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Neurodevelopmental impairment induced by prenatal valproic acid exposure shown with the human cortical organoid-on-a-chip model

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Microsystems & Nanoengineering 2020年第1期6卷 754-767页

作者： Kangli Cui Yaqing Wang Yujuan Zhu Tingting Tao Fangchao Yin yaqiong guo Haitao Liu Fei Li Peng Wang Yuejun Chen Jianhua Qin Division of Biotechnology CAS Key Laboratory of SSACDalian Institute of Chemical PhysicsChinese Academy of Sciences457 Zhongshan RoadDalian 116023China University of Chinese Academy of Sciences Beijing 100049China CAS Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijingChina

Prenatal exposure to environmental insults can increase the risk of developing neurodevelopmental *** of the antiepileptic drug valproic acid(VPA)during pregnancy is tightly associated with a high risk of neurological disorders in ***,the lack of an ideal human model hinders our comprehensive understanding of the impact of VPA exposure on fetal brain development,especially in early ***,we present the first report indicating the effects of VPA on brain development at early stages using engineered cortical organoids from human induced pluripotent stem cells(hiPSCs).Cortical organoids were generated on micropillar arrays in a controlled manner,recapitulating the critical features of human brain development during early *** VPA exposure,cortical organoids exhibited neurodevelopmental dysfunction characterized by increased neuron progenitors,inhibited neuronal differentiation and altered forebrain *** analysis showed new markedly altered genes(e.g.,KLHL1,LHX9,and MGARP)and a large number of differential expression genes(DEGs),some of which are related to *** particular,comparison of transcriptome data via GSEA and correlation analysis revealed the high similarity between VPA-exposed organoids with the postmortem ASD brain and autism patient-derived organoids,implying the high risk of autism with prenatal VPA exposure,even in early *** new findings facilitate a better understanding of the cellular and molecular mechanisms underlying postnatal brain disorders(such as autism)with prenatal VPA *** established cortical organoid-on-a-chip platform is valuable for probing neurodevelopmental disorders under environmental exposure and can be extended to applications in the study of diseases and drug testing.

关键词： markedly inhibited exposure

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A cholangiocyte organoid system for Cryptosporidium parvum cultivation and transcriptomic studies of biliary cryptosporidiosis

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hLife 2024年第7期2卷 360-370页

作者： Miner Deng Qing Tian Xinjie Mao Jie Zhang Yanting Wei Na Li yaqiong guo Lihua Xiao Yaoyu Feng State Key Laboratory for Animal Disease Control and Prevention South China Agricultural UniversityGuangdongChina Guangdong Laboratory for Lingnan Modern Agriculture Center for Emerging and Zoonotic DiseasesCollege of Veterinary MedicineSouth China Agricultural UniversityGuangdongChina

Biliary cryptosporidiosis caused by Cryptosporidium is life-threatening in immunocompromised individuals,particularly those with acquired immune deficiency syndrome(AIDS),resulting in AIDS ***,studies of biliary cryptosporidiosis have lagged due to the lack of in vitro models that allow complete pathogen *** we describe procedures for the generation of mouse cholangiocyte organoids(Chol-orgs).The Chol-orgs,which expressed stem and biliary cell markers,could be clonally expanded for three months and stored in liquid nitrogen for more than one *** with cell differentiation using the air-liquid interface(ALI)approach,we established a culture system for *** cultures using Chol-orgs have supported50-fold amplification of the pathogen and generated viable oocysts in *** addition,we analyzed the transcriptome of Chol-ALI cultures infected with the IId subtype of *** to characterize host cell ***-seq analysis revealed that *** upregulated immune and inflammatory responses and downregulated metabolic and cell proliferation signaling pathways in Cholorgs.A similar system using bovine cholangiocytes also supported the complete development of *** in *** in vitro models provide convenient methods to study biliary cryptosporidiosis and other hepatic infections and to develop effective therapies for AIDS cholangiopathy.

关键词： Cryptosporidium organoids cholangiocyte culture system host-pathogen interactions

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Evolutionary genomics of an Emerging Cryptosporidium hominis Subtype in the United States:IfA12G1R5

Evolutionary genomics of an Emerging Cryptosporidium hominis...

