lysis assays.

Results: c-Met and AXL were over-expressed in most glioblastoma cell lines (11/13), but not in neuroblastoma cell lines (0/8). FOLR1 was over-expressed only in one among 16 glioblastoma cell lines. Our antigen-specific CAR KHYG-1 cells eradicated target positive glioblastoma cells selectively.

Conclusion: Anti-c-Met and anti-AXL CAR NK or T cells could be effective in glioblastoma cells.
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http://dx.doi.org/10.21873/anticanres.14947DOI Listing
April 2021

WS nanosheets@ZIF-67-derived N-doped carbon composite as sodium ion battery anode with superior rate capability.

J Colloid Interface Sci 2021 Mar 24;595:59-68. Epub 2021 Mar 24.

School of Physics and Technology, Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education, Wuhan University, Wuhan 430072, China. Electronic address:

Devising novel composite electrodes with particular structural/electrochemical characteristics becomes an efficient strategy to advance the performance of rechargeable battery. Herein, considering the homogeneous transition metal sulfide with N-doped carbon derived from zeolitic imidazolate framework-67 (ZIF-67) and WS with large interlayer spacing, a laurel-leaf-like CoS/WS@N-doped carbon bimetallic sulfide (CoS/WS@NC) is engineered and prepared via a step-by-step method. As an electrode material for sodium ion batteries (SIBs), CoS/WS@NC composite delivers high capacities of 480 and 405 mA h g at 0.1 and 1.0 A g, respectively. As the current density increases from 0.1 to 5.0 A g, it provides specific capacity of 359 mA h g with a capacity retention rate of 78.0%, which is higher than that of CoS@NC (63.5%) and WS (58.6%). The CoS/WS@NC composite anode maintains a stable specific capacity (354 mA h g at 2.0 A g). It also exhibits a high capacitive contribution ratio of 90.8% at 1.0 mV s. This study provides a new and reliable insight for designing bimetallic sulfide with two-dimensional nanostructure for energy storage.
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http://dx.doi.org/10.1016/j.jcis.2021.03.127DOI Listing
March 2021

Sources of indoor PM gross α and β activities measured in 340 homes.

Environ Res 2021 Apr 2;197:111114. Epub 2021 Apr 2.

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Particle radioactivity (PR) exposure has been linked to adverse health effects. PR refers to the presence of α- and β-emitting radioisotopes attached to fine particulate matter (PM). This study investigated sources contributing to indoor PM gross α- and β-radioactivity levels. We measured activity from long-lived radon progeny radionuclides from archived PM samples collected in 340 homes in Massachusetts during the period 2006-2010. We analyzed the data using linear mixed effects models and positive matrix factorization (PMF) analysis. Indoor PM gross α-activity levels were correlated with sulfur (S), iron (Fe), bromine (Br), vanadium (V), sodium (Na), lead (Pb), potassium (K), calcium (Ca), silicon (Si), zinc (Zn), arsenic (As), titanium (Ti), radon (Rn) and black carbon (BC) concentrations (p <0.05). Indoor PM β-activity was correlated with S, As, antimony (Sb), Pb, Br and BC. We identified four indoor PM sources: outdoor air pollution (62%), salt aerosol source (14%), fireworks and environmental tobacco smoke (7%) and indoor mixed dust (17%). Outdoor air pollution was the most significant contributor to indoor PM α- and β-activity levels. The contributions of this source were during the summer months and when windows were open. Indoor mixed dust was also found to contribute to PM α-activity. PM α-activity was further associated with radon during winter months, showing radon's important role as an indoor source of ionizing radiation.
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http://dx.doi.org/10.1016/j.envres.2021.111114DOI Listing
April 2021

Development, Validation, and Comparison of a Nomogram Based on Radiologic Findings for Predicting Malignancy in Intraductal Papillary Mucinous Neoplasms of the Pancreas: An International Multicenter Study.

J Hepatobiliary Pancreat Sci 2021 Apr 2. Epub 2021 Apr 2.

Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.

Background: Although we previously proposed a nomogram to predict malignancy in intraductal papillary mucinous neoplasms (IPMN) and validated it in an external cohort, its application is challenging without data on tumor markers. Moreover, existing nomograms have not been compared. This study aimed to develop a nomogram based on radiologic findings and to compare its performance with previously proposed American and Korean/Japanese nomograms.

Methods: We recruited 3708 patients who underwent surgical resection at 31 tertiary institutions in eight countries, and patients with main pancreatic duct > 10 mm were excluded. To construct the nomogram, 2606 patients were randomly allocated 1:1 into training and internal validation sets, and area under the receiver operating characteristics curve (AUC) was calculated using 10-fold cross validation by exhaustive search. This nomogram was then validated and compared to the American and Korean/Japanese nomograms using 1102 patients.

