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Depletion of conventional mature B cells and compromised specific antibody response in bovine immunoglobulinμ heavy-chain transgenic mice

Min ZHANG,Xueqian CHENG,Dan CHU,Jingwen LIANG,Yi SUN,Li MA,Beilei XU,Min ZHENG,Meili WANG,Liming REN,Xiaoxiang HU,Qingyong MENG,Ran ZHANG,Ying GUO,Yunping DAI,Robert AITKEN,Ning LI,Yaofeng ZHAO

《农业科学与工程前沿（英文）》 2014年 第1卷 第2期   页码 158-173 doi: 10.15302/J-FASE-2014015

摘要： In this study, we introduced the bovine immunoglobulin μ heavy-chain gene (the orphaned gene on BTA11) into mouse germline cells. Bovine IgM was highly expressed in selected transgenic lines, and it largely inhibited rearrangements of the endogenous immunoglobulin heavy chain (IgH) genes in these lines. The forced expression of bovine IgM resulted in reduced numbers of pro- and pre-B cells but increased the number of immature B cells in the transgenic mice. Bovine IgM-expressing B cells can migrate from the bone marrow to the spleen, but most of the cells are arrested at the T1 transitional B cell stage, leading to a significantly lower number of T2 transitional and mature B cells in the spleen. Although the serum concentrations of endogenous IgM and IgG in the transgenic mice were significantly decreased, the IgA levels were slightly increased compared to the WT mice. The bovine IgM level in the serum was only one-tenth to one-fifth of that of endogenous mouse IgM, suggesting that most of the serum immunoglobulin were contributed by endogenous IgH gene-expressing B cells. These transgenic mice also exhibited a lower frequency of unique complementarity determining region 3 (CDR3) sequences in their VH repertoire and Vκ repertoire but exhibited an increased frequency of unique CDR3 in their Vλ repertoire. Compared to the WT mice, the transgenic mice had a significantly higher percentage of mouse IgM-expressing B cells that expressed λ chains. Finally, we showed that the transgenic mice were deficient in a specific antibody response to antigen stimulation.

关键词： bovine Ig μ heavy-chain     transgenic mice     B cell development     allelic exclusion     immune response     Ig repertoire    

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A comprehensive analysis of immunoglobulin heavy chain genes in the Bactrian camel (

Zuoxiang LIANG,Tao WANG,Yi SUN,Wenlong YANG,Zhihong LIU,Jing FEI,Ying GUO,Qingwei MA,Qingjie PAN,Liming REN

《农业科学与工程前沿（英文）》 2015年 第2卷 第3期   页码 249-259 doi: 10.15302/J-FASE-2015056

摘要： Heavy chain only antibodies (HCAbs) represent a rare type of antibody that is devoid of light chains and the CH1 domain that have been reported in cartilaginous fish and camelids. By analyzing transcript data and genome sequences, we conducted a comprehensive analysis of Bactrian camel immunoglobulin heavy chain genes. Based on the transcript data, one gene, five genes, one gene and one gene were found. Additionally, the variable region of HCAbs (VHH) and the conventional antibodies (VH) sequences associated with the , and genes were amplified. Based on these genome sequences, seven , six , , , , , and genes and a portion of a gene were observed. Different Kozak sequences within different VH families were found in our analysis, and the variability index differed between the VHH3 and VH3 families. Phylogenetic analysis of the constant regions of the camelid immunoglobulin genes indicates that these genes appeared before the evolutionary divergence of Bactrian camels and dromedaries.

关键词： Bactrian camel     heavy-chain antibodies     VHH     γ3    

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Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice

《医学前沿（英文）》   页码 957-971 doi: 10.1007/s11684-023-0988-8

摘要： Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD.

