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AGE-induced neuronal cell death is enhanced in G2019S LRRK2 mutation with increased RAGE expression

Translational Neurodegeneration 2018年第1期7卷 1-8页

作者： hyun jin cho Chengsong Xie Huaibin Cai Department of Biochemistry and Biomedical Sciences Seoul National UniversityCollege of Medicine28 Yungun-dongJongro-guSeoul 110-799South Korea Transgenics Section Laboratory of NeurogeneticsNational Institute on AgingNational Institutes of HealthBuilding 35Room 1A112MSC 370735 Convent DriveBethesdaMD 20892–3707USA

Background:Leucine-rich repeat kinase 2(LRRK2)mutations represent the most common genetic cause of sporadic and familial Parkinson’s disease(PD).Especially,LRRK2 G2019S missense mutation has been identified as the most prevalent genetic cause in the late-onset PD.Advanced glycation end products(AGEs)are produced in high amounts in diabetes and diverse aging-related disorders,such as cardiovascular disease,renal disease,and neurological disease.AGEs trigger intracellular signaling pathway associated with oxidative stress and inflammation as well as cell death.RAGE,receptor of AGEs,is activated by interaction with AGEs and mediates AGE-induced cytotoxicity.Whether AGE and RAGE are involved in the pathogenesis of mutant LRRK2 is unknown.Methods:Using cell lines transfected with mutant LRRK2 as well as primary neuronal cultures derived from LRRK2 wild-type(WT)and G2019S transgenic mice,we compared the impact of AGE treatment on the survival of control and mutant cells by immunostaining.We also examined the levels of RAGE proteins in the brains of transgenic mice and PD patients by western blots.Results:We show that LRRK2 G2019S mutant-expressing neurons were more sensitive to AGE-induced cell death compared to controls.Furthermore,we found that the levels of RAGE proteins were upregulated in LRRK2 G2019S mutant cells.Conclusions:These data suggest that enhanced AGE-RAGE interaction contributes to LRRK2 G2019S mutation-mediated progressive neuronal loss in PD.

关键词： Parkinson’s disease LRRK2 G2019S AGE RAGE Neuronal death

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Expression Pattern of the Hippo Pathway Effector TAZ in Cellular and Fibrotic Nonspecific Interstitial Pneumonia

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Chinese Medical Journal 2018年第5期131卷 626-628页

作者： Min-Kyung Yeo Hee Sun Park Yeon Hee Park choong-Sik Lee Geon Yoo Dong II Park Jeong Eun Lee Jae Young Moon Sung Soo Jung Ju Ock Kim Dahyun Kang hyun jin cho Min-Woong Kang jin-Whan Kim Song-Soo Kim Chaeuk Chung Department of Pathology Chungnam National University School of Medicine Daejeon 35015 South Korea Division of Pulmonology Department of Internal Medicine Chungnam National University 282 Munhwaro Jung-gu Daejeon 35015 South Korea Department of Internal Medicine Daejeonst Mary's Hospital College of Medicine Catholic University Daejeon 34943 South Korea ~Department of Toxicological Evaluation and Research Korea Institute of Toxicology 141 Gajeong-ro Yuseong-gu Daejeon 34114 South Korea Department of Thoracic Surgery College of Medicine Chungnam National University Daejeon 35015 South Korea Department of Radiology College of Medicine Chungnam National University Daejeon 35015 South Korea Infection Control Convergence Research Center College of Medicine Chungnam National University Jung-guMunhwa-ro 266 Daejeon 35015 South Korea

Interstitial lung disease （ILD） is a comprehensive term referring to a group of lung diseases affecting the interstitium of the lung. Idiopathic pulmonary fibrosis （IPF） is the most common idiopathic ILD, and nonspecific interstitial pneumonia （NSIP） is the second most common. As the name suggests, NSIP is diagnosed atter many other diseases are excluded. The main pathological finding in NSIP is homogeneous interstitial inflammation with or without fibrosis. NSIP can be categorized by cellular type or fibrotic type, according to the grade of inflammation and fibrosis. The cellular type has mostly inflammatory lesions with good responses to steroid, but the fibrotic type has a large proportion of fibrosis mixed with inflammatory lesions and a relatively poor response to steroid treatment So far, the exact mechanism underlying idiopathic lED has not been clarified. Determining key regulators of these ILDs will be helpful in the diagnosis and development of novel drugs for ILD.

