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| 1 | Generation of B Cell-Deficient Pigs by Highly Efficient CRISPR/Cas9-Mediated Gene Targeting显示文摘Generating B cell-deficient mutant is the first step to produce human antibody repertoires in large animal models. In this study, we applied the clustered regularly interspaced short palindromic repeat(CRISPR)/CRISPR-associated(Cas) system to target the JHregion of the pig Ig M heavy chain gene which is crucial for B cell development and differentiation. Transfection of Ig M-targeting Cas9 plasmid in primary porcine fetal fibroblasts(PFFs) enabled inducing gene knock out(KO) in up to 53.3% of colonies analyzed, a quarter of which harbored biallelic modification, which was much higher than that of the traditional homologous recombination(HR). With the aid of somatic cell nuclear transfer(SCNT) technology, three piglets with the biallelic Ig M heavy chain gene mutation were produced. The piglets showed no antibody-producing B cells which indicated that the biallelic mutation of the Ig M heavy chain gene effectively knocked out the function of the Ig M and resulted in a B cell-deficient phenotype. Our study suggests that the CRISPR/Cas9 system combined with SCNT technology is an efficient genome-editing approach in pigs. | Fengjiao Chen Ying Wang Yilin Yuan Wei Zhang Zijian Ren Yong Jin Xiaorui Liu Qiang Xiong Qin Chen Manling Zhang Xiaokang Li Lihua Zhao Ze Li Zhaoqiang Wu Yanfei Zhang Feifei Hu Juan Huang Rongfeng Li Yifan Dai | 2015 | Journal of Genetics and Genomics2015，42，8： | 15 |
| 2 | OSBPL2-disrupted pigs recapitulate dual features of human hearing loss and hypercholesterolaemia显示文摘Oxysterol binding protein like 2(OSBPL2), an important regulator in cellular lipid metabolism and transport, was identified as a novel deafness-causal gene in our previous work. To resemble the phenotypic features of OSBPL2 mutation in animal models and elucidate the potential genotypephenotype associations, the OSBPL2-disrupted Bama miniature(BM) pig model was constructed using CRISPR/Cas9-mediated gene editing, somatic cell nuclear transfer(SCNT) and embryo transplantation approaches, and then subjected to phenotypic characterization of auditory function and serum lipid profiles. The OSBPL2-disrupted pigs displayed progressive hearing loss(HL) with degeneration/apoptosis of cochlea hair cells(HCs) and morphological abnormalities in HC stereocilia, as well as hypercholesterolaemia. High-fat diet(HFD) feeding aggravated the development of HL and led to more severe hypercholesterolaemia. The dual phenotypes of progressive HL and hypercholesterolaemia resembled in OSBPL2-disrupted pigs confirmed the implication of OSBPL2 mutation in nonsydromic hearing loss(NSHL) and contributed to the potential linkage between auditory dysfunction and dyslipidaemia/hypercholesterolaemia. | Jun Yao Huasha Zeng Min Zhang Qinjun Wei Ying Wang Haiyuan Yang Yajie Lu Rongfeng Li Qiang Xiong Lining Zhang Zhibin Chen Guangqian Xing Xin Cao Yifan Dai | 2019 | Journal of Genetics and Genomics2019，46，8： | 7 |
| 3 | The potential of genetically-engineered pigs in providing an alternative source of organs and cells for transplantation显示文摘There is a critical shortage of organs, cells, and corneas from deceased human donors worldwide. There are also shortages of human blood for transfusion. A potential solution to all of these problems is the transplantation of organs, cells, and corneas from a readily available animal species, such as the pig, and the transfusion of red blood cells from pigs into humans. However, to achieve these ends, major immunologic and other barriers have to be overcome. Considerable progress has been made in this respect by the genetic modification of pigs to protect their tissues from the primate immune response and to correct several molecular incompatibilities that exist between pig and primate. These have included knockout of genes responsible for