Objective To develop and validate a preoperative clinical-radiomics model for predicting overall survival(OS)and disease-free survival(DFS)in patients with extrahepatic cholangiocarcinoma(eCCA)undergoing radical resec...Objective To develop and validate a preoperative clinical-radiomics model for predicting overall survival(OS)and disease-free survival(DFS)in patients with extrahepatic cholangiocarcinoma(eCCA)undergoing radical resection.Methods In this retrospective study,consecutive patients with pathologically-confirmed eCCA who underwent radical resection at our institution from 2015 to 2022 were included.The patients were divided into a training cohort and a validation cohort according to the chronological order of their CT examinations.Least absolute shrinkage and selection operator(LASSO)-Cox regression was employed to select predictive radiomic features and clinical variables.The selected features and variables were incorporated into a Cox regression model.Model performance for 1-year OS and DFS prediction was assessed using calibration curves,area under receiver operating characteristic curve(AUC),and concordance index(C-index).Results This study included 123 patients(mean age 64.0±8.4 years,85 males/38 females),with 86 in the training cohort and 37 in the validation cohort.The OS-predicting model included four clinical variables and four radiomic features.It achieved a training cohort AUC of 0.858(C-index=0.800)and a validation cohort AUC of 0.649(C-index=0.605).The DFS-predicting model included four clinical variables and four other radiomic features.It achieved a training cohort AUC of 0.830(C-index=0.760)and a validation cohort AUC of 0.717(C-index=0.616).Conclusion The preoperative clinical-radiomics models show promise as a tool for predicting 1-year OS and DFS in eCCA patients after radical surgery.展开更多
We carried out first-principles calculations to investigate the electronic properties of the monolayer blue phosphorene(BlueP)decorated by the group-IVB transition-metal adatoms(Cr,Mo and W),and found that the Cr-deco...We carried out first-principles calculations to investigate the electronic properties of the monolayer blue phosphorene(BlueP)decorated by the group-IVB transition-metal adatoms(Cr,Mo and W),and found that the Cr-decorated BlueP is a magnetic half metal,while the Mo-and W-decorated BlueP are semiconductors with band gaps smaller than 0.2 eV.Compressive biaxial strains make the band gaps close and reopen,and band inversions occur during this process,which induces topological transitions in the Mo-decorated BlueP(with strain of-5.75%)and W-decorated BlueP(with strain of-4.25%)from normal insulators to topological insulators(TIs).The TI gap is 94 meV for the Mo-decorated BlueP and218 me V for the W-decorated BlueP.Such large TI gaps demonstrate the possibility to engineer topological phases in the monolayer BlueP with transition-metal adatoms at high temperature.展开更多
Drought seriously impacts wheat production(Triticum aestivum L.),while the exploitation and utilization of genes for drought tolerance are insufficient.Leaf wilting is a direct reflection of drought tolerance in plant...Drought seriously impacts wheat production(Triticum aestivum L.),while the exploitation and utilization of genes for drought tolerance are insufficient.Leaf wilting is a direct reflection of drought tolerance in plants.Clade A PP2Cs are abscisic acid(ABA)co-receptors playing vital roles in the ABA signaling pathway,regulating drought response.However,the roles of other clade PP2Cs in drought tolerance,especially in wheat,remain largely unknown.Here,we identified a gain-of-function drought-induced wilting 1(DIW1)gene from the wheat Aikang 58 mutant library by map-based cloning,which encodes a cladeⅠprotein phosphatase 2C(TaPP2C158)with enhanced protein phosphatase activity.Phenotypic analysis of overexpression and CRISPR/Cas9 mutant lines demonstrated that DIW1/TaPP2C158 is a negative regulator responsible for drought resistance.We found that TaPP2C158 directly interacts with TaSnRK1.1 and de-phosphorylates it,thus inactivating the TaSnRK1.1–Ta AREB3 pathway.TaPP2C158 protein phosphatase activity is negatively correlated with ABA signaling.Association analysis suggested that C-terminal variation of TaPP2C158 changing protein phosphatase activity is highly correlated with the canopy temperature,and seedling survival rate under drought stress.Our data suggest that the favorable allele with lower phosphatase activity of TaPP2C158 has been positively selected in Chinese breeding history.This work benefits us in understanding the molecular mechanism of wheat drought tolerance,and provides elite genetic resources and molecular markers for improving wheat drought tolerance.展开更多
