Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after longterm use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an...Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after longterm use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saikosaponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-kB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.Furthermore,the mechanisms by which RPA attenuates RBinduced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to saikogenins in vivo.Different from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity.Based on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NFkB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosaponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.展开更多
The photoluminescence of four polyoxoniobates [Nb6O19]8-, [Nb10O28]6-, [Ti2Nb8O28]8- and [H2Si4Nb16O56]14- was observed, and its origin was revealed in the view of molecular orbital by means of the computational metho...The photoluminescence of four polyoxoniobates [Nb6O19]8-, [Nb10O28]6-, [Ti2Nb8O28]8- and [H2Si4Nb16O56]14- was observed, and its origin was revealed in the view of molecular orbital by means of the computational method. The photoluminescence is originated from singlet transitions, and the calculated values agree well with the experimental data. The results indicate that the size of clusters and the foreigner atoms can affect the fluorescent properties of PONbs. The absorption and emission of these PONbs are originated molecular orbitals contributed mainly by μ2-O and Nb atoms according to NBO analysis. These PONbs were also found as electrochemical catalysts with high performance for water oxidation, which can effectively split water into oxygen under basic condition with a high catalytic current, and pH values have remarkable influence on the electrocatalytic activities of these PONbs for water oxidation.展开更多
Due to the complicated three-dimensional behaviors and testing limitations of reinforced concrete(RC)members in torsion,torsional mechanism exploration and torsional performance prediction have always been difficult.I...Due to the complicated three-dimensional behaviors and testing limitations of reinforced concrete(RC)members in torsion,torsional mechanism exploration and torsional performance prediction have always been difficult.In the present paper,several machine learning models were applied to predict the torsional capacity of RC members.Experimental results of a total of 287 torsional specimens were collected through an overall literature review.Algorithms of extreme gradient boosting machine(XGBM),random forest regression,back propagation artificial neural network and support vector machine,were trained and tested by 10-fold cross-validation method.Predictive performances of proposed machine learning models were evaluated and compared,both with each other and with the calculated results of existing design codes,i.e.,GB 50010,ACI 318-19,and Eurocode 2.The results demonstrated that better predictive performance was achieved by machine learning models,whereas GB 50010 slightly overestimated the torsional capacity,and ACI 318-19 and Eurocode 2 underestimated it,especially in the case of ACI 318-19.The XGBM model gave the most favorable predictions with R^(2)=0.999,RMSE=1.386,MAE=0.86,andλ=0.976.Moreover,strength of concrete was the most sensitive input parameters affecting the reliability of the predictive model,followed by transverse-to-longitudinal reinforcement ratio and total reinforcement ratio.展开更多
Two-dimensional(2D)Ruddlesden-Popper(RP)halide perovskites with diverse structures and properties have drawn increasing attention due to their promising optoelectronic applications.Recently,a new all-inorganic Cs_(2)P...Two-dimensional(2D)Ruddlesden-Popper(RP)halide perovskites with diverse structures and properties have drawn increasing attention due to their promising optoelectronic applications.Recently,a new all-inorganic Cs_(2)Pb(SCN)_(2)Br_(2) has been reported that opens up new potential for the development of 2D RP perovskites.However,recent reports of unusual dual emissions and two-edge absorption in Cs_(2)Pb(SCN)_(2)Br_(2) have generated intense debate about its origin and remains controversial.Here,by combining continuous pressure tuning with in situ diagnostics,we have unambiguously revealed the underlying mechanisms that the 2D Cs_(2)Pb(SCN)_(2)Br_(2) exhibits an intrinsic blue emission at 2.66 eV and an absorption edge close to the emission peak.While the gradually formed CsPbBr_(3) is responsible for the green emission at 2.33 eV with the absorption shoulder at 2.41 eV.Furthermore,by fitting the temperature-dependent intensity of the intrinsic blue emission,we have determined the corrected value of exciton binding energy for 2D Cs_(2)Pb(SCN)_(2)Br_(2) to be 90 meV.Intriguingly,an emission enhancement of 2.5 times is achieved in Cs_(2)Pb(SCN)_(2)Br_(2) under a mild pressure within 0.8 GPa,caused by the pressuresuppressed exciton-phonon interaction.This work not only elucidates the origin of the dual emissions and two-edge absorption in Cs_(2)Pb(SCN)_(2)Br_(2),but it also provides a potential means to regulate and optimize the optoelectronic properties of 2D perovskites.展开更多
