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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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Comprehensive molecular characterization to predict immunotherapy response in advanced biliary tract cancer:a phase II trial of pembrolizumab

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Oncology Research 2025年第1期33卷 57-65页

作者： RYUL KIM JOO KYUNG PARK MINSUK KWON MINAE AN JUNG YONG HONG JOON OH PARK SUNG hee lim SEUNG TAE KIM Division of Hematology-Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea Division of Gastroenterology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea Department of Hematology-Oncology Ajou University School of MedicineSuwon-siGyeonggi-doKorea Samsung Advanced Institute of Health Science and Technology Sungkyunkwan University School of MedicineSeoulKorea

Background:Immune checkpoint inhibitors(ICIs)are effective in a subset of patients with metastatic solid ***,the patients who would benefit most from ICIs in biliary tract cancer(BTC)are still *** and methods:We molecularly characterized tissues and blood from 32 patients with metastatic BTC treated with the ICI pembrolizumab as second-line ***:All patients had microsatellite stable(MSS)type *** of the 32 patients achieved partial response(PR),with an objective response rate(ORR)of 9.4%(95%confidence interval[CI],2.0–25.2)and nine showed stable disease(SD),exhibiting a disease control rate(DCR)of 37.5%(95%CI,21.1–56.3).For the 31 patients who had access to PD-1 ligand 1(PD-L1)combined positive score(CPS)testing(cut-off value≥1%),the ORR was not different between those who had PD-L1-positive(PD-L1+;1/11,9.1%)and PDL1-(2/20,10.0%)tumors(p=1.000).The tumor mutational burden(TMB)of PD-L1+BTC was comparable to that of PD-L1-BTC(p=0.630).TMB and any exonic somatic mutations were also not predictive of pembrolizumab *** analysis of blood and tumor samples demonstrated a relatively high natural killer(NK)cell proportion in the peripheral blood before pembrolizumab treatment in patients who achieved tumor ***,the tumors of these patients presented high enrichment scores for NK cells,antitumor cytokines,and Th1 signatures,and a low enrichment score for cancer-associated ***:This study shows the molecular characteristics associated with the efficacy of pembrolizumab in BTC of the MSS type.

关键词： Pembrolizumab Whole-exome sequencing Whole-transcriptome sequencing Biliary tract cancer

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Single-cell and spatial omics:exploring hypothalamic heterogeneity

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Neural Regeneration Research 2025年第6期20卷 1525-1540页

作者： Muhammad Junaid Eun Jeong Lee Su Bin lim Department of Biochemistry&Molecular Biology Ajou University School of MedicineSuwonSouth Korea Department of Biomedical Sciences Graduate School of Ajou UniversitySuwonSouth Korea Department of Brain Science Ajou University School of MedicineSuwonSouth Korea

Elucidating the complex dynamic cellular organization in the hypothalamus is critical for understanding its role in coordinating fundamental body functions. Over the past decade, single-cell and spatial omics technologies have significantly evolved, overcoming initial technical challenges in capturing and analyzing individual cells. These high-throughput omics technologies now offer a remarkable opportunity to comprehend the complex spatiotemporal patterns of transcriptional diversity and cell-type characteristics across the entire hypothalamus. Current single-cell and single-nucleus RNA sequencing methods comprehensively quantify gene expression by exploring distinct phenotypes across various subregions of the hypothalamus. However, single-cell/single-nucleus RNA sequencing requires isolating the cell/nuclei from the tissue, potentially resulting in the loss of spatial information concerning neuronal networks. Spatial transcriptomics methods, by bypassing the cell dissociation, can elucidate the intricate spatial organization of neural networks through their imaging and sequencing technologies. In this review, we highlight the applicative value of single-cell and spatial transcriptomics in exploring the complex molecular-genetic diversity of hypothalamic cell types, driven by recent high-throughput achievements.

