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Protein Arginine Methyltransferase 1 Ablation in Motor Neurons Causes Mitochondrial Dysfunction Leading to Age-related Motor Neuron Degeneration with Muscle Loss

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Research 2024年第1期2023卷 637-649页

作者： Hyun-Kyung So Hyebeen Kim jinwoo Lee Chang-Lim You Chae-eun Yun Hyeon-Ju Jeong eun-Ju jin Yunju Jo Dongryeol Ryu Gyu-Un Bae Jong-sun Kang Department of Molecular Cell Biology Sungkyunkwan University School of MedicineSuwonKorea Single Cell Network Research Center Sungkyunkwan University School of MedicineSuwonKorea Research Institute of Aging-Related Diseases AniMusCureInc.SuwonKorea Drug Information Research Institute Muscle Physiome Research CenterCollege of PharmacySookmyung Women’s UniversitySeoulKorea

Neuromuscular dysfunction is tightly associated with muscle wasting that occurs with age or due to degenerative ***,the molecular mechanisms underlying neuromuscular dysfunction are currently *** studies have proposed important roles of Protein arginine methyltransferase 1(Prmt1)in muscle stem cell function and muscle *** the current study,we set out to determine the role of Prmt1 in neuromuscular function by generating mice with motor neuron-specific ablation of Prmt1(mnKO)using *** exhibited age-related motor neuron degeneration and neuromuscular dysfunction leading to premature muscle loss and ***1 deficiency also impaired motor function recovery and muscle reinnervation after sciatic nerve *** transcriptome analysis of aged mnKO lumbar spinal cords revealed alterations in genes related to inflammation,cell death,oxidative stress,and ***,mnKO lumbar spinal cords of sciatic nerve injury model or aged mice exhibited elevated cellular stress response in motor ***,Prmt1 inhibition in motor neurons elicited mitochondrial *** findings demonstrate that Prmt1 ablation in motor neurons causes agerelated motor neuron degeneration attributing to muscle ***,Prmt1 is a potential target for the prevention or intervention of sarcopenia and neuromuscular dysfunction related to aging.

关键词： degeneration impaired prevention

Neural Wiskott-Aldrich syndrome protein(N-WASP)promotes distant metastasis in pancreatic ductal adenocarcinoma via activation of LOXL2

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Oncology Research 2024年第4期32卷 615-624页

作者： HYUNG sun KIM YUN sun LEE SeunG MYUNG DONG HYO JUNG KIM DA eun LEE HYEON WOONG KANG MYEONG jin KIM JOON SEONG PARK Department of Surgery Gangnam Severance HospitalYonsei University College of MedicineSeoulKorea Department of Surgery Graduate School of Medical ScienceBrain Korea 21 ProjectYonsei University College of MedicineSeoulKorea Gibiome Co. Ltd.Gyeonggi-doKorea

Pancreatic ductal adenocarcinoma(PDAC)is one of the most aggressive solid malignancies.A specific mechanism of its metastasis has not been *** this study,we investigated whether Neural Wiskott-Aldrich syndrome protein(N-WASP)plays a role in distant metastasis of *** found that N-WASP is markedly expressed in clinical patients with *** analysis showed a notably more distant metastatic pattern in the N-WASP-high group compared to the N-WASP-low group.N-WASP was noted to be a novel mediator of epithelialmesenchymal transition(EMT)via gene expression profile *** of N-WASP in pancreatic cancer cells significantly inhibited cell invasion,migration,and *** also observed positive association of lysyl oxidase-like 2(LOXL2)and focal adhesion kinase(FAK)with the N-WASP-mediated response,wherein EMT and invadopodia function were *** N-WASP and LOXL2 depletion significantly reduced the incidence of liver and lung metastatic lesions in orthotopic mouse models of pancreatic *** results elucidate a novel role for N-WASP signaling associated with LOXL2 in EMT and invadopodia function,with respect to regulation of intercellular communication in tumor cells for promoting pancreatic cancer *** findings may aid in the development of therapeutic strategies against pancreatic cancer.

关键词： Pancreatic cancer Neural Wiskott-Aldrich syndrome protein(N-WASP)signaling Metastasis Epithelial-mesenchymal transition(EMT) Lysyl oxidase-like 2(LOXL2)

Changes in microorganisms and metabolites during long-term fermentation of commercially manufactured anchovy sauce

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Food Science and Human Wellness 2024年

作者： Daehyeon Kim Seong-eun Park eun-Ju Kim Seung-Ho Seo Kwang-Moon Cho sun Jae Kwon Hong-Seok Son Department of Biotechnology， College of Life Sciences and Biotechnology， Korea University Sonlab Inc. 3. AccuGene Inc.