the expression of major antigenic targets for primate natural anti-pig antibodies, insertion of human complementand coagulation-regulatory transgenes, and knockdown of swine leukocyte antigens that stimulate the primate's adaptive immune response. As a result of these manipulations, the administration of novel immunosuppressive agents, and other innovations, pig hearts have now functioned in baboons for 6-8 months, pig islets have maintained normoglycemia in diabetic monkeys for > 1 year, and pig corneas have maintained transparency for several months. Clinical trials of pig islet transplantation are already in progress. Future developments will involve further genetic manipulations of the organsource pig, with most of the genes that are likely to be beneficial already identified. | David K.C.Cooper Hidetaka Hara Mohamed Ezzelarab Rita Bottino Massimo Trucco Carol Phelps David Ayares Yifan Dai | 2013 | The Journal of Biomedical Research2013，27，4： | 6 |
| 4 | Local Path Planning and Tracking Control of Vehicle Collision Avoidance System显示文摘Automotive collision avoidance technology can effectively avoid the accidents caused by dangerous traffic conditions or driver's manipulation errors.Moreover,it can promote the development of autonomous driving for intelligent vehicle in intelligent transportation.We present a collision avoidance system,which is composed of an evasive trajectory planner and a path following controller.Considering the stability of the vehicle in the conflict-free process,the evasive trajectory planner is designed by polynomial parametric method and optimized by genetic algorithm.The path following controller is proposed to make the car drive along the designed path by controlling the vehicle's lateral movement.Simulation results show that the vehicle with the proposed controller has good stability in the collision process,and it can ensure the vehicle driving in accordance with the planned trajectory at different speeds.The research results can provide a certain basis for the research and development of automotive collision avoidance technology. | Xu Zhijiang Zhao Wanzhong Wang Chunyan Dai Yifan | 2018 | Transactions of Nanjing University of Aeronautics and Astronautics2018，35，4： | 5 |
| 5 | The heterogeneity of islet autoantibodies and the progression of islet failure in type 1 diabetic patients显示文摘Type 1 diabetes mellitus is heterogeneous in many facets. The patients suffered from type 1 diabetes present several levels of islet function as well as variable number and type of islet-specific autoantibodies. This study was to investigate prevalence and heterogeneity of the islet autoantibodies and clinical phenotypes of type 1 diabetes mellitus; and also discussed the process of islet failure and its risk factors in Chinese type 1 diabetic patients. A total of 1,291 type 1 diabetic patients were enrolled in this study. Demographic information was collected. Laboratory tests including mixed-meal tolerance test, human leukocyte antigen alleles, hemoglobin A1 c, lipids, thyroid function and islet autoantibodies were conducted. The frequency of islet-specific autoantibody in newly diagnosed T1 DM patients(duration shorter than half year) was 73% in East China. According to binary logistic regressions, autoantibody positivity, longer duration and lower Body Mass Index were the risk factors of islet failure. As the disease developed, autoantibodies against glutamic acid decarboxylase declined as well as the other two autoantibodies against zinc transporter 8 and islet antigen 2. The decrease of autoantibodies was positively correlated with aggressive beta cell destruction. Autoantibodies can facilitate the identification of classic T1 DM from other subtypes and predict the progression of islet failure. As there were obvious heterogeneity in autoantibodies and clinical manifestation in different phenotypes of the disease, we should take more factors into consideration