Results: Among the 2606 patients, 90 had main-duct type, 900 had branch-duct type, and 1616 had mixed-type IPMN. Pathologic results revealed 1628 low-grade dysplasia, 476 high-grade dysplasia, and 502 invasive carcinoma. Location, cyst size, duct dilatation, and mural nodule were selected to construct the nomogram. AUC of this nomogram was higher than the American nomogram (0.691 vs. 0.664, p = 0.014) and comparable with the Korean/Japanese nomogram (0.659 vs 0.653, p = 0.255).

Conclusions: A novel nomogram based on radiologic findings of IPMN is competitive for predicting risk of malignancy. This nomogram would be clinically helpful in circumstances where tumor markers are not available. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.
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http://dx.doi.org/10.1002/jhbp.962DOI Listing
April 2021

Non-Polio Enteroviruses from Acute Flaccid Paralysis Surveillance in Korea, 2012-2019.

Viruses 2021 Mar 5;13(3). Epub 2021 Mar 5.

Division of Viral Diseases, Korea Disease Control and Prevention Agency, Cheongju 28159, Korea.

The risk of polio importation and re-emergence persists since epidemic polio still occurs in some countries, and the resurgence of polio occurring almost 20 years after polio eradication was declared in Asia has been reported. We analyzed the results of acute flaccid paralysis (AFP) surveillance in Korea to assess the quality of AFP surveillance and understand the etiology of non-polio enterovirus (NPEV)-associated central nervous system diseases in a polio-free area. We investigated 637 AFP patients under 15 years of age whose cases were confirmed during 2012-2019 by virus isolation, real-time reverse transcription polymerase chain reaction, and VP1 gene sequencing. Among the 637 AFP cases, NPEV was detected in 213 (33.4%) patients, with the majority observed in EV-A71, with 54.9% of NPEV positives. EV-A71 has been shown to play a role as a major causative agent in most neurological diseases except for Guillain-Barré syndrome (GBS), acute disseminated encephalomyelitis (ADEM), and meningitis. This study provides information on the AFP surveillance situation in Korea and highlights the polio eradication stage in the monitoring and characterization of NPEV against the outbreak of neurological infectious diseases such as polio.
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http://dx.doi.org/10.3390/v13030411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001888PMC
March 2021

Reproductive Chances of Men with Azoospermia Due to Spermatogenic Dysfunction.

J Clin Med 2021 Mar 31;10(7). Epub 2021 Mar 31.

Department of Urology, Weill Cornell Medical College, New York, NY 10021, USA.

Non-obstructive azoospermia (NOA), or lack of sperm in the ejaculate due to spermatogenic dysfunction, is the most severe form of infertility. Men with this form of infertility should be evaluated prior to treatment, as there are various underlying etiologies for NOA. While a significant proportion of NOA men have idiopathic spermatogenic dysfunction, known etiologies including genetic disorders, hormonal anomalies, structural abnormalities, chemotherapy or radiation treatment, infection and inflammation may substantively affect the prognosis for successful treatment. Despite the underlying etiology for NOA, most of these infertile men are candidates for surgical sperm retrieval and subsequent use in intracytoplasmic sperm injection (ICSI). In this review, we describe common etiologies of NOA and clinical outcomes following surgical sperm retrieval and ICSI.
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http://dx.doi.org/10.3390/jcm10071400DOI Listing
March 2021

Synthesis of OmpA Oral Nanoparticles and Evaluation of Immune Functions against the Major Etiologic Agent of Cow Mastitis.

Vaccines (Basel) 2021 Mar 23;9(3). Epub 2021 Mar 23.

College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China.

is a major etiologic agent of cow mastitis, a condition that results in huge economic losses. There is a lack of an oral vaccine for cow mastitis. Previous studies have confirmed that the outer membrane protein A (OmpA) of is immunogenic and can be used for vaccine design. In the present study, OmpA was encapsulated into nanoparticles (NP-OmpA) for an oral vaccine for cow mastitis. OmpA was purified with Ni-NTA flow resin and encapsulated with chitosan (CS) to prepare NP-OmpA nanoparticles. The gastrointestinal tract was simulated in vitro (PBS, pH 1.2) to measure the protein release rate. The optimal preparation conditions for NP-OmpA were determined by analyzing the concentrations of OmpA and CS, magnetic mixing speed, mixing time, and the ratio of tripolyphosphate (TPP)/CS (). NP-OmpA safety was assessed by function factors and histopathological examination of livers and kidneys. The immune activity of NP-OmpA was determined using qRT-PCR to assess immune-related gene expression, leukocyte phagocytosis of , ELISA to evaluate antiserum titer and immune recognition of , and the organ index. The immune protection function of NP-OmpA was assessed by the protection rate of NP-OmpA to in mice, qRT-PCR for inflammation-related gene expression, assay kits for antioxidant factors, and visceral injury in the histopathological sections. NP-OmpA nanoparticles had a diameter of about 700 nm, loading efficiency (LE) of 79.27%, and loading capacity (LC) of 20.31%. The release rate of NP-OmpA (0~96 h) was less than 50% in vitro. The optimal preparation conditions for NP-OmpAs were OmpA protein concentration of 2 mg/mL, CS concentration of 5 mg/mL, TPP/CS () of 1:1, magnetic mixing speed of 150 r/min, and mixing time of 15 min. Histopathological sections and clinical analytes of uric acid (UA), creatinine (Cr), alanine aminotransferase (ALT), aspartate transaminase (AST), catalase (CAT), glutathione (GSH), and malondialdehyde (MDA) showed NP-OmpA did not damage mice livers or kidneys. NP-OmpA could enhance the immune-related gene expression of IFN-γ and HSP70 in the spleen, liver, and kidney and the leukocyte phagocytosis of . The antiserum titer (1:3200) was obtained from mice immunized with NP-OmpA, which had an immune recognition effect to . The immune protection rate of NP-OmpA was 71.43% ( < 0.05) to . NP-OmpA could down-regulate the inflammation-related gene expression of TNF-a, IL-6, and IL-10 in the spleen, liver, and kidney, and the antioxidant factors MDA and SOD in the liver, and reduce injury in the liver and kidney of mice induced by . A novel NP-OmpA nanoparticle was encapsulated, and the optimal preparation conditions were determined. The NP-OmpA was safe and had good immune functions. They are expected to induce a response that resists infection with the major etiologic agent () of cow mastitis.
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http://dx.doi.org/10.3390/vaccines9030304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005184PMC
March 2021