Simulating unsteady turbulent flow in turbomachines is still challenging due to the complexity of blade geometry and relative motion between rotor and stator.This study presents an Immersed Boundary Method(IBM)for hig...Simulating unsteady turbulent flow in turbomachines is still challenging due to the complexity of blade geometry and relative motion between rotor and stator.This study presents an Immersed Boundary Method(IBM)for high-Reynolds turbomachinery internal flows,and shows the advantage of the automatic grid generation techniques and flexible moving boundary treatments.The wall functions are used in the present method to alleviate the wall resolution restriction of turbulence simulation.The Two-Dimensional(2-D)IBM solver,which was previously developed and tested for a low-speed compressor,is further validated for a well-documented Low-Pressure Turbine(LPT)cascade.Both the blade loading and the total pressure losses in the wake are well captured by the present 2-D solver.The complex Three-Dimensional(3-D)effects in turbomachines motivate the further development of an extended 3-D IBM solver by using a curvilinear-coordinate system that facilitates the hub and casing boundary treatment.The good performance of the 3-D solver is demonstrated through comparison with CFX solver solutions for the rotor configuration of Advanced Noise Control Fan(ANCF).Further effects of the grid resolution on capturing the blade wake are discussed.The results indicate that the present 3-D solver is capable of reproducing the evolution of the blade wake with suitable computational grid.展开更多
Fast and accurate prediction of sound radiation of Contra-Rotating Open Rotors(CRORs)is an essential element of design methods of low-noise open rotor propulsion systems.In the present work,a previous frequency-domain...Fast and accurate prediction of sound radiation of Contra-Rotating Open Rotors(CRORs)is an essential element of design methods of low-noise open rotor propulsion systems.In the present work,a previous frequency-domain model is extended to predict CROR noise.It builds explicitly the relationship between harmonic loadings and corresponding tonal noise,by which the influential parameters to noise generation can be clearly understood.The real distribu-tions of steady and unsteady blade loadings are calculated by the Nonlinear Harmonic(NLH)method.In the present hybrid approach,both the CFD and acoustic modules are solved in the fre-quency domain.To assess the accuracy of the developed method,the loading noise of a CROR is calculated and compared against results by using the time-domain FW-H module of NUMECA.The predicted sound directivities by the two methods are in good agreements.The present acoustic model in the frequency domain is proven to be accurate and have high efficiency in far-field noise prediction and data processing.Furthermore,the characteristics of the CROR interaction tonal noise are analyzed and discussed.展开更多
Metal-organic framework(MOF)/polymer composites have attracted extensive attention in the recent years.However,it still remains challenging to efficiently and effectively fabricate these composite materials.In this st...Metal-organic framework(MOF)/polymer composites have attracted extensive attention in the recent years.However,it still remains challenging to efficiently and effectively fabricate these composite materials.In this study,we propose a facile one-pot electrospinning strategy for preparation of HKUST-1/polyacrylonitrile(PAN)nanofibrous membranes from a homogeneous stock solution containing HKUST-1 precursors and PAN.MOF crystallization and polymer solidification occur simultaneously during the electrospinning process,thus avoiding the issues of aggregation and troublesome multistep fabrication of the conventional approach.The obtained HKUST-1/PAN electrospun membranes show uniform MOF distribution throughout the nanofibers and yield good mechanical properties.The membranes are used as separators in Li-metal full batteries under harsh testing conditions,using an ultrathin Li-metal anode,a high mass loading cathode,and the HKUST-1/PAN nanofibrous separator.The results demonstrate significantly improved cycling performance(capacity retention of 83.1%after 200 cycles)under a low negative to positive capacity ratio(N/P ratio of 1.86).The improvement can be attributed to an enhanced wettability of the separator towards electrolyte stemmed from the nanofibrous structure,and a uniform lithium ion flux stabilized by the open metal sites of uniformly distributed HKUST-1 particles in the membrane during cycling.展开更多
