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Dogs lacking Apolipoprotein E show advanced atherosclerosis leading to apparent clinical complications

Science China(Life Sciences) 2022年第7期65卷 1342-1356页

作者： Hui Zhao Jianping Zhao Di Wu Zhaolin Sun yang Hua Min Zheng Yumei Liu Qi yang Xiahe Huang Yuan Li Yueshan piao Yingchun Wang Sin Man Lam Huijuan xu Guanghou Shui Yongjun Wang Haifeng Yao Liangxue Lai Zhuo Du Jidong Mi Enqi Liu xunming Ji Yong Q.Zhang Key Laboratory of Molecular Developmental Biology and CAS Center for Excellence in Brain Science and Intelligence TechnologyInstitute ofGenetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China Guangzhou Institutes of Biomedicine and Health Chinese Academy of SciencesGuangzhou 510530China Beijing Sinogene Biotechnology Co.Ltd Beijing 102200China xuanwu Hospital Capital Medical UniversityBeijing 100053China TianTan Hospital Capital Medical UniversityBeijing 100070China Beijing Petsguard Animal Hospital Beijing 100192China Laboratory Animal Center Xi’an Jiaotong University Health Science CenterXi’an 710049China

Atherosclerotic cardiovascular disease resulting from dysregulated lipid metabolism is the leading cause of morbidity and mortality *** E(ApoE)plays a critical role in cholesterol *** in lipid-metabolizing proteins including ApoE in multiple model organisms such as mice and rats exhibiting elevated levels of cholesterol have been widely used for dissecting the pathology of atherosclerosis,but few of these animal models exhibit advanced atherosclerotic plaques leading to ischemia-induced clinical symptoms,limiting their use for translational *** we report hypercholesterolemia and severe atherosclerosis characterized by stenosis and occlusion of arteries,together with clinical manifestations of stroke and gangrene,in ApoE knockout dogs generated by CRISPR/Cas9 and cloned by somatic cell nuclear transfer ***,the hypercholesterolemia and atherosclerotic complications in F0 mutants are recapitulated in their *** the ApoE-associated atherosclerosis and clinical manifestations in mutant dogs are more similar to that in human patients compared with those in other animal models,these mutant dogs will be invaluable in developing and evaluating new therapies,including endovascular procedures,against atherosclerosis and related disorders.

关键词： ApoE atherosclerosis hypercholesterolemia gangrene stroke

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Single-cell transcriptomic dissection of the cellular and molecular events underlying the triclosan-induced liver fibrosis in mice

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Military Medical Research 2023年第5期10卷 599-619页

作者： Yun-Meng Bai Fan yang piao Luo Lu-Lin Xie Jun-Hui Chen Yu-Dong Guan Hong-Chao Zhou Teng-Fei xu Hui-Wen Hao Bing Chen Jia-Hui Zhao Cai-Ling Liang Ling-Yun Dai Qing-Shan Geng Ji-Gang Wang Department of Nephrology Shenzhen Key Laboratory of Kidney Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People’s Hospitalthe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China Department of Urology Shenzhen People’s Hospitalthe First Affiliated HospitalSouthern University Science and Technologythe Second Clinical Medical CollegeJinan UniversityShenzhen 518020China Integrated Chinese and Western Medicine Postdoctoral Research Station Jinan UniversityGuangzhou 510632China Artemisinin Research Center and Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Center for Reproductive Medicine Dongguan Maternal and Child Health Care HospitalSouthern Medical UniversityDongguan 523125GuangdongChina

