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AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

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Neural Regeneration Research 2025年第1期20卷 253-264页

作者： Zhengwei Hu Jing Yang Shuo Zhang Mengjie Li Chunyan Zuo Chengyuan Mao Zhongxian Zhang Mibo Tang Changhe Shi Yuming Xu Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Academy of Medical Sciences of zhengzhou University ZhengzhouHenan ProvinceChina NHC Key Laboratory of Prevention and treatment of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Henan Key Laboratory of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina institute of Neuroscience Zhengzhou UniversityZhengzhouHenan ProvinceChina Sino-British Research Centre for Molecular Oncology National Centre for International Research in Cell and Gene TherapySchool of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina Department of Gerontology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control *** this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s *** used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse *** overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated *** also alleviated the concentration of microglia and astrocytes around *** APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin *** of HSP70 and HSP40,which have functional relevance to CHIP,were also *** nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of *** research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 ***,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

关键词： adeno-associated virus Alzheimer’s disease APP/PS1 mice carboxyl terminus of Hsp70 interacting protein gene therapy

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AAV2-PDE6B restores retinal structure and function in the retinal degeneration 10 mouse model of retinitis pigmentosa by promoting phototransduction and inhibiting apoptosis

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Neural Regeneration Research 2025年第8期20卷 2408-2419页

作者： Ruiqi Qiu Mingzhu Yang Xiuxiu Jin Jingyang Liu Weiping Wang Xiaoli Zhang Jinfeng Han Bo Lei Henan Eye Hospital Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Eye institute Henan Academy of Innovations in Medical ScienceZhengzhouHenan ProvinceChina Branch of National Clinical Research Center for Ocular Disease Henan Provincial People’s HospitalZhengzhouHenan ProvinceChina Academy of Medical Science Zhengzhou UniversityZhengzhouHenan ProvinceChina

Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell ***,there is no effective treatment for retinitis pigmentosa caused by PDE6B ***-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis *** aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal *** do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and ***-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western ***2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 *** expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type *** Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction ***,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B ***,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B *** data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upr

关键词： apoptosis AAV2-PDE6B ERK1/2 gene therapy phototransduction proteomics rd10 retinitis pigmentosa

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Rapid detection of the E198A mutation of carbendazim-resistant isolates in Colletotrichum gloeosporioides by loop-mediated isothermal amplification

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Horticultural Plant Journal 2022年第3期8卷 289-296页

作者： Hongbo Yuan Hui Hou Zengqiang Zhou Hongtao Tu Li Wang zhengzhou fruit Research institute Chinese Academy of Agricultural SciencesZhengzhou 450009China

Apple bitter rot is a serious agricultural disease caused by Colletotrichum *** recent years,carbendazim-resistant *** strains bearing an E198A point mutation in theβ-tubulin gene(GAG to GCG)have emerged,threatening global apple *** such,rapidly detecting the presence of this E198Amutation in *** isolates is essential in order to monitor the spread of this pathogen and to prevent outbreaks of ***,we developed a simple loop-mediated isothermal amplification(LAMP)approach to detecting the E198A mutation in *** isolates from‘Gala’apple *** optimized LAMP protocol was sufficient to establish the E198A genotype of a given isolate following a 60min incubation at 63℃ by using four specific *** results of this reaction could be interpreted visually based on a fluorescent yellow-green color change upon the addition of the SYBR Green I dye,and were additionally confirmed via gel ***,this LAMP assay was capable of rapidly and reliably detecting apples that were infected with carbendazim-resistant isolates harboring this E198A *** conclusion,this LAMP assay in this study can rapidly,specifically,and sensitively detect cases of apple bitter rot caused by *** isolates harboring the E198A mutation.

