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Key genes and regulatory networks for diabetic retinopathy based on hypoxia-related genes:a bioinformatics analysis
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作者 Cai-Han Yu Cai-Xia Wu +3 位作者 Dai Li Lan-Lan Gong Xu-Dong Lyu Jie Yang 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第8期1411-1417,共7页
AIM:To prevent neovascularization in diabetic retinopathy(DR)patients and partially control disease progression.METHODS:Hypoxia-related differentially expressed genes(DEGs)were identified from the GSE60436 and GSE1024... AIM:To prevent neovascularization in diabetic retinopathy(DR)patients and partially control disease progression.METHODS:Hypoxia-related differentially expressed genes(DEGs)were identified from the GSE60436 and GSE102485 datasets,followed by gene ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Potential candidate drugs were screened using the CMap database.Subsequently,a protein-protein interaction(PPI)network was constructed to identify hypoxia-related hub genes.A nomogram was generated using the rms R package,and the correlation of hub genes was analyzed using the Hmisc R package.The clinical significance of hub genes was validated by comparing their expression levels between disease and normal groups and constructing receiver operating characteristic curve(ROC)curves.Finally,a hypoxia-related miRNA-transcription factor(TF)-Hub gene network was constructed using the NetworkAnalyst online tool.RESULTS:Totally 48 hypoxia-related DEGs and screened 10 potential candidate drugs with interaction relationships to upregulated hypoxia-related genes were identified,such as ruxolitinib,meprylcaine,and deferiprone.In addition,8 hub genes were also identified:glycogen phosphorylase muscle associated(PYGM),glyceraldehyde-3-phosphate dehydrogenase spermatogenic(GAPDHS),enolase 3(ENO3),aldolase fructose-bisphosphate C(ALDOC),phosphoglucomutase 2(PGM2),enolase 2(ENO2),phosphoglycerate mutase 2(PGAM2),and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3).Based on hub gene predictions,the miRNA-TF-Hub gene network revealed complex interactions between 163 miRNAs,77 TFs,and hub genes.The results of ROC showed that the except for GAPDHS,the area under curve(AUC)values of the other 7 hub genes were greater than 0.758,indicating their favorable diagnostic performance.CONCLUSION:PYGM,GAPDHS,ENO3,ALDOC,PGM2,ENO2,PGAM2,and PFKFB3 are hub genes in DR,and hypoxia-related hub genes exhibited favorable diagnostic performance. 展开更多
关键词 diabetic retinopathy hypoxia-related genes hub genes miRNA-TF-Hub gene drug prediction
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Large-scale loss-of-function perturbations reveal a comprehensive epigenetic regulatory network in breast cancer
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作者 Yumei Wang Haiyan Wang +7 位作者 Wei Shao Yuhui Chen Yu Gui Chao Hu Xiaohong Yi Lijun Huang Shasha Li Dong Wang 《Cancer Biology & Medicine》 SCIE CAS CSCD 2024年第1期83-103,共21页
Objective:Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression;however,the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer... Objective:Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression;however,the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer remain elusive.It is important to decipher the comprehensive epigenetic regulatory network in breast cancer cells to identify master epigenetic regulators and potential therapeutic targets.Methods:We employed high-throughput sequencing-based high-throughput screening(HTS^(2))to effectively detect changes in the expression of 2,986 genes following the knockdown of 400 epigenetic regulators.Then,bioinformatics analysis tools were used for the resulting gene expression signatures to investigate the epigenetic regulations in breast cancer.Results:Utilizing these gene expression signatures,we classified the epigenetic regulators into five distinct clusters,each characterized by specific functions.We discovered functional similarities between BAZ2B and SETMAR,as well as CLOCK and CBX3.Moreover,we observed that CLOCK functions in a manner opposite to that of HDAC8 in downstream gene regulation.Notably,we constructed an epigenetic regulatory network based on the gene expression signatures,which revealed 8 distinct modules and identified 10 master epigenetic regulators in breast cancer.Conclusions:Our work deciphered the extensive regulation among hundreds of epigenetic regulators.The identification of 10 master epigenetic regulators offers promising therapeutic targets for breast cancer treatment. 展开更多
