Oligodendrocyte (OL) and myelin development are crucial for network integration and are associated with higher brain functions. Accumulating evidence has demonstrated structural and functional impairment of OLs and my...Oligodendrocyte (OL) and myelin development are crucial for network integration and are associated with higher brain functions. Accumulating evidence has demonstrated structural and functional impairment of OLs and myelin in serious mental illnesses. However, whether these deficits contribute to the brain dysfunction or pathogenesis of such diseases still lacks direct evidence. In this study, we conditionally deleted Olig2 in oligodendroglial lineage cells (Olig2 cKO) and screened the behavioral changes in adult mice. We found that Olig2 ablation impaired myelin development, which further resulted in severe hypomyelination in the anterior cingulate cortex. Strikingly, Olig2 cKO mice exhibited an anxious phenotype, aberrant responses to stress, and cognitive deficits. Moreover, Olig2 cKO mice showed increased vulnerability to social avoidance under the mild stress of social isolation. Together,these results indicate that developmental deficits in OL and myelin lead to cognitive impairment and increase the risk of phenotypes reminiscent of mental illnesses.展开更多
The accurate prediction of overpressure is one of the key issues that restrict the effective development of oil and gas resources in the Yinggehai Basin. In this paper, the formation mechanism of overpressure in Yingg...The accurate prediction of overpressure is one of the key issues that restrict the effective development of oil and gas resources in the Yinggehai Basin. In this paper, the formation mechanism of overpressure in Yinggehai Basin is studied. Based on this mechanism, the quantitative prediction model and empirical parameters of overpressure are optimized in Yinggehai Basin and applied in engineering. The results show that the formation mechanism of overpressure in the Yinggehai Basin is complicated, and the causes of overpressure in different blocks of basin are different. The eastern block mainly develops loading-type overpressure, while the Ledong block is dominated by unloading high pressure. Different blocks should employ different abnormal high-pressure prediction models. The East block mainly adopts the Eaton method, and the Ledong block mainly utilizes the Bowers method. The empirical parameters of different models can be determined according to the actual drilling conditions. The practical application demonstrates that the abnormal high-pressure prediction error is within 2%, and it is able to satisfy the requirements of on-site engineering.展开更多
A light-switchable transgene system called LightOn gene expression system could regulate gene expression with a high on/off ratio under blue light,and have great potential for spatiotemporally controllable gene expres...A light-switchable transgene system called LightOn gene expression system could regulate gene expression with a high on/off ratio under blue light,and have great potential for spatiotemporally controllable gene expression.We developed a nanoparticle drug delivery system(NDDS)to achieve tumor microenvironment-responsive and targeted delivery of diphtheria toxin A(DTA)fragment-encoded plasmids to tumor sites.The expression of DTA was induced by exposure to blue light.Nanoparticles composed of polyethylenimine and vitamin E succinate linked by a disulfide bond,and PEGylated hyaluronic acid modified with RGD peptide,accumulated in tumor tissues and were actively internalized into 4 T1 cells via dual targeting to CD44 andαvβ3 receptors.The LightOn gene expression system was able to control target protein expression through regulation of the intensity or duration of blue light exposure.In vitro studies showed that lisht-induced DTA expression reduced 4 T1 cell viability and induced apoptosis.Furthermore,the LightOn gene expression system enabled spatiotemporal control of the expression of DTA in a mouse 4 T1 tumor xenogratt model,which resulted in excellent antitumor effects,reduced tumor angiogenesis,and no systemic toxicity.The combination of the LightOn gene expression system and NDDS may be an effective strategy for treatment of breast cancer.展开更多
The need and critical importance of global land cover and change information has been well recognized.Although rich collection of such information has been made available,the lack of necessary information services to ...The need and critical importance of global land cover and change information has been well recognized.Although rich collection of such information has been made available,the lack of necessary information services to support its easy access,analysis and validation makes it difficult to find,evaluate,select and reuse them through well-designed workflows.Aiming at promoting the development of the needed global land cover information services,this paper presents a conceptual framework for developing a Collaborative Global Land Cover Information Service(CoGland),followed by discussions