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| 1 | Protein trans-splicing based dual-vector delivery of the coagulation factor Ⅷ gene显示文摘A dual-vector system was explored for the delivery of the coagulation factor VIII gene,using intein-mediated protein trans-splicing as a means to produce intact functional factor VIII post-translationally.A pair of eukaryotic expression vectors,expressing Ssp DnaB intein-fused heavy and light chain genes of B-domain deleted factor VIII (BDD-FVIII),was constructed.With transient co-transfection of the two vectors into 293 and COS-7 cells,the culture supernatants contained (137±23) and (109±22) ng mL–1 spliced BDD-FVIII antigen with an activity of (1.05±0.16) and (0.79±0.23) IU mL–1 for 293 and COS-7 cells,respectively.The spliced BDD-FVIII was also detected in supernatants from a mixture of cells transfected with inteinfused heavy and light chain genes.The spliced BDD-FVIII protein bands from cell lysates were visualized by Western blotting.The data demonstrated that intein could be used to transfer the split factor VIII gene and provided valuable information on factor VIII gene delivery by dual-adeno-associated virus in hemophilia A gene therapy. | ZHU FuXiang,LIU ZeLong,CHI XiaoYan & QU HuiGe Life Science College of Ludong University,Yantai 264025,China | 2010 | Science China(Life Sciences)2010，53，6： | 27 |
| 2 | NLRP3-dependent pyroptosis is required for HIV-1 gp120- induced neuropathology显示文摘The human immunodeficiency virus-1(HIV-1)envelope protein gp120 is the major contributor to the pathogenesis of HIVassociated neurocognitive disorder(HAND).Neuroinflammation plays a pivotal role in gp120-induced neuropathology,but how gp120 triggers neuroinflammatory processes and subsequent neuronal death remains unknown.Here,we provide evidence that NLRP3 is required for gp120-induced neuroinflammation and neuropathy.Our results showed that gp120-induced NLRP3-dependent pyroptosis and IL-1βproduction in microglia.Inhibition of microglial NLRP3 inflammasome activation alleviated gp120-mediated neuroinflammatory factor release and neuronal injury.Importantly,we showed that chronic administration of MCC950,a novel selective NLRP3 inhibitor,to gp120 transgenic mice not only attenuated neuroinflammation and neuronal death but also promoted neuronal regeneration and restored the impaired neurocognitive function.In conclusion,our data revealed that the NLRP3 inflammasome is important for gp120-induced neuroinflammation and neuropathology and suggest that NLRP3 is a potential novel target for the treatment of HAND. | Xiaolong He Weijun Yang Zhijie Zeng Yi Wei Jie Gao Bao Zhang Li Li Liqun Liu Yu Wan Qing Zeng Zelong Gong Liting Liu Hanyun Zhang Yubin Li Shaojie Yang Tongtong Hu Lixian Wu Eliezer Masliah Shenghe Huang Hong Cao | 2020 | Cellular & Molecular Immunology2020，17，3： | 11 |
| 3 | Identification and Characterization of Sulfur Compounds in Straight-Run Diesel Using Comprehensive Two-Dimensional GC Coupled with TOF MS显示文摘The solid-phase extraction using Pd-Al2O3 as the stationary phase was employed to pre-separate the sulfur compounds in straight-run diesel. The isolating effect was evaluated quantitatively by gas chromatography with a sulfur chemiluminescence detector to harvest a satisfactory result. The identification of the structure of sulfur compounds by comprehensive two-dimensional gas chromatography coupled with the time-of-flight mass spectrometry indicated that cyclo-sulfides, benzothiophenes, dibenzothiophenes, dihydro-benzothiophenes and tetrahydro-dibenzothiophenes were included in straightrun diesel obtained from the Arab medium crude(AM). A total of 259 individual compounds were detected and their molecular structures were identified. The analytical method was approved as an effective way to characterize the composition of sulfur compounds, which reduced the interference of other compounds, facilitated the data presentation and provided more detailed information about molecular composition of sulfur compounds. | Niu Luna Liu Zelong Tian Songbai | 2014 | China Petroleum Processing & Petrochemical Technology2014，16，3： | 10 |
| 4 | Halide perovskite quantum dots: potential candidates for display technology显示文摘Motivated by the color tunability and narrow-band emission peak of colloidal quantum dots(QDs),the concepts of quantum dot light-emitting diodes(QD-LEDs),based on either the photoluminescence(PL)or electroluminescence(EL)mechanism,have been proposed for a few years[1].Using QD-LEDs in the backlighting system of liquid crystal display(LCD)can significantly expand the | Zelong Bai Haizheng Zhong | 2015 | Science Bulletin2015，60，18： | 9 |
