Background:Aortic dissection(AD)is a fatal cardiovascular disease for which the key involved genes are largely unknown.Here,we aimed to identify promising AD biomarkers from high-throughput RNA expressing data.Methods...Background:Aortic dissection(AD)is a fatal cardiovascular disease for which the key involved genes are largely unknown.Here,we aimed to identify promising AD biomarkers from high-throughput RNA expressing data.Methods:In the GSE98770 dataset,differentially expressed mRNAs(DE-mRNAs)and microRNAs(DE-microRNAs)were identified through differentially expressed gene analysis and gene set enrichment analysis.The regulatory network between DE-mRNAs and DE-microRNAs was established,and hub genes were identified with Cytoscape.Relationships between hub genes and AD were confirmed in the Comparative Toxicogenomics Database(CTD).Potential key transcription factors were discovered with Cytoscape.Hub gene verification was performed by qPCR and immunofluorescence analyses of human specimens.Results:DE-mRNAs and DE-microRNAs were identified.Four mRNAs and microRNA-1321(miR-1321)were found to have the most connections with other genes.CBL was connected to the most genes and interacted with miR-1321,which was also connected to the most genes among the DE-microRNAs.In addition,CBL was associated with AD in the CTD.Among the top five transcription factors potentially regulating CBL transcription,only HOXB13 was a DE-mRNA.The findings were further successfully verified in human specimens.Conclusion:CBL,which may be transcriptionally regulated by HOXB13 and post-transcriptionally regulated by miR-1321,was identified as the most promising potential biomarker for AD.展开更多
目的:探讨同源异形盒基因B13(HOXB13)和c-myc在结直肠癌中表达的变化及意义。方法:用RT-PCR法和Western blot法检测54例结直肠癌患者癌组织及相应癌旁组织中HOXB13与c-myc的表达,并分析两者表达与结直肠癌的临床病理特征的关系。结果:...目的:探讨同源异形盒基因B13(HOXB13)和c-myc在结直肠癌中表达的变化及意义。方法:用RT-PCR法和Western blot法检测54例结直肠癌患者癌组织及相应癌旁组织中HOXB13与c-myc的表达,并分析两者表达与结直肠癌的临床病理特征的关系。结果:结直肠癌组织中的HOXB13 m RNA和蛋白的表达明显低于癌旁正常结直肠组织,而c-myc m RNA和蛋白的表达明显高于癌旁正常结直肠组织(均P<0.05);两者的表达均与淋巴转移以及TNM分期有关(均P<0.05);结直肠组织中HOXB13蛋白与c-myc蛋白的表达呈负相关(r=-0.572,P<0.001)。结论:HOXB13的表达降低可能促进了原癌基因c-myc的表达,从而促进结直肠癌的发生、发展和转移。展开更多
The influence ofγ-irradiation on properties of METGLAS 2605S2 and FC3-1 Fe78B13Si9 has been investigated by Möissbauer spectroscopy and bending test.The ductility and orientation of magnetization were changed by...The influence ofγ-irradiation on properties of METGLAS 2605S2 and FC3-1 Fe78B13Si9 has been investigated by Möissbauer spectroscopy and bending test.The ductility and orientation of magnetization were changed byγ-irradiation.They probably correlated with the change of microscopic free volume and release of stress in the ribbon,respectively.展开更多
Background:Kinesin family member 13B(KIF13B),a crucial motor protein,exerts multiple cellular biological functions.However,the implication of KIF13B in metabolic dysfunction-associated fatty liver disease(MAFLD)has no...Background:Kinesin family member 13B(KIF13B),a crucial motor protein,exerts multiple cellular biological functions.However,the implication of KIF13B in metabolic dysfunction-associated fatty liver disease(MAFLD)has not been explored yet.This study aimed to investigate KIF13B’s role and underlying mechanism in MAFLD and proposes it as a potential pharmacological target.Methods:We assessed KIF13B expression in MAFLD patients and rodent models.The roles of Kif13b in lipid metabolism and MAFLD were investigated using whole-body Kif13b knockout mice,hepatocyte-specific Kif13b-deficient mice and hamsters exposed to different diets.The underlying mechanisms by which Kif13bgoverned hepatic lipid homeostasis and MAFLD progression were explored in vitro.Finally,the Kif13b’s impact on atherosclerotic development was studied in the context of MAFLD.Results:KIF13B expression was reduced in patients and murine models with MAFLD.Rodents with global or liver-specific knockout of the Kif13b gene exhibit spontaneous