关键词： cellular diversity hypothalamus multi-omics single-cell transcriptomics spatial transcriptomics

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TT virus and hepatitis G virus infections in Korean blood donors and patients with chronic liver disease

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World Journal of Gastroenterology 2003年第4期9卷 741-744页

作者： Mee Juhng Jeon jong hee Shin Soon Pal Suh Young Chai lim Dong Wook Ryang Division of Medical Research Kwangju-Chonnan Red Cross Blood CenterChonnam National UniversityKwangju Republic of Korea Department of Clinical Pathology Chonnam National UniversityKwangju Republic of Korea Research Institute of Medical SciencesChonnam Nationa UniversityKwangjuRepublic of Korea Department of Pharmacology Medical SchoolChonnam National UniversityKwangjuRepublic of Korea Research Institute of Medical SciencesChonnam National UniversityKwangjuRepublic of Korea Department of Clinical Pathology Chonnam National UniversityKwangjuRepublic of Korea Research Institute of Medical Scienceschonnam National UniversityKwangjuRepublic of Korea

AIM:To determine the prevalences of TTV and HGV infections among blood donors and patients with chronic liver disease in Korea,to investigate the association of TTV and HGV infections with blood transfusion,and to assess the correlation between TTV and HGV viremia and hepatic damage. METHODS:A total of 391 serum samples were examined in this *** were obtained from healthy blood donors(n=110),hepatitis B surface antigen(HBsAg)-positive donors(n=112),anti-hepatitis C virus(anti-HCV)-positive donors(n=69),patients with type B chronic liver disease (n=81),and patients with type C chronic liver disease(n=19). Trv DNA was detected using the hemi-nested *** RNA was tested using RT-PCR.A history of blood transfusion and serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were also determined. RESULTS:TTV DNA was detected in 8.2%of healthy blood donors,16.1%of HBsAg-positive donors,20.3%of anti- HCV-positive donors,21.0%of patients with type B chronic liver disease,and 21.1%of patients with type C chronic liver *** RNA was detected in 1.8%of healthy blood donors,1.8%of HBsAg-positive donors,17.4%of anti-HCV-positive donors,13.6%of patients with type B chronic liver disease,and 10.5%of patients with type C chronic liver *** prevalence of TTV and HGV infections in HBV- or HCV-positive donors and patients was significantly higher than in healthy blood donors(P<0.05), except for the detection rate of HGV in HBsAg-positive donors which was the same as for healthy *** was a history of transfusion in 66.7%of TTV DNA-positive patients and 76.9%of HGV RNA-positive patients(P<0.05).No significant increase in serum ALT and AST was detected in the TTV or HGV-positive donors and patients. CONCLUSION:TTV and HGV infections are more frequently found in donors and patients infected with HBV or HCV than in healthy blood ***,there is no significant association between TTV or HGV infections and liver injury.

关键词： Blood Donors Blood Transfusion Chronic Disease DNA Virus Infections DNA, Viral Flaviviridae Infections GB virus C purification Hepatitis B Surface Antigens Hepatitis, Viral, Human Korea Liver Diseases Polymerase Chain Reaction Reference Values Reverse Transcriptase Polymerase Chain Reaction Torque teno virus

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Engineering Geometric Electrodes for Electric Field-Enhanced High-Performance Flexible In-Plane Micro-Supercapacitors

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Energy & Environmental Materials 2023年第4期6卷 114-120页

作者： Jihong Kim Sung Min Wi jong-Guk Ahn Sangjun Son hee Young lim Yeonsu Park Hye Ji Eun jong Bae Park Hyunseob lim Sangyeon Pak A-Rang Jang Young-Woo Lee Department of Energy Engineering Soonchunhyang UniversityAsan 31538Korea Department of Chemistry Gwangju Institute of Science and TechnologyGwangju 61005Korea Jeonju Centre Korea Basic Science InstituteJeonju 54907Korea Prof.S.Pak School of Electronic and Electrical Engineering Hongik UniversitySeoul 04066Korea Division of Electrical Electronic and Control EngineeringKongju National UniversityCheonan 31080Korea

In plane micro-supercapacitors that are miniaturized energy storage components have attracted significant attention due to their high power densities for various ubiquitous and sustainable device systems as well as their facile integration on various flexible/wearable *** implement the micro-supercapacitors in various practical applications that can accompany solid state or gel electrolyte and flexible substrates,ions must be readily transported to electrodes for achieving high power ***,we show large enhancement in electrochemical properties of flexible,inplane micro-supercapacitor using sharp-edged interdigitated electrode design,which was simply fabricated through direct laser scribing *** sharp-edged electrodes allowed strong electric field to be induced at the corners of the electrode fingers which led to the greater accumulation of ions near the surface of electrode,significantly enhancing the energy storage performance of *** electric field-enhanced in-plane micro-supercapacitor showed the volumetric energy density of 1.52 Wh L^(−1)and the excellent cyclability with capacitive retention of 95.4%after 20000 *** further showed various practicability of our sharp-edged design in micro-supercapacitors by showing circuit applicability,mechanical stability,and air *** results present an important pathway for designing electrodes in various energy storage devices.