关键词： YAP

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Defect Detection Model Using Time Series Data Augmentation and Transformation

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Computers, Materials & Continua 2024年第2期78卷 1713-1730页

作者： Gyu-Il Kim hyun Yoo Han-jin cho Kyungyong Chung Department of Computer Science Kyonggi UniversitySuwon-si16227Korea Contents Convergence Software Research Institue Kyonggi UniversitySuwon-si16227Korea Department of Energy IT Engineering Far East UniversityEumsung-gun27601Korea Division of AI Computer Science and Engineering Kyonggi UniversitySuwon-si16227Korea

Time-series data provide important information in many fields,and their processing and analysis have been the focus of much research.However,detecting anomalies is very difficult due to data imbalance,temporal dependence,and noise.Therefore,methodologies for data augmentation and conversion of time series data into images for analysis have been studied.This paper proposes a fault detection model that uses time series data augmentation and transformation to address the problems of data imbalance,temporal dependence,and robustness to noise.The method of data augmentation is set as the addition of noise.It involves adding Gaussian noise,with the noise level set to 0.002,to maximize the generalization performance of the model.In addition,we use the Markov Transition Field(MTF)method to effectively visualize the dynamic transitions of the data while converting the time series data into images.It enables the identification of patterns in time series data and assists in capturing the sequential dependencies of the data.For anomaly detection,the PatchCore model is applied to show excellent performance,and the detected anomaly areas are represented as heat maps.It allows for the detection of anomalies,and by applying an anomaly map to the original image,it is possible to capture the areas where anomalies occur.The performance evaluation shows that both F1-score and Accuracy are high when time series data is converted to images.Additionally,when processed as images rather than as time series data,there was a significant reduction in both the size of the data and the training time.The proposed method can provide an important springboard for research in the field of anomaly detection using time series data.Besides,it helps solve problems such as analyzing complex patterns in data lightweight.

关键词： Defect detection time series deep learning data augmentation data transformation

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Ungraded Matrix Factorizations as Mirrors of Non-orientable Lagrangians

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Acta Mathematica Sinica,English Series 2024年第1期40卷 26-42页

作者： Lino AMORIM Cheol-hyun cho Department of Mathematics Kansas State University138 Cardwell Hall1228 N.17th StreetManhattanKS 66506USA Department of Mathematical Sciences Research Institute of MathematicsSeoul National UniversitySan 56-1ShinrimdongGwanakguSeoul 47907South Korea

We introduce the notion of ungraded matrix factorization as a mirror of non-orientable Lagrangian submanifolds.An ungraded matrix factorization of a polynomial W,with coefficients in a field of characteristic 2,is a square matrix Q of polynomial entries satisfying Q^(2)=W·Id.We then show that non-orientable Lagrangians correspond to ungraded matrix factorizations under the localized mirror functor and illustrate this construction in a few instances.Our main example is the Lagrangian submanifold RP^(2)⊂CP^(2)and its mirror ungraded matrix factorization,which we construct and study.In particular,we prove a version of Homological Mirror Symmetry in this setting.

关键词： Mirror symmetry non-orientable Lagrangian submanifold matrix factorization

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Endoscopic ultrasound-guided tissue sampling induced pancreatic duct leak resolved by the placement of a pancreatic stent:A case report

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World Journal of Clinical Cases 2024年第9期12卷 1677-1684页

作者： Ki-hyun Kim Chang Hwan Park Eunae cho Yohan Lee Department of Internal Medicine Chonnam National University HospitalGwangju 61469South Korea Department of Gastroenterology Chonnam National University HospitalGwangju 61469South Korea

BACKGROUND Pancreatic ductal leaks complicated by endoscopic ultrasonography-guided tissue sampling(EUS-TS)can manifest as acute pancreatitis.CASE SUMMARY A 63-year-old man presented with persistent abdominal pain and weight loss.Diagnosis:Laboratory findings revealed elevated carbohydrate antigen 19-9(5920 U/mL)and carcinoembryonic antigen(23.7 ng/mL)levels.Magnetic resonance imaging of the pancreas revealed an approximately 3 cm ill-defined space-occupying lesion in the inferior aspect of the head,with severe encasement of the superior mesenteric artery.Pancreatic ductal adenocarcinoma was confirmed after pathological examination of specimens obtained by EUS-TS using the fanning method.Interventions and outcomes:The following day,the patient experienced severe abdominal pain with high amylase(265 U/L)and lipase(1173 U/L)levels.Computed tomography of the abdomen revealed edematous wall thickening of the second portion of the duodenum with adjacent fluid collections and a suspicious leak from either the distal common bile duct or the main pancreatic duct in the head.Endoscopic retrograde cholangiopancreatography revealed dye leakage in the head of the main pancreatic duct.Therefore,a 5F 7 cm linear plastic stent was deployed into the pancreatic duct to divert the pancreatic juice.The patient’s abdominal pain improved immediately after pancreatic stent insertion,and amylase and lipase levels normalized within a week.Neoadjuvant chemotherapy was then initiated.CONCLUSION Using the fanning method in EUS-TS can inadvertently cause damage to the pancreatic duct and may lead to clinically significant pancreatitis.Placing a pancreatic stent may immediately resolve acute pancreatitis and shorten the waiting time for curative therapy.When using the fanning method during EUSTS,ductal structures should be excluded to prevent pancreatic ductal leakage.