when identifying type 1 diabetes mellitus. | Jin Liu Lingling Bian Li Ji Yang Chen Heng Chen Yong Gu Bingqin Ma Wei Gu Xinyu Xu Yun Shi Jian Wang Dalong Zhu Zilin Sun Jianhua Ma Hui Jin Xing Shi Heng Miao Bing Xin Yan Zhu Zhenwen Zhang Ruifang Bu Lan Xu Guangde Shi Wei Tang Wei Li Dongmei Zhou Jun Liang Xingbo Cheng Bimin Shi Jixiang Dong Ji Hu Chen Fang Shao Zhong Weinan Yu Weiping Lu Chenguang Wu Li Qian Jiancheng Yu Jialin Gao Xiaoqiang Fei Qingqing Zhang Xueqin Wang Shiwei Cui Jinluo Cheng Ning Xu Guofeng Wang Guoqing Han Chunrong Xu Yun Xie Minmin An Wei Zhang Zhixiao Wang Yun Cai Qi Fu Yu Fu Shuai Zheng Fan Yang Qingfang Hu Hao Dai Yu Jin Zheng Zhang Kuanfeng Xu Yifan Li Jie Shen Hongwen Zhou Wei He Xuqin Zheng Xiao Han Liping Yu Jinxiong She Mei Zhang Tao Yang | 2016 | Science China(Life Sciences)2016，59，9： | 5 |
| 6 | Restraint of mid-spatial frequency error in magnetorheological finishing (MRF) process by maximum entropy method显示文摘In order to restrain the mid-spatial frequency error in magnetorheological finishing (MRF) process, a novel part-random path is designed based on the theory of maximum entropy method (MEM). Using KDMRF-1000F polishing machine, one flat work piece (98 mm in diameter) is polished. The mid-spatial frequency error in the region using part-random path is much lower than that by using common raster path. After one MRF iteration (7.46 min), peak-to-valley (PV) is 0.062 wave (1 wave =632.8 nm), root-mean-square (RMS) is 0.010 wave and no obvious mid-spatial frequency error is found. The result shows that the part-random path is a novel path, which results in a high form accuracy and low mid-spatial frequency error in MRF process. | DAI YiFan SHI Feng PENG XiaoQiang LI ShengYi | 2009 | Science China(Technological Sciences)2009，52，10： | 5 |
| 7 | Progress in graphene-based magnetic hybrids towards highly efficiency for microwave absorption显示文摘Nowadays, the yearning for microwave absorption materials(MAMs) are more and more urgent for dealing with the increasingly serious electromagnetic pollution and the demand of modern military security.Among potential candidates, the graphene(GE) based magnetic hybrids have advantages in structural controllable and designing flexibility, providing opportunities for achieving highly efficiency of microwave absorption(MA). Thus, the structural regulation and MA performances of GE-based magnetic hybrids arouse great attention in related fields. In this review, we summarize the recently progress in MA performance of GE-based magnetic hybrids. Typical absorption process and corresponding mechanism are firstly introduced, for guiding the design of GE-based magnetic MAMs. Then, the magnetic components, synthesis methods, structural features and regulation strategies of these GE-related magnetic materials are reviewed, and their influences on MA performances have also been discussed. Challenges, and prospects of the GE-based magnetic MAMs are suggested. This review provides a brief but systematic introduction to GE-based magnetic MAMs, which may pave the way for the design of MAMs with highly efficient MA performances. | Fuxi Peng Mingfeng Dai Zhenyu Wang Yifan Guo Zuowan Zhou | 2022 | Journal of Materials Science & Technology2022，，11： | 3 |
| 8 | Antigenicity of tissues and organs from GGTA1/CMAH/β4GalNT2 triple gene knockout pigs显示文摘Clinical xenotransplantations have been hampered by human preformed antibody-mediated damage of the xenografts.To overcome biological incompatibility between pigs and humans,one strategy is to remove the major antigens[Gal,Neu5 Gc,and Sd(a)]present on pig cells and tissues.Triple gene(GGTAI,CMAH,and β4 GalNT2)knockout(TKO)pigs were produced in our laboratory by CRISPR-Cas9 targeting.To investigate the antigenicity reduction in the TKO pigs,the expression levels of these three xenoantigens in the cornea,heart,liver,spleen,lung,kidney,and pancreas tissues were examined.The level of human IgG/IgM