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2021中国畜牧兽医学会兽医寄生虫学分会第二届青年科学家学术论坛

作者： Wanyi Huang Na Li yaqiong guo Yaoyu Feng Lihua Xiao Center for Emerging and Zoonotic Diseases College of Veterinary MedicineSouth China Agricultural University

Cryptosporidium hominis(***) is a global spread diarrhoeal pathogen caused human cryptosporidiosis,which is a leading cause of mortality in children under five years *** the USA,an accompanying dramatic increase in the incidence of human cryptosporidiosis was the appearance of a new *** subtype,IfA12 G1 R5 which is now the dominant subtype for outbreaks and sporadic ***,the source of the *** IfA12 G1 R5 subtype in the USA remains *** herein sequence 175 *** isolates and analyse them combined with previously published ones to illustrate the evolution of IfA12 G1 *** on the single-nucleotide polymorphisms(SNPs),phylogenetic and population structure analyses show that *** isolates cluster in 15 populations mainly according to their country origins or gp60 ***,IfA12 G1 R5 subtype in the USA splits into three of the 15 populations,IfA12 G1 R5 a,IfA12 G1 R5 b and IfA12 G1 R5 c,indicating that they have different evolutionary *** then evaluate genetic exchange and introgression among isolates,which show that recombination events are not only abundant among *** of different gp60 subtypes and geographical regions,but also act as a driving force for the emergence of hyper-transmissible *** subtypes in the *** conclude that IfA12 GlR5 a appears to have an East Africa origin and went through recombination with local American subtypes(IaA15 R3 and IaA28 R4)after its arrival;IfA12 GlR5 b appears to have been imported into the USA from Europe,where it went through recombination with IbA10 G2 subtype;IfA12 G1 R5 c is a progeny of recombination of IfA12 G1 R5 a and IfA12 G1 R5 b.

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潮间带滩涂沉积物与水体热通量模拟

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水科学进展 2018年第5期29卷 728-736页

作者：郭雅琼马进荣程梦妍南京水利科学研究院水文水资源与水利工程科学国家重点实验室江苏南京210024 河海大学港口海岸与近海工程学院江苏南京210098

为了揭示滩涂对近岸水温影响,开展潮间带滩涂沉积物与海水之间热量交换研究。以韩国西南海岸的滩涂为例,建立滩涂沉积物温度模型,模拟不同潮汐状态下沉积物垂向剖面温度以及沉积物与水体间的热通量,并分析了季节、滩涂位置、潮位-太阳... 详细信息

为了揭示滩涂对近岸水温影响,开展潮间带滩涂沉积物与海水之间热量交换研究。以韩国西南海岸的滩涂为例,建立滩涂沉积物温度模型,模拟不同潮汐状态下沉积物垂向剖面温度以及沉积物与水体间的热通量,并分析了季节、滩涂位置、潮位-太阳辐射相位对热通量的影响。研究表明:模拟出的沉积物温度与实测值吻合较好。沉积物与水体存在大量热量交换,且集中在淹没后的前3 h,最大热通量可达398. 7 W/m2。冬季月份海水向滩涂净传热。夏季月份滩涂向水体净传热,且当滩涂淹没时刻发生在当地正午或正午过后3 h内,滩涂传递给水体的热量相对较大,达2. 0 MJ/(m2·d);累积热通量随滩涂干滩率的减小而减小。研究成果为进一步深入研究滩涂影响下近岸水温变化提供了技术支撑。

关键词：潮间带滩涂沉积物温度温度模型沉积物-水体热通量

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Comparative genomic analysis of Cryptosporidium canis,a common pathogen in canine animals

Comparative genomic analysis of Cryptosporidium canis,a comm...

