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RANKL-responsive epigenetic mechanism reprograms macrophages into bone-resorbing osteoclasts

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Cellular & Molecular Immunology 2023年第1期20卷 94-109页

作者： Seyeon Bae Kibyeong Kim Keunsoo Kang Haemin Kim Minjoon Lee Brian Oh Kaichi Kaneko Sungkook Ma Jae Hoon Choi Hojoong Kwak eun Young Lee Sung Ho park Kyung-Hyun park-Min Arthritis and Tissue Degeneration Program David Z.Rosensweig Genomics Research CenterHospital for Special SurgeryNew YorkNY10021USA Department of Medicine Weill Cornell Medical CollegeNew YorkNY10065USA Department of Biological Science Ulsan National Institute of Science&Technology(UNIST)Ulsan44919Republic of Korea Department of Life Science College of Natural SciencesResearch Institute for Natural SciencesHanyang UniversitySeoulKorea Department of Microbiology Dankook UniversityCheonan3116Republic of Korea Department of Molecular Biology and Genetics Cornell UniversityIthacaUSA Division of Rheumatology Department of Internal MedicineSeoul National University College of MedicineSeoulKorea BCMB Allied Program Weill Cornell Graduate School of Medical SciencesNew YorkNY10021USA

Monocyte/macrophage lineage cells are highly plastic and can differentiate into various cells under different environmental stimuli. Bone-resorbing osteoclasts are derived from the monocyte/macrophage lineage in response to receptor activator of NF-κB ligand (RANKL). However, the epigenetic signature contributing to the fate commitment of monocyte/macrophage lineage differentiation into human osteoclasts is largely unknown. In this study, we identified RANKL-responsive human osteoclast-specific superenhancers (SEs) and SE-associated enhancer RNAs (SE-eRNAs) by integrating data obtained from ChIP-seq, ATAC-seq, nuclear RNA-seq and PRO-seq analyses. RANKL induced the formation of 200 SEs, which are large clusters of enhancers, while suppressing 148 SEs in macrophages. RANKL-responsive SEs were strongly correlated with genes in the osteoclastogenic program and were selectively increased in human osteoclasts but marginally presented in osteoblasts, CD4+ T cells, and CD34+ cells. In addition to the major transcription factors identified in osteoclasts, we found that BATF binding motifs were highly enriched in RANKL-responsive SEs. The depletion of BATF1/3 inhibited RANKL-induced osteoclast differentiation. Furthermore, we found increased chromatin accessibility in SE regions, where RNA polymerase II was significantly recruited to induce the extragenic transcription of SE-eRNAs, in human osteoclasts. Knocking down SE-eRNAs in the vicinity of the NFATc1 gene diminished the expression of NFATc1, a major regulator of osteoclasts, and osteoclast differentiation. Inhibiting BET proteins suppressed the formation of some RANKL-responsive SEs and NFATc1-associated SEs, and the expression of SE-eRNA:NFATc1. Moreover, SE-eRNA:NFATc1 was highly expressed in the synovial macrophages of rheumatoid arthritis patients exhibiting high-osteoclastogenic potential. Our genome-wide analysis revealed RANKL-inducible SEs and SE-eRNAs as osteoclast-specific signatures, which may contribute to t

关键词： Osteoclasts super-enhancers enhancer RNAs Rheumatoid arthritis

Enhanced delivery of a low dose of aducanumab via FUS in 5×FAD mice,an AD model

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Translational Neurodegeneration 2022年第1期11卷 31-45页

作者： Chanho Kong eun-Jeong Yang Jaewoo Shin Junwon park Si-Hyun Kim Seong-Wook park Won Seok Chang Chang-Han Lee Hyunju Kim Hye-Sun Kim Jin Woo Chang Department of Neurosurgery Yonsei University College of Medicine50 Yonsei-RoSeodaemun-GuSeoulRepublic of Korea Department of Pharmacology College of MedicineSeoul National University103 DaehakroJongro-GuSeoulRepublic of Korea Neuroscience Research Center College of MedicineSeoul National University103 DaehakroJongro-GuSeoulRepublic of Korea Department of Biomedical Sciences College of MedicineSeoul National University103 DaehakroJongro-GuSeoulRepublic of Korea Bundang Hospital Seoul National University College of MedicineBundang-GuSungnamRepublic of Korea.

