This paper carried out a study on U--Th--Pb behavior of zircons in a ＂dry＂ rock system during high-grade metamorphism in the Archean basement of eastern Sbandong. The studied sample has a mineral assemblage of plagi...This paper carried out a study on U--Th--Pb behavior of zircons in a ＂dry＂ rock system during high-grade metamorphism in the Archean basement of eastern Sbandong. The studied sample has a mineral assemblage of plagioclase ＋ K-feldspar ＋ clinopyroxene ＋ biotite ＋ quartz and its pro- tolith is considered to be diorite. The zircons are stubby, equant or irregular in shape and show fir-leaf, sectorial, banded or oscillatory zoning. They contain inclusions, including mineral assemblages of clinopyroxene ＋ orthopyroxene ＋ hornblende ＋ quartz and plagioclase ＋ K-feldspar ＋ biotite ＋ quartz. Fifty SHRIMP analyses were performed on 34 zircon grains, which commonly yielded high Th/U ratios （mostly 〉0.5）. Most analyses are distributed along concordia from 2.54 to 2.25 Ga, with the youngest age being - 1.95 Ga. Compositions and ages show large variations even in a same zircon grain. Combined with early studies, conclusions can be drawn as follows： 1） the diorite underwent two episodes of high-grade metamorphism, at the end of the Neoarchean and the Paleoproterozoic （-2.50 Ga and 1.95 Ga or slightly later）; 2） high-grade metamorphism in a ＂dry＂ rock system may partially reset the U--Th--Pb system of zircons and, in this case, the ages between the oldest and youngest are chronologically meaningless; and 3） high Th/U ratios may be common features of zircons formed during high-grade metamorphic conditions.展开更多
The Central Hebei Basin （CHB） is one of the largest sedimentary basins in the North China Craton, extending in a northeast-southwest direction with an area of 〉350 km2. We carried out SHRIMP zircon dating, Hf-in-zi...The Central Hebei Basin （CHB） is one of the largest sedimentary basins in the North China Craton, extending in a northeast-southwest direction with an area of 〉350 km2. We carried out SHRIMP zircon dating, Hf-in-zircon isotopic analysis and a whole-rock geochemical study on igneous and metasedi- mentary rocks recovered from drill holes that penetrated into the basement of the CHB, Two samples of gneissic granodiorite （XG1-1） and gneissic quartz diorite 048-1） have magmatic ages of 2500 and 2496 Ma, respectively. Their zircons also record metamorphic ages of 2.41-2.51 and ～2.5 Ga, respec- tively. Compared with the gneissic granodiorite, the gneissic quartz diorite has higher REE contents and lower Eu/Eu＊ and （La/Yb）n values. Two metasedimentary samples （MG1, H5） mainly contain ～2,5 Ga detrital zircons as well as late Paleoproterozoic metamorphic grains. The zircons of different origins have eHf （2.5 Ga） values and Hf crustal model ages ranging from 0 to 5 and 2.7 to 2,9 Ga, respectively, Therefore, ～2.5 Ga magmatic and Paleoproterozoic metasedimentary rocks and late Neoarchean to early Paleoproterozoic and late Paleoproterozoic tectono-thermal events have been identified in the basement beneath the CHB. Based on regional comparisons, we conclude that the early Precambrian basement beneath the CHB is part of the North China Craton.展开更多
With the development and regulatory approval of immune checkpoint inhibitors and adoptive cell therapies,cancer immunotherapy has undergone a profound transformation over the past decades.Recently,therapeutic cancer v...With the development and regulatory approval of immune checkpoint inhibitors and adoptive cell therapies,cancer immunotherapy has undergone a profound transformation over the past decades.Recently,therapeutic cancer vaccines have shown promise by eliciting de novo T cell responses targeting tumor antigens,including tumor-associated antigens and tumor-specific antigens.The objective was to amplify and diversify the intrinsic repertoire of tumor-specific T cells.However,the complete realization of these capabilities remains an ongoing pursuit.Therefore,we provide an overview of the current landscape of cancer vaccines in this review.The range of antigen selection,antigen delivery systems development the strategic nuances underlying effective antigen presentation have pioneered cancer vaccine design.Furthermore,this review addresses the current status of clinical trials and discusses their strategies,focusing on tumor-specific immunogenicity and anti-tumor efficacy assessment.However,current clinical attempts toward developing cancer vaccines have not yielded breakthrough clinical outcomes due to significant challenges,including tumor immune microenvironment suppression,optimal candidate identification,immune response evaluation,and vaccine manufacturing acceleration.Therefore,the field is poised to overcome hurdles and improve patient outcomes in the future by acknowledging these clinical complexities and persistently striving to surmount inherent constraints.展开更多
