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Single-base editing in IGF2 improves meat production and intramuscular fat deposition in Liang Guang Small Spotted pigs 被引量:4
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作者 Tianqi Duo xiaohong liu +11 位作者 Delin Mo Yu Bian Shufang Cai Min Wang Ruiqiang Li Qi Zhu Xian Tong Ziyun Liang Weilun Jiang Shiyi Chen Yaosheng Chen Zuyong He 《Journal of Animal Science and Biotechnology》 SCIE CAS CSCD 2024年第1期108-126,共19页
Background Chinese indigenous pigs are popular with consumers for their juiciness,flavour and meat quality,but they have lower meat production.Insulin-like growth factor 2(IGF2) is a maternally imprinted growth factor... Background Chinese indigenous pigs are popular with consumers for their juiciness,flavour and meat quality,but they have lower meat production.Insulin-like growth factor 2(IGF2) is a maternally imprinted growth factor that promotes skeletal muscle growth by regulating cell proliferation and differentiation.A single nucleotide polymorphism(SNP) within intron 3 of porcine IGF2 disrupts a binding site for the repressor,zinc finger BED-type containing 6(ZBED6),leading to up-regulation of IGF2 and causing major effects on muscle growth,heart size,and backfat thickness.This favorable mutation is common in Western commercial pig populations,but absent in most Chinese indigenous pig breeds.To improve meat production of Chinese indigenous pigs,we used cytosine base editor 3(CBE3)to introduce IGF2 intron3-C3071T mutation into porcine embryonic fibroblasts(PEFs) isolated from a male Liang Guang Small Spotted pig(LGSS),and single-cell clones harboring the desired mutation were selected for somatic cell nuclear transfer(SCNT) to generate the founder line of IGF2^(T/T) pigs.Results We found the heterozygous progeny IGF2^(C/T) pigs exhibited enhanced expression of IGF2,increased lean meat by 18%-36%,enlarged loin muscle area by 3%-17%,improved intramuscular fat(IMF) content by 18%-39%,marbling score by 0.75-1,meat color score by 0.53-1.25,and reduced backfat thickness by 5%-16%.The enhanced accumulation of intramuscular fat in IGF2^(C/T) pigs was identified to be regulated by the PI3K-AKT/AMPK pathway,which activated SREBP1 to promote adipogenesis.Conclusions We demonstrated the introduction of IGF2-intron3-C3071T in Chinese LGSS can improve both meat production and quality,and first identified the regulation of IMF deposition by IGF2 through SREBP1 via the PI3KAKT/AMPK signaling pathways.Our study provides a further understanding of the biological functions of IGF2and an example for improving porcine economic traits through precise base editing. 展开更多
关键词 CBE3 IGF2 Intramuscular fat Meat production PI3K-AKT/AMPK ZBED6
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Targeted anti-cancer therapy: Co-delivery of VEGF siRNA and Phenethyl isothiocyanate (PEITC) via cRGD-modified lipid nanoparticles for enhanced anti-angiogenic efficacy 被引量:1
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作者 Bao Li Haoran Niu +10 位作者 Xiaoyun Zhao Xiaoyu Huang Yu Ding Ke Dang Tianzhi Yang Yongfeng Chen Jizhuang Ma xiaohong liu Keda Zhang Huichao Xie Pingtian Ding 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2024年第2期170-187,共18页
Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target ... Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics. 展开更多
关键词 ANTI-ANGIOGENESIS Tumor apoptosis Nanoparticles VEGF siRNA Hypoxia inducible factor(HIF)-1 protein Phenethyl isothi ocyanate(PEITC)
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Decline in tree-ring growth of Picea mongolica and its intra-annual eco-physiological responses to drought and CO_(2) enrichment in semi-arid China
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作者 Xiaomin Zeng Ping Ni +3 位作者 xiaohong liu Wenzhi Wang Yao Li Wenchao Wang 《Journal of Forestry Research》 SCIE EI CAS CSCD 2024年第4期89-101,共13页
