Objective The aim of this review was to assess RNA interference (RNAi) and its possibility as a potential and powerful tool to develop highly specific double-stranded RNA ( dsRNA) or small interfering RNA (siRNA) base...Objective The aim of this review was to assess RNA interference (RNAi) and its possibility as a potential and powerful tool to develop highly specific double-stranded RNA ( dsRNA) or small interfering RNA (siRNA) based gene-silencing therapeutics. Data sources The data used in this review were obtained from the current RNAi-related research reports. Study selection dsRNA-mediated RNAi has recently emerged as a powerful reverse genetic tool to silence, gene expression in multiple organisms. The discovery that synthetic duplexes of 21 nucleotides siRNAs trigger gene-specific silencing in mammalian cells has further expanded the utility of RNAi in to the mammalian system. Data extraction The currently published papers reporting the discovery and mechanism of RNAi phenomena and application of RNAi on gene function in mammalian cells were included. Data synthesis Since the recent development of RNAi technology in the mammalian system, investigators have used RNAi to elucidate gene function, and to develop gene-based therapeutics by delivery exogenous siRNA or siRNA expressing vector. The general and sequence-specific inhibitory effects of RNAi that will be selective, long-term, and systemic to modulate gene targets mentioned in similar reports have caused much concern about its effectiveness in mammals and its eventual use as a therapeutic mordality. Conclusions It is certain that the ability of RNAi in mammals to silence specific genes, either when transfected directly as siRNAs or when generated from DNA vectors, will undoubtedly accelerate the study of gene function and might also be used as a potentially useful method to develop highly gene-specific therapeutic methods. It is also expected that RNAi might one day be used to treat human diseases.展开更多
With its high efficiency for site-specific genome editing and easy manipulation,the clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR associated protein 9(CAS9)system has become the most widely ...With its high efficiency for site-specific genome editing and easy manipulation,the clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR associated protein 9(CAS9)system has become the most widely used gene editing technology in biomedical research.In addition,significant progress has been made for the clinical development of CRISPR/CAS9 based gene therapies of human diseases,several of which are entering clinical trials.Here we report that CAS9 protein can function as a genome mutator independent of any exogenous guide RNA(gRNA)in human cells,promoting genomic DNA double-stranded break(DSB)damage and genomic instability.CAS9 interacts with the KU86 subunit of the DNA-dependent protein kinase(DNA-PK)complex and disrupts the interaction between KU86 and its kinase subunit,leading to defective DNA-PK-dependent repair of DNA DSB damage via non-homologous end-joining(NHEJ)pathway.XCAS9 is a CAS9 variant with potentially higher fidelity and broader compatibility,and dCAS9 is a CAS9 variant without nuclease activity.We show that XCAS9 and dCAS9 also interact with KU86 and disrupt DNA DSB repair.Considering the critical roles of DNA-PK in maintaining genomic stability and the pleiotropic impact of DNA DSB damage responses on cellular proliferation and survival,our findings caution the interpretation of data involving CRISPR/CAS9-based gene editing and raise serious safety concerns of CRISPR/CAS9 system in clinical application.展开更多
Endoplasmic reticulum(ER)stress occurs when ER homeostasis is perturbed with accumulation of unfolded/misfolded protein or calcium depletion.The unfolded protein response(UPR),comprising of inositol-requiring enzyme 1...Endoplasmic reticulum(ER)stress occurs when ER homeostasis is perturbed with accumulation of unfolded/misfolded protein or calcium depletion.The unfolded protein response(UPR),comprising of inositol-requiring enzyme 1 a(IRE1 a),double-stranded RNA-dependent protein kinase(PKR)-like ER kinase(PERK)and activating transcription factor 6(ATF6)signaling pathways,is a protective cellular response activated by ER stress.However,UPR activation can also induce cell death upon persistent ER stress.The liver is susceptible to ER stress given its synthetic and other biological functions.Numerous studies from human liver samples and animal disease models have indicated a crucial role of ER stress and the UPR signaling pathways in the pathogenesis of liver diseases,including non-alcoholic fatty liver disease(NAFLD),alcoholic liver disease(ALD),alpha-1 antitrypsin(AAT)deficiency(AATD),cholestatic liver disease,drug-induced liver injury,ischemia/reperfusion(I/R)injury,viral hepatitis and hepatocel-lular carcinoma(HCC).Extensive investigations have demonstrated the potential underlying mechanisms of the induction of ER stress and the contribution of the UPR pathways during the development of the diseases.Moreover,ER stress and the UPR proteins and genes have become emerging therapeutic targets to treat liver diseases.展开更多
