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[^(18)F]MAGL-4-11 positron emission tomography molecular imaging of monoacylglycerol lipase changes in preclinical liver fibrosis models

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Acta Pharmaceutica Sinica B 2022年第1期12卷 308-315页

作者： tuo Shao Zhen Chen Jian Rong Vasily Belov Jiahui Chen Andre Jeyarajan Xiaoyun Deng Hualong Fu Qingzhen Yu Steve H.Rwema Wenyu Lin Mikhail Papisov Lee Josephson raymond t.chung Steven H.Liang Division of Nuclear Medicine and Molecular Imaging Department of RadiologyMassachusetts General Hospital and Harvard Medical SchoolBostonmA 02114USA Liver Center and Gastrointestinal Division Department of MedicineMassachusetts General HospitalHarvard Medical SchoolBostonA 02114USA Shriners Hospitals for Children-Boston Boston BostonMA 02114USA

Monoacylglycerol lipase(MAGL) is a pivotal enzyme in the endocannabinoid system, which metabolizes 2-arachidonoylglycerol(2-AG) into the proinflammatory eicosanoid precursor arachidonic acid(AA). MAGL and other endogenous cannabinoid(EC) degrading enzymes are involved in the fibrogenic signaling pathways that induce hepatic stellate cell(HSC) activation and ECM accumulation during chronic liver disease. Our group recently developed an;F-labeled MAGL inhibitor([18F]MAGL-4-11)for PEt imaging and demonstrated highly specific binding in vitro and in vivo. In this study, we determined [18F]MAGL-4-11 PEt enabled imaging MAGL levels in the bile duct ligation(BDL) and carbon tetrachloride(CCl_(4)) models of liver cirrhosis;we also assessed the hepatic gene expression of the enzymes involved with EC system including MAGL, NAPE-PLD, FAAH and DAGL that as a function of disease severity in these models;[18F]MAGL-4-11 autoradiography was performed to assess tracer binding in frozen liver sections both in animal and human. [18F]MAGL-4-11 demonstrated reduced PEt signals in early stages of fibrosis and further significantly decreased with disease progression compared with control mice. We confirmed MAGL and FAAH expression decreases with fibrosisseverity, while its levels in normal liver tissue are high;in contrast, the EC synthetic enzymes NAPE-PLD and DAGL are enhanced in these different fibrosis models. In vitro autoradiography further supported that[18F]MAGL-4-11 bound specifically to MAGL in both animal and human fibrotic liver tissues. Our PEt ligand [18F]MAGL-4-11 shows excellent sensitivity and specificity for MAGL visualization in vivo and accurately reflects the histological stages of liver fibrosis in preclinical models and human liver tissues.

关键词： [18F]MAGL-4-11 PEt imaging Liver fibrosis MAGL

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SARt1是干扰素-α抗丙型肝炎病毒作用中不可缺少的人类基因

SART1是干扰素-α抗丙型肝炎病毒作用中不可缺少的人类基因

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中华医学会第四次全国感染性疾病中青年学术会议

作者：赵鸿林温玉王贵强 raymond t.chung 北京大学第一医院感染疾病科

目的目前尚未获得准确、详细的与干扰素-α(interferonα,IFNα)抗丙型肝炎病毒(hepatitis Cviral,HCV)相关的人类基因库。我们采用小干扰RNA(small interfere RNA,siRNA)、依托于3个丙型肝炎病毒复制的细胞模型,筛选与干扰素-α抗丙肝...

目的目前尚未获得准确、详细的与干扰素-α(interferonα,IFNα)抗丙型肝炎病毒(hepatitis Cviral,HCV)相关的人类基因库。我们采用小干扰RNA(small interfere RNA,siRNA)、依托于3个丙型肝炎病毒复制的细胞模型,筛选与干扰素-α抗丙肝病毒相关的人类基因。方法目前NCBI RefSeqdatabase中一共收录了21 094个人类基因,针对其中每个基因的siRNA即构成了siARRAY HumanGenome siRNA Library。Huh7/pRep-Feo是带有1b型丙型肝炎病毒部分基因组的肝癌细胞。转染了siRNAs的Huh7/Rep-Feo细胞经72小时孵育后,分别用或不用5 IU/mL PEG-IFN-α-2b处理24小时。挑选robust Z scores≥2.0的基因做进一步验证。通过验证的基因在含有HCV全长基因组的OR6细