Despite the remarkable success of immune checkpoint inhibitors(ICIs),primary resistance to ICIs causes only subsets of patients to achieve durable responses due to the complex tumor microenvironment(TME).Oncolytic vir...Despite the remarkable success of immune checkpoint inhibitors(ICIs),primary resistance to ICIs causes only subsets of patients to achieve durable responses due to the complex tumor microenvironment(TME).Oncolytic viruses(OVs)can overcome the immunosuppressive TME and promote systemic antitumor immunity in hosts.Engineered OVs armed with ICIs would likely have improved effectiveness as a cancer therapy.According to the diverse immune cell landscapes among different types of tumors,we rationally and precisely generated three recombinant oncolytic adenoviruses(OAds):OAd-SIRPα-Fc,OAd-Siglec10-Fc and OAd-TIGIT-Fc.These viruses were designed to locally deliver SIRPα-Fc,Siglec10-Fc or TIGIT-Fc fusion proteins recognizing CD47,CD24 or CD155,respectively,in the TME to achieve enhanced antitumor effects.Our results suggested that OAd-SIRPα-Fc and OAd-Siglec10-Fc both showed outstanding efficacy in tumor suppression of macrophage-dominated tumors,while OAd-TIGIT-Fc showed the best antitumor immunity in CD8+T-cell-dominated tumors.Importantly,the recombinant OAds activated an inflammatory immune response and generated long-term antitumor memory.In addition,the combination of OAd-Siglec10-Fc with anti-PD-1 significantly enhanced the antitumor effect in a 4T1 tumor model by remodeling the TME.In summary,rationally designed OAds expressing ICIs tailored to the immune cell landscape in the TME can precisely achieve tumor-specific immunotherapy of cancer.展开更多
Immunotherapy,a burgeoning field differs from traditional cancer treatments,is revolutionizing oncologic therapeutics.It aims to stimulate the innate and adaptive immune system of a patient to fight against tumor cell...Immunotherapy,a burgeoning field differs from traditional cancer treatments,is revolutionizing oncologic therapeutics.It aims to stimulate the innate and adaptive immune system of a patient to fight against tumor cells.However,low response rate and immune-related adverse effects(irAEs)remain problems during its management.A novel technology using nanomaterials may bring a solution.Various nanoparticles have been investigated as delivery systems to augment cancer therapeutic efficacy in the lab and clinic.In this review,we briefly summarize the connotation of immunotherapy,the application of nanotechnology in cancer,especially focusing on the synergistic effect of nanoplatform-based technology combined with cancer immunotherapy,hoping to make readers a deep insight into this interdisciplinary field.展开更多
基金supported by the Key Program of the Ministry of Land and Resources of China(Grant Nos.1212010811033, 1212010711815)
文摘This paper carried out a study on U--Th--Pb behavior of zircons in a ＂dry＂ rock system during high-grade metamorphism in the Archean basement of eastern Sbandong. The studied sample has a mineral assemblage of plagioclase ＋ K-feldspar ＋ clinopyroxene ＋ biotite ＋ quartz and its pro- tolith is considered to be diorite. The zircons are stubby, equant or irregular in shape and show fir-leaf, sectorial, banded or oscillatory zoning. They contain inclusions, including mineral assemblages of clinopyroxene ＋ orthopyroxene ＋ hornblende ＋ quartz and plagioclase ＋ K-feldspar ＋ biotite ＋ quartz. Fifty SHRIMP analyses were performed on 34 zircon grains, which commonly yielded high Th/U ratios （mostly 〉0.5）. Most analyses are distributed along concordia from 2.54 to 2.25 Ga, with the youngest age being - 1.95 Ga. Compositions and ages show large variations even in a same zircon grain. Combined with early studies, conclusions can be drawn as follows： 1） the diorite underwent two episodes of high-grade metamorphism, at the end of the Neoarchean and the Paleoproterozoic （-2.50 Ga and 1.95 Ga or slightly later）; 2） high-grade metamorphism in a ＂dry＂ rock system may partially reset the U--Th--Pb system of zircons and, in this case, the ages between the oldest and youngest are chronologically meaningless; and 3） high Th/U ratios may be common features of zircons formed during high-grade metamorphic conditions.
