Background and Aims:Hepatitis B virus(HBV)reactivation is commonly observed in individuals with chronic HBV infection undergoing antineoplastic drug therapy.Paclitaxel(PTX)treatment has been identified as a potential ...Background and Aims:Hepatitis B virus(HBV)reactivation is commonly observed in individuals with chronic HBV infection undergoing antineoplastic drug therapy.Paclitaxel(PTX)treatment has been identified as a potential trigger for HBV reactivation.This study aimed to uncover the mechanisms of PTX-induced HBV reactivation in vitro and in vivo,which may inform new strategies for HBV antiviral treatment.Methods:The impact of PTX on HBV replication was assessed through various methods including enzyme-linked immunosorbent assay,dual-luciferase reporter assay,quantitative real-time PCR,chromatin immunoprecipitation,and immunohistochemical staining.Transcriptome sequencing and 16S rRNA sequencing were employed to assess alterations in the transcriptome and microbial diversity in PTX-treated HBV transgenic mice.Results:PTX enhanced the levels of HBV 3.5-kb mRNA,HBV DNA,HBeAg,and HBsAg both in vitro and in vivo.PTX also promoted the activity of the HBV core promoter and transcription factor AP-1.Inhibition of AP-1 gene expression markedly suppressed PTX-induced HBV reactivation.Transcriptome sequencing revealed that PTX activated the immune-related signaling networks such as IL-17,NF-κB,and MAPK signaling pathways,with the pivotal common key molecule being AP-1.The 16S rRNA sequencing revealed that PTX induced dysbiosis of gut microbiota.Conclusions:PTX-induced HBV reactivation was likely a synergistic outcome of immune suppression and direct stimulation of HBV replication through the enhancement of HBV core promoter activity mediated by the transcription factor AP-1.These findings propose a novel molecular mechanism,underscoring the critical role of AP-1 in PTX-induced HBV reactivation.展开更多
The application of the valuable natural product thaxtomin A,a potent bioherbicide from the potato scab pathogenic Streptomyces strains,has been greatly hindered by the low yields from its native producers.Here,we deve...The application of the valuable natural product thaxtomin A,a potent bioherbicide from the potato scab pathogenic Streptomyces strains,has been greatly hindered by the low yields from its native producers.Here,we developed an orthogonal transcription system,leveraging extra-cytoplasmic function(ECF)sigma(σ)factor 17(ECF17)and its cognate promoter Pecf17,to express the thaxtomin gene cluster and improve the production of thaxtomin A.The minimal Pecf17 promoter was determined,and a Pecf17 promoter library with a wide range of strengths was constructed.Furthermore,a cumate inducible system was developed for precise temporal control of the ECF17 transcription system in S.venezuelae ISP5230.Theoretically,the switchable ECF17 transcription system could reduce the unwanted influences from host and alleviate the burdens introduced by overexpression of heterologous genes.The yield of thaxtomin A was significantly improved to 202.1±15.3μg/mL using the switchable ECF17 transcription system for heterologous expression of the thaxtomin gene cluster in S.venezuelae ISP5230.Besides,the applicability of this transcription system was also tested in Streptomyces albus J1074,and the titer of thaxtomin A was raised to as high as 239.3±30.6μg/mL.Therefore,the inducible ECF17 transcription system could serve as a complement of the generally used transcription systems based on strong native constitutive promoters and housekeepingσfactors for the heterologous expression of valuable products in diverse Streptomyces hosts.展开更多
Well-established targeted technologies to engi- neer genomes such as zinc-finger nuclease-based editing （ZFN）, transcription activator-like effector nuclease-based editing （TALEN）, and clustered regularly interspa...Well-established targeted technologies to engi- neer genomes such as zinc-finger nuclease-based editing （ZFN）, transcription activator-like effector nuclease-based editing （TALEN）, and clustered regularly interspaced short palindromic repeats and associated protein system-based editing （CRISPR/Cas） are proving to advance basic and applied research in numerous plant species. Compared with systems using ZFNs and TALENs, the most recently developed CRISPR/Cas system is more efficient due to its use of an RNA-guided nuclease to generate double-strand DNA breaks. To accelerate the applications of these technologies, we provide here a detailed overview of these systems, highlight the strengths and weaknesses of each, summarize research advances made with these technologies in model and crop plants, and discuss their applications in plant functional genomics. Such targeted approaches for genetically modifying plants will benefit agricultural production in the future.展开更多