Plant-mediated RNA interference(RNAi)has emerged as a promising technology for insect control.The green peach aphid,Myzus persicae,feeds on over 400 species of host plants.Brassica napus(rape)is the second most import...Plant-mediated RNA interference(RNAi)has emerged as a promising technology for insect control.The green peach aphid,Myzus persicae,feeds on over 400 species of host plants.Brassica napus(rape)is the second most important oilseed crop worldwide.Myzus persicae is highly reproductive and causes severe damage to the rape plants due to its quite flexible life cycle.In this study,we tested the RNAi effects of transgenic rape plants on M.persicae.By in vitro feeding M.persicae with artificial diets containing double-stranded RNAs(dsRNAs)targeting seven aphid genes,we identified a new gene encoding the partitioning-defective protein 6(Par6)as the most potent RNAi target.Tissue-and stage-expression analysis of Par6 suggested this gene is highly expressed in the embryo and adult stage of M.persicae.We next generated transgenic rape plants expressing ds Par6 by Agrobacteriummediated transformation and obtained nine independent transgenic lines.Compared to wild-type control plants,transgenic rape lines expressing ds Par6 showed strong resistance to M.persicae.Feeding assays revealed that feeding transgenic rape plants to M.persicae significantly decreased MpPar6 expression and survival rate and impaired fecundity.Furthermore,we showed that the resistance levels to M.persicae are positively correlated with ds Par6 expression levels in transgenic rape plants.Our study demonstrates that transgenic rape plants expressing ds Par6 are efficiently protected from M.persicae.Interfering with the genes involved in embryo development could be the effective RNAi targets for controlling aphids and potentially other insect pests.展开更多
The recent development of gene transfer approaches in plants and animals has revealed that transgene can undergo silencing after integration in the genome. Host genes can also be silenced as a consequence of the prese...The recent development of gene transfer approaches in plants and animals has revealed that transgene can undergo silencing after integration in the genome. Host genes can also be silenced as a consequence of the presence of a homologous transgene. More and more investigations have demonstrated that double- stranded RNA can silence genes by triggering degradation of homologous RNA in the cytoplasm and by directing methylation of homologous nuclear DNA sequences. Analyses of Arabidopsis mutants and plant viral suppressors of silencing are unraveling RNA-silencing mechanisms and are assessing the role of methy- lation in transcriptional and posttranscriptional gene silencing. This review will focus on double-stranded RNA mediated mRNA degradation and gene inactivation in plants.展开更多
Molecular weaving is a powerful approach to make molecularly woven materials that have showed unprecedented characteristics and properties intrinsically distinct to those of non-woven materials.We here report a facile...Molecular weaving is a powerful approach to make molecularly woven materials that have showed unprecedented characteristics and properties intrinsically distinct to those of non-woven materials.We here report a facile and efficient approach for the synthesis of 2D woven supramolecular polymers by differentiated self-assembly through orthogonal noncovalent interactions.Importantly,the difference in binding strength of two orthogonal noncovalent interactions can be used to control the process of molecular weaving.Consequently,single-layered 2D woven supramolecular polymers were synthesized and fully characterized by various techniques.This study demonstrates a controllable method for molecular weaving,and will significantly hasten the development of molecularly woven materials.展开更多