To overcome the shortcomings of traditional dairy cow feed intake assessment model andBP neural network, this paper proposes a method of optimizing BP neural network usingpolynomial decay learning rate, taking the cow...To overcome the shortcomings of traditional dairy cow feed intake assessment model andBP neural network, this paper proposes a method of optimizing BP neural network usingpolynomial decay learning rate, taking the cow’s body weight, lying duration, lying times,walking steps, foraging duration and concentrate-roughage ratio as input variables andtaking the actual feed intake is the output variable to establish a dairy cow feed intakeassessment model, and the model is trained and verified by experimental data collectedon site. For the sake of comparative study, feed intake is simultaneously assessed by SVRmodel, KNN logistic regression model, traditional BP neural network model, and multilayerBP neural network model. The results show that the established BP model using the polynomial decay learning rate has the highest assessment accuracy, the MSPE, RMSE, MAE,MAPE and R2 are 0.043 kg2/d and 0.208 kg/d, 0.173 kg/d, 1.37% and 0.94 respectively. Compared with SVR model and KNN mode, the RMSE value reduced by 43.9% and 26.5%, it isalso found that the model designed in this paper has many advantages in comparison withthe BP model and multilayer BP model in terms of precision and generalization. Therefore,this method is ready to be applied for accurately evaluating the dairy cow feed intake, andit can provide theoretical guidance and technical support for the precise-feeding and canalso be of high significance in the improvement of dairy precise-breeding.展开更多
Adenosine-to-inosine(A-to-I)RNA editing is a widespread posttranscriptional modification that has been shown to play an important role in tumorigenesis.Here,we evaluated a total of 19,316 RNA editing sites in the tiss...Adenosine-to-inosine(A-to-I)RNA editing is a widespread posttranscriptional modification that has been shown to play an important role in tumorigenesis.Here,we evaluated a total of 19,316 RNA editing sites in the tissues of 80 lung adenocarcinoma(LUAD)patients from our Nanjing Lung Cancer Cohort(NJLCC)and 486 LUAD patients from the TCGA database.The global RNA editing level was significantly increased in tumor tissues and was highly heterogeneous across patients.The high RNA editing level in tumors was attributed to both RNA(ADAR1 expression)and DNA alterations(mutation load).Consensus clustering on RNA editing sites revealed a new molecular subtype(EC3)that was associated with the poorest prognosis of LUAD patients.Importantly,the new classification was independent of classic molecular subtypes based on gene expression or DNA methylation.We further proposed a simplified model including eight RNA editing sites to accurately distinguish the EC3 subtype in our patients.The model was further validated in the TCGA dataset and had an area under the curve(AUC)of the receiver operating characteristic curve of 0.93(95%CI:0.91-0.95).In addition,we found that LUAD cell lines with the EC3 subtype were sensitive to four chemotherapy drugs.These findings highlighted the importance of RNA editing events in the tumorigenesis of LUAD and provided insight into the application of RNA editing in the molecular subtyping and clinical treatment of cancer.展开更多
基金This study is funded by the National Nature Science Foundation of China(Grant Nos.:82074323,and 81673572)Key Research and Development Program of Shanxi Province(Program No.:202102130501010)+2 种基金The major science and technology project for“Significant New Drugs Creation”(Project No.:2017ZX09301047)Research Project Supported by Shanxi Scholarship Council of China(Project No.:2020019)The special fund for Science and Technology Innovation Teams of Shanxi Province(Grant No.:202204051002011).
文摘Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after longterm use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saikosaponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-kB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.Furthermore,the mechanisms by which RPA attenuates RBinduced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to saikogenins in vivo.Different from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity.Based on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NFkB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosaponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.