on its implementation strategies.The framework supports connected and shared land cover and change web services around the world to address resource sharing,community service and cross-board collaboration needs.CoGland can benefit several recent international initiatives such as Future Earth,and many societal benefit areas.The paper further proposes that CoGland be developed within the framework of the Group on Earth Observations with the support of a number of key organizations such as the United Nations Expert Committee on Global Geospatial Information Management,the International Society for Photogrammetry and Remote Sensing,and International Society of Digital Earth.It is hoped that this paper can serve as a starting point for further discussions on CoGland developments.展开更多
Telomeres are the complexes composed of repetitive DNA sequences and associated proteins located at the end of chromatin.As a result of the DNA replication ending issue,telomeric DNA shortens during each cell cycle.Th...Telomeres are the complexes composed of repetitive DNA sequences and associated proteins located at the end of chromatin.As a result of the DNA replication ending issue,telomeric DNA shortens during each cell cycle.The shelterin protein complex caps telomeric ends and forms a high-order protein-DNA structure to protect telomeric DNA.The stability of telomeres is critical for cellular function and related to the progression of many human diseases.Telomeric repeat-containing RNA(TERRA)is a noncoding RNA transcribed from telomeric DNA regions.TERRA plays an essential role in regulating and maintaining the stability of telomeres.Heterogeneous nuclear ribonucleoproteins(hnRNPs)are RNA-binding proteins associated with complex and diverse biological processes.hnRNPA1 can recognize both TERRA and telomeric DNA.Previous research reported that hnRNPA1,TERRA,and POT1,a component of the shelterin complex,work coordinately and displace replication protein A from telomeric single-stranded DNA after DNA replication,promoting telomere capping to preserve genomic integrity.However,the detailed molecular mechanism has remained unclear for>20 years.Here,our study revealed the molecular structure through which the hnRNPA1 UP1 domain interacts with TERRA and identified critical residues on the interacting surface between UP1 and TERRA.Furthermore,we proved that nucleic acids significantly increase the phase-separating ability of hnRNPA1,while disrupting the UP1-TERRA interaction extraordinarily affects hnRNPA1 droplet formation both in vitro and in vivo.Taken together,these data reveal the molecular mechanism of the phase separation of hnRNPA1 and TERRA and the potential contribution of the droplets to maintaining genomic stability.展开更多
基金supported by the National Natural Science Foundation of China (31671117).
文摘Oligodendrocyte (OL) and myelin development are crucial for network integration and are associated with higher brain functions. Accumulating evidence has demonstrated structural and functional impairment of OLs and myelin in serious mental illnesses. However, whether these deficits contribute to the brain dysfunction or pathogenesis of such diseases still lacks direct evidence. In this study, we conditionally deleted Olig2 in oligodendroglial lineage cells (Olig2 cKO) and screened the behavioral changes in adult mice. We found that Olig2 ablation impaired myelin development, which further resulted in severe hypomyelination in the anterior cingulate cortex. Strikingly, Olig2 cKO mice exhibited an anxious phenotype, aberrant responses to stress, and cognitive deficits. Moreover, Olig2 cKO mice showed increased vulnerability to social avoidance under the mild stress of social isolation. Together,these results indicate that developmental deficits in OL and myelin lead to cognitive impairment and increase the risk of phenotypes reminiscent of mental illnesses.
文摘The accurate prediction of overpressure is one of the key issues that restrict the effective development of oil and gas resources in the Yinggehai Basin. In this paper, the formation mechanism of overpressure in Yinggehai Basin is studied. Based on this mechanism, the quantitative prediction model and empirical parameters of overpressure are optimized in Yinggehai Basin and applied in engineering. The results show that the formation mechanism of overpressure in the Yinggehai Basin is complicated, and the causes of overpressure in different blocks of basin are different. The eastern block mainly develops loading-type overpressure, while the Ledong block is dominated by unloading high pressure. Different blocks should employ different abnormal high-pressure prediction models. The East block mainly adopts the Eaton method, and the Ledong block mainly utilizes the Bowers method. The empirical parameters of different models can be determined according to the actual drilling conditions. The practical application demonstrates that the abnormal high-pressure prediction error is within 2%, and it is able to satisfy the requirements of on-site engineering.