Background:Aducanumab(Adu),which is a human IgG1 monoclonal antibody that targets oligomer and fibril forms of beta-amyloid,has been reported to reduce amyloid pathology and improve impaired cognition after administration of a high dose(10 mg/kg)of the drug in Alzheimer’s disease(AD)clinical *** purpose of this study was to investigate the effects of a lower dose of Adu(3 mg/kg)with enhanced delivery via focused ultrasound(FUS)in an AD mouse ***:The FUS with microbubbles opened the blood-brain barrier(BBB)of the hippocampus for the delivery of *** combined therapy of FUS and Adu was performed three times in total and each treatment was performed biweekly.Y-maze test,Brdu labeling,and immunohistochemical experimental methods were employed in this *** addition,RNA sequencing and ingenuity pathway analysis were employed to investigate gene expression profiles in the hippocampi of experimental ***:The FUS-mediated BBB opening markedly increased the delivery of Adu into the brain by approximately 8.1 times in the *** combined treatment induced significantly less cognitive decline and decreased the level of amyloid plaques in the hippocampi of the 5×FAD mice compared with Adu or FUS *** treatment with FUS and Adu activated phagocytic microglia and increased the number of astrocytes associated with amyloid plaques in the hippocampi of 5×FAD ***,RNA sequencing identified that 4 enriched canonical pathways including phagosome formation,neuroinflammation signaling,CREB signaling and reelin signaling were altered in the hippocami of 5×FAD mice receiving the combined ***:In conclusion,the enhanced delivery of a low dose of Adu(3 mg/kg)via FUS decreases amyloid deposits and attenuates cognitive function ***-mediated BBB opening increases adult hippocampal neurogenesis as well as drug *** present an AD treatment strategy through the synergistic effect of the combined therapy of

关键词： Aducanumab Alzheimer’s disease Focused ultrasound Transcriptome profiling

Employment of encapsulated Si with mesoporous TiO_2 layer as anode material for lithium secondary batteries

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中国有色金属学会会刊：英文版 2009年第4期19卷 1023-1026页

作者： Sang-eun park Bo-eun KIM Sang-Wha LEE Joong-Kee LEE Advanced Energy Materials Processing Laboratory Korea Institute of Science and Technology Department of Chemical & Bio Engineering Kyungwon University

Silicon composite of nano-capsule type is newly applied as an active anode material for lithium ion ***2-encapsulated silicon powders were synthesized by a sol-gel reaction with titanium *** nanoparticles were successfully embedded into porous titanium oxide capsules that played as a buffer layer against drastic volume changes of silicon during the charge-discharge cycling,consequently leading to the retardation of the capacity fading of intrinsic silicon *** electrochemical and structural properties of silicon nanocomposites with different surface areas of encapsulating TiO2 layer were characterized by X-ray diffraction(XRD),nitrogen gas adsorption analysis by the Brunauer-Emmett-Teller(BET) equation,transmission electron microscopy(TEM),and galvanostatic charge-discharge experiments.

关键词：二氧化钛硅材料锂二次电池负极材料封装纳米复合材料透射电子显微镜就业

Association between metabolic syndrome and agerelated cataract

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International Journal of Ophthalmology(English edition) 2015年第4期8卷 804-811页

作者： Sangshin park eun-Hee Lee Center for International Health Research Rhode Island Hospital The Warren Alpert Medical School of Brown University Department of Visual Optics and Graduate School of Health Science Far East University

