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Recombinant adeno-associated virus 8-mediated inhibition of microRNA let-7a ameliorates sclerosing cholangitis in a clinically relevant mouse model

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World Journal of Gastroenterology 2024年第5期30卷 471-484页

作者： Hui Hua Qian-Qian Zhao Miriam Nkesichi Kalagbor Guo-Zhi Yu Man Liu Zheng-Rui Bian Bei-Bei Zhang Qian Yu Yin-Hai Xu ren-xian tang Kui-Yang Zheng Chao Yan Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogenic Biology and ImmunologyNational Demonstration Center for Experimental Basic Medical Science EducationLaboratory of Infection and ImmunityXuzhou Medical UniversityXuzhou 221004Jiangsu ProvinceChina Department of Laboratory Medicine The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221002Jiangsu ProvinceChina

BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment *** adeno-associated virus(rAAV)provides a promising platform for gene therapy on such kinds of diseases.A microRNA(miRNA)let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been *** To investigate the therapeutic effects of inhibition of a miRNA let-7a transferred by recombinant adeno-associated virus 8(rAAV8)on a xenobiotic-induced mouse model of sclerosing *** A xenobiotic-induced mouse model of sclerosing cholangitis was induced by 0.1% 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine(DDC)feeding for 2 wk or 6 wk.A single dose of rAAV8-mediated anti-let-7a-5p sponges or scramble control was injected in vivo into mice onset of DDC *** sacrifice,the liver and the serum were collected from each *** hepatobiliary injuries,hepatic inflammation and fibrosis were *** targets of let-7a-5p and downstream molecule NF-κB were detected using Western *** rAAV8-mediated anti-let-7a-5p sponges can depress the expression of let-7a-5p in mice after DDC feeding for 2 wk or 6 *** reduced expression of let-7a-5p can alleviate hepato-biliary injuries indicated by serum markers,and prevent the proliferation of cholangiocytes and biliary ***,inhibition of let-7a mediated by rAAV8 can increase the expression of potential target molecules such as suppressor of cytokine signaling 1 and Dectin1,which consequently inhibit of NF-κB-mediated hepatic *** Our study demonstrates that a rAAV8 vector designed for liver-specific inhibition of let-7a-5p can potently ameliorate symptoms in a xenobiotic-induced mouse model of sclerosing cholangitis,which provides a possible clinical translation of PSC of human.

关键词： Primary sclerosing cholangitis Recombinant adeno-associated virus 8 Let-7a-5p Therapeutic effects Inflammation

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Diversity of Helicobacter pylori isolates in expression of antigens and induction of antibodies

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World Journal of Gastroenterology 2008年第30期14卷 4816-4822页

作者： ren-xian tang Dong-Jiao Luo Ai-Hua Sun Jie Yan Department of Medical Microbiology and Parasitology Xuzhou Medical College Xuzhou 221009 Jiangsu Province China Qianjiang College Hangzhou Normal University Hangzhou 310018 Zhejiang Province China Faculty of Basic Medicine Zhejiang Medical College Hangzhou 310053 Zhejiang Province China Department of Medical Microbiology and Parasitology College of Medicine Zhejiang University Hangzhou 310053 Zhejiang Province China

