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A novel IRAK4/PIM1 inhibitor ameliorates rheumatoid arthritis and lymphoid malignancy by blocking the TLR/MYD88-mediated NF-κB pathway

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Acta Pharmaceutica Sinica B 2023年第3期13卷 1093-1109页

作者： Sae-Bom Yoon Hyowon Hong Hee-Jong Lim Ji Hye Choi Yoon Pyo Choi Seong Wook Seo Hyuk Woo Lee chong hak chae Woo-Kyu Park Hyun Young Kim Daeyoung Jeong Tran Quang De Chang-Seon Myung Heeyeong Cho Therapeutics&Biotechnology Division Korea Research Institute of Chemical TechnologyYuseong-guDaejeon 34114Republic of Korea Department of Pharmacology Chungnam National University College of PharmacyYuseong-guDaejeon 34134Republic of Korea Future Medicine Co. Ltd.Rm616 LH-Business Growth CenterSeongnamGyeonggido 13449Republic of Korea Department of Chemistry College of Natural SciencesCan Tho UniversityCan Tho city 9000Viet Nam

Interleukin-1 receptor-associated kinase 4(IRAK4)is a pivotal enzyme in the Toll-like receptor(TLR)/MYD88 dependent signaling pathway,which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma(ABC-DLBCL).Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of ***,proviral integration site for Moloney murine leukemia virus 1(PIM1)functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib *** developed a dual IRAK4/PIM1 inhibitor KIC-0101 that potently suppresses the NF-κB pathway and proinflammatory cytokine induction in vitro and in *** rheumatoid arthritis mouse models,treatment with KIC-0101 significantly ameliorated cartilage damage and ***-0101 inhibited the nuclear translocation of NF-κB and activation of JAK/STAT pathway in *** addition,KIC-0101 exhibited an anti-tumor effect on ibrutinib-resistant cells by synergistic dual suppression of TLR/MYD88-mediated NF-κB pathway and PIM1 *** results suggest that KIC-0101 is a promising drug candidate for autoimmune diseases and ibrutinib-resistant B-cell lymphomas.

关键词： Drug discovery IRAK4 PIM1 NF-κB pathway Rheumatoid arthritis ABC-DLBCL Ibrutinib resistance Dual inhibitor

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3D cell-printing of gradient multi-tissue interfaces for rotator cuff regeneration

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Bioactive Materials 2023年第1期19卷 611-625页

作者： Suhun chae Uijung Yong Wonbin Park Yoo-mi Choi In-Ho Jeon Homan Kang Jinah Jang hak Soo Choi Dong-Woo Cho Department of Mechanical Engineering Pohang University of Science and Technology77 Cheongam-roNam-guGyeongsangbuk-doPohang37673South Korea EDmicBio Inc. 111 Hoegi-roDongdaemun-guSeoul 02445South Korea Institute for Convergence Research and Education in Advanced Technology Yonsei University50 Yonsei-roSeodaemun-guSeoul03722South Korea Gordon Center for Medical Imaging Department of RadiologyMassachusetts General Hospital&Harvard Medical School14913th StreetBostonMA02114USA Department of Convergence IT Engineering Pohang University of Science and Technology77 Cheongam-roNam-guGyeongsangbuk-doPohang37673South Korea School of Interdisciplinary Bioscience and Bioengineering Pohang University of Science and Technology77 Cheongam-roNam-guGyeongsangbuk-doPohang37673South Korea Department of Orthopaedic Surgery Asan Medical CenterCollege of MedicineUniversity of Ulsan86 Asanbyeongwon-gilSongpa-guSeoul05505South Korea

Owing to the prevalence of rotator cuff(RC)injuries and suboptimal healing outcome,rapid and functional regeneration of the tendon-bone interface(TBI)after RC repair continues to be a major clinical *** the essential role of the RC in shoulder movement,the engineering of biomimetic multi-tissue constructs presents an opportunity for complex TBI reconstruction after RC ***,we propose a gradient cell-laden multi-tissue construct combined with compositional gradient TBI-specific bioinks via 3D cell-printing *** vitro studies demonstrated the capability of a gradient scaffold system in zone-specific inducibility and multi-tissue formation mimicking *** regenerative performance of the gradient scaffold on RC regeneration was determined using a rat RC repair *** particular,we adopted nondestructive,consecutive,and tissue-targeted near-infrared fluorescence imaging to visualize the direct anatomical change and the intricate RC regeneration progression in real time in ***,the 3D cell-printed implant promotes effective restoration of shoulder locomotion function and accelerates TBI healing in *** summary,this study identifies the therapeutic contribution of cell-printed constructs towards functional RC regeneration,demonstrating the translational potential of biomimetic gradient constructs for the clinical repair of multi-tissue interfaces.

