In recent years,the introduction of fused rings own high density and low sensitivity has promoted the development of energetic materials.However,the development of energetic compounds containing fused and bridged ring...In recent years,the introduction of fused rings own high density and low sensitivity has promoted the development of energetic materials.However,the development of energetic compounds containing fused and bridged rings by introducing multiple nitrogen heterocycles at different sites of fused rings is still difficult to progress,which seriously limits the emergence of advanced energetic compounds.In this study,a series of energetic materials choosing different nitrogen rich heterocycles at the vacancies of the fused ring,i.e.,neutral compound 5,6 and their ionic derivatives(compounds 7-12)were designed and synthesized.Compounds 5 and 6 were further confirmed by single crystal X-ray diffraction,while the crystal analysis and theoretical calculations were carried out to explore the relationship between crystal structure and physicochemical properties.All of the newly synthesized compounds(5-12)are insensitive to mechanical stimulation(IS>40 J;FS≥342 N)and they own the high detonation velocity(D:8322-9075 m/s).Notably,hydrazine salt 11 own the higher detonation velocity(9075 m/s)and powder density(1.83 g/cm^(3)),but exhibits lower sensitivity(IS>40 J)than the classical energetic compound RDX(8795 m/s,1.80 g/cm^(3),7.5 J).It is obvious that the combination of 5,6-fused triazolo-triazine and nitropyrazole-tetrazole may be a new energetic skeleton for synthesising the heterocyclic compounds with balanced energy-stability.展开更多
Chinese tree shrews (Tupaia belangeri chinensis) have become an increasingly important experimental animal in biomedical research due to their close relationship to primates. An accurately sequenced and assembled geno...Chinese tree shrews (Tupaia belangeri chinensis) have become an increasingly important experimental animal in biomedical research due to their close relationship to primates. An accurately sequenced and assembled genome is essential for understanding the genetic features and biology of this animal. In this study, we used long-read single-molecule sequencing and high-throughput chromosome conformation capture (Hi-C) technology to obtain a high-qualitychromosome-scale scaffolding of the Chinese tree shrew genome. The new reference genome (KIZ version 2: TS_2.0) resolved problems in presently available tree shrew genomes and enabled accurate identification of large and complex repeat regions, gene structures, and species-specific genomic structural variants. In addition, by sequencing the genomes of six Chinese tree shrew individuals, we produced a comprehensive map of 12.8 M single nucleotide polymorphisms and confirmed that the major histocompatibility complex (MHC) loci and immunoglobulin gene family exhibited high nucleotide diversity in the tree shrew genome. We updated the tree shrew genome database (TreeshrewDB v2.0: http://www.treeshrewdb.org) to include the genome annotation information and genetic variations. The new high-quality reference genome of the Chinese tree shrew and the updated TreeshrewDB will facilitate the use of this animal in many different fields of research.展开更多
Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily us...Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.展开更多
Palaeognathae includes ratite and tinamou species that are important for understanding early avian evolution.Here,we analyzed the whole-genome sequences of 15 paleognathous species to infer their demographic histories...Palaeognathae includes ratite and tinamou species that are important for understanding early avian evolution.Here,we analyzed the whole-genome sequences of 15 paleognathous species to infer their demographic histories,which are presently unknown.We found that most species showed a reduction of population size since the beginning of the last glacial period,except for those species distributed in Australasia and in the far south of South America.Different degrees of contraction and expansion of transposable elements(TE)have shaped the paleognathous genome architecture,with a higher transposon removal rate in tinamous than in ratites.One repeat family,AviRTE,likely underwent horizontal transfer from tropical parasites to the ancestor of little and undulated tinamous about 30 million years ago.Our analysis of gene families identified rapid turnover of immune and reproductionrelated genes but found no evidence of gene family changes underlying the convergent evolution of flightlessness among ratites.We also found that mitochondrial genes have experienced a faster evolutionary rate in tinamous than in ratites,with the former also showing more degenerated W chromosomes.This result can be explained by the Hill-Robertson interference affecting genetically linked W chromosomes and mitochondria.Overall,we reconstructed the evolutionary history of the Palaeognathae populations,genes,and TEs.Our findings of co-evolution between mitochondria and W chromosomes highlight the key difference in genome evolution between species with ZW sex chromosomes and those with XY sex chromosomes.展开更多
The water-to-land transition was a major step in vertebrate evolution and eventually gave rise to the tetrapods, including amphibians, reptiles, birds, and mammals. The first land invasion of our fish ancestors is con...The water-to-land transition was a major step in vertebrate evolution and eventually gave rise to the tetrapods, including amphibians, reptiles, birds, and mammals. The first land invasion of our fish ancestors is considered to have occurred during the late Devonian period ~370 million years ago(Mya)(Daeschler et al., 2006).展开更多