Two Decades from the Introduction of Microdissection Testicular Sperm Extraction: How This Surgical Technique Has Improved the Management of NOA.

J Clin Med 2021 Mar 29;10(7). Epub 2021 Mar 29.

Department of Urology, Weill Cornell Medical College, New York, NY 10065, USA.

The treatment of men with non-obstructive azoospermia (NOA) has improved greatly over the past two decades. This is in part due to the discovery of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), but also significantly due to improvements in surgical sperm retrieval methods, namely the development of microdissection testicular sperm extraction (mTESE). This procedure has revolutionized the field by allowing for identification of favorable seminiferous tubules while simultaneously limiting the amount of testicular tissue removed. Improving sperm retrieval rates is imperative in this cohort of infertile men as there are a limited number of factors that are predictive of successful sperm retrieval. Currently, sperm retrieval in NOA men remains dependent on surgeon experience, preoperative patient optimization and teamwork with laboratory personnel. In this review, we discuss the evolution of surgical sperm retrieval methods, review predictors of sperm retrieval success, compare and contrast the data of conventional versus mTESE, share tips for optimizing sperm retrieval outcomes, and discuss the future of sperm retrieval in men with NOA.
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http://dx.doi.org/10.3390/jcm10071374DOI Listing
March 2021

Metal Oxide Nanorods-Based Sensor Array for Selective Detection of Biomarker Gases.

Sensors (Basel) 2021 Mar 9;21(5). Epub 2021 Mar 9.

KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Korea.

The breath gas analysis through gas phase chemical analysis draws attention in terms of non-invasive and real time monitoring. The array-type sensors are one of the diagnostic methods with high sensitivity and selectivity towards the target gases. Herein, we presented a 2 × 4 sensor array with a micro-heater and ceramic chip. The device is designed in a small size for portability, including the internal eight-channel sensor array. InO NRs and WO NRs manufactured through the E-beam evaporator's glancing angle method were used as sensing materials. Pt, Pd, and Au metal catalysts were decorated for each channel to enhance functionality. The sensor array was measured for the exhaled gas biomarkers CHCOCH, NO, and HS to confirm the respiratory diagnostic performance. Through this operation, the theoretical detection limit was calculated as 1.48 ppb for CHCOCH, 1.9 ppt for NO, and 2.47 ppb for HS. This excellent detection performance indicates that our sensor array detected the CHCOCH, NO, and HS as biomarkers, applying to the breath gas analysis. Our results showed the high potential of the gas sensor array as a non-invasive diagnostic tool that enables real-time monitoring.
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http://dx.doi.org/10.3390/s21051922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967152PMC
March 2021

Association of structural variation with cardiometabolic traits in Finns.

Am J Hum Genet 2021 Apr;108(4):583-596

McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address:

