Viral vector transfection systems are among the simplest of biological agents with the ability to transfer genes into the central nervous system.In brain research,a series of powerful and novel gene editing technologi...Viral vector transfection systems are among the simplest of biological agents with the ability to transfer genes into the central nervous system.In brain research,a series of powerful and novel gene editing technologies are based on these systems.Although many viral vectors are used in rodents,their full application has been limited in non-human primates.To identify viral vectors that can stably and effectively express exogenous genes within nonhuman primates,eleven commonly used recombinant adeno-associated viral and lentiviral vectors,each carrying a gene to express green or red fluorescence,were injected into the parietal cortex of four rhesus monkeys.The expression of fluorescent cells was used to quantify transfection efficiency.Histological results revealed that recombinant adeno-associated viral vectors,especially the serotype 2/9 coupled with the cytomegalovirus,human synapsin I,or Ca2+/calmodulin-dependentproteinkinaseII promoters,and lentiviral vector coupled with the human ubiquitin C promoter,induced higher expression of fluorescent cells,representing high transfection efficiency.This is the first comparison of transfection efficiencies of different viral vectors carrying different promoters and serotypes in non-human primates(NHPs).These results can be used as an aid to select optimal vectors to transfer exogenous genes into the central nervous system of non-human primates.展开更多
The limited capability to regenerate new neurons following injuries of the central neural system(CNS)still remains a major challenge for basic and clinical neuroscience.Neural stem cells(NSCs)could nearly have the pot...The limited capability to regenerate new neurons following injuries of the central neural system(CNS)still remains a major challenge for basic and clinical neuroscience.Neural stem cells(NSCs)could nearly have the potential to differentiate into all kinds of neural cells in vitro.Previous studies verified that exogenous transplanted NSCs are capable of展开更多
In animal societies, some stressful events can lead to higher levels of physiological stress. Such stressors, like social rank, also predict an increased vulnerability to an array of diseases. However, the physiologic...In animal societies, some stressful events can lead to higher levels of physiological stress. Such stressors, like social rank, also predict an increased vulnerability to an array of diseases. However, the physiological relationship between social rank and stress varies between different species, as well as within groups of a single species. For example, dominant individuals are more socially stressed at times, while at other times it is the subordinate ones who experience this stress. Together, these variations make it difficult to assess disease vulnerability as connected to social interactions. In order to learn more about how physiological rank relationships vary between groups of a single species, cortisol measurements from hair samples were used to evaluate the effects of dominance rank on long-term stress levels in despotic and less stringent female rhesus macaque hierarchal groups. In despotic groups, cortisol levels were found not to be correlated with social rank, but a negative correlation was found between social rank and cortisol levels in less stringent hierarchies. Low ranking monkeys in less stringent groups secreted elevated levels of cortisol compared to higher ranking animals. These data suggest that variations in the strictness of the dominance hierarchy are determining factors in rank related stress physiology. The further consideration of nonhuman primate social system diversity and the linear degree of their hierarchies may allow for the development of valid rank-related stress models that will help increase our understanding and guide the development of new therapeutics for diseases related to human socioeconomic status.展开更多
In animal societies,some stressful events can lead to higher levels of physiological stress.Such stressors,like social rank,also predict an increased vulnerability to an array of diseases.However,the physiological rel...In animal societies,some stressful events can lead to higher levels of physiological stress.Such stressors,like social rank,also predict an increased vulnerability to an array of diseases.However,the physiological relationship between social rank and stress varies between different species,as well as within groups of a single species.For example,dominant individuals are more socially stressed at times,while at other times it is the subordinate ones who experience this stress.Together,these variations make it difficult to assess disease vulnerability as connected to social interactions.In order to learn more about how physiological rank relationships vary between groups of a single species,cortisol measurements from hair samples were used to evaluate the effects of dominance rank on long-term stress levels in despotic and less stringent female rhesus macaque hierarchal groups.In despotic groups,cortisol levels were found not to be correlated with social rank,but a negative correlation was found between social rank and cortisol levels in less stringent hierarchies.Low ranking monkeys in less stringent groups secreted elevated levels of cortisol compared to higher ranking animals.These data suggest that variations in the strictness of the dominance hierarchy are determining factors in rank related stress physiology.The further consideration of nonhuman primate social system diversity and the linear degree of their hierarchies may allow for the development of valid rank-related stress models that will help increase our understanding and guide the development of new therapeutics for diseases related to human socioeconomic status.展开更多