关键词： electric field enhancement flexible energy storage device microsupercapacitors sharp electrodes

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Model development to estimate site index values for six major tree species in North Korea

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Journal of Forestry Research 2023年第2期34卷 387-400页

作者： Sohee Park A-Ram Yang Eun-hee Kim Joongbin lim Division of Global Forestry Department of Future Forest StrategyNational Institute of Forest ScienceSeoul 02455Republic of Korea Forest ICT Research Center National Institute of Forest ScienceSeoul 02455Republic of Korea

Due to considerable deforestation in North Korea,there is a need to plan forest restoration programs based on scientific forest *** this study,a methodology was developed for estimating the site index values of six major tree species and the forest productivity *** site index values of these tree species were derived in South Korea using the Chapman-Richards *** values were used with data from the 6th National Forest Inventory,which included 20 types of edaphic,topographic,and climatic factors,and random forest analysis—a widely used machine learning technique for spatial prediction—to develop a new model for estimating the site index values of these species across South *** prediction accuracy of this model was evaluated using the root mean square *** results show that the prediction accuracy was high,with a root mean square error of~***,the importance of the variables related to climate and geography was generally *** proposed site index estimation model for six tree species was applied across North Korea,and its effectiveness tested by comparing the estimated values with those reported in literature from North *** differences between the model outputs and recorded data in the northern alpine regions were presumably due to the lack of data for high-altitude regions in South *** model is based on the determination of the suitability of tree species in restoration ***,it can contribute to the evaluation of forest productivity in North Korea and may help plan efficient forest restoration programs.

关键词： Environmental factors Forest productivity Machine learning North Korea Random forest Site index

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Clinical course of subepithelial lesions detected on upper gastrointestinal endoscopy

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World Journal of Gastroenterology 2010年第4期16卷 439-444页

作者： Yeun Jung lim hee Jung Son jong-Soo Lee Young Hye Byun Hyun Joo Suh Pool Lyul Rhee Jae J Kim jong Chul Rhee Center for Health Promotion Department of MedicineSamsung Medical CenterSungkyunkwan University School of Medicine50Irwon-dongGangnam-guSeoul 135-710South Korea Division of Gastroenterology Department of MedicineSamsung Medical CenterSungkyunkwan University School of Medicine50Irwon-dongGangnam-guSeoul 135-710South Korea

AIM:To evaluate the natural history of subepithelial ***:We reviewed the medical records of 104 159 patients who underwent upper gastrointestinal endoscopy at the Center for Health Promotion of Samsung Medical Center between 1996 and *** lesions were detected in 795 patients(0.76%);252 patients were followed using upper gastrointestinal endoscopy for 82.5 ± 29.2 mo(range,12-160 mo;median,84 mo;1st quartile,60 mo;3rd quartile,105 mo).The median interval of follow-up endoscopy was 12 mo(range,6-105 mo;1st quartile,12 mo;3rd quartile,24 mo).RESULTS:The mean patient age was 53 years(range,22-80 years),and the male-to-female ratio was 2.36:1(177/75).The lesion size at initial measurement averaged 8.9 mm(range,2-25 mm;median,8 mm;1st quartile,5 mm;3rd quartile,10 mm).Of the 252 lesions,244(96.8%) were unchanged and 8(3.2%) were significantly increased in size(from 12.9 ± 6.0 to 21.2 ± 12.2 mm) after a mean interval of 59.1 ± 27.5 mo(range,12-86 mo).Surgical resection of lesions was performed when the lesions were ≥ 3 cm in *** lesions were diagnosed as gastrointestinal stromal tumors with an intermediate or high risk of malignancy and one lesion was classified as a ***:Most small subepithelial lesions do not change as shown by endoscopic examination,and regular follow-up with endoscopy may be considered in small,subepithelial lesions,especially lesions < 1 cm in size.

