The Hengduan Mountains Region(HMR)is the largest“evolutionary frontier”of the northern temperate zone,and the origin and maintenance of species in this area is a research hotspot.Exploring species-specific responses...The Hengduan Mountains Region(HMR)is the largest“evolutionary frontier”of the northern temperate zone,and the origin and maintenance of species in this area is a research hotspot.Exploring species-specific responses to historical and contemporary environmental changes will improve our understanding of the role of this region in maintaining biodiversity.In this study,mitochondrial and microsatellite diversities were used to assess the contributions of paleogeological events,Pleistocene climatic oscillations,and contemporary landscape characteristics to the rapid intraspecific diversification of Liangshantriton taliangensis,a vulnerable amphibian species endemic to several sky-island mountains in the southeastern HMR.Divergence date estimations suggested that the East Asian monsoon,local uplifting events(Xigeda Formation strata),and Early-Middle Pleistocene transition(EMPT)promoted rapid divergence of L.taliangensis during the Pleistocene,yielding eight mitochondrial lineages and six nuclear genetic lineages.Moreover,population genetic structures were mainly fixed through isolation by resistance.Multiple in situ refugia were identified by ecological niche models and high genetic diversity,which played crucial roles in the persistence and divergence of L.taliangensis during glacial-interglacial cycles.Dramatic climatic fluctuations further promoted recurrent isolation and admixing of populations in scattered glacial refugia.The apparent mitonuclear discordance was likely the result of introgression by secondary contact and/or female-biased dispersal.Postglacial expansion generated two major secondary contact zones(Ganluo(GL)and Chuhongjue(CHJ)).Identification of conservation management units and dispersal corridors offers important recommendations for the conservation of this species.展开更多
The current distribution of forest tree species is a result of natural or human mediated historical and contemporary processes. Knowledge of the spatial distribution of the diversity and divergence of populations is c...The current distribution of forest tree species is a result of natural or human mediated historical and contemporary processes. Knowledge of the spatial distribution of the diversity and divergence of populations is crucial for managing and conserving genetic resources in forest tree species. By combining tools from population genetics, landscape ecology and spatial statistics, landscape genetics thus represents a powerful method for evaluating the geographic patterns of genetic resources at the population level. In this study, we explore the possibility of combining genetic diversity data, spatial statistic tools and GIS technologies to map the genetic divergence and diversity of 31 Castanea sativa populations collected in Spain, Italy, Greece, and Turkey. The IDW technique was used to interpolate the diversity values and divergence indices as expected hetereozygosity (He), allelic richness (Rs), private allelic richness (PRs), and membership values (Q) of each population to different clusters. Genetic diversity maps and a synthetic map of the spatial genetic structure of European chestnut populations were produced. Spatial coincidences between landscape elements and statistically significant genetic discontinuities between populations were investigated. Evidence is provided of the significance of cartographic outputs produced in the study and on their usefulness in managing genetic resources.展开更多
The Chinese yew（Taxus wallichiana）,which is widely distributed in the Himalayas and in southern China,is now on the edge of extinction.In order to understand the evolutionary processes that control the current diver...The Chinese yew（Taxus wallichiana）,which is widely distributed in the Himalayas and in southern China,is now on the edge of extinction.In order to understand the evolutionary processes that control the current diversity within this species at the genetic and ecological levels,its genetic patterns and range dynamics must first be identified and mapped.This knowledge can then be applied in the development of an effective conservation strategy.Based on molecular data obtained from 48 populations of T.wallichiana,we used GIS-based interpolation approach for the explicit visualization of patterns of genetic divergence and diversity,and a number of potential evolutionary hotspots have been specifically identified within the genetic landscape maps.Within the maps of genetic divergence and diversity,five areas of high inter-population genetic divergence and six areas of high intra-population genetic diversity have been highlighted in a number of separate mountain regions,and these evolutionary hotspots should have the priority to be protected.Furthermore,four geographical barriers have been identified： the eastern Himalayas,the Yunnan Plateau,the Hengduan Mountains and the Taiwan Strait.According to ecological niche modeling（ENM）,the populations of T.wallichiana within the Sino-Himalayan Forest floristic subkingdom experienced westward expansion from the periods of Last Inter-glacial to Last Glacial Maximum（LGM）.Following the LGM,the distribution range overall became reduced and fragmented.These findings challenge the classic mode of contraction-expansion in response to the last glaciation.In conclusion,our findings suggest that the changes in geographical landscapes and climate that occurred during the Quaternary resulted in current genetic landscape patterns.展开更多