Open Access This is an open-access article distributed under the terms of theCreative Commons Attribution Non-Commercial License(http:1/creativecommons.org/licenses/by-nc/4.0/).which permits unrestrictednon-commercial...Open Access This is an open-access article distributed under the terms of theCreative Commons Attribution Non-Commercial License(http:1/creativecommons.org/licenses/by-nc/4.0/).which permits unrestrictednon-commercial use,distribution.and reproduction in any medium.展开更多
Entropic elasticity of single chains underlies many fundamental aspects of mechanical properties of polymers,such as high elasticity of polymer networks and viscoelasticity of polymer liquids.On the other hand,single ...Entropic elasticity of single chains underlies many fundamental aspects of mechanical properties of polymers,such as high elasticity of polymer networks and viscoelasticity of polymer liquids.On the other hand,single chain elasticity is further rooted in chain connectivity.Recently,mechanically interlocked polymers,including polycatenanes and polyrotaxanes,which are formed by connecting their building blocks(cyclic and linear chains)through topological bonds(e.g.,entanglements),emerge as a conceptually new kind of polymers.In this work,we employ computer simulations to study linear elasticity of single linear polycatenane(or[n]catenane),in which n rings are interlocked through catenation into a chain of linear architecture.Aim of this work is to illuminate the specific role of catenation topology in the elastic moduli of linear polycatenanes by comparing with those of their[n]bonded-ring counterparts,which are formed by connecting the same number of rings but via covalent bonds.Simulation results lead to a conclusion that topological catenation makes[n]catenanes exhibit larger elastic moduli than their linear and[n]bonded-ring counterparts,i.e.,larger elastic moduli in the case of[n]catenanes.Furthermore,it is revealed that those[n]catenanes composed of a smaller number of rings(smaller n)possesses larger elastic moduli than others of the same total chain lengths.Molecular mechanisms of these findings are discussed based on conformational entropy due to topological constraints.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.21875110,22075143)the Science Challenge Projectthe Qing Lan Project for the grant。
文摘In recent years,the introduction of fused rings own high density and low sensitivity has promoted the development of energetic materials.However,the development of energetic compounds containing fused and bridged rings by introducing multiple nitrogen heterocycles at different sites of fused rings is still difficult to progress,which seriously limits the emergence of advanced energetic compounds.In this study,a series of energetic materials choosing different nitrogen rich heterocycles at the vacancies of the fused ring,i.e.,neutral compound 5,6 and their ionic derivatives(compounds 7-12)were designed and synthesized.Compounds 5 and 6 were further confirmed by single crystal X-ray diffraction,while the crystal analysis and theoretical calculations were carried out to explore the relationship between crystal structure and physicochemical properties.All of the newly synthesized compounds(5-12)are insensitive to mechanical stimulation(IS>40 J;FS≥342 N)and they own the high detonation velocity(D:8322-9075 m/s).Notably,hydrazine salt 11 own the higher detonation velocity(9075 m/s)and powder density(1.83 g/cm^(3)),but exhibits lower sensitivity(IS>40 J)than the classical energetic compound RDX(8795 m/s,1.80 g/cm^(3),7.5 J).It is obvious that the combination of 5,6-fused triazolo-triazine and nitropyrazole-tetrazole may be a new energetic skeleton for synthesising the heterocyclic compounds with balanced energy-stability.
基金supported by the National Natural Science Foundation of China(U1402224,31601010,81571998,and U1702284)Yunnan Province(2015HA038 and 2018FB054)Chinese Academy of Sciences(CAS zsys-02)
文摘Chinese tree shrews (Tupaia belangeri chinensis) have become an increasingly important experimental animal in biomedical research due to their close relationship to primates. An accurately sequenced and assembled genome is essential for understanding the genetic features and biology of this animal. In this study, we used long-read single-molecule sequencing and high-throughput chromosome conformation capture (Hi-C) technology to obtain a high-qualitychromosome-scale scaffolding of the Chinese tree shrew genome. The new reference genome (KIZ version 2: TS_2.0) resolved problems in presently available tree shrew genomes and enabled accurate identification of large and complex repeat regions, gene structures, and species-specific genomic structural variants. In addition, by sequencing the genomes of six Chinese tree shrew individuals, we produced a comprehensive map of 12.8 M single nucleotide polymorphisms and confirmed that the major histocompatibility complex (MHC) loci and immunoglobulin gene family exhibited high nucleotide diversity in the tree shrew genome. We updated the tree shrew genome database (TreeshrewDB v2.0: http://www.treeshrewdb.org) to include the genome annotation information and genetic variations. The new high-quality reference genome of the Chinese tree shrew and the updated TreeshrewDB will facilitate the use of this animal in many different fields of research.
基金supported by the National Natural Science Foundation of China(81773711)to W.Y.Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13000000)+6 种基金Lundbeck Foundation Grant(R190-2014-2827)Carlsberg Foundation Grant(CF16-0663)to G.J.Z.Science and Technology Program of Guangzhou,China(201704020103)to W.Y.Introduction of Innovative R&D Team Program of Guangdong Province(2013Y104)Leading Talent Project in Science and Technology of Guangzhou Development District(2019-L002)National Major Scientific and Technological Special Project for “Significant New Drugs Development”(2016ZX09101026)to S.Z.L.Key Projects of the Military Science and Technology PLA(AWS14C007 and AWS16J023)to Y.Q.G
文摘Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.
