There has been ongoing interest in China's economic growth.What were the drivers of China's economic growth in past years?What policies were used to promote China's economic growth?Although different lense...There has been ongoing interest in China's economic growth.What were the drivers of China's economic growth in past years?What policies were used to promote China's economic growth?Although different lenses may be used to understand and explain China's economic growth,this paper draws on historical,theoretical,and empirical perspectives to discuss the nexus between China's regional policies and economic growth.First,we review the evolution of China's regional policy and the policy's changing emphasis in different development stages,from balanced,unbalanced,and coordinated development to synergistic development.Then we construct a theoretical model to illustrate the impact of regional policy on the local economy and conduct an empirical examination with a case study of regional policy using regression discontinuity design.This paper analyzes the concept of regional policy and the underpinning logic of economic growth and presents practical approaches to formulate a better regional policyframework.展开更多
Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictl...Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.展开更多
Purpose:Our previous study has shown that PTPRZ1-MET(ZM)fusion is a viable target for MET inhibitors in gliomas.However,the diversity and prevalence of somatic MET alterations in difuse gliomas are still elusive and n...Purpose:Our previous study has shown that PTPRZ1-MET(ZM)fusion is a viable target for MET inhibitors in gliomas.However,the diversity and prevalence of somatic MET alterations in difuse gliomas are still elusive and need to be extensively characterized for identifying novel therapeutic targets.Methods:Totally,1,350 glioma patients and 31 patient-derived cells were collected from the Chinese Glioma Genome Atlas(CGGA)and published data.All kinds of MET fusions and/or splicing variants(MET F/SVs)were identifed by bioinformatical methods.Single-cell RNA sequencing(scRNA-seq)were used for validation.In vitro experiments of drug resistance were conducted for the possibility of MET-targeted treatment.Results:MET F/SVs but not genomic amplifcation,were highly enriched in the secondary glioblastomas(sGBM)and marked worse prognosis.Further molecular and scRNA-seq analysis revealed that MET F/SVs were induced in the course of glioma evolution and highly associated with MET overexpression.Subsequent in vitro and the clinical study showed that cells and patients harboring MET F/SVs have better response to MET inhibitors.Conclusion:Our fndings expanded the percentage of gliomas with abnormal MET alterations and suggested that a subgroup of gliomas harboring MET F/SVs may beneft from MET-targeted therapy.展开更多
基金supported by the Fundamental Research Funds for the Central Universities,the Center for International Knowledge on Development,and the Department for International Development.
文摘There has been ongoing interest in China's economic growth.What were the drivers of China's economic growth in past years?What policies were used to promote China's economic growth?Although different lenses may be used to understand and explain China's economic growth,this paper draws on historical,theoretical,and empirical perspectives to discuss the nexus between China's regional policies and economic growth.First,we review the evolution of China's regional policy and the policy's changing emphasis in different development stages,from balanced,unbalanced,and coordinated development to synergistic development.Then we construct a theoretical model to illustrate the impact of regional policy on the local economy and conduct an empirical examination with a case study of regional policy using regression discontinuity design.This paper analyzes the concept of regional policy and the underpinning logic of economic growth and presents practical approaches to formulate a better regional policyframework.
基金supported by the National Natural Science Foundation of China(Nos.81773015 and 82072789)the National Key Research and Development Program of China(No.2019YFE0108100)the Erik Philip-Sörensen Foundation.
文摘Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
基金supported by grants from the Natural Science Foundation of China (NSFC)/Research Grants Council (RGC),Hong Kong,China Joint Research Scheme (81761168038)the National Natural Science Foundation of China (81802994,81903078,81972337,81972816,82002647,82192894,82103623,and 82002994)+3 种基金the Mainland-Hong Kong Joint Funding Scheme ITC grant MHP/004/19 and MOST grant 2019YFE0109400the Beijing Natural Science Foundation (JQ20030)Sino-German Center for Research Promotion (M-0020)the Beijing Nova Program (Z201100006820118).
文摘Purpose:Our previous study has shown that PTPRZ1-MET(ZM)fusion is a viable target for MET inhibitors in gliomas.However,the diversity and prevalence of somatic MET alterations in difuse gliomas are still elusive and need to be extensively characterized for identifying novel therapeutic targets.Methods:Totally,1,350 glioma patients and 31 patient-derived cells were collected from the Chinese Glioma Genome Atlas(CGGA)and published data.All kinds of MET fusions and/or splicing variants(MET F/SVs)were identifed by bioinformatical methods.Single-cell RNA sequencing(scRNA-seq)were used for validation.In vitro experiments of drug resistance were conducted for the possibility of MET-targeted treatment.Results:MET F/SVs but not genomic amplifcation,were highly enriched in the secondary glioblastomas(sGBM)and marked worse prognosis.Further molecular and scRNA-seq analysis revealed that MET F/SVs were induced in the course of glioma evolution and highly associated with MET overexpression.Subsequent in vitro and the clinical study showed that cells and patients harboring MET F/SVs have better response to MET inhibitors.Conclusion:Our fndings expanded the percentage of gliomas with abnormal MET alterations and suggested that a subgroup of gliomas harboring MET F/SVs may beneft from MET-targeted therapy.