Injuries to the central nervous system(CNS)such as stroke,brain,and spinal cord trauma often result in permanent disabilities because adult CNS neurons only exhibit limited axon regeneration.The brain has a surprising...Injuries to the central nervous system(CNS)such as stroke,brain,and spinal cord trauma often result in permanent disabilities because adult CNS neurons only exhibit limited axon regeneration.The brain has a surprising intrinsic capability of recovering itself after injury.However,the hostile extrinsic microenvironment significantly hinders axon regeneration.Recent advances have indicated that the inactivation of intrinsic regenerative pathways plays a pivotal role in the failure of most adult CNS neuronal regeneration.Particularly,substantial evidence has convincingly demonstrated that the mechanistic target of rapamycin(mTOR)signaling is one of the most crucial intrinsic regenerative pathways that drive axonal regeneration and sprouting in various CNS injuries.In this review,we will discuss the recent findings and highlight the critical roles of mTOR pathway in axon regeneration in different types of CNS injury.Importantly,we will demonstrate that the reactivation of this regenerative pathway can be achieved by blocking the key mTOR signaling components such as phosphatase and tensin homolog(PTEN).Given that multiple mTOR signaling components are endogenous inhibitory factors of this pathway,we will discuss the promising potential of RNA-based therapeutics which are particularly suitable for this purpose,and the fact that they have attracted substantial attention recently after the success of coronavirus disease 2019 vaccination.To specifically tackle the blood-brain barrier issue,we will review the current technology to deliver these RNA therapeutics into the brain with a focus on nanoparticle technology.We will propose the clinical application of these RNA-mediated therapies in combination with the brain-targeted drug delivery approach against mTOR signaling components as an effective and feasible therapeutic strategy aiming to enhance axonal regeneration for functional recovery after CNS injury.展开更多
Modern agribusiness plays a vital role in safeguarding and improving the production,quality,and quantity of food,feed,fiber,and fuel.Growing concerns over the impact of chemical pesticides on health and the environmen...Modern agribusiness plays a vital role in safeguarding and improving the production,quality,and quantity of food,feed,fiber,and fuel.Growing concerns over the impact of chemical pesticides on health and the environment have stimulated the industry to search for alternative and greener solutions.Over the last years,the RNA interference(RNAi)process has been identified as a very promising new approach to complement the arsenal of foliar spray,soil,or seed treatments applied as chemical and biological pest control agents,and of plant-incorporated protectants(PIPs).RNA-based active ingredients(AIs)possess a unique mode of action and can be implemented via both genetic modification(GM)and biocontrol approaches.RNA-based AIs promise to deliver the selectivity and sustainability desired in future crop protection agents.This is due to their utilization of a natural process to exert control and their high level of selectivity,which leads to reduced risk for non-target organisms(NTOs).This review discusses the advantages and limitations of RNA-based solutions in crop protection and recent research progress toward RNA-based biocontrols against the Colorado potato beetle(CPB),corn rootworm(CRW),and soy stink bug(SSB).Many challenges still exist on the road to the implementation of a broad range of RNA-based products and their widespread use and application.Despite these challenges,it can be expected that RNA-based AIs will become valuable new tools complementing the current arsenal of crop-protection solutions.展开更多
Aim:Our study aimed to explore the prognostic predictive potential of a novel RNA-based signature called ImmuneScore in advanced non-squamous NSCLC patients receiving combined immune checkpoint inhibitor(ICI)treatment...Aim:Our study aimed to explore the prognostic predictive potential of a novel RNA-based signature called ImmuneScore in advanced non-squamous NSCLC patients receiving combined immune checkpoint inhibitor(ICI)treatment and chemotherapy.Methods:RNA-sequencing data of 113 patients screened out from ORIENT-11 trial were retrospectively analyzed.ImmuneScore was calculated by the ESTIMATE algorithm.The association of ImmuneScore with early tumor progression,progression-free survival(PFS),and overall survival(OS)was analyzed using chi-square test,Cox regression test,and log-rank test.Receiver operating characteristic(ROC)curves were generated,with higher values of area