DEAR EDITOR,Since the epoch-making observations of circadian rhythm in Mimosaceae plants,sleep has been investigated for centuries(de Mairan,1729;Du Monceau,1758).As a natural and reversible state,sleep is marked by r...DEAR EDITOR,Since the epoch-making observations of circadian rhythm in Mimosaceae plants,sleep has been investigated for centuries(de Mairan,1729;Du Monceau,1758).As a natural and reversible state,sleep is marked by reduced responsiveness to external stimuli,relative inactivity,and loss of consciousness.Although reduced responsiveness could potentially introduce significant danger to survival,nearly all animals in nature sleep.展开更多
High fecundity is a common characteristic of insect pests which increases the difficulty of population control.Serine/threonine kinase Akt is an indispensable component of the insulin signaling pathway.Silencing of Ls...High fecundity is a common characteristic of insect pests which increases the difficulty of population control.Serine/threonine kinase Akt is an indispensable component of the insulin signaling pathway.Silencing of LsAkt severely hinders reproduction in Lasioderma serricorne,a stored product insect pest.However,the post-transcriptional pathway of LsAkt in L.serricorne remains unknown.This study identified 2 binding sites of miR-9c-5p and novel-mir50 in the coding sequences of LsAkt.The expression profiles of 2 microRNAs(miRNAs)and LsAkt displayed an opposite pattern during the adult stages.Luciferase reporter assay showed that novel-mir50 and miR-9c-5p could downregulate the expression of LsAkt.Overexpression of miR-9c-5p and novel-mir50 by injection of mimics inhibited the expression of LsAkt and reduced oviposition,decreased egg hatchability,and blocked ovarian development.It also decreased the expression of genes involved in ovarian development(LsVg and LsVgR)and the nutritional signaling pathway(LsTOR,LsS6K,and Ls4EBP),and reduced the phosphorylation of Akt.Conversely,injection of miR-9c-5p and novel-mir50 inhibitors induced the expressions of LsAkt,LsVg,LsVgR,LsTOR,LsS6K,and Ls4EBP,enhanced Akt phosphorylation level,and accelerated ovarian development.Injection of bovine insulin downregulated the expression of miR-9c-5p and novel-mir50 and upregulated the LsAkt expression.It also rescued the reproductive development defects associated with miR-9c-5p/novel-mir50 overexpression,forming a positive regulatory loop of insulin signaling.These results indicate that miR-9c-5p/novel-mir50 regulates the female reproduction of L.serricorne by targeting Akt in response to insulin signaling.The data also demonstrate the effects of the insulin/miRNA/Akt regulatory axis in insect reproduction.展开更多
The objective of this study was to investigate the potential of methoxy polyethylene glycol(m PEG)grafted chitosan(m PEG-g-CS) to be used as a drug carrier. m PEG-g-CS was successfully synthesized by one-step method w...The objective of this study was to investigate the potential of methoxy polyethylene glycol(m PEG)grafted chitosan(m PEG-g-CS) to be used as a drug carrier. m PEG-g-CS was successfully synthesized by one-step method with formaldehyde. The substitution degree of m PEG on chitosan was calculated by elemental analysis and was found to be(3.23 0.25)%. m PEG-g-CS self-assembled micelles were prepared by ultrasonic method with the controlled size of 178.5–195.1 nm and spherical morphology. Stable dispersion of the micelles was formed with the zeta potential of 2.3–30.2 m V. 5-Fluorouracil(5-FU), an anticancer chemotherapy drug, was used as a model drug to evaluate the efficiency of the new drug delivery carrier. The loading efficiency of 5-FU was(4.01 0.03)%, and the drug-loaded m PEG-g-CS self-assembled micelle showed a controlled-release effect. In summary, the m PEG-g-CS self-assembled micelle is proved to be a promising carrier with controlled particle size and controlled-release effect. Therefore, it has great potential for the application as 5-FU carriers for effective anti-tumor activity.展开更多
基金supported by the National Program on Key Basic Research Project(973 Programs 2015CB755605)the National Natural Science Foundation of China(81471312)
文摘Viral vector transfection systems are among the simplest of biological agents with the ability to transfer genes into the central nervous system.In brain research,a series of powerful and novel gene editing technologies are based on these systems.Although many viral vectors are used in rodents,their full application has been limited in non-human primates.To identify viral vectors that can stably and effectively express exogenous genes within nonhuman primates,eleven commonly used recombinant adeno-associated viral and lentiviral vectors,each carrying a gene to express green or red fluorescence,were injected into the parietal cortex of four rhesus monkeys.The expression of fluorescent cells was used to quantify transfection efficiency.Histological results revealed that recombinant adeno-associated viral vectors,especially the serotype 2/9 coupled with the cytomegalovirus,human synapsin I,or Ca2+/calmodulin-dependentproteinkinaseII promoters,and lentiviral vector coupled with the human ubiquitin C promoter,induced higher expression of fluorescent cells,representing high transfection efficiency.This is the first comparison of transfection efficiencies of different viral vectors carrying different promoters and serotypes in non-human primates(NHPs).These results can be used as an aid to select optimal vectors to transfer exogenous genes into the central nervous system of non-human primates.