关键词： DNAH10     mice     motile cilia     mutation     primary ciliary dyskinesia    

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of hemorrhagic diathesis in hemophilia A mice by an AAV-delivered hybrid FVIII composed of the human heavychain and the rat light chain

《医学前沿（英文）》 2022年 第16卷 第4期   页码 584-595 doi: 10.1007/s11684-021-0844-7

摘要： Conventional therapies for hemophilia A (HA) are prophylactic or on-demand intravenous FVIII infusions. However, they are expensive and inconvenient to perform. Thus, better strategies for HA treatment must be developed. In this study, a recombinant FVIII cDNA encoding a human/rat hybrid FVIII with an enhanced procoagulant potential for adeno-associated virus (AAV)-delivered gene therapy was developed. Plasmids containing human FVIII heavy chain (hHC), human light chain (hLC), and rat light chain (rLC) were transfected into cells and hydrodynamically injected into HA mice. Purified AAV viruses were intravenously injected into HA mice at two doses. Results showed that the hHC+ rLC protein had a higher activity than the hHC+ hLC protein at comparable expression levels. The specific activity of hHC+ rLC was about 4- to 8-fold higher than that of their counterparts. Hydrodynamic injection experiments obtained consistent results. Notably, the HA mice undergoing the AAV-delivered hHC+ rLC treatment exhibited a visibly higher activity than those treated with hHC+ hLC, and the therapeutic effects lasted for up to 40 weeks. In conclusion, the application of the hybrid FVIII (hHC+ rLC) via an AAV-delivered gene therapy substantially improved the hemorrhagic diathesis of the HA mice. These data might be of help to the development of optimized FVIII expression cassette for HA gene therapy.

关键词： hemophilia A     adeno-associated virus (AAV)     human/rat hybrid factor VIII     gene therapy     dual chain strategy    

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The past, present and future of bovine pluripotent stem cells: a brief overview

Xiuchun TIAN

《农业科学与工程前沿（英文）》 2019年 第6卷 第1期   页码 3-7 doi: 10.15302/J-FASE-2018247

摘要：

Although the pursuit of bovine embryonic stem cells started more than 26 years ago for the purpose of gene-targeting, true pluripotent stem cells in this economically important species are still elusive. With the rapid advances in genome-editing and cloning using homologously recombined somatic cells, the need for pluripotent stem cells for precise genetic modification in any species became questionable. With the pig being the better model for human regenerative biology, the identification of the commonalities and uniqueness of the pluripotency circuitry across mammalian species may be the main objective for studying pluripotent stem cells in the bovine.

关键词： bovine     embryonic     induced     pluripotent stem cells    

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Development of the expressed immunoglobulin μ chain repertoire during maturation of mice B cells

Jingwen LIANG,Yingfeng LUO,Yi SUN,Meng LEI,Bing ZHANG,Songnian HU,Yaofeng ZHAO

《农业科学与工程前沿（英文）》 2014年 第1卷 第3期   页码 201-213 doi: 10.15302/J-FASE-2014017

摘要： In the bone marrow and spleen, the developing B cell populations undergo both negative and positive selections to shape their B cell receptor repertoire. To gain insight into the shift of the immunoglobulin heavy (IgH) chain repertoire during B cell development, we undertook large scale Ig μ chain repertoire analysis of pre-B, immature B and spleen B cell populations. We found that the majority of V gene segments, V families, J and D gene segments, were observed to have significantly different usage frequencies when three B cell populations were compared, but the usage profile of the V D, and J genes between different B cell populations showed high correlations. In both productive and nonproductive rearrangements, the length of CDRH3 shortened significantly on average when B cells entered the periphery. However, the CDRH3 length distribution of nonproductive rearrangements did not follow a Gaussian distribution, but decreased successively in the order 3 -2, 3 -1 and 3 , suggesting a direct correlation between mRNA stability and CDRH3 length patterns of nonproductive rearrangements. Further analysis of the individual components comprising CDRH3 of productive rearrangements indicated that the decrease in CDRH3 length was largely due to the reduction of N addition at the 5′ and 3′ junctions. Moreover, with development, the amino acid content of CDRH3 progressed toward fewer positively charged and nonpolar residues but more polar residues. All these data indicated that the expressed Ig μ chain repertoire, especially the repertoire of CDRH3, was fine-tuned when B cells passed through several checkpoints of selection during the process of maturation.