Background: Triclosan [5-chloro-2-(2,4-dichlorophenoxy) phenol, TCS], a common antimicrobial additive in many personal care and health care products, is frequently detected in human blood and urine. Therefore, it has been considered an emerging and potentially toxic pollutant in recent years. Long-term exposure to TCS has been suggested to exert endocrine disruption effects, and promote liver fibrogenesis and tumorigenesis. This study was aimed at clarifying the underlying cellular and molecular mechanisms of hepatotoxicity effect of TCS at the initiation ***: C57BL/6 mice were exposed to different dosages of TCS for 2 weeks and the organ toxicity was evaluated by various measurements including complete blood count, histological analysis and TCS quantification. Single cell RNA sequencing(scRNA-seq) was then carried out on TCS-or mock-treated mice livers to delineate the TCS-induced hepatotoxicity. The acquired single-cell transcriptomic data were analyzed from different aspects including differential gene expression, transcription factor(TF) regulatory network, pseudotime trajectory, and cellular communication, to systematically dissect the cellular and molecular events after TCS exposure. To verify the TCS-induced liver fibrosis,the expression levels of key fibrogenic proteins were examined by Western blotting, immunofluorescence, Masson’s trichrome and Sirius red stainings. In addition, normal hepatocyte cell MIHA and hepatic stellate cell LX-2 were used as in vitro cell models to experimentally validate the effects of TCS by immunological, proteomic and metabolomic ***: We established a relatively short term TCS exposure murine model and found the TCS mainly accumulated in the liver. The scRNA-seq performed on the livers of the TCS-treated and control groups profiled the gene expressions of > 76,000 cells belonging to 13 major cell types. Among these types, hepatocytes and hepatic stellate cells(HSCs)were significantly increased in TCS-

关键词： Triclosan Single cell RNA sequencing Liver fibrogenesis Hepatic stellate cell

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Monte Carlo simulation fused with target distribution modeling via deep reinforcement learning for automatic high-efficiency photon distribution estimation

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Photonics Research 2021年第3期9卷 I0001-I0012页

作者： Jianhui Ma Zun piao Shuang Huang Xiaoman Duan Genggeng Qin Linghong Zhou Yuan xu School of Biomedical Engineering Southern Medical UniversityGuangzhou 510515China

Particle distribution estimation is an important issue in medical diagnosis. In particular, photon scattering in some medical devices extremely degrades image quality and causes measurement inaccuracy. The Monte Carlo(MC) algorithm is regarded as the most accurate particle estimation approach but is still time-consuming, even with graphic processing unit(GPU) acceleration. The goal of this work is to develop an automatic scatter estimation framework for high-efficiency photon distribution estimation. Specifically, a GPU-based MC simulation initially yields a raw scatter signal with a low photon number to hasten scatter generation. In the proposed method, assume that the scatter signal follows Poisson distribution, where an optimization objective function fused with sparse feature penalty is modeled. Then, an over-relaxation algorithm is deduced mathematically to solve this objective function. For optimizing the parameters in the over-relaxation algorithm, the deep Q-network in the deep reinforcement learning scheme is built to intelligently interact with the over-relaxation algorithm to accurately and rapidly estimate a scatter signal with the large range of photon *** results demonstrated that our proposed framework can achieve superior performance with structural similarity >0.94, peak signal-to-noise ratio >26.55 d B, and relative absolute error <5.62%, and the lowest computation time for one scatter image generation can be within 2 s.

关键词： estimation distribution scatter

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Effects of Biogas Slurry Recirculation on Anaerobic Digestion Performance of Maize Straw Silage

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Asian Agricultural Research 2018年第12期10卷 49-51,54页

作者： Xinhe LIU Nan LI Mengya yang Benyue ZHANG Guangbo xu Renzhe piao Hongyan ZHAO College of Agronomy Yanbian University

In order to investigate the effects of slurry recirculation technology on anaerobic digestion performance of maize straw silage,maize straw silage was fermented with recirculated biogas slurry,and the gas production,p H value,methane content,volatile organic acids( VFAs)contents,chemical oxygen demand( COD) removal rate and other indicators were studied. The results showed that the fermentation time was positively correlated with daily gas production,methane content,cumulative gas production,VFAs and COD removal rate. Although the p H value fluctuated,it was still in the normal reaction range. The daily gas production was about 1. 26 L. The acetic acid content increased first,then decreased,then increased,and finally stabilized. The biogas slurry recirculation technology saves water resources by 40 m L/d without affecting the normal gas production of anaerobic fermentation,and reduces the consumption of environmental resources. It has important development significance for the sustainable use of biomass resources.