binding to those tissues was also investigated,with wildtype pig tissues as control.The results showed that aGal,Neu5 Gc,and Sd(a)were markedly positive in all the examined tissues in wildtype pigs but barely detected in TKO pigs.Compared to wildtype pigs,the liver,spleen,and pancreas of TKO pigs showed comparable levels of human IgG and IgM binding,whereas corneas,heart,lung,and kidney of TKO pigs exhibited significantly reduced human IgG and IgM binding.These results indicate that the antigenicity of TKO pig is significantly reduced and the remaining xenoantigens on porcine tissues can be eliminated via a gene targeting approach. | Ronggen Wang Miaomiao Ruan Runjie Zhang Lei Chen Xiaoxue Li Bin Fang Chu Li Xueyang Ren Jiying Liu Qiang Xiong Lining Zhang Yong Jin Lin Li Rongfeng Li Ying Wang Haiyuan Yang Yifan Dai | 2019 | The Journal of Biomedical Research2019，33，4： | 3 |
| 9 | Endothelin-1-induced mini-stroke in the dorsal hippocampus or lateral amygdala results in deficits in learning and memory显示文摘Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied.However,the mechanism whereby local ischemia in deep brain region affect brain functions is still unknown.Here,we first established a mini-stroke model by infusion of endothelin-1(ET-1) into the dorsal hippocampus or the lateral amygdala,and then investigated how these mini-infarcts affected brain functions associated with these regions.We found that rats with ET-1 infusion showed deficit in recall of contextual fear memory,but not in learning process and recall of tone fear memory.In novel object task,ET-1 in the hippocampus also eliminated object identity memory.ET-1 in the lateral amygdale affected acquisition of fear conditioning and disrupted retention of tone-conditioned fear,but did not impair retention of contextual fear.These findings suggest that ET-1-induced mini-infarct in deep brain area leads to functional deficits in learning and memory associated with these regions. | Tao Sheng Xueting Zhang Shaoli Wang Jingyun Zhang Wei Lu Yifan Dai | 2015 | The Journal of Biomedical Research2015，29，5： | 3 |
| 10 | HMGB1 from Astrocytes Promotes EAE by Influencing the Immune Cell Infiltration-Associated Functions of BMECs in Mice显示文摘High mobility group box 1(HMGB1)has been reported to play an important role in experimental autoimmune encephalomyelitis(EAE).Astrocytes are important components of neurovascular units and tightly appose the endothelial cells of microvessels by their perivascular endfeet and directly regulate the functions of the blood-brain barrier.Astrocytes express more HMGB1 during EAE while the exact roles of astrocytic HMGB1 in EAE have not been well elucidated.Here,using conditional-knockout mice,we found that astrocytic HMGB1 depletion decreased morbidity,delayed the onset time,and reduced the disease score and demyelination of EAE.Meanwhile,there were fewer immune cells,especially pathogenic T cells infiltration in the central nervous system of astrocytic HMGB1 conditional-knockout EAE mice,accompanied by up-regulated expression of the tight-junction protein Claudin5 and down-regulated expression of the cell adhesion molecules ICAM1 and VCAM1 in vivo.In vitro,HMGB1 released from astrocytes decreased Claudin5 while increased ICAM1 and VCAM1 expressed by brain microvascular endothelial cells(BMECs)through TLR4 or RAGE.Taken together,our results demonstrate that HMGB1 derived from astrocytes aggravates EAE by directly influencing the immune cell infiltration-associated functions of BMECs. | Junyu Shi Yifan Xiao Na Zhang Mengya Jiao Xuhuan Tang Chan Dai Chenchen Wang Yong Xu Zheng Tan Feili Gong Fang Zheng | 2022 | Neuroscience Bulletin2022，38，11： | 3 |