·AIM: To determine the effect of metabolic syndrome on age-related cataract formation.·METHODS: We analyzed data for 2852 subjects [41.8%men and 58.2% women; mean(±SD) age, 52.9 ±13.9y],taken from the Korea National Health and Nutrition Examination Survey 2008. Metabolic syndrome was diagnosed by criteria proposed by the Joint Interim Societies. Cataract was diagnosed by using the Lens Opacities Classification System III. The association between metabolic syndrome and cataract was determined using age-adjusted and multivariable logistic regression analyses.· RESULTS: In multivariable analyses, men with metabolic syndrome had a 64% increased risk of nuclear cataract [odds ratio(OR), 1.64; 95% confidence interval(CI), 1.12-2.39]. Women with metabolic syndrome had a56% increased risk of cortical cataract(OR, 1.56; 95% CI,1.06-2.30). Men and women with metabolic syndrome had a 46%(OR, 1.46; 95% CI, 1.01-2.12) and 49%(OR,1.49; 95% CI, 1.07-2.08) increased risk of any cataract,respectively. The prevalence of nuclear and any cataract significantly increased with an increasing number of disturbed metabolic components in men, and prevalence of all types of cataracts increased in women. Men using hypoglycemic medication had an increased risk of nuclear(OR, 2.62; 95% CI, 1.41-4.86) and any(OR, 2.27;95% CI, 1.14-4.51) cataract, and women using antidyslipidemia medication had an increased risk of cortical(OR, 2.18; 95% CI, 1.12-4.24) and any(OR, 2.21;95% CI, 1.14-4.26) cataract.·CONCLUSION: Metabolic syndrome and its components,such as abdominal obesity, high blood pressure, andimpaired fasting glucose, are associated with age-related cataract formation in the Korean population.

关键词： cataract metabolic syndrome obesity diabetes mellitus hypertension

Efficacy and safety of conversion of percutaneous cholecystostomy to endoscopic transpapillary gallbladder stenting in high-risk surgical patients

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Hepatobiliary & Pancreatic Diseases International 2021年第5期20卷 478-484页

作者： Hyung Ku Chon Chan park Dong eun park Tae Hyeon Kim Division of Biliopancreas Department of Internal MedicineWonkwang University College of Medicine and Hospital895 MuwangRoIksanSouth Korea Institute of Wonkwang Medical Science Wonkwang University College of Medicine and HospitalIksanSouth Korea Department of Surgery Wonkwang University College of Medicine and HospitalIksanSouth Korea

Background:Endoscopic transpapillary gallbladder stenting(ETGBS)has been used as an alternative to percutaneous cholecystostomy in patients with acute cholecystitis who are considered unfit for ***,there are few data on the efficacy and safety of ETGBS replacement of percutaneous cholecystostomy in high-risk surgical *** study aimed to evaluate the feasibility,efficacy,and safety of ETGBS to replace percutaneous cholecystostomy in high-risk surgical ***:This single center retrospective study reviewed the data of patients who attempted ETGBS to replace percutaneous cholecystostomy between January 2017 and September *** technical success,clinical success,adverse events,and stent patency were ***:ETGBS was performed in 43 patients(24 male,mean age 80.7±7.4 years)to replace percutaneous cholecystostomy due to high surgical *** technical success rate and clinical success rate were 97.7%(42/43)and 90.5%(38/42),***-related adverse events and stent-related late adverse events occurred in 7.0%(3/43)and 11.6%(5/43),*** the patients who successfully underwent ETGBS(n=42),only one had recurrent acute cholecystitis during *** median stent patency was 415 days(interquartile range 240–528 days).Conclusions:ETGBS,as a secondary intervention for the purpose of internalizing gallbladder drainage in patients following placement of a percutaneous cholecystostomy,is safe,effective,and technically ***,conversion of percutaneous cholecystostomy to ETGBS may be considered as a viable option in high-risk surgical patients.

关键词： Cholecystitis Percutaneous cholecystostomy Endoscopic transpapillary gallbladder stenting High surgical risk

Submerged arc plasma system combined with ozone oxidation for the treatment of wastewater containing non-degradable organic compounds

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Frontiers of Environmental Science & Engineering 2021年第5期15卷 155-163页

作者： Byungjin Lee eun Seo Jo Dong-Wha park Jinsub Choi Department of Chemistry and Chemical Engineering and Regional Innovation Center for Environmental Technology of Thermal Plasma(RIC-ETTP) INHA UniversityIncheon402-751Republic of Korea

Submerged arc plasma technology was assessed for the removal of phenols from *** OH radicals generated from the boundary between the plasma and waste solution were considered as a significant factor on the degradation *** this study,the effects of highly energetic electrons released from the submerged arc plasma were mainly *** highly energetic electrons directly broke the strong chemical bond and locally increased the reaction temperatures in *** effects of the submerged-arc plasma on the decomposition of phenol are discussed in terms of the input energy and initial *** single use of submerged arc plasma easily decomposed the phenol but did not increase the mineralization ***,the submerged arc plasma,coupled with the ozone injection,was *** submerged arc plasma combined with ozone injection had a synergic effect,which led to significant improvements in mineralization with only a small increase in input *** decomposition mechanism of phenol by the submerged arc plasma with the ozone was analyzed.

