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Magnesium-enriched deep-sea water inhibits NLRP3 inflammasome activation and dampens inflammation

Heliyon 2024年第15期10卷 e35136页

作者： Wang, Hsueh-Hsiao Huang, Chi-Ruei Lin, Hsin-Chung Lin, Hsin-An Chen, Yu-Jen Tsai, Kuen-Jou Shih, Chieh-Tien Huang, Kuo-Yang Ojcius, David M. Tsai, Ming-Hang Tseng, Kuang-Wen Chen, Lih-Chyang Department of Medicine MacKay Medical College Master Program in Biomedicine College of Science and Engineering National Taitung University Biomedicine Agriculture and Food Sciences Research Center College of Science and Engineering National Taitung University Graduate Institute of Pathology and Parasitology National Defense Medical Center Division of Clinical Pathology Department of Pathology Tri-Service General Hospital National Defense Medical Center Division of Infection Department of Medicine Tri-Service General Hospital SongShan Branch National Defense Medical Center Department of Health Promotion and Health Education National Taiwan Normal University Department of Medical Research MacKay Memorial Hospital Department of Radiation Oncology MacKay Memorial Hospital Department of Artificial Intelligence and Medical Application MacKay Junior College of Medicine Nursing and Management Department of Medical Research China Medical University Hospital Department of Laboratory Medicine MacKay Memorial Hospital Department of Nursing MacKay Medical College Department of Biomedical Sciences University of the Pacific Arthur Dugoni School of Dentistry Department of Medicine Tri-Service General Hospital SongShan Branch National Defense Medical Center

The NLRP3 inflammasome is an essential component of the innate immune system, but excessive activation can lead to inflammatory diseases. Ion fluxes across the plasma membrane or from intracellular stores are known to regulate NLRP3 inflammasome activation. Deep-sea water (DSW) contains high concentrations of many mineral ions, which could potentially influence NLRP3 inflammasome activation. However, the impact of DSW on NLRP3 inflammasome activation has not been investigated. Here, we demonstrated that DSW with water hardness levels up to 500 mg/L did not affect cell viability or the expression of NLRP3 inflammasome components in macrophages derived from THP-1 cells. However, the DSW significantly inhibited IL-1β secretion and caspase-1 activation in response to NLRP3 activators such as nigericin, ATP, or monosodium urate (MSU) crystals. Mechanically, it was discovered that the presence of 5 mM magnesium ions (Mg2⁺), equivalent to the Mg2⁺ concentration found in the DSW with a water hardness of 500 mg/L, inhibits NLRP3 inflammasome activation. This indicates that Mg2⁺ contributes to the mechanism by which DSW mitigates NLRP3 inflammasome activation. Moreover, DSW administration effectively lessens MSU-triggered peritonitis in mice, a commonly used model for examining the impacts of NLRP3 inflammasome activation. These results show that DSW enriched with Mg²⁺ could potentially be beneficial in modulating NLRP3 inflammasome-associated diseases. © 2024 The Authors

关键词： Deep-sea water Macrophages Magnesium NLRP3 inflammasome

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Immunotherapy: engineering an Artificial T‐Cell Stimulating Matrix for Immunotherapy (Adv. Mater. 23/2019)

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Advanced Materials 2019年第23期31卷

作者： John W. Hickey Yi Dong Jae Wook Chung Sebastian F. Salathe Hawley C. Pruitt Xiaowei Li Calvin Chang Andrew K. Fraser Catherine A. Bessell Andrew J. Ewald Sharon Gerecht Hai‐Quan Mao Jonathan P. Schneck Department of Biomedical Engineering School of Medicine Baltimore MD 21218 USA Institute for Cell Engineering School of Medicine Baltimore MD 21205 USA Department of Pathology School of Medicine Baltimore MD 21287 USA Translational Tissue Engineering Center Baltimore MD 21287 USA Institute for NanoBioTechnology Baltimore MD 21218 USA Graduate Program in Immunology School of Medicine Baltimore MD 21205 USA Department of Chemical and Biomolecular Engineering Whiting School of Engineering Baltimore MD 21218 USA Department of Biology Krieger School of Arts and Sciences Baltimore MD 21218 USA Department of Materials Science and Engineering Whiting School of Engineering Baltimore MD 21218 USA Department of Cell Biology and Center for Cell Dynamics School of Medicine Baltimore MD 21205 USA Department of Oncology School of Medicine Baltimore MD 21205 USA Physical Sciences‐Oncology Center Baltimore MD 21218 USA Department of Medicine School of Medicine Johns Hopkins University Baltimore MD 21205 USA