关键词： Apple bitter rot Colletotrichum gloeosporioides Carbendazim resistance Loop-mediated isothermal amplification E198A mutation

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Genome-wide identification and expression analysis of NIN-like Protein(NLP)genes reveals their potential roles in the response to nitrate signaling in watermelon

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Horticultural Plant Journal 2022年第5期8卷 602-614页

作者： Gaopeng Yuan Dexi Sun Yifan Wang Guolin An Weihua Li Wenjing Si Junpu Liu Yingchun Zhu zhengzhou fruit Research institute of the Chinese Academy of Agricultural Sciences Zhengzhou 450000China

To balance the relationship between high yield and low nitrogen supply,the nitrogen utilization efficiency of watermelon needs to be improved *** inception-like Protein(NLP)transcription factors play a key node role in nitrate response and growth and development of plant,however,comprehensive analysis of the NLP gene family in watermelon is *** study explored the functional classification,evolutionary characteristics,and expression profile of the ClNLP gene *** ClNLPs were categorized into three groups according to their gene structure and *** of them contained the conserved RWP-RK and PB1 *** analysis of ClNLPs revealed that ClNLP1 and ClNLP3 underwent strong purified *** addition,cis-acting elements related to plant hormones and abiotic stresses were present in the ClNLP *** to tissue-specific analysis ClNLP was widely expressed in roots,stems,leaves,flowers and fruits,and ClNLP1 was significantly induced in the roots of different nitrogen utilization varieties under different nitrate nitrogen *** SRTING functional protein association network suggested that ClNLP1 is associated with most genes,such as NRT1.1,NRT2.1,NIA1,and NIR1,and the dual-luciferase reporter assay found that ClNLP1 positively regulates the expression of *** speculated that ClNLP1 might play a central role in regulating the response of watermelon to nitrate nitrogen.

关键词： Genome-wide identification NLP Nitrate signaling Nitrate nitrogen Watermelon

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Accumulated chilling hours during endodormancy impact blooming and fruit shape development in peach(Prunus persica L.)

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Journal of Integrative Agriculture 2016年第6期15卷 1267-1274页

作者： LI Yong FANG Wei-chao ZHU Geng-rui CAO Ke CHEN Chang-wen WANG Xin-wei WANG Li-rong zhengzhou fruit Research institute Chinese Academy of Agricultural Sciences

Winter chill is essential for the growth and development of deciduous species. To understand the relationship between accumulated chilling hours during endodormancy and blooming and fruit shape development, we controlled chilling hours and investigated their effects on blooming date and fruit shape of peaches. The results showed that the number of days to full bloom date and the heat requirement for blooming were negatively correlated with accumulated chilling hours. Accumulated chilling hours were significantly negatively correlated with fruit shape index and fruit tip lengths, suggesting that the number of chilling hours affect the fruit shape development. Fewer accumulated chilling hours may be the major reason for longer fruit shape and protruding fruit tips. In conclusion, our results indicate specifically that decreased winter chilling hours can delay the bloom date and may lead to aberrant fruit shape development in peaches. Our study provides preliminary insights into the response of temperate fruit species to global climate change.

关键词： accumulated chilling hours blooming fruit shape endodormancy Prunus persica

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Genetic Resources,Breeding Programs in China,and Gene Mining of Peach:A Review

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Horticultural Plant Journal 2020年第4期6卷 205-215页

作者： Yong Li Lirong Wang zhengzhou fruit Research institute Chinese Academy of Agricultural SciencesZhengzhou450009China

Research on peach genetic resources and breeding has achieved remarkable progress in recent decades,especially in *** this review,we first described the geographic distribution,ecology,phenotypes,and genetic diversity of peach landraces and wild relatives in *** also discussed the ***,breeding programs of peaches in China are summarized,including breeding history,breeding targets,breeding institutes,elite breeding materials,breeding solutions,and domestically bred representative ***,we reviewed the genes or loci that have been mined using both linkage mapping and genome wide association study(GWAS)as well as the evolutionary genetics and domestication history of the ***,we gave our perspectives and suggestions for future breeding in terms of breeding material selection and breeding technology innovation.

