Considering the increased anthropogenic impacts,species with a limited range and low detectability often lack fundamental information and conservation actions,placing them at a high risk of endangerment.The Chinting a...Considering the increased anthropogenic impacts,species with a limited range and low detectability often lack fundamental information and conservation actions,placing them at a high risk of endangerment.The Chinting alpine toad Scutiger chintingensis is a rare mountain amphibian endemic to the eastern margin of the Qinghai-Xizang Plateau in China.Within its whole distribution range,only three known populations(Wolong,Emei,and Wawu)exist and no recent population status report has been documented for this species over the past two decades.From 2020 to 2023,we investigated the species distribution,and assessed the risk factors for the main populations.We recorded this species in all distribution areas,and updated a new distribution site with a lower elevation limit.The relative population density was 0.024±0.012 ind./m^(2)on Mount Emei,whereas only 0.008±0.017 ind./m^(2)on Mount Wawu.No significant difference was observed in the number of individuals between the two populations;however,the relative population density was significantly different.Sewage and waste discharge resulting from the construction of scenic areas,as well as disturbances from tourism,were the primary anthropogenic factors that influenced the survival of this species.Our results provide the updated information on the distribution and population status of the Chinting alpine toad,and suggest that unrecorded populations,as well as a wider elevation range,may exist for this species.Our findings emphasise the importance of timely updates of species distribution and population information and offer a basis for the future conservation of endangered amphibians.展开更多
The Yellow River Delta Wetland is one of the youngest wetlands, and also the most complete, extensive wetlands in China. The wetland in this delta is ecologically important due to their hydrologic attributes and their...The Yellow River Delta Wetland is one of the youngest wetlands, and also the most complete, extensive wetlands in China. The wetland in this delta is ecologically important due to their hydrologic attributes and their roles as ecotones between terrestrial and aquatic ecosystems. In the study, the spatial and temporal variation characteristics of CH4 and CO2 emission flux under five kinds of land use types in the wetland were investigated. The results indicated that the greenhouse gas emission flux, especially the CO2 and CH4, showed distinctly spatial and temporal variation under different land use types in the wetland. In the spring, the emission flux of CO2 was higher than that of CO2 in the autumn, and appeared negative in HW3 and HW4 in the autumn. CH4 emission flux of HW4 and HW5 was negative in the spring and autumn, which indicated that the CH4 emission process was net absorption. Among the five kinds of land use types, the CO2 emission flux of HW4 discharged the largest emission flux reaching 29.3 mg.m-2.h-1, but the CH4 emission flux of HW2 discharged the largest emission flux reaching 0.15 mg.m-2.h-1. From the estuary to the inland, the emission flux of CO2 was decreased at first and then appeared increasing trend, but the emission flux of CH4 was contrary to CO2.展开更多
Trichloroethylene (TCE) is a chlorinated liquid that is commonly used for metal degreasing, household and industrial dry cleaning, and in paints and glues. Tetrachloroethylene, also known as perchloroethylene (PCE), i...Trichloroethylene (TCE) is a chlorinated liquid that is commonly used for metal degreasing, household and industrial dry cleaning, and in paints and glues. Tetrachloroethylene, also known as perchloroethylene (PCE), is an excellent solvent for organic materials. PCE is volatile, highly stable, non-flammable and widely used in dry cleaning. A new method has been developed for measuring TCE and PCE in ambient air in real-time. Based upon the chemical fingerprinting and concentration levels, the method was able to isolate the source of the emissions to the responsible facility. Real-time monitoring was accomplished by utilizing a low pressure chemical ionization source (LPCI) interfaced to a tandem mass spectrometer (TAGA). Monitoring the response of specific parent/daughter ion pairs, the TAGA was used to measure concentrations of TCE and PCE. By optimizing various TAGA parameters, detection limits (DL) as low as 0.5 μg/m3 was achieved for TCE and PCE. Unlike methods using cartridge sampling and GC/MS analysis, this new method provides a real time measurement for a wide range of TCE and PCE concentrations. This unique method was applied in 2000 and 2002 to measure TCE emitted from a manufacturer of stainless steel tubing in Eastern Ontario. The maximum half-hour average concentration of TCE measured downwind of the facility was 1300 μg/m3 and the maximum instantaneous level was measured at 115,000 μg/m3. The information collected by the TAGA unit was used by the Standard Development Branch of Ontario Ministry of the Environment to adopt the half-hour Point of Impingement (POI) standard of TCE to be 36 μg/m3 in 2010. This method successfully identified and simultaneously measured TCE and PCE during a 2011 air monitoring survey of a hazardous waste disposal and treatment facility in Southern Ontario.展开更多