The contribution of genome structural variation (SV) to quantitative traits associated with cardiometabolic diseases remains largely unknown. Here, we present the results of a study examining genetic association between SVs and cardiometabolic traits in the Finnish population. We used sensitive methods to identify and genotype 129,166 high-confidence SVs from deep whole-genome sequencing (WGS) data of 4,848 individuals. We tested the 64,572 common and low-frequency SVs for association with 116 quantitative traits and tested candidate associations using exome sequencing and array genotype data from an additional 15,205 individuals. We discovered 31 genome-wide significant associations at 15 loci, including 2 loci at which SVs have strong phenotypic effects: (1) a deletion of the ALB promoter that is greatly enriched in the Finnish population and causes decreased serum albumin level in carriers (p = 1.47 × 10) and is also associated with increased levels of total cholesterol (p = 1.22 × 10) and 14 additional cholesterol-related traits, and (2) a multi-allelic copy number variant (CNV) at PDPR that is strongly associated with pyruvate (p = 4.81 × 10) and alanine (p = 6.14 × 10) levels and resides within a structurally complex genomic region that has accumulated many rearrangements over evolutionary time. We also confirmed six previously reported associations, including five led by stronger signals in single nucleotide variants (SNVs) and one linking recurrent HP gene deletion and cholesterol levels (p = 6.24 × 10), which was also found to be strongly associated with increased glycoprotein level (p = 3.53 × 10). Our study confirms that integrating SVs in trait-mapping studies will expand our knowledge of genetic factors underlying disease risk.
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http://dx.doi.org/10.1016/j.ajhg.2021.03.008DOI Listing
April 2021

An inhibitor of programmed death ligand 1 enhances natural killer cell-mediated immunity against malignant melanoma cells.

PLoS One 2021 1;16(4):e0248870. Epub 2021 Apr 1.

Department of Biochemistry, Pusan National University School of Medicine, Yangsan, Republic of Korea.

Since ionizing radiation has showed the dramatic effect to kill the cancer cells through direct DNA damage as well as triggering anti-cancer immune responses including induction of NKG2D ligands, it has used for long time to treat many cancer patients. However, it has been known that radiotherapy might promote the remnant cancer cells to escape immune system and metastasis. One of the suggested ways of immune evasion is induction of a ligand for programmed death-1 (PD-L1) in head and neck cancer, bladder cancer and lung cancer cells which engages the receptor, programmed death-1 (PD-1) in immune cells. PD-1/PD-L1 axis transduces the inhibitory signal and suppresses the adaptive immunity. However, their role in innate immunity remains poorly understood. Therefore, we investigated whether ionizing radiation could change the expression of PD-L1 in malignant melanoma cells and the receptor, programmed death-1 (PD-1), in NK-92 cells. Surface PD-L1 levels on melanoma cells were increased by ionizing radiation in a dose-independent manner but the level of PD-L1 was not changed significantly in NK-92 cells. Radiation-induced PD-L1 suppressed the activity of the NK-92 cells against melanoma cells despite of upregulation of NKG2D ligands. Furthermore, activated NK cells had high level of PD-1 and could not kill PD-L1+ melanoma cells effectively. When we used PD-L1 inhibitor or silenced PD-L1 gene, inhibited PD-1/PD-L1 axis reversed the activity of the suppressed NK cells. Through these results, we supposed that PD-1/PD-L1 blockade could enhance the immune responses of NK cells against melanoma cells after radiotherapy and might overcome the PD-L1 mediated radioresistance of cancer cells.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248870PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016313PMC
April 2021

Trends in epidemiologic characteristics of end-stage renal disease from 2019 Korean Renal Data System (KORDS).

Kidney Res Clin Pract 2021 Mar 25;40(1):52-61. Epub 2021 Mar 25.

Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: The Korean Society of Nephrology (KSN) has maintained a nationwide end-stage renal disease (ESRD) registry data from Korean Renal Data System (KORDS) since 1985, as the representative registry of ESRD patients in Korea. This review is aimed to update the status of domestic ESRD and to provide evidence on the direction of dialysis therapy.

Methods: The KORDS Committee of KSN has collected data on dialysis centers and patients through an online registry program, and the data from 1986 to 2019 were analyzed.

Results: The incidence and prevalence of ESRD patients in Korea are increasing. The ESRD population numbered more than 100,000 in 2019, doubling during the 10 years since 2010. The proportion of diabetes mellitus as a major cause of ESRD seems to have reached a plateau. The increasing number of elderly dialysis patients is a constant trend, with more than half for the proportion of patients older than 65 years old in 2019. All-cause mortality decreased for the last approximately 20 years, regardless of sex, age, and cause of ESRD. The 5-year patient survival rate in both hemodialysis and peritoneal dialysis increased from 2001 to 2013. Since 2013, the patient survival rates in peritoneal dialysis were similar to those in hemodialysis. Cardiovascular complications were the leading cause of death in ESRD patients.

Conclusions: The incidence and prevalence of Korean ESRD patients have increased over time, although patient survival has also steadily increased. The establishment of a surveillance method to address the major cause of mortality in ESRD patients will help improve outcomes.
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http://dx.doi.org/10.23876/j.krcp.20.202DOI Listing
March 2021

Perilipin2 down-regulation in β cells impairs insulin secretion under nutritional stress and damages mitochondria.

JCI Insight 2021 Mar 30. Epub 2021 Mar 30.

Department of Internal Medicine, University of Iowa, Iowa City, United States of America.

