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New insights into the suppression of inflammation and lipid accumulation by JAZF1

Genes & Diseases 2023年第6期10卷 2457-2469页

作者： Wujun chen Yingjie Zhong Yang yuan Meng Zhu Wenchao Hu Ning Liu Dongming Xing Cancer Institute Department of NeurosurgeryThe Affiliated Hospital of Qingdao UniversityQingdao UniversityQingdao Cancer InstituteQingdaoShandong 266071China Department of Endocrinology Qilu Hospital(Qingdao)Cheeloo College of MedicineShandong UniversityQingdaoShandong 266035China School of Life Sciences Tsinghua UniversityBeijing 100084China

Atherosclerosis is one of the leading causes of disease and death *** identification of new therapeutic targets and agents is ***1 is expressed in many tissues and is found at particularly high levels in adipose tissue(AT).JAZF1 suppresses inflammation(including IL-1β,IL-4,IL-6,IL-8,IL-10,TNFα,IFN-γ,IAR-20,COL3A1,laminin,and MCP-1)by reducing NF-κB pathway activation and AT immune cell ***1 reduces lipid accumulation by regulating the liver X receptor response element(LXRE)of the SREBP-1c promoter,the cAMP-response element(CRE)of HMGCR,and the TR4 *** and CRE sites are present in many cytokine and lipid metabolism gene promoters,which suggests that JAZF1 regulates these genes through these ***-κB is the center of the JAZF1-mediated inhibition of the inflammatory ***1 suppresses NF-κB expression by suppressing TAK1 ***,TAK1 inhibition also decreases lipid accumulation.A dual-targeting strategy of NF-κB and TAK1 could inhibit both inflammation and lipid ***-target compounds(including prodrugs)1–5 exhibit nanomolar inhibition by targeting NF-κB and TAK1,EGFR,or ***,the NF-κB suppressing activity of these compounds is relatively low(IC50>300 nM).Compounds 6–14 suppress NF-κB expression with IC50 values ranging from 1.8 nM to 38.6 ***-276 is a highly selective,orally bioavailable TAK1 *** structural modifications of compounds using a prodrug strategy may enhance NF-κB *** review focused on the role and mechanism of JAZF1 in inflammation and lipid accumulation for the identification of new anti-atherosclerotic targets.

关键词： Atherosclerosis CRE JAZF1 LXRE NF-κB TAK1

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Wang-Bi tablet, a patented Chinese medicine, maintains the balance of Th1/Th2 in mice with collagen-induced arthritis

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Journal of Traditional Chinese Medicine 2020年第3期40卷 401-406页

作者： Wang Jianming Luo Jing Xu yuan Yan Zeran Qu Xiangke chen Mengxue Tao Qingwen Department of Rheumatology of Traditional Chinese Medicine China-Japan Friendship HospitalBeijing 100029China Integrative Chinese and Western Medicine of excellence in Beijing University of Chinese medicine Beijing 100029China

OBJECTIVE: To investigate the pharmacological mechanism of Wang-Bi tablets(WBTs), a Chinese patented medicine, in rheumatoid arthritis(RA) using mice with collagen-induced arthritis(CIA).METHODS: A mouse model of CIA was induced using bovine type Ⅱ collagen. WBT treatment was administered and efficacy was evaluated. The levels of interferon-γ(IFN-γ), interleukin-2(IL-2), and interleukin-4(IL-4) were examined using an enzyme-linked immunosorbent assay, and the proportions of Th1 and Th2 were detected using flow cytometry. T-bet and GATA-binding protein 3(GATA3)expression were demonstrated using Western blot ***: Paw swelling and the arthritis index decreased significantly following WBT treatment. Histopathological analysis revealed markedly alleviated damage to synovium tissue in the WBT and methotrexate treatment groups. WBT regulated the production of IFN-γ, IL-2, and IL-4 and modulated Th1 and Th2 cell populations, which might have been induced by the attenuation of Th1 and Th2 cell differentiation through a decrease in the expression of T-bet and an increase in the expression of GATA3 in the synovial tissue in CIA ***: These results indicate that WBT may produce a therapeutic effect on CIA through maintaining the balance of Th1/Th2 cells, which could result in a decrease in the autoinflammatory disorder observed in RA.