| 5 | Radiofrequency ablation combined with transcatheter arterial chemoembolization therapy versus surgical resection for Barcelona-Clinic Liver Cancer(BCLC) A hepatocellular carcinoma: a meta-analysis显示文摘Purpose: The objective of our study was to compare the effectiveness of the combination of transcatheter arterial chemoembolization(TACE) and radiofrequency ablation(RFA) with that of surgical resection(SR) in Barcelona-Clinic Liver Cancer(BCLC) A hepatocellular carcinoma. Materials and Methods: PubMed, Medline, Embase, and Cochrane Library were searched for comparisons of the two therapies from January 2006 to December 2017. Overall survival rate(OS), recurrence-free survival rate(RFS), complications, and the average length of hospital stay were compared and analyzed. Review Manager v. 5.2 from the Cochrane Collaboration was used for statistical analyses. Results: Seven case-control studies and one randomized controlled trial were identified, of which 717 were treated with a combination of TACE and RFA and 785 were treated with SR. Meta-analysis data revealed that TACE plus RFA had significantly better effectiveness on 1.0-y OS(OR = 0.50, p =.009). The major complications(ORcomplications = 1.88, p =.02) after the combined therapy were significantly lower than those after SR. There were three studies that reported the average length of hospital stay. The hospital stay for the SR group vs the combined therapy group was 19.8 ± 8.4 d vs 7.4 ± 2.2 d, respectively(p <.0001); 18.7 ± 4.9 d vs 11.5 ± 6.9 d, respectively(p <.0001); and 16.6 ± 6.7 d vs 8.5 ± 4.1 d, respectively(p <.0001). There was no significant difference in 3.0-or 5.0-y OS and 1.0-, 3.0-, or 5.0-y RFS. Conclusion: The combination of TACE and RFA has advantages in improving 1.0-y OS, reducing complications, and shortening the length of hospital stay over that of SR in the treatment of patients with BCLC A HCC. | Weidong Wang Sinan Hou Zelong Zhong JiaYan Ni Xiongying Jiang Dong Chen Yaoting Chen Jianghong Luo Hongliang Sun Linfeng Xu | 2018 | Journal of Interventional Medicine2018，1，1： | 9 |
| 6 | The effect of a secretion-enhanced heavy chain on improving intein-based dual-vector co-delivery of a full-length factor Ⅷ gene显示文摘Treatment of hemophilia A by gene therapy is adversely affected by inefficient FVIII secretion and the large FVIII gene,which is difficult to package in the promising adeno-associated virus (AAV) vectors.Inhibited secretion of FVIII is caused mainly by inefficient secretion of its heavy chain.Previously,we have employed a protein splicing-based dual-vector to co-transfer a B-domain-deleted FVIII (BDD-FVIII) gene,suggesting that the light chain,covalently ligated to a co-expressed heavy chain can improve the secretion of spliced BDD-FVIII.However,its level of secretion was affected by inefficient secretion the heavy chain.Here,we studied the effect of a mutant heavy chain with L303E/F309S substitutions,which enhance FVIII secretion on the heavy chain itself and spliced FVIII when using a protein splicing-based split-delivery of a full-length FVIII gene.Eukaryotic vectors expressing Ssp DnaB intein-fused mutant heavy and light chains were transiently co-transfected into cultured COS-7 cells.A spliced FVIII protein was seen in co-transfected cells by Western blot analysis.The heavy chain was secreted by cells transfected with the mutant heavy chain gene alone at (39±11) ng/mL and this secretion increased to (123±13) ng/mL when cells were co-transfected with the light chain gene,which was greater than the secretion of wild-type heavy chain.The amount of spliced FVIII in the culture supernatant of co-transfected cells was (86±14) ng/mL,with an activity of (0.61±0.08) IU/mL,which was greater than that of wild-type FVIII co-transfected cells.Spliced FVIII and bioactivity were also detected in the combined culture supernatant of cells individually transfected with mutant heavy and light chain gene at a higher level than that of combined wild-type heavy and light chain transfections.This suggested that the heavy chain with improved secretion markedly increased the efficacy of protein splicing-based split delivery of the full-length FVIII gene using a dual-vector.These results encourage the transfer of this technology to an animal model using a dual-AAV vector. | ZHU FuXiang YANG ShuDe LIU ZeLong MIAO Jing QU HuiGe CHI XiaoYan | 2011 | Chinese Science Bulletin2011，56，2： | 8 |