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AAA + ATPase Thorase inhibits mTOR signaling through the disassembly of the mTOR complex 1

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Nature Communications 2022年第1期13卷 4836页

作者： Umanah, George K. E. Abalde-Atristain, Leire Khan, Mohammed Repon Mitra, Jaba Dar, Mohamad Aasif Chang, Melissa Tangella, Kavya McNamara, Amy Bennett, Samuel Chen, Rong Aggarwal, Vasudha Cortes, Marisol Worley, Paul F. Ha, Taekjip Dawson, Ted M. Dawson, Valina L. Neuroregeneration and Stem Cell Programs Institute for Cell Engineering Johns Hopkins University School of Medicine Baltimore 21205 MD United States Department of Neurology Johns Hopkins University School of Medicine Baltimore 21205 MD United States Cellular and Molecular Medicine Graduate Program Johns Hopkins University School of Medicine Baltimore 21205 MD United States Department of Materials Science and Engineering University of Illinois at Urbana-Champaign Urbana 61801 IL United States Department of Biophysics and Biophysical Chemistry Johns Hopkins University Baltimore 21205 MD United States Solomon H. Snyder Department of Neuroscience Johns Hopkins University School of Medicine Baltimore 21205 MD United States Departments of Biophysics and Biophysical Chemistry Biophysics and Biomedical Engineering JHU Howard Hughes Medical Institute Baltimore 21205 MD United States Department of Pharmacology and Molecular Sciences Johns Hopkins University School of Medicine Baltimore 21205 MD United States Department of Physiology Johns Hopkins University School of Medicine Baltimore 21205 MD United States Division of Neuroscience National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda MD United States Vollum Institute Oregon Health & Science University Portland 97239 OR United States

The mechanistic target of rapamycin (mTOR) signals through the mTOR complex 1 (mTORC1) and the mTOR complex 2 to maintain cellular and organismal homeostasis. Failure to finely tune mTOR activity results in metabolic dysregulation and disease. While there is substantial understanding of the molecular events leading mTORC1 activation at the lysosome, remarkably little is known about what terminates mTORC1 signaling. Here, we show that the AAA + ATPase Thorase directly binds mTOR, thereby orchestrating the disassembly and inactivation of mTORC1. Thorase disrupts the association of mTOR to Raptor at the mitochondria-lysosome interface and this action is sensitive to amino acids. Lack of Thorase causes accumulation of mTOR-Raptor complexes and altered mTORC1 disassembly/re-assembly dynamics upon changes in amino acid availability. The resulting excessive mTORC1 can be counteracted with rapamycin in vitro and in vivo. Collectively, we reveal Thorase as a key component of the mTOR pathway that disassembles and thus inhibits mTORC1. © 2022, The Author(s).

关键词： Cell signalling Lysosomes Mechanisms of disease

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Radio-pathomic estimates of cellular growth kinetics predict survival in recurrent glioblastoma

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CNS Oncology 2024年第1期13卷 2415285页

作者： Oshima, Sonoko Yao, Jingwen Bobholz, Samuel Nagaraj, Raksha Raymond, Catalina Teraishi, Ashley Guenther, Anna-Marie Kim, Asher Sanvito, Francesco Cho, Nicholas S C Eldred, Blaine S Connelly, Jennifer M Nghiemphu, Phioanh L Lai, Albert Salamon, Noriko Cloughesy, Timothy F LaViolette, Peter S Ellingson, Benjamin M UCLA Brain Tumor Imaging Laboratory (BTIL) Center for Computer Vision & Imaging Biomarkers University of California Los Angeles Los Angeles 90024 CA United States Department of Radiological Sciences David Geffen School of Medicine University of California Los Angeles Los Angeles 90024 CA United States Department of Bioengineering Henry Samueli School of Engineering & Applied Science University of California Los Angeles Los Angeles 90024 CA United States Department of Radiology Medical College of Wisconsin Milwaukee 53226 WI United States Medical Scientist Training Program David Geffen School of Medicine University of California Los Angeles Los Angeles 90024 CA United States UCLA Neuro-Oncology Program David Geffen School of Medicine University of California Los Angeles Los Angeles 90024 CA United States Department of Neurology Medical College of Wisconsin Milwaukee 53226 WI United States Department of Neurology David Geffen School of Medicine University of California Los Angeles Los Angeles 90024 CA United States Department of Biophysics Medical College of Wisconsin Milwaukee 53226 WI United States Department of Biomedical Engineering Medical College of Wisconsin Milwaukee 53226 WI United States Department of Psychiatry & Biobehavioral Sciences David Geffen School of Medicine University of California Los Angeles Los Angeles 90024 CA United States Department of Neurosurgery David Geffen School of Medicine University of California Los Angeles Los Angeles 90024 CA United States