AIM: To obtain evidence for selection of antigens used in genetically engineered vaccine against Helicobacter pylori (H pylori). METHODS: Enzyme linked immunoabsorbent assay (ELISA) was established on the basis of recombinant protein antigens rUreB, rHpaA, rVacA, rCagA1, rNapA, rFlaA and rFlaB of H pylori to detect expression rates of the antigens in bacterial isolates as well as positive rates of the antibodies in sera from H pylori-infected patients. PCR was applied to the detection of carrying rates of the genes encoding antigens in the isolates. RESULTS: The outputs of rUreB, rHpaA, rVacA, rCagA1, rNapA, rFlaA and rFlaB were approximately 35%, 32%, 15%, 23%, 56%, 25% and 20% of the total bacterial proteins, respectively. One hundred and fifty-one strains of H pylori were isolated from 347 biopsy specimens of chronic gastritis, peptic ulcer or gastric adenocarcinoma, with a positive rate of 43.5%. All of the isolates expressed UreB, HpaA, FlaA and FlaB while 52.3%, 92.1% and 93.4% of the isolates expressed VacA, CagA and NapA, respectively. In the sera of 151 H pylori-infected patients, the positive ratesof IgG antibodies against UreB, HpaA, VacA, CagA, NapA, FlaA and FlaB were 100%, 87.4%, 43%, 71.5%, 89.4%, 84.8% and 79.5%, respectively. Furthermore, the expression frequencies of VacA and NapA were found to be relative to the severity of gastric diseases (P = 0.016 and P < 0.0001, respectively). CONCLUSION: UreB antigen is the top option of developing genetically engineered vaccine against H pylori followed by NapA or HpaA.

关键词： Helicobacter pylori Major protein antigens Expression frequency Antibody levels

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HBx activates FasL and mediates HepG2 cell apoptosis through MLK3-MKK7-JNKs signal module

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World Journal of Gastroenterology 2012年第13期18卷 1485-1495页

作者： ren-xian tang Fan-Yun Kong Bao-Feng Fan Xiao-Mei Liu Hong-Juan You Peng Zhang Kui-Yang Zheng Department of Pathogenic Biology and Lab of Infection and Immunology Xuzhou Medical CollegeXuzhou 221002Jiangsu ProvinceChina

AIM： To investigate the possible mechanism by which hepatitis B virus X protein （HBx） mediates apoptosis of HepG2 cells. METHODS： HBx expression vector pcDNA3.1-X was transfected into HepG2 cells to establish an HBx high- expression cellular model as pcDNA3.1-X transfected group. The pcDNA3.1-X and pSilencer3.1-shHBX （HBx antagonist） were cotransfected into HepG2 cells to es- tablish an HBx low-expression model as RNAi group. Untransfected HepG2 cells and HepG2 cells transfected with negative control plasmid were used as controls. Apoptosis rate, the expression of Fas/FasL signaling pathway-related proteins and the phosphorylation lev- els of MLK3, MKK7 and JNKs, which are upstream molecules of death receptor pathways and belong to the family of mitogen-activated protein kinases （MAPKs）,were measured in each group RESULTS： Compared with HepG2 cell group and RNAi group, apoptosis rate, the expression of Fas and FasL proteins, and the activation of MLK3, MKK7 and 3NKs were increased in the pcDNA3.1-X transfected group. The activation of JNKs and expression of FasL protein were inhibited in the pcDNA3.1-X transfected group when treated with a known JNK inhibitor, SP600125. When authors treated pcDNA3.1-X transfected group with K252a, a known MLK3 inhibitor, the activation of MLK3, MKK7 and 3NKs as well as expression of FasL protein was inhibited. Furthermore, cell apoptosis rate was also significantly declined in the presence of K252a in the pcDNA3.1-X transfected group. CONCLUSION： HBx can induce HepG2 cell apoptosis via a novel active MLK3-MKK7-JNKs signaling module to upregulate FasL protein expression.

关键词： Hepatitis B virus X protein MLK3 FasL HepG2cell Apoptosis

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Quasi-shadowing for Z^(d)-actions

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Acta Mathematica Sinica,English Series 2024年第6期40卷 1563-1580页

作者： Juan PAN xian Kun ren Yun Hua ZHOU School of Mathematics and Statistics Chongqing Technology and Business UniversityChongqing 400067P.R.China College of Mathematics and Statistics Chongqing UniversityChongqing 401331P.R.China

A diffeomorphism is non-uniformly partially hyperbolic if it preserves an ergodic measure with at least one zero Lyapunov *** prove that a C^(1)-smooth Z^(d)-action has the quasishadowing property if one of the genera... 详细信息

关键词： Quasi-shadowing Z^(d)-action non-uniformly partially hyperbolic ergodic measure

