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Base editing in pigs for precision breeding

Ruigao SONG, Yu WANG, Yanfang WANG, Jianguo ZHAO

《农业科学与工程前沿（英文）》 2020年 第7卷 第2期   页码 161-170 doi: 10.15302/J-FASE-2019308

摘要：

Pigs are one of the most important domesticated animals and have great value in agriculture and biomedicine. Single nucleotide polymorphisms (SNPs) are a dominant type of genetic variation among individual pigs and contribute to the formation of traits. Precision single base substitution provides a strategy for accurate genetic improvement in pig production with the characterization of functional SNPs and genetic variants in pigs. Base editing has recently been developed as the latest gene-editing tool that can directly make changes in single nucleotides without introducing double-stranded DNA breaks (DSBs), providing a promising solution for precise genetic modification in large animals. This review summarizes gene-editing developments and highlights recent genetic dissection related to SNPs in major economic traits which may have the potential to be modified using SNP-editing applications. In addition, limitations and future directions of base editing in pig breeding are discussed.

关键词： base editing     genetic improvement     pigs     single nucleotide polymorphisms    

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A post-GWAS replication study confirming the association of

Shaohua YANG,Chao QI,Yan XIE,Xiaogang CUI,Yahui GAO,Jianping JIANG,Li JIANG,Shengli ZHANG,Qin ZHANG,Dongxiao SUN

《农业科学与工程前沿（英文）》 2014年 第1卷 第4期   页码 321-330 doi: 10.15302/J-FASE-2014037

摘要： Genome-wide association studies with an Illumina Bovine50K chip have detected 105 SNPs associated with one or multiple milk production traits in the Chinese Holstein population. Of these, 38 significant SNPs detected with high confidence by both L1-TDT and MMRA methods were selected to further mine potential key genes affecting milk yield and milk composition. By blasting the flanking sequences of these 38 SNPs with the bovine genome sequence combined with comparative genomics analysis, 26 genes were found to contain or be near to such SNPs. Among them, the gene is merely 87 bp away from the significant SNP, Hapmap30383-BTC-005848. Hence, we report herein genotype-phenotype associations to further validate the genetic effects of the gene. By pooled DNA sequencing of 14 unrelated Holstein sires, a total of 18 with seven novel SNPs were identified. Among them, nine SNPs were in the 5′ regulatory region, one in exon 6 and the other in the 3′ UTR and 3′ regulatory region. A total of nine of these identified SNPs were successfully genotyped and analyzed by mass spectrometry for association with five milk production traits in an independent resource population. The results showed that these SNPs were statistically significant for more than two traits [ <(0.0001-0.0267)]. In addition, mRNA expression analyses revealed that was ubiquitous in eight different tissues, with a relatively higher expression level in the mammary gland than in other tissues. These findings, therefore, provide strong evidence for association of variants with milk yield and milk composition traits and may be applied in Chinese Holstein breeding programs.

关键词： GWAS     functional annotation     Chinese Holstein     milk production traits     C14H8orf33 gene     single nucleotide polymorphisms     association study    

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Cyclooxygenase-2 gene-1195G/A genotype is associated with the risk of HBV-induced HCC: A case-control study in Han Chinese people

Li-Feng LIU MD, PhD, Qiong CHEN MD, PhD, Ying CHANG MD, PhD, Ju-Sheng LIN MD, PhD, Jin-Liang ZHANG MM,

《医学前沿（英文）》 2010年 第4卷 第1期   页码 90-95 doi: 10.1007/s11684-010-0021-x

摘要： This study aimed to identify functional single nucleotide polymorphisms in the cyclooxygenase-2 gene promoter and evaluate their effects on the risk of primary hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) infection. We conducted a population-based, case-control study enrolling 630 Han Chinese people in Hubei province. Subjects included primary HCC patients with HBV infection (=210), chronic hepatitis B cases (=210) and healthy Han Chinese (=210). -1195G/A polymorphism was analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing analysis. We found-1195A allele carriers had a higher risk of HCC with HBV infection (OR, 0.72; 95% CI, 0.548–0.946). The-1195A allele might be used as a marker in screening individuals at high risk of HCC with HBV infection.