关键词： Biogas slurry recirculation Maize straw silage Anaerobic digestion performance Biomass resources

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Clinical features of upper gastrointestinal serrated lesions: An endoscopy database analysis of 98746 patients

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World Journal of Gastroenterology 2016年第45期22卷 10038-10044页

作者： Hai-long Cao Wen-xiao Dong Meng-que xu yu-jie Zhang Si-nan Wang Mei-yu piao xiao-Cang Cao Bang-Mao Wang Department of Gastroenterology and Hepatology General Hospital Tianjin Medical University Tianjin Institute of Digestive Disease Department of Pathology General Hospital Tianjin Medical University

AIM To analyse the clinical features of patients with the serrated lesions in the upper gastrointestinal tract(UPGI) *** Patients who underwent routine esophagogastroduodenoscopy(EGD) at the Digestive Endoscopy Centre of General Hospital, Tianjin Medical University between january 2011 and December 2015 were consecutively recruited. Patients with UPGI serrated lesions were consecutively identified. The patients' demographics and histopathology were recorded. The colorectal findings for patients who underwent colonoscopy simultaneously or within six months were also extracted from the colonoscopy database. In addition, we analyseddifferences in colorectal neoplasia detection between the study patients and randomly selected patients matched for age and gender who did not exhibit serrated lesions and who also underwent colonoscopy in the same *** A total of 21 patients out of 98746 patients(0.02%) who underwent EGD were confirmed to have serrated lesions with predominantly crenated, sawtooth-like configurations. The mean age of the 21 patients was(55.3 ± 17.2) years, and 11 patients were male(52.4%). In terms of the locations of the serrated lesions, 17 were found in the stomach(including 3 in the cardia, 9 in the corpus and 5 in the antrum), 3 were found in the duodenum, and 1 was found in the esophagus. Serrated lesions were found in different mucosal lesions, with 14 lesions were detected in polyps(8 hyperplastic polyps and 6 serrated adenomas with low grade dysplasia), 3 detected in Ménétrier gastropathy, 3 detected in an area of inflammation or ulcer, and 1 detected in the intramucosal carcinoma of the duodenum. In addition, colonoscopy data were available for 18 patients, and a significantly higher colorectal adenoma detection rate was observed in the UPGI serrated lesions group than in the randomly selected age- and gender-matched group without serrated lesions who also underwent colonoscopy in the same period(38.9% vs 11.1%, OR = 5.091, 95%

关键词： Clinical features Upper gastrointestinal tract Serrated lesions Colorectal adenoma Colorectal cancer

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日语格助词“と”的本质义及句法语义研究

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解放军外国语学院学报 2020年第4期43卷 87-95页

作者：许慈惠朴仙灵上海外国语大学日本经济文化学院上海200083 郑州大学外国语与国际关系学院河南郑州450001

日语格助词作为语法功能词先天性地具有语法本质义,在"名词+格助词+谓语"的句式中表示名词格成分与谓语之间的语法关系。本研究假设格助词"と"在"名词等+と+谓语"句式中的本质义为接在名词等后,以"と"格成分补充谓语信息。根据"と"格语... 详细信息

日语格助词作为语法功能词先天性地具有语法本质义,在"名词+格助词+谓语"的句式中表示名词格成分与谓语之间的语法关系。本研究假设格助词"と"在"名词等+と+谓语"句式中的本质义为接在名词等后,以"と"格成分补充谓语信息。根据"と"格语义与谓语语义是否一致,区分"直接补充"和"间接补充"两类,前者直接补充谓语信息,后者先直接和主语或宾语发生语义关系,由此再间接地补充谓语信息。根据句法语境语义,"补充"又可分为不可或缺的必需格的"必需补充"和非不可或缺的选择格的"非必需补充"两类。