Double-stranded RNA-mediated interference (RNAi), antisense oligonucleotides (ASO), and ribozymes have excellent specificity to their target oncogenic mRNA. They also seem to show great promise when it comes to treati...Double-stranded RNA-mediated interference (RNAi), antisense oligonucleotides (ASO), and ribozymes have excellent specificity to their target oncogenic mRNA. They also seem to show great promise when it comes to treating cancer. The problem is that RNAi, ASO, and ribozymes have poor stability and are constantly being degraded by nucleases. Researchers have made some efforts to increase antisense oligonucleotides’ stability by creating phospharimidate and Phosphorothioate. Currently, ribozymes, antisense oligonucleotides, and (RNAi) are the three main methods used to target RNA. These methods are currently undergoing clinical trials for the purpose of focusing on specific RNAs involved in disorders like cancer and neurodegeneration. In fact, ASOs that target amyotrophic lateral sclerosis and spinal muscular atrophy have produced promising results in clinical trials. The formation of chemical alterations that boost affinity and selectivity while reducing noxiousness owing to off-target impacts are two benefits of ASOs. Another benefit is increased affinity. With a focus on RNAi and ASOs, this review illustrated the main therapeutic strategies of RNA therapy now in use.展开更多
Post-embryonic development of insects is highly dependent on ecdysteroid hormone 20-hydroxyecdysone. Halloween gene spookier （spok, cyp307a2） has been documented to be involved in ecdysteroidogenesis in Drosophila m...Post-embryonic development of insects is highly dependent on ecdysteroid hormone 20-hydroxyecdysone. Halloween gene spookier （spok, cyp307a2） has been documented to be involved in ecdysteroidogenesis in Drosophila melanogaster and Bombyx mori. We describe here the cloning and characterization of Halloween gene spookier （Lsspok, Lscyp307a2） in the small brown planthopper Laodelphax striatellus, a hemipteran insect species. LsSPOK has three insect-conserved P450 motifs, that is, Helix-K, PERF motif and heme-binding domain. Temporal and spatial expression patterns of Lsspok were evaluated by quantitative polymerase chain reaction. Through the fouth- instar and the early fifth-instar stages, Lsspok showed two expression peaks in the second- and fifth-day fourth-instar nymphs, and two troughs in the first-day fourth and fifth in- stars. On day 5 of the fourth-instar nymphs, Lsspok clearly had a high transcript level in the thorax where prothoracic glands were located. Dietary introduction of double-stranded RNA of Lsspok in the nymph stage successfully knocked down the target gene, decreased expression level ofecdysone receptor （LsEcR） gene, caused nymphal lethality and delayed development. Ingestion of 20-hydroxyecdysone in Lsspok-dsRNA-exposed nymphs did not increase Lsspok expression level, but almost completely rescued the LsEcR mRNA level and relieved the negative effects on survival and development. Thus, our data suggest that the ecdysteroidogenic pathway is conserved in insects and LsSPOK is responsible for specific steps in ecdysteroidogenesis in L. striatellus.展开更多
RNA interference(RNAi)has emerged as a powerful technology for pest management.Previously,we have shown that plastid-mediated RNAi(PM-RNAi)can be utilized to control the Colorado potato beetle,an insect pest in the Ch...RNA interference(RNAi)has emerged as a powerful technology for pest management.Previously,we have shown that plastid-mediated RNAi(PM-RNAi)can be utilized to control the Colorado potato beetle,an insect pest in the Chrysomelidae family;however,whether this technology is suitable for controlling pests in the Coccinellidae remained unknown.The coccinellid 28-spotted potato ladybird(Henosepilachna vigintioctopunctata;HV)is a serious pest of solanaceous crops.In this study,we identified three efficient target genes(β-Actin,SRP54,and SNAP)for RNAi using in vitro double-stranded RNAs(dsRNAs)fed to HV,and found that dsRNAs targetingβ-Actin messenger RNA(dsACT)induced more potent RNAi than those targeting the other two genes.We next generated transplastomic and nuclear transgenic potato(Solanum tuberosum)plants expressing HV dsACT.Long dsACT stably accumulated to up to 0.7%of the total cellular RNA in the transplastomic plants,at least three orders of magnitude higher than in the nuclear transgenic plants.Notably,the transplastomic plants also exhibited a significantly stronger resistance to HV,killing all larvae within 6 d.Our data demonstrate the potential of PM-RNAi as an efficient pest control measure for HV,extending the application range of this technology to Coccinellidae pests.展开更多