关键词： Arthritis rheumatoid Collagen Th1-Th2 balance Wang-Bi tablet

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Suppression of HIV-1 Integration by Targeting HIV-1 Integrase for Degradation with A Chimeric Ubiquitin Ligase

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Virologica Sinica 2021年第3期36卷 424-437页

作者： Zuopeng Zhang Sen yuan Shuting Xu Deyin Guo Lang chen Wei Hou Min Wang School of Basic Medical Sciences Wuhan UniversityWuhan 430071China Centre for Infection and Inmunity Study(CHS) School of MedicineSun Yat-sen UniversityGuangzhou 518107China Renmin Hospital of Wuhan University Wuhan 430060China

Human immunodeficiency virus(HIV) attacks human immune system and causes life-threatening acquired immune deficiency syndrome(AIDS). Treatment with combination antiretroviral therapy(cART) could inhibit virus growth and slow progression of the disease, however, at the same time posing various adverse effects. Host ubiquitin-proteasome pathway(UPP) plays important roles in host immunity against pathogens including viruses by inducing degradation of viral proteins. Previously a series of methods for retargeting substrates for ubiquitin-proteasome degradation have been successfully established. In this study, we attempted to design and construct artificial chimeric ubiquitin ligases(E3 s) based on known human E3 s in order to manually target HIV-1 integrase for ubiquitin proteasome pathway-mediated ***, a series of prototypical chimeric E3 s have been designed and constructed, and original substrate-binding domains of these E3 s were replaced with host protein domains which interacted with viral proteins. After functional assessment screening, 146 LI was identified as a functional chimeric E3 for HIV-1 NL4-3 integrase. 146 LI was then further optimized to generate 146 LIS(146 LI short) which has been shown to induce Lys48-specific polyubiquitination and reduce protein level of HIV-1 NL4-3 integrase more effectively in cells. Lymphocyte cells with 146 LIS knock-in generated by CRISPR/Cas-mediated homology-directed repair(HDR) showed remarkably decreased integration of HIV-1 NL4-3 viral DNAs and reduced viral replication without obvious cell cytotoxicity. Our study successfully obtained an artificial chimeric E3 which can induce Lys48-specific polyubiquitination and proteasome-mediated degradation of HIV-1 NL4-3 integrase, thus effectively inhibiting viral DNA integration and viral replication upon virus infection.

关键词： HIV-1 Integrase Iduna LEDGF Chimeric E3s Ubiquitination

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Factors involved in the success of Castanea henryi stem cuttings in different cutting mediums and cutting selection periods

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Journal of Forestry Research 2021年第4期32卷 1627-1639页

作者： Wangzun chen Libing He Shiyi Tian Joseph Masabni Huan Xiong Feng Zou Deyi yuan Key Laboratory of Cultivation and Protection for Non-Wood Forest Trees Ministry of EducationCentral South University of Forestry and TechnologyChangsha 410004People’s Republic of China Texas A&M AgriLife Center at Dallas 17360 Coit RdDallasTX 75252USA

Chinquapin(Castanea henryi) is a dual-purpose tree species in China valued for as a source of timber and *** investigated the effect of four cutting mediums(pure vermiculite;peat:river sand at 3:1 v/v;peat:krasnozem at 1:1 v/v;and pure krasnozem) and three stem cutting periods(March,May,and July) on rooting performance of *** *** cutting periods and cutting mediums greatly influenced the rooting rate of ***,ranging from 3.35 to 77.31%.Principal component analysis indicated that the best combination of cutting period and cutting medium was semi-hardwood cuttings(May cuttings)+*** evidence indicated that adventitious root initials were present by week 5-6,and that the site of root primordia initiation was observed in the vascular *** anatomical structures observed at different periods indicated that a xylem/radius ratio of29.90-37.42% and a fractured phloem fiber ring are indicative of rooting *** relational model between rooting index and medium properties indicated that nutrient content and porosity significantly influenced callus ***,pH strongly affected *** root formation,with the Pearson correlation coefficients for May and July cuttings of-0.856 and-0.947,*** protocol is helpful to achieve mass clone propagation of improved *** genotypes,thus overcoming a common hurdle in chinquapin breeding programs.

关键词： Adventitious roots formation Castane henryi Medium pH Phloem fiber ring Xylem

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DES置入后5年以上支架内再狭窄新生内膜OCT分析

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中华心血管病杂志 2024年第2期52卷 150-157页

作者：韩燕袁晓航蒋梦婷冯欢欢张茜张颖倩荆晶陈韵岱高磊解放军总医院第一医学中心心血管内科北京100853 解放军医学院北京100853 解放军总医院第一医学中心急诊科北京100853

目的基于光学相干断层成像(OCT)探讨药物洗脱支架(DES)置入后5年以上支架内再狭窄(ISR)患者的新生内膜增生(NIH)特性。方法本研究为横断面研究。连续入组2010年3月至2022年3月于解放军总医院接受OCT检查的DES-ISR患者。依据发现ISR距离... 详细信息