Aim: A radio-pathomic machine learning (ML) model has been developed to estimate tumor cell density, cytoplasm density (Cyt) and extracellular fluid density (ECF) from multimodal MR images and autopsy pathology. In this multicenter study, we implemented this model to test its ability to predict survival in patients with recurrent glioblastoma (rGBM) treated with chemotherapy. Methods: Pre- and post-contrast T₁-weighted, FLAIR and ADC images were used to generate radio-pathomic maps for 51 patients with longitudinal pre- and post-treatment scans. Univariate and multivariate Cox regression analyses were used to test the influence of contrast-enhancing tumor volume, total cellularity, mean Cyt and mean ECF at baseline, immediately post-treatment and the pre- and post-treatment rate of change in volume and cellularity on overall survival (OS). Results: Smaller Cyt and larger ECF after treatment were significant predictors of OS, independent of tumor volume and other clinical prognostic factors (HR = 3.23 × 10^-6, p < 0.001 and HR = 2.39 × 10⁵, p < 0.001, respectively). Both post-treatment volumetric growth rate and the rate of change in cellularity were significantly correlated with OS (HR = 1.17, p = 0.003 and HR = 1.14, p = 0.01, respectively). Conclusion: Changes in histological characteristics estimated from a radio-pathomic ML model are a promising tool for evaluating treatment response and predicting outcome in rGBM. © 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

关键词： MRI rad-path radiopathomic mapping recurrent glioblastoma survival tumor growth rate

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Coconut waste to green nanomaterial: Large scale synthesis of N-doped graphene nano sheets

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Nano-Structures and Nano-Objects 2023年 36卷

作者： Siburian, Rikson Tang, Liang Wei Alias, Yatimah Tok, Alfred Iing Yoong Goei, Ronn Simanjuntak, Crystina Tarigan, Kerista Paiman, Suriati Goh, Boon Tong Anshori, Isa Kurniawan, Cepi Postgraduate Program Department of Chemistry Faculty of Mathematics and Natural Sciences Universitas Sumatera Utara Medan 20155 Indonesia Department of Chemistry Faculty of Mathematics and Natural Sciences Universitas Sumatera Utara Medan 20155 Indonesia Carbon and Frankincense Research Center Universitas Sumatera Utara Medan 20155 Indonesia Department of Chemistry Faculty of Science Universiti Malaya Kuala Lumpur 50603 Malaysia University Malaya Centre for Ionic Liquids (UMCiL) Universiti Malaya Kuala Lumpur 50603 Malaysia School of Materials Science and Engineering Nanyang Technological University 50 Nanyang Avenue Singapore 639798 Singapore Department of Physics Faculty of Mathematics and Natural Sciences Universitas Sumatera Utara Medan 20155 Indonesia Physics Department Faculty of Science Universiti Putra Malaysia Selangor (Serdang) Seri Kembangan 43400 Malaysia Low Dimensional Materials Research Centre Department of Physics Faculty of Science University of Malaya Kuala Lumpur 50603 Malaysia Biomedical Engineering Department School of Electrical Engineering and Informatics Bandung Institute of Technology Bandung 40132 Indonesia Research Center of Nanoscience and Nanotechnology Bandung Institute of Technology Bandung 40132 Indonesia Chemistry Department Faculty of Mathematics and Natural Sciences Universitas Negeri Semarang Semarang 50229 Indonesia Functional Material Research Center Universitas Negeri Semarang Semarang 50229 Indonesia