under the ROC curves(AUCs)indicating better prediction ability.Results:ImmuneScore was negatively correlated with early tumor progression rate(4.3%vs.18.6%,P=0.013)while positively correlated with PFS(HR=0.29,95%CI:0.16-0.53,P<0.001)and OS(HR=0.32,95%CI:0.18-0.58,P<0.001),demonstrating higher AUCs than that of Programmed death-ligand 1(PD-L1)tumor proportion score(TPS)(early tumor progression:0.64 vs.0.68;PFS:0.67 vs.0.58;OS:0.73 vs.0.63).Nomograms integrating ImmuneScore and other significant variables(age and T-stage for PFS,gender and T-stage for OS)yielded good performance in PFS and OS prediction.Conclusion:ImmuneScore serves as a novel RNA-based prognostic signature superior to PD-L1 in advanced non-squamous NSCLC patients receiving chemotherapy combined with ICI therapy.Higher ImmuneScore indicates lower early tumor progression rate,longer PFS,and longer OS.展开更多
Liver cancer is a heterogeneous disease and is one of the leading causes of cancer deaths worldwide.Hepatocellular carcinoma, comprising approximately 90% of cases, presents a formidable challenge with a lessthan 20% ...Liver cancer is a heterogeneous disease and is one of the leading causes of cancer deaths worldwide.Hepatocellular carcinoma, comprising approximately 90% of cases, presents a formidable challenge with a lessthan 20% 5-year survival rate despite recent treatment advancements. The impediments of drug resistance andoff-target effects underscore the critical need for innovative and efficacious therapies. Harnessing the growingunderstanding of RNA function offers a promising avenue to address previously "undruggable" proteins,transcripts, and genes. Various RNAs demonstrate the potential to selectively act on these targets, expanding thescope of therapeutic interventions. With diverse regulatory roles in cancer pathways, RNAs emerge as valuabletargets and tools for anticancer therapy development. This article provides an in-depth exploration of currentRNA-based therapies, elucidates their mechanisms of action, and discusses their combinations withchemo-/immunotherapies in clinical trials for hepatocellular carcinoma.展开更多
RNA-based nanomedicines encompass a range of therapeutic approaches that utilize RNA molecules or molecules that target RNAs for the treatment or prevention of diseases.These include antisense oligonucleotides(ASOs),s...RNA-based nanomedicines encompass a range of therapeutic approaches that utilize RNA molecules or molecules that target RNAs for the treatment or prevention of diseases.These include antisense oligonucleotides(ASOs),small interfering RNAs(siRNAs),endogenous microRNAs(miRNAs),messenger RNAs(mRNAs),clustered regularly interspersed short palindromic repeats-associated protein 9(CRISPR/Cas9),single guide RNAs(sgRNAs),as well as RNA aptamers.These therapeutic agents exert their effects through various mechanisms such as gene inhibition,addition,replacement,and editing.The advancement of RNA biology and the field of RNA therapy has paved the way for the development and utilization of RNA-based nanomedicine in human healthcare.One remarkable example of RNA-based nanomedicine is the mRNA-based vaccines including mRNA-1273(Moderna)and BNT162b2(Pfizer/BioNTech)that have been successfully employed in response to the coronavirus disease 2019(COVID-19)pandemic.This review aims to highlight the advantages of RNA-based nanomedicines,provides an overview of significant developments in delivery systems,elucidates the molecular mechanisms of action underlying RNA-based nanomedicines,and discusses their clinical applications.Additionally,the review will address the existing challenges and innovations in delivery platforms while exploring the future possibilities for these promising RNA-based nanomedicines.展开更多
Subject Code:C03With the support by the National Natural Science Foundation of China,the Chinese Academy of Sciences,and the National Key Basic Research Program of China,Prof.Zhang Yong(张勇)and colleagues at the Inst...Subject Code:C03With the support by the National Natural Science Foundation of China,the Chinese Academy of Sciences,and the National Key Basic Research Program of China,Prof.Zhang Yong(张勇)and colleagues at the Institute of Zoology,Chinese Academy of Sciences uncovered a general mechanism mediated by LTR retrotransposons to create transcribed RNA-based duplicates in metazoans,which展开更多