Episodes of drought-induced decline in tree growth and mortality are becoming more frequent as a result of climate warming and enhanced water stress in semi-arid areas.However,the ecophysiological mechanisms under-lyi... Episodes of drought-induced decline in tree growth and mortality are becoming more frequent as a result of climate warming and enhanced water stress in semi-arid areas.However,the ecophysiological mechanisms under-lying the impact of drought on tree growth remains unre-solved.In this study,earlywood and latewood tree-ring growth,δ^(13)C,andδ^(18)O chronologies of Picea mongolica from 1900 to 2013 were developed to clarify the intra-and inter-annual tree-ring growth responses to increasingly fre-quent droughts.The results indicate that annual basal area increment residuals(BAI_(res)),which removed tree age and size effects,have significantly decreased since 1960.How-ever,the decreasing trend of earlywood BAI_(res) was higher than that of latewood.Climate response analysis suggests that the dominant parameters for earlywood and latewood proxies(BAI_(res),δ^(13)C andδ^(18)O)were drought-related climate variables(Palmer drought severity index,temperature,rela-tive humidity,and vapor pressure deficit).The most signifi-cant period of earlywood and latewood proxies’responses to climate variables were focused on June-July and July-August,respectively.BAI_(res),andδ^(13)C were significantly affected by temperature and moisture conditions,whereasδ^(18)O was slightly affected.Decreasing stomatal conduct-ance due to drought outweighed the influence of increasing CO_(2) on intrinsic water use efficiency(iWUE),and ultimately led to a decline in BAI_(res).Compared to latewood,the faster decreasing BAI_(res) and smaller increasing iWUE of early-wood suggested trees were more vulnerable to water stress in the early growing season.Our study provides insights into the inter-and intra-annual mechanisms of tree-ring growth in semi-arid regions under rising CO_(2) and climate change. 展开更多
关键词 Tree growth DROUGHT Water-use efficiency Seasonal differences Stable isotopes
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Phase engineering of Ni-Mn binary layered oxide cathodes for sodiumion batteries
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作者 Feifei Hong Xin Zhou +9 位作者 xiaohong liu Guilin Feng Heng Zhang Weifeng Fan Bin Zhang Meihua Zuo Wangyan Xing Ping Zhang Hua Yan Wei Xiang 《Journal of Energy Chemistry》 SCIE EI CAS CSCD 2024年第4期501-511,共11页
Nickel-manganese binary layered oxides with high working potential and low cost are potential candidates for sodium-ion batteries,but their electrochemical properties are highly related to compositional diversity.Dive... Nickel-manganese binary layered oxides with high working potential and low cost are potential candidates for sodium-ion batteries,but their electrochemical properties are highly related to compositional diversity.Diverse composite materials with various phase structures of P3,P2/P3,P2,P2/O3,and P2/P3/O3 were synthesized by manipulating the sodium content and calcination conditions,leading to the construction of a synthetic phase diagram for Na_(x)Ni_(0.25)Mn_(0.75)O_(2)(0.45≤x≤1.1).Then,we compared the electrochemical characteristics and structural evolution during the desodiation/sodiation process of P2,P2/P3,P2/03,and P2/P3/O3-Na_(x)Ni_(0.25)Mn_(0.75)O_(2).Among them,P2/P3-Na0.75Ni0.25Mn0.75O2exhibits the best rate capability of 90.9 mA h g^(-1)at 5 C,with an initial discharge capacity of 142.62 mA h g^(-1)at 0.1 C and a capacity retention rate of 78.25%after 100 cycles at 1 C in the voltage range of 2-4.3 V.The observed superior sodium storage performance of P2/P3 hybrids compared to other composite phases can be attributed to the enhanced Na^(+)transfer dynamic,reduction of the Jahn-teller effect,and improved reaction reversibility induced by the synergistic effect of P2 and P3 phases.The systematic research and exploration of phases in Na_(x)Ni_(0.25)Mn_(0.75)O_(2)provide new sights into high-performance nickel-manganese binary layered oxide for sodium-ion batteries. 展开更多
关键词 Phase engineering Ni-Mn layered oxide CATHODE Sodium-ion batteries
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Rydberg-Atom Terahertz Heterodyne Receiver with Ultrahigh Spectral Resolution
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作者 Zhenyue She Xiaojie Zhu +10 位作者 Yayi Lin Xianzhe Li Xiaolin Yang Yanfei Shang Yuqin Teng Haitao Tu Kaiyu Liao Caixia Zhang xiaohong liu Jiehua Chen Wei Huang 《Chinese Physics Letters》 SCIE EI CAS CSCD 2024年第8期17-21,共5页
