Although the spatial characteristics within the tumor microenvironment of lung adenocarcinoma(LUAD)have been identified,the mechanisms by which these factors promote LUAD progression and immune evasion remain unclear....Although the spatial characteristics within the tumor microenvironment of lung adenocarcinoma(LUAD)have been identified,the mechanisms by which these factors promote LUAD progression and immune evasion remain unclear.Using spatial transcriptomics and single-cell RNA-sequencing data from multi-regional LUAD biopsies consisting of tumor core,tumor edge,and normal area,we sought to delineate the spatial heterogeneity and driving factors of cell colocalization.Two cancer cell sub-clusters(Cancer_c1 and Cancer_c2),associated with LUAD initiation and metastasis,respectively,exhibit distinct spatial distributions and immune cell colocalizations.In particular,Cancer_c1,enriched within the tumor core,could directly interact with B cells or indirectly recruit B cells through macrophages.Conversely,Cancer_c2 enriched within the tumor edge exhibits colocalization with CD8^(+)T cells.Collectively,our work elucidates the spatial distribution of cancer cell subtypes and their interaction with immune cells in the core and edge of LUAD,providing insights for developing therapeutic strategies for cancer intervention.展开更多
Most genome-wide association studies(GWAS)of Venous Thromboembolism(VTE)have used data from individuals of European descent,however,genetic factors for VTE have not been fully identified in Chinese populations,which c...Most genome-wide association studies(GWAS)of Venous Thromboembolism(VTE)have used data from individuals of European descent,however,genetic factors for VTE have not been fully identified in Chinese populations,which causes the limited use of existing polygenic risk scores(PRS)to identify subpopulations at high risk of VTE for prevention.We,therefore,aimed to curate all the potential VTE-related single-nucleotide polymorphisms(SNPs)for the construction of a new improved PRS model based on the self-adapting method,and then evaluate its utility and effectiveness in the stratification of VTE risk in Chinese populations.We comprehensively analyzed the mutation spectrum of VTE-associated SNPs in the Chinese cohort,and ranked their individual risk effects independently using risk ratio,logistic regression coefficient,and penalty regression coefficient as evaluation criteria.By integrating various algorithms and evaluating their performance,we trained the optimal prediction model of VTE risk in the Chinese population with the least SNP features,established an adaptive PRS model with progressive SNP overlay,and tested it on an independent Chinese population cohort.Self-adaptive polygenic risk score model based on all 318 SNPs or on the 44 most strongly associated SNPs performed similarly(areas under receiver-operating characteristic curves(AUCs)of 0.739 and 0.709,respectively)on the testing dataset of the Chinese VTE cohort,and that achieve the overall best level of the AUC from a conventional PRS model based on known genetic risk factors(0.620–0.718).In addition,we observed the self-adaptive PRS model was an independent effective risk stratification indicator beyond other clinical characteristics including age and smoking status.Our data revealed that only 44 SNPs-derived PRS model can be effectively used in discriminating subpopulations at high risk of VTE.To become clinically useful,our model could benefit from a practically feasible VTE screening program for precision prevention in Chinese populations.展开更多
The hyper-redundant manipulator(HRM)can explore narrow and curved pipelines by leveraging its high flexibility and redundancy.However,planning collision-free motion trajectories for HRMs in confined environments remai...The hyper-redundant manipulator(HRM)can explore narrow and curved pipelines by leveraging its high flexibility and redundancy.However,planning collision-free motion trajectories for HRMs in confined environments remains a significant challenge.To address this issue,a pipeline inspection approach that combines nonlinear model predictive control(NMPC)with the snake-inspired crawling algorithm(SCA)is proposed.The approach consists of three processes:insertion,inspection,and exit.The insertion and exit processes utilize the SCA,inspired by snake motion,to significantly reduce path planning time.The inspection process employs NMPC to generate collision-free motion.The prototype HRM is developed,and inspection experiments are conducted in various complex pipeline scenarios to validate the effectiveness and feasibility of the proposed method.Experimental results demonstrate that the approach effectively minimizes the computational cost of path planning,offering a practical solution for HRM applications in pipeline inspection.展开更多
