Publications by authors named "Joohee Kim"

45 Publications

Smart contact lens and transparent heat patch for remote monitoring and therapy of chronic ocular surface inflammation using mobiles.

Sci Adv 2021 Mar 31;7(14). Epub 2021 Mar 31.

Nano Science Technology Institute, Department of Materials Science and Engineering, Yonsei University, Seoul 03722, Republic of Korea.

Wearable electronic devices that can monitor physiological signals of the human body to provide biomedical information have been drawing extensive interests for sustainable personal health management. Here, we report a human pilot trial of a soft, smart contact lens and a skin-attachable therapeutic device for wireless monitoring and therapy of chronic ocular surface inflammation (OSI). As a diagnostic device, this smart contact lens enables real-time measurement of the concentration of matrix metalloproteinase-9, a biomarker for OSI, in tears using a graphene field-effect transistor. As a therapeutic device, we also fabricated a stretchable and transparent heat patch attachable on the human eyelid conformably. Both diagnostic and therapeutic devices can be incorporated using a smartphone for their wireless communications, thereby achieving instantaneous diagnosis of OSI and automated hyperthermia treatments. Furthermore, in vivo tests using live animals and human subjects confirm their good biocompatibility and reliability as a noninvasive, mobile health care solution.
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http://dx.doi.org/10.1126/sciadv.abf7194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011975PMC
March 2021

Loss of splicing factor IK impairs normal skeletal muscle development.

BMC Biol 2021 Apr 1;19(1):44. Epub 2021 Apr 1.

Department of Biological Sciences, Sookmyung Women's University, Seoul, 04310, Republic of Korea.

Background: IK is a splicing factor that promotes spliceosome activation and contributes to pre-mRNA splicing. Although the molecular mechanism of IK has been previously reported in vitro, the physiological role of IK has not been fully understood in any animal model. Here, we generate an ik knock-out (KO) zebrafish using the CRISPR/Cas9 system to investigate the physiological roles of IK in vivo.

Results: The ik KO embryos display severe pleiotropic phenotypes, implying an essential role of IK in embryonic development in vertebrates. RNA-seq analysis reveals downregulation of genes involved in skeletal muscle differentiation in ik KO embryos, and there exist genes having improper pre-mRNA splicing among downregulated genes. The ik KO embryos display impaired neuromuscular junction (NMJ) and fast-twitch muscle development. Depletion of ik reduces myod1 expression and upregulates pax7a, preventing normal fast muscle development in a non-cell-autonomous manner. Moreover, when differentiation is induced in IK-depleted C2C12 myoblasts, myoblasts show a reduced ability to form myotubes. However, inhibition of IK does not influence either muscle cell proliferation or apoptosis in zebrafish and C2C12 cells.

Conclusion: This study provides that the splicing factor IK contributes to normal skeletal muscle development in vivo and myogenic differentiation in vitro.
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http://dx.doi.org/10.1186/s12915-021-00980-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015194PMC
April 2021

Rutin inhibits DRP1-mediated mitochondrial fission and prevents ethanol-induced hepatotoxicity in HepG2 cells and zebrafish.

Anim Cells Syst (Seoul) 2021 Feb 11;25(1):74-81. Epub 2021 Feb 11.

Department of Biological Sciences, Sookmyung Women's University, Seoul, Korea.

Excessive alcohol consumption causes the cellular and tissue damage. The toxic metabolites of ethanol are harmful to multiple organ systems, such as the central nervous system, skeletal muscles, and liver, and cause alcohol-induced diseases like cancer, as well as induce hepatotoxicity, and alcoholic myopathy. Alcohol exposure leads to a surge in hepatic alcohol metabolism and oxygen consumption, a decrease in hepatic ATP, and the rapid accumulation of lipid within hepatocytes. Several pathologies are closely linked to defective mitochondrial dynamics triggered by abnormal mitochondrial function and cellular homeostasis, raising the possibility that novel drugs targeting mitochondrial dynamics may have therapeutic potential in restoring cellular homeostasis in ethanol-induced hepatotoxicity. Rutin is a phytochemical polyphenol known to protect cells from cytotoxic chemicals. We investigated the effects of rutin on mitochondrial dynamics induced by ethanol. We found that rutin enhances mitochondrial dynamics by suppressing mitochondrial fission and restoring the balance of the mitochondrial dynamics. Mitochondrial elongation following rutin treatment of ethanol exposed cells was accompanied by reduced DRP1 expression. These data suggest that rutin plays an important role in remodeling of mitochondrial dynamics to alleviate hepatic steatosis and enhance mitochondrial function and cell viability.
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http://dx.doi.org/10.1080/19768354.2021.1882565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935124PMC
February 2021

Smart, soft contact lens for wireless immunosensing of cortisol.

Sci Adv 2020 Jul 8;6(28):eabb2891. Epub 2020 Jul 8.

Nano Science Technology Institute, Department of Materials Science and Engineering, Yonsei University, Seoul 03722, Republic of Korea.