文摘The photoluminescence of four polyoxoniobates [Nb6O19]8-, [Nb10O28]6-, [Ti2Nb8O28]8- and [H2Si4Nb16O56]14- was observed, and its origin was revealed in the view of molecular orbital by means of the computational method. The photoluminescence is originated from singlet transitions, and the calculated values agree well with the experimental data. The results indicate that the size of clusters and the foreigner atoms can affect the fluorescent properties of PONbs. The absorption and emission of these PONbs are originated molecular orbitals contributed mainly by μ2-O and Nb atoms according to NBO analysis. These PONbs were also found as electrochemical catalysts with high performance for water oxidation, which can effectively split water into oxygen under basic condition with a high catalytic current, and pH values have remarkable influence on the electrocatalytic activities of these PONbs for water oxidation.
基金The authors are extremely grateful to the funds including the National Natural Science Foundation of China(Grant No.51808258)the Fundamental Research Funds for the Central Universities(No.2022QN1031).
文摘Due to the complicated three-dimensional behaviors and testing limitations of reinforced concrete(RC)members in torsion,torsional mechanism exploration and torsional performance prediction have always been difficult.In the present paper,several machine learning models were applied to predict the torsional capacity of RC members.Experimental results of a total of 287 torsional specimens were collected through an overall literature review.Algorithms of extreme gradient boosting machine(XGBM),random forest regression,back propagation artificial neural network and support vector machine,were trained and tested by 10-fold cross-validation method.Predictive performances of proposed machine learning models were evaluated and compared,both with each other and with the calculated results of existing design codes,i.e.,GB 50010,ACI 318-19,and Eurocode 2.The results demonstrated that better predictive performance was achieved by machine learning models,whereas GB 50010 slightly overestimated the torsional capacity,and ACI 318-19 and Eurocode 2 underestimated it,especially in the case of ACI 318-19.The XGBM model gave the most favorable predictions with R^(2)=0.999,RMSE=1.386,MAE=0.86,andλ=0.976.Moreover,strength of concrete was the most sensitive input parameters affecting the reliability of the predictive model,followed by transverse-to-longitudinal reinforcement ratio and total reinforcement ratio.
基金supported by the National Natural Science Foundation of China(NSFC)(grant nos.22275004,U1930401,and 52325309)the Shanghai Science and Technology Committee(grant no.22JC1410300)+2 种基金the Shanghai Key Laboratory of Novel Extreme Condition Materials(grant no.22dz2260800)supported by the NSFC(grant no.22275077).Q.H.is supported by the CAEP Research(grant no.CX20210048)the Tencent Xplorer Prize(grant no.XPLORER-2020-1013).
文摘Two-dimensional(2D)Ruddlesden-Popper(RP)halide perovskites with diverse structures and properties have drawn increasing attention due to their promising optoelectronic applications.Recently,a new all-inorganic Cs_(2)Pb(SCN)_(2)Br_(2) has been reported that opens up new potential for the development of 2D RP perovskites.However,recent reports of unusual dual emissions and two-edge absorption in Cs_(2)Pb(SCN)_(2)Br_(2) have generated intense debate about its origin and remains controversial.Here,by combining continuous pressure tuning with in situ diagnostics,we have unambiguously revealed the underlying mechanisms that the 2D Cs_(2)Pb(SCN)_(2)Br_(2) exhibits an intrinsic blue emission at 2.66 eV and an absorption edge close to the emission peak.While the gradually formed CsPbBr_(3) is responsible for the green emission at 2.33 eV with the absorption shoulder at 2.41 eV.Furthermore,by fitting the temperature-dependent intensity of the intrinsic blue emission,we have determined the corrected value of exciton binding energy for 2D Cs_(2)Pb(SCN)_(2)Br_(2) to be 90 meV.Intriguingly,an emission enhancement of 2.5 times is achieved in Cs_(2)Pb(SCN)_(2)Br_(2) under a mild pressure within 0.8 GPa,caused by the pressuresuppressed exciton-phonon interaction.This work not only elucidates the origin of the dual emissions and two-edge absorption in Cs_(2)Pb(SCN)_(2)Br_(2),but it also provides a potential means to regulate and optimize the optoelectronic properties of 2D perovskites.