Perilipin 2 (PLIN2) is the lipid droplet (LD) protein in β cells that increases under nutritional stress. Down-regulation of PLIN2 is often sufficient to reduce LD accumulation. To determine whether PLIN2 positively or negatively affects β cell function under nutritional stress, PLIN2 was down-regulated in mouse β cells, INS1 cells, and human islet cells. β cell specific deletion of PLIN2 in mice on a high fat diet reduced glucose-stimulated insulin secretion (GSIS) in vivo and in vitro. Down-regulation of PLIN2 in INS1 cells blunted GSIS after 24 h incubation with 0.2 mM palmitic acids. Down-regulation of PLIN2 in human pseudoislets cultured at 5.6 mM glucose impaired both phases of GSIS, indicating that PLIN2 is critical for GSIS. Down-regulation of PLIN2 decreased specific OXPHOS proteins in all three models and reduced oxygen consumption rates in INS1 cells and mouse islets. Moreover, we found that PLIN2 deficient INS1 cells increased the distribution of a fluorescent oleic acid analog to mitochondria and showed signs of mitochondrial stress as indicated by susceptibility to fragmentation and alterations of acyl-carnitines and glucose metabolites. Collectively, PLIN2 in β cells have an important role in preserving insulin secretion, β cell metabolism, and mitochondrial function under nutritional stress.
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http://dx.doi.org/10.1172/jci.insight.144341DOI Listing
March 2021

Psychometric properties of the Caregiver Strain Questionnaire among Chinese parents of children with ADHD or ASD.

Gen Psychiatr 2021 9;34(2):e100246. Epub 2021 Mar 9.

Department of Psychosomatic Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Background: There is an urgent need in clinical practice to measure the stress of parenting. The Caregiver Strain Questionnaire (CGSQ) was found to be useful to measure parenting stress, but it has not been validated among the Chinese population.

Aims: To assess the reliability and construct validity of the Chinese version of CGSQ among Chinese parents.

Methods: From 2016 to 2017, 266 parents (patient group) with a child having DSM-5-defined attention deficit hyperactivity disorder (ADHD) (n=107) or autism spectrum disorder (ASD) (n=159) and 268 parents of healthy children (control group) were recruited to the present study in Kunming, Yunnan province. All the parents were asked to fill out the Chinese version of CGSQ. We conducted exploratory factor analysis and confirmatory factor analysis (CFA) to verify construct validity of CGSQ in both patient and control groups. Cronbach's α coefficient as an index of internal consistency was assessed for each subscale. Fourteen days later, 23 subjects filled out the scale again. Intra-class correlation coefficient was calculated to evaluate the test-retest reliability.

Results: (1) Cronbach's alpha of the global scale was 0.901 for the control group and 0.952 for the patient group. The test-retest reliability for the whole scale was 0.890; (2) CFA indicated that the three-factor model had better fitting indices compared with the two-factor model in both groups. Besides, the fitting indices in the patient group were more favourable than those of the control group, with χ/df=1.564, Goodness-of-Fit Index=0.841, Comparative Fit Index=0.954, and root mean square error of approximation=0.065 for the patient group at three-factor model; (3) The caregiver strain of ASD parents was statistically higher than that of ADHD parents, and caregiver strain of ADHD parents was higher than that of control group.

Conclusion: These findings provide initial evidence to support the construct validity and reliability of CGSQ as a parenting stress measurement tool for Chinese parents, especially for parents of children with ADHD or ASD.
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http://dx.doi.org/10.1136/gpsych-2020-100246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944967PMC
March 2021

UXT chaperone prevents proteotoxicity by acting as an autophagy adaptor for p62-dependent aggrephagy.

Nat Commun 2021 03 29;12(1):1955. Epub 2021 Mar 29.

Department of Life Sciences, Korea University, Seoul, Republic of Korea.

p62/SQSTM1 is known to act as a key mediator in the selective autophagy of protein aggregates, or aggrephagy, by steering ubiquitinated protein aggregates towards the autophagy pathway. Here, we use a yeast two-hybrid screen to identify the prefoldin-like chaperone UXT as an interacting protein of p62. We show that UXT can bind to protein aggregates as well as the LB domain of p62, and, possibly by forming an oligomer, increase p62 clustering for its efficient targeting to protein aggregates, thereby promoting the formation of the p62 body and clearance of its cargo via autophagy. We also find that ectopic expression of human UXT delays SOD1(A4V)-induced degeneration of motor neurons in a Xenopus model system, and that specific disruption of the interaction between UXT and p62 suppresses UXT-mediated protection. Together, these results indicate that UXT functions as an autophagy adaptor of p62-dependent aggrephagy. Furthermore, our study illustrates a cooperative relationship between molecular chaperones and the aggrephagy machinery that efficiently removes misfolded protein aggregates.
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http://dx.doi.org/10.1038/s41467-021-22252-7DOI Listing
March 2021

Gender differences in the relationships between different types of childhood trauma and resilience on depressive symptoms among Chinese adolescents.

Prev Med 2021 Mar 26:106523. Epub 2021 Mar 26.