Despite various approaches to immunoassay and chromatography for monitoring cortisol concentrations, conventional methods require bulky external equipment, which limits their use as mobile health care systems. Here, we describe a human pilot trial of a soft, smart contact lens for real-time detection of the cortisol concentration in tears using a smartphone. A cortisol sensor formed using a graphene field-effect transistor can measure cortisol concentration with a detection limit of 10 pg/ml, which is low enough to detect the cortisol concentration in human tears. In addition, this soft contact lens only requires the integration of this cortisol sensor with transparent antennas and wireless communication circuits to make a smartphone the only device needed to operate the lens remotely without obstructing the wearer's view. Furthermore, in vivo tests using live rabbits and the human pilot experiment confirmed the good biocompatibility and reliability of this lens as a noninvasive, mobile health care solution.
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http://dx.doi.org/10.1126/sciadv.abb2891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455488PMC
July 2020

Effect of Ionic Polymer Membrane with Multiwalled Carbon Nanotubes on the Mechanical Performance of Ionic Electroactive Polymer Actuators.

Polymers (Basel) 2020 Feb 10;12(2). Epub 2020 Feb 10.

Department of Nanoscience and Engineering, Center for Nano Manufacturing, Inje University, Gimhae 50834, Korea.

Ionic electroactive polymer (IEAP) actuators have received interest because of their advantageous properties, including their large displacement, high energy density, light weight, and low power consumption under a low electric field. However, they have a low blocking force under driving, and it is difficult to control the thickness of the ionic polymer membrane. In this study, an IEAP actuator is fabricated using a Nafion membrane with added multiwalled carbon nanotubes to increase the blocking force. A heat press two-step process is also developed to produce a constant and uniform membrane. The fabricated Nafion membrane with 0.2 wt% multiwalled carbon nanotubes has the largest displacement and highest blocking force. As a result, the developed heat press two-step method can be used in various polymer-casting fields, and the fabricated carbon nanotube-based IEAP actuators can serve as useful references in fields such as flexible robotics and artificial muscles.
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http://dx.doi.org/10.3390/polym12020396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077732PMC
February 2020

Printing of wirelessly rechargeable solid-state supercapacitors for soft, smart contact lenses with continuous operations.

Sci Adv 2019 12 6;5(12):eaay0764. Epub 2019 Dec 6.

Nano Science Technology Institute, Department of Materials Science and Engineering, Yonsei University, Seoul 03722, Republic of Korea.

Recent advances in smart contact lenses are essential to the realization of medical applications and vision imaging for augmented reality through wireless communication systems. However, previous research on smart contact lenses has been driven by a wired system or wireless power transfer with temporal and spatial restrictions, which can limit their continuous use and require energy storage devices. Also, the rigidity, heat, and large sizes of conventional batteries are not suitable for the soft, smart contact lens. Here, we describe a human pilot trial of a soft, smart contact lens with a wirelessly rechargeable, solid-state supercapacitor for continuous operation. After printing the supercapacitor, all device components (antenna, rectifier, and light-emitting diode) are fully integrated with stretchable structures for this soft lens without obstructing vision. The good reliability against thermal and electromagnetic radiations and the results of the in vivo tests provide the substantial promise of future smart contact lenses.
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http://dx.doi.org/10.1126/sciadv.aay0764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957331PMC
December 2019

Intraocular Pressure Monitoring Following Islet Transplantation to the Anterior Chamber of the Eye.

Nano Lett 2020 03 21;20(3):1517-1525. Epub 2019 Nov 21.

Nano Science Technology Institute, Department of Materials Science and Engineering, Yonsei University, Seoul 03722, Republic of Korea.

Intraocular islet transplantation was investigated as a new procedure to treat diabetes. The development of this procedure requires close monitoring of the function of both eye and islet graft. We developed a soft, smart contact lens to monitor the intraocular pressure and applied this for noninvasive monitoring in association with the intraocular islet transplantation in diabetes. A strain sensor inside the lens can detect detailed changes in intraocular pressure by focusing the strain only in the desired, selective area of the contact lens. In addition, this smart contact lens can transmit the real-time value of the intraocular pressure wirelessly using an antenna. The wireless measurement of intraocular pressure that was obtained using this contact lens had a high correlation with the intraocular pressure measured by a rebound tonometer, thereby proving the good accuracy of the contact lens sensor. In the initial period, a slight elevation of intraocular pressure was observed, but the pressure returned to normal in the initial period after the transplantation. This type of monitoring will provide important information on potential changes in the intraocular pressure associated with the transplantation procedure, and it enables appropriate clinical safety steps to be taken, if needed.
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http://dx.doi.org/10.1021/acs.nanolett.9b03605DOI Listing
March 2020

Interactive Skin Display with Epidermal Stimuli Electrode.

Adv Sci (Weinh) 2019 Jul 26;6(13):1802351. Epub 2019 Apr 26.

Department of Materials Science and Engineering Yonsei University 50 Yonsei-ro, Seodaemun-gu Seoul 03722 Republic of Korea.

In addition to the demand for stimuli-responsive sensors that can detect various vital signals in epidermal skin, the development of electronic skin displays that quantitatively detect and visualize various epidermal stimuli such as the temperature, sweat gland activity, and conductance simultaneously are of significant interest for emerging human-interactive electronics used in health monitoring. Herein, a novel interactive skin display with epidermal stimuli electrode (ISDEE) allowing for the simultaneous sensing and display of multiple epidermal stimuli on a single device is presented. It is based on a simple two-layer architecture on a topographically patterned elastomeric polymer composite with light-emitting inorganic phosphors, upon which two electrodes are placed with a certain parallel gap. The ISDEE is directly mounted on human skin, which by itself serves as a field-responsive floating electrode of the display operating under an alternating current (AC). The AC field exerted on the epidermal skin layer depends on the conductance of the skin, which can be modulated based on a variety of physiological skin factors, such as the temperature, sweat gland activity, and pressure. Conductance-dependent field-induced electroluminescence is achieved, giving rise to an on-hand sensing display platform where a variety of human information can be directly sensed and visualized.
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http://dx.doi.org/10.1002/advs.201802351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662062PMC
July 2019

Structural Characteristics of Seven IL-32 Variants.