关键词 Epigenetic regulators breast cancer regulatory network HTS^(2)
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Target Entrapment Based on Adaptive Transformation of Gene Regulatory Networks
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作者 Wenji Li Pengxiang Ren +2 位作者 Zhaojun Wang Chaotao Guan Zhun Fan 《Journal of Beijing Institute of Technology》 EI CAS 2024年第5期389-398,共10页
The complexity of unknown scenarios and the dynamics involved in target entrapment make designing control strategies for swarm robots a formidable task,which in turn impacts their efficiency in complex and dynamic set... The complexity of unknown scenarios and the dynamics involved in target entrapment make designing control strategies for swarm robots a formidable task,which in turn impacts their efficiency in complex and dynamic settings.To address these challenges,this paper introduces an adaptive swarm robot entrapment control model grounded in the transformation of gene regulatory networks(AT-GRN).This innovative model enables swarm robots to dynamically adjust entrap-ment strategies by assessing current environmental conditions via real-time sensory data.Further-more,an improved motion control model for swarm robots is designed to dynamically shape the for-mation generated by the AT-GRN.Through two sets of rigorous experimental environments,the proposed model significantly enhances the trapping performance of swarm robots in complex envi-ronments,demonstrating remarkable adaptability and stability. 展开更多
关键词 swarm robots target entrapment adaptive transformation gene regulatory networks
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An overview of pigment gland morphogenesis and its regulatory mechanism
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作者 SUN Yue YANG Ping +5 位作者 HAN Yifei LI Huazu SUN Deli CHEN Jinhong ZHU Shuijin ZHAO Tianlun 《Journal of Cotton Research》 CAS 2024年第2期207-214,共8页
Cotton has enormous economic potential,providing high-quality protein,oil,and fibre.But the comprehensive utilization of cottonseed is limited by the presence of pigment gland and its inclusion.Pigment gland is a comm... Cotton has enormous economic potential,providing high-quality protein,oil,and fibre.But the comprehensive utilization of cottonseed is limited by the presence of pigment gland and its inclusion.Pigment gland is a common characteristic of Gossypium genus and its relatives,appearing as visible dark opaque dots in most tissues and organs of cotton plants.Secondary metabolites,such as gossypol,synthesized and stored in the cavities of pigment glands act as natural phytoalexins,but are toxic to humans and other monogastric animals.However,only a few cotton genes have been identified as being associated with pigment gland morphogenesis to date,and the developmental processes and regulatory mechanism involved in pigment gland formation remain largely unclear.Here,the research progress on the process of pigment gland morphogenesis and the genetic basis of cotton pigment glands is reviewed,for providing a theoretical basis for cultivating cotton with the ideal pigment gland trait. 展开更多
关键词 Cotton Pigment gland morphogenesis Transcriptional regulation Terpenoids biosynthesis
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Defect in an immune regulator gene BrSRFR1 leads to premature leaf senescence in Chinese cabbage
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作者 Yue Xin Gengxing Song +1 位作者 Chong Tan Hui Feng 《Horticultural Plant Journal》 SCIE CAS CSCD 2024年第6期1414-1423,共10页
Leaf senescence is the final stage of leaf development, where the nutrients and energy of senescent leaves are redistributed to developing tissues or organs for plant growth, reproduction, and defense. Outer leaves ar... Leaf senescence is the final stage of leaf development, where the nutrients and energy of senescent leaves are redistributed to developing tissues or organs for plant growth, reproduction, and defense. Outer leaves are photosynthetic organs that usually senesce at the late heading stage in Chinese cabbage, and premature leaf senescence often reduces leafy head yield and quality. In this study, 11 premature leaf senescence mutants were screened from an ethyl methanesulfonate-mutagenized population of the double haploid line ‘FT' in Chinese cabbage. At the early heading stage, the mutants exhibited