Capacity building is essential for developing a robust disease control and prevention system(1).Recognizing this,on December 25,2023,the General Office of China’s State Council issued the“Guidelines for Promoting th...Capacity building is essential for developing a robust disease control and prevention system(1).Recognizing this,on December 25,2023,the General Office of China’s State Council issued the“Guidelines for Promoting the High-Quality Development of Disease Control and Prevention”(hereinafter referred to as the“Guidelines”)(2),emphasizing the need to enhance six key professional capabilities within the disease control and prevention system.These Guidelines provide a foundational framework for the future growth and enhancement of centers for disease control and prevention(CDCs).展开更多
Organizational security in public health encompasses structural and supportive measures designed to ensure public health security and effectively prevent and control disease outbreaks.These measures include organizati...Organizational security in public health encompasses structural and supportive measures designed to ensure public health security and effectively prevent and control disease outbreaks.These measures include organizational leadership,investment mechanisms,information technology support,scientific research,and international exchange and cooperation.Disease prevention and control is often described as an“invisible war”,emphasizing the need for preparedness and proactive measures(1).As the adage states,“Before soldiers and horses move,food and grass go first,”highlighting the critical role of a robust organizational security foundation for successful disease prevention and control efforts.This foundation is essential for promoting high-quality development within the field.During its 14th Five-Year Plan period,the Chinese government has implemented policies to bolster organizational security.Furthering this commitment,on December 25,2023,the State Council issued the“Guiding Opinions on Promoting the High-Quality Development of Disease Prevention and Control.”展开更多
China’s Disease Control and Prevention(DCP)system has played a critical role in protecting population health and ensuring socioeconomic stability(1).Over the past two decades,China has made significant advancements i...China’s Disease Control and Prevention(DCP)system has played a critical role in protecting population health and ensuring socioeconomic stability(1).Over the past two decades,China has made significant advancements in disease surveillance,response,and control,particularly following the 2003 severe acute respiratory syndrome(SARS)outbreak and the 2009 national healthcare reforms(2–3).These initiatives have substantially strengthened the national DCP system and led to improved public health outcomes,including the effective control of outbreaks such as avian influenza and coronavirus disease 2019(COVID-19).Consequently,the incidence of major epidemics has declined markedly(1).展开更多
Talent is essential for development,and career development strategies should prioritize talent cultivation(1–2).China’s CDC workforce comprises a diverse,multidisciplinary team of disease prevention and control expe...Talent is essential for development,and career development strategies should prioritize talent cultivation(1–2).China’s CDC workforce comprises a diverse,multidisciplinary team of disease prevention and control experts.This workforce includes personnel from various CDC agencies,public medical institutions,township health centers,and community health service centers.Strengthening the development of this pool of talent is crucial for enhancing the quality of disease prevention and control systems and forms the foundation of a robust public health infrastructure(3).On December 25,2023,the State Council released the Guideline on Promoting the High-Quality Development of Disease Prevention and Control,outlining a comprehensive strategy for strengthening the CDC’s talent base.This paper analyzes this policy to clarify the historical context,principal actions,and future trajectory of workforce development within China’s CDC.展开更多
The importance of NAC(named as NAM,ATAF1,2,and CUC2)proteins in plant development,transcription regulation and regulatory pathways involving proteinprotein interactions has been increasingly recognized.We report here ...The importance of NAC(named as NAM,ATAF1,2,and CUC2)proteins in plant development,transcription regulation and regulatory pathways involving proteinprotein interactions has been increasingly recognized.We report here the high resolution crystal structure of SNAC1(stress-responsive NAC)NAC domain at 2.5Å.Although the structure of the SNAC1 NAC domain shares a structural similarity with the reported structure of the ANAC NAC1 domain,some key features,especially relating to two loop regions which potentially take the responsibility for DNA-binding,distinguish the SNAC1 NAC domain from other reported NAC structures.Moreover,the dimerization of the SNAC1 NAC domain is demonstrated by both soluble and crystalline conditions,suggesting this dimeric state should be conserved in this type of NAC family.Additionally,we discuss the possible NAC-DNA binding model according to the structure and reported biological evidences.展开更多