关键词：格助词本质义 “と”格直接补充间接补充必需补充非必需补充

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基于启发式模型仿真的货车转向架悬挂非线性研究

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振动与冲击 2019年第3期38卷 116-124页

作者：杨晶李华朴明伟徐世峰吴荣坤大连交通大学机械工程学院辽宁大连116028 中车齐齐哈尔车辆有限公司大连研发中心辽宁大连116042

为了合理挖掘技术潜能,货车转向架设计及运用需要依靠基础试验手段,通过启发式模型仿真,逐步形成对其悬挂非线性的正确认知,在轻量化车体与走行部之间尽可能避免产生相关激励。利用刚柔耦合仿真技术,典型工程案例分析表明:在轻量化车体... 详细信息

为了合理挖掘技术潜能,货车转向架设计及运用需要依靠基础试验手段,通过启发式模型仿真,逐步形成对其悬挂非线性的正确认知,在轻量化车体与走行部之间尽可能避免产生相关激励。利用刚柔耦合仿真技术,典型工程案例分析表明:在轻量化车体与走行部之间,重载卡滞是相关激励形成的1项主要成因。在重载卡滞的影响下,如中部横向支架斜撑杆局部结构失稳和中部侧墙横向结构不稳定,两者均会转变为振动开裂或振动疲劳问题。等效斜楔摩擦模型具有对干摩擦强非线性影响的启示意义,且形成了如下2点正确认知:相对摩擦因子并非恒定不变,在重载工况下,一般不得大于0.10;加载卡滞单边力学特性迫使心盘垂向动荷趋于脉冲载荷类型,其对轻量化车体结构疲劳损伤的负面影响不容忽视。结合快捷铁路货运需求,合理制订了解决重载卡滞问题的技术方案,利用复合斜楔新技术,参考典型配置形式,适当增大斜楔尖角,消除或减轻干摩擦强非线性影响。

关键词：货车转向架黏滑振动重载卡滞刚柔耦合仿真技术相关激励

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纺锤状羟基氧化铁@聚吡咯复合纳米粒子的制备及其光热治疗肿瘤应用

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复合材料学报 2022年第7期39卷 3469-3477页

作者：黄漂易昌凤徐祖顺湖北大学材料科学与工程学院武汉430062

肿瘤是世界上死亡率最高的疾病,研制新型肿瘤药物也是一项极具开发性的研究。首先制备纺锤状羟基氧化铁纳米粒子(FeOOH NPs)并作为模板,与吡咯(Py)聚合得到纺锤状羟基氧化铁@聚吡咯(FeOOH@PPy)复合纳米粒子。采用FTIR、DLS、TEM和UV-vi... 详细信息

肿瘤是世界上死亡率最高的疾病,研制新型肿瘤药物也是一项极具开发性的研究。首先制备纺锤状羟基氧化铁纳米粒子(FeOOH NPs)并作为模板,与吡咯(Py)聚合得到纺锤状羟基氧化铁@聚吡咯(FeOOH@PPy)复合纳米粒子。采用FTIR、DLS、TEM和UV-vis等测试方法对FeOOH@PPy进行了结构、性质表征,通过光热转换实验证明了该复合纳米粒子具有优异的光热转换性能,探究了复合纳米粒子的生物相容性以及肿瘤治疗中的应用潜力。结果表明,所得到的复合纳米粒子平均粒径100 nm左右,且分布均一,粒子呈纺锤状结构,在水溶液中具有良好的稳定性。FeOOH@PPy复合纳米粒子可以吸收808 nm的近红外光,并将其转化为足够的热量,使肿瘤细胞凋亡;在为期14天的4T1细胞的小鼠模型体内治疗实验中,FeOOH@PPy复合纳米粒子治疗组表现出优异的治疗肿瘤效果,组织分析表明FeOOH@PPy复合纳米粒子对小鼠正常组织无明显影响,具有作为光热治疗剂的潜力。

关键词：纳米材料聚吡咯光热性能生物相容性肿瘤治疗

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Identify old drugs as potent and selective microbiome β-glucuronidase inhibitors

Identify old drugs as potent and selective microbiome β-glu...