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2021中国畜牧兽医学会兽医寄生虫学分会第二届青年科学家学术论坛

作者： Yingying Fan Jiayu Li Na Li yaqiong guo Yaoyu Feng Lihua Xiao Center for Emerging and Zoonotic Diseases College of Veterinary MedicineSouth China Agricultural University Guangdong Laboratory for Lingnan Modern Agriculture

Cryptosporidium canis is a key species that infect humans and other canine *** understand the genetic evolution characteristics of Cryptosporidium canis,the genome of *** was sequenced and compared with other common Cryptosporidium *** most intestinal Cryptosporidium species have similar genomic characteristics and almost complete genome synteny,fewer protein-coding genes and some sequence inversions and translocations were found in the genome of *** analysis suggests that *** and *** share many genomic features,such as GC content in CDS and GC content at 3 rd position in ***,*** genome exhibits much higher genomic GC content(40.6%) than other species(24.3%～33.6%),especially at the third codon position(GC3) of protein-coding *** high GC content reveals that *** has a unique codon usage pattern and likely prefers to use less energy costly amino acids(Gly and Ala) encoded by GC-rich *** analysis suggested that both mutational pressures and natural selection are associated with the evolution of the codon usage in Cryptosporidium spp.,while natural selection largely drives the codon usage in *** and *** findings improve our understanding of the evolution characteristics of ***.

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Characterization of insulinase-like protease INS-16 in Cryptosporidium parvum

Characterization of insulinase-like protease INS-16 in Crypt...

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2021中国畜牧兽医学会兽医寄生虫学分会第16次学术研讨会

作者： Hao Cui Rui Xu Na Li yaqiong guo Lihua Xiao Yaoyu Feng Center for Emerging and Zoonotic Diseases South China Agricultural University

Cryptosporidium parvum is a protozoan that infects intestinal epithelial cells and can cause diarrhea in humans and young *** results of comparative genomics analysis showed that *** contained multiple genes encoding over 20 insulinase-like proteases（INS）,indicating that this protease family has important biological *** this study,a member of the INS family,INS-16 encoded by the cgd3270 gene,was expressed and *** it has high sequence identity to INS-15 encoded by the cgd3260 gene,we compared the expression level and localization of INS-16 and *** full length INS-16 and protein and its active domain I were expressed in ***,with antibodies against the domain I and an INS-16-specific peptide being produced in rabbits.A 60 kD protein of INS-16 in sporozoite lysate was recognized by the polyclonal antibodies against the INS-16 specific peptide,indicating that INS-16 may undergo a cleavage event before *** gene expression level and protein localization suggested that INS-16 was involved in ***-localization of INS-15 and INS-16 showed significant differences in the distribution of the native NS-15 and INS-16 proteins in sporozoites and *** the INS-16 antibodies alone did not inhibit *** invasion,the mixture of anti-INS-15 domain I and anti-INS-16 domain I antibodies partially neutralized the invasion（inhibition rate=35.4%）.Results of this study suggest that INS-15 and INS-16 may play different roles in the invasion and development stage of ***.

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儿童高危消化道异物及其并发症的内镜治疗

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中华实用儿科临床杂志 2019年第19期34卷 1447-1449页

作者：李小芹郭亚琼郑州大学附属儿童医院河南省儿童医院郑州儿童医院消化科450003

消化道异物是儿科常见的急症,尤其是食管异物或尖锐性、腐蚀性、磁性异物等,极易出现并发症,常需内镜紧急处理。且因异物所致的出血、穿孔和瘘、管腔狭窄等并发症亦可行内镜下治疗,现对高危消化道异物的特点及治疗方案的选择进行阐述。

关键词：高危消化道异物并发症内镜治疗儿童

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基于反射谱重构的光纤光栅再生过程研究

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半导体光电 2018年第2期39卷 165-169页

作者：郭亚琼陆林北京航空航天大学精密光机电一体化技术教育部重点实验室北京100191 北京航空航天大学惯性技术国防科技重点实验室北京100191

提出一种新的光纤光栅反射谱重构方法,通过再生过程中反射谱的重构,对再生规律进行总结。基于耦合模理论,推导了光栅的主要参数,包括栅区长度、周期及折射率调制深度平均值的表达式。结合传输矩阵法中的特征参数,即光栅有效折射率和折... 详细信息