关键词： peach genetic resources landrace wild relatives breeding gene mining GWAS

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Mapping subgenomic promoter of coat protein gene of Cucumber green mottle mosaic virus

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Journal of Integrative Agriculture 2020年第1期19卷 153-163页

作者： LIU Mei LIU Li-ming WU Hui-jie KANG Bao-shan GU Qin-sheng Henan Provencial Key Laboratory of fruit and Cucurbit Biology Zhengzhou Fruit Research InstituteChinese Academy of Agricultural Sciences

Many plant viruses utilize subgenomic RNA as gene expression strategy, therefore mapping subgenomic promoter(SGP) is extremely important for constructing viral vectors. Although Cucumber green mottle mosaic virus(CGMMV)-based virus vectors have been constructed, SGP of the coat protein(CP) has not yet mapped. To this end, we firstly presumed 13 nucleotides upstream of the start codon as the transcription starting site(TSS) as previous study identified by random amplification of c DNA ends(RACE). Secondly, the region from nucleotides –110 to +175 is the putative CP SGP, as predicted, a long stem loop structure by the secondary structure of RNA covering movement protein(MP) and CP. To map the CGMMV CP SGP, we further constructed a series of deletion mutants according to RNA secondary structure prediction. The deletion of TSS upstream significantly enhanced CP transcription when 105 nucleotides were retained before the CP TSS. For the downstream of CP TSS, we analyzed the expression of enhanced green fluorescent protein(EGFP) in a series of vectors with partial deletion of the CGMMV CP and found that the nucleotides from +71 to +91 played a key role in the EGFP expression at the transcription level, while EGFP showed the highest expression level when 160 nucleotides were retained downstream of the CP TSS. To confirm these results, we applied online software MEME to predict the motifs and cis-acting elements in the 466 nucleotides covering the sequences of deletion analysis. Conserved motifs and relative acting elements were in regions in which transcription levels were the highest or enhanced. To our best knowledge, this is the first mapping of CGMMV SGP.

关键词： Cucumber green mottle mosaic virus coat protein subgenomic promoter

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Establishment and application of an SNP molecular identification system for grape cultivars

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Journal of Integrative Agriculture 2022年第4期21卷 1044-1057页

作者： WANG Fu-qiang FAN Xiu-cai ZHANG Ying SUN Lei LIU Chong-huai JIANG Jian-fu zhengzhou fruit Research institute Chinese Academy of Agricultural SciencesZhengzhou 450009P.R.China

We aimed to develop a set of single nucleotide polymorphism(SNP) markers that can be used to distinguish the main cultivated grape(Vitis L.) cultivars in China and provide technical support for domestic grape cultivar protection, cultivar registration, and market rights protection. A total of 517 high-quality loci were screened from 4 241 729 SNPs obtained by sequencing 304 grape accessions using specific locus amplified fragment sequencing, of which 442 were successfully designed as Kompetitive Allele Specific PCR(KASP) markers. A set of 27 markers that completely distinguishes 304 sequenced grape accessions was determined by using the program, and 26 effective markers were screened based on 23 representative grape cultivars. Finally, a total of 46 out of 48 KASP markers, including 22 markers selected by the research group in the early stage, were re-screened based on 348 grape accessions. Population structure, principal component, and cluster analyses all showed that the 348 grape accessions were best divided into two populations. In addition, cluster analysis subdivided them into six subpopulations. According to genetic distance, V. labrusca, V. davidii, V. heyneana, and V. amurensis were far from V. vinifera, while V. vinifera×V. labrusca and V. amurensis×V. vinifera were somewhere in between these two groups. Furthermore, a core set of 25 KASP markers could distinguish 95.69% of the 348 grape accessions, and the other 21 markers were used as extended markers. Therefore, SNP molecular markers based on KASP typing technology provide a new way for mapping DNA fingerprints in grape cultivars. With high efficiency and accuracy and low cost, this technology is more competitive than other current identification methods. It also has excellent application prospects in the grape distinctness, uniformity, and stability(DUS) test, as well as in promoting market rights protection in the near future.