edge yellowing within its outer leaves, and at the mature stage, its leafy head weight decreased significantly. Genetic analysis revealed that the mutated trait of all 11 mutants corresponds to single gene recessive inheritance. Semi-diallel cross tests showed that 5 of the 11 were allelic mutants. MutMap and Kompetitive Allele Specific PCR genotyping revealed that BraA01g001400.3C was the candidate gene, which is orthologous of Arabidopsis SUPPRESSOR OF rps4-RLD 1, encoding an immune regulator, so we named it as BrSRFR1. All the BrSRFR1 in the five allelic mutants exhibited single nucleotide polymorphisms at different positions on their exons and led to premature translation termination, which confirmed that defect in BrSRFR1 led to premature leaf senescence. These results verify the role of Br SRFR1 on leaf senescence and provide a new insight into the mechanisms of leaf senescence in Chinese cabbage, which reveals a novel function of SRFR1 in plant development. 展开更多
关键词 Chinese cabbage Premature leaf senescence SRFR1 gene cloning
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Genetic analysis of Chinese families reveals a novel truncation allele of the retinitis pigmentosa GTPase regulator gene 被引量:1
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作者 Fang Hu Xiang-Yun Zeng +7 位作者 Lin-Lin Liu Yao-Ling Luo Yi-Ping Jiang Hui Wang Jing Xie Cheng-Quan Hu Lin Gan Liang Huang 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2014年第5期753-758,共6页
AIMTo make comprehensive molecular diagnosis for retinitis pigmentosa (RP) patients in a consanguineous Han Chinese family using next generation sequencing based Capture-NGS screen technology.
关键词 retinitis pigmentosa GTPase regulator retinitis pigmentosa next-generation sequencing genetic diagnosis
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Transcription regulators differentiate mesenchymal stem cells into chondroprogenitors,and their in vivo implantation regenerated the intervertebral disc degeneration 被引量:2
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作者 Shumaila Khalid Sobia Ekram +2 位作者 Asmat Salim G.Rasul Chaudhry Irfan Khan 《World Journal of Stem Cells》 SCIE 2022年第2期163-182,共20页
BACKGROUND Intervertebral disc degeneration(IVDD)is the leading cause of lower back pain.Disc degeneration is characterized by reduced cellularity and decreased production of extracellular matrix(ECM).Mesenchymal stem... BACKGROUND Intervertebral disc degeneration(IVDD)is the leading cause of lower back pain.Disc degeneration is characterized by reduced cellularity and decreased production of extracellular matrix(ECM).Mesenchymal stem cells(MSCs)have been envisioned as a promising treatment for degenerative illnesses.Cell-based therapy using ECM-producing chondrogenic derivatives of MSCs has the potential to restore the functionality of the intervertebral disc(IVD).AIM To investigate the potential of chondrogenic transcription factors to promote differentiation of human umbilical cord MSCs into chondrocytes,and to assess their therapeutic potential in IVD regeneration.METHODS MSCs were isolated and characterized morphologically and immunologically by the expression of specific markers.MSCs were then transfected with Sox-9 and Six-1 transcription factors to direct differentiation and were assessed for chondrogenic lineage based on the expression of specific markers.These differentiated MSCs were implanted in the rat model of IVDD.The regenerative potential of transplanted cells was investigated using histochemical and molecular analyses of IVDs.RESULTS Isolated cells showed fibroblast-like morphology and expressed CD105,CD90,CD73,CD29,and Vimentin but not CD45 antigens.Overexpression of Sox-9 and Six-1 greatly enhanced the gene expression of transforming growth factor beta-1 gene,BMP,Sox-9,Six-1,and Aggrecan,and protein expression of Sox-9 and Six-1.The implanted cells integrated,survived,and homed in the degenerated intervertebral disc.Histological grading showed that the transfected MSCs regenerated the IVD and restored normal architecture.CONCLUSION Genetically modified MSCs accelerate cartilage regeneration,providing a unique opportunity and impetus for stem cell-based therapeutic approach for degenerative disc diseases. 展开更多
关键词 Intervertebral disc degeneration Human umbilical cord Transcription factors Mesenchymal stem cells gene expression REgeneRATION
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Fluctuation Resonance of Feed Forward Loops in Gene Regulatory Networks 被引量:1