Immune Netw 2019 Apr 16;19(2):e8. Epub 2019 Apr 16.

Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea.

IL-32 exists as seven mRNA transcripts that can translate into distinct individual IL-32 variants with specific protein domains. These translated protein domains of IL-32 variants code for specific functions that allow for interaction with different molecules intracellularly or extracellularly. The longest variant is IL-32γ possessing 234 amino acid residues with all 11 protein domains, while the shortest variant is IL-32α possessing 131 amino acid residues with three of the protein domains. The first domain exists in 6 variants except IL-32δ variant, which has a distinct translation initiation codon due to mRNA splicing. The last eleventh domain is common domain for all seven IL-32 variants. Numerous studies in different fields, such as inflammation, autoimmunity, pathogen infection, and cancer biology, have claimed the specific biological activity of individual IL-32 variant despite the absence of sufficient data. There are 4 additional IL-32 variants without proper transcripts. In this review, the structural characteristics of seven IL-32 transcripts are described based on the specific protein domains.
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http://dx.doi.org/10.4110/in.2019.19.e8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494766PMC
April 2019

Fast and Stable Ionic Electroactive Polymer Actuators with PEDOT:PSS/(Graphene⁻Ag-Nanowires) Nanocomposite Electrodes.

Sensors (Basel) 2018 Sep 16;18(9). Epub 2018 Sep 16.

Department of Nanoscience and Engineering, Center for Nano Manufacturing, Inje University, Gimhae 50834, Korea.

Ionic electroactive polymer (IEAP) actuators that are driven by electrical stimuli have been widely investigated for use in practical applications. However, conventional electrodes in IEAP actuators have a serious drawback of poor durability under long-term actuation in open air, mainly because of leakage of the inner electrolyte and hydrated cations through surface cracks on the metallic electrodes. To overcome this problem, a top priority is developing new high-performance ionic polymer actuators with graphene electrodes that have superior mechanical, electrical conductivity, and electromechanical properties. However, the task is made difficultby issues such as the low electrical conductivity of graphene (G). The percolation network of silver nanowires (Ag-NWs) is believed to enhance the conductivity of graphene, while poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), which exhibits excellent stability under ambient conditions, is expected to improve the actuation performance of IEAP actuators. In this study, we developed a very fast, stable, and durable IEAP actuator by employing electrodes made of a nanocomposite comprising PEDOT:PSS and graphene⁻Ag-NWs (P/(G⁻Ag)). The cost-effective P/(G⁻Ag) electrodes with high electrical conductivity displayed a smooth surface resulting from the PEDOT:PSS coating, which prevented oxidation of the surface upon exposure to air, and showedstrong bonding between the ionic polymer and the electrode surface. More interestingly, the proposed IEAP actuator based on the P/G⁻Ag electrode can be used in active biomedical devices, biomimetic robots, wearable electronics, and flexible soft electronics.
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http://dx.doi.org/10.3390/s18093126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163802PMC
September 2018

L1 Recombinant Proteins of HPV Tested for Antibody Forming Using Sera of HPV Quadrivalent Vaccine.

Immune Netw 2018 Jun 4;18(3):e19. Epub 2018 Jun 4.

Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea.

Virus-like particles (VLPs) derived from human papillomavirus (HPV) L1 capsid proteins were used for HPV quadrivalent recombinant vaccine. The HPV quadrivalent vaccine is administrated in a 3-dose regimen of initial injection followed by subsequent doses at 2 and 6 months to prevent cervical cancer, vulvar, and vaginal cancers. The type 6, 11, 16, or 18 of HPV infection is associated with precancerous lesions and genital warts in adolescents and young women. The HPV vaccine is composed of viral L1 capsid proteins are produced in eukaryotic expression systems and purified in the form of VLPs. Four different the L1 protein of 3 different subtypes of HPV: HPV11, HPV16, and HPV18 were expressed in divided into 2 fragments as N- and C-terminal of each protein in order to examine the efficacy of HPV vaccine. Vaccinated sera failed to recognize N-terminal L1 HPV type 16 and type 18 by western blot while they detected N-terminal L1 protein of HPV type 11. Moreover, the recombinant C-terminal L1 proteins of type 16 was non-specifically recognized by the secondary antibody conjugated with horseradish peroxidase. This expression and purification system may provide simple method to obtain robust recombinant L1 protein of HPV subtypes to improve biochemical analysis of antigens with immunized sera.
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http://dx.doi.org/10.4110/in.2018.18.e19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026689PMC
June 2018

Lactobacillus gasseri BNR17 Supplementation Reduces the Visceral Fat Accumulation and Waist Circumference in Obese Adults: A Randomized, Double-Blind, Placebo-Controlled Trial.

J Med Food 2018 May 24;21(5):454-461. Epub 2018 Apr 24.

