Background:Alzheimer’sdisease(AD)is a prevalent neurodegenerative disorder causing progressive dementia.Research suggests that microRNAs(miRNAs)could serve as biomarkers and therapeutic targets for AD.Reduced levels ...Background:Alzheimer’sdisease(AD)is a prevalent neurodegenerative disorder causing progressive dementia.Research suggests that microRNAs(miRNAs)could serve as biomarkers and therapeutic targets for AD.Reduced levels of miR-137 have been observed in the brains of AD patients,but its specific role and down stream mechanisms remain unclear.This study sought to examine the therapeutic potential of miR-137-5p agomir in alleviating cognitive dysfunction induced in AD models and explore its potential mechanisms.Methods:This study utilized bioinformatic analysis and a dual-l uciferase reporter assay to investigate the relationship between miR-137-5p and ubiquitin-specific peptidase 30(USP30).In vitro experiments were conducted using SH-SY5Y cells to assess the impact of miR-137-5p on Aβ1-42 neurotoxicity.In vivo experiments on AD mice evaluated the effects of miR-137-5p on cognition,Aβ1-42 deposition,Tau hyperphosphorylation,and neuronal apoptosis,as well as its influence on USP30 levels.Results:It was discovered that miR-137-5p mimics efficiently counteract Aβ1-42 neurotoxicity in SH-SY5Y cells,a protective effect that is negated by USP30 overexpression.In vivo experiments demonstrated that miR-137-5p enhances the cognition and mobility of AD mice,significantly reducing Aβ1-42 deposition,Tau hyperphosphorylation,and neuronal apoptosis within the hippocampus and cortex regions.Mechanistically,miR-137-5p significantly suppresses USP30 levels in mice,though USP30 overexpression partially buffers against miR-137-5p-i nduced AD symptom improvement.Conclusion:Our study proposes that miR-137-5p,by instigating the downregulation of USP30,has the potential to act as a novel and promising therapeutic target for AD.展开更多
The spike architecture of wheat plays a crucial role in determining grain number,making it a key trait for optimization in wheat breeding programs.In this study,we used a multi-omic approach to analyze the transcripto...The spike architecture of wheat plays a crucial role in determining grain number,making it a key trait for optimization in wheat breeding programs.In this study,we used a multi-omic approach to analyze the transcriptome and epigenome profiles of the young spike at eight developmental stages,revealing co-ordinated changes in chromatin accessibility and H3K27me3 abundance during the flowering transition.We constructed a core transcriptional regulatory network(TRN)that drives wheat spike formation and experimentally validated a multi-layer regulatorymodule involving TaSPL15,TaAGLG1,and TaFUL2.By integrating the TRN with genome-wide association studies,we identified 227 transcription factors,including 42 with known functions and 185 with unknown functions.Further investigation of 61 novel transcription factors using multiple homozygous mutant lines revealed 36 transcription factors that regulate spike architecture or flowering time,such as TaMYC2-A1,TaMYB30-A1,and TaWRKY37-A1.Of particular interest,TaMYB30-A1,downstream of and repressed by WFzP,was found to regulate fertile spikelet number.Notably,the excellent haplotype of TaMYB30-A1,which contains a C allele at the WFzP binding site,was enriched during wheat breeding improvement in China,leading to improved agronomic traits.Finally,we constructed a free and open access Wheat Spike Multi-Omic Database(http://39.98.48.156:8800/#/).Our study identifies novel and high-confidence regulators and offers an effective strategy for dissecting the genetic basis of wheat spike development,with practical value forwheat breeding.展开更多
基金Liaoning Province Science and Technology Project(grant/award number:2019-BS-221)Shenyang Science and Technology Project(grant/award number:19-112-4-040)。
文摘Background:Alzheimer’sdisease(AD)is a prevalent neurodegenerative disorder causing progressive dementia.Research suggests that microRNAs(miRNAs)could serve as biomarkers and therapeutic targets for AD.Reduced levels of miR-137 have been observed in the brains of AD patients,but its specific role and down stream mechanisms remain unclear.This study sought to examine the therapeutic potential of miR-137-5p agomir in alleviating cognitive dysfunction induced in AD models and explore its potential mechanisms.Methods:This study utilized bioinformatic analysis and a dual-l uciferase reporter assay to investigate the relationship between miR-137-5p and ubiquitin-specific peptidase 30(USP30).In vitro experiments were conducted using SH-SY5Y cells to assess the impact of miR-137-5p on Aβ1-42 neurotoxicity.In vivo experiments on AD mice evaluated the effects of miR-137-5p on cognition,Aβ1-42 deposition,Tau hyperphosphorylation,and neuronal apoptosis,as well as its influence on USP30 levels.Results:It was discovered that miR-137-5p mimics efficiently counteract Aβ1-42 neurotoxicity in SH-SY5Y cells,a protective effect that is negated by USP30 overexpression.In vivo experiments demonstrated that miR-137-5p enhances the cognition and mobility of AD mice,significantly reducing Aβ1-42 deposition,Tau hyperphosphorylation,and neuronal apoptosis within the hippocampus and cortex regions.Mechanistically,miR-137-5p significantly suppresses USP30 levels in mice,though USP30 overexpression partially buffers against miR-137-5p-i nduced AD symptom improvement.Conclusion:Our study proposes that miR-137-5p,by instigating the downregulation of USP30,has the potential to act as a novel and promising therapeutic target for AD.
基金supported by the National Natural Science Foundation of China(31921005)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA24010204)+1 种基金the National Key Research and Development Program of China(2021YFD1201500)the Major Basic Research Program of Shandong Natural Science Foundation of China(ZR2019ZD15).
文摘The spike architecture of wheat plays a crucial role in determining grain number,making it a key trait for optimization in wheat breeding programs.In this study,we used a multi-omic approach to analyze the transcriptome and epigenome profiles of the young spike at eight developmental stages,revealing co-ordinated changes in chromatin accessibility and H3K27me3 abundance during the flowering transition.We constructed a core transcriptional regulatory network(TRN)that drives wheat spike formation and experimentally validated a multi-layer regulatorymodule involving TaSPL15,TaAGLG1,and TaFUL2.By integrating the TRN with genome-wide association studies,we identified 227 transcription factors,including 42 with known functions and 185 with unknown functions.Further investigation of 61 novel transcription factors using multiple homozygous mutant lines revealed 36 transcription factors that regulate spike architecture or flowering time,such as TaMYC2-A1,TaMYB30-A1,and TaWRKY37-A1.Of particular interest,TaMYB30-A1,downstream of and repressed by WFzP,was found to regulate fertile spikelet number.Notably,the excellent haplotype of TaMYB30-A1,which contains a C allele at the WFzP binding site,was enriched during wheat breeding improvement in China,leading to improved agronomic traits.Finally,we constructed a free and open access Wheat Spike Multi-Omic Database(http://39.98.48.156:8800/#/).Our study identifies novel and high-confidence regulators and offers an effective strategy for dissecting the genetic basis of wheat spike development,with practical value forwheat breeding.
