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Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 241-248页

作者： Chao Sun George Boon-Bee Goh Wan-Cheng Chow Wah-Kheong Chan Grace Lai-Hung Wong Wai-Kay Seto Yi-Hsiang Huang Han-Chieh Lin I-Cheng Lee Hye Won Lee seung up kim Vincent Wai-Sun Wong Jian-Gao Fan Center for Fatty Liver Disease Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Key Lab of Pediatric Gastroenterology and NutritionShanghai 200092China Department of Gastroenterology&Hepatology Singapore General HospitalSingaporeSingapore Gastroenterology and Hepatology Unit Department of MedicineFaculty of MedicineUniversity of MalayaKuala LumpurMalaysia Department of Medicine and Therapeutics and State Key Laboratory of Digestive Disease The Chinese University of Hong KongHong KongChina Department of Medicine The University of Hong KongHong KongChina Institute of Clinical Medicine National Yang Ming Chiao Tung University School of MedicineTaipeiTaiwanChina Division of Gastroenterology and Hepatology Taipei Veterans General HospitalTaipeiTaiwanChina Faculty of Medicine National Yang Ming Chiao Tung University School of MedicineTaipeiTaiwanChina Department of Internal Medicine Yonsei University College of MedicineSeoulKorea

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic disorders.However,the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear.The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients.Methods:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study.Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 scores.Impaired renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value of<90 mL/min/1.73 m^(2) and<60 mL/min/1.73 m^(2),respectively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)equation.Results:Among 529 included NAFLD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,respectively.In multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(P<0.05).Furthermore,increased fasting plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(P<0.05).Compared with patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(P<0.05).Conclusions:Agile 3+and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD.Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

关键词： Nonalcoholic fatty liver disease Impaired renal function Agile 3+ Agile 4 Metabolic syndrome

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Obesity is an important determinant of severity in newly defined metabolic dysfunction-associated fatty liver disease

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Hepatobiliary & Pancreatic Diseases International 2022年第3期21卷 241-247页

作者： Ji Hye Huh Kwang Joon kim seung up kim Bong-Soo Cha Byung-Wan Lee Division of Endocrinology and Metabolism Department of Internal MedicineHallym University Sacred Heart HospitalAnyang 14068Korea Division of Geriatrics Department of Internal MedicineYonsei University College of MedicineSeoul 03722Korea Division of Endocrinology and Metabolism Department of Internal MedicineYonsei University College of MedicineSeoul 03722Korea Institute of Gastroenterology Department of Internal MedicineYonsei University College of MedicineSeoul 03722Korea

Background: The recently proposed definition of metabolic dysfunction-associated fatty liver disease(MAFLD) is based on the co-existence of hepatic steatosis with other metabolic disorders, including obesity and metabolic risk abnormalities such as hyperglycemia, high blood pressure and dyslipidemia. This study aimed to assess MAFLD severity according to the presence of metabolic abnormalities and obesity. Methods: Using transient elastography, hepatic steatosis and fibrosis severity were assessed by measuring the controlled attenuation parameter and liver stiffness measurement. A total of 1163 patients with MAFLD were categorized into the following four groups according to metabolic risk abnormalities and obesity presence: non-obese without metabolic risk abnormality group(Group 1;reference group);nonobese with metabolic risk abnormality group(Group 2);obese without metabolic risk abnormality group(Group 3);and obese with metabolic risk abnormality group(Group 4). A multiple logistic regression analysis was performed to determine severe hepatic steatosis and fibrosis risk in each group in both unadjusted and adjusted models. Results: In the adjusted model, the odds ratios(ORs) [95% confidence interval(CI)] for severe hepatic steatosis in Groups 2, 3, and 4 were 1.07(0.61-1.88), 2.43(1.44-4.08), and 4.07(2.56-6.48), respectively( P trend up 1, Group 2 showed no significant increases in OR, whereas Groups 3 and 4(obese groups) showed significant increases(OR = 4.70, 95% CI: 1.24-17.82 and OR = 6.43, 95% CI: 1.88-22.02, respectively). Conclusions: Obesity, rather than metabolic abnormality, is the principal determinant of severe hepatic steatosis and fibrosis in patients with MAFLD.