In this paper, a breakthrough was achieved in large-scale production of N-doped Graphene Nano Sheets (N-GNS) using coconut fruits. The main objectives were to produce N-GNS on a large scale and assess its electrical conductivity. The process involved two key steps: first, producing GNS from coconut fruits through pyrolysis, and then generating N-GNS by doping with nitrogen using ammonia solution at room temperature. Various analytical techniques were used to characterize the produced N-GNS, including X-ray Diffraction (XRD), Scanning Electron Microscopy with Energy Dispersive Spectroscopy (SEM-EDS), Transmission Electron Microscopy (TEM), X-ray Photoelectron Spectroscopy (XPS), Raman spectroscopy, and electrochemical cyclic voltammetry and electrochemical impedance spectroscopy. The XRD data indicated that the C (002) peak of N-GNS shifted to a higher 2θ value (2θ = 24.72°) compared to GNS (2θ = 23.86°), suggesting an incorporation of nitrogen into carbon structure in N-GNS. This was further supported by XPS data, which identified N-pyridine (BE = 402.0 eV) and C-N (BE = 286.8 eV) in N-GNS. TEM images showed that N-GNS had a flat surface, and the distance between graphene layers slightly expanded (0.36 nm) compared to graphene layers (0.34 nm). SEM images and EDX data validated the morphology, resembling honeycomb lattices, with a significant content of N atoms. Raman data successfully identified the D-band and G-band in N-GNS, further validating its production. Most importantly, N-GNS exhibited electrical conductivity, making it a promising candidate for conductive and supporting materials in various applications. The significance of this research extends beyond N-GNS production, opening up new avenues for the sustainable synthesis of valuable nanomaterials from coconut fruit waste, contributing to both graphene technology and environmental conservation. © 2023 Elsevier B.V.

关键词： C-sp2 Electrical conductivity Graphene nano sheets N-graphene nano sheets N-pyridine XPS

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The College of Podiatry Annual Conference 2015: meeting abstracts Abstracts

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JOURNAL OF FOOT AND ANKLE RESEARCH 2016年第1-Sup期9卷 1-14页

作者： [Anonymous] Allied Health Specialties KK Women’s and Children’s Hospital Singapore Singapore Physical Education and Sports Science Academic Group National Institute of Education Nanyang Technological University Singapore Singapore Queen Margaret University Musselburgh Scotland University of Brighton Brighton UK Ministry of Defence Headley Court Complex Trauma Department Surrey UK University of Roehampton London UK University of Brighton Brighton UK Ministry of Defence Headley Court Complex Trauma Department Surrey UK University of Roehampton London UK Birmingham City University Birmingham UK Staffordshire University Stoke-on-Trent UK Universitat Ramon Llun Barcelona Spain Sheffield Teaching Hospitals NHS Foundation Trust Sheffield UK Sociological Studies University of Sheffield Sheffield UK University of Roehampton London UK Sheffield Teaching Hospitals NHS Foundation Trust Sheffield UK University of Brighton Brighton UK Counties Manuaku District Health Board Auckland New Zealand Auckland District Health Board Auckland New Zealand Waitemata District Health Board Auckland New Zealand Brighton & Sussex Medical School Brighton UK East Sussex HealthcareTrust Eastbourne UK AUT University Auckland New Zealand Cambridgeshire and Peterborough NHS Foundation Trust Cambridge UK University of Northampton Northampton UK University of Newcastle Newcastle upon Tyne UK Betsi Cadwaladr University Health Board Bangor Wales UK National University of Ireland Galway Ireland Health Service Executive West Galway Ireland National University of Ireland Galway Galway Ireland University of Brighton Brighton UK University of Brighton Brighton UK Queen Margaret University Musselburgh Scotland University of Newcastle Newcastle upon Tyne Tyne and Wear UK Hunter Medical Research Institute 1 Kookaburra Circuit New Lambton Heights NSW Australia University of Brighton Lewes Rd Brighton UK University Of Surrey Guildford UK Liverpool John Moore University 70 Mount Pleasant Liv