关键词： cyclooxygenase-2 gene     single nucleotide polymorphisms     susceptibility     primary hepatocellular carcinoma     hepatitis B virus infection    

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FMO3--TMAO axis modulates the clinical outcome in chronic heart-failure patients with reduced ejection fraction: evidence from an Asian population

《医学前沿（英文）》 2022年 第16卷 第2期   页码 295-305 doi: 10.1007/s11684-021-0857-2

摘要： The association among plasma trimethylamine-N-oxide (TMAO), FMO3 polymorphisms, and chronic heart failure (CHF) remains to be elucidated. TMAO is a microbiota-dependent metabolite from dietary choline and carnitine. A prospective study was performed including 955 consecutively diagnosed CHF patients with reduced ejection fraction, with the longest follow-up of 7 years. The concentrations of plasma TMAO and its precursors, namely, choline and carnitine, were determined by liquid chromatography-mass spectrometry, and the FMO3 E158K polymorphisms (rs2266782) were genotyped. The top tertile of plasma TMAO was associated with a significant increment in hazard ratio (HR) for the composite outcome of cardiovascular death or heart transplantation (HR=1.47, 95% CI=1.13–1.91, P=0.004) compared with the lowest tertile. After adjustments of the potential confounders, higher TMAO could still be used to predict the risk of the primary endpoint (adjusted HR=1.33, 95% CI=1.01–1.74, P=0.039). This result was also obtained after further adjustment for carnitine (adjusted HR=1.33, 95% CI=1.01–1.74, P=0.039). The FMO3 rs2266782 polymorphism was associated with the plasma TMAO concentrations in our cohort, and lower TMAO levels were found in the AA-genotype. Thus, higher plasma TMAO levels indicated increased risk of the composite outcome of cardiovascular death or heart transplantation independent of potential confounders, and the FMO3 AA-genotype in rs2266782 was related to lower plasma TMAO levels.

关键词： chronic heart failure     trimethylamine-N-oxide     flavin monooxygenase 3     single nucleotide polymorphism    

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Carcinogens that induce the A:T>T:A nucleotide substitutions in the genome

null

《医学前沿（英文）》 2018年 第12卷 第2期   页码 236-238 doi: 10.1007/s11684-017-0611-y

摘要：

Recently, Ng . reported that the A:T>T:A substitutions, proposed to be a signature of aristolochic acid (AA) exposure, were detected in 76/98 (78%) of patients with hepatocellular carcinoma (HCC) from the Taiwan Province of China, and 47% to 1.7% of HCCs from the Chinese mainland and other countries harbored the nucleotide changes. However, other carcinogens, e.g., tobacco carcinogens 4-aminobiphenyl and 1,3-butadiene, air toxic vinyl chloride and its reactive metabolites chloroethylene oxide, melphalan and chlorambucil, also cause this signature in the genome. Since tobacco smoke is a worldwide public health threat and vinyl chloride distributes globally and is an air pollutant in Taiwan Province, the estimation of the patients’ exposure history is the key to determine the “culprit” of the A:T>T:A mutations. Apparently, without estimation of the patients’ exposure history, the conclusion of Ng is unpersuasive and misleading.