Mitochondrial diseases are maternally inherited hetero- geneous disorders that are primarily caused by mitochondrial DNA (mtDNA) mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy,...Mitochondrial diseases are maternally inherited hetero- geneous disorders that are primarily caused by mitochondrial DNA (mtDNA) mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruc- tion of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells (MiPSCs) that harbored a high proportion of m.3243A〉G mtDNA mutations and caused mitochondrial encephalomyopathy and stroke-like episodes (MELAS). We engineered mitochondrial-targeted transcription activator-like effector nucleases (mitoTALENs) and successfully eliminated the m.3243A〉G mutation in MiPSCs. Off-target mutagenesis was not detected in the targeted MiPSC clones. Utilizing a dual fluorescence iPSC reporter cell line expressing a 3243G mutant mtDNA sequence in the nuclear genome, mitoTALENs displayed a significantly limited ability to target the nuclear genome compared with nuclear-localized TALENs. Moreover, genetically rescued MiPSCs displayed normal mitochondrial respiration and energy production. Moreover, neuronal progenitor cells differentiated from the rescued MiPSCs also demonstrated normal metabolic profiles. Further- more, we successfully achieved reduction in the human m.3243A〉G mtDNA mutation in porcine oocytes via injection of mitoTALEN mRNA. Our study shows the great potential for using mitoTALENs for specific targeting of mutant mtDNA both in iPSCs and mammalian oocytes, which not only provides a new avenue for studying mitochondrial biology and disease but also suggests a potential therapeutic approach for the treatment of mitochondrial disease, as well as the prevention of germline transmission of mutant mtDNA.展开更多
We have recently discovered a unique CD34loCD133lo cell population in the human fetal liver (FL) that gives rise to cells in the hepatic lineage. In this study, we further characterized the biological functions of F...We have recently discovered a unique CD34loCD133lo cell population in the human fetal liver (FL) that gives rise to cells in the hepatic lineage. In this study, we further characterized the biological functions of FL CD341~CD133~~ cells. Our findings show that these CD341~CD133I~ cells express markers of both endodermal and mesodermal lineages and have the capability to differentiate into hepatocyte and mesenchymal lineage cells by ex vivo differentiation assays. Furthermore, we show that CD34~~CD 133I~ cel Is express growth factors that are important for human hematopoietic stem cell (HSC) expansion: stem cell factor (SCF), insulin-like growth factor 2 (IGF2), C-X-C motif chemokine 12 (CXCL12), and factors in the angiopoietin-like protein family. Co-culture of autologous FL HSCs and allogenic HSCs derived from cord blood with CD34loCD133lo cells supports and expands both types of HSCs.These findings are not only essential for extending our understanding of the HSC niche during the development of embryonic and fetal hematopoiesis but will also potentially benefit adult stem cell transplantations in clinics because expanded HSCs demonstrate the same capacity as primary cells to reconstitute the human immune system and mediate long-term hematopoiesis in vivo. Together,CD34loCD133lo cells not only serve as stem/progenitor cells for liver development but are also an essential component of the HSC niche in the human FL.展开更多
Humanized mice are immunodeficient animals engrafted with human hematopoietic stem cells that give rise to various lineages of human blood cells throughout the life of the mouse. This article reviews recent advances i...Humanized mice are immunodeficient animals engrafted with human hematopoietic stem cells that give rise to various lineages of human blood cells throughout the life of the mouse. This article reviews recent advances in the generation of humanized mice, focusing on practical considerations. We discuss features of different immunodeficient recipient mouse strains, sources of human hematopoietic stem cells, advances in expansion and genetic modification of hematopoietic stem cells, and techniques to modulate the cytokine environment of recipient mice, in order to enhance reconstitution of specific human blood lineage cells. We highlight the opportunities created by new technologies and discuss practical considerations on how to make best use of the widening array of basic models for specific research applications.展开更多
Background:MicroRNAs(miRNAs)are a significant type of non-coding RNAs,which usually were encoded by endogenous genes with about?22 nt nucleotides.Accumulating biological experiments have shown that miRNAs have close a...Background:MicroRNAs(miRNAs)are a significant type of non-coding RNAs,which usually were encoded by endogenous genes with about?22 nt nucleotides.Accumulating biological experiments have shown that miRNAs have close associations with various human diseases.Although traditional experimental methods achieve great successes in miRNA-disease interaction identification,these methods also have some limitations.Therefore,it is necessary to develop computational method to predict miRNA-disease interactions.Methods:Here,we propose a computational framework(MDVSI)to predict interactions between miRNAs