Medical imaging is involved in all processes of clinical practice.Approximately 70%of diagnostic information originates from radiologic images,which also account for 90%of the digital data volume of a hospital.However...Medical imaging is involved in all processes of clinical practice.Approximately 70%of diagnostic information originates from radiologic images,which also account for 90%of the digital data volume of a hospital.However,the number of physicians has increased only modestly compared to the rapid growth in the number of medical images.In China,data from medical imaging increases by 30%every year,whereas the number of radiologists increases by only 4%annually.Artificial intelligence(AI),which is representative technology of the fourth industrial revolution,may alleviate the increasing pressure and job burnout,and further improve the diagnostic efficiency of radiology services[1].Despite the urgent and realistic demand for AI technology,many challenges remain in the development and translation of AI products.The rate of the scientific translation of AI research into clinical applications is extremely low.Furthermore,AI models that are applied in clinical settings exhibit unreliable performance and are often impractical[2].Therefore,radiologists may not have access to suitable medical imaging AI models to solve specific clinical problems.This paper analyzes and discusses this problem according to two aspects:the data sources and the AI algorithm(Fig.1).展开更多
Human intestinal carboxyl esterase （hiCE） is a drug target for ameliorating irinotecan-induced diarrhea. By reducing irinotecan- induced diarrhea, hiCE inhibitors can improve the anti-cancer efficacy of irinotecan. ...Human intestinal carboxyl esterase （hiCE） is a drug target for ameliorating irinotecan-induced diarrhea. By reducing irinotecan- induced diarrhea, hiCE inhibitors can improve the anti-cancer efficacy of irinotecan. To find effective hiCE inhibitors, a new virtual screening protocol that combines pharmacophore models derived from the hiCE structure and its ligands has been pro- posed. The hiCE structure has been constructed through homology techniques using hCESI＇s crystal structure. The hiCE structure was optimized via molecular dynamics simulations with the most known active hiCE inhibitors docked into the structure. An optimized pharmacophore, derived from the receptor, was then generated. A ligand-based pharmacophore was also generated from a larger set of known hiCE inhibitors. The final hiCE inhibitor predictions were based upon the virtual screening hits from both ligand-based and receptor-based pharmacophore models. The hit rates from the ligand-based and receptor-based pharmacophore models are 88% and 86%, respectively. The final hit rate is 94%. The two models are highly consistent with one another （85%）. This proves that both models are reliable.展开更多
文摘Objective To develop and validate a preoperative clinical-radiomics model for predicting overall survival(OS)and disease-free survival(DFS)in patients with extrahepatic cholangiocarcinoma(eCCA)undergoing radical resection.Methods In this retrospective study,consecutive patients with pathologically-confirmed eCCA who underwent radical resection at our institution from 2015 to 2022 were included.The patients were divided into a training cohort and a validation cohort according to the chronological order of their CT examinations.Least absolute shrinkage and selection operator(LASSO)-Cox regression was employed to select predictive radiomic features and clinical variables.The selected features and variables were incorporated into a Cox regression model.Model performance for 1-year OS and DFS prediction was assessed using calibration curves,area under receiver operating characteristic curve(AUC),and concordance index(C-index).Results This study included 123 patients(mean age 64.0±8.4 years,85 males/38 females),with 86 in the training cohort and 37 in the validation cohort.The OS-predicting model included four clinical variables and four radiomic features.It achieved a training cohort AUC of 0.858(C-index=0.800)and a validation cohort AUC of 0.649(C-index=0.605).The DFS-predicting model included four clinical variables and four other radiomic features.It achieved a training cohort AUC of 0.830(C-index=0.760)and a validation cohort AUC of 0.717(C-index=0.616).Conclusion The preoperative clinical-radiomics models show promise as a tool for predicting 1-year OS and DFS in eCCA patients after radical surgery.
基金the National Natural Science Foundation of China(No.11574223)the Natural Science Foundation of Jiangsu Province(BK20150303)the Six Talent Peaks Project of Jiangsu Province(2019-XCL-081)。
文摘We carried out first-principles calculations to investigate the electronic properties of the monolayer blue phosphorene(BlueP)decorated by the group-IVB transition-metal adatoms(Cr,Mo and W),and found that the Cr-decorated BlueP is a magnetic half metal,while the Mo-and W-decorated BlueP are semiconductors with band gaps smaller than 0.2 eV.Compressive biaxial strains make the band gaps close and reopen,and band inversions occur during this process,which induces topological transitions in the Mo-decorated BlueP(with strain of-5.75%)and W-decorated BlueP(with strain of-4.25%)from normal insulators to topological insulators(TIs).The TI gap is 94 meV for the Mo-decorated BlueP and218 me V for the W-decorated BlueP.Such large TI gaps demonstrate the possibility to engineer topological phases in the monolayer BlueP with transition-metal adatoms at high temperature.