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Genetic diversity and phylogenetic analysis of EG95 sequences of Echinococcus granulosus:Implications for EG95 vaccine application

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Asian Pacific Journal of Tropical Medicine 2017年第5期10卷 497-500页

作者： Wei Pan De-Sheng Chen Yun-Juan Lu Hui-Wen Xu Wen-Ting Hao Ya-Wen Zhang Su-Ping Qin Kui-Yang Zheng ren-xian tang Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogenic Biology and ImmunologyLaboratory of Infection and ImmunityXuzhou Medical University Department of Clinical Medicine Xuzhou Medical University

Objective:To analyse the genetic variability of EG95 sequences and provide guidance for EG95 vaccine application against Echinococcus granulosus(E. granulosus). Methods:We analysed EG95 polymorphism by collecting total 97 different E. granulosus isolates from 12 different host species that originated from 10 different countries. Multiple sequence alignments and the homology were performed by Lasergene 1(DNASTAR Inc.,Madison,WI),and the phylogenetic analysis was performed by using MEGA5.1(CEMI,Tempe,AZ,USA). In addition,linear and conformational epitopes were analysed,including secondary structure,NXT/S glycosylation,fibronectin type ecoⅢ(Fnndary Ⅲ) domain and glycosylphosphatidylinositol anchor signal(GPIanchor). The s structure was predicted by PSIPRED method. Results:Our results indicated that most isolates overall shared 72.6-100% identity in EG95 gene sequence with the published standard EG95 sequence,X90928. However,EG95 gene indeed has polymorphism in different isolates. Phylogenetic analysis showed that different isolates could be divided into three subgroups. Subgroup 1 contained 87 isolates while Subgroup 2 and Subgroup 3 consisted of 3 and 7 isolates,respectively. Four sequences cloned from oncosphere shared a high identity with the parental sequence of the current vaccine,X90928,and they belonged to Subgroup 1. However,in comparison to X90928,several amino acid mutations occurred in most isolates besides oncosphere,which potentially altered the immunodominant linear epitopes,glycosylation sites and secondary structures in EG95 genes. All these variations might change their previous antigenicity and thereby affecting the efficacy of current EG95 vaccine. Conclusions:This study reveals the genetic variability of EG95 sequences in different E. granulosus isolates,and proposed that more vaccination trials would be needed to test the effectiveness of current EG95 vaccine against distinct isolates in different countries.

关键词： Echinococcus granulosus Cystic echinococcosis EG95 Vaccine Genetic diversity

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High-precision modeling of tide-induced 3-D magnetic field and analysis of geomagnetic satellite orbit requirements

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Science China Earth Sciences 2024年第1期67卷 165-178页

作者： Zhengyong ren Cong YANG Hongbo YAO Xu tang Jingtian tang Keke ZHANG Key Laboratory of Metallogenic Prediction of Nonferrous Metals and Geological Environment Monitoring Ministry of Education Central South UniversityChangsha 410083China Hunan Key Laboratory of Nonferrous Resources and Geological Hazards Exploration Changsha 410083China School of Geosciences and Info-Physics Central South UniversityChangsha 410083China State Key Laboratory of Lunar and Planetary Sciences Macao University of Science and TechnologyMacao 999078China

Ground-based magnetic observatories and geomagnetic satellites can observe the induced magnetic field generated by the motion of seawater containing sodium and chlorine *** the three-dimensional(3-D)spatial distribution of tide-induced magnetic fields(TIMF)is crucial for inverting the electrical conductivity structure of the oceanic *** also serves as an essential basis for designing optimal geomagnetic observatories and satellite ***,existing methods for simulating TIMF suffer from limitations in inaccurately modeling realistic coastlines,heterogeneous land and sea surface properties,and complex deep Earth structures,thereby the interpretational level of TIMF data is *** overcome this issue,we developed a tetrahedral-based finite element method for simulating TIMF,which can efficiently approximate realistic coastlines,heterogeneous land and sea surface properties,and complex deep Earth ***,we derived the boundary value problem for the seawater motion-induced electromagnetic field,which was solved using the vector finite element method based on tetrahedral ***,using the latest ocean depth and seafloor sediment layer models,we constructed a 3-D conductivity model of the Earth,which includes realistic coastlines,heterogeneous land and sea conductivity *** then computed the TIMF using the M_(2)tidal source as an example and validated our method by comparing it with results obtained from spherical harmonic finite element and integral equation ***,utilizing the computed high-precision M_(2),N_(2),and O1 TIMF signals,we marked global observatories capable of observing strong M_(2),N_(2),and O1 TIMF signals and predicted alternative stations suitable for tide signal ***,we calculated TIMF at heights of 450 and 200 km for the Macao Science Satellite 1 and its subsequent *** results indicate that the amplitude of the tidal-induced magnetic field at

