Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emerge...Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.展开更多
It is urgent to develop catalysts with application potential for oxidative coupling of methane(OCM)at relatively lower temperature.Herein,three-dimensional ordered macro porous(3 DOM)La_(2-x)Sr_(x)Ce_(2-y)CayO_(7-δ)(...It is urgent to develop catalysts with application potential for oxidative coupling of methane(OCM)at relatively lower temperature.Herein,three-dimensional ordered macro porous(3 DOM)La_(2-x)Sr_(x)Ce_(2-y)CayO_(7-δ)(A_(2)B_(2)O_(7)-type)catalysts with disordered defective cubic fluorite phased structure were successfully prepared by a colloidal crystal template method.3DOM structure promotes the accessibility of the gaseous reactants(O2and CH4)to the active sites.The co-doping of Ca and Sr ions in La_(2-x)Sr_(x)Ce_(2-y)CayO_(7-δ)catalysts improved the formation of oxygen vacancies,thereby leading to increased density of surface-active oxygen species(O_(2)^(-))for the activation of CH4and the formation of C2products(C2H6and C2H4).3DOM La_(2-x)Sr_(x)Ce_(2-y)CayO_(7-δ)catalysts exhibit high catalytic activity for OCM at low temperature.3DOM La1.7Sr0.3Ce1.7Ca0.3O7-δcatalyst with the highest density of O_(2)^(-)species exhibited the highest catalytic activity for low-temperature OCM,i.e.,its CH4conversion,selectivity and yield of C2products at 650℃are 32.2%,66.1%and 21.3%,respectively.The mechanism was proposed that the increase in surface oxygen vacancies induced by the co-doping of Ca and Sr ions boosts the key step of C-H bond breaking and C-C bond coupling in catalyzing low-temperature OCM.It is meaningful for the development of the low-temperature and high-efficient catalysts for OCM reaction in practical application.展开更多
The spontaneous bursts of electrical activity in the developing auditory system are derived from the periodic release of adenosine triphosphate(ATP)by supporting cells in the Kölliker’s organ.However,the mechani...The spontaneous bursts of electrical activity in the developing auditory system are derived from the periodic release of adenosine triphosphate(ATP)by supporting cells in the Kölliker’s organ.However,the mechanisms responsible for initiating spontaneous ATP release have not been determined.Our previous study revealed that telomerase reverse transcriptase(TERT)is expressed in the basilar membrane during the first postnatal week.Its role in cochlear development remains unclear.In this study,we investigated the expression and role of TERT in postnatal cochlea supporting cells.Our results revealed that in postnatal cochlear Kölliker’s organ supporting cells,TERT shifts from the nucleus into the cytoplasm over time.We found that the TERT translocation tendency in postnatal cochlear supporting cells in vitro coincided with that observed in vivo.Further analysis showed that TERT in the cytoplasm was mainly located in mitochondria in the absence of oxidative stress or apoptosis,suggesting that TERT in mitochondria plays roles other than antioxidant or anti-apoptotic functions.We observed increased ATP synthesis,release and activation of purine signaling systems in supporting cells during the first 10 postnatal days.The phenomenon that TERT translocation coincided with changes in ATP synthesis,release and activation of the purine signaling system in postnatal cochlear supporting cells suggested that TERT may be involved in regulating ATP release and activation of the purine signaling system.Our study provides a new research direction for exploring the spontaneous electrical activity of the cochlea during the early postnatal period.展开更多
Verticillium longisporum(Vl43)is a soilborne hemibiotrophic fungal pathogen causing stem striping on oilseed rape(OSR)and severe yield losses.Breeding for resistant varieties is the most promising approach to control ...Verticillium longisporum(Vl43)is a soilborne hemibiotrophic fungal pathogen causing stem striping on oilseed rape(OSR)and severe yield losses.Breeding for resistant varieties is the most promising approach to control this disease.Here,we report the identification of Hva22c as a novel susceptibility factor and its potential for improving OSR resistance.Hva22c is a member of the Hva22 gene family,originally described for barley(Hordeum vulgare).Several Hva22 members have been located at the endoplasmic reticulum.Hva22c is up-regulated in response to Vl43 in both Arabidopsis and OSR.We demonstrate that knock-out of Hva22c in OSR by CRISPR/Cas9 and its homolog in Arabidopsis by T-DNA insertion reduced plants’susceptibility to Vl43 infection and impaired the development of disease symptoms.To understand the underlying mechanism,we analysed transcriptomic data from infected and non-infected roots of hva22c knock-out and wild type plants.We identified a homozygous mutant with frame-shifts in all four BnHva22c loci displaying a vastly altered transcriptional landscape at 6 dpi.Significantly,a large set of genes was suppressed under mock conditions including genes related to the endomembrane systems.Among the up-regulated genes we found several defense-related and phytohormone-responsive genes when comparing mutant to the wild type.These results demonstrate that Hva22c is functionally required for a fully compatible plant-fungus interaction.Its loss of function reduces plant susceptibility,most likely due to endoplasmatic reticulum and Golgi dysfunction accompanied by additionally activated defense responses.These findings can help improve OSR resistance to V.longisporum infection.展开更多
文摘Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.