and diseases by integrating miRNA topological similarity and functional similarity.Firstly,the CosRA index is utilized to measure miRNA similarity based on network topological feature.Then,in order to enhance the reliability of miRNA similarity,the functional similarity and CosRA similarity are integrated based on linear weight method.Further,the potential miRNA-disease associations are predicted by using recommendation method.In addition,in order to overcome limitation of recommendation method,for new disease,a new strategy is proposed to predict potential interactions between miRNAs and new disease based on disease functional similarity.Results:To evaluate the performance of different methods,we conduct ten-fold cross validation and de novo test in experiment and compare MDVSI with two the-state-of-art methods.The experimental result shows that MDVSI achieves an AUC of 0.91,which is at least 0.012 higher than other compared methods.Conclusions:In summary,we propose a computational framework(MDSVI)for miRNA-disease interaction prediction.The experiment results demonstrate that it outperforms other the-state-of^the-art methods.Case study shows that it can effectively identify potential miRNA-disease interactions.展开更多
Transplantation of hematopoietic stem/progenitor cells(HSPC)has become one of the most effective treatments for several hematological malignancies,cancers and genetic immune disorders.However,the lack of histocompatib...Transplantation of hematopoietic stem/progenitor cells(HSPC)has become one of the most effective treatments for several hematological malignancies,cancers and genetic immune disorders.However,the lack of histocompatible donor sources and the number of stem cells suitable for engraftment are major constraints in the clinic,and these constraints greatly hamper the use of stem cell therapy.In humans,fetal liver and bone marrow are the two major locations of hematopoiesis before and after birth,respectively.Thus,understanding the specialized stem cell microenvironment supporting the self-renewal and expansion of HSPC in fetal liver and bone marrow is not only essential for extending the current knowledge of stem cell biology but is also beneficial to adult regenerative medicine in the clinic.展开更多
The interaction between gene loci,namely epistasis,is a widespread biological genetic phenomenon.In genome-wide association studies(GWAS),epistasis detection of complex diseases is a major challenge.Although many appr...The interaction between gene loci,namely epistasis,is a widespread biological genetic phenomenon.In genome-wide association studies(GWAS),epistasis detection of complex diseases is a major challenge.Although many approaches using statistics,machine learning,and information entropy were proposed for epistasis detection,the privacy preserving for single nucleotide polymorphism(SNP)data has been largely ignored.Thus,this paper proposes a novel two-stage approach.A fusion strategy assists in combining and sorting the SNPs importance scores obtained by the relief and mutual information,thereby obtaining a candidate set of SNPs.This avoids missing some SNPs with strong interaction.Furthermore,differentially private decision tree is applied to search for SNPs.This achieves the efficient epistasis detection of complex diseases on the basis of privacy preserving compared with heuristic methods.The recognition rate on simulation data set is more than 90%.Also,several susceptible loci including rs380390 and rs1329428 are found in the real data set for Age-related Macular Degeneration(AMD).This demonstrates that our method is promising in epistasis detection.展开更多
The interaction between gene loci,namely epistasis,is a widespread biological genetic phenomenon.In genome-wide association studies(GWAS),epistasis detection of complex diseases is a major challenge.Although many appr...The interaction between gene loci,namely epistasis,is a widespread biological genetic phenomenon.In genome-wide association studies(GWAS),epistasis detection of complex diseases is a major challenge.Although many approaches using statistics,machine learning,and information entropy were proposed for epistasis detection,the privacy preserving for single nucleotide polymorphism(SNP)data has been largely ignored.Thus,this paper proposes a novel two-stage approach.A fusion strategy assists in combining and sorting the SNPs importance scores obtained by the relief and mutual information,thereby obtaining a candidate set of SNPs.This avoids missing some SNPs with strong interaction.Furthermore,differentially private decision tree is applied to search for SNPs.This achieves the efficient epistasis detection of complex diseases on the basis of privacy preserving compared with heuristic methods.The recognition rate on simulation data set is more than 90%.Also,several susceptible loci including rs380390 and rs1329428 are found in the real data set for Age-related Macular Degeneration(AMD).This demonstrates that our method is promising in epistasis detection.展开更多
基金supported by the National Natural Science Foundation of China(32271737,32071544)the Interdisciplinary Innovation Team of the Chinese Academy of Sciences(CAS)“Light of West China”Program(xbzg-zdsys-202207)+1 种基金the Shenzhen Zhilan Foundation(2021070451A)Nature Science Foundation of Sichuan Province(2022NSFSC0125).