关键词： genomic signature     carcinogen     aristolochic acid     tobacco smoke     vinyl chloride     hepatocellular carcinoma    

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宿主微生物组内的基因组突变——适应性进化或净化选择 Review

张家超, Rob Knight

《工程（英文）》 2023年 第20卷 第1期   页码 96-102 doi: 10.1016/j.eng.2021.11.018

摘要：

二代测序技术转变了人们评估宿主相关微生物区系和微生物组的分类组成功能的能力。未来10 年将会开展更多的人类微生物组研究，特别是那些探索微生物组内基因组突变的研究。本文聚焦于微生物组内菌株之间的共同进化，塑造了宿主肠道微生物种内和种间的菌株水平多样性。还探讨了微生物基因组突变与常见代谢疾病之间的关联，以及病原体和益生菌在入侵和定植过程中的适应性进化。最后，讨论了注释和分析微生物基因组突变方法和算法的研究进展。

关键词： 肠道菌群     基因组突变     适应性进化     净化选择     单核苷酸变异    

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The role of natriuretic peptide precursor A gene polymorphism in the development of coronary heart disease in Chinese Han population?

Ripen NSENGA MD, Longxian CHENG PhD, Mei’an HE PhD, Tangchun WU PhD,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 437-442 doi: 10.1007/s11684-009-0074-x

摘要： Natriuretic peptide precursor A (NPPA) is synthesized, stored, and released by atrial myocytes. Previous studies have shown that NPPA plays a significant role in the regulation of coronary circulation and in atherosclerosis. Rs5065 NPPA gene polymorphism leads to the translation of NPPA with two additional arginines and has been suggested to be associated with salt-sensitive hypertension. The purpose of the present study was to investigate the relationship between the rs5065 NPPA gene polymorphism and the risk of coronary heart disease (CHD) in Chinese Han population. We genotyped the single nucleotide polymorphism (SNP) rs5065 NPPA in the human NPPA gene in 1861 sex- and age-matched subjects, comprising of 904 CHD cases and 957 controls of Chinese Han population. Genotyping of SNP was performed with Taqman SNP allelic discrimination assays by means of an ABI 7900HT. Our study showed that the frequencies of rs5065 NPPA C allele in the case and the control groups were 0.012 and 0.005, respectively. There was significant difference in C allele frequency distribution between the two groups (OR=2.607, 95% CI: 1.197−5.678, =0.012). In the case group, there was significant difference between smokers and nonsmokers with subjects carrying C allele (=0.037), and no significant difference in gender, age, fasting total cholesterol (TC), triglycerides (TG), fasting plasma glucose (FPG), body mass index (BMI), and blood pressure (BP) between the cases and the controls (>0.05). Our results suggest that the C allele of rs5065 NPPA gene polymorphism may be associated with the risk of CHD.

关键词： natriuretic peptide precursor A     coronary heart disease     gene polymorphism     allelic discrimination     polymorphism     single nucleotide    

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Functional XPF polymorphisms associated with lung cancer susceptibility in a Chinese population

Dian-Ke YU PhD, Chen WU MD, Wen TAN MD, Dong-Xin LIN MD,

《医学前沿（英文）》 2010年 第4卷 第1期   页码 82-89 doi: 10.1007/s11684-010-0014-9

摘要： Variation of individuals’ DNA repair capacity has been linked to cancer susceptibility. The xeroderma pigmentsum group F (XPF) plays a pivotal role in nucleotide-excision repair (NER) pathway. This study was to examine the functional significance of promoter polymorphisms and their association with lung cancer risk. The function of promoter polymorphisms was tested by a set of biochemical assays, and their effects on lung cancer risk were determined by a case-control analysis of 988 patients with lung cancer and 986 controls. The −673T allele showed a significantly higher transcriptional activity as compared with the −673C allele. The −673TT genotype was associated with a decreased risk of lung cancer compared with the CC genotype (adjusted OR=0.62, 95% CI=0.42–0.91; =0.015) and this effect was more significant among males (adjusted OR=0.55, 95% CI=0.35–0.86; =0.009), elder subjects (adjusted OR=0.51, 95% CI=0.30–0.86; =0.012), and light smokers (adjusted OR=0.35, 95% CI=0.14–0.88; =0.026). These findings suggest that functional polymorphisms influencing DNA repair capacity may confer susceptibility to lung cancer.

