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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

Colonoscopy procedural skills and training for new beginners

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World Journal of Gastroenterology 2014年第45期20卷 16984-16995页

作者： Seung-Hwa Lee Young-kyu park Duck-Joo Lee Kwang-Min Kim Center for Health Promotion Ajou University School of Medicine Center for Health Promotion Bundang Jesaeng Hospital

The incidence of colorectal cancer has been increasing in the developed world including South Korea and *** allows for greater diagnostic specificity and sensitivity compared with other types of examinations,such as the stool occult blood test,barium enema,and computed tomography ***,in recent years,the demand for colonoscopies has grown *** beginners including primary care physicians may help meet the increasing demand by performing ***,it is a challenge to learn the procedure due to the long learning-curve and the high rate of complications,such as perforation and bleeding,as compared to ***,considerable training and experience are required for optimal performance of *** order to perform a complete colonoscopic examination,there were a few important thingsto learn and remember,such as the position of examinee(e.g.,left and right decubitus,supine,and prone)and examiner(two-man method vs one-man standing method vs one-man sitting method),basic skills(e.g.,tip deflection,push forward and pull back,torque,air suction and insufflation),advanced skills(e.g.,jiggling and shaking,right and left turn shortening,hooking,and slide-by technique),assisting skills(e.g.,position change of examinee,abdominal compression,breathing-holding,and liquid-infusion technique),and intubation techniques along the lower gastrointestinal *** this article,we attempt to describe the methods of insertion and advancement of the colonoscope to the new beginners including primary care *** believe that this article may be helpful to the new beginners who wish to learn the procedure.

关键词： Colonoscopy Beginner Training Proce-dural skills

公元1840年以来东亚夏季风降水变化——以中国和韩国的树轮记录为例

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中国科学（D辑） 2003年第6期33卷 543-549页

作者：刘禹 Won-kyu park 蔡秋芳 Jung-Wook Seo Hyun-Sook Jung 中国科学院地球环境研究所黄土与第四纪地质国家重点实验室西安710075 韩国忠北大学林学院韩国国家气象局气象研究院

根据中国和韩国3条树木年轮降水记录,本文分析了过去160a以来东亚夏季风降水的变迁历史。统计分析表明,年际间中国和韩国季风降水不存在线性相关,而在10a尺度上则表现出同步变化的趋势。1860～1890,1910～1925,1940～1960年是3个降水量... 详细信息

根据中国和韩国3条树木年轮降水记录,本文分析了过去160a以来东亚夏季风降水的变迁历史。统计分析表明,年际间中国和韩国季风降水不存在线性相关,而在10a尺度上则表现出同步变化的趋势。1860～1890,1910～1925,1940～1960年是3个降水量较多的时段;1890～1910,1925～1940,1960～1998年,则是3个降水量较少的时段。3条降水重建序列均揭示1920年代中期东亚夏季风降水快速由多转少。同时树木年轮季风降水重建序列也被基于中国历史文献记载所划分的旱涝指数和韩国雨量记录所证实。

关键词：中国韩国树木年轮东亚夏季风降水降水变化降水量气候变化

Programmed death ligand-1 expression and its prognostic role in esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2016年第37期22卷 8389-8397页

作者： Ryul Kim Bhumsuk Keam Dohee Kwon Chan-Young Ock Miso Kim Tae Min Kim Hak Jae Kim Yoon kyung Jeon In kyu park Chang Hyun Kang Dong-Wan Kim Young Tae Kim Dae Seog Heo Department of Internal Medicine Seoul National University HospitalSeoul 03080South Korea Cancer Research Institute Seoul National University College of MedicineSeoul 03080South Korea Department of Pathology Seoul National University HospitalSeoul 03080South Korea Department of Radiation Oncology Seoul National University HospitalSeoul 03080South Korea Department of Thoracic and Cardiovascular Surgery Seoul National University HospitalSeoul 03080South Korea