关键词： Metabolic dysfunction-associated fatty liver disease Metabolically-healthy obesity Liver fibrosis

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Nuclear receptor coactivator 6 is a critical regulator of NLRP3 inflammasome activation and gouty arthritis

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Cellular & Molecular Immunology 2024年第3期21卷 227-244页

作者： Kang-Gu Lee Bong-Ki Hong Saseong Lee Naeun Lee seung-Whan kim Donghyun kim Wan-Uk kim Center for Integrative Rheumatoid Transcriptomics and Dynamics The Catholic University of KoreaSeoul 06591Republic of Korea Department of Biomedicine&Health Sciences The Catholic University of KoreaSeoul 06591Republic of Korea Department of Pharmacology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea Bio-Medical Institute of Technology University of UlsanSeoul 05505Republic of Korea Department of Microbiology and Immunology Seoul National University College of MedicineSeoul 03080Republic of Korea Institute of Infectious Diseases Seoul National University College of MedicineSeoul 03080Republic of Korea Division of Rheumatology Department of Internal MedicineThe Catholic University of KoreaSeoul 06591Republic of Korea

Transcriptional coactivators regulate the rate of gene expression in the nucleus.Nuclear receptor coactivator 6(NCOA6),a coactivator,has been implicated in embryonic development,metabolism,and cancer pathogenesis,but its role in innate immunity and inflammatory diseases remains unclear.Here,we demonstrated that NCOA6 was expressed in monocytes and macrophages and that its level was increased under proinflammatory conditions.Unexpectedly,nuclear NCOA6 was found to translocate to the cytoplasm in activated monocytes and then become incorporated into the inflammasome with NLRP3 and ASC,forming cytoplasmic specks.Mechanistically,NCOA6 associated with the ATP hydrolysis motifs in the NACHT domain of NLRP3,promoting the oligomerization of NLRP3 and ASC and thereby instigating the production of IL-1βand active caspase-1.Of note,Ncoa6 deficiency markedly inhibited NLRP3 hyperactivation caused by the Nlrp3^(R258W) gain-of-function mutation in macrophages.Genetic ablation of Ncoa6 substantially attenuated the severity of two NLRP3-dependent diseases,folic-induced acute tubular necrosis and crystal-induced arthritis,in mice.Consistent with these findings,NCOA6 was highly expressed in macrophages derived from gout patients,and NCOA6-positive macrophages were significantly enriched in gout macrophages according to the transcriptome profiling results.Conclusively,NCOA6 is a critical regulator of NLRP3 inflammasome activation and is therefore a promising target for NLRP3-dependent diseases,including gout.

关键词： Nuclear receptor coactivator 6 Nuclear-to-cytoplasmic translocation NLRP3 inflammasome NACHT domain Gouty arthritis

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MXene-based hybrid materials for electrochemical and photoelectrochemical H_(2) generation

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Journal of Energy Chemistry 2024年第6期93卷 111-125,I0004页

作者： Jun Young kim seung Hun Roh Chengkai Xia Uk Sim Jung Kyu kim School of Material Science and Engineering North University of ChinaTaiyuan 030051China School of Chemical Engineering Sungkyunkwan University(SKKU)2066Seobu-roJangan-guSuwon 16419Republic of Korea Hydrogen Energy Technology Laboratory Korea Institute of Energy Technology(KENTECH)NajuJeollanamdo 58330Republic of Korea SKKU Advanced Institute of Nano Technology(SAINT) Sungkyunkwan University(SKKU)2066Seobu-roJangan-guSuwon 16419Republic of Korea