Terahertz heterodyne receivers with high sensitivity and spectral resolution are crucial for various applications.Here,we present a room-temperature atomic terahertz heterodyne receiver that achieves ultrahigh sensiti... Terahertz heterodyne receivers with high sensitivity and spectral resolution are crucial for various applications.Here,we present a room-temperature atomic terahertz heterodyne receiver that achieves ultrahigh sensitivity and frequency resolution.At a signal frequency of 338.7 GHz,we obtain a sensitivity of 2.88±0.09V·cm^(−1)·Hz^(−1/2) for electric field measurements.The calibrated linear dynamical range spans approximately 89 dB,ranging from−110 dBV/cm to−21 dBV/cm.We demodulate a 400 symbol stream encoded in 4-state phase-shift keying,demonstrating excellent phase detection capability.By scanning the frequency of the local oscillator,we realize a terahertz spectrometer with Hz level frequency resolution.This resolution is more than two orders of magnitude higher than that of existing terahertz spectrometers.The demonstrated terahertz heterodyne receiver holds promising potential for working across the entire terahertz spectrum,significantly advancing its practical applications. 展开更多
关键词 MAGNITUDE holds RESOLUTION
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Allelopathic Potential and Mechanism of Rosebay Willowherb[Chamaenerion angustifolium(L.)Scop.]Demonstrated on Model Plant Lettuce
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作者 Hailin Shi Shiwei Sun +4 位作者 xiaohong liu Jiahe Fan Jin Wang Ke Zhao Wei Wang 《Phyton-International Journal of Experimental Botany》 SCIE 2021年第1期159-170,共12页
Allelopathic plants are important resources for the discovery of bioherbicides.Rosebay willowherb[Chamaenerion angustifolium(L.)Scop.syn.Epilobium angustifolium L.]widely distributes in Western Asia,Europe,and North A... Allelopathic plants are important resources for the discovery of bioherbicides.Rosebay willowherb[Chamaenerion angustifolium(L.)Scop.syn.Epilobium angustifolium L.]widely distributes in Western Asia,Europe,and North America,and behaves as a dominant species within the community due to the production of substances that restrict growth of other plants.This study aims at investigating the allelopathic potential of rosebay willowherb by evaluation of the effects of aqueous extracts from different parts on seed germination and seedling growth in lettuce(Lactuca sativa L.),as well as measuring the accumulation of reactive oxygen species and structural analysis of root tips via scanning electron and transmission electron microscopy.It was observed that the aqueous extracts from the leaves of rosebay willowherb had the strongest inhibitory effect on the germination index,germination energy and total germination of lettuce seeds,followed by capsular fruits and flowers,and the inhibition effect of stems was the weakest.All aqueous extracts(100 mg/mL)showed a significant inhibitory effect on radicle elongation of lettuce seedlings.Additionally,after treatment with the aqueous extract of rosebay willowherb leaves,accumulation of reactive oxygen species increased in columella cells,which correlated with disruption of root tip structure. 展开更多
关键词 Chamaenerion angustifolium(L.)Scop. PHYTOTOXICITY seed germination seedling growth MORPHOLOGY reactive oxygen species
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Tunable vacancy defect chemistry on free-standing carbon cathode for lithium-sulfur batteries 被引量:2
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作者 Xi Zhang xiaohong liu +1 位作者 Wei Zhang Yingze Song 《Green Energy & Environment》 SCIE EI CSCD 2023年第2期354-359,共6页
The defect chemistry is successfully modulated on free-standing and binder-free carbon cathodes for highly efficient Li-S redox reactions.Such rationally regulated defect engineering realizes the synchronization of io... The defect chemistry is successfully modulated on free-standing and binder-free carbon cathodes for highly efficient Li-S redox reactions.Such rationally regulated defect engineering realizes the synchronization of ion/electron-conductive and defect-rich networks on the threedimension carbon cathode,leading to its tunable activity for both relieving the shuttle phenomenon and accelerating the sulfur redox reaction kinetics.As expected,the defective carbon cathode harvests a high rate capacity of 1217.8 mAh g^(-1)at 0.2 C and a superior capacity retention of61.7%at 2 C after 500 cycles.Even under the sulfur mass loading of 11.1 mg cm^(-2),the defective cathode still holds a remarkable areal capacity of 8.5 mAh cm^(-2). 展开更多