关键词： XPF     polymorphism     lung cancer    

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secretion from peripheral blood monocular cells by triptolid is associated with TNF-alpha-308 gene polymorphisms

Xiu-Liang TAO MM, Sheng-Hao TU MD, Ri-Bo XIONG MM, Yong-Hong HU BM,

《医学前沿（英文）》 2010年 第4卷 第2期   页码 220-224 doi: 10.1007/s11684-010-0025-6

摘要： This study examined the inhibitory effect of triptolid (TP) on tumor necrosis factor-α (TNF-α) secreted from peripheral blood monocular cells (PBMCs) and the association of the inhibitory effect with TNF-α-308 gene polymorphisms in rheumatoid arthritis (RA) patients. Gene polymorphism at A-G site 308 in the promoter region of TNF-α gene was detected in 42 RA patients by using allele specific polymerase chain reaction (AS-PCR) assay. PBMCs were harvested from these patients and treated first with lipopolysaccharides (LPS) and then with different doses of TP (1, 5.4 and 15 ng/mL). The TNF-α level in the supernatants was measured by enzyme-linked immunosorbent assay (ELISA). The results showed that TNF-α level in the supernatants of TP (1 ng/mL)-treated PBMCs was decreased by 3.80% and 4.91%, respectively, in the patients with AA and AG genotypes, when compared with those treated with LPS alone (>0.05). Moreover, the TNF-α level in the patients with GG genotype was reduced by 20.74% (<0.05). When PBMCs were treated with TP at 5.4 ng/mL, TNF-α levels in the patients with AA, AG, and GG genotypes were decreased by 20.42%, 34.73%, and 41.69%, respectively (<0.05). The TNF-α level was slightly higher in the PBMCs treated with 15 ng/mL of TP than those in the two TP groups in the patients carrying AA, AG, and GG genotypes (>0.05). It was concluded that gene polymorphism at TNF-α-308 sites may relate to the secretion of TNF-α in RA patients. TP has different inhibitory effects on the secretion of TNF-α in the patients harboring different genotypes, which may be one of the reasons for individual variation in response to TP.

关键词： arthritis     rheumatoid     molonuclear cells     tumor necrosis factor     gene polymorphisms     triptolid    

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Advances in newly developing therapy for chronic hepatitis C virus infection

null

《医学前沿（英文）》 2014年 第8卷 第2期   页码 166-174 doi: 10.1007/s11684-014-0334-2

摘要：

Chronic hepatitis C virus (HCV) infection afflicts a reported 170 million people worldwide and is often complicated by cirrhosis and hepatocellular carcinoma. Morbidity and mortality are decreased with the successful treatment of chronic HCV infection. Increased understanding of the HCV has allowed further development of new direct-acting antiviral (DAA) agents against the HCV and has also allowed the development of IFN-free oral treatment regimens. In late 2013 the first nucleotide polymerase inhibitor regimen with RBV alone for genotypes 2/3 and in combination with a 12-week regimen of PEG-IFN+RBV for genotypes 1, 4 was approved for use in the US. A number of promising new DAA regimens which are IFN-free are in phase 3 development and the first will likely be approved for use in the US in 2014. The currently approved regimens are discussed in detail and currently available data on future regimens are reviewed herein.

关键词： direct-acting antiviral (DAA)     nucleotide polymerase inhibitors     protease inhibitors    

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Crystallographic orientation effect on cutting-based single atomic layer removal