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作者 董翊 侯中怀 辛厚文 《Chinese Journal of Chemical Physics》 SCIE CAS CSCD 2009年第4期359-365,447,共8页
The feed forward loop (FFL), wherein a gene X can regulate target gene Z alone or cooperatively with gene Y, is one of the most important motifs in gene regulatory networks. Gene expression often involves a small nu... The feed forward loop (FFL), wherein a gene X can regulate target gene Z alone or cooperatively with gene Y, is one of the most important motifs in gene regulatory networks. Gene expression often involves a small number of reactant molecules and thus internal molecular fluctuation is considerable. Here we studied how an FFL responds to small external signal inputs at gene X, with particular attention paid to the fluctuation resonance (FR) phenomenon of gene Z. We found that for all coherent FFLs, where the sign of the direct regulation path from X to Z is the same as the overall sign of the indirect path via Y, the FR shows a regular single peak, while for incoherent FFLs, the FR exhibits distinct bimodal shapes. The results indicate that one could use small external signals to help identify the regulatory structure of an unknown FFL in complex gene networks. 展开更多
关键词 gene regulatory network Fluctuation resonance Feed-forward-loop
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Combination of Neuro-Fuzzy Network Models with Biological Knowledge for Reconstructing Gene Regulatory Networks 被引量:1
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作者 Guixia Liu Lei Liu +3 位作者 Chunyu Liu Ming Zheng Lanying Su Chunguang Zhou 《Journal of Bionic Engineering》 SCIE EI CSCD 2011年第1期98-106,共9页
Inferring gene regulatory networks from large-scale expression data is an important topic in both cellular systems and computational biology. The inference of regulators might be the core factor for understanding actu... Inferring gene regulatory networks from large-scale expression data is an important topic in both cellular systems and computational biology. The inference of regulators might be the core factor for understanding actual regulatory conditions in gene regulatory networks, especially when strong regulators do work significantly. In this paper, we propose a novel approach based on combining neuro-fu^zy network models with biological knowledge to infer strong regulators and interrelated fuzzy rules. The hybrid neuro-fuzzy architecture can not only infer the fuzzy rules, which are suitable for describing the regulatory conditions in regulatory nctworks+ but also explain the meaning of nodes and weight value in the neural network. It can get useful rules automatically without lhctitious judgments. At the same time, it does not add recursive layers to the model, and the model can also strengthen the relationships among genes and reduce calculation. We use the proposed approach to reconstruct a partial gene regulatory network of yeast, The results show that this approach can work effectively. 展开更多
关键词 neuro-fuzzy network biological knowledge regulatorS gene regulatory networks
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Establishment of high frequency shoot regeneration system in Himalayan poplar(Populus ciliata Wall. ex Royle) from petiole explants using Thidiazuron cytokinin as plant growth regulator 被引量:4
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作者 G. Aggarwal A. Gaur D. K. Srivastava 《Journal of Forestry Research》 SCIE CAS CSCD 2015年第3期651-656,共6页
Populus species are important resources for industry and in scientific study on biological and agricul- tural systems. Our objective was to enhance the frequency of plant regeneration in Himalayan poplar (Populus cil... Populus species are important resources for industry and in scientific study on biological and agricul- tural systems. Our objective was to enhance the frequency of plant regeneration in Himalayan poplar (Populus ciliata wall. ex Royle). The effect of TDZ alone and in combi- nation with adenine and NAA was studied on the regen- eration potential of petiole explants. The explants were excised from Himalayan poplar plants grown in glass- houses. After surface sterilization the explants were cul- tured on shoot induction medium. High percentage shoot regeneration (86 %) was recorded on MS medium sup- plemented with 0.004 mg L-1 TDZ and 79.7 mg L-1 adenine. The regenerated shoots for elongation and multi- plication were transferred to MS + 0.5 mg L-1 BAP + 0.2 mg L-1 IAA + 0.3 mg L-1 GA3. Root re- generation from shoots developed in vitro was observed on MS medium supplemented with 0.10 mg L-1 IBA. Hi- malayan poplar plantlets could be produced within 2 months after acclimatization in a sterile mixture of sand and soil. We developed a high efficiency plant regeneration protocol from petiole explants of P. ciliata. 展开更多