目的基于光学相干断层成像(OCT)探讨药物洗脱支架(DES)置入后5年以上支架内再狭窄(ISR)患者的新生内膜增生(NIH)特性。方法本研究为横断面研究。连续入组2010年3月至2022年3月于解放军总医院接受OCT检查的DES-ISR患者。依据发现ISR距离DES置入时间,将入选患者分为支架置入时间≤5年组和支架置入时间>5年组。对OCT图像进行定量和定性分析,比较两组患者的临床资料及病变特征,并通过多因素logistic回归分析支架内新生动脉粥样硬化(ISNA)的临床独立相关因素。结果纳入DES-ISR患者230例,年龄(63.1±10.4)岁,男性188例(81.7%),包含249个病变。DES-ISR中位发现时间为6(2,9)年。支架置入时间≤5年组117例(ISR病变122个),支架置入时间>5年组113例(ISR病变127个)。与支架置入时间≤5年组相比,支架置入时间>5年组中异质性[65.4%(83/127)比48.4%(59/122),P=0.007]、弥漫性[46.5%(59/127)比31.2%(38/122),P=0.013]以及伴有巨噬细胞聚集[44.1%(56/127)比31.2%(38/122),P=0.035]的NIH更多见,且ISNA患病率更高[83.5%(106/127)比72.1%(88/122),P=0.031]。多因素logistic回归分析结果显示,ISNA的独立相关因素为女性(OR=0.44,95%CI 0.21~0.90,P=0.026),脂质型ISNA的独立相关因素包括女性(OR=0.48,95%CI 0.23~0.99,P=0.046)及低密度脂蛋白胆固醇水平(OR=1.62,95%CI 1.01~2.59,P=0.046),而钙化型ISNA与支架置入时间(OR=1.18,95%CI 1.07~1.29,P=0.001)独立相关。结论支架置入>5年的DES-ISR患者ISNA患病率更高且病变更复杂。性别、低密度脂蛋白胆固醇水平及支架置入时间与ISNA、脂质型ISNA及钙化型ISNA独立相关。

关键词：药物洗脱支架支架内再狭窄光学相干断层成像新生内膜增生新生动脉粥样硬化

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3-photon fluorescence and third-harmonic generation imaging of myelin sheaths in mouse digital skin in vivo:A comparative study

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Journal of Innovative Optical Health Sciences 2022年第1期15卷 120-127页

作者： Ke Wang Yi Pan Xinlin chen Shen Tong Huiping Liang yuan Lu Ping Qiu Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province College of Physics and Optoelectronic Engineering Shenzhen University Shenzhen 518060P.R.China Department of Dermatology The sixth Hospital of Shenzhen University(Nanshan Hospital)Shenzhen 518052 P.R.China

Myelin sheaths wrapping axons are key structures that help maintain the propagation speed of action potentials in both central and peripheral nervous systems(CNS and PNS).However,noninvasive,deep imaging technologies visualizing myelin sheaths in the digital skin in vivo are lacking in animal models.3-photon°uorescence(3PF)imaging excited at the 1700-nm window enables deep imaging of myelin sheaths,but necessitates labeling by exogenous°uorescent *** myelin sheaths are lipid-rich structures which generate strong third-harmonic signals,in this paper,we perform a detailed comparative experimental study of both third-harmonic generation(THG)and 3PF imaging in the mouse digital skin in *** results show that THG imaging also enables visualization of myelin sheaths deep in the mouse digital skin,which shows colocalization with 3PF signals from labeled myelin *** its superior label-free advantage,THG does not su®er from photobleaching due to its 3PF property.

关键词： 3-photon microscopy digital skin myelin 1700-nm window.

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Visible-light induced cascade radical cyclization of sulfinic acids and o-(allyloxy)arylaldehydes towards functionalized chroman-4-ones

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Chinese Chemical Letters 2020年第12期31卷 3255-3258页

作者： Guang-Hui Li Qing-Qing Han yuan-yuan Sun De-Mao chen Zu-Li Wang Xin-Ming Xu Xian-Yong Yu College of Chemistry and Pharmaceutical Sciences Qingdao Agricultural UniversityQingda 266109China College of Chemistry and Chermical Engineering Yantai UniversityYantai 264005China School of Chernistry and Chemical Engineering Hunan UIniversity of Science and TechnologyXiangtan 411201China

An efficient method for the synthesis of functionalized chroman-4-ones induced by visible light via the radical cyclization reaction of sulfinic acids and o-(allyloxy)arylaldehydes at room temperature was *** corresponding products were isolated with moderate to good *** mechanism was proposed fo r this trans ***-microbial activity of some desired compounds we re screened.