关键词 Li–S chemistry Tunable vacancy defects Free-standing cathode Electrocatalytic activity Sulfur redox reaction kinetics
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CTCs Detection and Whole-exome Sequencing Might Be Used to Differentiate Benign and Malignant Pulmonary Nodules 被引量:1
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作者 Changdan XU xiaohong XU +12 位作者 Weipeng SHAO Hongliang SUN xiaohong liu Hongxiang FENG Xianbo ZUO Jingyang GAO Guohui WANG Xiongtao YANG Runchuan GU Shutong GE Shijie WANG Liwei GAO Guangying ZHU 《中国肺癌杂志》 CAS CSCD 北大核心 2023年第6期449-460,共12页
Background and objective Low-density computed tomography(LDCT)improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data.Hence,accurate diagnosis of early-stage lung cancer ... Background and objective Low-density computed tomography(LDCT)improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data.Hence,accurate diagnosis of early-stage lung cancer remains challenging.The purpose of the study was to assess the feasibility of using circulating tumour cells(CTCs)to differentiate malignant from benign pulmonary nodules.Materials and methods 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited.Peripheral blood samples were collected before surgery,and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis.Laser capture microdissection,MALBAC amplification,and whole-exome sequencing were performed on 8 samples.The diagnostic efficacy of CTCs counting,and the genomic variation profile of benign and malignant CTCs samples were analysed.Results Using 2.5 cells/5 m L as the cut-off value,the area under the receiver operating characteristic curve was of 0.651(95%confidence interval:0.538-0.764),with a sensitivity and specificity of 0.526 and 0.800,respectively,and positive and negative predictive values of 91.1%and 30.3%,respectively.Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples.TP53 mutations were identified in CTCs of four malignant cases;in particular,g.7578115T>C,g.7578645C>T,and g.7579472G>C were exclusively detected in all four malignant samples.Conclusion CTCs play an ancillary role in the diagnosis of pulmonary nodules.TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules. 展开更多
关键词 Chest computed tomography Circulating tumour cells Lung nodule TP53 Whole-exome sequencing
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学科交叉视域下高锰酸钾法测定水样中化学需氧量实验的设计与实践 被引量:1
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作者 刘晓红 李姝 +1 位作者 叶世海 楼兰兰 《大学化学》 CAS 2023年第11期148-154,共7页
新工科背景下的复合型人才培养需要学科的交叉融合。以学科交叉为切入点,对无机及分析化学实验课程实验教学进行了改革和实践。以校内自来水和生活污水作为测试对象,采用高锰酸钾法测定了水样的化学需氧量。通过实验旨在提高学生的实践... 新工科背景下的复合型人才培养需要学科的交叉融合。以学科交叉为切入点,对无机及分析化学实验课程实验教学进行了改革和实践。以校内自来水和生活污水作为测试对象,采用高锰酸钾法测定了水样的化学需氧量。通过实验旨在提高学生的实践动手能力、跨学科思维能力、数据收集计算能力以及解决实际问题能力,增强学生环境保护意识,适合为化学、环境工程和资源循环科学与工程等专业学生开课。问卷调查发现,学生和教师对该实验内容都给予了高度评价,教学实践效果良好。 展开更多
关键词 化学需氧量 高锰酸钾法 无机及分析化学实验 学科交叉融合 实验教学改革
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Action Mechanism of Radix Aucklandiae against Gastric Ulcer Based on Network Pharmacology 被引量:1
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作者 Run YIN xiaohong liu +2 位作者 Yun CHEN Na LEI Gang LI 《Medicinal Plant》 CAS 2023年第4期14-17,23,共5页
[Objectives] To explore the potential targets and action mechanism of radix aucklandiae (RA) in the treatment of gastric ulcer (GU) by network pharmacology. [Methods] Gene targets were obtained through TCMSP, DisGeNet... [Objectives] To explore the potential targets and action mechanism of radix aucklandiae (RA) in the treatment of gastric ulcer (GU) by network pharmacology. [Methods] Gene targets were obtained through TCMSP, DisGeNet, OMIM, GeneCards databases, which related to GU and the active components of RA. The mutual potential functional targets were selected through Venny to constitute the PPI protein interaction network. The DAVID database was applied for GO and KEGG enrichment analysis of the common targets to construct the "Active component-Target-Pathway" network and analyze the relationship between them. [Results] There are 31 active components, 82 related targets and 16 common targets in the treatment of GU. The active components in Ra may exert anti-ulcer effects through six signaling pathways, including NF-κB, Toll-like receptors, VEGF and HIF-1. In addition, PTGS2, TNF, TLR4, JUN, IL2, SRC, RELA, KDR, NOS2 and PLAU may be the 10 key targets of Ra in the treatment of GU. [Conclusions] Ra controls GU through the synergies of multiple components, targets and pathways. It can provide a theoretical basis for further study on the mechanism of RA in treating GU. 展开更多
关键词 Network pharmacology Radix Aucklandiae Gastric ulcer
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Cu-Zn原电池标准电动势测定实验的计算化学设计 被引量:1
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作者 刘宇昂 刘晓红 +3 位作者 李姝 叶世海 李国然 言天英 《大学化学》 CAS 2023年第9期227-233,共7页
基于量子化学计算软件Gaussian 16,对“电动势的测定”这一经典物理化学实验进行了计算化学设计。用密度泛函方法计算了Cu^(2+)和Zn^(2+)的溶剂化自由能,通过热力学循环计算得到电池反应的标准摩尔吉布斯自由能变,进而求出Cu-Zn原电池... 基于量子化学计算软件Gaussian 16,对“电动势的测定”这一经典物理化学实验进行了计算化学设计。用密度泛函方法计算了Cu^(2+)和Zn^(2+)的溶剂化自由能,通过热力学循环计算得到电池反应的标准摩尔吉布斯自由能变,进而求出Cu-Zn原电池的标准电动势。该实验旨在帮助学生加深对标准摩尔吉布斯自由能、电极电势和能斯特方程等物理化学基本概念的理解,发挥学生的主观能动性,培养学生设计实验能力、动手实践能力以及科学思维。 展开更多
关键词 原电池 标准电动势 热力学循环 溶剂化自由能 计算化学实验
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Effects of Huangzhou Radish Powder on the Quality of Silver Carp Surimi Products
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作者 Qi YANG xiaohong liu +6 位作者 Xinghui TIAN Yujuan JIN Yanyu YANG Fa QIU Siyao MA Peng WU Ting HU 《Agricultural Biotechnology》 CAS 2023年第2期138-141,147,共5页
[Objectives]This study was conducted to improve the quality of frozen silver carp surimi products.[Methods]Huangzhou radish powder and silver carp surimi were used as raw materials to analyze the effects of different ... [Objectives]This study was conducted to improve the quality of frozen silver carp surimi products.[Methods]Huangzhou radish powder and silver carp surimi were used as raw materials to analyze the effects of different amounts(1%,2%,3%,4%,5%)of Huangzhou radish powder on the water-holding capacity,cooking loss rate,whiteness value,TPA,gel strength and sensory quality of surimi products.[Results]When the addition amount of Huangzhou radish powder was 1%,water-holding capacity,hardness,chewiness and the gel strength of the surimi product reached their maximum values,which were 86.86%,3470.36 g,2628.50 g and 707.48 g·mm,respectively.Meanwhile,the cooking loss rate was reduced to a minimum value(13.66%),and the sensory quality reached the best.The whiteness of surimi products showed a decreasing trend with the increase of the addition amount of Huangzhou radish powder.However,the whiteness of the surimi product was not significantly affected when the addition amount of Huangzhou radish powder was 1%.Therefore,when the addition amount of Huangzhou radish powder was 1%,the quality of surimi products could be improved.[Conclusions]This study provides a new idea for the development and utilization of Huangzhou radish. 展开更多
关键词 Huangzhou radish Surimi product QUALITY Gel strength
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编辑MSTN半胱氨酸节基元促进两广小花猪肌肉生长 被引量:13
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作者 彭定威 李瑞强 +6 位作者 曾武 王敏 石翾 曾检华 刘小红 陈瑶生 何祖勇 《遗传》 CAS CSCD 北大核心 2021年第3期261-270,共10页
肌生长抑制素(myostatin,MSTN)是转化生长因子β(transforming growth factor-β,TGF-β)家族成员之一,是一种肌肉生长抑制因子。解除MSTN的生长抑制功能是提高畜禽肌肉产量的一种有效途径。TGF-β的半胱氨酸节结构基元(cystine knot mo... 肌生长抑制素(myostatin,MSTN)是转化生长因子β(transforming growth factor-β,TGF-β)家族成员之一,是一种肌肉生长抑制因子。解除MSTN的生长抑制功能是提高畜禽肌肉产量的一种有效途径。TGF-β的半胱氨酸节结构基元(cystine knot motif)能够稳定MSTN蛋白结构,对MSTN生物学功能的发挥具有重要调控作用。本研究应用CRISRP/Cas9基因编辑技术在两广小花猪肾细胞(Liang Guang small spotted pig kidney cells,LPKCs)中对MSTN基因外显子3进行编辑,破坏了其半胱氨酸节基元,以解除MSTN对靶基因的抑制功能。将流式分选获得的混合阳性MSTN编辑LPKCs作为供体细胞进行核移植和胚胎移植,获得8头MSTN基因编辑两广小花猪仔猪,其中2头存活至10日龄,经鉴定这2头均为基因编辑杂合子,它们在构成MSNT蛋白半胱氨酸节基元的两个半胱氨残基C106和C108编码序列附近分别发生碱基的缺失与替换,导致移码突变,使C106和C108突变为其他氨基酸。MSTN基因编辑两广小花猪杂合子肩部和臀部肌肉较为发达。H&E切片分析显示,MSTN基因编辑猪肌纤维横截面积显著减少,肌纤维数量显著增多。Western Blot分析结果显示,C106和C108缺失对MSTN蛋白表达无显著性影响,但显著促进其靶基因Myf5、MyoD和Myogenin等成肌相关因子的表达。本研究获得的基因编辑猪模型没有造成MSTN表达完全缺失,可保留MSTN其他生物学功能,在促进两广小花猪肌肉生长的同时还消除了MSTN完全缺失可能对小花猪造成的潜在影响。 展开更多
关键词 MSTN CRISPR/Cas9 两广小花猪 基因编辑