The RNA found in the circular system is known as extracellular RNA(exRNA).This kind of RNA has been found to play a biological role similar to that of a messenger.They can be used as indicators of disease status or th...The RNA found in the circular system is known as extracellular RNA(exRNA).This kind of RNA has been found to play a biological role similar to that of a messenger.They can be used as indicators of disease status or the physiological health of an organism.A large number of RNA-based biomaterials have been developed by simulating the biological function and structure of natural RNA molecules.The structural programmability of RNA-based biomaterials provides the spur for scientists to pioneer new approaches in disease detection and prevention.Nevertheless,the link between exRNA function and the design of RNAbased biomaterials has not been fully understood.Understanding the biological structure and function of exRNA will contribute to the clinical translation of this novel biotechnology.The present review discusses the research progress associated with exRNA and their derivatives to bridge the gap between natural exRNA and RNA-based biomaterials.展开更多
Global food production is at risk from many abiotic and biotic stresses and can be affected by multiple stresses simultaneously.Virus diseases damage cultivated plants and decrease the marketable quality of produce.Im...Global food production is at risk from many abiotic and biotic stresses and can be affected by multiple stresses simultaneously.Virus diseases damage cultivated plants and decrease the marketable quality of produce.Importantly,the progression of virus diseases is strongly affected by changing climate conditions.Among climate-changing vari-ables,temperature increase is viewed as an important factor that affects virus epidemics,which may in turn require more efficient disease management.In this review,we discuss the effect of elevated temperature on virus epidem-ics at both macro-and micro-climatic levels.This includes the temperature effects on virus spread both within and between host plants.Furthermore,we focus on the involvement of molecular mechanisms associated with tempera-ture effects on plant defence to viruses in both susceptible and resistant plants.Considering various mechanisms proposed in different pathosystems,we also offer a view of the possible opportunities provided by RNA-based technologies for virus control at elevated temperatures.Recently,the potential of these technologies for topical field applications has been strengthened through a combination of genetically modified(GM)-free delivery nanoplat-forms.This approach represents a promising and important climate-resilient substitute to conventional strategies for managing plant virus diseases under global warming scenarios.In this context,we discuss the knowledge gaps in the research of temperature effects on plant-virus interactions and limitations of RNA-based emerging technologies,which should be addressed in future studies.展开更多
基金supported by the National Natural Science Foundation of China(No.81974210)the Science and Technology Planning Project of Guangdong Province,China(No.2020A0505100045)the Natural Science Foundation of Guangdong Province(No.2019A1515010671),all to CKT.
文摘Injuries to the central nervous system(CNS)such as stroke,brain,and spinal cord trauma often result in permanent disabilities because adult CNS neurons only exhibit limited axon regeneration.The brain has a surprising intrinsic capability of recovering itself after injury.However,the hostile extrinsic microenvironment significantly hinders axon regeneration.Recent advances have indicated that the inactivation of intrinsic regenerative pathways plays a pivotal role in the failure of most adult CNS neuronal regeneration.Particularly,substantial evidence has convincingly demonstrated that the mechanistic target of rapamycin(mTOR)signaling is one of the most crucial intrinsic regenerative pathways that drive axonal regeneration and sprouting in various CNS injuries.In this review,we will discuss the recent findings and highlight the critical roles of mTOR pathway in axon regeneration in different types of CNS injury.Importantly,we will demonstrate that the reactivation of this regenerative pathway can be achieved by blocking the key mTOR signaling components such as phosphatase and tensin homolog(PTEN).Given that multiple mTOR signaling components are endogenous inhibitory factors of this pathway,we will discuss the promising potential of RNA-based therapeutics which are particularly suitable for this purpose,and the fact that they have attracted substantial attention recently after the success of coronavirus disease 2019 vaccination.To specifically tackle the blood-brain barrier issue,we will review the current technology to deliver these RNA therapeutics into the brain with a focus on nanoparticle technology.We will propose the clinical application of these RNA-mediated therapies in combination with the brain-targeted drug delivery approach against mTOR signaling components as an effective and feasible therapeutic strategy aiming to enhance axonal regeneration for functional recovery after CNS injury.
