As a newly discovered type of RNA, circular RNAs(circRNAs) are widespread throughout the eukaryotic genome. The expression of circRNAs is regulated by both cis-elements and trans-factors, and the expression pattern of...As a newly discovered type of RNA, circular RNAs(circRNAs) are widespread throughout the eukaryotic genome. The expression of circRNAs is regulated by both cis-elements and trans-factors, and the expression pattern of circRNAs is cell type-and diseasespecific. Similar to other types of non-coding RNAs, functions of circRNAs are also versatile. CircRNAs have been reported previously to function as microRNA(miRNA) sponges, protein sponges, coding RNAs or scaffolds for protein complexes.Recently, several circRNAs have been reported to play important roles in human malignancies, including glioma. Here, we reviewed several reports related to circRNAs and glioma, as well as the potential diagnostic and therapeutic applications of circRNAs in brain cancer. In general, some circRNAs, such as circSMARCA5 and circCFH, are found to be expressed in a gliomaspecific pattern, these circRNAs may be used as tumor biomarkers. In addition, some circRNAs have been found to play oncogenic roles in glioma(e.g., circNFIX and circNT5E), whereas others have been reported to function as tumor suppressors(e.g.,circFBXW7 and circSHPRH). Furthermore, circRNA is a good tool for protein expression because of its higher stability compared to linear RNAs. Thus, circRNAs may also be an ideal choice for gene/protein delivery in future brain cancer therapies. There are some challenges in circRNA research in glioma and other diseases. Research related to circRNAs in glioma is comparatively new and many mysteries remain to be solved.展开更多
In the published article1,we omitted the Acknowledgements section on page 21,and it should be as below.We apologize for the errors and for any confusion it may have caused.
Significant progress has been made in circular RNA(circRNA)research in recent years.Increasing evidence suggests that circRNAs play important roles in many cellular processes,and their dysregulation is implicated in t...Significant progress has been made in circular RNA(circRNA)research in recent years.Increasing evidence suggests that circRNAs play important roles in many cellular processes,and their dysregulation is implicated in the pathogenesis of various diseases.CircRNAs are highly stable and usually expressed in a tissue-or cell type-specific manner.Therefore,they are currently being explored as potential therapeutic targets.Gain-of-function and loss-of-function approaches are typically performed using circRNA expression plasmids and RNA interference-based strategies,respectively.These strategies have limitations that can be mitigated using nanoparticle and exosome delivery systems.Furthermore,recent developments show that the cre-lox system can be used to knockdown circRNAs in a cell-specific manner.While still in the early stages of development,the CRISPR/Cas13 system has shown promise in knocking down circRNAs with high specificity and efficiency.In this review,we describe circRNA properties and functions and highlight their significance in disease.We summarize strategies that can be used to overexpress or knockdown circRNAs as a therapeutic approach.Lastly,we discuss major challenges and propose future directions for the development of circRNA-based therapeutics.展开更多
Mitochondrial DNA (mtDNA) mutations have been impli- cated in a broad range of disorders which severely affect human health (Wallace, 1999). Some drugs have been developed to slow down pathological changes of mito...Mitochondrial DNA (mtDNA) mutations have been impli- cated in a broad range of disorders which severely affect human health (Wallace, 1999). Some drugs have been developed to slow down pathological changes of mitochon- drial disorders. However, there is no effective treatment for patients with mtDNA mutations, mtDNA is less protected and has fewer repair mechanisms than nuclear DNA (nDNA). Such a reality results in a much higher mutation rate in mtDNA than that in nDNA. The mixture of mutated mtDNA versus wild-type mtDNA is known as hetero- plasmy. Mitochondrial threshold effect refers to the fact that mtDNA mutation must accumulate to high proportions (60%-90%) before respiratory activity is affected (Schon et al., 2012). It is feasible to selectively reduce the levels of mu- tated mtDNA while sparing wild-type mtDNA to skew this ratio back to a healthier range. Here, we describe the link between mtDNA mutation and mitochondrial diseases, and we summarize several newly developed approaches with regard to the reduction or elimination of mtDNA mutation in mammals. These methods include nuclear gene modula- tion, molecular approaches targeting mutated mtDNA, mtDNA replacement, and induced pluripotent stem cell (iPSC) modeling. These various methods have their own advantages and limitations.展开更多