Department of Maternal, Child and Adolescent Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Growing studies have paid attention to the relationships between childhood trauma, resilience and depressive symptoms. Depression is more common in girls, while gender differences in these associations have been rarely studied. Yet the study will be beneficial for prevention and intervention of depression in adolescents. The aim of this study is to examine gender differences in the effects of different types of childhood trauma and resilience on depressive symptoms. Data was collected from 6510 students (3408 males, aged 10-17 years) in Wuhan, Hubei, China from 2015 to 2016. Participants completed a self-report questionnaire assessing childhood trauma, resilience, and depressive symptoms. Multiple regression analysis was used to determine gender differences in the relationships between childhood trauma, resilience and depressive symptoms. We found that childhood trauma was positively related to depressive symptoms for both genders, but the relationship in females was stronger than in males. No significant gender difference was found in the independent effect of resilience to depressive symptoms. Resilience moderated the effects of emotional abuse, physical abuse and sexual abuse on depressive symptoms in both males and females. However, the interaction effect of resilience with emotional abuse on depressive symptoms was stronger in females compared to males. Our findings revealed gender differences in the links between childhood trauma and depressive symptoms among adolescents, and the interaction effect of resilience and childhood emotional abuse on depressive symptoms was gender-specific. These provide the basis for gender-special prevention and intervention measures for depressive symptoms in adolescents.
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http://dx.doi.org/10.1016/j.ypmed.2021.106523DOI Listing
March 2021

Pharmacogenetic associations of NRG1 polymorphisms with neurocognitive performance and clinical symptom response to risperidone in the untreated schizophrenia.

Schizophr Res 2021 Mar 23;231:67-69. Epub 2021 Mar 23.

Department of Psychiatry, the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, China.

Objective: To explore pharmacogenetic relationships of NRG1 genotypes with neurocognitive performance and clinical symptoms after 12 week treatment of risperidone in Chinese Han first-episode schizophrenia.

Methods: A cohort of 221 patients with schizophrenia were recruited for this research. Finally 177 untreated first-episode patients were clinically evaluated with the Positive and Negative Syndrome Scale (PANSS), Raven's Standard Progressive Matrices (RSPM), Digit Vigilance Test (DVT), Digit Span (DS), underwent genotyping for five polymorphisms of NRG1, and completed a 12-week prospective study of risperidone monotherapy.

Results: 1. After risperidone treatment of 12 weeks, the total scores, positive score, negative score and general score of PANSS decreased significantly; the scores of RSPM, DVT and DS increased significantly. 2. No significant association with PANSS scores at baseline or change in scores after 12 weeks'treatment was found with any of the five SNPs. There was also neither significant association of DVT, DS or RSPM at baseline with any of the five SNPs. 3. After risperidone treatment of 12 weeks, rs3924999 and rs35753505 showed significant association with change in DVT and in RSPM in which there were significant differences among different genotype groups.

Conclusion: This study suggested pharmacogenetic relationships between NRG1 variants and changes in cognition response with exposure to 12 weeks of treatment with risperidone. Two variants, rs3924999 and rs35753505, in the NRG1 gene were associated with the changes in attention and reasoning ability after risperidone treatment of 12 weeks.
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http://dx.doi.org/10.1016/j.schres.2021.03.001DOI Listing
March 2021

Social Inferences in Agenesis of the Corpus Callosum and Autism: Semantic Analysis and Topic Modeling.

J Autism Dev Disord 2021 Mar 25. Epub 2021 Mar 25.

Fuller Graduate School of Psychology, Travis Research Institute, Pasadena, CA, USA.

Impoverished capacity for social inference is one of several symptoms that are common to both agenesis of the corpus callosum (AgCC) and Autism Spectrum Disorder (ASD). This research compared the ability of 14 adults with AgCC, 13 high-functioning adults with ASD and 14 neurotypical controls to accurately attribute social meaning to the interactions of animated triangles. Descriptions of the animations were analyzed in three ways: subjective ratings, Linguistic Inquiry and Word Count, and topic modeling (Latent Dirichlet Allocation). Although subjective ratings indicated that all groups made similar inferences from the animations, the index of perplexity (atypicality of topic) generated from topic modeling revealed that inferences from individuals with AgCC or ASD displayed significantly less social imagination than those of controls.
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http://dx.doi.org/10.1007/s10803-021-04957-2DOI Listing
March 2021

Primary Borderline Mucinous Testicular Tumor: A Case Report and Literature Review.

Front Oncol 2020 9;10:619774. Epub 2021 Mar 9.

Department of Ultrasound, Shanxi Bethune Hospital affiliated to Shanxi Medical University, Taiyuan, China.