关键词： 3D cell-printing Tissue-specific bioink Gradient tissue scaffolds Near-infrared fluorophores Rotator cuff repair

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Multiple malignant extragastrointestinal stromal tumors of the greater omentum and results of immunohistochemistry and mutation analysis:A case report

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World Journal of Gastroenterology 2007年第24期13卷 3392-3395页

作者： Jong-Han Kim Yoon-Jung Boo Cheol-Woong Jung Sung-Soo Park Seung-Joo Kim Young-Jae Mok Sang-Dae Kim Yang-Suk chae chong-Suk Kim Kim Korea University Hospital Seoul 136-705 Korea Deparment of Surgery Pathology KoreaUniversity College of medicine Seoul 136-705 Korea

To report an extragastrointestinal stromal tumor （EGIST） that occurs outside the gastrointestinal tract and shows unique clinicopathologic and immunohistochemical features. In our case, we experienced multiple soft tissue tumors that originate primarily in the greater omentum, and in immunohistochemical analysis, the tumors showed features that correspond to malignant EGIST. Two large omental masses measured 15 cm×10 cm and 5 cm×4 cm sized and several small ovoid fragments were attached to small intestine, mesentery and peritoneum. On histologic findings, the masses were separated from small bowel serosa and had high mitotic count （115/50 HPFs）. In the results of immunohistochemical stains, the tumor showed CDl17 （c-kit） positive reactivity and high Ki-67 labeling index. On mutation analysis, the c-kit gene mutation was found in the juxtamembrane domain （exon 11）and it was heterozygote. Platelet-derived growth factor receptor （PDGFR） gene mutation was also found in the juxtamemembrane （exon 12） and it was polymorphism. From above findings, we proposed that there may be several mutational pathways to malignant EGIST, so further investigations could be needed to approach this unfavorable disease entity.

关键词： Extragastrointestinal stromal tumor Greater omentum c-kit Platelet-derived growth factor receptor Mutation

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Novel endogenous endoplasmic reticulum transmembrane protein SURF4 suppresses cell death by negatively regulating the STING-STAT6 axis inmyeloid leukemia

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Cancer Communications 2023年第3期43卷 395-399页

作者： Jayoung Kim Hansong Lee chae Mi Hong Ji Ho Nam Hye Ju Yeo Woo Hyun Cho Hyung-Sik Kim Changwan Hong Yun hak Kim Dongjun Lee Department of Convergence Medicine School of MedicinePusan National UniversityYangsanGyeongsangnam-do 50612Republic of Korea Department of Biomedical Informatics School of MedicinePusan National UniversityYangsanGyeongsangnam-do 50612Republic of Korea Department of Radiation Oncology School of MedicinePusan National UniversityYangsanGyeongsangnam-do 50612Republic of Korea Division of Allergy Pulmonaryand Critical Care MedicineDepartment of Internal MedicinePusan National University Yangsan HospitalYangsanGyeongsangnam-do 50612Republic of Korea Department of Oral Pathology Dental and Life Science InstituteSchool of DentistryPusan National UniversityYangsanGyeongsangnam-do 50612Republic of Korea Department of Anatomy School of MedicinePusan National UniversityYangsanGyeongsangnam-do 50612Republic of Korea

Dear Editor,Myeloid differentiation was shown to be associated with reduced leukemic cell burden and leukemia-initiating cells and improved survival[1].Reactive oxygen species(ROS)are associated with leukemia and can induce endoplasmic reticulum(ER)*** stress induces several mechanisms,including cell death[2].The stimulator of interferon genes(STING)is also an ER transmembrane protein and promotes anti-tumor immunity by linking innate and adaptive immunity[3].Signal transducer and activator of transcription 6(STAT6)plays a prominent role in adaptive immunity by transducing signals fromextracellular cytokines and inducing apoptosis in cancer cells[4].