关键词： Endoscopic ultrasound-guided tissue sampling Pancreatitis Pancreatic duct leak Pancreatic stent Case report

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Capsosiphon fulvescens suppresses LPS-stimulated inflammatory responses by suppressing TLR4/NF-κB activation in RAW264.7 murine macrophages

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Asian Pacific Journal of Tropical Biomedicine 2024年第3期14卷 115-126页

作者： Seon Yeong Ji Eunjin Bang hyun Hwangbo Min Yeong Kim Da Hye Kim Su hyun Hong Shin-hyung Park Chang-Young Kwon Gi-Young Kim You-jin Jeon Suengmok cho Yung hyun choi Department of Biochemistry Dong-eui University College of Korean MedicineBusan 47227Republic of Korea Basic Research Laboratory for the Regulation of Microplastic-Mediated Diseases and Anti-Aging Research Center Dong-eui UniversityBusan 47227Republic of Korea Department of Pathology Dong-eui University College of Korean MedicineBusan 47227Republic of Korea Department of Oriental Neuropsychiatry Dong-eui University College of Korean MedicineBusan 47227Republic of Korea Department of Marine Life Science Jeju National UniversityJeju 63243Republic of Korea Department of Food Science and Technology/Institute of Food Science Pukyong National UniversityBusan 48513Republic of Korea

Objective:To evaluate the effects of Capsosiphon fulvescens(C.fulvescens)ethanolic extract on inflammation in lipopolysaccharide(LPS)-induced RAW296.7 macrophages.Methods:The protective effects of C.fulvescens ethanolic extract on LPS-induced inflammation in RAW264.7 macrophages were assessed using biochemical analysis,including enzyme-linked immunosorbent assay,quantitative reverse transcription-polymerase chain reaction,and Western blot analysis.To examine reactive oxygen species(ROS)production,flow cytometry analysis,and immunofluorescence staining were used.Furthermore,the modulatory effect of C.fulvescens ethanolic extract on NF-κB activation was investigated.Results:C.fulvescens ethanolic extract significantly attenuated LPS-induced levels of pro-inflammatory cytokines and notably reduced the secretion and mRNA levels of LPS-mediated matrix metalloproteinases.In addition,C.fulvescens ethanolic extract decreased ROS production and suppressed the TLR4/NF-κB signaling pathway.Conclusions:C.fulvescens ethanolic extract alleviates inflammation as well as oxidative stress by modulating the TLR4/NF-κB signaling in LPS-induced RAW264.7 macrophages.C.fulvescens can be used as a potential therapeutic agent to suppress inflammation and oxidative stress-associated diseases.

关键词： Capsosiphon fulvescens Inflammation Oxidative stress NF-κB Nrf2 TLR4

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Depolarization mitigated in ferroelectric Hf_(0.5)Zr_(0.5)O_(2)ultrathin films(<5 nm)on Si substrate by interface engineering

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Journal of Advanced Ceramics 2024年第3期13卷 282-292页

作者： Se hyun Kim Younghwan Lee Dong hyun Lee Geun Hyeong Park hyun Woo Jeong Kun Yang Yong Hyeon cho Young Yong Kim Min Hyuk Park Department of Materials Science and Engineering College of EngineeringSeoul National UniversitySeoul 08826Republic of Korea Research Institute of Advanced Materials College of EngineeringSeoul National UniversitySeoul 08826Republic of Korea Inter-university Semiconductor Research Center College of EngineeringSeoul National UniversitySeoul 08826Republic of Korea Pohang Accelerator Laboratory Pohang University of Science&TechnologyPohang 790784Republic of Korea