Glioblastoma(GBM)remains the most aggressive and lethal brain tumor in adults and poses significant challenges to patient survival.This review provides a comprehensive exploration of the molecular and genetic landscap...Glioblastoma(GBM)remains the most aggressive and lethal brain tumor in adults and poses significant challenges to patient survival.This review provides a comprehensive exploration of the molecular and genetic landscape of GBM,focusing on key oncogenic drivers,such as epidermal growth factor receptor(EGFR),platelet-derived growth factor receptor(PDGFR),and the PI3K/AKT/mTOR pathway,which are critical for tumorigenesis and progression.We delve into the role of epigenetic alterations,including DNA methylation and histone modifications,in driving therapy resistance and tumor evolution.The tumor microenvironment is known for its pivotal role in immune evasion,with tumor-associated macrophages,myeloid-derived suppressor cells,and regulatory T cells creating an immunosuppressive niche that sustains GBM growth.Emerging therapies,such as immunotherapies,oncolytic viral therapies,extracellular vesicle-based approaches,and non-coding RNA interventions,are highlighted as promising avenues to disrupt GBM pathogenesis.Advances in precision medicine and innovative technologies,including electric field therapy and locoregional treatments,are discussed for their potential to overcome the blood‒brain barrier and treatment resistance.Additionally,this review underscores the importance of metabolic reprogramming,particularly hypoxia-driven adaptations and altered lipid metabolism,in fueling GBM progression and influencing the therapeutic response.展开更多
Intrahepatic cholangiocarcinoma(iCCA)is a highly aggressive primary liver cancer with limited treatment options and poor prognosis.Although gemcitabine combined with cisplatin(GEMCIS)or newly GEMCIS plus durvalumab is...Intrahepatic cholangiocarcinoma(iCCA)is a highly aggressive primary liver cancer with limited treatment options and poor prognosis.Although gemcitabine combined with cisplatin(GEMCIS)or newly GEMCIS plus durvalumab is the first-line systemic therapy for iCCA,several promising treatment targets have been identified in the past decade in both first-and subsequent-line settings,including neurotrophic tropomyosin-receptor tyrosine kinase(NTRK)fusions,RET fusions,high microsatellite instability(MSI-H),high tumor mutation burden(TMB-H),as well as fibroblast growth factor receptor 2(FGFR2)fusions,BRAF V600E mutation,isocitrate dehydrogenase(IDH)-1 and IDH-2 mutations,and human epidermal growth factor receptor 2[HER2(ERBB2)]amplifications.Corresponding small molecule inhibitors and monoclonal antibodies have demonstrated improved efficacy and survival benefits in phase 2 or phase 3 studies,gained regulatory approvals or recommendations in guidelines,and reshaped the therapeutic management for advanced cholangiocarcinoma.Numerous novel targeted drugs and combination therapies have been developed and are under evaluation.Despite the progress made in targeted therapy,it still faces challenges such as acquired drug resistance,precise patient selection,and serious adverse events.Therefore,large-scale randomized phase 3 trials of novel targeted agents and innovative regimens are warranted to benefit this population.Herein,we present a comprehensive review of the literature of clinical significance on targeted therapy for iCCA in recent years,focusing on the advances in mutation-based targeted therapy.展开更多
基金supported by the National Key Research and Development Programs of China(2017YFC0505202)Construction of Basic Conditions Platform of Sichuan Science and Technology Department(2019JDPT0020)Species Conservation Project of Liziping National Nature Reserve。
文摘The Hengduan Mountains Region(HMR)is the largest“evolutionary frontier”of the northern temperate zone,and the origin and maintenance of species in this area is a research hotspot.Exploring species-specific responses to historical and contemporary environmental changes will improve our understanding of the role of this region in maintaining biodiversity.In this study,mitochondrial and microsatellite diversities were used to assess the contributions of paleogeological events,Pleistocene climatic oscillations,and contemporary landscape characteristics to the rapid intraspecific diversification of Liangshantriton taliangensis,a vulnerable amphibian species endemic to several sky-island mountains in the southeastern HMR.Divergence date estimations suggested that the East Asian monsoon,local uplifting events(Xigeda Formation strata),and Early-Middle Pleistocene transition(EMPT)promoted rapid divergence of L.taliangensis during the Pleistocene,yielding eight mitochondrial lineages and six nuclear genetic lineages.Moreover,population genetic structures were mainly fixed through isolation by resistance.Multiple in situ refugia were identified by ecological niche models and high genetic diversity,which played crucial roles in the persistence and divergence of L.taliangensis during glacial-interglacial cycles.Dramatic climatic fluctuations further promoted recurrent isolation and admixing of populations in scattered glacial refugia.The apparent mitonuclear discordance was likely the result of introgression by secondary contact and/or female-biased dispersal.Postglacial expansion generated two major secondary contact zones(Ganluo(GL)and Chuhongjue(CHJ)).Identification of conservation management units and dispersal corridors offers important recommendations for the conservation of this species.
文摘The current distribution of forest tree species is a result of natural or human mediated historical and contemporary processes. Knowledge of the spatial distribution of the diversity and divergence of populations is crucial for managing and conserving genetic resources in forest tree species. By combining tools from population genetics, landscape ecology and spatial statistics, landscape genetics thus represents a powerful method for evaluating the geographic patterns of genetic resources at the population level. In this study, we explore the possibility of combining genetic diversity data, spatial statistic tools and GIS technologies to map the genetic divergence and diversity of 31 Castanea sativa populations collected in Spain, Italy, Greece, and Turkey. The IDW technique was used to interpolate the diversity values and divergence indices as expected hetereozygosity (He), allelic richness (Rs), private allelic richness (PRs), and membership values (Q) of each population to different clusters. Genetic diversity maps and a synthetic map of the spatial genetic structure of European chestnut populations were produced. Spatial coincidences between landscape elements and statistically significant genetic discontinuities between populations were investigated. Evidence is provided of the significance of cartographic outputs produced in the study and on their usefulness in managing genetic resources.