Wenkun XIE, Fengzhou FANG

《机械工程前沿（英文）》 2020年 第15卷 第4期   页码 631-644 doi: 10.1007/s11465-020-0599-x

摘要： The ever-increasing requirements for the scalable manufacturing of atomic-scale devices emphasize the significance of developing atomic-scale manufacturing technology. The mechanism of a single atomic layer removal in cutting is the key basic theoretical foundation for atomic-scale mechanical cutting. Material anisotropy is among the key decisive factors that could not be neglected in cutting at such a scale. In the present study, the crystallographic orientation effect on the cutting-based single atomic layer removal of monocrystalline copper is investigated by molecular dynamics simulation. When undeformed chip thickness is in the atomic scale, two kinds of single atomic layer removal mechanisms exist in cutting-based single atomic layer removal, namely, dislocation motion and extrusion, due to the differing atomic structures on different crystallographic planes. On close-packed crystallographic plane, the material removal is dominated by the shear stress-driven dislocation motion, whereas on non-close packed crystallographic planes, extrusion-dominated material removal dominates. To obtain an atomic, defect-free processed surface, the cutting needs to be conducted on the close-packed crystallographic planes of monocrystalline copper.

关键词： ACSM     single atomic layer removal mechanism     crystallographic orientation effect     mechanical cutting     Manufacturing III    

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Design and analysis of partially decoupled translational parallel mechanisms with single-loop structures

《机械工程前沿（英文）》 2022年 第17卷 第3期 doi: 10.1007/s11465-022-0695-1

摘要： This study presents a family of novel translational parallel mechanisms (TPMs) with single-loop topological structures. The proposed mechanism consists of only revolute and prismatic joints. The novel TPMs are simpler in structure and have fewer joints and components than the well-known Delta Robot. Four types of 2-degree of freedom driving systems are applied to different limb structures to avoid the moving actuator that causes the problem of increased moving mass. Four sample TPMs are constructed using the synthesized limbs, and one of them is investigated in terms of kinematic performance. First, a position analysis is performed and validated through numerical simulation to reveal the characteristics of partially decoupled motion, which improves the controllability of TPM. Second, singular configurations are identified, and the resulting singularity curve is obtained. Lastly, the workspace of TPM is analyzed, and the relationship between the singular configurations and the reachable workspace is explored. The workspace of the 3-CRR (C denotes the cylindrical joint and R denotes the revolute joint) translational mechanism is also presented to prove that the proposed TPM has a fairly large workspace.

关键词： translational parallel mechanism     single loop     multiple driving system     workspace analysis     singularity    

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Moving policy and regulation forward for single-use plastic alternatives

《环境科学与工程前沿（英文）》 2021年 第15卷 第3期 doi: 10.1007/s11783-021-1423-5

摘要： Single-use plastics are often used once or cannot be reused for extended periods. They are widely consumed with the rapid development of social economy. The waste generated by single-use plastics threatens ecosystem health by entering the environment and ultimately restricts sustainable human development. The innovation of sustainable and environmentally friendly single-use plastic alternative materials and the joint participation of governments, enterprises and the public are promising technologies and management approaches that can solve the problem of single-use plastics wastes. The development of single-use plastic alternative products can be promoted fundamentally only by improving relevant legislation and standards, providing differentiated industrial policies, encouraging scientific and technological innovation and expanding public participation.

关键词： Single-use plastic alternatives     Policy     Regulation     Sustainable development    

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Damage propagation and strength prediction of a single-lap interference-fit laminate structure

Peng ZOU, Xiangming CHEN, Hao CHEN, Guanhua XU

《机械工程前沿（英文）》 2020年 第15卷 第4期   页码 558-570 doi: 10.1007/s11465-020-0591-5

摘要： Experimental and finite element research was conducted on the bolted interference fit of a single-lap laminated structure to reveal the damage propagation mechanism and strength change law. A typical single-lap statically loading experiment was performed, and a finite element damage prediction model was built based on intralaminar progress damage theory. The model was programmed with a user subroutine and an interlaminar cohesive zone method. The deformation and damage propagation of the specimen were analyzed, and the failure mechanism of intralaminar and interlaminar damage during loading was discussed. The effect of secondary bending moment on load translation and damage distribution was revealed. The experimental and simulated load–displacement curves were compared to validate the developed model’s reliability, and the ultimate bearing strengths under different fit percentages were predicted. An optimal percentage was also recommended.