文摘Considering the increased anthropogenic impacts,species with a limited range and low detectability often lack fundamental information and conservation actions,placing them at a high risk of endangerment.The Chinting alpine toad Scutiger chintingensis is a rare mountain amphibian endemic to the eastern margin of the Qinghai-Xizang Plateau in China.Within its whole distribution range,only three known populations(Wolong,Emei,and Wawu)exist and no recent population status report has been documented for this species over the past two decades.From 2020 to 2023,we investigated the species distribution,and assessed the risk factors for the main populations.We recorded this species in all distribution areas,and updated a new distribution site with a lower elevation limit.The relative population density was 0.024±0.012 ind./m^(2)on Mount Emei,whereas only 0.008±0.017 ind./m^(2)on Mount Wawu.No significant difference was observed in the number of individuals between the two populations;however,the relative population density was significantly different.Sewage and waste discharge resulting from the construction of scenic areas,as well as disturbances from tourism,were the primary anthropogenic factors that influenced the survival of this species.Our results provide the updated information on the distribution and population status of the Chinting alpine toad,and suggest that unrecorded populations,as well as a wider elevation range,may exist for this species.Our findings emphasise the importance of timely updates of species distribution and population information and offer a basis for the future conservation of endangered amphibians.
文摘The Yellow River Delta Wetland is one of the youngest wetlands, and also the most complete, extensive wetlands in China. The wetland in this delta is ecologically important due to their hydrologic attributes and their roles as ecotones between terrestrial and aquatic ecosystems. In the study, the spatial and temporal variation characteristics of CH4 and CO2 emission flux under five kinds of land use types in the wetland were investigated. The results indicated that the greenhouse gas emission flux, especially the CO2 and CH4, showed distinctly spatial and temporal variation under different land use types in the wetland. In the spring, the emission flux of CO2 was higher than that of CO2 in the autumn, and appeared negative in HW3 and HW4 in the autumn. CH4 emission flux of HW4 and HW5 was negative in the spring and autumn, which indicated that the CH4 emission process was net absorption. Among the five kinds of land use types, the CO2 emission flux of HW4 discharged the largest emission flux reaching 29.3 mg.m-2.h-1, but the CH4 emission flux of HW2 discharged the largest emission flux reaching 0.15 mg.m-2.h-1. From the estuary to the inland, the emission flux of CO2 was decreased at first and then appeared increasing trend, but the emission flux of CH4 was contrary to CO2.
文摘Trichloroethylene (TCE) is a chlorinated liquid that is commonly used for metal degreasing, household and industrial dry cleaning, and in paints and glues. Tetrachloroethylene, also known as perchloroethylene (PCE), is an excellent solvent for organic materials. PCE is volatile, highly stable, non-flammable and widely used in dry cleaning. A new method has been developed for measuring TCE and PCE in ambient air in real-time. Based upon the chemical fingerprinting and concentration levels, the method was able to isolate the source of the emissions to the responsible facility. Real-time monitoring was accomplished by utilizing a low pressure chemical ionization source (LPCI) interfaced to a tandem mass spectrometer (TAGA). Monitoring the response of specific parent/daughter ion pairs, the TAGA was used to measure concentrations of TCE and PCE. By optimizing various TAGA parameters, detection limits (DL) as low as 0.5 μg/m3 was achieved for TCE and PCE. Unlike methods using cartridge sampling and GC/MS analysis, this new method provides a real time measurement for a wide range of TCE and PCE concentrations. This unique method was applied in 2000 and 2002 to measure TCE emitted from a manufacturer of stainless steel tubing in Eastern Ontario. The maximum half-hour average concentration of TCE measured downwind of the facility was 1300 μg/m3 and the maximum instantaneous level was measured at 115,000 μg/m3. The information collected by the TAGA unit was used by the Standard Development Branch of Ontario Ministry of the Environment to adopt the half-hour Point of Impingement (POI) standard of TCE to be 36 μg/m3 in 2010. This method successfully identified and simultaneously measured TCE and PCE during a 2011 air monitoring survey of a hazardous waste disposal and treatment facility in Southern Ontario.