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利用CRISPR/Cas9系统构建人HPRT1基因定点突变细胞株 被引量:6
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作者 张楷 刘蔚 +3 位作者 刘小凤 陈瑶生 刘小红 何祖勇 《遗传》 CAS CSCD 北大核心 2019年第10期939-949,共11页
Hypoxanthine-guanine phosphoribosyltransferase1(HPRT1)基因突变会导致次黄嘌呤和鸟嘌呤代谢异常,严重的代谢障碍被称为Lesch-Nyhan综合征,表现为智力低下,行为上出现强迫性自我毁伤,并伴随痛风或肾结石等症状。HPRT1基因具有多种突... Hypoxanthine-guanine phosphoribosyltransferase1(HPRT1)基因突变会导致次黄嘌呤和鸟嘌呤代谢异常,严重的代谢障碍被称为Lesch-Nyhan综合征,表现为智力低下,行为上出现强迫性自我毁伤,并伴随痛风或肾结石等症状。HPRT1基因具有多种突变模式,近年来对其突变谱的研究表明该基因具有一些"突变热点"。本研究选取了导致翻译提前终止的热点突变c.508C>T突变和c.151C>T突变,在HEK293T和HeLa细胞中,以单链寡核苷酸(single-stranded oligo-deoxyribonucleotides,ssODN)作为同源重组模板,利用CRISPR/Cas9技术构建了这两种突变的单克隆细胞株,发生定点突变的效率分别为16.3%和10%。进一步通过Westernblot检测点突变的单克隆细胞的HPRT1蛋白表达水平,通过6-TG毒性实验检测点突变的单克隆细胞的次黄嘌呤/鸟嘌呤磷酸核糖转移酶活性,结果表明纯合突变的单细胞克隆不能正常表达HPRT1蛋白,其次黄嘌呤/鸟嘌呤磷酸核糖转移酶活性丧失;杂合突变的单细胞克隆的HPRT1蛋白表达量降低,仍具有部分次黄嘌呤/鸟嘌呤磷酸核糖转移酶活性。HPRT1基因定点突变细胞模型的建立可为今后建立其他HPRT1基因突变的细胞系或动物模型提供借鉴,为研究Lesch-Nyhan致病机制提供基础。 展开更多
关键词 CRISPR/Cas9 HPRT1 基因定点突变
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城市家长对学前融合教育的接纳度 被引量:29
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作者 刘晓红 邓宇超 《学前教育研究》 CSSCI 北大核心 2018年第11期27-39,共13页
家长对学前融合教育的接纳度是顺利开展学前融合教育的前提和保障。以河南省15所城市幼儿园家长为例,通过编制科学有效的问卷,从认知、情感和行为三个维度对900名家长进行调查,结果发现家长对学前融合教育在认知、情感和行为方面的接纳... 家长对学前融合教育的接纳度是顺利开展学前融合教育的前提和保障。以河南省15所城市幼儿园家长为例,通过编制科学有效的问卷,从认知、情感和行为三个维度对900名家长进行调查,结果发现家长对学前融合教育在认知、情感和行为方面的接纳度均比较高,但是对相关概念和法律意识的接纳度较低。对学前融合教育接纳度的人口统计学分析显示,家长的接纳度在性别、年龄上存在显著差异,在学历上无显著差异。家长对学前融合教育接纳度不高的主要原因在于社会宣传不够,广大民众不了解;幼儿园缺乏开展学前融合教育的资源,相关师资力量匮乏等。为促进家长对学前融合教育的接纳度,应扩大社会舆论宣传,提高民众对特殊儿童的关注;加大职前融合教育师资的培养,提高教师的融合教育专业能力;为幼儿园提供充分的相关支持;研究者应加快有关学前融合教育的理论研究。 展开更多
关键词 融合教育 学前融合教育 接纳度 城市家长
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Changes in compressed neurons from dogs with acute and severe cauda equina constrictions following intrathecal injection of brain-derived neurotrophic factor-conjugated polymer nanoparticles 被引量:2
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作者 Junming Tan Jiangang Shi +10 位作者 Guodong Shi Yanling liu xiaohong liu Chaoyang Wang Dechun Chen Shunming Xing Lianbing Shen Lianshun Jia Xiaojian Ye Hailong He Jiashun Li 《Neural Regeneration Research》 SCIE CAS CSCD 2013年第3期233-243,共11页
This study established a dog model of acute multiple cauda equina constriction by experimental constriction injury (48 hours) of the lumbosacral central processes in dorsal root ganglia neurons. The repair effect of... This study established a dog model of acute multiple cauda equina constriction by experimental constriction injury (48 hours) of the lumbosacral central processes in dorsal root ganglia neurons. The repair effect of intrathecal injection of brain-derived neurotrophic factor with 15 mg encapsulated biodegradable poly(lactide-co-glycolide) nanoparticles on this injury was then analyzed. Dorsal root ganglion cells (LT) of all experimental dogs were analyzed using hematoxylin-eosin staining and immunohistochemistry at 1,2 and 4 weeks following model induction. Intrathecal injection of brain-derived neurotrophic factor can relieve degeneration and inflammation, and elevate the expression of brain-derived neurotrophic factor in sensory neurons of compressed dorsal root ganglion Simultaneously, intrathecal injection of brain-derived neurotrophic factor obviously improved neurological function in the dog model of acute multiple cauda equina constriction. Results verified that sustained intraspinal delivery of brain-derived neurotrophic factor encapsulated in biodegradable nanoparticles promoted the repair of histomorphology and function of neurons within the dorsal root ganglia in dogs with acute and severe cauda equina syndrome. 展开更多
关键词 neural regeneration peripheral nerve injury cauda equina syndrome dorsal root ganglion brain-derived neurotrophic factor multiple cauda equina constrictions neurotrophic factors neuralprotection grants-supported paper photographs-containing paper NEUROREGENERATION
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Preparation and evaluation of sustained-release diltiazem hydrochloride pellets 被引量:3
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作者 Xiaopeng Han Linan Wang +5 位作者 Yinghua Sun xiaohong liu Wanjun liu Yuqian Du Lin Li Jin Sun 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2013年第4期244-251,共8页