为了解决传统的荧光光谱采集系统与光探测磁共振(optically detected magnetic resonance,后文简称ODMR)光谱采集系统存在的搭建繁琐、检测样品聚焦精度较低、采集系统之间转换困难以及ODMR光谱采集信号信噪比和采集精度较低的问题,设...为了解决传统的荧光光谱采集系统与光探测磁共振(optically detected magnetic resonance,后文简称ODMR)光谱采集系统存在的搭建繁琐、检测样品聚焦精度较低、采集系统之间转换困难以及ODMR光谱采集信号信噪比和采集精度较低的问题,设计了基于光纤传感的荧光采集与ODMR光谱采集转换系统。通过光纤将激发光源电路、微波传感天线、光纤传感器、显微聚焦光路、PD(photodetector)放大电路、信号处理模块以及荧光光谱仪各模块进行耦合集成,为信号处理的软件提供硬件部分支持。在软件部分,通过开源程序编写实现信号数据处理以及光谱成像功能,利用PD放大电路对数据进行初步处理之后,在软件部分通过信号处理模块进行进一步处理,数据以图谱形式呈现,并且最终磁灵敏度达到0.51 nT/Hz^(1/2)。展开更多
As a macronutrient,Phosphorus(P)takes many roles in plant growth and development.It should be significant to explore the molecular mechanism of low-phosphorus stress response of plants.Phosphate starvation response(PH...As a macronutrient,Phosphorus(P)takes many roles in plant growth and development.It should be significant to explore the molecular mechanism of low-phosphorus stress response of plants.Phosphate starvation response(PHR)transcription factors play important roles in response to phosphorus deficiency stress in plants.In this study,we isolated a gene related to the plant phosphorus signaling system from the acid-soil-resistant centipedegrass(Eremochloa ophiuroides[Munro]Hack.),termed EoPHR2.The subcellular localization of EoPHR2 protein was observed to be nuclear located.The expression patterns of EoPHR2 in different tissues and Al/Pi-stress conditions were analyzed by qRT-PCR,they suggested a potential role in response to the multiple-stress under acid soil adversity.Based on the functional identification through transgenic plants,we found that(1)EoPHR2 is involved in the Pi-signaling pathway,and(2)overexpression of EoPHR2 mimics Pi-starvation signalling resulting on enhanced roots whether under Pi-deficiency stress or not.In conclusion,EoPHR2 transcription factor plays a role in response to the multiple stresses under acid soil conditions,improving the low-phosphorus stress resistance of Eremochloa ophiuroides.展开更多
基金This research received financial support from various sources including the Innovation and Development Joint Fund of Chongqing Natural Science Foundation(Grant number CSTB2023NSCQ-LZX0099)Chongqing Science and Health Joint Medical High-end Talent Project(Grant No.2022GDRC012)+3 种基金Chongqing Biomedical R&D Major Special Project(Grant No.CSTB2022TIAD-STX0013)Science and Technology Research Program of Chongqing Municipal Education Commission(Grant No.KJZD-K202100402)CQMU Program for Youth Innovation in Future Medicine(Grant No.W0073)the Southwest Medical University and Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University Joint Project(Grant No.2020XYLH-021).
文摘Background and Aims:Hepatitis B virus(HBV)reactivation is commonly observed in individuals with chronic HBV infection undergoing antineoplastic drug therapy.Paclitaxel(PTX)treatment has been identified as a potential trigger for HBV reactivation.This study aimed to uncover the mechanisms of PTX-induced HBV reactivation in vitro and in vivo,which may inform new strategies for HBV antiviral treatment.Methods:The impact of PTX on HBV replication was assessed through various methods including enzyme-linked immunosorbent assay,dual-luciferase reporter assay,quantitative real-time PCR,chromatin immunoprecipitation,and immunohistochemical staining.Transcriptome sequencing and 16S rRNA sequencing were employed to assess alterations in the transcriptome and microbial diversity in PTX-treated HBV transgenic mice.Results:PTX enhanced the levels of HBV 3.5-kb mRNA,HBV DNA,HBeAg,and HBsAg both in vitro and in vivo.PTX also promoted the activity of the HBV core promoter and transcription factor AP-1.Inhibition of AP-1 gene expression markedly suppressed PTX-induced HBV reactivation.Transcriptome sequencing revealed that PTX activated the immune-related signaling networks such as IL-17,NF-κB,and MAPK signaling pathways,with the pivotal common key molecule being AP-1.The 16S rRNA sequencing revealed that PTX induced dysbiosis of gut microbiota.Conclusions:PTX-induced HBV reactivation was likely a synergistic outcome of immune suppression and direct stimulation of HBV replication through the enhancement of HBV core promoter activity mediated by the transcription factor AP-1.These findings propose a novel molecular mechanism,underscoring the critical role of AP-1 in PTX-induced HBV reactivation.
基金supported by the National Key Research and Development Program of China[2018YFA0900700]Natural Science Foundation of China[31900901 and 31500069]+1 种基金the Chinese Academy of Sciences[No.QYZDB-SSW-SMC050,No.XDPB1801 of the Strategic Priority Research Program]the Shenzhen Science and Technology Innovation Committee[No.JCYJ20180507182241844,JCHZ20200005,DWKF20190009].