关键词： Thermal plasma Submerged arc plasma Wastewater Ozone Phenol Highly energetic electron

A dynamic infiltration technique to synthesize nanolayered cathodes for high performance and robust solid oxide fuel cells

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Journal of Energy Chemistry 2022年第7期31卷 201-210,I0006页

作者： Saeed Ur Rehman Ho-Seon Song Hye-Sung Kim Muhammad Haseeb Hassan Dong-Woo Joh Rak-Hyun Song Tak-Hyoung Lim Jong-eun Hong Seok-Joo park Seung-Bok Lee High Temperature Energy Conversion Laboratory Korea Institute of Energy Research152Gajeong-roYuseong-gu.Daejeon34129.Republic of Korea Department of Advanced Energy and System Engineering University of Science and Technology.217 Gajeong-ro.Yuseong-gu.Daejeon 34113.Republicof Korea

Solution infiltration is a popular technique for the surface modification of solid oxide fuel cell(SOFC)***,the synthesis of nanostructured SOFC cathodes by infiltration is a tedious process that often requires several infiltration and high temperature(≥500℃)calcination ***,fabricating large-area nanostructured cathodes via infiltration still requires serious ***,we propose a facile and scalable urea assisted ultrasonic spray infiltration technique for nanofabrication of SOFC *** is demonstrated that by using urea as a precipitating agent,the calcination after each infiltration cycle can be omitted and the next infiltration can be performed just after a drying step(≤100℃).Finally,the precipitates can be converted into a desired catalyst phase in single calcination thus,a nanostructured cathode can be fabricated in a much faster *** is also shown that the low calcination temperature of the cathode(≤900℃)can produce highly durable SOFC performance even without employing a Ce_(0.9)Gd_(0.1)O_(2)(GDC)diffusion barrier layer which provides the ease of SOFC *** coupling with an ultrasonic spray technique,the urea assisted infiltration can be scaled up for any desired cathode ***_(0.6)Sr_(0.4)Co_(0.2)Fe_(0.8)O_(3) nanolayered cathode was fabricated and it was characterized by scanning electron microscope(SEM),X-ray diffraction(XRD),and transmission electron microscopy(TEM)*** showed the formation of a nanolayer cathode just after 5 cycles of the urea assisted infiltration while the XRD and TEM confirmed the phase and stoichiometric uniformity of the 100 nm cathode *** effectiveness of the newly developed technique was further verified by the stable operation of a GDC buffer layer free SOFC having an active cathode area of 25 cm^(2) during a 1200 h durability *** research outcomes propose urea assisted ultrasonic spray infiltration as a facile,scalable,and commercially viable method

关键词： Solid oxide fuel cell(SOFC) Cathode Infiltration Nanolayer Nanofabrication GDC barrier layer free SOFC

Sprayable nanomicelle hydrogels and inflammatory bowel disease patient cell chips for development of intestinal lesion-specific therapy

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Bioactive Materials 2022年第12期7卷 433-445页

作者： Hyo-Jin Yoon Songhyun Lee Tae Young Kim Seung eun Yu Hye-Seon Kim Young Shin Chung Seyong Chung Suji park Yong Cheol Shin eun Kyung Wang Jihye Noh Hyun Jung Kim Cheol Ryong Ku Hong Koh Chang-Soo Kim Joon-Sang park Young Min Shin Hak-Joon Sung Department of Medical Engineering Yonsei University College of MedicineSeoul03722Republic of Korea School of Electrical and Electronic Engineering Yonsei UniversitySeoul03722Republic of Korea Department of Obstetrics and Gynecology Institution of Women’s Life Medical ScienceSeverance HospitalYonsei University College of MedicineSeoul03722Republic of Korea Department of Biomedical Engineering The University of Texas at AustinAustinTX78712USA Department of Internal Medicine EndocrinologyInstitute of Endocrine ResearchYonsei University College of MedicineSeoul03722Republic of Korea Department of Pediatrics GastroenterologySeverance HospitalYonsei University College of MedicineSeoul03722Republic of Korea Department of Computer Engineering Hongik UniversitySeoul04066Republic of Korea Institute of Tissue Regeneration Engineering(ITREN) Dankook UniversityCheonan31116Republic of Korea Numais Co. Ltd.Korea Seoul 04799Republic of Korea