| 7 | Changes of Petroleum Acid Distribution Characterized by FT-ICR MS in Heavy Acidic Crude Oil after True Boiling Point Distillation显示文摘The molecular transformations of carboxylic acids in heavy acidic SL crude before and after true boiling point distillation were examined by ultra-high resolution negative-ion electrospray ionization(ESI) Fourier transform ion cyclotron resonance mass spectrometry(FT-ICR MS). The acid class(heteroatom number), type(z numbers) and carbon number distributions were positively characterized. It was found out that the total acid number(TAN) of SL crude decreased after true boiling point distillation, and the abundance of O2 class in mass spectra was also found to be reduced from 67.6% to 34.5% in SL TBP mixed crude as measured by MS spectra, indicating to a potential carboxylic acid decomposition. However, it was interesting that the carboxylic acids type distribution in both oils was almost the same although their relative abundance in SL TBP mixed crude turned to be much lower, suggesting that various petroleum carboxylic acid types have the similar thermal decomposition reaction behavior. Furthermore, for each O2 type of acids in SL TBP mixed crude, the abundance of carboxylic acids with carbon number higher than 35 was reduced greatly, especially for those with carbon number higher than 60, the mass peaks of which were nearly totally removed, indicating that the large carboxylic acid molecules in heavy fractions decomposed more significantly because of longer heating time during the true boiling point distillation process. As a result, the reduction of TAN may be caused by the thermal decomposition of carboxylic acids especially those with high carbon number, suggesting that quick distillation or much lower pressure is required to avoid the thermal decomposition. | Liu Yingrong Zhang Qundan Wang Wei Liu Zelong Zhu Xinyi Tian Songbai | 2014 | China Petroleum Processing & Petrochemical Technology2014，16，1： | 8 |
| 8 | Service-oriented manufacturing:A literature review and future research directions显示文摘This study presents a systematic review of the literature on service-oriented manufacturing(SOM).Specifically,we focus on the impact of SOM on firm operating decisions,which distinguishes this work from previous reviews.This study proposes a classification framework for SOM research based on product flow,from its design to its final disposal.Although SOM has been studied for many years,most related research remains conceptual.Our criterion for choosing papers is that they must be relevant to practical problems.This review aims to provide readers a guide that will facilitate their search for papers in their field of interest.More importantly,we hope that this review can provide insightful managerial implications for SOM. | Zhong-Zhong JIANG Guangqi FENG Zelong YI Xiaolong GUO | 2022 | Frontiers of Engineering Management2022，9，1： | 6 |
| 9 | Chemical compound cinobufotalin potently induces FOXO1-stimulated cisplatin sensitivity by antagonizing its binding partner MYH9显示文摘In this study,we present novel molecular mechanisms by which FOXO1 functions as a tumor suppressor to prevent the pathogenesis of nasopharyngeal carcinoma(NPC).First,we observed that FOXO1 not only controlled tumor stemness and metastasis,but also sensitized NPC cells to cisplatin(DDP)in vitro and in vivo.Mechanistic studies demonstrated that FOXO1-induced miR-200b expression through the GSK3β/β-catenin/TCF4 network-mediated stimulation of ZEB1,which reduced tumor stemness and the epithelial–mesenchymal transition(EMT)signal.Furthermore,we observed FOXO1 interaction with MYH9 and suppression of MYH9 expression by modulating the PI3K/AKT/c-Myc/P53/miR-133a-3p pathway.Decreased MYH9 expression not only reduced its interactions with GSK3β,but also attenuated TRAF6 expression,which then decreased the ubiquitin-mediated degradation of GSK3βprotein.Increased GSK3βexpression stimulated theβ-catenin/TCF4/ZEB1/miR-200b network,which increased the downstream tumor stemness and EMT signals.Subsequently,we observed that chemically synthesized cinobufotalin(CB)strongly increased FOXO1-induced DDP chemosensitivity by reducing MYH9 expression,and the reduction in MYH9 modulated GSK3β/β-catenin and its downstream tumor stemness and EMT signal in NPC.In clinical samples,the combination of low FOXO1 expression and high MYH9 expression indicated the worst overall survival rates.Our studies demonstrated that CB potently induced FOXO1-mediated DDP sensitivity by antagonizing its binding partner MYH9 to modulate tumor stemness in NPC. | YongHao Li Xiong Liu Xian Lin Menyang Zhao Yanyi Xiao Chen Liu Zixi Liang Zelong Lin Renhui Yi Zibo Tang Jiahao Liu Xin Li Qingping Jiang Libo Li Yinyin Xie Zhen Liu Weiyi Fang | 2019 | Signal Transduction and Targeted Therapy2019，4，1： | 6 |
