Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(P...Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(PC)remain not fully explored.The study aimed to explore how gut metabolites regulate death-ligand 1(PD-L1)blockade via exosomes and boost immune checkpoint inhibitors(ICIs)in PC.Methods:We recruited 70 PC patients to set up into five subgroups.The integrated multi-omics analysis was performed.In parallel,we validated the function of gut microbiome-associated metabolites on PD-L1 production and immunotherapy treatment efficacy in PC cell lines and transgenic adenocarcinoma of the mouse prostate(TRAMP)models.Results:We identified two metabolites,16(R)-Hydroxyeicosatetraenoic acid(16(R)-HETE)and 6-Keto-Prostaglandin E1(6-Keto-PGE1),that positively correlated with the plasma exosomal PD-L1 levels.The in vitro experiments found that both 16(R)-HETE and 6-Keto-PGE1 can enhance PD-L1 expression at the mRNA,protein,and exosome levels in both human and mouse PC cell lines,which were also validated in vivo based on subcutaneous mouse models.Both metabolites significantly promoted the anti-PD-L1 efficacy against PC in situ on a TRAMP mouse model.Conclusions:Targeting the“gut-tumor metabolic axis”is a promising strategy to improve the efficacy of immune checkpoint inhibitors in tumors.展开更多
Through reviewing development history of concession gardens in Tianjin City,features,advantages and problems of these gardens were analyzed.It was stressed that cultural context should be inherited,and features of the...Through reviewing development history of concession gardens in Tianjin City,features,advantages and problems of these gardens were analyzed.It was stressed that cultural context should be inherited,and features of the city highlighted.The gardens should be protected from the perspective of development,combined with urban green space system,integrated with cultural life of local citizens,and coordinated with contemporary architectural style of the city.In addition,plant landscapes should be enriched,and infrastructure of the gardens supplemented to properly handle the relationship between urban construction and protection of historical image,and provide reference for inheriting cultural context of the city in the urban development.展开更多
Through the overview of the development history of Tianjin Concession Parks, this paper analyzed the historical significance of Tianjin Concession Parks and put forward its existing problems, then summed up a series o...Through the overview of the development history of Tianjin Concession Parks, this paper analyzed the historical significance of Tianjin Concession Parks and put forward its existing problems, then summed up a series of strategies of sustainable development as follows: adhering to the Florence Charter; retaining the original form and texture of the Concession Parks; adopting a dynamic philosophy of protection and preservation; integrating with citizens' social life; supplementing and improving infrastructure facilities; and achieving environmental regeneration by planting. All these efforts are expected to contribute to making a balance between the development and construction of urban cities and the preservation of historical features, as well as provide lessons for inheriting urban history and culture in the future.展开更多
We report new material of the zalambdalestid,Zhangolestes jilinensis,from the Quantou Formation(lower Upper Cretaceous,Cenomanian to Turonian),Gongzhuling City,Jilin Province,NE China.Using micro-CT-scan,the material ...We report new material of the zalambdalestid,Zhangolestes jilinensis,from the Quantou Formation(lower Upper Cretaceous,Cenomanian to Turonian),Gongzhuling City,Jilin Province,NE China.Using micro-CT-scan,the material is shown to include dentocranial and postcranial elements recovered from the same matrix block containing the holotype specimen.The CT-images also show the labial and internal structures of the holotype fragment of the lower jaw of Z.jilinensis.Based on the preservation,relative size,and tooth wear,the new material and the holotype lower jaw likely belong to the same individual animal,whereas the hypodigm mandibular fragment assigned to Z.jilinensis in the original study is thought now to belong to a different individual,potentially representing a different species,which,if true,would increase the eutherian diversity in the Late Cretaceous Changchunsaurus Fauna.Furthermore,the new CT-images show that the incisor morphology is diverse within zalambdalestids and probably evolved independently from the enlarged incisors in placental mammals,such as Glires.展开更多