This study was performed to investigate the changes in microbial communities and metabolites during the long-term fermentation of commercially manufactured anchovy sauce. Samples of commercial anchovy sauce were collected from large-scale fermentation tanks with fermentation periods of up to 7.87 years. The complex bacterial community was simplified to two genera， Tetragenococcus and Halanaerobium， after approximately 0.55 years of fermentation. Although genera， such as Saccharomyces， Cladosporium， Candida， and Aspergillus， were relatively dominant， no clear pattern was identified in fungal community analysis. The longitudinal metabolite profile demonstrated that approximately half (55.8%) of the metabolites present in anchovy sauce were produced within a year of fermentation due to rapid fermentation. Despite the static microbial community， the contents of several metabolites including amino acids and biogenic amines changed continuously during the long-term fermentation of anchovy sauce. This study provides novel insights into the changes in microbiota and metabolites in fish sauce produced without any starter inoculation.

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Galectin 3-binding protein(LGALS3BP)depletion attenuates hepatic fibrosis by reducing transforming growth factor-β1(TGF-β1)availability and inhibits hepatocarcinogenesis

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Cancer Communications 2024年第10期44卷 1106-1129页

作者： Dae-Hwan Kim Minjeong sung Myong-Suk Park eun-Gene sun Sumin Yoon Kyung Hyun Yoo Kamalakannan Radhakrishnan sung Yun Jung Woo-Kyun Bae Sang-Hee Cho Ik-Joo Chung Department of Internal Medicine Division of Hematology and OncologyChonnam National University Medical SchoolHwasunSouth Korea Department of Internal Medicine Division of Hematology and OncologyChonnam National University Hwasun HospitalHwasunSouth Korea Combinatorial Tumor Immunotherapy MRC Center Chonnam National University Medical SchoolHwasunSouth Korea National Immunotherapy Innovation Center HwasunSouth Korea BioMedical Sciences Graduate Program Chonnam National UniversityHwasunSouth Korea Department of Biological Science SookmyungWomen’s UniversitySeoulSouth Korea Clinical Vaccine R&D Center Chonnam National UniversityHwasunSouth Korea Department of Biochemistry and Molecular Pharmacology Baylor College of MedicineHoustonTexasUSA

Background:Increased Galectin 3-binding protein(LGALS3BP)serum levels have been used to assess hepatic fibrosis stages and the severity of hepatocellular carcinoma(HCC).Considering the crucial role of transforming growth factor-β1(TGF-β1)in the emergence of these diseases,the present study tested the hypothesis that LGALS3BP regulates the TGF-β1 signaling ***:The expression levels of LGALS3BP and TGFB1 were analyzed in patients with metabolic dysfunction-associated steatohepatitis(MASH)and *** omics techniques,such as RNA-sequencing,transposaseaccessible chromatin-sequencing assay,and liquid chromatography-tandem mass spectrometry proteomics,were used to identify the regulatory mechanisms for the LGALS3BP-TGF-β1 *** effects of altered TGF-β1 signaling by LGALS3BP were investigated in conditional LGALS3BP-knockin and LGALS3BP-knockout ***:In patients with MASH and HCC,the levels of LGALS3BP and TGFB1 exhibited positive *** of LGALS3BP by the inflammatory cytokine interferonαin HCC cells or ectopic overexpression of LGALS3BP in hepatocytes promoted the expression levels of *** fibrosis was observed in the livers of hepatocyte-specific LGALS3BP-knockin mice,with increased TGFB1 ***3BP directly bound to and assembled integrinαV,an integral mediator required for releasing active TGF-β1 from extracellular latent complex with the rearranged F-actin *** released TGF-β1 activated JunB transcription factor,which in turn promoted the TGF-β1 positive feedback ***3BP deletion in the hepatocytes downregulated TGF-β1 signaling and CCl4 induced ***,LGALS3BP depletion hindered hepatocarcinogenesis by limiting the availability of fibrogenic TGF-β***:LGALS3BP plays a crucial role in hepatic fibrosis and carcinogenesis by controlling the TGF-β1 signaling pathway,making it a promising therapeutic target in TGF-β1-related diseases.