| 10 | Influence of wave normal angle on gyroresonance between chorus waves and outer radiation belt electrons显示文摘In this paper,using a Gaussian distribution of wave normal angle X=tan,and considering contributions of harmonic resonances n up to±5,we analyze the effect of normal angle on diffusion coefficients induced by gyroresonance between chorus waves and electrons with energies 0.1 and 1.0 MeV on the dayside and nightside at L=4.5.When pitch angle e>10°,for 0.1and 1.0 MeV electrons on the dayside and nightside,diffusion coefficients of five orders(2,1,0,1,2)decrease with increasing normal angle peak,leading to the total diffusion coefficients decreasing with increasing peak.When e<10°,for 1.0MeV electrons on the dayside and 0.1 MeV electrons on the dayside and nightside,the positive order diffusion coefficients are generally smaller than the same negative order ones;in the meanwhile,diffusion coefficients of orders(2,1,2)are very small,the dominant order n=1 diffusion coefficients change very little,hence the total diffusion coefficients almost remain unchanged.However,for 1.0 MeV electrons on the nightside,diffusion coefficients of orders(2,1,2)which are larger than those of the order(1)resonance increase with increasing peak,hence the total diffusion coefficients increase with increasing peak.The current results show that the wave normal angle plays an important role in the quantitative analysis of gyroresonance between chorus waves and electrons in the outer radiation belt. | DING YuanHui HE ZhaoGuo ZHANG ZeLong XIAO FuLiang | 2013 | Science China(Technological Sciences)2013，56，11： | 5 |
| 11 | Molecular Characterization of Hydrotreated Atmospheric Residue Derived from Arabian Heavy Crude by GC FI/FD TOF MS and APPI FT-ICR MS显示文摘High resolution mass spectrometry in combination with distillation and SARA fractionation provides us an opportunity for in-depth understanding about the hydrotreating process at the molecular level. In this study, the atmospheric residue derived from Arabian heavy crude and its hydrotreated products were initially subjected to distillation and SARA fractionation. The saturates were characterized by GC FI/FD TOF MS. The aromatics and resins were characterized by APPI FT-ICR MS. Compositional changes of different compounds (paraffins, naphthenes, aromatic hydrocarbons, and heteroatomic compounds) contained in different distillates (vacuum gas oil, vacuum residue) were obtained. More detailed knowledge about the hydrotreating process was achieved. | Diao Rui Wang Wei Wang Naixin Liu Zelong Dai Lishun Tian Songbai | 2012 | China Petroleum Processing & Petrochemical Technology2012，14，4： | 4 |
| 12 | Optimal reaction conditions for pyridine synthesis in riser reactor显示文摘Pyridine has been generally synthesized by aldehydes and ammonia in a turbulent fluidized-bed reactor. In this paper, a novel riser reactor was proposed for pyridine synthesis. Experiment result showed that the yield of pyridine and 3-picoline decreased, but the selectivity of pyridine over 3-picoline increased compared to turbulent fluidized-bed reactor. Based on experimental data, a modified kinetic model was used for the determination of optimal operating condition for riser reactor. The optimal operating condition of riser reactor given by this modified model was as follows: The reaction temperature of 755 K, catalyst to feedstock ratio(CTFR) of 87, residence time of 3.8 s and initial acetaldehydes concentration of 0.0029 mol·L^(-1)(acetaldehydes to formaldehydes ratio by mole(ATFR) of 0.65 and ammonia to aldehydes ratio by mole(ATAR) of 0.9, water contention of 63 wt%(formaldehyde solution)). | Shuaishuai Zhou Zelong Liu Xiao Yan Qin Di Mengxi Liu Chunxi Lu Guangzhou Jin | 2018 | Chinese Journal of Chemical Engineering2018，26，7： | 3 |
| 13 | Quantitative Analysis Using Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Correlation between Mass Spectrometry Data and Sulfur Content of Crude Oils显示文摘Fourier transform ion cyclotron resonance mass spectrometry(FT-ICR MS) has become a powerful tool for analyzing the detailed composition of petroleum samples. However, the correlation between the numerous peaks obtained by FT-ICR MS and bulk properties of petroleum samples is still a challenge. In this study, the internal standard method was applied for the quantitative analysis of four straight-run vacuum gas oils(VGO) by atmospheric pressure photoionization(APPI) FT-ICR MS. The heteroatom class distribution of these VGO samples turned to be different when the concentration changed. Linear relationship between the normalized abundance and the concentration of VGO samples was identified for the total aromatic compounds, aromatic hydrocarbons, S1 and N1 species. The differences of the response factors were also discussed. The sulfur contents of a series of crude oils were proved to be linear with the FT-ICR MS data calibrated by the response factor of S1 species. This study demonstrated the feasibility of the internal standard method in quantitative analysis with APPI FT-ICR MS, and the bulk properties of petroleum samples could be correlated directly with the FT-ICR MS data. | Wang Wei Liu Yingrong Liu Zelong Tian Songbai | 2015 | China Petroleum Processing & Petrochemical Technology2015，17，4： | 3 |