文摘The application of the valuable natural product thaxtomin A,a potent bioherbicide from the potato scab pathogenic Streptomyces strains,has been greatly hindered by the low yields from its native producers.Here,we developed an orthogonal transcription system,leveraging extra-cytoplasmic function(ECF)sigma(σ)factor 17(ECF17)and its cognate promoter Pecf17,to express the thaxtomin gene cluster and improve the production of thaxtomin A.The minimal Pecf17 promoter was determined,and a Pecf17 promoter library with a wide range of strengths was constructed.Furthermore,a cumate inducible system was developed for precise temporal control of the ECF17 transcription system in S.venezuelae ISP5230.Theoretically,the switchable ECF17 transcription system could reduce the unwanted influences from host and alleviate the burdens introduced by overexpression of heterologous genes.The yield of thaxtomin A was significantly improved to 202.1±15.3μg/mL using the switchable ECF17 transcription system for heterologous expression of the thaxtomin gene cluster in S.venezuelae ISP5230.Besides,the applicability of this transcription system was also tested in Streptomyces albus J1074,and the titer of thaxtomin A was raised to as high as 239.3±30.6μg/mL.Therefore,the inducible ECF17 transcription system could serve as a complement of the generally used transcription systems based on strong native constitutive promoters and housekeepingσfactors for the heterologous expression of valuable products in diverse Streptomyces hosts.
文摘Well-established targeted technologies to engi- neer genomes such as zinc-finger nuclease-based editing （ZFN）, transcription activator-like effector nuclease-based editing （TALEN）, and clustered regularly interspaced short palindromic repeats and associated protein system-based editing （CRISPR/Cas） are proving to advance basic and applied research in numerous plant species. Compared with systems using ZFNs and TALENs, the most recently developed CRISPR/Cas system is more efficient due to its use of an RNA-guided nuclease to generate double-strand DNA breaks. To accelerate the applications of these technologies, we provide here a detailed overview of these systems, highlight the strengths and weaknesses of each, summarize research advances made with these technologies in model and crop plants, and discuss their applications in plant functional genomics. Such targeted approaches for genetically modifying plants will benefit agricultural production in the future.
文摘为了解决传统的荧光光谱采集系统与光探测磁共振(optically detected magnetic resonance,后文简称ODMR)光谱采集系统存在的搭建繁琐、检测样品聚焦精度较低、采集系统之间转换困难以及ODMR光谱采集信号信噪比和采集精度较低的问题,设计了基于光纤传感的荧光采集与ODMR光谱采集转换系统。通过光纤将激发光源电路、微波传感天线、光纤传感器、显微聚焦光路、PD(photodetector)放大电路、信号处理模块以及荧光光谱仪各模块进行耦合集成,为信号处理的软件提供硬件部分支持。在软件部分,通过开源程序编写实现信号数据处理以及光谱成像功能,利用PD放大电路对数据进行初步处理之后,在软件部分通过信号处理模块进行进一步处理,数据以图谱形式呈现,并且最终磁灵敏度达到0.51 nT/Hz^(1/2)。
基金This work was supported by the National Natural Science Foundation of China(Grant No.31902046)the National Natural Science Foundation of China(Grant No.32072608)+1 种基金the National Natural Science Foundation of China(Grant No.31902060)the Natural Science Foundation of Jiangsu Province,China(Grant No.BK20180315),and the Foundation of Jiangsu Key Laboratory for the Research and Utilization of Plant Resources(Institute of Botany,Jiangsu Province and Chinese Academy of Sciences).
文摘As a macronutrient,Phosphorus(P)takes many roles in plant growth and development.It should be significant to explore the molecular mechanism of low-phosphorus stress response of plants.Phosphate starvation response(PHR)transcription factors play important roles in response to phosphorus deficiency stress in plants.In this study,we isolated a gene related to the plant phosphorus signaling system from the acid-soil-resistant centipedegrass(Eremochloa ophiuroides[Munro]Hack.),termed EoPHR2.The subcellular localization of EoPHR2 protein was observed to be nuclear located.The expression patterns of EoPHR2 in different tissues and Al/Pi-stress conditions were analyzed by qRT-PCR,they suggested a potential role in response to the multiple-stress under acid soil adversity.Based on the functional identification through transgenic plants,we found that(1)EoPHR2 is involved in the Pi-signaling pathway,and(2)overexpression of EoPHR2 mimics Pi-starvation signalling resulting on enhanced roots whether under Pi-deficiency stress or not.In conclusion,EoPHR2 transcription factor plays a role in response to the multiple stresses under acid soil conditions,improving the low-phosphorus stress resistance of Eremochloa ophiuroides.