Mitochondria,double-membrane organelles,are known to participate in a variety of metabolic and signal transduction pathways.The intermembrane space(IMS)of mitochondria is proposed to subject to multiple damages emanat...Mitochondria,double-membrane organelles,are known to participate in a variety of metabolic and signal transduction pathways.The intermembrane space(IMS)of mitochondria is proposed to subject to multiple damages emanating from the respiratory chain.The optic atrophy 1(OPA1),an important protein for mitochondrial fusion,is cleaved into soluble short-form(S-OPA1)under stresses.Here we report that S-OPA1 could function as a molecular chaperone in IMS.We purified the S-OPA1(amino acid sequence after OPA1 isoform 5 S1 site)protein and showed it protected substrate proteins from thermally and chemically induced aggregation and strengthened the thermotolerance of Escherichia coli(E.coli).We also showed that S-OPA1 conferred thermotolerance on IMS proteins,e.g.,neurolysin.The chaperone activity of S-OPA1 may be required for maintaining IMS homeostasis in mitochondria.展开更多
Surface modification is a direct and effective way to enhance the efficiency of heat exchangers. Surface modification by forming a microporous coated layer can greatly enhance the boiling heat transfer and thus achiev...Surface modification is a direct and effective way to enhance the efficiency of heat exchangers. Surface modification by forming a microporous coated layer can greatly enhance the boiling heat transfer and thus achieve a high performance. In this paper, we systematically investigate the boiling behavior on a plain surface with/ without sintered microporous coatings of copper powder. The results demonstrated that the sintered surface has a better performance in nucleate boiling due to the increased nucleation sites. The superheat degree is lower and the bubble departure diameter is larger for the sintered surface than for the plain surface, so the heat can be carried away more efficiently on the sintered surface. In addition, the heat transfer capacity on the sintered surface depends on both the powder size and the coating thickness for a high flux tube. The optimum heat transfer capacity can be obtained when the thickness of the microporous coating layer is 3-5 times of the sintered powder diameter. As a result, the heat transfer coefficient tube can be up to 3 times higher for the tube with a sintered surface than that with a plain surface, showing a pronounced enhancement in heat transfer and a high potential in chemical engineering industry application.展开更多
Approximations based on random Fourier features have recently emerged as an efficient and elegant method for designing large-scale machine learning tasks.Unlike approaches using the Nystr?m method,which randomly sampl...Approximations based on random Fourier features have recently emerged as an efficient and elegant method for designing large-scale machine learning tasks.Unlike approaches using the Nystr?m method,which randomly samples the training examples,we make use of random Fourier features,whose basis functions(i.e.,cosine and sine)are sampled from a distribution independent from the training sample set,to cluster preference data which appears extensively in recommender systems.Firstly,we propose a two-stage preference clustering framework.In this framework,we make use of random Fourier features to map the preference matrix into the feature matrix,soon afterwards,utilize the traditional k-means approach to cluster preference data in the transformed feature space.Compared with traditional preference clustering,our method solves the problem of insufficient memory and greatly improves the efficiency of the operation.Experiments on movie data sets containing 100000 ratings,show that the proposed method is more effective in clustering accuracy than the Nystr?m and k-means,while also achieving better performance than these clustering approaches.展开更多
文摘As a newly discovered type of RNA, circular RNAs(circRNAs) are widespread throughout the eukaryotic genome. The expression of circRNAs is regulated by both cis-elements and trans-factors, and the expression pattern of circRNAs is cell type-and diseasespecific. Similar to other types of non-coding RNAs, functions of circRNAs are also versatile. CircRNAs have been reported previously to function as microRNA(miRNA) sponges, protein sponges, coding RNAs or scaffolds for protein complexes.Recently, several circRNAs have been reported to play important roles in human malignancies, including glioma. Here, we reviewed several reports related to circRNAs and glioma, as well as the potential diagnostic and therapeutic applications of circRNAs in brain cancer. In general, some circRNAs, such as circSMARCA5 and circCFH, are found to be expressed in a gliomaspecific pattern, these circRNAs may be used as tumor biomarkers. In addition, some circRNAs have been found to play oncogenic roles in glioma(e.g., circNFIX and circNT5E), whereas others have been reported to function as tumor suppressors(e.g.,circFBXW7 and circSHPRH). Furthermore, circRNA is a good tool for protein expression because of its higher stability compared to linear RNAs. Thus, circRNAs may also be an ideal choice for gene/protein delivery in future brain cancer therapies. There are some challenges in circRNA research in glioma and other diseases. Research related to circRNAs in glioma is comparatively new and many mysteries remain to be solved.