hepatic steatosis,which is further exacerbated by different overnutrition diets.Overexpression of human KIF13B by lentivirus effectively prevented metabolic dysfunction-associated steatohepatitis(MASH)in methionine-choline-deficient diet(MCD)-fed mice.Furthermore,Kif13b deficiency accelerates atherosclerosis in the context of MAFLD.Mechanistically,Kif13b depletion increases hepatic lipid synthesis and impairs mitochondrial oxidative phosphorylation.Further screening reveals that Kif13b interacts with AMP-activated catalytic subunit alpha 1(AMPKα1)to regulate the phosphorylation of AMPKα1,governing mitochondrial homeostasis and suppressing sterol regulatory element binding protein 1(Srebp1)-mediated denovo lipogenesis in the liver.Conclusion:This work establishes a causal relationship between KIF13B deficiency and MAFLD,emphasizing KIF13B as a potential therapeutic target for treating MAFLD.展开更多
CRISPR-Cas endonucleases mediate prokaryotic adaptive immunity by targeting foreign nucleic acids.CRISPR/Cas13b is a class 2 type VI-B ribonuclease that targets and cleaves single-stranded RNA.It exhibits higher RNA i...CRISPR-Cas endonucleases mediate prokaryotic adaptive immunity by targeting foreign nucleic acids.CRISPR/Cas13b is a class 2 type VI-B ribonuclease that targets and cleaves single-stranded RNA.It exhibits higher RNA interference activity than Cas13a and Cas13c and causes fewer collateral effects than RxCas13d in mammalian cells.However,a programmable CRISPR/Cas13b-mediated RNA interference system for endogenous transcripts in rice has not yet been established.Here,we developed a CRISPR/Cas13b-mediated system to target endogenous transcripts in rice.Our CRISPR/Cas13b system could inhibit multiple endogenous mRNAs simultaneously.In addition,this system efficiently repressed endogenous long noncoding RNAs with more than 50% inhibition in stable transgenic plants.Furthermore,we found only weak collateral effects of the CRISPR/Cas13b-mediated system at the transcriptome-wide level,and no difference in the agronomic traits of stable transgenic rice in the field.We present a programmable CRISPR/Cas13b-mediated knockdown system for rice,offering a potential biotechnological tool for functional genomics and crop improvement.展开更多
基金supported by grants from the Guangzhou Basic and Applied Basic Research Foundation(202201010940)National Natural Science Foundation of China(82200306)Guangdong Basic and Applied Basic Research Foundation(2021A1515111092).
文摘Background:Aortic dissection(AD)is a fatal cardiovascular disease for which the key involved genes are largely unknown.Here,we aimed to identify promising AD biomarkers from high-throughput RNA expressing data.Methods:In the GSE98770 dataset,differentially expressed mRNAs(DE-mRNAs)and microRNAs(DE-microRNAs)were identified through differentially expressed gene analysis and gene set enrichment analysis.The regulatory network between DE-mRNAs and DE-microRNAs was established,and hub genes were identified with Cytoscape.Relationships between hub genes and AD were confirmed in the Comparative Toxicogenomics Database(CTD).Potential key transcription factors were discovered with Cytoscape.Hub gene verification was performed by qPCR and immunofluorescence analyses of human specimens.Results:DE-mRNAs and DE-microRNAs were identified.Four mRNAs and microRNA-1321(miR-1321)were found to have the most connections with other genes.CBL was connected to the most genes and interacted with miR-1321,which was also connected to the most genes among the DE-microRNAs.In addition,CBL was associated with AD in the CTD.Among the top five transcription factors potentially regulating CBL transcription,only HOXB13 was a DE-mRNA.The findings were further successfully verified in human specimens.Conclusion:CBL,which may be transcriptionally regulated by HOXB13 and post-transcriptionally regulated by miR-1321,was identified as the most promising potential biomarker for AD.