AIM To investigate the expression and prognostic role of programmed death ligand-1(PD-L1) in locally advanced esophageal squamous cell carcinoma(ESCC).METHODS A total of 200 patients with ESCC who underwent radical esophagectomy with standard lymphadenectomy as the initial definitive treatment in Seoul National University Hospital from December 2000 to April 2013 were eligible for this analysis. Tissue microarrays were constructed by collecting tissue cores from surgical specimens, and immunostained with antibodies directed against PD-L1, p16, and c-Met. Medical records were reviewed retrospectively to assess clinical outcomes. Patients were divided into two groups by PD-L1 status, and significant differences in clinicopathologic characteristics between the two groups were assessed. RESULTS Tumor tissues from 67 ESCC patients(33.5%) were PDL1-positive. Positive p16 expression was observed in 21 specimens(10.5%). The H-score for c-Met expression was ≥ 50 in 42 specimens(21.0%). Although PDL1-positivity was not significantly correlated with any clinical characteristics including age, sex, smoking/alcoholic history, stage, or differentiation, H-scores for c-Met expression were significantly associated with PDL1-positivity(OR = 2.34, 95%CI: 1.16-4.72, P = 0.017). PD-L1 expression was not significantly associated with a change in overall survival(P = 0.656). In contrast, the locoregional relapse rate tended to increase(P = 0.134), and the distant metastasis rate was significantly increased(HR = 1.72, 95%CI: 1.01-2.79, P = 0.028) in patients with PD-L1-positive ESCC compared to those with PD-L1-negative *** PD-L1 expression is positively correlated with c-Met expression in ESCC. PD-L1 may play a critical role in distant failure and progression of ESCC.

关键词： Esophageal neoplasm Programmed death ligand-1 protein c-Met protein Prognosis p16INK4A protein

Omni-functional simultaneous interfacial treatment for enhancing stability and outgassing suppression of lithium-ion batteries

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Journal of Energy Chemistry 2024年第7期94卷 677-687页

作者： Youbean Lee Chanjoo park Kyoungmin Min Kwangjin park Department of Mechanical Engineering Gachon UniversityGyeonggi-do 13120Republic of Korea Department of Battery Engineering Gachon UniversityGyeonggi-do 13120Republic of Korea School of Mechanical Engineering Soongsil UniversitySeoul 06978Republic of Korea

Ni-rich layered oxides in lithium-ion batteries have problems with gas generation and electrochemical performance reduction due to residual lithium's reaction on the surface with the *** address this issue,in this study,the Acid solvent evaporation(AsE)method has been proposed as a potential method to remove residual lithium while promoting the formation of a new LiNO_(3)-derived coating layer on the cathode *** reduction of residual lithium using the ASE method and the construction of a LiNO_(3)-derived coating layer suppresses gas evolution caused by the side effects of the electrolyte,improves electrochemical performance,and improves thermal stability by facilitating the smooth movement of lithium ***,the structural stability and resistance change due to the LiNO_(3)-derived coating layer effects is guaranteed through cycling and DCIR of the pouch *** a result,compared to Pristine,the capacity retention of coin cells increased by 8%after 100 cycles,and pouch cells increased by 25%after 160 *** addition,after cycling the pouch cell,CO_(2) gas has significantly reduced by about 30%compared to Pristine using gas *** ASE method effectively forms a robust LiNO_(3)-derived coating layer on the cathode active material,which helps minimize electrolyte reactivity,suppress ,CO_(2) emissions,enhance surface structure stability,improve thermal stability,and improveoverallbatteryperformance.

关键词： Lithium-ion batteries Ni-rich NCM Acid solvent evaporation LiNO_(3)-derived coating Gasevolution

Mechanisms of fibrogenesis in liver cirrhosis:The molecular aspects of epithelial-mesenchymal transition

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World Journal of Hepatology 2014年第4期6卷 207-216页

作者： Sun-Jae Lee kyung-Hyun Kim Kwan-kyu park Department of Pathology Catholic University of DaeguCollege of Medicine

Liver injuries are repaired by fibrosis and *** cause of fibrosis and diminished regeneration,especially in liver cirrhosis,is still *** transition(EMT) has been found to be associated with liver *** possibility that EMT could contribute to hepatic fibrogenesis reinforced the concept that activated hepatic stellate cells are not the only key players in the hepatic fibrogenic process and that other cell types,either hepatic or bone marrow-derived cells could contribute to this *** an initial enthusiasm for the discovery of this novel pathway in fibrogenesis,more recent research has started to cast serious doubts upon the real relevance of this phenomenon in human fibrogenetic *** debate on the authenticity of EMT or on its contribution to the fibrogenic process has become very *** overall result is a general confusion on the meaning and on the definition of several key *** aim of this article is to describe how EMT participates to hepatic fibrosis and discuss the evidence of supporting this possibility in order to reach reasonable and useful conclusions.