基金co-supported by the National Natural Science Foundation of China(No.52022009)the Science Center for Gas Turbine Project of China(No.P2022-A-II-003-001)the Key Laboratory Foundation,China(No.2021-JCJQ-LB-062-0102).
文摘Simulating unsteady turbulent flow in turbomachines is still challenging due to the complexity of blade geometry and relative motion between rotor and stator.This study presents an Immersed Boundary Method(IBM)for high-Reynolds turbomachinery internal flows,and shows the advantage of the automatic grid generation techniques and flexible moving boundary treatments.The wall functions are used in the present method to alleviate the wall resolution restriction of turbulence simulation.The Two-Dimensional(2-D)IBM solver,which was previously developed and tested for a low-speed compressor,is further validated for a well-documented Low-Pressure Turbine(LPT)cascade.Both the blade loading and the total pressure losses in the wake are well captured by the present 2-D solver.The complex Three-Dimensional(3-D)effects in turbomachines motivate the further development of an extended 3-D IBM solver by using a curvilinear-coordinate system that facilitates the hub and casing boundary treatment.The good performance of the 3-D solver is demonstrated through comparison with CFX solver solutions for the rotor configuration of Advanced Noise Control Fan(ANCF).Further effects of the grid resolution on capturing the blade wake are discussed.The results indicate that the present 3-D solver is capable of reproducing the evolution of the blade wake with suitable computational grid.
基金co-supported by the National Natural Science Foundation of China(Nos.52022009,51790514)the National Science and Technology Major Project,China(No.2017-II-003-0015)the Key Laboratory Foundation,China(No.2021-JCJQ-LB-062-0102).
文摘Fast and accurate prediction of sound radiation of Contra-Rotating Open Rotors(CRORs)is an essential element of design methods of low-noise open rotor propulsion systems.In the present work,a previous frequency-domain model is extended to predict CROR noise.It builds explicitly the relationship between harmonic loadings and corresponding tonal noise,by which the influential parameters to noise generation can be clearly understood.The real distribu-tions of steady and unsteady blade loadings are calculated by the Nonlinear Harmonic(NLH)method.In the present hybrid approach,both the CFD and acoustic modules are solved in the fre-quency domain.To assess the accuracy of the developed method,the loading noise of a CROR is calculated and compared against results by using the time-domain FW-H module of NUMECA.The predicted sound directivities by the two methods are in good agreements.The present acoustic model in the frequency domain is proven to be accurate and have high efficiency in far-field noise prediction and data processing.Furthermore,the characteristics of the CROR interaction tonal noise are analyzed and discussed.
基金We sincerely thank the State Key Laboratory of Chemical Engineering at Zhejiang University(No.SKL-ChE-20D01)the Program for Guangdong Introducing Innovative and Entrepreneurial Teams(No.2017ZT07C291)+1 种基金Shenzhen Science and Technology Program(No.KQTD20170810141424366)2019 Special Program for Central Government Guiding Local Science and Technology Development:Environmental Purification Functional Materials Research Platform,and Shenzhen Key Laboratory of Advanced Materials Product Engineering(No.ZDSYS20190911164401990)for supporting this research work。
文摘Metal-organic framework(MOF)/polymer composites have attracted extensive attention in the recent years.However,it still remains challenging to efficiently and effectively fabricate these composite materials.In this study,we propose a facile one-pot electrospinning strategy for preparation of HKUST-1/polyacrylonitrile(PAN)nanofibrous membranes from a homogeneous stock solution containing HKUST-1 precursors and PAN.MOF crystallization and polymer solidification occur simultaneously during the electrospinning process,thus avoiding the issues of aggregation and troublesome multistep fabrication of the conventional approach.The obtained HKUST-1/PAN electrospun membranes show uniform MOF distribution throughout the nanofibers and yield good mechanical properties.The membranes are used as separators in Li-metal full batteries under harsh testing conditions,using an ultrathin Li-metal anode,a high mass loading cathode,and the HKUST-1/PAN nanofibrous separator.The results demonstrate significantly improved cycling performance(capacity retention of 83.1%after 200 cycles)under a low negative to positive capacity ratio(N/P ratio of 1.86).The improvement can be attributed to an enhanced wettability of the separator towards electrolyte stemmed from the nanofibrous structure,and a uniform lithium ion flux stabilized by the open metal sites of uniformly distributed HKUST-1 particles in the membrane during cycling.