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No evidence for higher rates of hepatocellular carcinoma after direct-acting antiviral treatment: a meta-analysis

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Hepatoma Research 2019年第8期5卷 11-22页

作者： Stephanie M.Rutledge Hui Zheng Darrick K.Li raymond t.chung Department of Medicine Massachusetts General HospitalGastroenterology Unit/Warren 10BostonMA02114USA Liver Center Gastrointestinal DivisionDepartment of MedicineMassachusetts General HospitalHarvard Medical SchoolBostonMA 02114USA

Aim:Hepatitis C virus(HCV)is the leading cause of hepatocellular carcinoma(HCC)in the United *** sustained viral response with interferon(IFN)treatment reduces the risk from 3%-5%to 0.5%-1%*** studies reported unexpectedly high rates of HCC after treatment with direct-acting antivirals(DAAs).the aim of our study was to compare HCC rates in DAA-,IFN-treated and untreated ***:A literature search was conducted using ScienceDirect,Ovid?,Web of Science and MEDLINE through January *** were included if they measured rates of de novo or recurrent HCC(following curative treatment)in HCV-infected *** included 138 studies(n=177,512).Simple pooling of data and meta-analysis were performed,using the random effects ***:Mean age was higher in the DAA-treated ***-treated group(58.4 years vs.52.6 years;P=0.0073),as were diabetes prevalence(34.5%vs.11.7%;P≤0.001)and incident cirrhosis(47.8%vs.34.2%,P=0.0017).the incidence rate of de novo HCC was 2.01/100 person-years(py)(95%CI:1.38,2.67)in the DAA group and 1.45/100py(95%CI:0.98,1.94)in the IFN-treated *** recurred at 16.76/100py(95%CI:10.75,22.91)in the DAA-treated group vs.20.04/100py(95%CI:2.58,45.21)after *** adjusting for factors such as age and cirrhosis,the hazard ratio was 0.58(95%CI:0.20,1.07)for HCC occurrence and 0.59(95%CI:0.24,1.03)for HCC recurrence after DAA treatment compared to IFN-based treatment. ;Conclusion:We did not find evidence for increased rates of HCC in DAA-treated compared with IFN-treated *** to those treated with IFN,older patients with additional risk factors for HCC were treated with *** imbalance appears to explain the higher numerical incidence of HCC among DAA-treated patients.

关键词： Humans hepatitis C virus liver cirrhosis liver neoplasms interferons

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Homogenization with the Quasistatic tresca Friction Law:Qualitative and Quantitative Results

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Chinese Annals of Mathematics,Series B 2023年第5期44卷 781-802页

作者： Changqing YE Eric t.chung Jun-zhi CUI Department of Mathematics the Chinese University of Hong KongShatinHong Kong SARChina LSEC Academy of Mathematics and Systems ScienceChinese Academy of SciencesBeijing 100190China

Modeling of frictional contacts is crucial for investigating mechanical performances of composite materials under varying service *** paper considers a linear elasticity system with strongly heterogeneous coefficients and quasistatic tresca friction law,and studies the homogenization theories under the frameworks of H-convergence and small ε-*** qualitative result is based on H-convergence,which shows the original oscillating solutions will converge weakly to the homogenized solution,while the author’s quantitative result provides an estimate of asymptotic errors in H^(1)-norm for the periodic *** paper also designs several numerical experiments to validate the convergence rates in the quantitative analysis.

关键词： Homogenization Frictional contact mechanics Quasistatic tresca frictionlaw

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Immunoregulatory and Anti-cancer Activities of Combination treatment of Novel Four-Herb Formula and Doxorubicin in 4t1-Breast Cancer Bearing Mice

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Chinese Journal of Integrative Medicine 2024年第4期30卷 311-321页

作者： Lea Ling-Yu Kan Ben chung-Lap Chan Grace Gar-Lee Yue LI Pei-ting Sharon Sze-Man Hon HUANG Dan-qi Miranda Sin-Man tsang Clara Bik-San Lau Ping-chung Leung Chun-Kwok Wong Institute of Chinese Medicine The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Department of Chemical Pathology The Chinese University of Hong KongHong Kong SARChina China-Australia International Research Centre for Chinese Medicine School of Health and Biomedical SciencesSTEM CollegeRMIT UniversityBundooraVictoriaAustralia Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine The Chinese University of Hong Kong SARHong KongChina