文摘Capacity building is essential for developing a robust disease control and prevention system(1).Recognizing this,on December 25,2023,the General Office of China’s State Council issued the“Guidelines for Promoting the High-Quality Development of Disease Control and Prevention”(hereinafter referred to as the“Guidelines”)(2),emphasizing the need to enhance six key professional capabilities within the disease control and prevention system.These Guidelines provide a foundational framework for the future growth and enhancement of centers for disease control and prevention(CDCs).
文摘Organizational security in public health encompasses structural and supportive measures designed to ensure public health security and effectively prevent and control disease outbreaks.These measures include organizational leadership,investment mechanisms,information technology support,scientific research,and international exchange and cooperation.Disease prevention and control is often described as an“invisible war”,emphasizing the need for preparedness and proactive measures(1).As the adage states,“Before soldiers and horses move,food and grass go first,”highlighting the critical role of a robust organizational security foundation for successful disease prevention and control efforts.This foundation is essential for promoting high-quality development within the field.During its 14th Five-Year Plan period,the Chinese government has implemented policies to bolster organizational security.Furthering this commitment,on December 25,2023,the State Council issued the“Guiding Opinions on Promoting the High-Quality Development of Disease Prevention and Control.”
文摘China’s Disease Control and Prevention(DCP)system has played a critical role in protecting population health and ensuring socioeconomic stability(1).Over the past two decades,China has made significant advancements in disease surveillance,response,and control,particularly following the 2003 severe acute respiratory syndrome(SARS)outbreak and the 2009 national healthcare reforms(2–3).These initiatives have substantially strengthened the national DCP system and led to improved public health outcomes,including the effective control of outbreaks such as avian influenza and coronavirus disease 2019(COVID-19).Consequently,the incidence of major epidemics has declined markedly(1).
文摘Talent is essential for development,and career development strategies should prioritize talent cultivation(1–2).China’s CDC workforce comprises a diverse,multidisciplinary team of disease prevention and control experts.This workforce includes personnel from various CDC agencies,public medical institutions,township health centers,and community health service centers.Strengthening the development of this pool of talent is crucial for enhancing the quality of disease prevention and control systems and forms the foundation of a robust public health infrastructure(3).On December 25,2023,the State Council released the Guideline on Promoting the High-Quality Development of Disease Prevention and Control,outlining a comprehensive strategy for strengthening the CDC’s talent base.This paper analyzes this policy to clarify the historical context,principal actions,and future trajectory of workforce development within China’s CDC.
基金the National Natural Science Foundation of China(Grant Nos.30730022 and 30870486)the National Basic Research Program(973 Program)(Grant No.2007CB914304)the National Major Projects(grant Nos.2009ZX09311-001 and 2009ZX10004-304).
文摘The importance of NAC(named as NAM,ATAF1,2,and CUC2)proteins in plant development,transcription regulation and regulatory pathways involving proteinprotein interactions has been increasingly recognized.We report here the high resolution crystal structure of SNAC1(stress-responsive NAC)NAC domain at 2.5Å.Although the structure of the SNAC1 NAC domain shares a structural similarity with the reported structure of the ANAC NAC1 domain,some key features,especially relating to two loop regions which potentially take the responsibility for DNA-binding,distinguish the SNAC1 NAC domain from other reported NAC structures.Moreover,the dimerization of the SNAC1 NAC domain is demonstrated by both soluble and crystalline conditions,suggesting this dimeric state should be conserved in this type of NAC family.Additionally,we discuss the possible NAC-DNA binding model according to the structure and reported biological evidences.
基金This work was supported in part by the "Reproductive health and major birth defects prevention and control research" Key Special Fund (No. 2016YFC1000601), the National Natural Science Foundation of China (Grant Nos. 31371521, 81370766, 81401254, 81570101, 81671121, 31601187, 81521002), the Guangdong Province Science and Technology Project (2014TQ01R683, 2017A020 214005, 2016A020216023, 2015A030310119, 2016B030229008), the Bureau of Science and Technology of Guangzhou Municipality (201505011111498), the "Reproductive health and major birth defects prevention and control research" Key Special Fund (Nos. 2016YFC1000201 and 2016YFC1000302), the Ministry of Science and Technology of China Grants (973 program 2014CB943203), and the Beijing Nova Program (xxjh2015011).