Primary mucinous tumors of the testis and paratestis are very rare, with only 29 reported cases detected in a PubMed search. The histopathological characteristics of primary testicular mucinous tumors are similar to their ovarian counterparts, and the diagnosis and naming criteria refer to the criteria for female ovarian mucinous tumors. However, the clinical and imaging features of primary testicular mucinous tumors are poorly understood, and they are thus frequently undiagnosed or misdiagnosed. We present the case of a patient with a primary testicular mucinous tumor. A 52-year-old man presented with a 1-year history of painless enlargement of the left scrotum. Ultrasound examination revealed a cystic mass in the left testis, with viscous fluid areas and calcified spots, irregular solid bulges on the cyst wall, and a small blood supply. Serum alpha-fetoprotein, β-human chorionic gonadotropin, lactate dehydrogenase, renal function, inflammatory markers, and routine urine and blood examinations were all normal. The patient underwent radical resection of the left testis. Postoperative pathology showed a multilocular cystic mass, with the inner wall of the sac lined with mucous columnar epithelial cells, some with mild nuclear atypia, and no interstitial infiltration. The pathological diagnosis was testicular mucinous tumor. Postoperative abdominal and pelvic computed tomography, colonoscopy, and gastroscopy showed no suspicious lesions. The final diagnosis was primary testicular borderline mucinous tumor. The patient underwent postoperative follow-up examinations once a year for 4 years. Serum tumor markers, scrotal ultrasound, abdominal and pelvic computed tomography scans, and colonoscopy and gastroscopy revealed no evidence of metastases or other primary adenocarcinoma. This case highlights the clinical and imaging characteristics of primary testicular mucinous tumors, which might aid their differential diagnosis.
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http://dx.doi.org/10.3389/fonc.2020.619774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986722PMC
March 2021

Optimal Time Intervals in Two-Stage Takeover Warning Systems With Insight Into the Drivers' Neuroticism Personality.

Front Psychol 2021 8;12:601536. Epub 2021 Mar 8.

Department of Psychology, Zhejiang Sci-Tech University, Hangzhou, China.

Conditional automated driving [level 3, Society of Automotive Engineers (SAE)] requires drivers to take over the vehicle when an automated system's failure occurs or is about to leave its operational design domain. Two-stage warning systems, which warn drivers in two steps, can be a promising method to guide drivers in preparing for the takeover. However, the proper time intervals of two-stage warning systems that allow drivers with different personalities to prepare for the takeover remain unclear. This study explored the optimal time intervals of two-stage warning systems with insights into the drivers' neuroticism personality. A total of 32 drivers were distributed into two groups according to their self-ratings in neuroticism (high vs. low). Each driver experienced takeover under the two-stage warning systems with four time intervals (i.e., 3, 5, 7, and 9 s). The takeover performance (i.e., hands-on-steering-wheel time, takeover time, and maximum resulting acceleration) and subjective opinions (i.e., appropriateness and usefulness) for time intervals and situation awareness (SA) were recorded. The results showed that drivers in the 5-s time interval had the best takeover preparation (fast hands-on steering wheel responses and sufficient SA). Furthermore, both the 5- and 7-s time intervals resulted in more rapid takeover reactions and were rated more appropriate and useful than the 3- and 9-s time intervals. In terms of personality, drivers with high neuroticism tended to take over immediately after receiving takeover messages, at the cost of SA deficiency. In contrast, drivers with low neuroticism responded safely by judging whether they gained enough SA. We concluded that the 5-s time interval was optimal for drivers in two-stage takeover warning systems. When considering personality, drivers with low neuroticism had no strict requirements for time intervals. However, the extended time intervals were favorable for drivers with high neuroticism in developing SA. The present findings have reference implications for designers and engineers to set the time intervals of two-stage warning systems according to the neuroticism personality of drivers.
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http://dx.doi.org/10.3389/fpsyg.2021.601536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982420PMC
March 2021

SVEP1 is a human coronary artery disease locus that promotes atherosclerosis.

Sci Transl Med 2021 Mar;13(586)

Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.

A low-frequency variant of sushi, von Willebrand factor type A, EGF, and pentraxin domain-containing protein 1 (SVEP1), an extracellular matrix protein, is associated with risk of coronary disease in humans independent of plasma lipids. Despite a robust statistical association, if and how SVEP1 might contribute to atherosclerosis remained unclear. Here, using Mendelian randomization and complementary mouse models, we provide evidence that SVEP1 promotes atherosclerosis in humans and mice and is expressed by vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque. VSMCs also interact with SVEP1, causing proliferation and dysregulation of key differentiation pathways, including integrin and Notch signaling. Fibroblast growth factor receptor transcription increases in VSMCs interacting with SVEP1 and is further increased by the coronary disease-associated variant p.D2702G. These effects ultimately drive inflammation and promote atherosclerosis. Together, our results suggest that VSMC-derived SVEP1 is a proatherogenic factor and support the concept that pharmacological inhibition of SVEP1 should protect against atherosclerosis in humans.
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http://dx.doi.org/10.1126/scitranslmed.abe0357DOI Listing
March 2021

Longitudinal Analysis of Human Memory T-Cell Response according to the Severity of Illness up to 8 Months after SARS-CoV-2 Infection.