Ancient cities and towns are popular tourism destinations worldwide.In this paper,Guangfu Ancient City in Yongnian County,Hebei Province,China,is taken as the case study and the modifed creative destruction model is a...Ancient cities and towns are popular tourism destinations worldwide.In this paper,Guangfu Ancient City in Yongnian County,Hebei Province,China,is taken as the case study and the modifed creative destruction model is applied as the analytical framework to evaluate the multiactor dynamics of heritage tourism development.A mixed method approach is adopted,including a local resident survey,in-depth interviews with staf of the Guangfu Ancient City tourism site and government ofcials responsible for the heritage conservation and tourism development of the site,and a review of online tourist reviews,relevant government documents and reports.Based on the modifed creative destruction model,local residents’attitudes towards tourism development,changes in tourist numbers,the level of business and government investments,and the motivations of diferent stakeholders in tourism development are assessed by synthesising on-site research,historical data and other materials.Then,the tourism development stages for Guangfu Ancient City are identifed as the precommodifcation stage before 2006,the early commodifcation stage from 2006 to 2011 and the advanced commodifcation stage from 2012 to 2017.The fndings indicate that with rapid increases in investments from both corporate and government sources and in the number of tourists,the attitude of local residents towards tourism development remained positive.The results show that instead of entering the initial destruction stage,Guangfu Ancient City is in the transition stage from advanced commodifcation to creative enhancement given the government’s dominant role in tourism development,the heritage conservation motives of tourism entrepreneurs,the benefts to residents from tourism development ensured by government policies,and the shift in tourist type to postmodern tourists with double demands.The applicability of the modifed creative destruction model is further discussed,and policy and management recommendations are generated to support the sustainable development of Guangfu Ancient City after the COVID-19 pandemic.展开更多
基金supported by the National Natural Science Foundation of China(82002432 to J.W.,82302068 to M.Z.,and 32300568 to T.W.)the Natural Science Foundation of Shandong Province(ZR2024MH159 to Y.Z.,ZR2020QH179 to J.W.,ZR2022QH057 to M.Z.,and ZR2021QH005 to T.W.)the China Postdoctoral Science Foundation(2024M752006 to S.M.)。
文摘Although the spatial characteristics within the tumor microenvironment of lung adenocarcinoma(LUAD)have been identified,the mechanisms by which these factors promote LUAD progression and immune evasion remain unclear.Using spatial transcriptomics and single-cell RNA-sequencing data from multi-regional LUAD biopsies consisting of tumor core,tumor edge,and normal area,we sought to delineate the spatial heterogeneity and driving factors of cell colocalization.Two cancer cell sub-clusters(Cancer_c1 and Cancer_c2),associated with LUAD initiation and metastasis,respectively,exhibit distinct spatial distributions and immune cell colocalizations.In particular,Cancer_c1,enriched within the tumor core,could directly interact with B cells or indirectly recruit B cells through macrophages.Conversely,Cancer_c2 enriched within the tumor edge exhibits colocalization with CD8^(+)T cells.Collectively,our work elucidates the spatial distribution of cancer cell subtypes and their interaction with immune cells in the core and edge of LUAD,providing insights for developing therapeutic strategies for cancer intervention.
基金National High Level Hospital Clinical Research Funding 2023-NHLHCRF-YGJH-03.