文摘Mitochondrial diseases are maternally inherited hetero- geneous disorders that are primarily caused by mitochondrial DNA (mtDNA) mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruc- tion of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells (MiPSCs) that harbored a high proportion of m.3243A〉G mtDNA mutations and caused mitochondrial encephalomyopathy and stroke-like episodes (MELAS). We engineered mitochondrial-targeted transcription activator-like effector nucleases (mitoTALENs) and successfully eliminated the m.3243A〉G mutation in MiPSCs. Off-target mutagenesis was not detected in the targeted MiPSC clones. Utilizing a dual fluorescence iPSC reporter cell line expressing a 3243G mutant mtDNA sequence in the nuclear genome, mitoTALENs displayed a significantly limited ability to target the nuclear genome compared with nuclear-localized TALENs. Moreover, genetically rescued MiPSCs displayed normal mitochondrial respiration and energy production. Moreover, neuronal progenitor cells differentiated from the rescued MiPSCs also demonstrated normal metabolic profiles. Further- more, we successfully achieved reduction in the human m.3243A〉G mtDNA mutation in porcine oocytes via injection of mitoTALEN mRNA. Our study shows the great potential for using mitoTALENs for specific targeting of mutant mtDNA both in iPSCs and mammalian oocytes, which not only provides a new avenue for studying mitochondrial biology and disease but also suggests a potential therapeutic approach for the treatment of mitochondrial disease, as well as the prevention of germline transmission of mutant mtDNA.
文摘We have recently discovered a unique CD34loCD133lo cell population in the human fetal liver (FL) that gives rise to cells in the hepatic lineage. In this study, we further characterized the biological functions of FL CD341~CD133~~ cells. Our findings show that these CD341~CD133I~ cells express markers of both endodermal and mesodermal lineages and have the capability to differentiate into hepatocyte and mesenchymal lineage cells by ex vivo differentiation assays. Furthermore, we show that CD34~~CD 133I~ cel Is express growth factors that are important for human hematopoietic stem cell (HSC) expansion: stem cell factor (SCF), insulin-like growth factor 2 (IGF2), C-X-C motif chemokine 12 (CXCL12), and factors in the angiopoietin-like protein family. Co-culture of autologous FL HSCs and allogenic HSCs derived from cord blood with CD34loCD133lo cells supports and expands both types of HSCs.These findings are not only essential for extending our understanding of the HSC niche during the development of embryonic and fetal hematopoiesis but will also potentially benefit adult stem cell transplantations in clinics because expanded HSCs demonstrate the same capacity as primary cells to reconstitute the human immune system and mediate long-term hematopoiesis in vivo. Together,CD34loCD133lo cells not only serve as stem/progenitor cells for liver development but are also an essential component of the HSC niche in the human FL.
文摘Humanized mice are immunodeficient animals engrafted with human hematopoietic stem cells that give rise to various lineages of human blood cells throughout the life of the mouse. This article reviews recent advances in the generation of humanized mice, focusing on practical considerations. We discuss features of different immunodeficient recipient mouse strains, sources of human hematopoietic stem cells, advances in expansion and genetic modification of hematopoietic stem cells, and techniques to modulate the cytokine environment of recipient mice, in order to enhance reconstitution of specific human blood lineage cells. We highlight the opportunities created by new technologies and discuss practical considerations on how to make best use of the widening array of basic models for specific research applications.
基金The work reported in this paper was partially supported by the National Natural Science Foundation of China(Nos.61702122,61751314 and 31560317)the Natural Science Foundation of Guangxi(Nos.2017GXNSFDA198033 and 2018GXNSFBA281193)+3 种基金the Key Research and Development Plan of Guangxi(No.AB 17195055)the Bossco Project of Guangxi University(No.20190240)the Hunan Provincial Science and Technology Program(No.2018WK4001)111 Project(No.Bl8059).