提出一种新的光纤光栅反射谱重构方法,通过再生过程中反射谱的重构,对再生规律进行总结。基于耦合模理论,推导了光栅的主要参数,包括栅区长度、周期及折射率调制深度平均值的表达式。结合传输矩阵法中的特征参数,即光栅有效折射率和折射率调制深度对反射谱的影响规律,提出重构方法,并用相关系数进行了评价。进行光纤光栅再生实验记录反射谱的演变,重构出光栅参数变化。研究发现:再生过程中折射率呈幂指数函数形式,指数随退火时间增长而减小。据有效折射率退火时的变化,分析光栅再生时所产生的不同程度内应力的释放,引起有效折射率的周期性调制。

关键词：光纤光栅再生光栅反射谱重构应力释放

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Characterization of calcium-dependent protein kinases 2A,a protein expressed during early development of Cryptosporidium parvum

Characterization of calcium-dependent protein kinases 2A,a p...

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2021中国畜牧兽医学会兽医寄生虫学分会第16次学术研讨会

作者： Fanfan Shu Na Li yaqiong guo Fuxian Yang Yu Li Ziding Zhang Yaoyu Feng Lihua Xiao

Calcium-dependent protein kinases(CDPKs) are important kinases in response to calcium,functioning as a trigger for several biological functions in Cryptosporidium *** they are not present in mammals,CDPKs are considered promising drug *** studies have characterized CpCDPK1 and CpCDPK3,but the role of CpCPK2 A is still not fully *** this work,we have expressed and purified recombinant CpCDPK2 A in Escherichia *** biologic functions of CpCDPK2 A were characterized using qRT-PCR,immunofluorescence microscopy,immuno-electron microscopy,and in vitro *** results revealed that CpCDPK2 A protein was highly expressed in sporozoites and merozoites and was located in the apical region of the two invasion *** antibodies of CpCDPK2 A failed to block the invasion of host *** of 44 candidate inhibitors screened through molecular docking of CpCDPK2 A,one inhibitor-K292-0423 was identified as having a potential effect on both *** development and CpCDPK2 A enzyme *** data suggests that CpCDPK2 A may play an essential role in the invasion of C parvum.

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Molecular characterization of waterborne pathogens Cryptosporidium spp.,Giardia duodenalis,Enterocytozoon bieneusi,Cyclospora cayetanensis,and Eimeria *** wastewater and sewage in Guangzhou,China

Molecular characterization of waterborne pathogens Cryptospo...

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2021中国畜牧兽医学会兽医寄生虫学分会第16次学术研讨会

作者： Yingying Fan Xinrui Wang Ruohong Yang Wentao Zhao Na Li yaqiong guo Lihua Xiao Yaoyu Feng

The waterborne pathogens Cryptosporidium spp.,Giardia duodenalis,Enterocytozoon bieneusi and Cyclospora cayetanensis can cause intestinal diseases in *** their occurrence and transport in the environment is essential for accurate quantitative microbial risk ***,238 influent samples were collected from four wastewater treatment plants(WWTPs) and 88 samples from eight sewer locations in Guangzhou,China. PCR-based tools were used to detect and genetically characterize Cryptosporidium spp.,*** and *** *** Cyclospora *** also analyzed to assess the sources of Cryptosporidium spp.,***,and *** in *** overall occurrence rates were 14.3%(34/238)and 13.6%(12/88) for Cryptosporidium spp.,55.5%(132/238) and 33.0%(29/88) for ***,56.3%(134/238) and 26.1%(23/88) for ***,and 45.4%(108/238) and 47.7%(42/88) for Eimeria *** WWTP and sewer samples,***,11 Cryptosporidium species and genotypes,six *** genotypes,11 *** genotypes and four *** were found,together with the presence of nine Eimeria *** common occurrence of Cryptosporidium rat genotype Ⅳ,Cryptosporidium muris and Eimeria papillata and Eimeria nieschulzi suggested that rodents were significant sources of the enteric pathogens detected in wastewater *** the dominant Cryptosporidium *** detected raw wastewater in the study are not human-pathogenic,the widely detected *** assemblage A and *** genotypes D and Type Ⅳ are well-known zoonotic *** studies are needed to monitor the occurrence of these waterborne pathogens in WWTPs to better understand their transmission and environmental transport in China.

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