关键词： Subepithelial tumor Ultrasonography Gastrointestinal diseases Gastrointestinal endoscopy Time factors

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Characteristic analysis of bleeding effect on standing column well (SCW) type geothermal heat exchanger

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Journal of Central South University 2012年第11期19卷 3202-3207页

作者： CHOI Hoon-ki YOO Geun-jong lim Kyung-bin LEE Sang-hoon LEE Chang-hee Department of Mechanical Design/Manufacturing Engineering Changwon National UniversityChangwon 641-773Korea Department of Mechanical Design Engineering Hanbat National UniversityDaejon 305-719Korea Department of Energy Engineering Jeonju UniversityJeonju 560-759Korea STX Institute of Technology Gyeongnam 642-845Korea

Thermal performance is the most important factor in the development of a borehole heat exchanger utilizing geothermal *** thermal performance is affected by many different design parameters and different operating conditions such as *** eventually determines the operation and cost efficiency of the borehole heat exchanger *** thermal performance of an open standing column well (SCW) type geothermal heat exchanger was assessed under the influence of *** this,a thermal response test rig was established with line-source *** test rig also had a bleeding function by releasing fluid while taking additional underground water through the heat *** thermal response test was performed with an additional constant input heat *** thermal conductivity and thermal resistance were obtained from the measured *** the measurement,the effective thermal conductivity is found to have 1.47 times higher value when bleeding is *** thermal resistance also increases by 1.58 times compared to a non-bleeding *** trend indicates enhanced heat transfer in the SCW type heat exchanger with a bleeding ***,therefore,could be an effective method of achieving a high heat transfer rate in the SCW type heat exchanger with sufficient underground water supply.

关键词： standing column well type thermal response test effective thermal conductivity thermal resistance bleeding effect

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Thermal performance analysis of borehole size effect on geothermal heat exchanger

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Journal of Central South University 2012年第12期19卷 3524-3529页

作者： CHOI Hoon-ki YOO Geun-jong lim Kyung-bin LEE Sang-hoon LEE Chang-hee Department of Mechanical Design and Manufacturing Engineering Changwon National UniversityChangwon 641-773Korea Department of Mechanical Design Engineering Hanbat National UniversityDaejon 305-719Korea Department of Energy Engineering Jeonju UniversityJeonju 560-759Korea STX Institute of Technology Changwon 642-845Korea

Thermal performance was the most important factor in the development of borehole heat exchanger utilizing geothermal energy. The thermal performance was affected by many different design parameters, such as configuration type and borehole size of geothermal heat exchanger. These eventually determined the operation and cost efficiency of the geothermal heat exchanger system. The main purpose of this work was to assess the thermal performance of geother^nal heat exchanger with variation of borehole sizes and numbers of U-tubes inside a borehole. For this, a thermal response test rig was established with line-source theory. The thermal response test was performed with in-line variable input heat source. Effective thermal conductivity and thermal resistance were obtained from the measured data. From the measurement, the effective thermal conductivity is found to have similar values for two- pair type （4 U-tubes） and three-pair type （6 U-tubes） borehole heat exchanger systems indicating similar heat transfer ability. Meanwhile, the thermal resistance shows lower value for the three-pair type compared to the two-pair type. Measured data based resistance have lower value compared to computed result from design programs. Overall comparison finds better thermal performance for the three-pair type, however, fluctuating temperature variation indicates complex flow behavior inside the borehole and requires further study on flow characteristics.

关键词： large size borehole heat exchanger thermal response test effective thermal conductivity thermal resistance borehole

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Role of the tumor microenvironment in the pathogenesis of gastric carcinoma

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World Journal of Gastroenterology 2014年第7期20卷 1667-1680页

作者： Hye Won Chung jong-Baeck lim Department of Internal Medicine Institute of GastroenterologyYonsei University College of MedicineSeoul 135-720South Korea Department of Laboratory Medicine Yonsei University College of MedicineSeoul 135-720South Korea

Gastric carcinoma (GC) is the 4th most prevalent cancer and has the 2nd highest cancer-related mortality rate worldwide. Despite the incidence of GC has decreased over the past few decades, it is still a serious health problem. Chronic inflammatory status of the stomach, caused by the infection of Helicobacter pylori (H. pylori) and through the production of inflammatory mediators within the parenchyma is suspected to play an important role in the initiation and progression of GC. In this review, the correlation between chronic inflammation and H. pylori infection as an important factor for the development of GC will be discussed. Major components, including tumor-associated macrophages, lymphocytes, cancer-associated fibroblasts, angiogenic factors, cytokines, and chemokines of GC microenvironment and their mechanism of action on signaling pathways will also be discussed. Increasing our understanding of how the components of the tumor microenviroment interact with GC cells and the signaling pathways involved could help identify new therapeutic and chemopreventive targets.

关键词： Tumor microenvironment Gastric carcinoma Inflammation Helicobacter pylori Cytokine

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