文摘Modern agribusiness plays a vital role in safeguarding and improving the production,quality,and quantity of food,feed,fiber,and fuel.Growing concerns over the impact of chemical pesticides on health and the environment have stimulated the industry to search for alternative and greener solutions.Over the last years,the RNA interference(RNAi)process has been identified as a very promising new approach to complement the arsenal of foliar spray,soil,or seed treatments applied as chemical and biological pest control agents,and of plant-incorporated protectants(PIPs).RNA-based active ingredients(AIs)possess a unique mode of action and can be implemented via both genetic modification(GM)and biocontrol approaches.RNA-based AIs promise to deliver the selectivity and sustainability desired in future crop protection agents.This is due to their utilization of a natural process to exert control and their high level of selectivity,which leads to reduced risk for non-target organisms(NTOs).This review discusses the advantages and limitations of RNA-based solutions in crop protection and recent research progress toward RNA-based biocontrols against the Colorado potato beetle(CPB),corn rootworm(CRW),and soy stink bug(SSB).Many challenges still exist on the road to the implementation of a broad range of RNA-based products and their widespread use and application.Despite these challenges,it can be expected that RNA-based AIs will become valuable new tools complementing the current arsenal of crop-protection solutions.
基金supported by the Medical Science and Technology Research Fund of Guangdong Province(Grant No.C2018062).
文摘Aim:Our study aimed to explore the prognostic predictive potential of a novel RNA-based signature called ImmuneScore in advanced non-squamous NSCLC patients receiving combined immune checkpoint inhibitor(ICI)treatment and chemotherapy.Methods:RNA-sequencing data of 113 patients screened out from ORIENT-11 trial were retrospectively analyzed.ImmuneScore was calculated by the ESTIMATE algorithm.The association of ImmuneScore with early tumor progression,progression-free survival(PFS),and overall survival(OS)was analyzed using chi-square test,Cox regression test,and log-rank test.Receiver operating characteristic(ROC)curves were generated,with higher values of area under the ROC curves(AUCs)indicating better prediction ability.Results:ImmuneScore was negatively correlated with early tumor progression rate(4.3%vs.18.6%,P=0.013)while positively correlated with PFS(HR=0.29,95%CI:0.16-0.53,P<0.001)and OS(HR=0.32,95%CI:0.18-0.58,P<0.001),demonstrating higher AUCs than that of Programmed death-ligand 1(PD-L1)tumor proportion score(TPS)(early tumor progression:0.64 vs.0.68;PFS:0.67 vs.0.58;OS:0.73 vs.0.63).Nomograms integrating ImmuneScore and other significant variables(age and T-stage for PFS,gender and T-stage for OS)yielded good performance in PFS and OS prediction.Conclusion:ImmuneScore serves as a novel RNA-based prognostic signature superior to PD-L1 in advanced non-squamous NSCLC patients receiving chemotherapy combined with ICI therapy.Higher ImmuneScore indicates lower early tumor progression rate,longer PFS,and longer OS.
基金supported by the National Natural Science Foundation of China (82122048).
文摘Liver cancer is a heterogeneous disease and is one of the leading causes of cancer deaths worldwide.Hepatocellular carcinoma, comprising approximately 90% of cases, presents a formidable challenge with a lessthan 20% 5-year survival rate despite recent treatment advancements. The impediments of drug resistance andoff-target effects underscore the critical need for innovative and efficacious therapies. Harnessing the growingunderstanding of RNA function offers a promising avenue to address previously "undruggable" proteins,transcripts, and genes. Various RNAs demonstrate the potential to selectively act on these targets, expanding thescope of therapeutic interventions. With diverse regulatory roles in cancer pathways, RNAs emerge as valuabletargets and tools for anticancer therapy development. This article provides an in-depth exploration of currentRNA-based therapies, elucidates their mechanisms of action, and discusses their combinations withchemo-/immunotherapies in clinical trials for hepatocellular carcinoma.