Lupus nephritis is the most common visceral complication in the patients with systemic lupus erythematosus （SLE）.It was evident that the anti-dsDNA antibodies were closely related to lupus nephritis, as seen in pat...Lupus nephritis is the most common visceral complication in the patients with systemic lupus erythematosus （SLE）.It was evident that the anti-dsDNA antibodies were closely related to lupus nephritis, as seen in patients who had higher titers of serum anti-dsDNA antibodies had more severe renal lesions and even worse prognosis. So far it is still unknown how the dsDNA or anti-dsDNA antibody plays a role in the pathogenesis of lupus nephritis. The Trypanosoma equiperdum （TE） has uniformed dsDNA, no histone is found in both the cell nucleus and kinetonucleus. For this reason, TE became an optimal substrate used for detecting anti-dsDNA antibodies in SLE patients. It is proved that TE substrate is highly sensitive and specific. This reminds us to concern whether TE dsDNA share same SLE antigenic determinants with the pathogenic dsDNA in patients. Compared to the mammalian dsDNA, the kinetoplast DNA （kDNA） of TE has simpler molecular structure which makes it easier for purification. It offers us the possibility to establish lupus-like nephritis model by TE kDNA. We subcutaneously injected TE kDNA into normal mice. The result indicated lupus-like nephritis has been successfully induced by this simple and convenient protocol, which is useful to elucidate the particular role of dsDNA or anti-dsDNA antibody in lupus nephritis.展开更多
We reported a type of strong and highly directional non-covalent interactions based on the dimerization of single-stranded helix to double-stranded helix that can achieve supramolecular polymerization, giving rise to ...We reported a type of strong and highly directional non-covalent interactions based on the dimerization of single-stranded helix to double-stranded helix that can achieve supramolecular polymerization, giving rise to the formation of linear supramolecular polymers.展开更多
Sepsis, which refers to a systemic inflammatory response syndrome resulting from a microbial infection, represents the leading cause of death in intensive care units. The pathogenesis of sepsis remains poorly understo...Sepsis, which refers to a systemic inflammatory response syndrome resulting from a microbial infection, represents the leading cause of death in intensive care units. The pathogenesis of sepsis remains poorly understood although it is attributable to dysregulated immune responses orchestrated by innate immune cells that sequentially release early(e.g., tumor necrosis factor(TNF), interleukin-1(IL-1), and interferon-γ(IFN-γ) and late(e.g., high mobility group box 1(HMGB1)) pro-inflammatory mediators. As a ubiquitous nuclear protein, HMGB1 can be passively released from pathologically damaged cells, thereby converging infection and injury on commonly dysregulated inflammatory responses. We review evidence that supports extracellular HMGB1 as a late mediator of inflammatory diseases and discuss the potential of several Chinese herbal components as HMGB1-targeting therapies. We propose that it is important to develop strategies for specifically attenuating injury-elicited inflammatory responses without compromising the infection-mediated innate immunity for the clinical management of sepsis and other inflammatory diseases.展开更多
文摘Objective The aim of this review was to assess RNA interference (RNAi) and its possibility as a potential and powerful tool to develop highly specific double-stranded RNA ( dsRNA) or small interfering RNA (siRNA) based gene-silencing therapeutics. Data sources The data used in this review were obtained from the current RNAi-related research reports. Study selection dsRNA-mediated RNAi has recently emerged as a powerful reverse genetic tool to silence, gene expression in multiple organisms. The discovery that synthetic duplexes of 21 nucleotides siRNAs trigger gene-specific silencing in mammalian cells has further expanded the utility of RNAi in to the mammalian system. Data extraction The currently published papers reporting the discovery and mechanism of RNAi phenomena and application of RNAi on gene function in mammalian cells were included. Data synthesis Since the recent development of RNAi technology in the mammalian system, investigators have used RNAi to elucidate gene function, and to develop gene-based therapeutics by delivery exogenous siRNA or siRNA expressing vector. The general and sequence-specific inhibitory effects of RNAi that will be selective, long-term, and systemic to modulate gene targets mentioned in similar reports have caused much concern about its effectiveness in mammals and its eventual use as a therapeutic mordality. Conclusions It is certain that the ability of RNAi in mammals to silence specific genes, either when transfected directly as siRNAs or when generated from DNA vectors, will undoubtedly accelerate the study of gene function and might also be used as a potentially useful method to develop highly gene-specific therapeutic methods. It is also expected that RNAi might one day be used to treat human diseases.