关键词： Ocean motional induction Electromagnetic induction Ocean tides Geomagnetic satellite Macao Science Satellite 1

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A novel route to enhance high-temperature mechanical property and thermal shock resistance of low-carbon Mgo-C bricks by introducing ZrSiO_(4)

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Journal of Iron and Steel Research International 2024年第6期31卷 1436-1448页

作者： Chun-hui Sun Ling-ling Zhu Hao Yan Wei Zhao Jing-xuan Liu Lin ren xian-tang Zhao Xiao-song Tong Shu-wen Yu Beijing Lirr High-Temperature Materials Co. Ltd.Beijing 102211China School of Materials Science and Engineering Henan Province Industrial Technology Research Institute of Resources and MaterialsZhengzhou UniversityZhengzhou 450001HenanChina School of Chemistry and Chemical Engineering Suzhou UniversitySuzhou 234000AnhuiChina

Conventional MgO-C bricks(graphite content>14 wt.%)produce a great deal of greenhouse gas emission,while low-carbon MgO-C bricks have serious thermal shock resistance during high-temperature *** enhance the high-temperature mechanical property and thermal shock resistance of low-carbon MgO-C bricks,a novel route of introducing ZrSiO_(4) powder into low-carbon MgO-C bricks was reported in such refractories with 2 wt.% flaky *** results indicate that the low-carbon MgO-C brick with 0.5 wt.%ZrSiO_(4) addition has the maximum hot modulus of rupture at 1400℃ and the corresponding specimen fired in the carbon embedded atmosphere has the maximum residual strength ratio(98.6%)after three thermal shock *** is found that some needle-like AlON and plate-like Al_(2)O_(3)-ZrO_(2) composites were in situ formed in the matrices after the low-carbon MgO-C bricks were coked at 1400℃,which can enhance the high-temperature mechanical property and thermal shock resistance due to the effect of fiber toughening and particle ***,CO_(2) emission of the newly developed low-carbon MgO-C bricks is reduced by 58.3% per ton steel after using them as the working lining of a 90 t vacuum oxygen decarburization ladle.

关键词： Low-carbon MgO-C brick ZrsiO_(4) Synergistic toughening effect High-temperature mechanical property Thermal shock resistance Vacuum oxygen decarburization ladle

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An anti-icing scaling method for wind tunnel tests of aircraft thermal ice protection system

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Chinese Journal of Aeronautics 2024年第6期37卷 1-6页

作者： Yu LIU Qiang WANG xian YI Ningli CHEN Jinghao ren Weihao LI Key Laboratory of Icing and Anti/de-icing China Aerodynamics Research and Development CenterMianyang 621000China State Key Laboratory of Aerodynamics Mianyang 621000China

The efficiency of the aircraft Ice Protection Systems(IPSs)needs to be verified through icing wind tunnel ***,the scaling method for testing the IPSs has not been systematically established yet,and further research is *** the present study,a scaling method specifically designed for thermal IPSs was derived from the governing equation of thin water *** scaling parameters were adopted to address the heat and mass transfer involved in the thermal anti-icing *** method validation,icing wind tunnel tests were conducted using a jet engine nacelle model equipped with a bleed air *** non-dimensional surface temperature and runback ice closely matched for both the reference and scaled *** validation confirms that the scaling method is capable of achieving the similarity of surface temperature and the runback ice *** anti-icing scaling method can serve as an important supplement to the existing icing similarity theory.