关键词： repertoire     complementarity determining region 3 of the IgH chain (CDRH3)     immunoglobulin     heavy chain     variable region    

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Factors affecting early embryonic development in cattle: relevance for bovine cloning

Yanna DANG, Kun ZHANG

《农业科学与工程前沿（英文）》 2019年 第6卷 第1期   页码 33-41 doi: 10.15302/J-FASE-2018228

摘要：

Female infertility represents a major challenge for improving the production efficiency in the dairy industry. Historically, fertility has declined whereas milk yield has increased tremendously due to intensive genetic selection. evidence reveals about 60% pregnancy loss takes place during the first month following fertilization. Meanwhile, early embryo development is significant for somatic cell nuclear transfer in cattle as a large proportion of cloned embryos fail to develop beyond peri-implantation stage. Oocyte quality is of utmost importance for the early embryo to develop to term for both fertilized and cloned embryos. Epigenetic reprogramming is a key process occurring after fertilization and critical roles of epigenetic modifiers during preimplantation development are now clear. Incomplete epigenetic reprogramming is believed to be a major limitation to cloning efficiency. Treatment of cloned embryos with epigenetic modifying drugs (e.g., Trichostatin A) could greatly improve cloning efficiency in both mice and cattle. Recently, the rapid progress in high-throughput sequencing technologies has enabled detailed deciphering of the molecular mechanisms underlying these events. The robust efficiency of genomic editing tools also presents an alternative approach to the functional annotation of genes critical to early development.

关键词： bovine cloning     embryo development     somatic cell nuclear transfer     X-inactive specific transcript    

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病毒性疾病对奶牛繁殖力的重要影响 Review

D. Claire Wathes, Chike F. Oguejiofor, Carole Thomas, Zhangrui Cheng

《工程（英文）》 2020年 第6卷 第1期   页码 26-33 doi: 10.1016/j.eng.2019.07.020

摘要： 妊娠中期非细胞病变型牛病毒性腹泻病毒（bovine viral diarrhea virus, BVDV）的急性感染会使流产率升高或导致持续感染的犊牛出生。牛疱疹病毒（bovine herpesvirus, BHV）-1型在青春期前的小母牛中最常见，会导致它们生长减缓，延迟繁殖并提高首次产犊的年龄，先前受感染的动物继而表现出繁殖力的降低。

关键词： 牛病毒性腹泻病毒     牛疱疹病毒1型     牛疱疹病毒4型     施马伦贝格病毒     蓝舌病毒     免疫抑制     胚胎死亡率    

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Structural prediction of porcine sialoadhesin V-set Ig-like domain sheds some light on its role in porcine

Jie HOU,Rui LI,Hongfang MA,Songlin QIAO,Gaiping ZHANG

《农业科学与工程前沿（英文）》 2016年 第3卷 第1期   页码 65-71 doi: 10.15302/J-FASE-2016086

摘要： Porcine reproductive and respiratory syndrome (PRRS) is characterized by reproductive failures in sows and respiratory diseases in pigs of all ages. PRRS virus (PRRSV) is its causative agent and has caused huge economic losses in the swine industry. Porcine sialoadhesin (pSn) is a putative receptor of PRRSV. Previous studies have shown that a pSn V-set Ig-like domain is significant in PRRSV infection. However, its structural details are not fully known, hindering our deep understanding of PRRSV infection. In this study, we successfully cloned, expressed and purified the pSn V-set Ig-like domain in S2 cells. Then we tried to crystallize the target protein and predicted its structure. This will establish the foundation for the further structural study of pSn, deepen our understanding of the invasion mechanism of PRRSV, and support the structural information for the development of clinical drugs and vaccines against PRRSV.