Table of content P3 Medial longitudinal arch development of school children Jasper W.K. Tong, Veni P. Kong P4 Is measuring the subtalar joint reliable? Lily Sze, Susie Gale, John Veto, Carla McArdle P5 Comparison of turning gait biomechanics between able-bodied and unilateral transtibial amputee participants Thanaporn Tunprasert, Victoria Bradley, Siobhan Strike P6 Comparison of walking gait biomechanics between able-bodied and unilateral transtibial amputee participants using a new model of energy-storage-and-return (ESAR) prosthetic Thanaporn Tunprasert, Victoria Bradley, Siobhan Strike P7 An observational study of in-shoe plantar and dorsal pressures of skilled downhill skiers on a dry ski slope Robert Ashford, Roozbeth Naemi, Nachiappan Chocklingam, Xavi de Blasc P8 If the shoe fits: a footwear choice toolkit informed by social science methodologies Lisa Farndon, Vicki Robinson, Emily Nicholls P9 The identification of emotions from gait Tabitha Birch, Ivan Birch P11 Experience of foot problems in patients with systemic lupus erythematosus Simon Otter, Sunil Kumar, Peter Gow, Nicola Dalbeth, Michael Corkill, Kevin Davies, Sam Panthakalam, Maheswaran Rohan, Keith Rome P14 Negative pressure wound therapy for the management of foot wounds in the diabetic population: a review of the literature Chloe Egan, Lisa Chandler P15 Lower limb vascular assessment in diabetes: a multifaceted assessment of objective screening techniques Peta Tehan, Vivienne Chuter, Jennifer Sonter, Sean Lanting P16 Improving outcomes for diabetes foot complications Lorna Hicks P17 Acupuncture… an alternative or adjunctive treatment option for diabetes-related neuropathic pain? Christopher Joyce, David Watterson, Caroline McIntosh P18 “My back is in agony” - A cross-sectional study into the relationship between musculoskeletal complaints and a whole body postural risk assessment in podiatry students Christopher Joyce, Nigel Roberts P19 Swabs of the treatment couches: Do

关键词： National Health Service Peripheral Arterial Disease Ankle Brachial Index Negative Pressure Wound Therapy Musculoskeletal Complaint

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Inside Back Cover: In Vitro and In Vivo Uncaging and Bioluminescence Imaging by Using Photocaged Upconversion Nanoparticles (Angew. Chem. Int. Ed. 13/2012)

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Angewandte Chemie International Edition 2012年第13期51卷

作者： Yanmei Yang Qing Shao Renren Deng Chao Wang Xue Teng Kai Cheng Prof. Zhen Cheng Prof. Ling Huang Prof. Zhuang Liu Prof. Xiaogang Liu Prof. Bengang Xing Division of Chemistry and Biological Chemistry School of Physical & Mathematical Sciences Nanyang Technological University Singapore 637371 (Singapore) Department of Chemistry National University of Singapore 3 Science Drive 3 Singapore 117543 (Singapore) Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices Institute of Functional Nano & Soft Materials Soochow University (P. R. China) Division of Biomedical Engineering School of Chemical and Biomedical Engineering Nanyang Technological University (Singapore) Molecular Imaging Program at Stanford (MIPS) Department of Radiology Stanford University Medical Center (USA) Institute of Materials Research and Engineering Agency for Science Technology and Research (A*STAR) 3 Research Link Singapore 117602 (Singapore) Xiaogang Liu Department of Chemistry National University of Singapore 3 Science Drive 3 Singapore 117543 (Singapore) Bengang Xing Division of Chemistry and Biological Chemistry School of Physical & Mathematical Sciences Nanyang Technological University Singapore 637371 (Singapore)

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Tissue engineering: Controlled Apoptosis of Stromal Cells to Engineer Human Microlivers (Adv. Funct. Mater. 48/2020)

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Advanced Functional Materials 2020年第48期30卷

作者： Amanda X. Chen Arnav Chhabra Hyun‐Ho Greco Song Heather E. Fleming Christopher S. Chen Sangeeta N. Bhatia Department of Biological Engineering Massachusetts Institute of Technology Cambridge MA 02139 USA Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology Cambridge MA 02139 USA Harvard–MIT Program in Health Sciences and Technology Institute for Medical Engineering and Science Massachusetts Institute of Technology Cambridge MA 02139 USA Biological Design Center Department of Biomedical Engineering Boston University Boston MA 02215 USA Wyss Institute for Biologically Inspired Engineering Boston MA 02115 USA Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology Cambridge MA 02142 USA Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston MA 02115 USA Broad Institute of Massachusetts Institute of Technology and Harvard Cambridge MA 02139 USA Howard Hughes Medical Institute Chevy Chase MD 20815 USA