文摘Most genome-wide association studies(GWAS)of Venous Thromboembolism(VTE)have used data from individuals of European descent,however,genetic factors for VTE have not been fully identified in Chinese populations,which causes the limited use of existing polygenic risk scores(PRS)to identify subpopulations at high risk of VTE for prevention.We,therefore,aimed to curate all the potential VTE-related single-nucleotide polymorphisms(SNPs)for the construction of a new improved PRS model based on the self-adapting method,and then evaluate its utility and effectiveness in the stratification of VTE risk in Chinese populations.We comprehensively analyzed the mutation spectrum of VTE-associated SNPs in the Chinese cohort,and ranked their individual risk effects independently using risk ratio,logistic regression coefficient,and penalty regression coefficient as evaluation criteria.By integrating various algorithms and evaluating their performance,we trained the optimal prediction model of VTE risk in the Chinese population with the least SNP features,established an adaptive PRS model with progressive SNP overlay,and tested it on an independent Chinese population cohort.Self-adaptive polygenic risk score model based on all 318 SNPs or on the 44 most strongly associated SNPs performed similarly(areas under receiver-operating characteristic curves(AUCs)of 0.739 and 0.709,respectively)on the testing dataset of the Chinese VTE cohort,and that achieve the overall best level of the AUC from a conventional PRS model based on known genetic risk factors(0.620–0.718).In addition,we observed the self-adaptive PRS model was an independent effective risk stratification indicator beyond other clinical characteristics including age and smoking status.Our data revealed that only 44 SNPs-derived PRS model can be effectively used in discriminating subpopulations at high risk of VTE.To become clinically useful,our model could benefit from a practically feasible VTE screening program for precision prevention in Chinese populations.
文摘The hyper-redundant manipulator(HRM)can explore narrow and curved pipelines by leveraging its high flexibility and redundancy.However,planning collision-free motion trajectories for HRMs in confined environments remains a significant challenge.To address this issue,a pipeline inspection approach that combines nonlinear model predictive control(NMPC)with the snake-inspired crawling algorithm(SCA)is proposed.The approach consists of three processes:insertion,inspection,and exit.The insertion and exit processes utilize the SCA,inspired by snake motion,to significantly reduce path planning time.The inspection process employs NMPC to generate collision-free motion.The prototype HRM is developed,and inspection experiments are conducted in various complex pipeline scenarios to validate the effectiveness and feasibility of the proposed method.Experimental results demonstrate that the approach effectively minimizes the computational cost of path planning,offering a practical solution for HRM applications in pipeline inspection.
基金supported by the Fundamental Research Funds for the Central Universities,and the Research Funds of Renmin University of China(19XNI004)to Dr.Ming Ming Su.
文摘Ancient cities and towns are popular tourism destinations worldwide.In this paper,Guangfu Ancient City in Yongnian County,Hebei Province,China,is taken as the case study and the modifed creative destruction model is applied as the analytical framework to evaluate the multiactor dynamics of heritage tourism development.A mixed method approach is adopted,including a local resident survey,in-depth interviews with staf of the Guangfu Ancient City tourism site and government ofcials responsible for the heritage conservation and tourism development of the site,and a review of online tourist reviews,relevant government documents and reports.Based on the modifed creative destruction model,local residents’attitudes towards tourism development,changes in tourist numbers,the level of business and government investments,and the motivations of diferent stakeholders in tourism development are assessed by synthesising on-site research,historical data and other materials.Then,the tourism development stages for Guangfu Ancient City are identifed as the precommodifcation stage before 2006,the early commodifcation stage from 2006 to 2011 and the advanced commodifcation stage from 2012 to 2017.The fndings indicate that with rapid increases in investments from both corporate and government sources and in the number of tourists,the attitude of local residents towards tourism development remained positive.The results show that instead of entering the initial destruction stage,Guangfu Ancient City is in the transition stage from advanced commodifcation to creative enhancement given the government’s dominant role in tourism development,the heritage conservation motives of tourism entrepreneurs,the benefts to residents from tourism development ensured by government policies,and the shift in tourist type to postmodern tourists with double demands.The applicability of the modifed creative destruction model is further discussed,and policy and management recommendations are generated to support the sustainable development of Guangfu Ancient City after the COVID-19 pandemic.