2 Department of Family Medicine, Seoul National University Hospital , Seoul, Korea.

Lactobacillus gasseri BNR17 is a probiotic strain isolated from human breast milk. Animal studies reported that BNR17 inhibited increases in body weight and adipose tissue weights. The purpose of this study was to evaluate the antiobesity effects of BNR17 in humans. In a randomized, double-blind, placebo-controlled trial, 90 volunteers aged 20-75 years with body mass index (BMI) from 25 to 35 kg/m were randomized to receive a placebo, low-dose BNR (BNR-L, 10 CFU/day), or high-dose BNR (BNR-H, 10 CFU/day) for 12 weeks. Body weight, BMI, waist and hip circumferences, waist-to-hip ratio, abdominal adipose tissue areas, body fat mass, lean body mass, and biochemical parameters were assessed at the beginning and end of the trial. Visceral adipose tissue (VAT) was significantly decreased in the BNR-H group compared with the placebo group (P = .038). Difference of VAT areas of the BNR-H group compared with the placebo group after 12-week consumption of BNR17 was significant (-21.6 cm, P = .012). Waist circumferences were significantly decreased in both the BNR-L and BNL-H groups (P = .045 and .012, respectively) compared with the baseline values, but not in the placebo group. Biochemical parameters were not significantly different among the groups. These findings suggest that daily consumption of BNR17 may contribute to reduced visceral fat mass in obese adults.
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http://dx.doi.org/10.1089/jmf.2017.3937DOI Listing
May 2018

A double blind, placebo-controlled, randomized clinical trial that breast milk derived- BNR17 mitigated diarrhea-dominant irritable bowel syndrome.

J Clin Biochem Nutr 2018 Mar 11;62(2):179-186. Epub 2018 Jan 11.

Digestive Disease Center, CHA University Bundang Medical Center, 59 Yatap-roBundang-gu, Seongnam 13496, Korea.

The exact pathogenesis of diarrhea-dominant irritable bowel syndrome (IBS) is not known, but the abnormal microbiota of the gastrointestinal tract is considered to be one of the important contributing factors as in other gastrointestinal diseases such as inflammatory bowel disease, antibiotic-associated diarrhea, and colorectal cancer as well as systemic diseases. Though diverse trials of probiotics had been continued in the treatment of diarrhea-IBS, only a few proved by randomized clinical trial. To prove the efficacy of BNR17 isolated from breast milk in patients with diarrhea-IBS, prospective, randomized, placebo controlled clinical trial was done including health related-quality of life analysis, colon transit time, and the changes of fecal microbiota. BNR17 significantly improved the symptoms of diarrhea compared to control group. Health related-QOL analysis showed significant improvement of abdominal pain, distension, disturbed daily life, and mean defecation frequency with BNR17. On comparative CTT before and after BNR17, 6 out of 24 subjects showed significant correction of rapid colon transit pattern, while only 2 out of 24 in placebo (<0.01). Upon fecal microbiota analysis, BNR17 significantly increased , , , and . Conclusively, BNR17 can be a potential probiotics to ameliorate diarrhea-IBS.
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http://dx.doi.org/10.3164/jcbn.17-73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874236PMC
March 2018

Soft, smart contact lenses with integrations of wireless circuits, glucose sensors, and displays.

Sci Adv 2018 01 24;4(1):eaap9841. Epub 2018 Jan 24.

School of Materials Science and Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.

Recent advances in wearable electronics combined with wireless communications are essential to the realization of medical applications through health monitoring technologies. For example, a smart contact lens, which is capable of monitoring the physiological information of the eye and tear fluid, could provide real-time, noninvasive medical diagnostics. However, previous reports concerning the smart contact lens have indicated that opaque and brittle components have been used to enable the operation of the electronic device, and this could block the user's vision and potentially damage the eye. In addition, the use of expensive and bulky equipment to measure signals from the contact lens sensors could interfere with the user's external activities. Thus, we report an unconventional approach for the fabrication of a soft, smart contact lens in which glucose sensors, wireless power transfer circuits, and display pixels to visualize sensing signals in real time are fully integrated using transparent and stretchable nanostructures. The integration of this display into the smart lens eliminates the need for additional, bulky measurement equipment. This soft, smart contact lens can be transparent, providing a clear view by matching the refractive indices of its locally patterned areas. The resulting soft, smart contact lens provides real-time, wireless operation, and there are in vivo tests to monitor the glucose concentration in tears (suitable for determining the fasting glucose level in the tears of diabetic patients) and, simultaneously, to provide sensing results through the contact lens display.
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http://dx.doi.org/10.1126/sciadv.aap9841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5787380PMC
January 2018

Species Specific Antiviral Activity of Porcine Interferon-α8 (IFNα8).

Immune Netw 2017 Dec 19;17(6):424-436. Epub 2017 Dec 19.

Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea.

Interferons (IFNs) have been known as antiviral genes and they are classified by type 1, type 2, and type 3 IFN. The type 1 IFN consists of IFNα, IFNβ, IFNτ, and IFNω whereas the type 2 IFN consists of only IFNγ, which is a key cytokine driving T helper cell type 1 immunity. IFNλ belongs to the type 3 IFN, which is also known as IL-28 and IL-29 possessing antiviral activities. Type 1 IFN is produced by viral infection whereas type 2 IFN is induced by mitogenic or antigenic T-cell stimuli. The IFNτ of bovine was first discovered in an ungulate ruminant recognition hormone. IFNτ belongs to the type 1 IFN with the common feature of type 1 IFN such as antiviral activity. IFNs have been mostly studied for basic research and clinical usages therefore there was no effort to investigate IFNs in industrial animals. Here we cloned porcine IFNα8 from peripheral blood mononuclear cells of Korean domestic pig (). The newly cloned IFNα8 amino acid sequence from Korean domestic pig shares 98.4% identity with the known porcine IFNα8 in databank. The recombinant porcine IFNα8 showed potent antiviral activity and protected bovine Madin-Darby bovine kidney epithelial (MDBK) cells from the cytopathic effect of vesicular stomatitis virus, but it failed to protect human Wistar Institute Susan Hayflick (WISH) cells and canine Madin-Darby canine kidney epithelial-like (MDCK) cells. The present study demonstrates species specific antiviral activity of porcine IFNα8.
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http://dx.doi.org/10.4110/in.2017.17.6.424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746612PMC
December 2017

Direct diversification of unmasked quinazolin-4(3H)-ones through orthogonal reactivity modulation.