In this study,diltiazem hydrochloride(DTZ)pellets were prepared successfully by extrusionespheronization method.Then methacrylic acid and ethylcellulose coating formulations were employed to make the DTZ pellets sus... In this study,diltiazem hydrochloride(DTZ)pellets were prepared successfully by extrusionespheronization method.Then methacrylic acid and ethylcellulose coating formulations were employed to make the DTZ pellets sustained release.The pellets with different coatings were investigated by in vitro dissolution tests.At last,the pellets with the best coating copolymer were subjected to pharmacokinetic studies in beagle dogs.The dissolution profiles of pellets coated with EudragitNE30D were similar to Herbesser,one of the marketed sustained release capsules.In the bioavailability study,the principal pharmacokinetic parameters of self-made pellets and the marketed ones were comparable;the relative bioavailability of DTZ sustained release capsules compared with Herbesserwas 98.536.4%.All the data indicated self-made sustained pellets could prolong the release of DTZ,decrease the fluctuation of drug level in vivo,and increase the compliance of patients. 展开更多
关键词 Diltiazem hydrochloride Sustained release PELLETS In vitro and in vivo studies
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Pharmacokinetics of oxiracetam and its degraded substance (HOPAA) after oral and intravenous administration in rats 被引量:2
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作者 Xinhuan Wan xiaohong liu +4 位作者 Zheng liu Panqin Ma Feitong Zhang Xiangrong Zhang Jin Sun 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2014年第6期342-347,共6页
The pharmacokinetics of oxiracetam and its degraded substance(4-hydroxy-2-oxo-1-pyrrolidine acetic acid,HOPAA)after oral and intravenous administration in rats were studied using an established UPLC-MS/MS method.Three... The pharmacokinetics of oxiracetam and its degraded substance(4-hydroxy-2-oxo-1-pyrrolidine acetic acid,HOPAA)after oral and intravenous administration in rats were studied using an established UPLC-MS/MS method.Three groups of rats after an overnight fasted received 10 g/kg(n=6)oxiracetam suspensions orally,and 2 g/kg(n=6)normal or degraded oxiracetam injections intravenously via a caudal tail vein,respectively.Before the pharmacokinetic experiment,a simple safety evaluation testwas conducted on the degraded oxiracetam injections containing 16.16% HOPAA in mice.There was no mortality by a single intravenous dose of 2 g/kg of degraded oxiracetam injections within twoweeks,demonstrating that HOPAA was non-toxic in mice.Following intravenous administration of the normal injections,the plasma concentration-time curves of oxiracetam and HOPAA both showed a rapid elimination phase.The values of t_(1/2)were 3.1±1.5 h for oxiracetamand 0.8±0.2 h for HOPAA,andthemean residencetimes(MRT)were 1.2±0.1h and 0.8±0.1h,respectively.Oxiracetam and HOPAA after intravenous administration of the degraded oxiracetam injections presented elimination patterns similar to those observed in the normal injections.Oral pharmacokinetic results showed that the Tmax was less than 1.5 h for the two analytes,and both had a longer t_(1/2) and MRT than those of intravenous administration.Contents of HOPAA in three groupswere calculated based on AUC_(0-t) values of the two analytes.The quantitative change of HOPAA in vivo was also evaluated by comparing the plasma concentrations of HOPAA and oxiracetamat the same time for every group.Additionally,the values of absolute bioavailability of oxiracetam were about 8.0%and 7.4%calculated by the normal or degraded oxiracetam injections,whichwere far less than the value of 75%reported in literature,indicating the necessity of further study. 展开更多
关键词 OXIRACETAM 4-Hydroxy-2-oxo-1-pyrrolidine acetic acid(HOPAA) High performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) PHARMACOKINETICS Toxicity
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Early ABA-stimulated maintenance of Cl^(−) homeostasis by mepiquat chloride priming confers salt tolerance in cotton seeds 被引量:2