基金funded by the National Natural Science Foundation of China(32061143040)the Agricultural Science and Technology Innovation Program(ZDRW202002)the Central Public-interest Scientific Institution Basal Research Fund(Y2022GH06)。
文摘Drought seriously impacts wheat production(Triticum aestivum L.),while the exploitation and utilization of genes for drought tolerance are insufficient.Leaf wilting is a direct reflection of drought tolerance in plants.Clade A PP2Cs are abscisic acid(ABA)co-receptors playing vital roles in the ABA signaling pathway,regulating drought response.However,the roles of other clade PP2Cs in drought tolerance,especially in wheat,remain largely unknown.Here,we identified a gain-of-function drought-induced wilting 1(DIW1)gene from the wheat Aikang 58 mutant library by map-based cloning,which encodes a cladeⅠprotein phosphatase 2C(TaPP2C158)with enhanced protein phosphatase activity.Phenotypic analysis of overexpression and CRISPR/Cas9 mutant lines demonstrated that DIW1/TaPP2C158 is a negative regulator responsible for drought resistance.We found that TaPP2C158 directly interacts with TaSnRK1.1 and de-phosphorylates it,thus inactivating the TaSnRK1.1–Ta AREB3 pathway.TaPP2C158 protein phosphatase activity is negatively correlated with ABA signaling.Association analysis suggested that C-terminal variation of TaPP2C158 changing protein phosphatase activity is highly correlated with the canopy temperature,and seedling survival rate under drought stress.Our data suggest that the favorable allele with lower phosphatase activity of TaPP2C158 has been positively selected in Chinese breeding history.This work benefits us in understanding the molecular mechanism of wheat drought tolerance,and provides elite genetic resources and molecular markers for improving wheat drought tolerance.
基金This work was supported by the Scientific and Technological Innovation 2030—a Major Project of New Generation Artificial Intelligence(2020AAA0109503)the Beijing Science and Technology Planning Project(Z201100005620008 and Z211100003521007)+1 种基金the National Natural Science Foundation(82171934)the National Key Research and Development Program of China(2021ZD0111105).
文摘Medical imaging is involved in all processes of clinical practice.Approximately 70%of diagnostic information originates from radiologic images,which also account for 90%of the digital data volume of a hospital.However,the number of physicians has increased only modestly compared to the rapid growth in the number of medical images.In China,data from medical imaging increases by 30%every year,whereas the number of radiologists increases by only 4%annually.Artificial intelligence(AI),which is representative technology of the fourth industrial revolution,may alleviate the increasing pressure and job burnout,and further improve the diagnostic efficiency of radiology services[1].Despite the urgent and realistic demand for AI technology,many challenges remain in the development and translation of AI products.The rate of the scientific translation of AI research into clinical applications is extremely low.Furthermore,AI models that are applied in clinical settings exhibit unreliable performance and are often impractical[2].Therefore,radiologists may not have access to suitable medical imaging AI models to solve specific clinical problems.This paper analyzes and discusses this problem according to two aspects:the data sources and the AI algorithm(Fig.1).
基金funded in part of the National High-tech R&D Program of China(863 Program)(2012AA020307)the introduction of innovative R&D team program of Guangdong Province(2009010058)+1 种基金the National Natural Science Foundation of China(81001372,81173470)the Fundamental Research Funds for the Central Universities(10ykjc01)
文摘Human intestinal carboxyl esterase （hiCE） is a drug target for ameliorating irinotecan-induced diarrhea. By reducing irinotecan- induced diarrhea, hiCE inhibitors can improve the anti-cancer efficacy of irinotecan. To find effective hiCE inhibitors, a new virtual screening protocol that combines pharmacophore models derived from the hiCE structure and its ligands has been pro- posed. The hiCE structure has been constructed through homology techniques using hCESI＇s crystal structure. The hiCE structure was optimized via molecular dynamics simulations with the most known active hiCE inhibitors docked into the structure. An optimized pharmacophore, derived from the receptor, was then generated. A ligand-based pharmacophore was also generated from a larger set of known hiCE inhibitors. The final hiCE inhibitor predictions were based upon the virtual screening hits from both ligand-based and receptor-based pharmacophore models. The hit rates from the ligand-based and receptor-based pharmacophore models are 88% and 86%, respectively. The final hit rate is 94%. The two models are highly consistent with one another （85%）. This proves that both models are reliable.