All-in-one treatments represent a paradigm shift in future *** example,inflammatory bowel disease(IBD)is mainly diagnosed by endoscopy,which could be applied for not only on-site monitoring but also the intestinal lesion-targeted spray of injectable ***,molecular conjugation to the hydrogels would program both lesion-specific adhesion and drug-free *** study validated this concept of all-in-one treatment by first utilizing a well-known injectable hydrogel that underwent efficient solution-to-gel transition and nanomicelle formation as a translatable *** properties enabled spraying of the hydrogel onto the intestinal walls during ***,peptide conjugation to the hydrogel guided endoscopic monitoring of IBD progress upon adhesive gelation with subsequent moisturization of inflammatory lesions,specifically by *** peptide was designed to mimic the major component that mediates intestinal interaction with Bacillus subtilis flagellin during IBD ***,the peptide-guided efficient adhesion of the hydrogel nanomicelles onto Toll-like receptor 5(TLR5)as the main target of flagellin binding and *** peptide binding potently suppressed inflammatory signaling without drug loading,where TLR5 and Notch-1 operated collaboratively through downstream actions of tumor necrosis *** results were produced using a human colorectal cell line,clinical IBD patient cells,gut-on-a-chip,a mouse IBD model,and pig experiments to validate the translational utility.

关键词： Nanomicelle Injectable hydrogel Peptide display Theranostic All-in-one treatment Inflammatory bowel disease

Acute respiratory distress syndrome and severe pneumonitis after atezolizumab plus bevacizumab for hepatocellular carcinoma treatment:A case report

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World Journal of Gastrointestinal Oncology 2023年第5期15卷 892-901页

作者： Su Hyeon Cho Ga Ram You Chan park Sang-Geon Cho Jong eun Lee Sung Kyu Choi Sung Bum Cho Jae Hyun Yoon Department of Gastroenterology and Hepatology Chonnam National University Hospital and Medical SchoolGwangju 61469South Korea Department of Gastroenterology and Hepatology Hwasun Chonnam National University Hospital and Medical SchoolHwasun 58128South Korea Department of Radiology Chonnam National University Hospital and Medical SchoolGwangju 61469South Korea Department of Nuclear Medicine Chonnam National University HospitalHwasun 58128South Korea

BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common cancers worldwide and has a high ***,the treatment options for advanced HCC are limited to tyrosine kinase inhibitors,such as sorafenib and *** previous regimens have an insufficient efficacy,the combination therapy of atezolizumab and bevacizumab(Ate/Bev)has been investigated,which showed an improvement in progression-free and overall ***,the adverse events of this combination therapy in advanced HCC have not been ***,we report a novel case of an unresectable HCC and acute respiratory distress syndrome(ARDS)after a combination therapy of Ate/*** SUMMARY An 82-year-old male visited our outpatient clinic for an incidentally detected liver *** magnetic resonance imaging and enhanced chest computed tomography(CT)were performed,which showed arterial hyperenhancement with washout in delayed phase suggesting HCC,and a well-defined metastatic solid nodule,respectively.F-18 fluorodeoxyglucose positron emission tomography(PET)-CT exhibited multiple hypermetabolic lesions in the iliac bone,lumbar vertebrae,and *** of the high burden of the intrahepatic tumor,transarterial radioembolization was initially performed;after 37 d,a combination therapy of Ate/Bev was *** patient visited the emergency department three days after Ate/Bev treatment complaining of *** was diagnosed with severe pneumonitis based on *** administering oxygen via a high-flow nasal cannula,the P/F ratio was only 74;therefore,the patient was diagnosed with ARDS based on the overall examination *** tidal volume with high positive end-expiratory pressure,sedative agents combined with a neuromuscular blocker,and a systemic steroid were promptly applied to manage the ***,the patient did not recover from the hypoxia and expired 31 h after being *** Clinicians should be aware of severe pneumonitis due to the immune-

关键词： Hepatocellular carcinoma Systemic therapy Adverse events Pneumonitis Atezolizumab Acute respiratory distress syndrome