关键词 In vitro regeneration Petiole explants Growth regulator THIDIAZURON Populus ciliata
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Reconstruction of Gene Regulatory Networks Based on Two-Stage Bayesian Network Structure Learning Algorithm 被引量:4
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作者 Gui-xia Liu, Wei Feng, Han Wang, Lei Liu, Chun-guang ZhouCollege of Computer Science and Technology, Jilin University, Changchun 130012,P.R. China 《Journal of Bionic Engineering》 SCIE EI CSCD 2009年第1期86-92,共7页
In the post-genomic biology era,the reconstruction of gene regulatory networks from microarray gene expression data is very important to understand the underlying biological system,and it has been a challenging task i... In the post-genomic biology era,the reconstruction of gene regulatory networks from microarray gene expression data is very important to understand the underlying biological system,and it has been a challenging task in bioinformatics.The Bayesian network model has been used in reconstructing the gene regulatory network for its advantages,but how to determine the network structure and parameters is still important to be explored.This paper proposes a two-stage structure learning algorithm which integrates immune evolution algorithm to build a Bayesian network.The new algorithm is evaluated with the use of both simulated and yeast cell cycle data.The experimental results indicate that the proposed algorithm can find many of the known real regulatory relationships from literature and predict the others unknown with high validity and accuracy. 展开更多
关键词 gene regulatory networks two-stage learning algorithm Bayesian network immune evolutionary algorithm
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Stochastic resonance induced by a multiplicative periodic signal in the gene transcriptional regulatory system with correlated noises 被引量:2
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作者 白春燕 闫勇 梅冬成 《Chinese Physics B》 SCIE EI CAS CSCD 2010年第6期88-92,共5页
This paper investigates the stochastic resonance (SR) induced by a multiplicative periodic signal in the gene transcriptional regulatory system with correlated noises. The expression of the signal-to-noise ratio (... This paper investigates the stochastic resonance (SR) induced by a multiplicative periodic signal in the gene transcriptional regulatory system with correlated noises. The expression of the signal-to-noise ratio (SNR) is derived. The results indicate that the existence of a maximum in SNR vs. the additive noise intensity α the multiplicative noise intensity D and the cross-correlated noise intensity λ is the identifying characteristic of the SR phenomenon and there is a critical phenomenon in the SNR as a function of λ, i.e., for the case of smaller values of noise intensity (α or D), the SNR decreases as λ increases; however, for the case of larger values of noise intensity (α or D), the SNR increases as λ increases. 展开更多
关键词 gene transcriptional regulatory system stochastic resonance critical phenomenon
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Stochastic resonance in the gene transcriptional regulatory system subjected to noises 被引量:1
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作者 王参军 《Chinese Physics B》 SCIE EI CAS CSCD 2010年第3期112-116,共5页
We have investigated in the adiabatic limit the phenomenon of stochastic resonance in the gene transcriptional regulatory system subjected to an additive noise, a multiplicative noise, and a weakly periodic signal. Us... We have investigated in the adiabatic limit the phenomenon of stochastic resonance in the gene transcriptional regulatory system subjected to an additive noise, a multiplicative noise, and a weakly periodic signal. Using the general two-state approach for the asymmetry system, the analytic expression of signal-to-noise ratio is obtained. The effects of the additive noise intensity a, the multiplicative noise intensity D and the amplitude of input periodic signal A on the signal-to-noise ratio are analysed by numerical calculation. It is found that the existence of a maximum in the RSNR a and RSNR D plots is the identifying characteristic of the stochastic resonance phenomenon in the weakened noise intensity region. The stochastic resonance phenomena are restrained with increasing a and D, and enhanced with increasing A. 展开更多