基金This research is financially supported by National Thirteenth Five-Year National Key R&D Plan(2016YFD0700204)China Postdoctoral Science Foundation(2017M611346)+3 种基金the China Agriculture Research System(CARS-36)the Natural Science Foundation of Heilongjiang Province of China(C2018018)Postdoctoral Science Foundation of Heilongjiang(LBHZ12040)the University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province under Grant(UNPYSCT-2018143).
文摘To overcome the shortcomings of traditional dairy cow feed intake assessment model andBP neural network, this paper proposes a method of optimizing BP neural network usingpolynomial decay learning rate, taking the cow’s body weight, lying duration, lying times,walking steps, foraging duration and concentrate-roughage ratio as input variables andtaking the actual feed intake is the output variable to establish a dairy cow feed intakeassessment model, and the model is trained and verified by experimental data collectedon site. For the sake of comparative study, feed intake is simultaneously assessed by SVRmodel, KNN logistic regression model, traditional BP neural network model, and multilayerBP neural network model. The results show that the established BP model using the polynomial decay learning rate has the highest assessment accuracy, the MSPE, RMSE, MAE,MAPE and R2 are 0.043 kg2/d and 0.208 kg/d, 0.173 kg/d, 1.37% and 0.94 respectively. Compared with SVR model and KNN mode, the RMSE value reduced by 43.9% and 26.5%, it isalso found that the model designed in this paper has many advantages in comparison withthe BP model and multilayer BP model in terms of precision and generalization. Therefore,this method is ready to be applied for accurately evaluating the dairy cow feed intake, andit can provide theoretical guidance and technical support for the precise-feeding and canalso be of high significance in the improvement of dairy precise-breeding.
基金supported by the National Natural Science Foundation of China(81922061,82072579,81521004,81973123and 81871885)the National Key Research and Development Project(2017YFC0907905)Research Unit of Prospective Cohort of Cardiovascular Diseases and Cancer,Chinese Academy of Medical Sciences(2019RU038)。
文摘Adenosine-to-inosine(A-to-I)RNA editing is a widespread posttranscriptional modification that has been shown to play an important role in tumorigenesis.Here,we evaluated a total of 19,316 RNA editing sites in the tissues of 80 lung adenocarcinoma(LUAD)patients from our Nanjing Lung Cancer Cohort(NJLCC)and 486 LUAD patients from the TCGA database.The global RNA editing level was significantly increased in tumor tissues and was highly heterogeneous across patients.The high RNA editing level in tumors was attributed to both RNA(ADAR1 expression)and DNA alterations(mutation load).Consensus clustering on RNA editing sites revealed a new molecular subtype(EC3)that was associated with the poorest prognosis of LUAD patients.Importantly,the new classification was independent of classic molecular subtypes based on gene expression or DNA methylation.We further proposed a simplified model including eight RNA editing sites to accurately distinguish the EC3 subtype in our patients.The model was further validated in the TCGA dataset and had an area under the curve(AUC)of the receiver operating characteristic curve of 0.93(95%CI:0.91-0.95).In addition,we found that LUAD cell lines with the EC3 subtype were sensitive to four chemotherapy drugs.These findings highlighted the importance of RNA editing events in the tumorigenesis of LUAD and provided insight into the application of RNA editing in the molecular subtyping and clinical treatment of cancer.