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作者 Ning Wang Xiangru Wang +7 位作者 Hengheng Zhang xiaohong liu Jianbin Shi Qiang Dong Qinghua Xu Huiping Gui Meizhen Song Gentu Yan 《The Crop Journal》 SCIE CSCD 2021年第2期387-399,共13页
Mepiquat chloride(MC)priming alleviates the effects of salt stress during seed germination in cotton(Gossypium hirsutum L.),but the mechanisms underlying its effects are unknown.We found that MC priming increases salt... Mepiquat chloride(MC)priming alleviates the effects of salt stress during seed germination in cotton(Gossypium hirsutum L.),but the mechanisms underlying its effects are unknown.We found that MC priming increases salt tolerance,as evidenced by marked increases in seed vigor and germination rates,and alleviated salt toxicity by reducing Cl^(−)accumulation in germinating seeds.Consistently,electrophysiological experiments revealed that the seeds with MC priming displayed superior Cl^(−)exclusion ability in the root apex.These beneficial effects of MC priming were abolished by the abscisic acid(ABA)-synthesis blocker fluridone under salt stress.MC priming induced an early response to acclimatization and stress,as indicated by rapidly increasing ABA content during initial exposure to salt stress.Transcriptome analyses revealed that MC priming induced an array of differentially expressed genes(DEGs)in germinating seeds.The most noticeable changes in germinating seeds were MC priming-induced increases in the expression of DEGs encoding components of ABA biosynthesis,ABA catabolism,and ABA signaling pathways under salt stress.MC priming also increased the expression of some DEGs encoding Cl^(−)ion transporters(e.g.CCC,SLAC1/SLAH1/SLAH3,CLC,and ALMT9)in germinating seeds.These results indicate that MC priming-induced ABA contributes to Cl^(−)homeostasis in tissues and acts as a positive regulator of salt tolerance via regulation of Cl^(−)transporters(particularly CCC and SLAC1/SLAH1/SLAH3).Taken together,these findings shed light on the molecular mechanism underlying MC-mediated tolerance to salt stress during seed germination. 展开更多
关键词 Seed priming Salinity tolerance Ionic flux RNA-SEQ ABA
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Gradient high performance liquid chromatography method for simultaneous determination of ilaprazole and its related impurities in commercial tablets 被引量:2
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作者 Shang Wang Dong Zhang +3 位作者 Yingli Wang xiaohong liu Yan liu Lu Xu 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2015年第2期146-151,共6页
A methodology(HPLC)proposed in this paper for simultaneously quantitative determination of ilaprazole and its related impurities in commercial tablets was developed and validated.The chromatographic separation was car... A methodology(HPLC)proposed in this paper for simultaneously quantitative determination of ilaprazole and its related impurities in commercial tablets was developed and validated.The chromatographic separation was carried out by gradient elution using an Agilent C8 column(4.6 mm×250 mm,5 mm)which was maintained at 25℃.The mobile phase composed of solvent A(methanol)and solvent B(solution consisting 0.02 mmol/l monopotassium phosphate and 0.025 mmol/l sodium hydroxide)was at a flow rate of 1.0 ml/min.The samples were detected and quantified at 237 nm using an ultraviolet absorbance detector.Calibration curves of all analytes from 0.5 to 3.5 mg/ml were good linearity(r≥0.9990)and recovery was greater than 99.5% for each analyte.The lower limit of detection(LLOD)and quantification(LOQ)of this analytical method were 10 ng/ml and 25 ng/ml for all impurities,respectively.The stress studies indicated that the degradation products could not interfere with the detection of ilaprazole and its related impurities and the assay can thus be considered stability-indicating.The method precisions were in the range of 0.41-1.21 while the instrument precisions were in the range of 0.38-0.95 in terms of peak area RSD% for all impurities,respectively.This method is considered stabilityindicating and is applicable for accurate and simultaneous measuring of the ilaprazole and its related impurities in commercial enteric-coated tablets. 展开更多
关键词 Ilaprazole Enteric-coated tablets Related impurities HPLC Validation
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