关键词 gene transcriptional regulatory system stochastic resonance NOISES
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Reconstructing gene regulatory networks in single-cell transcriptomic data analysis 被引量:3
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作者 Hao Dai Qi-Qi Jin +1 位作者 Lin Li Luo-Nan Chen 《Zoological Research》 SCIE CAS CSCD 2020年第6期599-604,共6页
Gene regulatory networks play pivotal roles in our understanding of biological processes/mechanisms at the molecular level.Many studies have developed sample-specific or cell-type-specific gene regulatory networks fro... Gene regulatory networks play pivotal roles in our understanding of biological processes/mechanisms at the molecular level.Many studies have developed sample-specific or cell-type-specific gene regulatory networks from single-cell transcriptomic data based on a large amount of cell samples.Here,we review the state-of-the-art computational algorithms and describe various applications of gene regulatory networks in biological studies. 展开更多
关键词 gene regulatory network Single-cell RNA sequencing Computational algorithm Sample-specificnetwork Cell-type-specific network Cell-specific network
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A cluster of mutagenesis revealed an osmotic regulatory role of the OsPIP1 genes in enhancing rice salt tolerance 被引量:1
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作者 Leyuan Tao Bing Wang +6 位作者 Shichao Xin Wei Li Shengcai Huang Laihua Liu Jing Cui Qianru Zhang Xianguo Cheng 《The Crop Journal》 SCIE CSCD 2023年第4期1204-1217,共14页
Aquaporins play important regulatory roles in improving plant abiotic stress tolerance.To better understand whether the Os PIP1 genes collectively dominate the osmotic regulation in rice under salt stress,a cluster ed... Aquaporins play important regulatory roles in improving plant abiotic stress tolerance.To better understand whether the Os PIP1 genes collectively dominate the osmotic regulation in rice under salt stress,a cluster editing of the Os PIP1;1,Os PIP1;2 and Os PIP1;3 genes in rice was performed by CRISPR/Cas9 system.Sequencing showed that two mutants with Cas9-free,line 14 and line 18 were successfully edited.Briefly,line 14 deleted a single C base in both the Os PIP1;1 and Os PIP1;3 genes,and inserted a single T base in the Os PIP1;2 gene,respectively.While line 18 demonstrated an insertion of a single A base in the Os PIP1;1gene and a single T base in both the Os PIP1;2 and Os PIP1;3 genes,respectively.Multiplex editing of the Os PIP1 genes significantly inhibited photosynthetic rate and accumulation of compatible metabolites,but increased MDA contents and osmotic potentials in the mutants,thus delaying rice growth under salt stress.Functional loss of the Os PIP1 genes obviously suppressed the expressions of the Os PIP1,Os SOS1,Os CIPK24 and Os CBL4 genes,and increased the influxes of Na+and effluxes of K^(+)/H^(+)in the roots,thus accumulating more Na+in rice mutants under salt stress.This study suggests that the Os PIP1 genes are essential modulators collectively contributing to the enhancement of rice salt stress tolerance,and multiplex editing of the Os PIP1 genes provides insight into the osmotic regulation of the PIP genes. 展开更多
关键词 AQUAPORIN Multiplex gene editing CRISPR/Cas9 OsPIP1 genes Rice(Oryza sativa L.) Salt tolerance
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Mutations in epigenetic regulator KMT2C detected by liquid biopsy are associated with worse survival in prostate cancer patients 被引量:1
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作者 SHA ZHU NANWEI XU +10 位作者 JIAYU LIANG FENGNIAN ZHAO ZILIN WANG YUCHAO NI JINDONG DAI JINGE ZHAO XINGMING ZHANG JUNRU CHEN GUANGXI SUN PENGFEI SHEN HAO ZENG 《Oncology Research》 SCIE 2023年第4期605-614,共10页