关键词： Scaling method Ice protection system Water film Anti-icing test Icing wind tunnel

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Projected changes in Köppen-Trewartha climate zones under 1.5-4℃global warming targets over mid-high latitudes of Northern Asia using an ensemble of RegCM4 simulations

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Advances in Climate Change Research 2024年第2期15卷 185-196页

作者： Jie WU Xue-Jie GAO xian-Bing tang Filippo GIORGI School of Geography and Environmental Engineering Gannan Normal UniversityGanzhou 341000China Climate Change Research Center Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters Nanjing University of Information Science&TechnologyNanjing 210044China University of Chinese Academy of Sciences Beijing 100049China The Abdus Salam International Centre for Theoretical Physics Trieste 34100Italy

Mid-high latitude Northern Asia is one of the most vulnerable and sensitive areas to global warming,but relatively less studied *** used an ensemble of a regional climate model(RegCM4)projections to assess future changes in surface air temperature,precipitation and Köppen-Trewartha(K-T)climate types in Northern Asia under the 1.5-4℃global warming ***4 is driven by five CMIP5 global models over an East Asia domain at a grid spacing of 25 *** of the present day(1986-2005)simulations shows that the ensembles of RegCM4(ensR)and driving GCMs(ensG)reproduce the major characters of the observed temperature,precipitation and K-T climate zones reasonably *** and more realistic spatial detail is found in RegCM4 compared to the driving GCMs.A general warming and overall increases in precipitation are projected over the region,with these changes being more pronounced at higher warming *** projected warming by ensR shows different spatial patterns,and is in general lower,compared to ensG in most months of the year,while the percentage increases of precipitation are maximum during the cold *** future changes in K-T climate zones are characterized by a substantial expansion of Dc(temperature oceanic)and retreat of Ec(sub-arctic continental)over the region,reaching∼20%under the 4℃warming *** most notable change in climate types in ensR is found over Japan(∼60%),followed by Southern Siberia,Mongolia,and the Korean Peninsula(∼40%).The largest change in the K-T climate types is found when increasing from 2 to 3℃.The results will help to better assess the impacts of climate change and in implementation of appropriate adaptation measures over the region.

关键词： Mid-high latitudes of Northern Asia Köppen climate zones Global warming targets Regional climate model

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Attention-based network embedding with higher-order weights and node attributes

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CAAI Transactions on Intelligence Technology 2024年第2期9卷 440-451页

作者： xian Mo Binyuan Wan Rui tang Junkai Ding Guangdi Liu School of Information Engineering Ningxia UniversityYinchuanChina School of Cyber Science and Engineering Sichuan UniversityChengduChina Computer Science and Information Technology University of MalayaKuala LumpurMalaysia Academy of Medical Sciences Zhengzhou UniversityZhengzhouChina

Network embedding aspires to learn a low-dimensional vector of each node in networks,which can apply to diverse data mining *** real-life,many networks include rich attributes and temporal ***,most existing embedding approaches ignore either temporal information or network attributes.A self-attention based architecture using higher-order weights and node attributes for both static and temporal attributed network embedding is presented in this article.A random walk sampling algorithm based on higher-order weights and node attributes to capture network topological features is *** static attributed networks,the algorithm incorporates first-order to k-order weights,and node attribute similarities into one weighted graph to preserve topological features of *** temporal attribute networks,the algorithm incorporates previous snapshots of networks containing first-order to k-order weights,and nodes attribute similarities into one weighted *** addition,the algorithm utilises a damping factor to ensure that the more recent snapshots allocate a greater *** features are then incorporated into topological ***,the authors adopt the most advanced architecture,Self-Attention Networks,to learn node *** results on node classification of static attributed networks and link prediction of temporal attributed networks reveal that our proposed approach is competitive against diverse state-of-the-art baseline approaches.

关键词： data mining deep neural networks social network

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