基金This study was supported by the a grant from the National High-tech R&D Program(863 Program No.2015AA020310)National Natural Science Foundation of China(Nos.815300045,91959204,81930084,81871197,U1601222)+4 种基金the leading talents of Guangdong Province Program(No.00201516)a grant from the Key Research and Development Program of Guangdong Province(2019B020235003)Major basic research developmental project of the Natural Science Foundation of Guangdong Province(2014A030308018)Development and Reform Commission of Shenzhen Municipality(S2016004730009)Shenzhen“Sanming”Project of Medicine(SZSM201602102).
文摘With its high efficiency for site-specific genome editing and easy manipulation,the clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR associated protein 9(CAS9)system has become the most widely used gene editing technology in biomedical research.In addition,significant progress has been made for the clinical development of CRISPR/CAS9 based gene therapies of human diseases,several of which are entering clinical trials.Here we report that CAS9 protein can function as a genome mutator independent of any exogenous guide RNA(gRNA)in human cells,promoting genomic DNA double-stranded break(DSB)damage and genomic instability.CAS9 interacts with the KU86 subunit of the DNA-dependent protein kinase(DNA-PK)complex and disrupts the interaction between KU86 and its kinase subunit,leading to defective DNA-PK-dependent repair of DNA DSB damage via non-homologous end-joining(NHEJ)pathway.XCAS9 is a CAS9 variant with potentially higher fidelity and broader compatibility,and dCAS9 is a CAS9 variant without nuclease activity.We show that XCAS9 and dCAS9 also interact with KU86 and disrupt DNA DSB repair.Considering the critical roles of DNA-PK in maintaining genomic stability and the pleiotropic impact of DNA DSB damage responses on cellular proliferation and survival,our findings caution the interpretation of data involving CRISPR/CAS9-based gene editing and raise serious safety concerns of CRISPR/CAS9 system in clinical application.
基金This work was supported by USA National Institute of Diabetes and Digestive and Kidney Diseases(NIDDK)R01 DK093807.
文摘Endoplasmic reticulum(ER)stress occurs when ER homeostasis is perturbed with accumulation of unfolded/misfolded protein or calcium depletion.The unfolded protein response(UPR),comprising of inositol-requiring enzyme 1 a(IRE1 a),double-stranded RNA-dependent protein kinase(PKR)-like ER kinase(PERK)and activating transcription factor 6(ATF6)signaling pathways,is a protective cellular response activated by ER stress.However,UPR activation can also induce cell death upon persistent ER stress.The liver is susceptible to ER stress given its synthetic and other biological functions.Numerous studies from human liver samples and animal disease models have indicated a crucial role of ER stress and the UPR signaling pathways in the pathogenesis of liver diseases,including non-alcoholic fatty liver disease(NAFLD),alcoholic liver disease(ALD),alpha-1 antitrypsin(AAT)deficiency(AATD),cholestatic liver disease,drug-induced liver injury,ischemia/reperfusion(I/R)injury,viral hepatitis and hepatocel-lular carcinoma(HCC).Extensive investigations have demonstrated the potential underlying mechanisms of the induction of ER stress and the contribution of the UPR pathways during the development of the diseases.Moreover,ER stress and the UPR proteins and genes have become emerging therapeutic targets to treat liver diseases.
基金supported by the National Natural Science Foundation of China(32102297 and 32272634)。
文摘Plant-mediated RNA interference(RNAi)has emerged as a promising technology for insect control.The green peach aphid,Myzus persicae,feeds on over 400 species of host plants.Brassica napus(rape)is the second most important oilseed crop worldwide.Myzus persicae is highly reproductive and causes severe damage to the rape plants due to its quite flexible life cycle.In this study,we tested the RNAi effects of transgenic rape plants on M.persicae.By in vitro feeding M.persicae with artificial diets containing double-stranded RNAs(dsRNAs)targeting seven aphid genes,we identified a new gene encoding the partitioning-defective protein 6(Par6)as the most potent RNAi target.Tissue-and stage-expression analysis of Par6 suggested this gene is highly expressed in the embryo and adult stage of M.persicae.We next generated transgenic rape plants expressing ds Par6 by Agrobacteriummediated transformation and obtained nine independent transgenic lines.Compared to wild-type control plants,transgenic rape lines expressing ds Par6 showed strong resistance to M.persicae.Feeding assays revealed that feeding transgenic rape plants to M.persicae significantly decreased MpPar6 expression and survival rate and impaired fecundity.Furthermore,we showed that the resistance levels to M.persicae are positively correlated with ds Par6 expression levels in transgenic rape plants.Our study demonstrates that transgenic rape plants expressing ds Par6 are efficiently protected from M.persicae.Interfering with the genes involved in embryo development could be the effective RNAi targets for controlling aphids and potentially other insect pests.