The conversion of solar energy to produce clean hydrogen fuel through water splitting is an emerging strategy for efficiently storing solar energy in the form of solar fuel.This aligns with the increasing global demand for the development of an ideal energy alternative to fossil fuels that does not emit greenhouse gases.Electrochemical(EC) and photoelectrochemical(PEC) water splitting technologies have garnered significant attention worldwide for advanced hydrogen solar fuel production in recent decades.To achieve sustainable green H_(2) production,it is essential to create efficient catalyst materials that are low-cost and can replace expensive noble metal-based catalysts.These characteristics make them an ideal catalyst material for the process.Two-dimensional MXenes with M_(n+1)X_(n) structure have been identified as a promising option for EC and PEC water splitting due to their superior hydrophilicity,metal-like conductivity,large surface area,and adjustable surface chemistry.Here,we present a summary of recent advancements in the synthesis and performance enhancement methods for MXene hybrid materials in hydrogen production through EC and PEC water splitting.Furthermore,we examine the challenges and insights associated with the rational design of MXene-based hybrid materials to facilitate efficient water splitting for sustainable solar fuel production.

关键词： MXene Hybrid materials EC PEC HER OER Water splitting

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Oncology Research 2024年第2期32卷 421-432页

作者： seung-HEE GWAK JUHYUN LEE EUNJI OH DOHYUN LEE WONSHIK HAN JONGMIN kim KYONG-TAI kim Department of Life Sciences Pohang University of Science and TechnologyPohang37673Korea R&D Center NovMetaPharma Co.Ltd.Pohang37668Korea Department of Surgery and Cancer Research Institute Seoul National University College of MedicineSeoul03080Korea Generative Genomics Research Center Global Green Research&Development CenterHandong Global UniversityPohang37554Korea

Genetic information is transcribed from genomic DNA to mRNA,which is then translated into threedimensional proteins.mRNAs can undergo various post-transcriptional modifications,including RNA editing that alters mRNA sequences,ultimately affecting protein function.In this study,RNA editing was identified at the 499th base(c.499)of human vaccinia-related kinase 2(VRK2).This RNA editing changes the amino acid in the catalytic domain of VRK2 from isoleucine(with adenine base)to valine(with guanine base).Isoleucine-containing VRK2 has higher kinase activity than the valine-containing VRK2,which leads to an increase in tumor cell proliferation.Earlier we reported that VRK2 directly interacts with dystrobrevin-binding protein(dysbindin)and results in reducing its stability.Herein,we demonstrate that isoleucine-containing VRK2 decreases the level of dysbindin than valinecontaining VRK2.Dysbindin interacts with cyclin D and thereby regulates its expression and function.The reduction in the level of dysbindin by isoleucine-containing VRK2 further enhances the cyclin D expression,resulting in increased tumor growth and reduction in survival rates.It has also been observed that in patient samples,VRK2 level was elevated in breast cancer tissue compared to normal breast tissue.Additionally,the isoleucine form of VRK2 exhibited a greater increase in breast cancer tissue.Therefore,it is concluded that VRK2,especially dependent on the 167th variant amino acid,can be one of the indexes of tumor progression and proliferation.

关键词： VRK2 Kinase activity Breast cancer Tumor RNA editing Cell proliferation Cell growth

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Comparative efficacy and optimal duration of first-line antibiotic regimens for acute otitis media in children and adolescents:a systematic review and network meta-analysis of 89 randomized clinicaltrials

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World Journal of Pediatrics 2024年第3期20卷 219-229页

作者： Min Seo kim Jae Han kim Seohyun Ryu seung Won Lee Dong Keon Yon Eunyoung kim Ai Koyanagi Elena Dragioti Jae Il Shin Lee Smith Samsung Advanced Institute forHealth Sciences&Technology(SAIHST) Samsung Medical CenterSungkyunkwan UniversitySeoulRepublic of Korea Yonsei University Collegeof Medicine SeoulRepublicof Korea Department of Precision Medicine Sungkyunkwan University School of MedicineSuwonRepublic of Korea Center for Digital Health Medical Science Research InstituteKyung Hee University College of MedicineSeoulRepublic of Korea Evidence-Based Research Laboratory Department of Clinical Pharmacy and Pharmaceutical CareCollege of PharmacyChung-Ang UniversitySeoulRepublic of Korea Parc Sanitari Sant Joan de Deu/CIBERSAM/ISCIII Universitat de BarcelonaFundacio Sant Joan de Déu.Sant Boi de LlobregatBarcelonaSpain ICREA Pg.Lluis Companys 23BarcelonaSpain Pain and Rehabilitation Centre and Department of Medical and Health SciencesLinkoping University58185 LinkopingSweden Department of Pediatrics Yonsei University College of MedicineYonsei-ro 50Seodaemun-gu8044Seoul 03722Republic of Korea Centre for Health Performanceand WellbeingAnglia Ruskin UniversityCambridge CB11PTUK Research Laboratory Psychology of Patients Families&Health ProfessionalsDepartment of NursingSchool of Health SciencesUniversity of IoanninaIoannina 45500Greece