文摘目的:探讨同源异形盒基因B13(HOXB13)和c-myc在结直肠癌中表达的变化及意义。方法:用RT-PCR法和Western blot法检测54例结直肠癌患者癌组织及相应癌旁组织中HOXB13与c-myc的表达,并分析两者表达与结直肠癌的临床病理特征的关系。结果:结直肠癌组织中的HOXB13 m RNA和蛋白的表达明显低于癌旁正常结直肠组织,而c-myc m RNA和蛋白的表达明显高于癌旁正常结直肠组织(均P<0.05);两者的表达均与淋巴转移以及TNM分期有关(均P<0.05);结直肠组织中HOXB13蛋白与c-myc蛋白的表达呈负相关(r=-0.572,P<0.001)。结论:HOXB13的表达降低可能促进了原癌基因c-myc的表达,从而促进结直肠癌的发生、发展和转移。
文摘The influence ofγ-irradiation on properties of METGLAS 2605S2 and FC3-1 Fe78B13Si9 has been investigated by Möissbauer spectroscopy and bending test.The ductility and orientation of magnetization were changed byγ-irradiation.They probably correlated with the change of microscopic free volume and release of stress in the ribbon,respectively.
基金supported by the National Natural Science Foundation of China(82270479,82070460)the Beijing Natural Science Foundation(7242084 to Xun-De Xian)the National Key Research and Development Program of China from the Ministry of Science and Technology(2021YFF0702802 to Yu-Hui Wang).
文摘Background:Kinesin family member 13B(KIF13B),a crucial motor protein,exerts multiple cellular biological functions.However,the implication of KIF13B in metabolic dysfunction-associated fatty liver disease(MAFLD)has not been explored yet.This study aimed to investigate KIF13B’s role and underlying mechanism in MAFLD and proposes it as a potential pharmacological target.Methods:We assessed KIF13B expression in MAFLD patients and rodent models.The roles of Kif13b in lipid metabolism and MAFLD were investigated using whole-body Kif13b knockout mice,hepatocyte-specific Kif13b-deficient mice and hamsters exposed to different diets.The underlying mechanisms by which Kif13bgoverned hepatic lipid homeostasis and MAFLD progression were explored in vitro.Finally,the Kif13b’s impact on atherosclerotic development was studied in the context of MAFLD.Results:KIF13B expression was reduced in patients and murine models with MAFLD.Rodents with global or liver-specific knockout of the Kif13b gene exhibit spontaneous hepatic steatosis,which is further exacerbated by different overnutrition diets.Overexpression of human KIF13B by lentivirus effectively prevented metabolic dysfunction-associated steatohepatitis(MASH)in methionine-choline-deficient diet(MCD)-fed mice.Furthermore,Kif13b deficiency accelerates atherosclerosis in the context of MAFLD.Mechanistically,Kif13b depletion increases hepatic lipid synthesis and impairs mitochondrial oxidative phosphorylation.Further screening reveals that Kif13b interacts with AMP-activated catalytic subunit alpha 1(AMPKα1)to regulate the phosphorylation of AMPKα1,governing mitochondrial homeostasis and suppressing sterol regulatory element binding protein 1(Srebp1)-mediated denovo lipogenesis in the liver.Conclusion:This work establishes a causal relationship between KIF13B deficiency and MAFLD,emphasizing KIF13B as a potential therapeutic target for treating MAFLD.
基金supported by the Natural Science Foundation of Zhejiang Province,China(Grant Nos.LZ22C150002 and LR24C150001)the National Key Research and Development Program of China(Grant Nos.2021YFF1000402 and 2022YFD1401600)+1 种基金the National Natural Science Foundation of China(Grant No.32170262)the Fundamental Research Funds for the Central Universities,China(Grant No.K20240124).
文摘CRISPR-Cas endonucleases mediate prokaryotic adaptive immunity by targeting foreign nucleic acids.CRISPR/Cas13b is a class 2 type VI-B ribonuclease that targets and cleaves single-stranded RNA.It exhibits higher RNA interference activity than Cas13a and Cas13c and causes fewer collateral effects than RxCas13d in mammalian cells.However,a programmable CRISPR/Cas13b-mediated RNA interference system for endogenous transcripts in rice has not yet been established.Here,we developed a CRISPR/Cas13b-mediated system to target endogenous transcripts in rice.Our CRISPR/Cas13b system could inhibit multiple endogenous mRNAs simultaneously.In addition,this system efficiently repressed endogenous long noncoding RNAs with more than 50% inhibition in stable transgenic plants.Furthermore,we found only weak collateral effects of the CRISPR/Cas13b-mediated system at the transcriptome-wide level,and no difference in the agronomic traits of stable transgenic rice in the field.We present a programmable CRISPR/Cas13b-mediated knockdown system for rice,offering a potential biotechnological tool for functional genomics and crop improvement.