基金supported by National Program on Key Basic Research Project(973 Programs 2015CB755605)National Natural Science Foundation of China(81471312)
文摘The limited capability to regenerate new neurons following injuries of the central neural system(CNS)still remains a major challenge for basic and clinical neuroscience.Neural stem cells(NSCs)could nearly have the potential to differentiate into all kinds of neural cells in vitro.Previous studies verified that exogenous transplanted NSCs are capable of
基金funded by the National Science Foundation of China (NSFC 31271167, and 31070963)the 973 program (2007CB947703 and 2011CB707800)the Key Program of the Chinese Academy of Sciences, China (KSCX2-EW-R-13)
文摘In animal societies, some stressful events can lead to higher levels of physiological stress. Such stressors, like social rank, also predict an increased vulnerability to an array of diseases. However, the physiological relationship between social rank and stress varies between different species, as well as within groups of a single species. For example, dominant individuals are more socially stressed at times, while at other times it is the subordinate ones who experience this stress. Together, these variations make it difficult to assess disease vulnerability as connected to social interactions. In order to learn more about how physiological rank relationships vary between groups of a single species, cortisol measurements from hair samples were used to evaluate the effects of dominance rank on long-term stress levels in despotic and less stringent female rhesus macaque hierarchal groups. In despotic groups, cortisol levels were found not to be correlated with social rank, but a negative correlation was found between social rank and cortisol levels in less stringent hierarchies. Low ranking monkeys in less stringent groups secreted elevated levels of cortisol compared to higher ranking animals. These data suggest that variations in the strictness of the dominance hierarchy are determining factors in rank related stress physiology. The further consideration of nonhuman primate social system diversity and the linear degree of their hierarchies may allow for the development of valid rank-related stress models that will help increase our understanding and guide the development of new therapeutics for diseases related to human socioeconomic status.
基金This study was funded by the National Science Foundation of China(NSFC 31271167,and 31070963)the 973 program(2007CB947703 and 2011CB707800)the Key Program of the Chinese Academy of Sciences,China(KSCX2-EW-R-13)。
文摘In animal societies,some stressful events can lead to higher levels of physiological stress.Such stressors,like social rank,also predict an increased vulnerability to an array of diseases.However,the physiological relationship between social rank and stress varies between different species,as well as within groups of a single species.For example,dominant individuals are more socially stressed at times,while at other times it is the subordinate ones who experience this stress.Together,these variations make it difficult to assess disease vulnerability as connected to social interactions.In order to learn more about how physiological rank relationships vary between groups of a single species,cortisol measurements from hair samples were used to evaluate the effects of dominance rank on long-term stress levels in despotic and less stringent female rhesus macaque hierarchal groups.In despotic groups,cortisol levels were found not to be correlated with social rank,but a negative correlation was found between social rank and cortisol levels in less stringent hierarchies.Low ranking monkeys in less stringent groups secreted elevated levels of cortisol compared to higher ranking animals.These data suggest that variations in the strictness of the dominance hierarchy are determining factors in rank related stress physiology.The further consideration of nonhuman primate social system diversity and the linear degree of their hierarchies may allow for the development of valid rank-related stress models that will help increase our understanding and guide the development of new therapeutics for diseases related to human socioeconomic status.
基金This study was supported by the National Natural Science Foundation of China(31700897,31960178)Yunnan Provincial Natural Science Foundation of China(2018FB053,2019FA007)+1 种基金China Postdoctoral Science Foundation(2018M631105)Post-Doctoral Training Program in Yunnan Province,and Key Realm R&D Program of Guangdong Province(2019B030335001)。
文摘DEAR EDITOR,Since the epoch-making observations of circadian rhythm in Mimosaceae plants,sleep has been investigated for centuries(de Mairan,1729;Du Monceau,1758).As a natural and reversible state,sleep is marked by reduced responsiveness to external stimuli,relative inactivity,and loss of consciousness.Although reduced responsiveness could potentially introduce significant danger to survival,nearly all animals in nature sleep.