关键词： STAT6 immunity reticulum

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Hamartomatous Polyp of Minor Salivary Gland Arising in the Tongue: A Report of the First Case

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Open Journal of Pathology 2014年第3期4卷 83-85页

作者： Yosep chong Young hak Park Tae-Jung Kim Chang Suk Kang Department of Hospital Pathology Yeouido St. Mary’s Hospital The Catholic University of Korea College of Medicine Seoul South Korea Department of Otolaryngology-Head and Neck Surgery Yeouido St. Mary’s Hospital The Catholic University of Korea College of Medicine Seoul South Korea

Benign tumorous condition can be encountered at very unusual location in oral cavity and pharyngeal region, which leads diagnostic difficulty. Here we describe a very unusual presentation of polypoid hamartoma on the root of the tongue. A 59-year-old woman presented with a polypoid tumor mass on the dorsal root of the tongue. Microscopically, it was hamartoma showing normal salivary glands of mucinous and serous types, lymphoid hyperplasia, and skeletal muscle bundles. Major differential diagnoses include accessory tongue, adenomatoid hyperplasia, and idiopathic hyperplasia of sublingual glands. To our knowledge, this is the first report of hamartoma arising in the root of the tongue presenting as polypoid mass. Correct diagnosis based on pathologic examination is essential for proper treatment.

关键词： Hamartoma Minor Salivary Gland Tongue Neoplasm Polyps

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Isolated MicroGrid’s Voltage and Frequency Characteristic with Induction Generator Based Wind Turbine

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Smart Grid and Renewable Energy 2014年第7期5卷 180-192页

作者： Woo-Kyu chae hak-Ju Lee Sung-Wook Hwang Il-Keun Song Jae-Eon Kim Chungbuk National University Chungbuk Korea Research Institute Korea Electric Power Corporation Daejeon-si Korea

To save on the island area's power supply cost and protect the clean environment, the Isolated MicroGrid is being duly considered. Consisting of the Wind Turbine Generator (WT), photovoltaic generator, battery system, back-up diesel generator, etc., Isolated MicroGrid, which usually uses the inverter to maintain voltage and frequency of the system, is very weak in terms of voltage and frequency stability compared to the large-scale electrical power system. If wind turbine generator is applied to this weak power system, it could experience many problems in terms of maintaining its voltage and frequency. In this paper, the measurement result of voltage and frequency is presented for MicroGrid, which consists of the Wind Turbine Generator adopting the induction generator and the battery system. MicroGrid’s voltage waveform distortion and Wind Turbine Generator’s output oscillation problems are analyzed using PSCAD/EMTDC. Based on the analyzed result, the importance of type and capacity choice has been suggested in case the Wind Turbine Generator is applied to the Isolated MicroGrid.

关键词： MicroGrid Wind Turbine Induction Generator Battery Voltage Frequency PSCAD/EMTDC

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Epidermal growth factor upregulates Skp2/Cks1 and p27^(kip1) in human extrahepatic cholangiocarcinoma cells

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World Journal of Gastroenterology 2014年第3期20卷 755-773页

作者： Ja-yeon Kim Hong Joo Kim Jung Ho Park Dong Il Park Yong Kyun Cho chong Il Sohn Woo Kyu Jeon Byung Ik Kim Dong Hoon Kim Seoung Wan chae Jin Hee Sohn Kangbuk Samsung Medical Research Institute Sungkyunkwan University Kangbuk Samsung Hospital Department of Internal Medicine Sungkyunkwan University Kangbuk Samsung Hospital Department of Pathology Sungkyunkwan University Kangbuk Samsung Hospital

AIM:To evaluate the expression status of S-phase kinase-associated protein 2(Skp2)/cyclin-dependent kinases regulatory subunit 1(Cks1)and p27kip1,and assess the prognostic significance of Skp2/Cks1 expression with p27kip1in patients with extrahepatic ***:Seventy-six patients who underwent curative resection for histologically confirmed extrahepatic cholangiocarcinoma at our institution from December1994 to March 2008 were *** staining for Skp2,Cks1,p27kip1,and Ki67,along with other relevant molecular biologic experiments,were ***:By Cox regression analyses,advanced age(>65 years),advanced AJCC tumor stage,poorly differentiated histology,and higher immunostaining intensity of Skp2 were identified as independent prognostic factors in patients with extrahepatic *** epidermal growth factor(EGF,especially 0.1-10 ng/mL)significantly increased the proliferation indices by MTT assay and the mRNA levels of Skp2/Cks1 and p27kip1in SNU-1196,SNU-1079,and SNU-245 *** protein levels of Skp2/Cks1(from nuclear lysates)and p27kip1(from cytosolic lysate)were also significantly increased in these *** were significant reductions in the protein levels of Skp2/Cks1and p27kip1(from nuclear lysate)after the treatment of *** chromatin immunoprecipitation assay,we found that E2F1 transcription factor directly binds to the promoter site of ***:Higher immunostaining intensity of Skp2/Cks1 was an independent prognostic factor for patients with extrahepatic *** upregulates the mRNA and protein levels of Skp2/Cks1and p27kip1via the PI3K/Akt pathway and direct binding of E2F1 transcription factor with the Skp2 promoter.