J Infect Dis 2021 Mar 23. Epub 2021 Mar 23.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: Understanding the memory T-cell response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is crucial for assessing the longevity of protective immunity after SARS-CoV-2 infection or coronavirus disease-2019 (COVID-19) vaccination. However, the longitudinal memory T-cell response up to 8 months post-symptom onset (PSO) according to the severity of illness is unknown.

Methods: We analyzed peripheral blood mononuclear cells (PBMCs) from healthy volunteers or patients with COVID-19 who experienced asymptomatic, mild, or severe illness at 2, 5, and 8 months PSO. SARS-CoV-2 spike, nucleocapsid, and membrane protein-stimulated PBMCs were subjected to flow cytometry analysis.

Results: A total of 24 patients-seven asymptomatic and nine with mild and eight with severe disease-as well as six healthy volunteers were analyzed. SARS-CoV-2-specific OX40 +CD137 + CD4 + T cells and CD69 +CD137 + CD8 + T cells persisted at 8 months PSO. Also, antigen-specific cytokine-producing or polyfunctional CD4 + T cells were maintained for up to 8 months PSO. Memory CD4 + T-cell responses tended to be greater in patients who had severe illness than in those with mild or asymptomatic disease.

Conclusions: Memory response to SARS-CoV-2, based on the frequency and functionality, persists for 8 months PSO. Further investigations involving its longevity and protective effect from reinfection are warranted.
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http://dx.doi.org/10.1093/infdis/jiab159DOI Listing
March 2021

Effect of Transport Time on the Use of Reperfusion Therapy for Patients with Acute Ischemic Stroke in Korea.

J Korean Med Sci 2021 Mar 22;36(11):e77. Epub 2021 Mar 22.

Department of Neurology, University of California San Francisco, San Francisco, CA, USA.

Background: We investigated the association between geographic proximity to hospitals and the administration rate of reperfusion therapy for acute ischemic stroke.

Methods: We identified patients with acute ischemic stroke who visited the hospital within 12 hours of symptom onset from a prospective nationwide multicenter stroke registry. Reperfusion therapy was classified as intravenous thrombolysis (IVT), endovascular therapy (EVT), or combined therapy. The association between the proportion of patients who were treated with reperfusion therapy and the ground transport time was evaluated using a spline regression analysis adjusted for patient-level characteristics. We also estimated the proportion of Korean population that lived within each 30-minute incremental service area from 67 stroke centers accredited by the Korean Stroke Society.

Results: Of 12,172 patients (mean age, 68 ± 13 years; men, 59.7%) who met the eligibility criteria, 96.5% lived within 90 minutes of ground transport time from the admitting hospital. The proportion of patients treated with IVT decreased significantly when stroke patients lived beyond 90 minutes of the transport time ( = 0.006). The proportion treated with EVT also showed a similar trend with the transport time. Based on the residential area, 98.4% of Korean population was accessible to 67 stroke centers within 90 minutes.

Conclusion: The use of reperfusion therapy for acute stroke decreased when patients lived beyond 90 minutes of the ground transport time from the hospital. More than 95% of the South Korean population was accessible to 67 stroke centers within 90 minutes of the ground transport time.
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http://dx.doi.org/10.3346/jkms.2021.36.e77DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985286PMC
March 2021

Solar Energy Conversion through Thylakoid Membranes Wired by Osmium Redox Polymer and Indium Tin Oxide Nanoparticles.

ChemSusChem 2021 Mar 22. Epub 2021 Mar 22.

Chonbuk National University: Jeonbuk National University, Chemical Engineering, KOREA, REPUBLIC OF.

For several decades, much attention has been paid to thylakoid membranes (TMs) as photocatalysts for converting solar light to electricity. Despite extensive research, current technology provides only limited photocurrents. Here we report a novel method based on TM-composite material for achieving high photocurrent. When a thin film composed of TMs, osmium redox polymer (Os-RP), and indium tin oxide nanoparticles (ITOnp) was formed on a porous graphite surface, appreciable photocurrent as high as 0.5 mA cm -2 was achieved at 0.4 V vs. Ag/AgCl. Each component plays its own role in transferring electrons from TMs to the anode, resulting in sharp drop in phohtocurrent with missing any component. Optimization between these three components showed 1:0.5:30 (TM:Os-RP:ITOnp) was the best ratio. Action spectra confirmed that TMs was the origin of photocurrent. It was inferred from blocking experiments using 3-(3,4-dichlorophenyl)-1,1-dimethylurea as an inhibitor that about 41% of photocurrent was transferred from Q A in photosystem II to the electrode via Os-RP and ITOnp. Quantum efficiencies at 430 nm and 660 nm were 12.2% and 18.5%, respectively. Turnover frequency for water oxidation depended upon the amount of the composite. A complete cell with Pt/C cathode produced P max of 122 μW cm -2 at 758 μA cm -2 under one sun illumination, which is the highest power density to our knowledge. This study opened a possibility of using TMs as photocatalysts for solar energy conversion.
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http://dx.doi.org/10.1002/cssc.202100288DOI Listing
March 2021