基金supported by the National Natural Science Foundation of China(No.32371458)the Key Research and Development Programs of the Ministry of Science and Technology(No.2022YFA1205700)+1 种基金the Basic Research Cooperation Special Foundation of Beijing-Tianjin-Hebei(Nos.H_(2)022205047,22JCZXJC00060,and E3B33911DF)funding from the National Center for Nanoscience and Technology and Chinese Academy of Sciences.
文摘RNA-based nanomedicines encompass a range of therapeutic approaches that utilize RNA molecules or molecules that target RNAs for the treatment or prevention of diseases.These include antisense oligonucleotides(ASOs),small interfering RNAs(siRNAs),endogenous microRNAs(miRNAs),messenger RNAs(mRNAs),clustered regularly interspersed short palindromic repeats-associated protein 9(CRISPR/Cas9),single guide RNAs(sgRNAs),as well as RNA aptamers.These therapeutic agents exert their effects through various mechanisms such as gene inhibition,addition,replacement,and editing.The advancement of RNA biology and the field of RNA therapy has paved the way for the development and utilization of RNA-based nanomedicine in human healthcare.One remarkable example of RNA-based nanomedicine is the mRNA-based vaccines including mRNA-1273(Moderna)and BNT162b2(Pfizer/BioNTech)that have been successfully employed in response to the coronavirus disease 2019(COVID-19)pandemic.This review aims to highlight the advantages of RNA-based nanomedicines,provides an overview of significant developments in delivery systems,elucidates the molecular mechanisms of action underlying RNA-based nanomedicines,and discusses their clinical applications.Additionally,the review will address the existing challenges and innovations in delivery platforms while exploring the future possibilities for these promising RNA-based nanomedicines.
文摘Subject Code:C03With the support by the National Natural Science Foundation of China,the Chinese Academy of Sciences,and the National Key Basic Research Program of China,Prof.Zhang Yong(张勇)and colleagues at the Institute of Zoology,Chinese Academy of Sciences uncovered a general mechanism mediated by LTR retrotransposons to create transcribed RNA-based duplicates in metazoans,which
基金National Clinical ResearchCenterforOral Diseases,Grant/Award Number:LCA202004Shaanxi Key Scientific and Technological Innovation Team,Grant/Award Number:2020TD-033National Natural Science Foundation of China,Grant/Award Numbers:82301043,82325012。
文摘The RNA found in the circular system is known as extracellular RNA(exRNA).This kind of RNA has been found to play a biological role similar to that of a messenger.They can be used as indicators of disease status or the physiological health of an organism.A large number of RNA-based biomaterials have been developed by simulating the biological function and structure of natural RNA molecules.The structural programmability of RNA-based biomaterials provides the spur for scientists to pioneer new approaches in disease detection and prevention.Nevertheless,the link between exRNA function and the design of RNAbased biomaterials has not been fully understood.Understanding the biological structure and function of exRNA will contribute to the clinical translation of this novel biotechnology.The present review discusses the research progress associated with exRNA and their derivatives to bridge the gap between natural exRNA and RNA-based biomaterials.
文摘Global food production is at risk from many abiotic and biotic stresses and can be affected by multiple stresses simultaneously.Virus diseases damage cultivated plants and decrease the marketable quality of produce.Importantly,the progression of virus diseases is strongly affected by changing climate conditions.Among climate-changing vari-ables,temperature increase is viewed as an important factor that affects virus epidemics,which may in turn require more efficient disease management.In this review,we discuss the effect of elevated temperature on virus epidem-ics at both macro-and micro-climatic levels.This includes the temperature effects on virus spread both within and between host plants.Furthermore,we focus on the involvement of molecular mechanisms associated with tempera-ture effects on plant defence to viruses in both susceptible and resistant plants.Considering various mechanisms proposed in different pathosystems,we also offer a view of the possible opportunities provided by RNA-based technologies for virus control at elevated temperatures.Recently,the potential of these technologies for topical field applications has been strengthened through a combination of genetically modified(GM)-free delivery nanoplat-forms.This approach represents a promising and important climate-resilient substitute to conventional strategies for managing plant virus diseases under global warming scenarios.In this context,we discuss the knowledge gaps in the research of temperature effects on plant-virus interactions and limitations of RNA-based emerging technologies,which should be addressed in future studies.