关键词： Epithelial-mesenchymal transition Liver Fibrosis Transforming growth factor-beta1 Biological markers

Defect Engineering in Earth-Abundant Cu_(2)ZnSnSe_(4) Absorber Using Efficient Alkali Doping for Flexible and Tandem Solar Cell Applications

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Energy & Environmental Materials 2024年第2期7卷 249-256页

作者： Muhammad Rehan Ara Cho Inyoung Jeong Kihwan Kim Asmat Ullah Jun-Sik Cho Joo Hyung park Yunae Jo Sung Jun Hong Seung kyu Ahn SeJin Ahn Jae Ho Yun Jihye Gwak Donghyeop Shin Photovoltaics Research Department Korea Institute of Energy Research(KIER)152-Gajeong-roYuseong-guDaejeon 34129Korea Department of Renewable Energy Engineering University of Science and Technology(UST)217-Gajeong-roYuseong-guDaejeon 34113Korea Korea Institute of Energy Technology(KENTECH) 50772 Ujeong-roNaju Jeonnam 58217Korea

To demonstrate flexible and tandem device applications,a low-temperature Cu_(2)ZnSnSe_(4)(CZTSe)deposition process,combined with efficient alkali doping,was ***,high-quality CZTSe films were grown at 480℃by a single co-evaporation,which is applicable to polyimide(PI)*** of the alkali-free substrate,Na and K alkali doping were systematically studied and optimized to precisely control the alkali distribution in *** bulk defect density was significantly reduced by suppression of deep acceptor states after the(NaF+KF)*** the low-temperature deposition with(NaF+KF)PDTs,the CZTSe device on glass yields the best efficiency of 8.1%with an improved Voc deficit of 646 *** developed deposition technologies have been applied to *** the first time,we report the highest efficiency of 6.92%for flexible CZTSe solar cells on ***,CZTSe devices were utilized as bottom cells to fabricate four-terminal CZTSe/perovskite tandem cells because of a low bandgap of CZTSe(~1.0 eV)so that the tandem cell yielded an efficiency of 20%.The obtained results show that CZTSe solar cells prepared by a low-temperature process with in-situ alkali doping can be utilized for flexible thin-film solar cells as well as tandem device applications.

关键词： alkali doping Earth-abundant Cu_(2)ZnSnSe_(4) flexible solar cells four-terminal tandem cells low-temperature process

Non-interleaved chiral metasurfaces and neural networks enhance the spatial resolution of polarimetry

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Light(Science & Applications) 2024年第3期13卷 396-398页

作者： Jaewon Jang Minsu park Yeonsang park Department of Physics Chungnam National UniversityDaejeon 34134Korea Institute of Quantum Systems Chungnam National UniversityDaejeon 34134Korea

Non-interleaved chiral metasurfaces for high-spatial-resolution polarimetry are proposed and ***,a convolutional neural network is incorporated to analyze interferometric images with the polarization state of light,an... 详细信息

关键词： parameters chiral resolution

Technical skills and training of upper gastrointestinal endoscopy for new beginners

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World Journal of Gastroenterology 2015年第3期21卷 759-785页

作者： Seung-Hwa Lee Young-kyu park Sung-Min Cho Joon-Koo Kang Duck-Joo Lee Health Promotion Center Ajou University School of MedicineSuwon 443-380South Korea Health Promotion Center Bundang Jaesang HospitalKwandong University School of MedicineSeongnam 463-774South Korea Department of Gastroenterology Ajou University School of MedicineSuwon 443-380South Korea

The incidence of gastric cancer remains high in *** gastrointestinal(GI) endoscopy,i.e.,esophagogastroduodenoscopy(EGD),has a higher diagnostic specificity and sensitivity than the upper GI ***,EGD has the ability to biopsy,through taking a tissue of the pathologic *** training of EGD procedural skills require a few important things to be learned and remembered,including the posture of an examinee(e.g.,left lateral decubitus and supine) and examiner(e.g.,one-man standing method vs one-man sitting method),basic skills(e.g.,tip deflection,push forward and pull back,and air suction and infusion),advanced skills(e.g.,paradoxical movement,J-turn,and U-turn),and intubation techniques along the upper GI tract(e.g.,oral cavity,pharynx,larynx including vocal cord,upper and middle and lower esophagus,gastroesophageal junction,gastric fundus,body,and antrum,duodenal bulb,and descending part of duodenum).In the current review,despite several limitations,we explained the intubation method of EGD for *** hope this will be helpful to beginners who wish to learn the procedure.

关键词： Upper gastrointestinal endoscopy Esophagogastroduo