文摘Background:MicroRNAs(miRNAs)are a significant type of non-coding RNAs,which usually were encoded by endogenous genes with about?22 nt nucleotides.Accumulating biological experiments have shown that miRNAs have close associations with various human diseases.Although traditional experimental methods achieve great successes in miRNA-disease interaction identification,these methods also have some limitations.Therefore,it is necessary to develop computational method to predict miRNA-disease interactions.Methods:Here,we propose a computational framework(MDVSI)to predict interactions between miRNAs and diseases by integrating miRNA topological similarity and functional similarity.Firstly,the CosRA index is utilized to measure miRNA similarity based on network topological feature.Then,in order to enhance the reliability of miRNA similarity,the functional similarity and CosRA similarity are integrated based on linear weight method.Further,the potential miRNA-disease associations are predicted by using recommendation method.In addition,in order to overcome limitation of recommendation method,for new disease,a new strategy is proposed to predict potential interactions between miRNAs and new disease based on disease functional similarity.Results:To evaluate the performance of different methods,we conduct ten-fold cross validation and de novo test in experiment and compare MDVSI with two the-state-of-art methods.The experimental result shows that MDVSI achieves an AUC of 0.91,which is at least 0.012 higher than other compared methods.Conclusions:In summary,we propose a computational framework(MDSVI)for miRNA-disease interaction prediction.The experiment results demonstrate that it outperforms other the-state-of^the-art methods.Case study shows that it can effectively identify potential miRNA-disease interactions.
基金by the Singapore National Research Foundation Fellowship(NRF-NRFF2017-03).
文摘Transplantation of hematopoietic stem/progenitor cells(HSPC)has become one of the most effective treatments for several hematological malignancies,cancers and genetic immune disorders.However,the lack of histocompatible donor sources and the number of stem cells suitable for engraftment are major constraints in the clinic,and these constraints greatly hamper the use of stem cell therapy.In humans,fetal liver and bone marrow are the two major locations of hematopoiesis before and after birth,respectively.Thus,understanding the specialized stem cell microenvironment supporting the self-renewal and expansion of HSPC in fetal liver and bone marrow is not only essential for extending the current knowledge of stem cell biology but is also beneficial to adult regenerative medicine in the clinic.
基金The work reported in this paper was partially supported by two National Natural Science Foundation of China projects 61363025,61751314a key project of Natural Science Foundation of Guangxi 2017GXNSFDA198033a key research and development plan of Guangxi AB17195055.
文摘The interaction between gene loci,namely epistasis,is a widespread biological genetic phenomenon.In genome-wide association studies(GWAS),epistasis detection of complex diseases is a major challenge.Although many approaches using statistics,machine learning,and information entropy were proposed for epistasis detection,the privacy preserving for single nucleotide polymorphism(SNP)data has been largely ignored.Thus,this paper proposes a novel two-stage approach.A fusion strategy assists in combining and sorting the SNPs importance scores obtained by the relief and mutual information,thereby obtaining a candidate set of SNPs.This avoids missing some SNPs with strong interaction.Furthermore,differentially private decision tree is applied to search for SNPs.This achieves the efficient epistasis detection of complex diseases on the basis of privacy preserving compared with heuristic methods.The recognition rate on simulation data set is more than 90%.Also,several susceptible loci including rs380390 and rs1329428 are found in the real data set for Age-related Macular Degeneration(AMD).This demonstrates that our method is promising in epistasis detection.
基金partially supported by two National Natural Science Foundation of China projects 61363025,61751314a key project of Natural Science Foundation of Guangxi 2017GXNSFDA198033a key research and development plan of Guangxi AB17195055.
文摘The interaction between gene loci,namely epistasis,is a widespread biological genetic phenomenon.In genome-wide association studies(GWAS),epistasis detection of complex diseases is a major challenge.Although many approaches using statistics,machine learning,and information entropy were proposed for epistasis detection,the privacy preserving for single nucleotide polymorphism(SNP)data has been largely ignored.Thus,this paper proposes a novel two-stage approach.A fusion strategy assists in combining and sorting the SNPs importance scores obtained by the relief and mutual information,thereby obtaining a candidate set of SNPs.This avoids missing some SNPs with strong interaction.Furthermore,differentially private decision tree is applied to search for SNPs.This achieves the efficient epistasis detection of complex diseases on the basis of privacy preserving compared with heuristic methods.The recognition rate on simulation data set is more than 90%.Also,several susceptible loci including rs380390 and rs1329428 are found in the real data set for Age-related Macular Degeneration(AMD).This demonstrates that our method is promising in epistasis detection.