| 11 | Frequency-domain analysis of computer-controlled optical surfacing processes显示文摘Mid-high spatial frequency errors are often induced on optical surfaces polished by computer-controlled optical surfacing (CCOS) processes. In order to efficiently remove these errors, which would degrade the performances of optical systems, the ability of a CCOS process to correct the errors have been investigated based on the convolution integral model in view of the availability of material removal. To quantify the ability, some conceptions, such as figure correcting ability and material removal availability (MRA), have been proposed. The research result reveals that the MRA of the CCOS process to correct a single spatial frequency error is determined by its tool removal function (TRF), and it equals the normalized amplitude spectrum of the Fourier transform of its TRF. Finally, three sine surfaces were etched using ion beam figuring (IBF), which is a typical CCOS process. The experimental results have verified the theoretical analysis. The employed method and the conclusions of this work provide a useful mathematical basis to analyze and optimize CCOS processes. | ZHOU Lin DAI YiFan XIE XuHui LI ShengYi | 2009 | Science China(Technological Sciences)2009，52，7： | 2 |
| 12 | Overexpressing dominant-negative FGFR2-IIIb impedes lung branching morphogenesis in pigs显示文摘Genetic studies with mouse models have shown that fibroblast growth factor receptor 2-IIIb(FGFR2-IIIb)plays crucial roles in lung development and differentiation. To evaluate the effect of FGFR2-IIIb in pig lung development, we employed somatic cell nuclear transfer(SCNT) technology to generate transgenic pig fetuses overexpressing the transmembrane(dn FGFR2-IIIb-Tm) and soluble(dn FGFR2-IIIb-HFc) forms of the dominant-negative human FGFR2-IIIb driven by the human surfactant protein C(SP-C) promoter,which was specifically expressed in lung epithelia. Eight dn FGFR2-IIIb-Tm transgenic and twelve dn FGFR2-IIIb-HFc transgenic pig fetuses were collected from three and two recipient sows, respectively.Repression of FGFR2-IIIb in lung epithelia resulted in smaller lobes and retardation of alveolarization in both forms of dn FGFR2-IIIb transgenic fetuses. Moreover, the dn FGFR2-IIIb-HFc transgenic ones showed more deterioration in lung development. Our results demonstrate that disruption of FGFR2-IIIb signaling in the epithelium impedes normal branching and alveolarization in pig lungs, which is less severe than the results observed in transgenic mice. The dn FGFR2-IIIb transgenic pig is a good model for the studies of blastocyst complementation as well as the mechanisms of lung development and organogenesis. | Qin Chen Bin Fang Ying Wang Chu Li Xiaoxue Li Ronggen Wang Qiang Xiong Lining Zhang Yong Jin Manling Zhang Xiaorui Liu Lin Li Lisha Mou Rongfeng Li Haiyuan Yang Yifan Dai | 2018 | Journal of Genetics and Genomics2018，45，3： | 2 |
| 13 | A Bama miniature pig model of monoallelic TSC1 mutation for human tuberous sclerosis complex显示文摘Tuberous sclerosis complex(TSC)is a dominant genetic neurocutaneous syndrome characterized by multiple organ hamartomas.Although rodent models bearing a germline mutation in either TSC1 or TSC2 gene have been generated,they do not develop pathogenic lesions matching those seen in patients with TSC because of the significant differences between mice and humans,highlighting the need for an improved large animal model of TSC.Here,we successfully generate monoallelic TSC1-modified Bama miniature pigs using the CRISPR/Cas9 system along with somatic cell nuclear transfer(SCNT)technology.The expression of phosphorylated target ribosomal protein S6 is significantly enhanced in the piglets,indicating that disruption of a TSC1 allele activate the mechanistic target of rapamycin(mTOR)signaling pathway.Notably,differing from the mouse TSC models reported previously,the TSC1^(+/−)Bama miniature pig developed cardiac rhabdomyoma and subependymal nodules,resembling the major clinical features that occur in patients with TSC.These TSC1^(+/−)Bama miniature pigs could serve as valuable large animal models for further elucidation of the pathogenesis of TSC and the development of therapeutic strategies for TSC disease. | Xiaoxue Li Tingdong Hu Jiying Liu Bin Fang Xue Geng Qiang Xiong Lining Zhang Yong Jin Xiaorui Liu Lin Li Ying Wang Rongfeng Li Xiaochun Bai Haiyuan Yang Yifan Dai | 2020 | Journal of Genetics and Genomics2020，47，12： | 2 |