Objective to investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula(4HF)and doxorubicin in triple-negative breast cancer(tNBC).Methods Murine-derived triple-negative mammary carcinoma cell line,4t1 cells,was cultured and inoculated into mouse mammary ***-six mice were randomly assigned into 6 groups(n=11 in ench):naive,control,LD 4HF(low dose 4HF),HD 4HF(high dose 4HF),LD 4HF+D(low dose and doxorubicin),and D(doxorubicin).Apart from the naive group,each mouse received subcutaneous inoculation with 5×10^(5)4t1 cells resuspended in 100µL of normal saline in the mammary fat *** from the day of tumor cell inoculation,tumors were grown for 6 *** LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF,*** LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin(5 mg/kg).the D group received weekly intraperitoneal injections of doxorubicin(5 mg/kg).the treatment naive mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a *** control group received daily oral gavage of 0.2 mL double-distilled *** treatment period was 30 *** the end of treatment,mice organs were harvested to analyze immunological activities via immunophenotyping,gene and multiplex analysis,histological staining,and gut microbiota *** Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens(Ptered the hypoxia and overall immune lymphocyte landscape,and manipulated gut microbiota to favor the anti-tumor immunological ***,immunosuppressive genes,cytokines,and chemokines such as C-C motif chemokine 2 and interleukin-10 of tumors were significantly downregulated(Ption treatment demonstrated synergetic activities and was most effective

关键词： adjunctivetherapy breast cancer cytokines Chinese medicine tumor microenvironment

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Achieving High CO_(2)Photoreduction Activity by Conductive Crosslinks of Metal–Organic Framework

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CCS Chemistry 2024年第5期6卷 1211-1221页

作者： Ning Li Gui-Qi Lai Lai-Hon chung Fei Yu Jun He Ya-Qian Lan Department School of Chemical Engineering and Light Industry Guangdong University of TechnologyGuangzhouGuangdong 510006 School of Chemistry South China Normal UniversityGuangzhou 510006 School of Chemistry and Materials Science Nanjing Normal UniversityNanjing 210023

Fast photogenerated charge migration is crucial for the improvement of photocatalytic performance,but its deliberate modulation is *** work presents two Zr-based metal–organic framework catalysts,GDUt-8 and GDUt-8-Ox,for photocatalytic CO_(2)***,thiophene pendants in GDUt-8 were coupled covalently via Scholl reaction to give GDUt-8-Ox,a catalyst with at least two orders of magnitude(up to 6.1×10^(−3)S cm^(−1))enhanced conductivity and faster transport of photogenerated carriers during ***,from GDUt-8 to GDUt-8-Ox,stronger ligand-to-cluster charge transfer with pronounced light absorption extension was *** a result,GDUt-8-Ox exhibited the highest photocatalytic CO_(2)-to-HCOO−conversion rate(1725μmol g^(−1)h^(−1))to date,in the absence of photosensitizer,as well as turnover number,turnover frequency,and quantum efficiency much higher than *** work presents an unprecedented strategy to accelerate the photogenerated carrier transport of photocatalysts.

关键词： metal-organic framework Scholl reaction covalent crosslinks high conductivity CO_(2)photoreduction CO_(2)-to-HCOO−conversion

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Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism

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Neural Regeneration Research 2024年第3期19卷 650-656页

作者： Jie Li Wen Jiang Yuefang Cai Zhenqiu Ning Yingying Zhou Chengyi Wang Sookja Ki chung Yan Huang Jingbo Sun Minzhen Deng Lihua Zhou Xiao Cheng Guangzhou University of traditional Chinese Medicine GuangzhouGuangdong ProvinceChina State Key Laboratory of Dampness Syndrome of Chinese Medicine The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhouGuangdong ProvinceChina Guangdong Provincial Key Laboratory of Research on Emergency in tCM GuangzhouGuangdong ProvinceChina Department of Anesthesiology West China HospitalSichuan UniversityChengduSichuan ProvinceChina Department of Anatomy Sun Yat-Sen School of MedicineSun Yat-Sen UniversityShenzhenGuangdong ProvinceChina Faculty of Medicine Macao University of Science and TechnologyMacao Special Administration RegionChina

Vascular etiology is the second most prevalent cause of cognitive impairment ***-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of ***,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well ***,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery *** proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic ***,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway *** chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic ***,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.