关键词： S-phase kinase-associated protein 2 Cyclindependent kinases regulatory subunit 1 P27kip1 Cholangiocarcinoma E2F1 PI3K/Akt

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RUN-UP HEIGHTS OF 1983 CENTRAL EAST SEA TSUNAMI ALONG THE KOREAN PENINSULA

RUN-UP HEIGHTS OF 1983 CENTRAL EAST SEA TSUNAMI ALONG THE KO...

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第十八届国际反应堆结构力学大会

作者： Keum-Seok Kang So-Beom Jin Yong-Sik Cho chong-hak Kim Korea Electric Power Research Institute Korea Institute of Nuclear Safety Dept. of Civil Eng. Hanyang University Korea Hydro ＆ Nuclear Power Co. Ltd.

＜正＞ Tsunamis are huge but long water waves triggered by landslides, submarine volcanic explosions, or sea-bottom deformations associated with large submarine earthquakes. These tsunamis not only killed many human beings but also caused serious property damages. For example, the 1992 Flores tsunami killed more than 264 people in Indonesia and the 1993 Hokkaido tsunami in Japan killed 239 people and caused the huge run-up heights of Babi and Okushiri Islands located near to Flores and Hokkaido Islands, respectively. More recently, the South Asia tsunami occurred in December 26, 2004 have killed approximately 280,000 people along the coastlines of Indonesia, Thailand, India, Sri Lanka and several African countries faced to the Indian Ocean.

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Growth Performance, Carcass Yield and Meat Quality of Korean Native Duck

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Journal of Agricultural Science and Technology(A) 2014年第1期4卷 76-85页

作者： Eei-Chul Hong Kang-Nyeong Heo hak-Kyu Kim Bo-Seok Kang chong-Dae Kim Hyo-Jun Choo Hee-CholChoi Mirza Muhammad Haroon Mushtaq Rana Parvin Ji-Hyuk Kim Poultry Science Division National Institute of Animal Science RDA Cheonan Chungnam 331-801 Republic of Korea

This study was carried out to investigate the growth performance, carcass yield and meat quality of large-type Korean native ducks （KND）. A total of 420 day-old ducklings were divided into four treatments （seven replicates/treatment, 15 birds/replicate） by strains （A and B） and gender （male and female） in a 2 × 2 factorial arrangement under complete randomized design. The body weight （BW） of female KND was higher at week 2 and for male it was higher in week 8 （P 〈 0.05）. BW gain, feed intake and feed conversion ratio of male KND were higher than those of female KND （P 〈 0.05） during week 0 to week 8. The carcass yield of both strains increased from 6 weeks to 8 weeks （P 〈 0.05）. The breast meat ratio was the highest at week 8 whereas the leg meat ratio was the highest at 6 weeks of age in both strains （P 〈 0.01）. Lightness （L＊）, yellowness （b＊） and juiciness of meat were the highest at 6 weeks （P 〈 0.05）. Moisture, ash and fat contents of meat were the highest at 7 weeks （P 〈 0.05） and protein content was the highest at 8 weeks （P 〈 0.01）. These results may provide the basic data on growth performance and meat quality of large-type KND, which can be used for genetic improvements and rearing at commercial scale.

关键词： Korean native duck performance carcass yield meat quality.

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The Effect of Surfactant on the Shear-induced Structure and Rheological Properties of SAA/Oil/Fatty Alcohol/Water Quaternary System

The Effect of Surfactant on the Shear-induced Structure and ...

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第八届中国化妆品学术研讨会

作者： Sung-Ho Moon Chang Seok Ki Woori Bae Pi Bongsoo Heeseon An Chang Man Park Soonae An Byung-guen chae Sang-Hoon Han hak-Hee Kang Jae Ho Yeon Cosmetics & Personal Care Research Institute Amore-Pacific R&D CenterKorea Amore-Pacific Shanghai R&D Center China

The effect of surfactant on the rheological properties of quaternary systems consisting of surfactant, oil,fatty alcohol and water is studied to improve the stability of O/W *** basic ternary systems show the formation of lamella liquid crystals called∝gel(alpha).On the other hand,the quaternary systems behave lamella liquid crystals including M and D *** is the study of the diverse rheological responses was done by a polarizing microscope,rheometer,differential scanning calorimetry,small angle X-ray scattering(SAXS) and *** the different kinds of surfactant is added,quaternary systems show the diverse rheological *** surfactants are used as emulsifier which is nonionic surfactant,anionic surfactant,cationic surfactant and surfactant mixtures.

关键词： Lamella liquid crystals quaternary systems Rheological Properties

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