基金This research was funded by the National Natural Science Foundation of China(32160637)the Project of China Tobacco Guizhou Industrial Co.,Ltd.(2017-25)+2 种基金the Special Project for Local(Guizhou)Science and Technology Development under the guidance of the Central Government(QKZYD[2022]4013)the Graduate Research Project of Guizhou Province(QJHYJSKYJJ[2021]194)the Program of Excellent Innovation Talents in Guizhou Province(20206003).
文摘High fecundity is a common characteristic of insect pests which increases the difficulty of population control.Serine/threonine kinase Akt is an indispensable component of the insulin signaling pathway.Silencing of LsAkt severely hinders reproduction in Lasioderma serricorne,a stored product insect pest.However,the post-transcriptional pathway of LsAkt in L.serricorne remains unknown.This study identified 2 binding sites of miR-9c-5p and novel-mir50 in the coding sequences of LsAkt.The expression profiles of 2 microRNAs(miRNAs)and LsAkt displayed an opposite pattern during the adult stages.Luciferase reporter assay showed that novel-mir50 and miR-9c-5p could downregulate the expression of LsAkt.Overexpression of miR-9c-5p and novel-mir50 by injection of mimics inhibited the expression of LsAkt and reduced oviposition,decreased egg hatchability,and blocked ovarian development.It also decreased the expression of genes involved in ovarian development(LsVg and LsVgR)and the nutritional signaling pathway(LsTOR,LsS6K,and Ls4EBP),and reduced the phosphorylation of Akt.Conversely,injection of miR-9c-5p and novel-mir50 inhibitors induced the expressions of LsAkt,LsVg,LsVgR,LsTOR,LsS6K,and Ls4EBP,enhanced Akt phosphorylation level,and accelerated ovarian development.Injection of bovine insulin downregulated the expression of miR-9c-5p and novel-mir50 and upregulated the LsAkt expression.It also rescued the reproductive development defects associated with miR-9c-5p/novel-mir50 overexpression,forming a positive regulatory loop of insulin signaling.These results indicate that miR-9c-5p/novel-mir50 regulates the female reproduction of L.serricorne by targeting Akt in response to insulin signaling.The data also demonstrate the effects of the insulin/miRNA/Akt regulatory axis in insect reproduction.
基金support from the Fundamental Research Funds for the Central Universities(No.WY1213013ECUST)supported by Science and Technology Commission of Shanghai Municipality(STCSM,contract Nos.11DZ2260600 and 10DZ2220500)
文摘The objective of this study was to investigate the potential of methoxy polyethylene glycol(m PEG)grafted chitosan(m PEG-g-CS) to be used as a drug carrier. m PEG-g-CS was successfully synthesized by one-step method with formaldehyde. The substitution degree of m PEG on chitosan was calculated by elemental analysis and was found to be(3.23 0.25)%. m PEG-g-CS self-assembled micelles were prepared by ultrasonic method with the controlled size of 178.5–195.1 nm and spherical morphology. Stable dispersion of the micelles was formed with the zeta potential of 2.3–30.2 m V. 5-Fluorouracil(5-FU), an anticancer chemotherapy drug, was used as a model drug to evaluate the efficiency of the new drug delivery carrier. The loading efficiency of 5-FU was(4.01 0.03)%, and the drug-loaded m PEG-g-CS self-assembled micelle showed a controlled-release effect. In summary, the m PEG-g-CS self-assembled micelle is proved to be a promising carrier with controlled particle size and controlled-release effect. Therefore, it has great potential for the application as 5-FU carriers for effective anti-tumor activity.
基金supported by the Key-Area Research and Development Program of Guangdong Province (2019B03035001)the National Natural Science Foundation of China (81941014, 31625013, 91732302, 81471312, 81771387, 81460352, 81500983, 31700897, 31700910, 31800901, 31700897, 31960178, and 81460352)+7 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences (XDBS32060200)the Shanghai Brain-Intelligence Project from the Science and Technology Commission of the Shanghai Municipality (16JC1420501)the Shanghai Municipal Science and Technology Major Project (2018SHZDZX05)the Applied Basic Research Programs of Science and Technology Commission Foundation of Yunnan Province (2017FB109, 2018FB052, 2018FB053, and 2019FA007)the China Postdoctoral Science Foundation (2018M631105)the CAS ‘‘Light of West China” Programthe National Key R&D Program of China (2018YFA0801403)the Key Scientific and Technological Projects of Guangdong Province (2018B030335001)。