关键词： F-actin FAK hepatic carcinogenesis IntegrinαV Interferonα JunB LGALS3BP metabolic dysfuntion-associated steatohepatitis tensile force TGF-β1

Glucose-mediated mitochondrial reprogramming by cholesterol export at TM4SF5-enriched mitochondria-lysosome contact sites

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Cancer Communications 2024年第1期44卷 47-75页

作者： Ji Eon Kim So-Young Park Chulhwan Kwak Yoonji Lee Dae-Geun Song Jae Woo Jung Haesong Lee eun-Ae Shin Yangie Pinanga Kyung-hee Pyo eun Hae Lee Wonsik Kim Soyeon Kim Chang-Duck Jun Jeanho Yun sun Choi Hyun-Woo Rhee Kwang-Hyeon Liu Jung Weon Lee Department of Pharmacy College of PharmacySeoul National UniversitySeoulRepublic of Korea Research Institute of Pharmaceutical Sciences College of PharmacySeoul National UniversitySeoulRepublic of Korea BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit College of Pharmacy and Research Institute of Pharmaceutical SciencesKyungpook National UniversityDaeguRepublic of Korea Department of Chemistry Seoul National UniversitySeoulRepublic of Korea College of Pharmacy Chung-Ang UniversitySeoulRepublic of Korea Natural Product Informatics Research Center Korea Institute of Science and Technology(KIST)Gangneung-siGangwon-doRepublic of Korea School of Life Sciences Gwangju Institute of Science and Technology(GIST)GwangjuRepublic of Korea Department of Biochemistry College of MedicineDong-A UniversityBusanRepublic of Korea Global AI Drug Discovery Center College of Pharmacy and Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoulRepublic of Korea Interdisciplinary Program in Genetic Engineering Seoul National UniversitySeoulRepublic of Korea

Background:Transmembrane 4 L six family member 5(TM4SF5)translocates subcellularly and functions metabolically,although it is unclear how intracellu-lar TM4SF5 translocation is linked to metabolic *** is thus of interests to understand how the traffic dynamics of TM4SF5 to subcellular endosomal membranes are correlated to regulatory roles of ***:Here,we explored the metabolic significance of TM4SF5 localization at mitochondria-lysosome contact sites(MLCSs),using in vitro cells and in vivo animal systems,via approaches by immunofluorescence,proximity labelling based proteomics analysis,organelle reconstitution ***:Upon extracellular glucose repletion following depletion,TM4SF5 became enriched at MLCSs via an interaction between mitochondrial FK506-binding protein 8(FKBP8)and lysosomal *** labeling showed molecular clustering of phospho-dynamic-related protein I(DRP1)and certain mitophagy receptors at TM4SF5-enriched MLCSs,leading to mitochondrial fis-sion and ***4SF5 bound NPC intracellular cholesterol transporter 1(NPC1)and free cholesterol,and mediated export of lysosomal cholesterol to mitochondria,leading to impaired oxidative phosphorylation but intact tri-carboxylic acid(TCA)cycle andβ-*** mouse models,hepatocyte Tm4sf5 promoted mitophagy and cholesterol transport to mitochondria,both with positive relations to liver ***:Our findings suggested that TM4SF5-enriched MLCSs regu-late glucose catabolism by facilitating cholesterol export for mitochondrial reprogramming,presumably while hepatocellular carcinogenesis,recapitulating aspects for hepatocellular carcinoma metabolism with mitochondrial repro-gramming to support biomolecule synthesis in addition to glycolytic energetics.

关键词： cholesterol fluorescent imaging glucose catabolism hepatocellular carcinogenesis mem-brane contact sites mitochondria function mitophagy oxidative phosphorylation protein-protein interaction tetraspanin

Machine Learning-Based Efficient Discovery of Software Vulnerability for Internet of Things

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Intelligent Automation & Soft Computing 2023年第8期37卷 2407-2419页

作者： So-eun Jeon sun-jin Lee Il-Gu Lee Department of Future Convergence Technology Engineering Sungshin Women’s UniversitySeoul02844Korea

With the development of the 5th generation of mobile communi-cation(5G)networks and artificial intelligence(AI)technologies,the use of the Internet of Things(IoT)has expanded throughout *** IoT networks have improved industrial productivity and convenience,they are highly dependent on nonstandard protocol stacks and open-source-based,poorly validated software,resulting in several security ***-ever,conventional AI-based software vulnerability discovery technologies cannot be applied to IoT because they require excessive memory and com-puting *** study developed a technique for optimizing training data size to detect software vulnerabilities rapidly while maintaining learning *** results using a software vulnerability classification dataset showed that different optimal data sizes did not affect the learning performance of the learning ***,the minimal data size required to train a model without performance degradation could be determined in *** example,the random forest model saved 85.18%of memory and improved latency by 97.82%while maintaining a learning accuracy similar to that achieved when using 100%of data,despite using only 1%.

