Nanocarriers have therapeutic potential to facilitate drug delivery,including biological agents,smallmolecule drugs,and nucleic acids.However,their efficiency is limited by several factors;among which,endosomal/lysoso...Nanocarriers have therapeutic potential to facilitate drug delivery,including biological agents,smallmolecule drugs,and nucleic acids.However,their efficiency is limited by several factors;among which,endosomal/lysosomal degradation after endocytosis is the most important.This review summarizes advanced strategies for overcoming endosomal/lysosomal barriers to efficient nanodrug delivery based on the perspective of cellular uptake and intracellular transport mechanisms.These strategies include promoting endosomal/lysosomal escape,using non-endocytic methods of delivery to directly cross the cell membrane to evade endosomes/lysosomes and making a detour pathway to evade endosomes/lysosomes.On the basis of the findings of this review,we proposed several promising strategies for overcoming endosomal/lysosomal barriers through the smarter and more efficient design of nanodrug delivery systems for future clinical applications.展开更多
In a recent paper published in Nature,Xu et al.present a cryo-EM structure of a,spliced,de novo DNA methyltransferase complex,DNMT3A2-DNMT3B3,bound to a mono-nucleosome with extended linker DNA.1 Reinforced by biochem...In a recent paper published in Nature,Xu et al.present a cryo-EM structure of a,spliced,de novo DNA methyltransferase complex,DNMT3A2-DNMT3B3,bound to a mono-nucleosome with extended linker DNA.1 Reinforced by biochemical assays and genomic studies,this structure reveals the molecular mechanism underlying de novo cytosine methylation on nucleosomal substrate.Notably,the catalytically inactive DNMT3B3 occupies the nucleosome core and orients the active DNMT3A2 to target the linker DNA as its substrate,suggesting the necessity of chromosomal remodeler in the deposition of DNA methylation on nucleosomes.展开更多
Exosomes play a role as mediators of cell-to-cell communication,thus exhibiting pleiotropic activities to homeostasis regulation.Exosomal non-coding RNAs(ncRNAs),mainly microRNAs(miRNAs),long non-coding RNAs(lncRNAs),...Exosomes play a role as mediators of cell-to-cell communication,thus exhibiting pleiotropic activities to homeostasis regulation.Exosomal non-coding RNAs(ncRNAs),mainly microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs),are closely related to a variety of biological and functional aspects of human health.When the exosomal ncRNAs undergo tissuespecific changes due to diverse internal or external disorders,they can cause tissue dysfunction,aging,and diseases.In this review,we comprehensively discuss the underlying regulatory mechanisms of exosomes in human diseases.In addition,we explore the current knowledge on the roles of exosomal miRNAs,lncRNAs,and circRNAs in human health and diseases,including cancers,metabolic diseases,neurodegenerative diseases,cardiovascular diseases,autoimmune diseases,and infectious diseases,to determine their potential implication in biomarker identification and therapeutic exploration.展开更多
Exosomes are small extracellular vesicles that contain a potpourri of nucleic acids,including microRNAs(miRNAs).Importantly,exosomes and these miRNAs are actively secreted from multiple cell populations and play a cri...Exosomes are small extracellular vesicles that contain a potpourri of nucleic acids,including microRNAs(miRNAs).Importantly,exosomes and these miRNAs are actively secreted from multiple cell populations and play a critical role in intercellular communication.The exosomal miRNA profile reflects the cellular pathophysiological status and modulates multiple biological processes.Accumulating evidence indicates that exosomes and miRNAs are biomarkers for disease diagnosis and may have therapeutic targets.Research studies on exosomal miRNAs have brought new insights into understanding autoimmune diseases.This article summarizes the detection methodologies and updates the potential applications of exosomal miRNAs in autoimmune diseases.展开更多
Interaction between an essential element calcium andtwo heavy metals (Cr and Hg) was observed in micebone marrow cells in vivo.Mercuric chloride andcalcium chloride (1:1 ratio) were administered orallyto laboratory br...Interaction between an essential element calcium andtwo heavy metals (Cr and Hg) was observed in micebone marrow cells in vivo.Mercuric chloride andcalcium chloride (1:1 ratio) were administered orallyto laboratory bred Swiss albino mice,singly;onefollowed by the other,or both simultaneously.展开更多
In recent years, cytogenetic studies show that sister chromatid exchanges (SCE) during mitosis in higher organisms are the exchanges between DNA double-strands, and the frequencies of exchanges may be enhanced when ce...In recent years, cytogenetic studies show that sister chromatid exchanges (SCE) during mitosis in higher organisms are the exchanges between DNA double-strands, and the frequencies of exchanges may be enhanced when cells are treated with various exogenous agents. Furthemore, the formation of SCE is closely related to the展开更多
Late prenatal growth,early postnatal growth,and layering of the neocortical neurons(NC-Ns)play determining roles in the development of the cerebral cortex(CC).Here,we systematically explore the interactive role of neu...Late prenatal growth,early postnatal growth,and layering of the neocortical neurons(NC-Ns)play determining roles in the development of the cerebral cortex(CC).Here,we systematically explore the interactive role of neuronal surface receptors(NSRs)on cytoskeleton activation(CA)and the piconewton(pN)force generation(P-FG)and their influence on the proper development,growth,and functioning of neurons using a designed DNA nanomechanical device(DNA-NMD).展开更多
基金the Fundamental Research Funds for the National Natural Science Foundation(nos.82204322 and 82104480)the Central Public Welfare Research Institutes(grant nos.:ZZ16-ND-10-05,ZZ16-ND10-13,ZZ16-ND-10-17,ZZ16-ND-10-19,ZZ14-YQ-050,ZZ14-YQ-055,ZZ14-YQ-059,ZZ14-YQ-060,and ZZ16-YQ-046)the Young Elite Scientists Sponsorship Program by CACM(2021QNRC2B29).