Chem Commun (Camb) 2017 Sep;53(75):10394-10397

School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), 50 UNIST-gil, Ulsan 44919, Republic of Korea. and Center for Genomic Integrity (CGI), Institute for Basic Science (IBS), School of Life Science, UNIST, 50 UNIST-gil, Ulsan 44919, Republic of Korea.

Here we report a set of direct functionalization methods of unmasked 2-phenylquinazolin-4(3H)-ones, a privileged alkaloid core, without the installation/removal event of protecting groups or exogenous coordinating moieties. Divergent pathways were modulated with transition-metal catalysts by suppressing competitive reactivities, leading to N-arylation, annulative π-extension, or C-H fluorination.
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http://dx.doi.org/10.1039/c7cc05794fDOI Listing
September 2017

Clinical Significance of Four Molecular Subtypes of Gastric Cancer Identified by The Cancer Genome Atlas Project.

Clin Cancer Res 2017 Jul 26. Epub 2017 Jul 26.

Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

The Cancer Genome Atlas (TCGA) project recently uncovered four molecular subtypes of gastric cancer: Epstein-Barr virus (EBV), microsatellite instability (MSI), genomically stable (GS), and chromosomal instability (CIN). However, their clinical significances are currently unknown. We aimed to investigate the relationship between subtypes and prognosis of patients with gastric cancer. Gene expression data from a TCGA cohort ( = 262) were used to develop a subtype prediction model, and the association of each subtype with survival and benefit from adjuvant chemotherapy was tested in 2 other cohorts ( = 267 and 432). An integrated risk assessment model (TCGA risk score) was also developed. EBV subtype was associated with the best prognosis, and GS subtype was associated with the worst prognosis. Patients with MSI and CIN subtypes had poorer overall survival than those with EBV subtype but better overall survival than those with GS subtype ( = 0.004 and 0.03 in two cohorts, respectively). In multivariate Cox regression analyses, TCGA risk score was an independent prognostic factor [HR, 1.5; 95% confidence interval (CI), 1.2-1.9; = 0.001]. Patients with the CIN subtype experienced the greatest benefit from adjuvant chemotherapy (HR, 0.39; 95% CI, 0.16-0.94; = 0.03) and those with the GS subtype had the least benefit from adjuvant chemotherapy (HR, 0.83; 95% CI, 0.36-1.89; = 0.65). Our prediction model successfully stratified patients by survival and adjuvant chemotherapy outcomes. Further development of the prediction model is warranted.
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http://dx.doi.org/10.1158/1078-0432.CCR-16-2211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785562PMC
July 2017

Smart Sensor Systems for Wearable Electronic Devices.

Polymers (Basel) 2017 Jul 25;9(8). Epub 2017 Jul 25.

School of Materials Science and Engineering, Wearable Electronics Research Group, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea.

Wearable human interaction devices are technologies with various applications for improving human comfort, convenience and security and for monitoring health conditions. Healthcare monitoring includes caring for the welfare of every person, which includes early diagnosis of diseases, real-time monitoring of the effects of treatment, therapy, and the general monitoring of the conditions of people's health. As a result, wearable electronic devices are receiving greater attention because of their facile interaction with the human body, such as monitoring heart rate, wrist pulse, motion, blood pressure, intraocular pressure, and other health-related conditions. In this paper, various smart sensors and wireless systems are reviewed, the current state of research related to such systems is reported, and their detection mechanisms are compared. Our focus was limited to wearable and attachable sensors. Section 1 presents the various smart sensors. In Section 2, we describe multiplexed sensors that can monitor several physiological signals simultaneously. Section 3 provides a discussion about short-range wireless systems including bluetooth, near field communication (NFC), and resonance antenna systems for wearable electronic devices.
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http://dx.doi.org/10.3390/polym9080303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418677PMC
July 2017

Wearable smart sensor systems integrated on soft contact lenses for wireless ocular diagnostics.

Nat Commun 2017 04 27;8:14997. Epub 2017 Apr 27.

School of Materials Science and Engineering, School of Energy and Chemical Engineering, Wearable Electronics Research Group, Center for Smart Sensor Systems, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.

Wearable contact lenses which can monitor physiological parameters have attracted substantial interests due to the capability of direct detection of biomarkers contained in body fluids. However, previously reported contact lens sensors can only monitor a single analyte at a time. Furthermore, such ocular contact lenses generally obstruct the field of vision of the subject. Here, we developed a multifunctional contact lens sensor that alleviates some of these limitations since it was developed on an actual ocular contact lens. It was also designed to monitor glucose within tears, as well as intraocular pressure using the resistance and capacitance of the electronic device. Furthermore, in-vivo and in-vitro tests using a live rabbit and bovine eyeball demonstrated its reliable operation. Our developed contact lens sensor can measure the glucose level in tear fluid and intraocular pressure simultaneously but yet independently based on different electrical responses.
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http://dx.doi.org/10.1038/ncomms14997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414034PMC
April 2017

An Annulative Synthetic Strategy for Building Triphenylene Frameworks by Multiple C-H Bond Activations.