(Hf,Zr)O_(2)offers considerable potential for next-generation semiconductor devices owing to its nonvolatile spontaneous polarization at the nanoscale.However,scaling this material to sub-5 nm thickness poses several challenges,including the formation of an interfacial layer and high trap concentration.In particular,a low-k SiO_(2)interfacial layer is naturally formed when(Hf,Zr)O_(2)films are directly grown on a Si substrate,leading to high depolarization fields and rapid reduction of the remanent polarization.To address these issues,we conducted a study to significantly improve ferroelectricity and switching endurance of(Hf,Zr)O_(2)films with sub-5 nm thicknesses by inserting a TiO_(2)interfacial layer.The deposition of a Ti film prior to Hf_(0.5)Zr_(0.5)O_(2)film deposition resulted in a high-k TiO_(2)interfacial layer and prevented the direct contact of Hf_(0.5)Zr_(0.5)O_(2)with Si.Our findings show that the high-k TiO_(2)interfacial layer can reduce the SiO_(2)/Si interface trap density and the depolarization field,resulting in a switchable polarization of 60.2μC/cm^(2)for a 5 nm thick Hf_(0.5)Zr_(0.5)O_(2)film.Therefore,we propose that inserting a high-k TiO_(2)interfacial layer between the Hf_(0.5)Zr_(0.5)O_(2)film and the Si substrate may offer a promising solution to enhancing the ferroelectricity and reliability of(Hf,Zr)O_(2)grown on the Si substrate and can pave the way for next-generation semiconductor devices with improved performance.

关键词： ferroelectric charge trapping hafnia depolarization

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Two distinct subpopulations of marginal zone B cells exhibit differential antibody-producing capacities and radioresistance

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Cellular & Molecular Immunology 2024年第4期21卷 393-408页

作者： Sujin Lee Yeunjung Ko hyun Woo Lee Won Joon Oh Hun Gi Hong Dinuka Ariyaratne Se jin Im Tae jin Kim Department of Immunology Graduate School of Basic Medical ScienceSungkyunkwan University School of MedicineSuwon16419Republic of Korea Department of Immunology and Molecular Medicine Faculty of Medical SciencesUniversity of Sri JayewardenepuraNugegodaSri Lanka Present address:Immunology and Microbiology Graduate Program Baylor College of MedicineHoustonTX77030USA

Marginal zone(MZ)B cells,which are splenic innate-like B cells that rapidly secrete antibodies(Abs)against blood-borne pathogens,are composed of heterogeneous subpopulations.Here,we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression levels.CD80^(high)MZ B cells exhibited greater Ab-producing,proliferative,and IL-10-secreting capacities than did CD80^(low)MZ B cells.Notably,CD80^(high)MZ B cells survived 2-Gy whole-body irradiation,whereas CD80^(low)MZ B cells were depleted by irradiation and then repleted with one month after irradiation.Depletion of CD80^(low)MZ B cells led to accelerated development of type II collagen(CII)-induced arthritis upon immunization with bovine CII.CD80^(high)MZ B cells exhibited higher expression of genes involved in proliferation,plasma cell differentiation,and the antioxidant response.CD80^(high)MZ B cells expressed more autoreactive B cell receptors(BCRs)that recognized double-stranded DNA or CII,expressed more immunoglobulin heavy chain sequences with shorter complementarity-determining region 3 sequences,and included more clonotypes with no N-nucleotides or with B-1a BCR sequences than CD80^(low)MZ B cells.Adoptive transfer experiments showed that CD21^(+)CD23^(+)transitional 2 MZ precursors preferentially generated CD80^(low)MZ B cells and that a proportion of CD80^(low)MZ B cells were converted into CD80^(high)MZ B cells;in contrast,CD80^(high)MZ B cells stably remained CD80^(high)MZ B cells.In summary,MZ B cells can be divided into two subpopulations according to their CD80 expression levels,Ab-producing capacity,radioresistance,and autoreactivity,and these findings may suggest a hierarchical composition of MZ B cells with differential stability and BCR specificity.

关键词： Marginal Zone B Cell CD80 Autoreactivity Radioresistance

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Effect of Meteorological Data Assimilation on Regional Air Quality Forecasts over the Korean Peninsula

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Journal of Meteorological Research 2024年第2期38卷 262-284页

作者： Yunjae cho hyun Mee KIM Eun-Gyeong YANG Yonghee LEE Jae-Bum LEE Soyoung HA Department of Atmospheric Sciences Yonsei UniversitySeoul 03722Republic of Korea Air Quality Forecasting Center National Institute of Environmental ResearchIncheon 22689Republic of Korea National Center for Atmospheric Research BoulderCO 80305USA University of Maryland Baltimore County BaltimoreMD 21250USA Global Modeling and Assimilation Office NASA Goddard Space Flight CenterGreenbeltMD 20771USA