Introduction Antibiotic use for acute otitis media(AOM)is one of the major sources of antimicrobial resistance.However,the effective minimal antibiotic duration for AOM remains unclear.Moreover,guidelines often recommend broad ranges(5-10 days)of antibiotic use,yet the clinical impact of such a wide window has not been assessed.Methods We systematically searched PubMed/MEDLINE,Embase,Scopus,Web of Science,and Cochrane Library from database inception to 6 October 2021.Network meta-analysis was conducted on randomized controlled trials that assessed antibiotic treatment for AOM in children(PROSPERO CRD42020196107).Results For amoxicillin and amoxicillin-clavulanate,7-day regimens were noninferior to 10-day regimens in clinical responses[amoxicillin:risk ratio(RR)0.919(95%CI 0.820-1.031),amoxicillin-clavulanate:RR 1.108(0.957-1.282)],except for≤2 years.For the third-generation cephalosporins,7-day and 10-day regimens had similar clinical responses compared to placebo[7-day:RR 1.420(1.190-1.694),10-day:RR 1.238(1.125-1.362)compared to placebo].However,5-day regimens of amoxicillin-clavulanate and third-generation cephalosporins were inferior to 10-day regimens.Compared to amoxicillin,a shorter treatment duration was tolerable with amoxicillin-clavulanate.Conclusions Our findings indicated that 1O days of antibiotic use may be unnecessarily long,while the treatment duration should be longer than 5 days.Otherwise,5-day regimens would be sufficient for a modest treatment goal.Our findings revealed that the current wide range of recommended antibiotic durations may have influenced the clinical outcome of AOM,and a narrower antibiotic duration window should be re-established.

关键词： Amoxicillin-potassium Amoxicillin Antibacterial agents Cephalosporins Duration of therapy

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Electric-field-controlled highly regioselective thiocyanation of N-containing heterocycles

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Science China Chemistry 2024年第4期67卷 1263-1269页

作者： Ming Gong Qian Wu Jung Keun kim Mengmeng Huang Yabo Li Yangjie Wu Jong seung kim Henan Key Laboratory of Chemical Biology and Organic Chemistry Key Laboratory of Applied Chemistry of Henan UniversitiesCollege of ChemistryZhengzhou UniversityZhengzhou 450052China Department of Chemistry Korea UniversitySeoul 02841Korea

Achieving highly regioselective synthesis in organic chemistry is challenging due to the uncontrollable orientation between reacting partners.External electric fields(EEFs)can influence the reactivity and selectivity of the substrate by causing directional adsorption.However,scalable and efficient techniques for using EEFs as“smart catalysts”have been lacking,hindering their application.In this study,we present a novel method for modifying the regioselectivity of quinoxaline-2(1H)-ones by functionalizing their C7-position using the electric double layer(EDL)theory.This approach led to moderate to good yields of the corresponding C7-thiocyanation products.DFT calculations and control experiments demonstrated that EEFs could reverse the regioselectivity of quinoxaline-2(1H)-ones,allowing the C7-thiocyanation to proceed via a radical reaction mechanism.Additionally,the resulting 7-thiocyano-1-methylquinoxaline-2(1H)-ones exhibited promising AIE properties.Our work showcases a promising strategy for achieving highly regioselective functionalization by aligning the electric field with the desired reaction/bond axis.