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P-selectin Targeting Stimulates Caveolin-1-Mediated Endothelial Transcytosis in Medulloblastoma

Research Square

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Research Square 2021年

作者： Tylawsky, Daniel E. Kiguchi, Hiro Vaynshteyn, Jake Gerwin, Jeffrey Shah, Janki Islam, Taseen Snuderl, Matija Greenblatt, Matthew B. Boué, Daniel R. Shamay, Yosi Raju, G. Praveen Heller, Daniel A. Molecular Pharmacology Program Memorial Sloan Kettering Cancer Center New YorkNY10065 United States Department of Pharmacology Weill Cornell Graduate School of Medical Sciences New YorkNY10065 United States Department of Pediatrics Weill Cornell Medicine New YorkNY10065 United States Department of Pediatrics Memorial Sloan Kettering Cancer Center New YorkNY10065 United States Departments of Pathology & Laboratory Medicine Nationwide Children’s Hospital The Ohio State University ColumbusOH43205 United States Division of Neuropathology Department of Pathology NYU Langone Medical Center New YorkNY10016 United States Department of Pathology and Laboratory Medicine Weill Cornell Medicine & Research Division Hospital for Special Surgery New YorkNY10065 United States Faculty of Biomedical Engineering The Technion Israel Institute of Technology Haifa Israel Departments of Neurology and Pediatrics Icahn School of Medicine at Mount Sinai New YorkNY10029 United States

Medulloblastoma (MB) is the most common malignant pediatric brain tumor with ~30% mediated by Sonic hedgehog (SHH) signaling. While SHH effector Smoothened inhibition is promising, therapeutic index is reduced by high systemic doses required for sufficient intracranial drug concentrations. Treatment-related toxicities associated with radiation therapy result in lifelong morbidity, and SHH pathway inhibition in children notably results in permanent bone defects. Here, we found that nanoparticle-mediated P-selectin targeting on tumor vasculature induces caveolin-1-dependent transcellular passage across the blood-brain barrier. A vismodegib nanocarrier that targets P-selectin exhibited striking efficacy and markedly reduced both bone-related toxicities and drug exposure to healthy brain. These findings demonstrate a potent strategy and novel mechanism for targeted intracranial pharmacodelivery that overcomes the restrictive endothelial barrier to achieve enhanced tumor-selective penetration and has therapeutic implications for other diseases within the central nervous system. © 2021, CC BY.

关键词： Toxicity

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Author Correction: O-GlcNAc modification of leucyl-tRNA synthetase 1 integrates leucine and glucose availability to regulate mTORC1 and the metabolic fate of leucine

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Nature communications 2022年第1期13卷 6253页

作者： Kibum Kim Hee Chan Yoo Byung Gyu Kim Sulhee Kim Yulseung Sung Ina Yoon Ya Chun Yu Seung Joon Park Jong Hyun Kim Kyungjae Myung Kwang Yeon Hwang Sunghoon Kim Jung Min Han Interdisciplinary Program of Integrated OMICS for Biomedical Science Graduate School Yonsei University Seoul 03722 South Korea. Yonsei Institute of Pharmaceutical Sciences College of Pharmacy Yonsei University Incheon 21983 South Korea. Center for Genomic Integrity Institute for Basic Science Ulsan 44919 South Korea. Department of Biotechnology College of Life Sciences and Biotechnology Korea University Seoul 02841 South Korea. Institute for Artificial Intelligence and Biomedical Research Medicinal Bioconvergence Research Center Yonsei University Incheon 21983 South Korea. College of Medicine Gangnam Severance Hospital Yonsei University Seoul 06273 South Korea. Department of Biochemistry School of Medicine Catholic University of Daegu Daegu 42472 South Korea. Department of Biomedical Engineering Ulsan National Institute of Science and Technology Ulsan 44919 South Korea. Interdisciplinary Program of Integrated OMICS for Biomedical Science Graduate School Yonsei University Seoul 03722 South Korea. jhan74@yonsei.ac.kr. Yonsei Institute of Pharmaceutical Sciences College of Pharmacy Yonsei University Incheon 21983 South Korea. jhan74@yonsei.ac.kr. POSTECH Biotech Center Pohang University of Science and Technology Pohang 37673 South Korea. jhan74@yonsei.ac.kr.

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