文摘The recent development of gene transfer approaches in plants and animals has revealed that transgene can undergo silencing after integration in the genome. Host genes can also be silenced as a consequence of the presence of a homologous transgene. More and more investigations have demonstrated that double- stranded RNA can silence genes by triggering degradation of homologous RNA in the cytoplasm and by directing methylation of homologous nuclear DNA sequences. Analyses of Arabidopsis mutants and plant viral suppressors of silencing are unraveling RNA-silencing mechanisms and are assessing the role of methy- lation in transcriptional and posttranscriptional gene silencing. This review will focus on double-stranded RNA mediated mRNA degradation and gene inactivation in plants.
基金supported by the National Natural Science Foundation of China(Nos.92156012 and 22071078).
文摘Molecular weaving is a powerful approach to make molecularly woven materials that have showed unprecedented characteristics and properties intrinsically distinct to those of non-woven materials.We here report a facile and efficient approach for the synthesis of 2D woven supramolecular polymers by differentiated self-assembly through orthogonal noncovalent interactions.Importantly,the difference in binding strength of two orthogonal noncovalent interactions can be used to control the process of molecular weaving.Consequently,single-layered 2D woven supramolecular polymers were synthesized and fully characterized by various techniques.This study demonstrates a controllable method for molecular weaving,and will significantly hasten the development of molecularly woven materials.
文摘Double-stranded RNA-mediated interference (RNAi), antisense oligonucleotides (ASO), and ribozymes have excellent specificity to their target oncogenic mRNA. They also seem to show great promise when it comes to treating cancer. The problem is that RNAi, ASO, and ribozymes have poor stability and are constantly being degraded by nucleases. Researchers have made some efforts to increase antisense oligonucleotides’ stability by creating phospharimidate and Phosphorothioate. Currently, ribozymes, antisense oligonucleotides, and (RNAi) are the three main methods used to target RNA. These methods are currently undergoing clinical trials for the purpose of focusing on specific RNAs involved in disorders like cancer and neurodegeneration. In fact, ASOs that target amyotrophic lateral sclerosis and spinal muscular atrophy have produced promising results in clinical trials. The formation of chemical alterations that boost affinity and selectivity while reducing noxiousness owing to off-target impacts are two benefits of ASOs. Another benefit is increased affinity. With a focus on RNAi and ASOs, this review illustrated the main therapeutic strategies of RNA therapy now in use.
文摘Post-embryonic development of insects is highly dependent on ecdysteroid hormone 20-hydroxyecdysone. Halloween gene spookier （spok, cyp307a2） has been documented to be involved in ecdysteroidogenesis in Drosophila melanogaster and Bombyx mori. We describe here the cloning and characterization of Halloween gene spookier （Lsspok, Lscyp307a2） in the small brown planthopper Laodelphax striatellus, a hemipteran insect species. LsSPOK has three insect-conserved P450 motifs, that is, Helix-K, PERF motif and heme-binding domain. Temporal and spatial expression patterns of Lsspok were evaluated by quantitative polymerase chain reaction. Through the fouth- instar and the early fifth-instar stages, Lsspok showed two expression peaks in the second- and fifth-day fourth-instar nymphs, and two troughs in the first-day fourth and fifth in- stars. On day 5 of the fourth-instar nymphs, Lsspok clearly had a high transcript level in the thorax where prothoracic glands were located. Dietary introduction of double-stranded RNA of Lsspok in the nymph stage successfully knocked down the target gene, decreased expression level ofecdysone receptor （LsEcR） gene, caused nymphal lethality and delayed development. Ingestion of 20-hydroxyecdysone in Lsspok-dsRNA-exposed nymphs did not increase Lsspok expression level, but almost completely rescued the LsEcR mRNA level and relieved the negative effects on survival and development. Thus, our data suggest that the ecdysteroidogenic pathway is conserved in insects and LsSPOK is responsible for specific steps in ecdysteroidogenesis in L. striatellus.