Background:KMT2(lysine methyltransferase)family enzymes are epigenetic regulators that activate gene transcription.KMT2C is mainly involved in enhancer-associated H3K4me1,and is also one of the top mutated genes in ca... Background:KMT2(lysine methyltransferase)family enzymes are epigenetic regulators that activate gene transcription.KMT2C is mainly involved in enhancer-associated H3K4me1,and is also one of the top mutated genes in cancer(6.6%in pan-cancer).Currently,the clinical significance of KMT2C mutations in prostate cancer is understudied.Methods:We included 221 prostate cancer patients diagnosed between 2014 and 2021 in West China Hospital of Sichuan University with cell-free DNA-based liquid biopsy test results in this study.We investigated the association between KMT2C mutations,other mutations,and pathways.Furthermore,we evaluated the prognostic value of KMT2C mutations,measured by overall survival(OS)and castration resistance-free survival(CRFS).Also,we explored the prognostic value of KMT2C mutations in different patient subgroups.Lastly,we investigated the predictive value of KMT2C mutations in individuals receiving conventional combined anti-androgen blockade(CAB)and abiraterone(ABI)as measured by PSA progression-free survival(PSA-PFS).Results:The KMT2C mutation rate in this cohort is 7.24%(16/221).KMT2C-mutated patients showed worse survival than KMT2C-wild type(WT)patients regarding both CRFS and OS(CRFS:mutated:9.9 vs.WT:22.0 months,p=0.015;OS:mutated:71.9 vs.WT 137.4 months,p=0.012).KMT2C mutations were also an independent risk factor in OS[hazard ratio:3.815(1.461,9.96),p=0.006]in multivariate analyses.Additionally,we explored the association of KMT2C mutations with other genes.This showed that KMT2C mutations were associated with Serine/Threonine-Protein Kinase 11(STK11,p=0.004)and Catenin Beta 1(CTNNB1,p=0.008)mutations.In the CAB treatment,KMT2C-mutated patients had a significantly shorter PSA-PFS compared to KMT2C-WT patients.(PSA-PFS:mutated:9.9 vs.WT:17.6 months,p=0.014).Moreover,KMT2C mutations could effectively predict shorter PSA-PFS in 10 out of 23 subgroups and exhibited a strong trend in the remaining subgroups.Conclusions:KMT2C-mutated patients showed worse survival compared to KMT2C-WT patients in terms of both CRFS and OS,and KMT2C mutations were associated with STK11 and CTNNB1 mutations.Furthermore,KMT2C mutations indicated rapid progression during CAB therapy and could serve as a potential biomarker to predict therapeutic response in prostate cancer. 展开更多
关键词 KMT2C Epigenetic regulator Liquid biopsy Prostate cancer SURVIVAL Biomarker
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Mutagenesis reveals that the rice OsMPT3 gene is an important osmotic regulatory factor 被引量:2
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作者 Shengcai Huang Shichao Xin +6 位作者 Guoqiang Xie Jiao Han Zhonglai Liu Bing Wang Shuqing Zhang Qingyu Wu Xianguo Cheng 《The Crop Journal》 SCIE CAS CSCD 2020年第3期465-479,共15页
Plant mitochondrial phosphate transporters regulate phosphate transport and ATP synthesis. Determining whether they function in abiotic stress response process would shed light on their response to salt stress. We use... Plant mitochondrial phosphate transporters regulate phosphate transport and ATP synthesis. Determining whether they function in abiotic stress response process would shed light on their response to salt stress. We used the CRISPR/Cas9 gene-editing system to mutagenize two mitochondrial phosphate transporters, OsMPT3;1 and OsMPT3;2, to investigate their regulatory roles under salt stress. Two cas9(CRISPR-associated protein9)-free homozygous mutants, mpt33 and mpt30, were confirmed to be stable. Both OsMPT3;1 and OsMPT3;2 were markedly induced by salt stress, and their mutagenesis strongly inhibited growth and development, especially under salt stress. Mutagenesis sharply reduced the accumulation of ATP, phosphate, calcium, soluble sugar, and proline and increased osmotic potential, malondialdehyde, and Na^+ /K^+ ratio under salt stress. Both mutants demonstrate normal growth and development in the presence of ATP, revealing high sensitivity to exogenous ATP under salt stress. The mutants showed lowered rates of Na^+ efflux but also of K^+ and Ca^(2+) influx under salt stress. Mutagenesis of OsMPT3;2 altered the enrichment profiles of differentially expressed genes involved mainly in synthesis of secondary metabolites, metabolism of glycolysis, pyruvate, tricarboxylic acid cycle, in response to salt stress. The mutant displayed significant accumulation differences in 14 metabolites involved in 17 metabolic pathways, and strongly up-regulated the accumulation of glutamine, a precursor in proline synthesis, under salt stress. These findings suggest that the OsMPT3 gene modulates phosphate transport and energy supply for ATP synthesis and triggers changes in accumulation of ions and metabolites participating in osmotic regulation in rice under salt stress, thus increasing rice salt tolerance. This study demonstrates the effective application of CRISPR/Cas9 gene-editing to the investigation of plant functional genes. 展开更多