| 14 | Linkage of Aromatic Ring Structures in Saturates, Aromatics, Resins and Asphaltenes Fractions of Vacuum Residues Determined by Collision-Induced Dissociation Technology显示文摘The linkage of aromatic ring structures in vacuum residues was important for the refining process. The Fourier transform ion cyclotron resonance mass spectrometry(FT-ICR MS) combined with collision-induced dissociation(CID) is a powerful method to characterize the molecular structure of petroleum fractions. In this work, model compounds with different aromatic ring structures were measured by CID FT-ICR MS. The cracking of the parent ions and the generated fragment ions were able to distinguish different linkage of the model compounds. Then, vacuum residues were separated into saturates, aromatics, resins and asphaltenes fractions(SARA), and each fraction was characterized by CID technology. According to the experimental results, the aromatic rings in saturates and aromatics fractions were mainly of the island-type structures, while the aromatic rings in resins and asphaltenes fractions had a significant amount of archipelago-type structures. | Wang Wei Liu Yingrong Liu Zelong Hou Huandi Tian Songbai | 2016 | China Petroleum Processing & Petrochemical Technology2016，18，1： | 3 |
| 15 | Fracture property identification method based on shrinkage factor particle swarm optimization显示文摘In the multi-wave and multi-component seismic exploration,shear-wave will be split into fast wave and slow wave,when it propagates in anisotropic media. Then the authors can predict polarization direction and density of crack and detect the development status of cracks underground according to shear-wave splitting phenomenon. The technology plays an important role and shows great potential in crack reservoir detection. In this study,the improved particle swarm optimization algorithm based on shrinkage factor is combined with the Pearson correlation coefficient method to obtain the fracture azimuth angle and density. The experimental results show that the modified method can improve the convergence rate,accuracy,anti-noise performance and computational efficiency. | ZHOU Chao FENG Xuan ZHANG Bing LU Xiaoman JIN Zelong XU Cong | 2015 | Global Geology2015，18，4： | 2 |
| 16 | Geophysical and Production Data History Matching Based on Ensemble Smoother with Multiple Data Assimilation显示文摘The Ensemble Kalman Filter(EnKF),as the most popular sequential data assimilation algorithm for history matching,has the intrinsic problem of high computational cost and the potential inconsistency of state variables updated at each loop of data assimilation and its corresponding reservoir simulated result.This problem forbids the reservoir engineers to make the best use of the 4D seismic data,which provides valuable information about the fluid change inside the reservoir.Moreover,only matching the production data in the past is not enough to accurately forecast the future,and the development plan based on the false forecast is very likely to be suboptimal.To solve this problem,we developed a workflow for geophysical and production data history matching by modifying ensemble smoother with multiple data assimilation(ESMDA).In this work,we derived the mathematical expressions of ESMDA and discussed its scope of applications.The geophysical data we used is P-wave impedance,which is typically included in a basic seismic interpretation,and it directly reflects the saturation change in the reservoir.Full resolution of the seismic data is not necessary,we subsampled the P-wave impedance data to further reduce the computational cost.With our case studies on a benchmark synthetic reservoir model,we also showed the supremacy of matching both geophysical and production data,than the traditional reservoir history matching merely on the production data:the overall percentage error of the observed data is halved,and the variances of the updated forecasts are reduced by two orders of the magnitude. | Zelong Wang Xiangui Liu Haifa Tang Zhikai Lv Qunming Liu | 2020 | Computer Modeling in Engineering & Sciences2020，，5： | 2 |