关键词： PRRSV     porcine sialoadhesin     V-set Ig-like domain     Drosophila S2 cell     crystallization    

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Effect of electrokinetic property of charged polyether sulfone membrane on bovine serum albumin fouling

Xiaorong Meng, Shanshan Huo, Lei Wang, Xudong Wang, Yongtao Lv, Weiting Tang, Rui Miao, Danxi Huang

《环境科学与工程前沿（英文）》 2017年 第11卷 第2期 doi: 10.1007/s11783-017-0907-9

摘要： Negatively charged CMPES and positively charged QAPES membranes were fabricated. Charge modification reduced the adhesion forces between PES UF membranes and BSA. QAPES-BSA / was weaker than that of CMPES-BSA at pH 3 and on the contrary at pH 9. Flux decline rate was positively correlated with the adhesion forces of membrane-BSA. Variation of adhesion was consistent with that of potential absolute values. Negatively charged carboxymethylated polyethersulfone (CMPES) and positively charged quaternized polyethersulfone (QAPES) ultrafiltration (UF) membranes were prepared by bulk chemical modification and non-solvent induced phase separation method. The effects of PES membrane interfacial electrokinetic property on the bovine serum albumin (BSA) membrane fouling behavior were studied with the aid of the membrane-modified colloidal atomic force microscopy (AFM) probe. Electrokinetic test results indicated that the streaming potential (D ) of QAPES membrane was not consistent with its expected value, however, within the pH range of 3–10, the potentials of two charged-modified PES membranes were more stable than the unmodified membrane. When pH value was 3, 4.7 or 9, the interaction behavior between charged PES membrane and BSA showed that there was significant linear correlation between the jump distance of membrane-BSA adhesion force ( ) and the potential absolute value. Charged modification significantly reduced the adhesion of PES membrane-BSA, and the adhesion data was good linear correlated with the flux decline rate in BSA filtration process, especially reflected in the CMPES membrane. The above experimental facts proved that the charged membrane interfacial electric double layer structure and its electrokinetic property had strong ties with the protein membrane fouling behavior.

关键词： Charged PES UF membrane     BSA     Electrokinetic characterization     Adhesion force     Jump distance    

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Co-pyrolysis of sludge and kaolin/zeolite in a rotary kiln: Analysis of stabilizing heavy metals

《环境科学与工程前沿（英文）》 2022年 第16卷 第7期 doi: 10.1007/s11783-021-1488-1

摘要：

• Adding kaolin/zeolite promotes the formation of stable heavy metals.

关键词： Co-pyrolysis     Sewage sludge     Heavy metals     Rotary kiln     Immobilization mechanism    

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Effects of sulfur on variations in the chemical speciation of heavy metals from fly ash glass

《环境科学与工程前沿（英文）》 2023年 第17卷 第10期 doi: 10.1007/s11783-023-1728-7

摘要：

● A higher sulfur content reduced the curing rate of Cr in glass.

关键词： Dechlorinated fly ash     SO3     Heavy metal     Chemical speciation     Glass solidification    

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Pricing and production strategies in remanufacturing from the perspectives of supply chain: Review and

《工程管理前沿（英文）》 doi: 10.1007/s42524-023-0251-7

摘要： Remanufacturing is widely recognized as beneficial to the environment and a circular economy. However, remanufacturing is more complex than traditional manufacturing due to the effects of government policy, uncertainty of consumer preferences, competition and cooperation among firms, and so on. These factors motivate academics to optimize remanufacturing outcomes, especially for product pricing and production. This study reviews the published literature on pricing and production strategies in remanufacturing from four perspectives of supply chain, namely, government policy, consumer characteristics, relationships among firms, and supply chain structures. Review results can benefit scholars/practitioners in the future by highlighting the challenges and opportunities in remanufacturing strategies.

关键词： remanufacturing     reverse and closed-loop supply chain     circular economy    

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ASSESSMENT OF HEAVY METALS IN HYDROCHAR PRODUCED BY HYDROTHERMAL CARBONIZATION OF DAIRY MANURE

《农业科学与工程前沿（英文）》 2023年 第10卷 第3期   页码 437-447 doi: 10.15302/J-FASE-2023507

摘要：

● Content of heavy metals in hydrochar varies considerably, from 50% to 100%.