关键词： grape KASP marker variety identification fingerprint genetic diversity analysis

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Transcriptomic profiling of watermelon(Citrullus lanatus) provides insights into male flowers development

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Journal of Integrative Agriculture 2022年第2期21卷 407-421页

作者： ZHU Ying-chun YUAN Gao-peng JIA Sheng-feng AN Guo-lin LI Wei-hua SUN De-xi LIU Jun-pu zhengzhou fruit Research institute Chinese Academy of Agricultural SciencesZhengzhou 450000P.R.China

Watermelon(Citrullus lanatus(Thunb.) Matsum. & Nakai) is an important cucurbit crop grown worldwide. Watermelon fruit quality, fertility, and seed-setting rate are closely related to male flower development. In this study, the different developmental stages of flower buds of the watermelon cultivar ’Xinteda Zhengkang 9’ were distinguished by cytological observation, and transcriptome sequencing analysis was performed subsequently. Acetocarmine staining of anthers was performed and the longitudinal and transverse diameters of the unopened male flower buds were measured. Cytological observations of anthers at different developmental stages showed that the anther grew from the tetrad to the mature stage, and the longitudinal and transverse diameters of the flower buds increased. The length of the male flower buds also changed significantly during development. Transcriptome sequencing analysis at four periods, the tetrad(A group), mononuclear(B group), dikaryophase(C group), and mature stages(D group). A total of 16 288 differentially expressed genes(DEGs) were detected in the four stages, with the prolongation of developmental stages, the number of DEGs increased gradually in the comparison groups, there was 2 014, 3 259, 4 628, 1 490, 3 495 and 1 132 DEGs revealed in six comparison groups(A-vs.-B, A-vs.-C, A-vs.-D, B-vs.-C, B-vs.-D, and C-vs.-D), respectively. Gene Ontology(GO) and KEGG enrichment analysis showed that the DEGs were mainly enriched in cellular component and starch and sucrose metabolism, phenylpropanoid biosynthesis and pentose sugar, etc. Finally, we completely screened 59 DEGs in the six comparison groups, interestingly, we found one pollen-specific protein(Cla001608) that was significantly down-regulated(the value of log2 Fold Change up to 17.32), which indicated that it may play an important role in the development of male flowers. This work provides insight into the molecular basis of the developmental stages of male flowers in watermelon and may

关键词： watermelon male flowers development cytological observation transcriptome sequencing

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Changes in nutritional composition,volatile organic compounds and antioxidant activity of peach pulp fermented by lactobacillus

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Food Bioscience 2022年第5期49卷 417-427页

作者： Wenbo Yang Jiechao Liu Qiang Zhang Hui Liu Zhenzhen Lv Chunling Zhang Zhonggao Jiao zhengzhou fruit Research institute Chinese Academy of Agricultural ScienceZhengzhou450009HenanChina

Fermentation with lactobacillus offers a natural means to modify nutritional and flavor properties of foods,and strains have crucial effects on *** this study,peach pulp was fermented by five commercial probiotics(*** 21802,*** 6239,*** 21798,*** 21852 and *** 21832)to screen out a strain with higher adaptability ability and polyphenol bio-transformation ***,dynamics changes in microbial properties,nutritional composition,volatile organic compounds and DPPH radical-scavenging activity of peach pulp fermented by selected strain were studied and compared with the control ***,LC-ESI-MS/MS and GC-MS were used for identification and quantification of *** showed that the most efficient strain was *** 21802 caused a significant(P1),namely linalool,benzaldehyde,damascenone and eugenol,increased significantly(Pfruit as a novel material for functional plant-based fermentation beverages.

关键词： Peach pulp Lactobacillus fermentation Polyphenols Antioxidant activity Volatile organic compounds

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