文摘Nanocarriers have therapeutic potential to facilitate drug delivery,including biological agents,smallmolecule drugs,and nucleic acids.However,their efficiency is limited by several factors;among which,endosomal/lysosomal degradation after endocytosis is the most important.This review summarizes advanced strategies for overcoming endosomal/lysosomal barriers to efficient nanodrug delivery based on the perspective of cellular uptake and intracellular transport mechanisms.These strategies include promoting endosomal/lysosomal escape,using non-endocytic methods of delivery to directly cross the cell membrane to evade endosomes/lysosomes and making a detour pathway to evade endosomes/lysosomes.On the basis of the findings of this review,we proposed several promising strategies for overcoming endosomal/lysosomal barriers through the smarter and more efficient design of nanodrug delivery systems for future clinical applications.
基金supported by the China National Fund for Distinguished Young Scholars(Grant No.31725014).
文摘In a recent paper published in Nature,Xu et al.present a cryo-EM structure of a,spliced,de novo DNA methyltransferase complex,DNMT3A2-DNMT3B3,bound to a mono-nucleosome with extended linker DNA.1 Reinforced by biochemical assays and genomic studies,this structure reveals the molecular mechanism underlying de novo cytosine methylation on nucleosomal substrate.Notably,the catalytically inactive DNMT3B3 occupies the nucleosome core and orients the active DNMT3A2 to target the linker DNA as its substrate,suggesting the necessity of chromosomal remodeler in the deposition of DNA methylation on nucleosomes.
基金This work was supported by the National Natural Science Foundation of China(No.82071593,81770833,81974223,and 82101663)the Fundamental Research Funds For the Central Universities of Central South University(NO.2019zzts354).
文摘Exosomes play a role as mediators of cell-to-cell communication,thus exhibiting pleiotropic activities to homeostasis regulation.Exosomal non-coding RNAs(ncRNAs),mainly microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs),are closely related to a variety of biological and functional aspects of human health.When the exosomal ncRNAs undergo tissuespecific changes due to diverse internal or external disorders,they can cause tissue dysfunction,aging,and diseases.In this review,we comprehensively discuss the underlying regulatory mechanisms of exosomes in human diseases.In addition,we explore the current knowledge on the roles of exosomal miRNAs,lncRNAs,and circRNAs in human health and diseases,including cancers,metabolic diseases,neurodegenerative diseases,cardiovascular diseases,autoimmune diseases,and infectious diseases,to determine their potential implication in biomarker identification and therapeutic exploration.
文摘Exosomes are small extracellular vesicles that contain a potpourri of nucleic acids,including microRNAs(miRNAs).Importantly,exosomes and these miRNAs are actively secreted from multiple cell populations and play a critical role in intercellular communication.The exosomal miRNA profile reflects the cellular pathophysiological status and modulates multiple biological processes.Accumulating evidence indicates that exosomes and miRNAs are biomarkers for disease diagnosis and may have therapeutic targets.Research studies on exosomal miRNAs have brought new insights into understanding autoimmune diseases.This article summarizes the detection methodologies and updates the potential applications of exosomal miRNAs in autoimmune diseases.
文摘Interaction between an essential element calcium andtwo heavy metals (Cr and Hg) was observed in micebone marrow cells in vivo.Mercuric chloride andcalcium chloride (1:1 ratio) were administered orallyto laboratory bred Swiss albino mice,singly;onefollowed by the other,or both simultaneously.
文摘In recent years, cytogenetic studies show that sister chromatid exchanges (SCE) during mitosis in higher organisms are the exchanges between DNA double-strands, and the frequencies of exchanges may be enhanced when cells are treated with various exogenous agents. Furthemore, the formation of SCE is closely related to the
基金supported by grants from the National Key R&D Program of China(no.2017YFA0700500)the National Natural Science Foundation of China(no.21635004)the Excellent Research Program of Nanjing University(no.ZYJH004).
文摘Late prenatal growth,early postnatal growth,and layering of the neocortical neurons(NC-Ns)play determining roles in the development of the cerebral cortex(CC).Here,we systematically explore the interactive role of neuronal surface receptors(NSRs)on cytoskeleton activation(CA)and the piconewton(pN)force generation(P-FG)and their influence on the proper development,growth,and functioning of neurons using a designed DNA nanomechanical device(DNA-NMD).