基金supported by grants from the Natural Science Foundation of Hubei Province(2020CFA012)the National Natural Science Foundation of China(32271912)to J.Z。
文摘RNA interference(RNAi)has emerged as a powerful technology for pest management.Previously,we have shown that plastid-mediated RNAi(PM-RNAi)can be utilized to control the Colorado potato beetle,an insect pest in the Chrysomelidae family;however,whether this technology is suitable for controlling pests in the Coccinellidae remained unknown.The coccinellid 28-spotted potato ladybird(Henosepilachna vigintioctopunctata;HV)is a serious pest of solanaceous crops.In this study,we identified three efficient target genes(β-Actin,SRP54,and SNAP)for RNAi using in vitro double-stranded RNAs(dsRNAs)fed to HV,and found that dsRNAs targetingβ-Actin messenger RNA(dsACT)induced more potent RNAi than those targeting the other two genes.We next generated transplastomic and nuclear transgenic potato(Solanum tuberosum)plants expressing HV dsACT.Long dsACT stably accumulated to up to 0.7%of the total cellular RNA in the transplastomic plants,at least three orders of magnitude higher than in the nuclear transgenic plants.Notably,the transplastomic plants also exhibited a significantly stronger resistance to HV,killing all larvae within 6 d.Our data demonstrate the potential of PM-RNAi as an efficient pest control measure for HV,extending the application range of this technology to Coccinellidae pests.
文摘Lupus nephritis is the most common visceral complication in the patients with systemic lupus erythematosus （SLE）.It was evident that the anti-dsDNA antibodies were closely related to lupus nephritis, as seen in patients who had higher titers of serum anti-dsDNA antibodies had more severe renal lesions and even worse prognosis. So far it is still unknown how the dsDNA or anti-dsDNA antibody plays a role in the pathogenesis of lupus nephritis. The Trypanosoma equiperdum （TE） has uniformed dsDNA, no histone is found in both the cell nucleus and kinetonucleus. For this reason, TE became an optimal substrate used for detecting anti-dsDNA antibodies in SLE patients. It is proved that TE substrate is highly sensitive and specific. This reminds us to concern whether TE dsDNA share same SLE antigenic determinants with the pathogenic dsDNA in patients. Compared to the mammalian dsDNA, the kinetoplast DNA （kDNA） of TE has simpler molecular structure which makes it easier for purification. It offers us the possibility to establish lupus-like nephritis model by TE kDNA. We subcutaneously injected TE kDNA into normal mice. The result indicated lupus-like nephritis has been successfully induced by this simple and convenient protocol, which is useful to elucidate the particular role of dsDNA or anti-dsDNA antibody in lupus nephritis.
基金financially supported by the National Natural Science Foundation of China(Nos.21574054,21722403,and 21420102007)
文摘We reported a type of strong and highly directional non-covalent interactions based on the dimerization of single-stranded helix to double-stranded helix that can achieve supramolecular polymerization, giving rise to the formation of linear supramolecular polymers.
基金supported by grants from the National Center of Complementary and Alternative Medicine (NCCAM, R01AT005076)the National Institute of General Medical Sciences (NIGMS, R01GM063075)
文摘Sepsis, which refers to a systemic inflammatory response syndrome resulting from a microbial infection, represents the leading cause of death in intensive care units. The pathogenesis of sepsis remains poorly understood although it is attributable to dysregulated immune responses orchestrated by innate immune cells that sequentially release early(e.g., tumor necrosis factor(TNF), interleukin-1(IL-1), and interferon-γ(IFN-γ) and late(e.g., high mobility group box 1(HMGB1)) pro-inflammatory mediators. As a ubiquitous nuclear protein, HMGB1 can be passively released from pathologically damaged cells, thereby converging infection and injury on commonly dysregulated inflammatory responses. We review evidence that supports extracellular HMGB1 as a late mediator of inflammatory diseases and discuss the potential of several Chinese herbal components as HMGB1-targeting therapies. We propose that it is important to develop strategies for specifically attenuating injury-elicited inflammatory responses without compromising the infection-mediated innate immunity for the clinical management of sepsis and other inflammatory diseases.