关键词： electric fields reaction-axis rule electric double layer C7-thiocyanation C-S bond formation

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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 established.In this study,we investigated whether Neural Wiskott-Aldrich syndrome protein(N-WASP)plays a role in distant metastasis of PDAC.We found that N-WASP is markedly expressed in clinical patients with PDAC.Clinical 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 studies.Knockdown of N-WASP in pancreatic cancer cells significantly inhibited cell invasion,migration,and EMT.We 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 modulated.Both N-WASP and LOXL2 depletion significantly reduced the incidence of liver and lung metastatic lesions in orthotopic mouse models of pancreatic cancer.These 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 metastasis.These 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)

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Machine-learned wearable sensors for real-time hand-motion recognition: toward practical applications

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National Science Review 2024年第2期11卷 231-263页

作者： Kyung Rok Pyun Kangkyu Kwon Myung Jin Yoo Kyun Kyu kim Dohyeon Gong Woon-Hong Yeo seungyong Han seung Hwan Ko Department of Mechanical Engineering Seoul National University IEN Center for Human-Centric Interfaces and Engineering Institute for Electronics and NanotechnologyGeorgia Institute of Technology School of Electrical and Computer Engineering Georgia Institute of Technology Department of Chemical Engineering Stanford University Department of Mechanical Engineering Ajou University George W.Woodruff School of Mechanical Engineering Georgia Institute of Technology Institute of Advanced Machinery and Design(SNU-IAMD) Seoul National University

Soft electromechanical sensors have led to a new paradigm of electronic devices for novel motion-based wearable applications in our daily lives. However, the vast amount of random and unidentified signals generated by complex body motions has hindered the precise recognition and practical application of this technology. Recent advancements in artificial-intelligence technology have enabled significant strides in extracting features from massive and intricate data sets, thereby presenting a breakthrough in utilizing wearable sensors for practical applications. Beyond traditional machine-learning techniques for classifying simple gestures, advanced machine-learning algorithms have been developed to handle more complex and nuanced motion-based tasks with restricted training data sets. Machine-learning techniques have improved the ability to perceive, and thus machine-learned wearable soft sensors have enabled accurate and rapid human-gesture recognition, providing real-time feedback to users. This forms a crucial component of future wearable electronics, contributing to a robust human–machine interface. In this review, we provide a comprehensive summary covering materials, structures and machine-learning algorithms for hand-gesture recognition and possible practical applications through machine-learned wearable electromechanical sensors.

关键词： wearable sensor soft electronics artificial intelligence machine learning human–machine interfaces gesture recognition

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Lighting up plants with near-infrared fluorescence probes

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Science China Chemistry 2024年第3期67卷 774-787页

作者： Yida Pang Mengjiao Lu Hyeonji Rha Wenchao Yang Amit Sharma Yao Sun Jong seung kim National Key Laboratory of Green Pesticide Key Laboratory of Green Pesticide and Agricultural BioengineeringMinistry of EducationCenter for R&D of Fine Chemicals of Guizhou UniversityGuiyang 550025China National Key Laboratory of Green Pesticide College of ChemistryCentral China Normal UniversityWuhan 430079China Department of Chemistry Korea UniversitySeoul 02841Korea CSIR-Central Scientific Instruments Organisation Sector-30CChandigarh160030India TheranoChem Incorporation Seongbuk-guSeoul02856Korea

Fluorescence imaging is a non-invasive and highly sensitive bioimaging technique that has shown remarkable strides in plant science. It enables real-time monitoring and analysis of biological and pathological processes in plants by labeling specific molecular or cellular structures with fluorescent probes. However, tissue scattering and phytochrome interference have been obstacles for conventional fluorescence imaging of plants in the ultraviolet and visible spectrum, resulting in unsatisfactory imaging quality. Fortunately, advances in near-infrared(NIR) fluorescence imaging technology(650-900 nm) offer superior spatial-temporal resolution and reduced tissue scattering, which is sure to improve plant imaging quality. In this review, we summarize recent progress in the development of NIR fluorescence imaging probes and their applications for in vivo plant imaging and the identification of plant-related biomolecules. We hope this review provides a new perspective for plant science research and highlights NIR fluorescence imaging as a powerful tool for analyzing plant physiology, adaptive mechanisms, and coping with environmental stress in the near future.

关键词： NIR fluorescent probe plant imaging biologic application

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