关键词： single-lap     interference fit     secondary bending moment     damage mechanism     bearing strength    

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Novel casting processes for single-crystal turbine blades of superalloys

Dexin MA

《机械工程前沿（英文）》 2018年 第13卷 第1期   页码 3-16 doi: 10.1007/s11465-018-0475-0

摘要：

This paper presents a brief review of the current casting techniques for single-crystal (SC) blades, as well as an analysis of the solidification process in complex turbine blades. A series of novel casting methods based on the Bridgman process were presented to illustrate the development in the production of SC blades from superalloys. The grain continuator and the heat conductor techniques were developed to remove geometry-related grain defects. In these techniques, the heat barrier that hinders lateral SC growth from the blade airfoil into the extremities of the platform is minimized. The parallel heating and cooling system was developed to achieve symmetric thermal conditions for SC solidification in blade clusters, thus considerably decreasing the negative shadow effect and its related defects in the current Bridgman process. The dipping and heaving technique, in which thin-shell molds are utilized, was developed to enable the establishment of a high temperature gradient for SC growth and the freckle-free solidification of superalloy castings. Moreover, by applying the targeted cooling and heating technique, a novel concept for the three-dimensional and precise control of SC growth, a proper thermal arrangement may be dynamically established for the microscopic control of SC growth in the critical areas of large industrial gas turbine blades.

关键词： superalloy     investment casting     Bridgman process     directional solidification     single crystal     turbine blade    

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标题 作者 时间 类型 操作

Base editing in pigs for precision breeding

Ruigao SONG, Yu WANG, Yanfang WANG, Jianguo ZHAO

期刊论文

A post-GWAS replication study confirming the association of

Shaohua YANG,Chao QI,Yan XIE,Xiaogang CUI,Yahui GAO,Jianping JIANG,Li JIANG,Shengli ZHANG,Qin ZHANG,Dongxiao SUN

期刊论文

Cyclooxygenase-2 gene-1195G/A genotype is associated with the risk of HBV-induced HCC: A case-control study in Han Chinese people

Li-Feng LIU MD, PhD, Qiong CHEN MD, PhD, Ying CHANG MD, PhD, Ju-Sheng LIN MD, PhD, Jin-Liang ZHANG MM,

期刊论文

FMO3--TMAO axis modulates the clinical outcome in chronic heart-failure patients with reduced ejection fraction: evidence from an Asian population

期刊论文

Carcinogens that induce the A:T>T:A nucleotide substitutions in the genome

null

期刊论文

宿主微生物组内的基因组突变——适应性进化或净化选择

张家超, Rob Knight

期刊论文

The role of natriuretic peptide precursor A gene polymorphism in the development of coronary heart disease in Chinese Han population?

Ripen NSENGA MD, Longxian CHENG PhD, Mei’an HE PhD, Tangchun WU PhD,

期刊论文

Functional XPF polymorphisms associated with lung cancer susceptibility in a Chinese population

Dian-Ke YU PhD, Chen WU MD, Wen TAN MD, Dong-Xin LIN MD,

期刊论文

secretion from peripheral blood monocular cells by triptolid is associated with TNF-alpha-308 gene polymorphisms

Xiu-Liang TAO MM, Sheng-Hao TU MD, Ri-Bo XIONG MM, Yong-Hong HU BM,

期刊论文

Advances in newly developing therapy for chronic hepatitis C virus infection

null

期刊论文

Crystallographic orientation effect on cutting-based single atomic layer removal

Wenkun XIE, Fengzhou FANG

期刊论文

Design and analysis of partially decoupled translational parallel mechanisms with single-loop structures

期刊论文

Moving policy and regulation forward for single-use plastic alternatives

期刊论文

Damage propagation and strength prediction of a single-lap interference-fit laminate structure

Peng ZOU, Xiangming CHEN, Hao CHEN, Guanhua XU

期刊论文

Novel casting processes for single-crystal turbine blades of superalloys

Dexin MA

期刊论文