关键词： Visible light Sulfinic acids Radical cyclization Chroman-4-one o-(Allyloxy)arylaldehydes

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A New Robust Risk Measure:Quantile Shortfall

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Acta Mathematica Sinica,English Series 2020年第9期36卷 1014-1024页

作者： You Li chen Yan Yan LIU Guang Cai MAO yuan Shan WU Fei YAN Law School Wuhan UniversityWuhan 430072P.R.China School of Mathematics and Statistics Wuhan UniversityWuhan 430072P.R.China School of Mathematics and Statistics Central China Normal UniversityWuhan 430079P.R.China School of Statistics and Mathematics Zhongnan University of Economics and LawWuhan 430073P.R.China

Among recent measures for risk management,value at risk(VaR)has been criticized because it is not coherent and expected shortfall(ES)has been criticized because it is not robust to ***,[***.,38,393–417(2013)]proposed a risk measure called median shortfall(MS)which is distributional robust and easy to *** this paper,we propose a more generalized risk measure called quantile shortfall(QS)which includes MS as a special *** measures the conditional quantile loss of the tail risk and inherits the merits of *** construct an estimator of the QS and establish the asymptotic normality behavior of the *** simulation shows that the newly proposed measures compare favorably in robustness with other widely used measures such as ES and VaR.

关键词： Nonparametric estimation quantile shortfall risk measure robust

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Evaluation of the etiology and risk factors for maternal sepsis: A single center study in Guangzhou, China

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World Journal of Clinical Cases 2021年第26期9卷 7704-7716页

作者： Lin Lin Lu-Wen Ren Xue-yuan Li Wen Sun Yan-Hong chen Jing-Si chen Dun-Jin chen Department of Obstetrics and Gynecology The Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510150Guangdong ProvinceChina Key Laboratories for Major Obstetric Diseases of Guangdong Province Guangzhou 510150Guangdong ProvinceChina Department of Fetal Medicine and Prenatal Diagnosis The Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510150Guangdong ProvinceChina

BACKGROUND Maternal sepsis is a major cause of gestational morbidity and neonatal mortality worldwide and particularly in *** To evaluate the etiology of maternal sepsis and further identify its risk *** In this retrospective study,we evaluated 70698 obstetric patients who were admitted to the Third Affiliated Hospital of Guangzhou Medical University between January 1,2009 and June 30,*** were divided into sepsis group and non-sepsis group based on the incidence of *** about medical history(surgical and obstetric history)and demographic information were *** Mann-Whitney U test was used to compare patient age,gestational age and duration of hospitalization between the two *** and multivariate logistic regression models were used to analyze the etiology and the risk factors for maternal *** and adjusted odds ratios(OR)are *** A total of 561 of 70698 obstetric patients were diagnosed with infection;of the infected patients,492 had non-sepsis associated infection(87.7%),while 69 had sepsis(12.3%).The morbidity rate of maternal sepsis was 9.76/10000;the fatality rate in the sepsis group was 11.6%(8/69).Emergency admission(OR=2.183)or transfer(OR=2.870),irregular prenatal care(OR=2.953),labor induction(OR=4.665),cervical cerclage(OR=14.214),first trimester(OR=6.806)and second trimester(OR=2.09)were significant risk factors for maternal *** Mode of admission,poor prenatal care,labor induction,cervical cerclage,first trimester and second trimester pregnancy were risk factors for maternal *** coli was the most common causative organism for maternal sepsis,and the uterus was the most common site of infection.

关键词： Maternal sepsis Sepsis-3 Infection Risk factors

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Geological characteristics of the Qiaoyue Seamount and associated ultramafic-hosted seafloor hydrothermal system(~52.1°E,Southwest Indian Ridge)

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Acta Oceanologica Sinica 2021年第11期40卷 138-146页

作者： Yongjin Huang Chunhui Tao Jin Liang Shili Liao yuan Wang Dong chen Weifang Yang Key Laboratory of Submarine Geosciences Ministry of Natural ResourcesHangzhou 310012China Second Institute of Oceanography Ministry of Natural ResourcesHangzhou 310012China School of Oceanography Shanghai Jiao Tong UniversityShanghai 200030China College of Oceanography Hohai UniversityNanjing 210098China

Hydrothermal vent incidence was once thought to be proportional to the spreading rate of the mid-ocean ridges(MORs).However,more and more studies have shown that the ultraslow-spreading ridges(e.g.,Southwest Indian Ridge(SWIR))have a relatively higher incidence of hydrothermal venting *** Qiaoyue Seamount(52.1°E)is located at the southern side of segment#25 of the SWIR,to the west of the Gallieni transform *** Chinese Dayang cruises conducted eight preliminary deep-towed surveys of hydrothermal activity in the area during 2009 and ***,through comprehensive analyses of the video and photos obtained by the deep-towed platforms,rock samples,and water column turbidity anomalies,a high-temperature,ultramafic-hosted hydrothermal system is predicted on the northern flank of the Qiaoyue *** propose that this hydrothermal system is most likely to be driven by gabboric *** hydrothermal circulation channels appear against a backdrop of high rock permeability related to the detachment fault.

关键词： Southwest Indian Ridge Qiaoyue Seamount hydrothermal activity detachment fault

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