基金supported by the Major State Basic Research Program of the People's Republic of China(Grant No.2012CB416600)the National Natural Science Foundation of China(Grant No.40672127)the Key Program of the Ministry of Land and Resources of China(Grant Nos.1212010811033,12120113013700)
文摘The Central Hebei Basin （CHB） is one of the largest sedimentary basins in the North China Craton, extending in a northeast-southwest direction with an area of 〉350 km2. We carried out SHRIMP zircon dating, Hf-in-zircon isotopic analysis and a whole-rock geochemical study on igneous and metasedi- mentary rocks recovered from drill holes that penetrated into the basement of the CHB, Two samples of gneissic granodiorite （XG1-1） and gneissic quartz diorite 048-1） have magmatic ages of 2500 and 2496 Ma, respectively. Their zircons also record metamorphic ages of 2.41-2.51 and ～2.5 Ga, respec- tively. Compared with the gneissic granodiorite, the gneissic quartz diorite has higher REE contents and lower Eu/Eu＊ and （La/Yb）n values. Two metasedimentary samples （MG1, H5） mainly contain ～2,5 Ga detrital zircons as well as late Paleoproterozoic metamorphic grains. The zircons of different origins have eHf （2.5 Ga） values and Hf crustal model ages ranging from 0 to 5 and 2.7 to 2,9 Ga, respectively, Therefore, ～2.5 Ga magmatic and Paleoproterozoic metasedimentary rocks and late Neoarchean to early Paleoproterozoic and late Paleoproterozoic tectono-thermal events have been identified in the basement beneath the CHB. Based on regional comparisons, we conclude that the early Precambrian basement beneath the CHB is part of the North China Craton.
基金supported by the National Natural Science Foundation of China 81573008 and 81860547(Chunyan Dong)National Natural Science Foundation of China 82203861(Wanlu Cao).
文摘With the development and regulatory approval of immune checkpoint inhibitors and adoptive cell therapies,cancer immunotherapy has undergone a profound transformation over the past decades.Recently,therapeutic cancer vaccines have shown promise by eliciting de novo T cell responses targeting tumor antigens,including tumor-associated antigens and tumor-specific antigens.The objective was to amplify and diversify the intrinsic repertoire of tumor-specific T cells.However,the complete realization of these capabilities remains an ongoing pursuit.Therefore,we provide an overview of the current landscape of cancer vaccines in this review.The range of antigen selection,antigen delivery systems development the strategic nuances underlying effective antigen presentation have pioneered cancer vaccine design.Furthermore,this review addresses the current status of clinical trials and discusses their strategies,focusing on tumor-specific immunogenicity and anti-tumor efficacy assessment.However,current clinical attempts toward developing cancer vaccines have not yielded breakthrough clinical outcomes due to significant challenges,including tumor immune microenvironment suppression,optimal candidate identification,immune response evaluation,and vaccine manufacturing acceleration.Therefore,the field is poised to overcome hurdles and improve patient outcomes in the future by acknowledging these clinical complexities and persistently striving to surmount inherent constraints.
基金funded by the National Major Scientific and Technological Special Project for“Significant New Drugs Development”(No.2018ZX09201018-013)by Natural Science Foundation Project of Sichuan(No.2022NSFSC0848)+1 种基金as well as supported by the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYGD18007)The Frontiers Medical Center,Tianfu Jincheng Laboratory Foundation(TFJC202310005).
文摘Despite the remarkable success of immune checkpoint inhibitors(ICIs),primary resistance to ICIs causes only subsets of patients to achieve durable responses due to the complex tumor microenvironment(TME).Oncolytic viruses(OVs)can overcome the immunosuppressive TME and promote systemic antitumor immunity in hosts.Engineered OVs armed with ICIs would likely have improved effectiveness as a cancer therapy.According to the diverse immune cell landscapes among different types of tumors,we rationally and precisely generated three recombinant oncolytic adenoviruses(OAds):OAd-SIRPα-Fc,OAd-Siglec10-Fc and OAd-TIGIT-Fc.These viruses were designed to locally deliver SIRPα-Fc,Siglec10-Fc or TIGIT-Fc fusion proteins recognizing CD47,CD24 or CD155,respectively,in the TME to achieve enhanced antitumor effects.Our results suggested that OAd-SIRPα-Fc and OAd-Siglec10-Fc both showed outstanding efficacy in tumor suppression of macrophage-dominated tumors,while OAd-TIGIT-Fc showed the best antitumor immunity in CD8+T-cell-dominated tumors.Importantly,the recombinant OAds activated an inflammatory immune response and generated long-term antitumor memory.In addition,the combination of OAd-Siglec10-Fc with anti-PD-1 significantly enhanced the antitumor effect in a 4T1 tumor model by remodeling the TME.In summary,rationally designed OAds expressing ICIs tailored to the immune cell landscape in the TME can precisely achieve tumor-specific immunotherapy of cancer.
文摘Immunotherapy,a burgeoning field differs from traditional cancer treatments,is revolutionizing oncologic therapeutics.It aims to stimulate the innate and adaptive immune system of a patient to fight against tumor cells.However,low response rate and immune-related adverse effects(irAEs)remain problems during its management.A novel technology using nanomaterials may bring a solution.Various nanoparticles have been investigated as delivery systems to augment cancer therapeutic efficacy in the lab and clinic.In this review,we briefly summarize the connotation of immunotherapy,the application of nanotechnology in cancer,especially focusing on the synergistic effect of nanoplatform-based technology combined with cancer immunotherapy,hoping to make readers a deep insight into this interdisciplinary field.