关键词： Lightweight devices machine learning deep learning software vulnerability detection common weakness enumeration

Pancreatic fistula after pancreaticoduodenectomy:A comparison between the two pancreaticojejunostomy methods for approximating the pancreatic parenchyma to the jejunal seromuscular layer:Interrupted vs continuous stitches

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World Journal of Gastroenterology 2007年第40期13卷 5351-5356页

作者： Seung eun Lee sung Hoon Yang jin-Young Jang sun-Whe Kim Department of Surgery Seoul National University College of Medicine28 Yongon-dongChongno-guSeoul 110-744Korea

AIM： The purpose of this study is to find a better operative technique by comparing interrupted stitches with continuous stitches for the outer layer of the pancreaticojejunostomy, i.e. the stitches between the stump parenchyma of the pancreas and the jejunal seromuscular layer, and other risk factors for the incidence of pancreatic leakage.METHODS： During the period January 1997 to October 2004, 133 patients have undergone the end-to-side and duct-to-mucosa pancreaticojejunostomy reconstruction after pancreaticoduodenectomy with interrupted suture for outer layer of the pancreaticojejunostomy and 170 patients with a continuous suture at our institution by one surgeon.RESULTS： There were no significant differences between the two groups in the diagnosis, texture of the pancreas, use of octreotide and pathologic stage. Pancreatic fistula occurred in 14 patients （11%） among the interrupted suture cases and in 10 （6%） among the continuous suture cases （P = 0.102）. Major pancreatic leakage developed in three interrupted suture patients （2%） and zero continuous suture patients （P = 0.026）. In multivariate analysis, soft pancreatic consistency （odds ratio, 5.5; 95% confidence interval 2.3-13.1） and common bile duct cancer （odds ratio, 3.7; 95%CI 1.6-8.5） were＇predictive of pancreatic leakage.CONCLUSION： Pancreatic texture and pathology are the most important factors in determining the fate of pancreaticojejunal anastomosis and our continuous suture method was performed with significantly decreased occurrence of major pancreatic fistula. In conclusion, the continuous suture method is more feasible and safer in performing duct-to-mucosa pancreaticojejunostomy.

关键词： Pancreaticoduodenectomy Pancreaticojejunostomy Pancreatic fistula

Intraductal papillary mucinous carcinoma with atypical manifestations:Report of two cases

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World Journal of Gastroenterology 2007年第10期13卷 1622-1625页

作者： Seung eun Lee jin-Young Jang sung Hoon Yang sun-Whe Kim Department of Surgery Seoul National University College of MedicineSeoulKorea

Intraductal papillary mucinous neoplasms （IPMNs） are a well-characterized group of rnucin-producing cystic neoplasms of the clear malignant potential type. We report here two cases of intraductal papillary mucinous carcinoma （IPMC） with atypical manifestations. In one case, we discussed a pseudomyxoma peritonei caused by a ruptured IPMC. In the other case we discussed the fistulization of IPMC into the stomach and duodenum. These two cases suggest that IPMN can either spontaneously rupture causing mucinous materials to spill into the free abdominal cavity or directly invade adjacent organs resulting in fistula development.

关键词： Intraductal papillary mucinous neoplasm Intraductal papillary mucinous carcinoma Pseudomyxoma peritonei Fistula

Injection molding of micro patterned PMMA plate

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Transactions of Nonferrous Metals Society of China 2011年第A1期21卷 148-152页

作者： Yeong-eun YOO Tae-Hoon KIM Tae-jin JE Doo-sun CHOI Chang-Wan KIM sun-Kyung KIM Department of Nanomanufacturing Technology KIMM 171 Jang-dong Yusung-gu Daejeon 305-343 Korea Department of Product Design and Manufacturing Seoul National University of Technology

A plastic plate with surface micro features was injection molded to investigate the effect of pressure rise of melt on the replication of the micro structures. Prism pattern, which is used in many optical applications, was selected as a model pattern. The prism pattern is 50 μm in pitch and 108° in the vertical angle. The overall size of the plate was 335 minx213 mm and the thickness of the plate varied linearly from 2.6 mm to 0.7 ram. The prism pattern was firstly machined on the nickel plated core block using micro diamond tool and this machined pattern core was installed in a mold for injection molding of prism patterned plate. Polymethyl methacrylate （PMMA） was used as a molding material. The pressure and temperature of the melt in the cavity were measured at different positions in the cavity and the replication of the pattern was also measured at the same positions. The results show that the pressure or temperature profile through the process depends on the shape and the size of the plate. The replication is affected by the temperature and pressure profiles at the early stage of filling, which is right after the melt reaches the position to be measured.

关键词： micro prism pattern injection molding replication pressure profile temperature profile