文摘In the published article1,we omitted the Acknowledgements section on page 21,and it should be as below.We apologize for the errors and for any confusion it may have caused.
基金supported by grants from Canadian Institutes of Health Research to BBY(PJT-153105,PJT-155962,and PJT-166107).
文摘Significant progress has been made in circular RNA(circRNA)research in recent years.Increasing evidence suggests that circRNAs play important roles in many cellular processes,and their dysregulation is implicated in the pathogenesis of various diseases.CircRNAs are highly stable and usually expressed in a tissue-or cell type-specific manner.Therefore,they are currently being explored as potential therapeutic targets.Gain-of-function and loss-of-function approaches are typically performed using circRNA expression plasmids and RNA interference-based strategies,respectively.These strategies have limitations that can be mitigated using nanoparticle and exosome delivery systems.Furthermore,recent developments show that the cre-lox system can be used to knockdown circRNAs in a cell-specific manner.While still in the early stages of development,the CRISPR/Cas13 system has shown promise in knocking down circRNAs with high specificity and efficiency.In this review,we describe circRNA properties and functions and highlight their significance in disease.We summarize strategies that can be used to overexpress or knockdown circRNAs as a therapeutic approach.Lastly,we discuss major challenges and propose future directions for the development of circRNA-based therapeutics.
基金supported by the National Basic Research Program of China (2013CB967403, 2012CB721105)the ‘‘Strategic Priority Research Program’’ of the Chinese Academy of Sciences (XDA01020108)+7 种基金the National High-tech R&D Program (2012AA02A708)the National Natural Science Foundation projects of China (31271527, 81570520)Guangzhou Science and Technology Program (2014Y2-00161)Guangdong Natural Science Foundation for Distinguished Young Scientists (S20120011368)Guangdong Province Science and Technology Innovation Young Talents Program (2014TQ01R559)Guangdong Province Science and Technology Program (2015A020212031)the Ph D Start-up Fund of Natural Science Foundation of Guangdong Province (2014A030310071)the ‘‘One Hundred Talents’’ Project for Prof. Xingguo Liu from the Chinese Academy of Sciences
文摘Mitochondrial DNA (mtDNA) mutations have been impli- cated in a broad range of disorders which severely affect human health (Wallace, 1999). Some drugs have been developed to slow down pathological changes of mitochon- drial disorders. However, there is no effective treatment for patients with mtDNA mutations, mtDNA is less protected and has fewer repair mechanisms than nuclear DNA (nDNA). Such a reality results in a much higher mutation rate in mtDNA than that in nDNA. The mixture of mutated mtDNA versus wild-type mtDNA is known as hetero- plasmy. Mitochondrial threshold effect refers to the fact that mtDNA mutation must accumulate to high proportions (60%-90%) before respiratory activity is affected (Schon et al., 2012). It is feasible to selectively reduce the levels of mu- tated mtDNA while sparing wild-type mtDNA to skew this ratio back to a healthier range. Here, we describe the link between mtDNA mutation and mitochondrial diseases, and we summarize several newly developed approaches with regard to the reduction or elimination of mtDNA mutation in mammals. These methods include nuclear gene modula- tion, molecular approaches targeting mutated mtDNA, mtDNA replacement, and induced pluripotent stem cell (iPSC) modeling. These various methods have their own advantages and limitations.