| 17 | Simple manganese carbonyl catalyzed hydrogenation of quinolines and imines显示文摘Manganese-catalyzed hydrogenation of unsaturated molecules has made tremendous progresses recently benefiting from non-innocent pincer or bidentate ligands for manganese.Herein,we describe the hydrogenation of quinolines and imines catalyzed by simple manganese carbonyls,Mn2(CO)10 or MnBr(CO)5,thus eliminating the prerequisite pincer-type or bidentate ligands. | Zelong Wang Lei Chen Guoliang Mao Congyang Wang | 2020 | Chinese Chemical Letters2020，31，7： | 2 |
| 18 | Characteristic of Soil Hydro-Physical Properties and Water Dynamics under Different Vegetation Restoration Types显示文摘By combining the observation of the soil profile at field and the chemical and physical analysis in laboratory, a study on the hydro-physical properties of soil in six different vegetation types and the dynamics of water content after rain was conducted in Wanchanggou, Guangyuan City to find out the vegetation types with effective water-conservation functions in order to serve the ecological restoration in the low hill heavy rain area upper the Jialing River. Results showed that:the hydro-physical properties of soil in the mixed Alnus cremastogyne and Cupressua Leyland forest (AcCl) were best. But in the depth of 0-20 cm. The properties of soil in the abandoned cropland (Fm) was better than that in the AcCl. The soil bulk densities varied significantly between the layers of 0-20 cm and 20-40 cm in all the six vegetation types except that in the Robinia pseudoacacia shrub forest (RpII), and the changes of the maximum and the capillary moisture capacity between layers were significant only in the Fm and in the AcCl. Of these stands, the AcCl had the shortest water-absorbing period and the strongest moisture changes in the upper layer (0-15 cm). In the same stand, the deeper the soil layer, the slighter the soil moisture varied, and the longer the soil moisture accumulating process lasted. | MA Zelong GONG Yuanbo HU Tingxing | 2006 | Wuhan University Journal of Natural Sciences2006，11，4： | 2 |
| 19 | A videogrammetric technique for measuring the vibration displacement of stay cables显示文摘Stay cables in cable-stayed bridges are prone to large amplitude oscillations under external excitations.The vibration of the cables is predominantly measured by using accelerometers to measure the acceleration.The dynamic displacement is then usually obtained indirectly from the double integration of the acceleration data.This paper reports an experimental method of measuring the displacement of stayed cables using a digital video camera.With the newly developed videogrammetric technique,the video clips are transferred into image frames,from which the shape and location of the target are identified.The displacement time history is then captured.The technique is applied to a cable-stayed bridge to measure the dynamic displacement of stay cables.The displacement is compared with the acceleration data in the frequency and time domains.The results show that the displacement measured by the digital video camera is comparable to the counterparts integrated from the acceleration data.The vibration frequencies identified from the acceleration are finally used to estimate the tension forces of the cables.The results show that the tension forces have insignificant changes after one year’s operation. | ZHOU Xiaoqing XIA Yong WEI Zelong WU Qingxiong | 2012 | Geo-Spatial Information Science2012，15，2： | 2 |
| 20 | Enhanced plasma factor Ⅷ activity in mice via cysteine mutation using dual vectors显示文摘Hemophilia A is caused by a genetic mutation in coagulation factor Ⅷ(FⅧ) gene and gene therapy is considered to be a promising strategy for its treatment.We recently demonstrated that co-delivery of two vectors expressing M662C mutated heavy and D1828C mutated light chain genes of B-domain-deleted coagulation factor Ⅷ(BDD-FⅧ) leads to inter-chain disulfide cross-linking and improved heavy chain secretion in vitro.In this study,co-injection of both M662C and D1828C mutated BDD-FⅧ gene expression vectors into mice resulted in increased heavy chain secretion and coagulation activity in plasma in vivo.Approximately(239±56) ng mL 1 above endogenous levels of transgenic FⅧ heavy chain was found in mouse plasma using a chain-specific ELISA.For FⅧ coagulation activity,approximately(1.09±0.25) IU mL 1 above endogenous levels were detected in co-injected transgenic mouse plasma using a chromogenic assay.These data demonstrate that inter-chain disulfide bonds likely increase heavy chain secretion and coagulation activity in the plasma of transgenic mice with an improved efficacy of a dual-vector delivery of BDD-FⅧ gene.These findings support our ongoing efforts to develop a gene therapy for hemophilia A treatment using dual-AAV vectors. | ZHU FuXiang LIU ZeLong MIAO Jing QU HuiGe CHI XiaoYan | 2012 | Science China(Life Sciences)2012，55，6： | 2 |
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