基金National Basic Research Program of China(No.2010CB951704)National Natural Science Foundation of China(No.41271068)
文摘The Chinese yew（Taxus wallichiana）,which is widely distributed in the Himalayas and in southern China,is now on the edge of extinction.In order to understand the evolutionary processes that control the current diversity within this species at the genetic and ecological levels,its genetic patterns and range dynamics must first be identified and mapped.This knowledge can then be applied in the development of an effective conservation strategy.Based on molecular data obtained from 48 populations of T.wallichiana,we used GIS-based interpolation approach for the explicit visualization of patterns of genetic divergence and diversity,and a number of potential evolutionary hotspots have been specifically identified within the genetic landscape maps.Within the maps of genetic divergence and diversity,five areas of high inter-population genetic divergence and six areas of high intra-population genetic diversity have been highlighted in a number of separate mountain regions,and these evolutionary hotspots should have the priority to be protected.Furthermore,four geographical barriers have been identified： the eastern Himalayas,the Yunnan Plateau,the Hengduan Mountains and the Taiwan Strait.According to ecological niche modeling（ENM）,the populations of T.wallichiana within the Sino-Himalayan Forest floristic subkingdom experienced westward expansion from the periods of Last Inter-glacial to Last Glacial Maximum（LGM）.Following the LGM,the distribution range overall became reduced and fragmented.These findings challenge the classic mode of contraction-expansion in response to the last glaciation.In conclusion,our findings suggest that the changes in geographical landscapes and climate that occurred during the Quaternary resulted in current genetic landscape patterns.
文摘Glioblastoma(GBM)remains the most aggressive and lethal brain tumor in adults and poses significant challenges to patient survival.This review provides a comprehensive exploration of the molecular and genetic landscape of GBM,focusing on key oncogenic drivers,such as epidermal growth factor receptor(EGFR),platelet-derived growth factor receptor(PDGFR),and the PI3K/AKT/mTOR pathway,which are critical for tumorigenesis and progression.We delve into the role of epigenetic alterations,including DNA methylation and histone modifications,in driving therapy resistance and tumor evolution.The tumor microenvironment is known for its pivotal role in immune evasion,with tumor-associated macrophages,myeloid-derived suppressor cells,and regulatory T cells creating an immunosuppressive niche that sustains GBM growth.Emerging therapies,such as immunotherapies,oncolytic viral therapies,extracellular vesicle-based approaches,and non-coding RNA interventions,are highlighted as promising avenues to disrupt GBM pathogenesis.Advances in precision medicine and innovative technologies,including electric field therapy and locoregional treatments,are discussed for their potential to overcome the blood‒brain barrier and treatment resistance.Additionally,this review underscores the importance of metabolic reprogramming,particularly hypoxia-driven adaptations and altered lipid metabolism,in fueling GBM progression and influencing the therapeutic response.
基金supported by the National Natural Science Foundation of China(Dr Bin Yi,No.82173213)by the Shanghai Natural Science Foundation(Dr Bin Yi,No.21Y11912500).
文摘Intrahepatic cholangiocarcinoma(iCCA)is a highly aggressive primary liver cancer with limited treatment options and poor prognosis.Although gemcitabine combined with cisplatin(GEMCIS)or newly GEMCIS plus durvalumab is the first-line systemic therapy for iCCA,several promising treatment targets have been identified in the past decade in both first-and subsequent-line settings,including neurotrophic tropomyosin-receptor tyrosine kinase(NTRK)fusions,RET fusions,high microsatellite instability(MSI-H),high tumor mutation burden(TMB-H),as well as fibroblast growth factor receptor 2(FGFR2)fusions,BRAF V600E mutation,isocitrate dehydrogenase(IDH)-1 and IDH-2 mutations,and human epidermal growth factor receptor 2[HER2(ERBB2)]amplifications.Corresponding small molecule inhibitors and monoclonal antibodies have demonstrated improved efficacy and survival benefits in phase 2 or phase 3 studies,gained regulatory approvals or recommendations in guidelines,and reshaped the therapeutic management for advanced cholangiocarcinoma.Numerous novel targeted drugs and combination therapies have been developed and are under evaluation.Despite the progress made in targeted therapy,it still faces challenges such as acquired drug resistance,precise patient selection,and serious adverse events.Therefore,large-scale randomized phase 3 trials of novel targeted agents and innovative regimens are warranted to benefit this population.Herein,we present a comprehensive review of the literature of clinical significance on targeted therapy for iCCA in recent years,focusing on the advances in mutation-based targeted therapy.