关键词： astrocytic endothelin-1 dentate gyrus differentially expressed proteins hippocampus ischemic stroke learning and memory deficits lipid metabolism neural stem cells neurogenesis proliferation

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Investigation of Acoustomagnetoelectric Effect in Bandgap Graphene by the Boltzmann transport Equation

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World Journal of Condensed Matter Physics 2024年第1期14卷 10-20页

作者： raymond Edziah Samuel S. Bentsiefi Kwadwo Dompreh Anthony twum Emmanuel Kofi Amewode Patrick Mensah-Amoah Ebenezer t. tatchie Cynthia Jebuni-Adanu Samuel Y. Mensah Department of Physics University of Cape Coast Cape Coast Ghana Department of Physics Education University of Education Winneba Ghana

We study the acoustomagnetoelectric (AME) effect in two-dimensional graphene with an energy bandgap using the semiclassical Boltzmann transport equation within the hypersound regime, (where represents the acoustic wavenumber and is the mean free path of the electron). the Boltzmann transport equation and other relevant equations were solved analytically to obtain an expression for the AME current density, consisting of longitudinal and Hall components. Our numerical results indicate that both components of the AME current densities display oscillatory behaviour. Furthermore, geometric resonances and Weiss oscillations were each defined using the relationship between the current density and Surface Acoustic Wave (SAW) frequency and the inverse of the applied magnetic field, respectively. Our results show that the AME current density of bandgap graphene, which can be controlled to suit a particular electronic device application, is smaller than that of (gapless) graphene and is therefore, more suited for nanophotonic device applications.

关键词： Boltzmann transport Equation Acoustomagnetoelctric Effect Surface Acoustic Wave Gapless Graphene Weiss Oscillations

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A Sub-Grid Structure Enhanced Discontinuous Galerkin Method for Multiscale Diffusion and Convection-Diffusion Problems

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Communications in Computational Physics 2013年第7期14卷 370-392页

作者： Eric t.chung Wing tat Leung Department of Mathematics The Chinese University of Hong KongHong Kong

In this paper,we present an efficient computational methodology for diffusion and convection-diffusion problems in highly heterogeneous media as well as convection-dominated diffusion *** is well known that the numerical computation for these problems requires a significant amount of computermemory and ***,the solutions to these problems typically contain a coarse component,which is usually the quantity of interest and can be represented with a small number of degrees of *** are many methods that aim at the computation of the coarse component without resolving the full details of the *** proposed method falls into the framework of interior penalty discontinuous Galerkin method,which is proved to be an effective and accurate class of methods for numerical solutions of partial differential equations.A distinctive feature of our method is that the solution space contains two components,namely a coarse space that gives a polynomial approximation to the coarse component in the traditional way and a multiscale space which contains sub-grid structures of the solution and is essential to the computation of the coarse *** addition,stability of the method is *** numerical results indicate that the method can accurately capture the coarse behavior of the solution for problems in highly heterogeneous media as well as boundary and internal layers for convection-dominated problems.

关键词： Multiscale problem sub-grid capturing multiscale basis function boundary layer internal layer

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Efficient Simulation of Wave Propagation with Implicit Finite Difference Schemes

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Numerical Mathematics(theory,Methods and Applications) 2012年第2期5卷 205-228页

作者： Wensheng Zhang Li tong Eric t.chung LSEC Institute of Computational Mathematics and Scientific/Engineering ComputingAcademy of Mathematics and Systems ScienceChinese Academy of SciencesBeijing P.O.Box 2719100190 China Department of Mathematics The Chinese University of Hong KongHong Kong

Finite difference method is an important methodology in the approximation of *** this paper,we will study two implicit finite difference schemes for the simulation of *** are the weighted alternating direction implicit(ADI)scheme and the locally one-dimensional(LOD)*** approximation errors,stability conditions,and dispersion relations for both schemes are *** analysis shows that the LOD implicit scheme has less dispersion error than that of the ADI ***,the unconditional stability for both schemes with arbitrary spatial accuracy is established for the first *** order to improve computational efficiency,numerical algorithms based on message passing interface(MPI)are *** examples of wave propagation in a three-layer model and a standard complex model are *** analysis and comparisons show that both ADI and LOD schemes are able to efficiently and accurately simulate wave propagation in complex media.

关键词： Acoustic wave equation implicit schemes ADI LOD stability condition dispersion curve MPI parallel computations

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