| 14 | Unbalanced omega-6/omega-3 ratio in red meat products in China显示文摘Dietary meats play a crucial role in human health.The objective of this survey was to determine the fatty acid content and omega-6/omega-3 polyunsaturated fatty acids(n-6/n-3 PUFA)ratio of fresh red meat(beef and pork)from four cities(Shanghai,Nanjing,Yinchuan and Hohhot)in China.The results showed that the n-6/n-3 PUFA ratio from all the samples ranged from 6 to 23.The total n-6 PUFA concentrations ranged from 290.54 mg/100g in beef from Nanjing to 1601.48 mg/100 g in pork from Hohhot,whereas the total concentrations of n-3 PUFA ranged from 46.34 mg/100 g in beef from Nanjing to 96.03 mg/100 g in pork from Nanjing.The results indicated that the n-6/n-3 ratio in the red meat from all four regions is unbalanced and is much higher than that(<5:1)recommended by the WHO/FAO.The total amount of n-3 PUFA was far lower than the required daily dose.Therefore,potential solutions to increase the n-3 PUFA content in meat products or to provide alternative source of n-3PUFA should be explored. | Ming Yu Qianqian Gao Yan Wang Wei Zhang Lin Li Ying Wang Yifan Dai | 2013 | The Journal of Biomedical Research2013，27，5： | 2 |
| 15 | competitive and collaborative quality and warranty management in supply chain显示文摘 | YUE DAI SEAN X ZHOU YIFAN XU | | 0，，01： | 1 |
| 16 | Competitive and Collaborative Quality and Warranty Management in Supply Chains显示文摘 | Dai Yue Zhou Sean X Xu Yifan | 2012 | Produc- tion and Operations Management2012，21，1： | 1 |
| 17 | Overbooking with bilateral transference in parallel flights显示文摘 | Yanming Ge Yifan Xu Yue Dai | 2010 | International Journal of Production Economics2010，，2： | 1 |
| 18 | Production of cloned transgenic cow expressing omega-3 fatty acids显示文摘 | Xia Wu Hongsheng Ouyang Biao Duan Daxin Pang Li Zhang Ting Yuan Lian Xue Daibang Ni Lei Cheng Shuhua Dong Zhuying Wei Lin Li Ming Yu Qing-Yuan Sun Da-Yuan Chen Liangxue Lai Yifan Dai Guang-Peng Li | 2012 | Transgenic Research2012，，3： | 1 |
| 19 | Overbooking with bilateral transference in parallel flights显示文摘 | Yanming Ge Yifan Xu Yue Dai | | 0，，02： | 1 |
| 20 | Nanoparticle accumulation in liver may induce resistance to immune checkpoint blockade therapy显示文摘Despite immune checkpoint blockade(ICB)therapy has transformed cancer treatment,only 20.2%of these patients achieved a response.Understanding resistance mechanisms to ICB is important for the treatment of a wider population.In this work,we occasionally found that the silica nanoparticles(SiO_(2)NPs)accumulated in the liver can induce resistance to following ICB therapy to a subcutaneous tumor in mice.By analysis of T cells frequency,we uncovered that SiO_(2)NPs in the liver resulted in a siphoning of T cells from circulation to the liver by produced chemokines.In addition,liver immunosuppressive cells further inhibit the function and induce apoptosis of recruited T cells,leading to a systemic loss and reduced tumor infiltration of T cells,which contributes to poor responses to ICB therapy.However,such effect is not observed in poly(lactic-co-glycolic acid)(PLGA)NPs treated mice under the same conditions,likely due to their much lower immunogenicity in perturbing the liver immune microenvironment,indicating that cancer is not a local disease but an ecosystem that is linked to the distal environment.We further provide a new mechanism insight into ICB resistance induced by liver accumulation of nanoparticles. | Huaxing Dai Qianyu Yang Rong Sun Yue Zhang Qingle Ma Yifan Shen Beilei Wang Yitong Chen Jialu Xu Bo Tian Fang Xu Chao Wang | 2023 | Nano Research2023，16，4： | 1 |
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