Angew Chem Int Ed Engl 2017 04 30;56(18):5007-5011. Epub 2017 Mar 30.

School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), 50 UNIST-gil, Ulsan, 44919, Republic of Korea.

C-H activation is a versatile tool for appending aryl groups to aromatic systems. However, heavy demands on multiple catalytic cycle operations and site-selectivity have limited its use for graphene segment synthesis. A Pd-catal- yzed one-step synthesis of functionalized triphenylene frameworks is disclosed, which proceeds by 2- or 4-fold C-H arylation of unactivated benzene derivatives. A Pd (dibenzylideneacetone) catalytic system, using cyclic diaryliodonium salts as π-extending agents, leads to site-selective inter- and intramolecular tandem arylation sequences. Moreover, N-substituted triphenylenes are applied to a field-effect transistor sensor for rapid, sensitive, and reversible alcohol vapor detection.
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http://dx.doi.org/10.1002/anie.201700405DOI Listing
April 2017

Integrated arrays of air-dielectric graphene transistors as transparent active-matrix pressure sensors for wide pressure ranges.

Nat Commun 2017 03 31;8:14950. Epub 2017 Mar 31.

School of Materials Science and Engineering, SDC-UNIST Research Center, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Republic of Korea.

Integrated electronic circuitries with pressure sensors have been extensively researched as a key component for emerging electronics applications such as electronic skins and health-monitoring devices. Although existing pressure sensors display high sensitivities, they can only be used for specific purposes due to the narrow range of detectable pressure (under tens of kPa) and the difficulty of forming highly integrated arrays. However, it is essential to develop tactile pressure sensors with a wide pressure range in order to use them for diverse application areas including medical diagnosis, robotics or automotive electronics. Here we report an unconventional approach for fabricating fully integrated active-matrix arrays of pressure-sensitive graphene transistors with air-dielectric layers simply formed by folding two opposing panels. Furthermore, this realizes a wide tactile pressure sensing range from 250 Pa to ∼3 MPa. Additionally, fabrication of pressure sensor arrays and transparent pressure sensors are demonstrated, suggesting their substantial promise as next-generation electronics.
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http://dx.doi.org/10.1038/ncomms14950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381006PMC
March 2017

A dietary cholesterol challenge study to assess Chlorella supplementation in maintaining healthy lipid levels in adults: a double-blinded, randomized, placebo-controlled study.

Nutr J 2016 05 13;15(1):54. Epub 2016 May 13.

Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, 03760, Republic of Korea.

Background: Previous animal studies suggested that Chlorella, a unicellular green alga, has a preventive role in maintaining serum cholesterol levels against excess dietary cholesterol intake. This study aimed to conduct a pioneering investigation to clarify this issue in healthy subjects by adopting a dietary cholesterol challenge, which has not been used previously in similar studies of Chlorella in hypercholesterolemia.

Methods: In this double blind, randomized, placebo-controlled study, 34 participants ingested 510 mg of dietary cholesterol from three eggs concomitantly with a usual dose of Chlorella (5 g/d) or a matched placebo for 4 weeks.

Results: The dietary cholesterol challenge induced consistently higher concentrations of serum total cholesterol (TC, P < 0.001), LDL-C (P = 0.004), and HDL-C (P = 0.010) compared with baseline values, suggesting that the challenge was reliable. Thus, we observed a preventive action of Chlorella in maintaining serum TC versus placebo levels (3.5 % versus 9.8 %, respectively; P = 0.037) and LDL-C versus placebo levels (1.7 % versus 14.3 %, respectively; P = 0.012) against excessive dietary cholesterol intake and in augmenting HDL-C versus placebo levels (8.3 % versus 3.8 %, respectively). Furthermore, serum α-carotene showed the best separation between the placebo and Chlorella groups (R(2)X and R(2)Y > 0.5; Q(2) > 0.4).

Conclusion: The results suggest that a fully replicated dietary cholesterol challenge may be useful in assessing the effectiveness of dietary supplements in maintaining the serum lipid profiles of adults whose habitual diets are high in cholesterol.

Trial Registration: WHO International Clinical Trials Registry Platform ( KCT0000258 ).
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http://dx.doi.org/10.1186/s12937-016-0174-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4866071PMC
May 2016

Wearable, wireless gas sensors using highly stretchable and transparent structures of nanowires and graphene.

Nanoscale 2016 May;8(20):10591-7

School of Materials Science and Engineering, Wearable Electronics Research Group, Center for Smart Sensor Systems, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.

Herein, we report the fabrication of a highly stretchable, transparent gas sensor based on silver nanowire-graphene hybrid nanostructures. Due to its superb mechanical and optical characteristics, the fabricated sensor demonstrates outstanding and stable performances even under extreme mechanical deformation (stable until 20% of strain). The integration of a Bluetooth system or an inductive antenna enables the wireless operation of the sensor. In addition, the mechanical robustness of the materials allows the device to be transferred onto various nonplanar substrates, including a watch, a bicycle light, and the leaves of live plants, thereby achieving next-generation sensing electronics for the 'Internet of Things' area.
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http://dx.doi.org/10.1039/c6nr01468bDOI Listing
May 2016

Persimmon vinegar and its fractions protect against alcohol-induced hepatic injury in rats through the suppression of CYP2E1 expression.