基金supportedby Shanghai Municipal Natural Science Foundation(No.17ZR1406600,China)Science and Technology Commission of Shanghai Municipality(No.10DZ2220500,China)+1 种基金The Shanghai Committee of Science and Technology(Grant No.11DZ2260600,China)National Natural Science Foundation of China(Grant No.81973700)
文摘A light-switchable transgene system called LightOn gene expression system could regulate gene expression with a high on/off ratio under blue light,and have great potential for spatiotemporally controllable gene expression.We developed a nanoparticle drug delivery system(NDDS)to achieve tumor microenvironment-responsive and targeted delivery of diphtheria toxin A(DTA)fragment-encoded plasmids to tumor sites.The expression of DTA was induced by exposure to blue light.Nanoparticles composed of polyethylenimine and vitamin E succinate linked by a disulfide bond,and PEGylated hyaluronic acid modified with RGD peptide,accumulated in tumor tissues and were actively internalized into 4 T1 cells via dual targeting to CD44 andαvβ3 receptors.The LightOn gene expression system was able to control target protein expression through regulation of the intensity or duration of blue light exposure.In vitro studies showed that lisht-induced DTA expression reduced 4 T1 cell viability and induced apoptosis.Furthermore,the LightOn gene expression system enabled spatiotemporal control of the expression of DTA in a mouse 4 T1 tumor xenogratt model,which resulted in excellent antitumor effects,reduced tumor angiogenesis,and no systemic toxicity.The combination of the LightOn gene expression system and NDDS may be an effective strategy for treatment of breast cancer.
基金funded by the National Science Foundation of China[Project#41231172]and the Natural Science and Engineering Research Council of Canada.
文摘The need and critical importance of global land cover and change information has been well recognized.Although rich collection of such information has been made available,the lack of necessary information services to support its easy access,analysis and validation makes it difficult to find,evaluate,select and reuse them through well-designed workflows.Aiming at promoting the development of the needed global land cover information services,this paper presents a conceptual framework for developing a Collaborative Global Land Cover Information Service(CoGland),followed by discussions on its implementation strategies.The framework supports connected and shared land cover and change web services around the world to address resource sharing,community service and cross-board collaboration needs.CoGland can benefit several recent international initiatives such as Future Earth,and many societal benefit areas.The paper further proposes that CoGland be developed within the framework of the Group on Earth Observations with the support of a number of key organizations such as the United Nations Expert Committee on Global Geospatial Information Management,the International Society for Photogrammetry and Remote Sensing,and International Society of Digital Earth.It is hoped that this paper can serve as a starting point for further discussions on CoGland developments.
基金supported by the National Natural Science Foundation of China(32090040,32293213,and 92149302)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB37010105 and XDB39010300)+1 种基金the Fundamental Research Funds for the Central Universities(WK9100000067)the Ministry of Science and Technology of China(2019YFA0508403 and 2022YFA1303100).
文摘Telomeres are the complexes composed of repetitive DNA sequences and associated proteins located at the end of chromatin.As a result of the DNA replication ending issue,telomeric DNA shortens during each cell cycle.The shelterin protein complex caps telomeric ends and forms a high-order protein-DNA structure to protect telomeric DNA.The stability of telomeres is critical for cellular function and related to the progression of many human diseases.Telomeric repeat-containing RNA(TERRA)is a noncoding RNA transcribed from telomeric DNA regions.TERRA plays an essential role in regulating and maintaining the stability of telomeres.Heterogeneous nuclear ribonucleoproteins(hnRNPs)are RNA-binding proteins associated with complex and diverse biological processes.hnRNPA1 can recognize both TERRA and telomeric DNA.Previous research reported that hnRNPA1,TERRA,and POT1,a component of the shelterin complex,work coordinately and displace replication protein A from telomeric single-stranded DNA after DNA replication,promoting telomere capping to preserve genomic integrity.However,the detailed molecular mechanism has remained unclear for>20 years.Here,our study revealed the molecular structure through which the hnRNPA1 UP1 domain interacts with TERRA and identified critical residues on the interacting surface between UP1 and TERRA.Furthermore,we proved that nucleic acids significantly increase the phase-separating ability of hnRNPA1,while disrupting the UP1-TERRA interaction extraordinarily affects hnRNPA1 droplet formation both in vitro and in vivo.Taken together,these data reveal the molecular mechanism of the phase separation of hnRNPA1 and TERRA and the potential contribution of the droplets to maintaining genomic stability.