基金the National Key Re-search and Development Program of China(2017YFA0106300)the Stra-tegic Priority Research Program of the Chinese Academy of Sciences(XDA16030505)+6 种基金the National Key Research and Development Program of China(2017YFA0102900,2019YFA09004500,2017YFC1001602,2016YFA0100300,2018YFA0107100)the National Natural Science Foundation of China(32025010,31801168,31900614,31970709,81901275,32070729)the Key Research Program of Frontier Sciences,CAS(QYZDB-SSW-SMC001)International Cooperation Program,CAS(154144KYSB20200006)Guangdong Province Science and Technol-ogy Program(2020B1212060052,2018A030313825,2018GZR110103002,2020A1515011200,2020A1515010919,2020A1515011410,2021A1515012513)Guangzhou Science and Technology Program(201807010067,202002030277,202102021250,202102020827,202102080066)CAS Youth Innovation Promotion Association.
文摘Mitochondria,double-membrane organelles,are known to participate in a variety of metabolic and signal transduction pathways.The intermembrane space(IMS)of mitochondria is proposed to subject to multiple damages emanating from the respiratory chain.The optic atrophy 1(OPA1),an important protein for mitochondrial fusion,is cleaved into soluble short-form(S-OPA1)under stresses.Here we report that S-OPA1 could function as a molecular chaperone in IMS.We purified the S-OPA1(amino acid sequence after OPA1 isoform 5 S1 site)protein and showed it protected substrate proteins from thermally and chemically induced aggregation and strengthened the thermotolerance of Escherichia coli(E.coli).We also showed that S-OPA1 conferred thermotolerance on IMS proteins,e.g.,neurolysin.The chaperone activity of S-OPA1 may be required for maintaining IMS homeostasis in mitochondria.
文摘Surface modification is a direct and effective way to enhance the efficiency of heat exchangers. Surface modification by forming a microporous coated layer can greatly enhance the boiling heat transfer and thus achieve a high performance. In this paper, we systematically investigate the boiling behavior on a plain surface with/ without sintered microporous coatings of copper powder. The results demonstrated that the sintered surface has a better performance in nucleate boiling due to the increased nucleation sites. The superheat degree is lower and the bubble departure diameter is larger for the sintered surface than for the plain surface, so the heat can be carried away more efficiently on the sintered surface. In addition, the heat transfer capacity on the sintered surface depends on both the powder size and the coating thickness for a high flux tube. The optimum heat transfer capacity can be obtained when the thickness of the microporous coating layer is 3-5 times of the sintered powder diameter. As a result, the heat transfer coefficient tube can be up to 3 times higher for the tube with a sintered surface than that with a plain surface, showing a pronounced enhancement in heat transfer and a high potential in chemical engineering industry application.
基金supported by the National Natural Science Foundation of China(Nos.61872260 and 61592419)the Natural Science Foundation of Shanxi Province(No.201703D421013).
文摘Approximations based on random Fourier features have recently emerged as an efficient and elegant method for designing large-scale machine learning tasks.Unlike approaches using the Nystr?m method,which randomly samples the training examples,we make use of random Fourier features,whose basis functions(i.e.,cosine and sine)are sampled from a distribution independent from the training sample set,to cluster preference data which appears extensively in recommender systems.Firstly,we propose a two-stage preference clustering framework.In this framework,we make use of random Fourier features to map the preference matrix into the feature matrix,soon afterwards,utilize the traditional k-means approach to cluster preference data in the transformed feature space.Compared with traditional preference clustering,our method solves the problem of insufficient memory and greatly improves the efficiency of the operation.Experiments on movie data sets containing 100000 ratings,show that the proposed method is more effective in clustering accuracy than the Nystr?m and k-means,while also achieving better performance than these clustering approaches.