基金supported by Tianjian advanced biomedical laboratory key research and development projectHenan Province Natural Science Foundation(Grant Number 242300421283)Major Science and Technology Project of Henan Province(221100310200)。
文摘Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(PC)remain not fully explored.The study aimed to explore how gut metabolites regulate death-ligand 1(PD-L1)blockade via exosomes and boost immune checkpoint inhibitors(ICIs)in PC.Methods:We recruited 70 PC patients to set up into five subgroups.The integrated multi-omics analysis was performed.In parallel,we validated the function of gut microbiome-associated metabolites on PD-L1 production and immunotherapy treatment efficacy in PC cell lines and transgenic adenocarcinoma of the mouse prostate(TRAMP)models.Results:We identified two metabolites,16(R)-Hydroxyeicosatetraenoic acid(16(R)-HETE)and 6-Keto-Prostaglandin E1(6-Keto-PGE1),that positively correlated with the plasma exosomal PD-L1 levels.The in vitro experiments found that both 16(R)-HETE and 6-Keto-PGE1 can enhance PD-L1 expression at the mRNA,protein,and exosome levels in both human and mouse PC cell lines,which were also validated in vivo based on subcutaneous mouse models.Both metabolites significantly promoted the anti-PD-L1 efficacy against PC in situ on a TRAMP mouse model.Conclusions:Targeting the“gut-tumor metabolic axis”is a promising strategy to improve the efficacy of immune checkpoint inhibitors in tumors.
文摘Through reviewing development history of concession gardens in Tianjin City,features,advantages and problems of these gardens were analyzed.It was stressed that cultural context should be inherited,and features of the city highlighted.The gardens should be protected from the perspective of development,combined with urban green space system,integrated with cultural life of local citizens,and coordinated with contemporary architectural style of the city.In addition,plant landscapes should be enriched,and infrastructure of the gardens supplemented to properly handle the relationship between urban construction and protection of historical image,and provide reference for inheriting cultural context of the city in the urban development.
基金Sponsored by Art and Science Planning Foundation of Tianjin City(A12069)
文摘Through the overview of the development history of Tianjin Concession Parks, this paper analyzed the historical significance of Tianjin Concession Parks and put forward its existing problems, then summed up a series of strategies of sustainable development as follows: adhering to the Florence Charter; retaining the original form and texture of the Concession Parks; adopting a dynamic philosophy of protection and preservation; integrating with citizens' social life; supplementing and improving infrastructure facilities; and achieving environmental regeneration by planting. All these efforts are expected to contribute to making a balance between the development and construction of urban cities and the preservation of historical features, as well as provide lessons for inheriting urban history and culture in the future.
基金supported by the National Natural Science Foundation of China(Grant Nos.42122010,42072017)the Youth Innovation Promotion Association CAS(Y2023017)+1 种基金the National Mineral Rock and Fossil Specimens Resource Center(NCSTI-RMF20240203)China Geological Survey(DD20230221)。
文摘We report new material of the zalambdalestid,Zhangolestes jilinensis,from the Quantou Formation(lower Upper Cretaceous,Cenomanian to Turonian),Gongzhuling City,Jilin Province,NE China.Using micro-CT-scan,the material is shown to include dentocranial and postcranial elements recovered from the same matrix block containing the holotype specimen.The CT-images also show the labial and internal structures of the holotype fragment of the lower jaw of Z.jilinensis.Based on the preservation,relative size,and tooth wear,the new material and the holotype lower jaw likely belong to the same individual animal,whereas the hypodigm mandibular fragment assigned to Z.jilinensis in the original study is thought now to belong to a different individual,potentially representing a different species,which,if true,would increase the eutherian diversity in the Late Cretaceous Changchunsaurus Fauna.Furthermore,the new CT-images show that the incisor morphology is diverse within zalambdalestids and probably evolved independently from the enlarged incisors in placental mammals,such as Glires.