Pharm Biol 2016 Nov 4;54(11):2437-2442. Epub 2016 Apr 4.

a Department of Nutritional Science and Food Management , Ewha Womans University , Seoul , Korea.

Context: Medical therapies for alcohol-induced liver disease are often difficult to handle and limited in efficacy.

Objective: In an attempt to find natural therapeutics, here, we investigate the preventive effect of persimmon vinegar (PV) and its fractions against alcohol-induced hepatic injury, in addition to the underlying mechanism, in rats chronically administered with alcohol.

Materials And Methods: Forty male Wistar rats were randomized into five groups (n = 8 per group); normal control (NC), ethanol control (EC), ethanol + PV, ethanol + water-insoluble PV fraction (PI) and ethanol + water-soluble PV fraction (PS). PV, PI or PS was orally administrated at the level of 100 mg/kg B.W by oral gavage every day for 4 weeks prior to ethanol administration. The liver sections were stained with hematoxylin & eosin and gene expression was assessed by real-time polymerase chain reaction.

Results: After a 4-week treatment, histological observation revealed that PV and its fractions mitigated alcohol-induced changes in the liver. CYP2E1 expression was significantly increased in the EC group compared with the NC group, but was significantly suppressed in the PV group compared with the EC group (p = 0.044). We also found significant decreases in hepatic mRNA expression of interleukin (IL)-1β, IL-12β, toll-like receptor (TLR)-4 and cyclooxygenase (COX)-2 in the PV-, PI- and PS-treated groups compared with those of the EC group.

Discussion And Conclusion: Taken together, the present findings suggest that PV and its fractions hold great promise as natural remedies with anti-inflammatory activities that alleviate alcohol-induced liver damage.
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http://dx.doi.org/10.3109/13880209.2016.1158842DOI Listing
November 2016

Stretchable and transparent electrodes based on in-plane structures.

Nanoscale 2015 Sep 19;7(35):14577-94. Epub 2015 Aug 19.

School of Materials Science and Engineering, Wearable Electronics Research Group, Low-Dimensional Carbon Materials Research Center, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Republic of Korea.

Stretchable electronics has attracted great interest with compelling potential applications that require reliable operation under mechanical deformation. Achieving stretchability in devices, however, requires a deeper understanding of nanoscale materials and mechanics beyond the success of flexible electronics. In this regard, tremendous research efforts have been dedicated toward developing stretchable electrodes, which are one of the most important building blocks for stretchable electronics. Stretchable transparent thin-film electrodes, which retain their electrical conductivity and optical transparency under mechanical deformation, are particularly important for the favourable application of stretchable devices. This minireview summarizes recent advances in stretchable transparent thin-film electrodes, especially employing strategies based on in-plane structures. Various approaches using metal nanomaterials, carbon nanomaterials, and their hybrids are described in terms of preparation processes and their optoelectronic/mechanical properties. Some challenges and perspectives for further advances in stretchable transparent electrodes are also discussed.
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http://dx.doi.org/10.1039/c5nr04341gDOI Listing
September 2015

Highly transparent and stretchable field-effect transistor sensors using graphene-nanowire hybrid nanostructures.

Adv Mater 2015 Jun 17;27(21):3292-7. Epub 2015 Apr 17.

School of Materials Science and Engineering, Wearable Electronics Research Group, Low-Dimensional Carbon Materials Research Center, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 689-798, Republic of Korea.

Transparent and stretchable electronics with remarkable bendability, conformability, and lightness are the key attributes for sensing or wearable devices. Transparent and stretchable field-effect transistor sensors using graphene-metal nanowire hybrid nanostructures have high mobility (≈3000 cm(2) V(-1) s(-1) ) with low contact resistance, and they are transferrable onto a variety of substrates. The integration of these sensors for RLC circuits enables wireless monitoring.
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http://dx.doi.org/10.1002/adma.201500710DOI Listing
June 2015

Studies on the mechanical stretchability of transparent conductive film based on graphene-metal nanowire structures.

Nanoscale Res Lett 2015 31;10:27. Epub 2015 Jan 31.

School of Materials Science and Engineering, Wearable Electronics Research Group, Low-Dimensional Carbon Materials Research Center, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 689-798 Republic of Korea.

Transparent electrodes with superior flexibility and stretchability as well as good electrical and optical properties are required for applications in wearable electronics with comfort designs and high performances. Here, we present hybrid nanostructures as stretchable and transparent electrodes based on graphene and networks of metal nanowires, and investigate their optical, electrical, and mechanical properties. High electrical and optical characteristics, superb bendability (folded in half), excellent stretchability (10,000 times in stretching cycles with 100% in tensile strain toward a uniaxial direction and 30% in tensile strain toward a multi-axial direction), strong robustness against electrical breakdown and thermal oxidation were obtained through comprehensive study. We believe that these results suggest a substantial promise application in future electronics.
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http://dx.doi.org/10.1186/s11671-015-0748-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384901PMC
April 2015

Mulberry leaf extract improves postprandial glucose response in prediabetic subjects: a randomized, double-blind placebo-controlled trial.

J Med Food 2015 Mar 24;18(3):306-13. Epub 2014 Oct 24.