关键词 MPT ATP CRISPR Mutagenesis reveals that the rice OsMPT3 gene is an important osmotic regulatory factor
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Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease
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作者 Mackenzie M.Spicer Jianqi Yang +5 位作者 Daniel Fu Alison N.DeVore Marisol Lauffer Nilufer S.Atasoy Deniz Atasoy Rory A.Fisher 《Neural Regeneration Research》 SCIE CAS 2025年第10期2969-2981,共13页
Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rode... Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease. 展开更多
关键词 adult hippocampal neurogenesis Alzheimer’s disease dentate gyrus EXERCISE learning/memory neural precursor cells regulator of G protein signaling 6(RGS6)
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Determining Nodulation Regulatory (Rj) Genes of Myanmar Soybean Cultivars and Their Symbiotic Effectiveness with <i>Bradyrhizobium japonicum</i>USDA110
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作者 Aung Zaw Htwe Yuichi Saeki +1 位作者 Kyi Moe Takeo Yamakawa 《American Journal of Plant Sciences》 2015年第18期2799-2810,共12页
Soybean (Glycine max L.) plays an essential role in human nutrition as a protein source, and in plant nutrition as a N source. The rate of N fixation varies depending on the cultivars and compatibility between the ino... Soybean (Glycine max L.) plays an essential role in human nutrition as a protein source, and in plant nutrition as a N source. The rate of N fixation varies depending on the cultivars and compatibility between the inoculated Rhizobium strain and the host cultivar. Characterizing the nodulation regulatory (Rj) genes is necessary to determine the compatibility of cultivars and Rhizobium strains. Rj genes were previously identified based on inoculation tests and PCR analyses. The six cultivars Yezin-3, Yezin-7, Yezin-11, Shan Seine (Local), Madaya (Local), and Hinthada (Local) were identified as harboring the Rj4 gene. Two cultivars, Yezin-6 and Yezin-8, were classified as non-Rj-gene harboring. Two other cultivars, Yezin-9 and Yezin-10, were identified as Rj3- and Rj2Rj3-gene harboring, respectively. Ours is the first report on Rj3- and Rj2Rj3-gene harboring cultivars in Myanmar. We evaluated Myanmar soybean cultivars for symbiotic effectiveness, relying on the standard strain Bradyrhizobium japonicum USDA110. In our first experiment, the soybean cultivar Yezin-11 (Rj4) showed the highest N fixing potential. Based on their potential for fixing N and nodulation, the top six soybean cultivars were Yezin-11 (Rj4), Yezin-9 (Rj3), Yezin-6 (non-Rj), Yezin-8 (non-Rj), Yezin-3 (Rj4) and Yezin-10 (Rj2Rj3). These cultivars were selected for a second experiment, which revealed that the N fixation, nodulation, and plant growth of Yezin-11 (Rj4) *Corresponding author. A. Z. Htwe et al. 2800 were superior to the other cultivars. We conclude that Yezin-11 (Rj4) is the most efficient cultivar for nodulation and N fixation when inoculated with B. japonicum USDA110. 展开更多
关键词 B. JAPONICUM USDA110 Inoculation Test PCR Analysis NODULATION regulatorY geneS (Rj gene) Symbiotic Effectiveness
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Targeting transcriptional regulators to regenerate midbrain dopaminergic axons in Parkinson's disease
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作者 Shane V.Hegarty Aideen M.Sullivan Gerard W.O'Keeffe 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第11期1814-1815,共2页
Introduction: Parkinson's disease (PD) is a chronic, age-re- lated neurodegenerative disorder that affects 1-2% of the population over the age of 65. PD is characterised by the progressive degeneration of nigrostr... Introduction: Parkinson's disease (PD) is a chronic, age-re- lated neurodegenerative disorder that affects 1-2% of the population over the age of 65. PD is characterised by the progressive degeneration of nigrostriatal dopaminergic (DA) neurons. This leads to disabling motor symptoms, due to the striatal DA denervation. Despite decades of research, there is still no therapy that can slow, stop or regenerate the dying midbrain DA neurons in PD. 展开更多
关键词 Targeting transcriptional regulators regenerate midbrain dopaminergic axons
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