基金supported by the National Key Research and Development Program of China(Nos.2022YFB3504100,2022YFB3506200)the National Natural Science Foundation of China(Nos.22208373,22376217)+1 种基金the Beijing Nova Program(No.20220484215)the Science Foundation of China University of Petroleum,Beijing(No.2462023YJRC030)。
文摘It is urgent to develop catalysts with application potential for oxidative coupling of methane(OCM)at relatively lower temperature.Herein,three-dimensional ordered macro porous(3 DOM)La_(2-x)Sr_(x)Ce_(2-y)CayO_(7-δ)(A_(2)B_(2)O_(7)-type)catalysts with disordered defective cubic fluorite phased structure were successfully prepared by a colloidal crystal template method.3DOM structure promotes the accessibility of the gaseous reactants(O2and CH4)to the active sites.The co-doping of Ca and Sr ions in La_(2-x)Sr_(x)Ce_(2-y)CayO_(7-δ)catalysts improved the formation of oxygen vacancies,thereby leading to increased density of surface-active oxygen species(O_(2)^(-))for the activation of CH4and the formation of C2products(C2H6and C2H4).3DOM La_(2-x)Sr_(x)Ce_(2-y)CayO_(7-δ)catalysts exhibit high catalytic activity for OCM at low temperature.3DOM La1.7Sr0.3Ce1.7Ca0.3O7-δcatalyst with the highest density of O_(2)^(-)species exhibited the highest catalytic activity for low-temperature OCM,i.e.,its CH4conversion,selectivity and yield of C2products at 650℃are 32.2%,66.1%and 21.3%,respectively.The mechanism was proposed that the increase in surface oxygen vacancies induced by the co-doping of Ca and Sr ions boosts the key step of C-H bond breaking and C-C bond coupling in catalyzing low-temperature OCM.It is meaningful for the development of the low-temperature and high-efficient catalysts for OCM reaction in practical application.
基金supported by the National Natural Science Foundation of China,Nos.81870732(to DZ),82171161(to DZ),81900933(to YS),and 82000978(to ZL).
文摘The spontaneous bursts of electrical activity in the developing auditory system are derived from the periodic release of adenosine triphosphate(ATP)by supporting cells in the Kölliker’s organ.However,the mechanisms responsible for initiating spontaneous ATP release have not been determined.Our previous study revealed that telomerase reverse transcriptase(TERT)is expressed in the basilar membrane during the first postnatal week.Its role in cochlear development remains unclear.In this study,we investigated the expression and role of TERT in postnatal cochlea supporting cells.Our results revealed that in postnatal cochlear Kölliker’s organ supporting cells,TERT shifts from the nucleus into the cytoplasm over time.We found that the TERT translocation tendency in postnatal cochlear supporting cells in vitro coincided with that observed in vivo.Further analysis showed that TERT in the cytoplasm was mainly located in mitochondria in the absence of oxidative stress or apoptosis,suggesting that TERT in mitochondria plays roles other than antioxidant or anti-apoptotic functions.We observed increased ATP synthesis,release and activation of purine signaling systems in supporting cells during the first 10 postnatal days.The phenomenon that TERT translocation coincided with changes in ATP synthesis,release and activation of the purine signaling system in postnatal cochlear supporting cells suggested that TERT may be involved in regulating ATP release and activation of the purine signaling system.Our study provides a new research direction for exploring the spontaneous electrical activity of the cochlea during the early postnatal period.
基金supported by Bundesministerium für Bildung und Forschung(BMBF,Grant no.031B0033C)Bundesministerium für Ern?hrung und Landwirtschaft(BMEL,Grant no.22006516)Bundesanstalt für Landwirtschaft and Ern?hrung(BLE,Grant No.2814IP004)。
文摘Verticillium longisporum(Vl43)is a soilborne hemibiotrophic fungal pathogen causing stem striping on oilseed rape(OSR)and severe yield losses.Breeding for resistant varieties is the most promising approach to control this disease.Here,we report the identification of Hva22c as a novel susceptibility factor and its potential for improving OSR resistance.Hva22c is a member of the Hva22 gene family,originally described for barley(Hordeum vulgare).Several Hva22 members have been located at the endoplasmic reticulum.Hva22c is up-regulated in response to Vl43 in both Arabidopsis and OSR.We demonstrate that knock-out of Hva22c in OSR by CRISPR/Cas9 and its homolog in Arabidopsis by T-DNA insertion reduced plants’susceptibility to Vl43 infection and impaired the development of disease symptoms.To understand the underlying mechanism,we analysed transcriptomic data from infected and non-infected roots of hva22c knock-out and wild type plants.We identified a homozygous mutant with frame-shifts in all four BnHva22c loci displaying a vastly altered transcriptional landscape at 6 dpi.Significantly,a large set of genes was suppressed under mock conditions including genes related to the endomembrane systems.Among the up-regulated genes we found several defense-related and phytohormone-responsive genes when comparing mutant to the wild type.These results demonstrate that Hva22c is functionally required for a fully compatible plant-fungus interaction.Its loss of function reduces plant susceptibility,most likely due to endoplasmatic reticulum and Golgi dysfunction accompanied by additionally activated defense responses.These findings can help improve OSR resistance to V.longisporum infection.