关键词： heavy metals     dairy manure     hydrochar     hydrothermal carbonization     waste management    

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Modeling of the resilient supply chain system from a perspective of production design changes

《工程管理前沿（英文）》   页码 96-106 doi: 10.1007/s42524-022-0235-z

摘要： Building an effective resilient supply chain system (RSCS) is critical and necessary to reduce the risk of supply chain disruptions in unexpected scenarios such as COVID-19 pandemic and trade wars. To overcome the impact of insufficient raw material supply on the supply chain in mass disruption scenarios, this study proposes a novel RSCS considering product design changes (PDC). An RSCS domain model is first developed from the perspective of PDC based on a general conceptual framework, i.e., function-context-behavior-principle-state-structure (FCBPSS), which can portray complex systems under unpredictable situations. Specifically, the interaction among the structure, state and behavior of the infrastructure system and substance system is captured, and then a quantitative analysis of the change impact process is presented to evaluate the resilience of both the product and supply chain. Next, a case study is conducted to demonstrate the PDC strategy and to validate the feasibility and effectiveness of the RSCS domain model. The results show that the restructured RSCS based on the proposed strategy and model can remedy the huge losses caused by the unavailability of raw materials.

关键词： resilient supply chain     supply chain disruption     domain modeling     product design changes    

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标题 作者 时间 类型 操作

Depletion of conventional mature B cells and compromised specific antibody response in bovine immunoglobulinμ heavy-chain transgenic mice

Min ZHANG,Xueqian CHENG,Dan CHU,Jingwen LIANG,Yi SUN,Li MA,Beilei XU,Min ZHENG,Meili WANG,Liming REN,Xiaoxiang HU,Qingyong MENG,Ran ZHANG,Ying GUO,Yunping DAI,Robert AITKEN,Ning LI,Yaofeng ZHAO

期刊论文

A comprehensive analysis of immunoglobulin heavy chain genes in the Bactrian camel (

Zuoxiang LIANG,Tao WANG,Yi SUN,Wenlong YANG,Zhihong LIU,Jing FEI,Ying GUO,Qingwei MA,Qingjie PAN,Liming REN

期刊论文

Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice

期刊论文

of hemorrhagic diathesis in hemophilia A mice by an AAV-delivered hybrid FVIII composed of the human heavychain and the rat light chain

期刊论文

The past, present and future of bovine pluripotent stem cells: a brief overview

Xiuchun TIAN

期刊论文

Development of the expressed immunoglobulin μ chain repertoire during maturation of mice B cells

Jingwen LIANG,Yingfeng LUO,Yi SUN,Meng LEI,Bing ZHANG,Songnian HU,Yaofeng ZHAO

期刊论文

Factors affecting early embryonic development in cattle: relevance for bovine cloning

Yanna DANG, Kun ZHANG

期刊论文

病毒性疾病对奶牛繁殖力的重要影响

D. Claire Wathes, Chike F. Oguejiofor, Carole Thomas, Zhangrui Cheng

期刊论文

Structural prediction of porcine sialoadhesin V-set Ig-like domain sheds some light on its role in porcine

Jie HOU,Rui LI,Hongfang MA,Songlin QIAO,Gaiping ZHANG

期刊论文

Effect of electrokinetic property of charged polyether sulfone membrane on bovine serum albumin fouling

Xiaorong Meng, Shanshan Huo, Lei Wang, Xudong Wang, Yongtao Lv, Weiting Tang, Rui Miao, Danxi Huang

期刊论文

Co-pyrolysis of sludge and kaolin/zeolite in a rotary kiln: Analysis of stabilizing heavy metals

期刊论文

Effects of sulfur on variations in the chemical speciation of heavy metals from fly ash glass

期刊论文

Pricing and production strategies in remanufacturing from the perspectives of supply chain: Review and

期刊论文

ASSESSMENT OF HEAVY METALS IN HYDROCHAR PRODUCED BY HYDROTHERMAL CARBONIZATION OF DAIRY MANURE

期刊论文

Modeling of the resilient supply chain system from a perspective of production design changes

期刊论文