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第十届全国化学生物学学术会议

作者： Ren Kong Lianhua piao Xiaoshuang xu Institute of Bioinformatics and Medical Engineering School of Electrical and Information EngineeringJiangsu University of Technology

By using β-glucuronidase enzyme,microbiota in gastrointestinal(GI) scavenge sugar from glucuronidated compounds as a source of carbon,resulting in activation of drugs from its non-toxic form to toxic *** symptoms includes the severe lately occurred diarrhea in irinotecan treated patients and GI ulcer in non-steroidal anti-inflammatory drugs(NSAID) treated patients are shown to directly related to microbiome β-*** inhibition of microbiome β-glucuronidase may provide potential therapeutic opportunities for these unmet medical ***,by using an integrated platform of virtual screening and in vitro enzyme activity determination,several old drugs were identified as potent and selective microbiomeβ-glucuronidase *** ICS from *** enzyme-based assay and cell based assay range from 0.039-3.604 μM and 0.010-5.373 μM,*** obvious influence on Bovine β-glucuronidase was observed with 100μM compounds ***,the results from bacterial cytotoxicity assay demonstrate that these old drugs showed no signs of toxicity for bacterial *** identified old drugs may have great clinical potentials to treat microbiome P-glucuronidase related diseases.

关键词： β-glucuronidase inhibitors old drug new use virtual screening

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Evaluating correlation between the ocular biometry and genetic variants of MYOC and ABCA1 with primary angleclosure glaucoma in a cohort from northern China

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International Journal of Ophthalmology(English edition) 2019年第8期12卷 1317-1322页

作者： Shao-Lin Wang Shun-Yu piao Man-Yun xu Wen Zhang Jian-Qing Ma Juan Hao Hao Chi Zhong-Qi xue Shao-Ping Ha Wen-Juan Zhuang Clinical Medical College of Ningxia Medical University Yinchuan750001Ningxia Hui Autonomous RegionChina Ningxia Eye Hospital People’s Hospital of Ningxia HuiAutonomous Region(First Affiliated Hospital of NorthwestUniversity For Nationalities)Yinchuan750011Ningxia HuiAutonomous RegionChina Department of Ophthalmology Wuzhong People’sHospitalWuzhong751100Ningxia Hui AutonomousRegionChina Department of Ophthalmology Taiyuan Central HospitalTaiyuan030000Shanxi ProvinceChina Shandong Academy of Medical Sciences Jinan UniversityJinan250000Shandong ProvinceChina

AIM: To investigate whether the gene variants in MYOC and ABCA1 are associated with primary angle-closure glaucoma(PACG) and anterior chamber depth(ACD) and axial length(AL) in samples from northern China. METHODS: The present case-control association study consisted of 500 PACG patients and 720 unrelated controls. Each participant was genotyped for eleven single nucleotide polymorphisms(SNPs) in MYOC and ABCA1 genes(rs12076134, rs183532, rs235875 and rs235913 in MYOC, rs2422493, rs2487042, rs2472496, rs2472493, rs2487032, rs2472459 and rs2472519 near ABCA1) using an improved multiplex ligation detection reaction(iMLDR) technique. The genetic association analyses were performed by PLINK using a logistic regression model. The association between genotypes and ocular biometric parameters was performed by SPSS using generalized estimation equation. Bonferroni corrections wereimplemented and the statistical power was calculated by the Power and Sample Size Calculation. RESULTS: Two SNPs rs183532 and rs235875 as well as a haplotype TTC in MYOC were nominally associated with PACG despite the significance was lost after Bonferroni correction. No association was observed between ABCA1 and PACG, neither did the association between these variants and ACD as well as AL. CONCLUSION: The present study suggests MYOC and ABCA1 do not play a part in the pathogenesis of PACG as well as the regulation of ocular biometric parameters in a northern Chinese population. Further investigations with large sample size are needed to verify this consequence.

关键词： MYOC ABCA1 primary angle-closure glaucoma anterior chamber depth axial length single nucleotide polymorphisms

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