1 Department of Food Science and Technology, Seoul National University of Science and Technology , Seoul, Korea.

This study was a randomized, double-blind placebo-controlled trial to assess the efficacy of 4 weeks of mulberry leaf aqueous extract (MLAE) supplementation (5 g/day) for postprandial glycemic control in 36 subjects with impaired fasting glucose (IFG) tolerance. Postprandial responses in the glucose, insulin, and C-peptide levels were measured after a carbohydrate load both at baseline and after 4 weeks of MLAE supplementation. The postprandial glycemic response was attenuated in the MLAE group after the treatment period, particularly 30 and 60 min after loading (P=.003 and 0.0325 for glucose, P=.0005 and .0350 for insulin, and P=.0151 and .0864 for C-peptide). Additionally, the incremental area under the curve for insulin was significantly lower in the MLAE group than in the placebo group (P=.0207). Four weeks of MLAE supplementation improved postprandial glycemic control in individuals with IFG tolerance.
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http://dx.doi.org/10.1089/jmf.2014.3160DOI Listing
March 2015

Impact of daily Chlorella consumption on serum lipid and carotenoid profiles in mildly hypercholesterolemic adults: a double-blinded, randomized, placebo-controlled study.

Nutr J 2014 Jun 11;13:57. Epub 2014 Jun 11.

Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 120-750, Republic of Korea.

Background: High level of serum cholesterol is considered to be a major risk factor for cardiovascular disease (CVD). A double-blinded, randomized, placebo-controlled trial was performed to test the hypothesis that a daily intake of Chlorella may improve serum lipid profile through enhancement of serum carotenoid concentration in mildly hypercholesterolemic subjects.

Methods: Eligible subjects (n = 63) were randomized to either Chlorella (5 g/day) or placebo for a double-blinded trial with a 2-week lead-in period and a 4-week intervention period. Serum triglycerides, total cholesterol, lipoproteins, apolipoproteins and carotenoids were assessed at the beginning and the end of the trial.

Results: Compared with the control group, the Chlorella group exhibited remarkable changes in total cholesterol (Chlorella -1.6%; placebo 0.03%; P = 0.036), triglycerides (Chlorella -10.3%; placebo 11.9%; P = 0.002), lutein/zeaxanthin (Chlorella 89.6%; placebo -1.7%; P < 0.0001), and α-carotene (Chlorella 163.6%; placebo 15%; P < 0.0001). Improvement of serum lipids was supported by significant reductions of very low-density lipoprotein cholesterol (Chlorella -11%; placebo 11.8%; P = 0.006), apolipoprotein B (Chlorella -1.5%; placebo 1.7%; P = 0.044), non high-density lipoprotein (Chlorella -2.6%; placebo -0.5%; P = 0.032), and high-density lipoprotein/triglycerides (Chlorella 4.0%; placebo -9.5%; P = 0.023), suggesting an inhibitory effect of Chlorella on the intestinal absorption of dietary and endogenous lipids. Further, the changes of serum lipids appeared to be associated with the changes of serum carotenoids.

Conclusion: Daily consumption of Chlorella supplements provided the potential of health benefits reducing serum lipid risk factors, mainly triglycerides and total cholesterol, in mildly hypercholesterolemic subjects. The effect was related to carotenoid consumption.

Trial Registration: WHO International Clinical Trials Registry Platform KCT0000259.
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http://dx.doi.org/10.1186/1475-2891-13-57DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066283PMC
June 2014

Blood pressure lowering effect of Korea ginseng derived ginseol K-g1.

Am J Chin Med 2014 ;42(3):605-18

Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang, Republic of Korea.

We investigated the effect of Panax ginseng extract, which is rich in the ginsenoside protopanaxatriol (Ginseol K-g1), on blood pressure (BP). Adults over 20 years old with a systolic BP (SBP) between 120 and 159 mm Hg or a diastolic BP (DBP) between 80 and 99 mm Hg were included. At the end of an initial 2-week washout period, the patients were divided into three groups: the control group (placebo), the low-dose Ginseol K-g1 group (100 mg), and the high-dose Ginseol K-g1 (300 mg) group. The primary end point was the difference in seated SBP (seSBP) and seated DBP (seDBP) changes between the placebo and Ginseol K-g1 groups after 8 weeks of treatment. A total of 90 subjects participated in the study (mean age; 55.2 ± 11.8 years, 43 males). At week 8, levels of seSBP and seDBP were significantly decreased from baseline in the high-dose Ginseol K-g1 group (-3.1 mm Hg and -2.3 mm Hg, respectively, p < 0.05). In contrast, there was no significant decrease in seSBP or seDBP in the control or low-dose Ginseol K-g1 groups. No significant difference of seSBP and seDBP was identified among the three treatment groups at week 8. In patients who had a seSBP ≥ 130 mm Hg or an seDBP ≥ 85 mm Hg, the high dose of Ginseol K-g1 decreased the BP compared with the control group at week 4; however, there was no significant difference at week 8. The proportions of patients who experienced adverse events were comparable among the treatment groups. In conclusion, Ginseol K-g1 has a favorable effect on BP after 4 weeks of treatment, especially at a high dose. However, the effect is not maintained over 8 weeks. (Clinical trial registration information is available at http://www.clinicaltrials.gov , identifier: NCT01483430.).
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http://dx.doi.org/10.1142/S0192415X14500396DOI Listing
December 2014