基金This study was supported by the National Natural Science Foundation of China(31671319,31722050,32061130208)Natural Science Foundation of Zhejiang Province(LD19C190001)+5 种基金European Research Council Starting Grant(grant agreement 677696)to Q.Z.the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB31020000,XDB13000000)International Partnership Program of Chinese Academy of Sciences(152453KYSB20170002)Carlsberg Foundation(CF16-0663)Villum Foundation(25900)to G.J.ZWe thank China National Genebank at BGI for contributing to the sequencing.We would like to thank Christopher C.Witt,Mariel L.Campbell and Ariel M.Gaffney from the Museum of Southwestern Biology,Gary Graves from Smithsonian Institute,Robb T.Brumfield and Donna L.Dittman from Louisiana State University Museum of Natural Science,Jack Withrow and Andy Kratter from Florida Museum of Natural History,University of New Mexico for providing bird DNA samples for this work.
文摘Palaeognathae includes ratite and tinamou species that are important for understanding early avian evolution.Here,we analyzed the whole-genome sequences of 15 paleognathous species to infer their demographic histories,which are presently unknown.We found that most species showed a reduction of population size since the beginning of the last glacial period,except for those species distributed in Australasia and in the far south of South America.Different degrees of contraction and expansion of transposable elements(TE)have shaped the paleognathous genome architecture,with a higher transposon removal rate in tinamous than in ratites.One repeat family,AviRTE,likely underwent horizontal transfer from tropical parasites to the ancestor of little and undulated tinamous about 30 million years ago.Our analysis of gene families identified rapid turnover of immune and reproductionrelated genes but found no evidence of gene family changes underlying the convergent evolution of flightlessness among ratites.We also found that mitochondrial genes have experienced a faster evolutionary rate in tinamous than in ratites,with the former also showing more degenerated W chromosomes.This result can be explained by the Hill-Robertson interference affecting genetically linked W chromosomes and mitochondria.Overall,we reconstructed the evolutionary history of the Palaeognathae populations,genes,and TEs.Our findings of co-evolution between mitochondria and W chromosomes highlight the key difference in genome evolution between species with ZW sex chromosomes and those with XY sex chromosomes.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No.XDB13000000 and XDB31020000)the Villum Foundation (Villum Investigator Grant No. 25900)。
文摘The water-to-land transition was a major step in vertebrate evolution and eventually gave rise to the tetrapods, including amphibians, reptiles, birds, and mammals. The first land invasion of our fish ancestors is considered to have occurred during the late Devonian period ~370 million years ago(Mya)(Daeschler et al., 2006).
基金This study was supported by the National Natural Science Foundation of China(81773711)to W.Y.Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13000000)to G.J.Z.+4 种基金Science and Technology Programof Guangzhou,China(201704020103)to W.Y.Introduction of Innovative R&D Team Program of Guangdong Province(2013Y104)Leading Talent Projectin Science and Technology of Guangzhou Development District(2019-L002)National Major Scientific and Technological Special Project for"Significant New Drugs Development"(2016ZX09101026)to S.Z.L.Key Projects of the Military Science and Technology PLA(AWS14C007 and AWS16J023)to Y.Q.G.
文摘Open Access This is an open-access article distributed under the terms of theCreative Commons Attribution Non-Commercial License(http:1/creativecommons.org/licenses/by-nc/4.0/).which permits unrestrictednon-commercial use,distribution.and reproduction in any medium.
基金financially supported by the National Natural Science Foundation of China(No.21873023)。
文摘Entropic elasticity of single chains underlies many fundamental aspects of mechanical properties of polymers,such as high elasticity of polymer networks and viscoelasticity of polymer liquids.On the other hand,single chain elasticity is further rooted in chain connectivity.Recently,mechanically interlocked polymers,including polycatenanes and polyrotaxanes,which are formed by connecting their building blocks(cyclic and linear chains)through topological bonds(e.g.,entanglements),emerge as a conceptually new kind of polymers.In this work,we employ computer simulations to study linear elasticity of single linear polycatenane(or[n]catenane),in which n rings are interlocked through catenation into a chain of linear architecture.Aim of this work is to illuminate the specific role of catenation topology in the elastic moduli of linear polycatenanes by comparing with those of their[n]bonded-ring counterparts,which are formed by connecting the same number of rings but via covalent bonds.Simulation results lead to a conclusion that topological catenation makes[n]catenanes exhibit larger elastic moduli than their linear and[n]bonded-ring counterparts,i.e.,larger elastic moduli in the case of[n]catenanes.Furthermore,it is revealed that those[n]catenanes composed of a smaller number of rings(smaller n)possesses larger elastic moduli than others of the same total chain lengths.Molecular mechanisms of these findings are discussed based on conformational entropy due to topological constraints.