The Weather Research and Forecasting model coupled with Chemistry(WRF-Chem),a type of online coupled chemistry-meteorology model(CCMM),considers the interaction between air quality and meteorology to improve air quality forecasting.Meteorological data assimilation(DA)can be used to reduce uncertainty in meteorological field,which is one factor causing prediction uncertainty in the CCMM.In this study,WRF-Chem and three-dimensional variational DA were used to examine the impact of meteorological DA on air quality and meteorological forecasts over the Korean Peninsula.The nesting model domains were configured over East Asia(outer domain)and the Korean Peninsula(inner domain).Three experiments were conducted by using different DA domains to determine the optimal model domain for the meteorological DA.When the meteorological DA was performed in the outer domain or both the outer and inner domains,the root-mean-square error(RMSE),bias of the predicted particulate matter(PM)concentrations,and the RMSE of predicted meteorological variables against the observations were smaller than those in the experiment where the meteorological DA was performed only in the inner domain.This indicates that the improvement of the synoptic meteorological fields by DA in the outer domain enhanced the meteorological initial and boundary conditions for the inner domain,subsequently improving air quality and meteorological predictions.Compared to the experiment without meteorological DA,the RMSE and bias of the meteorological and PM variables were smaller in the experiments with DA.The effect of meteorological DA on the improvement of PM predictions lasted for approximately 58-66 h,depending on the case.Therefore,the uncertainty reduction in the meteorological initial condition by the meteorological DA contributed to a reduction of the forecast errors of both meteorology and air quality.

关键词： meteorological data assimilation regional air quality forecast particulate matter concentration optimal model domain forecast error WRF-Chem

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Highly Aligned Ternary Nanofiber Matrices Loaded with MXene Expedite Regeneration of Volumetric Muscle Loss

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Nano-Micro Letters 2024年第4期16卷 269-292页

作者： Moon Sung Kang Yeuni Yu Rowoon Park Hye jin Heo Seok hyun Lee Suck Won Hong Yun Hak Kim Dong‑Wook Han Department of Cogno‑Mechatronics Engineering College of Nanoscience and NanotechnologyPusan National UniversityBusan 46241Republic of Korea Medical Research Institute School of MedicinePusan National UniversityYangsan 50612Republic of Korea Department of Anatomy School of MedicinePusan National UniversityYangsan 50612Republic of Korea Engineering Research Center for Color‑Modulated Extra‑Sensory Perception Technology Pusan National UniversityBusan 46241Republic of Korea Department of Biomedical Informatics School of MedicinePusan National UniversityYangsan 50612Republic of Korea Periodontal Disease Signaling Network Research Center and Dental and Life Science Institute School of DentistryPusan National UniversityYangsan 50612Republic of Korea BIO‑IT Fusion Technology Research Institute Pusan National UniversityBusan 46241Republic of Korea Present Address:Osstem Implant Inc. Seoul 07789Republic of Korea

Current therapeutic approaches for volumetric muscle loss(VML)face challenges due to limited graft availability and insufficient bioactivities.To overcome these limitations,tissue-engineered scaffolds have emerged as a promising alternative.In this study,we developed aligned ternary nanofibrous matrices comprised of poly(lactide-co-ε-caprolactone)integrated with collagen and Ti_(3)C_(2)T_(x)MXene nanoparticles(NPs)(PCM matrices),and explored their myogenic potential for skeletal muscle tissue regeneration.The PCM matrices demonstrated favorable physicochemical properties,including structural uniformity,alignment,microporosity,and hydrophilicity.In vitro assays revealed that the PCM matrices promoted cellular behaviors and myogenic differentiation of C2C12 myoblasts.Moreover,in vivo experiments demonstrated enhanced muscle remodeling and recovery in mice treated with PCM matrices following VML injury.Mechanistic insights from next-generation sequencing revealed that MXene NPs facilitated protein and ion availability within PCM matrices,leading to elevated intracellular Ca^(2+)levels in myoblasts through the activation of inducible nitric oxide synthase(i NOS)and serum/glucocorticoid regulated kinase 1(SGK1),ultimately promoting myogenic differentiation via the m TOR-AKT pathway.Additionally,upregulated i NOS and increased NO–contributed to myoblast proliferation and fiber fusion,thereby facilitating overall myoblast maturation.These findings underscore the potential of MXene NPs loaded within highly aligned matrices as therapeutic agents to promote skeletal muscle tissue recovery.

关键词： Ti_(3)C_(2)T_(x)MXene nanoparticle Ternary nanofibrous matrices Myogenesis Regeneration of volumetric muscle loss Next generation sequencing

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