The Paleogene is a crucial period when terrestrial and marine ecosystems recovered from major disruptions and gradually approached their modern states.In the Qinghai-Tibetan Plateau and its surrounding regions,the Pal...The Paleogene is a crucial period when terrestrial and marine ecosystems recovered from major disruptions and gradually approached their modern states.In the Qinghai-Tibetan Plateau and its surrounding regions,the Paleogene also represents a significant phase of tectonic evolution in the Qinghai-Tibetan Plateau-Himalaya orogeny,reorganization of Asian climates,and evolution of biodiversity.Due to limitations in research conditions and understanding,there are still many controversies regarding stratigraphic divisions in the Qinghai-Tibetan Plateau and its surrounding regions.In recent years,extensive studies on sedimentary petrology,magnetostratigraphy,and isotope dating have been conducted in the region.Numerous fossils have been discovered and reported,contributing to a more systematic understanding of biostratigraphy.These studies have laid a solid foundation for the comprehensive investigation of the stratigraphy,biotas and paleogeographic evolution of the Qinghai-Tibetan Plateau and its surrounding regions during the Paleogene.In this paper,we integrate recent research on fossils,isotopic dating,magnetostratigraphy,and geochemistry to refine the stratigraphic divisions and correlation framework of different tectonic units in the region,building upon previous studies.Since the Second Tibetan Plateau Scientific Expedition and Research,the knowledge of Paleogene floras has gradually expanded.This paper discusses the biostratigraphic significance of extinct and newly appeared taxa based on the latest dating results of these plant species.The new understanding of fossil species such as the“Eucalyptus”and Arecaceae establishes connections between the Paleogene flora of the Qinghai-Tibetan region and the biotas of Gondwana,specifically Oceania and South America.The evolutionary history of key taxa near the Yarlung Zangbo suture zone indicates that the collision between the Indian and Eurasian plates occurred approximately 65-54 Ma.Paleoelevation reconstructions,based on plant fossils,suggest that the Hengduan Mountain had already formed their current topographic pattern prior to the Early Oligocene.The warm and humid lowlands adjacent to the main suture zones in the Paleogene Qinghai-Tibetan Plateau served as the primary pathway for biota exchanges.The relatively low elevation of the Himalaya during the Paleogene did not effectively block the moisture from the Indian Ocean.展开更多
化学事故具有突发性强、环境污染破坏严重、救援难度大等特点,对突发化学事故的影响范围、破坏程度进行快速评估,为事故抢险救援提供决策支持,是应对重特大突发化学事故、降低事故损失的重要手段。本文基于三维地理信息系统(Three-dimen...化学事故具有突发性强、环境污染破坏严重、救援难度大等特点,对突发化学事故的影响范围、破坏程度进行快速评估,为事故抢险救援提供决策支持,是应对重特大突发化学事故、降低事故损失的重要手段。本文基于三维地理信息系统(Three-dimensional Geographic Information System,3D GIS),在充分考虑下垫面影响的前提下,研究了大气污染扩散模型,提出了扩散场快速构建技术及兼顾污染分区的救援力量调度方法,并以此为核心建立了系统总体框架,形成了集扩散模拟、危害分析、救援调度等功能于一体的突发化学事故危害评估与救援辅助决策支持系统,可为突发化学事故危害后果评估与辅助救援决策提供有效的技术支撑。展开更多
BACKGROUND Immune checkpoint inhibitors(ICIs)targeting programmed cell death protein 1(PD-1)and T cell immunoglobulin and mucin domain-containing protein 3(TIM-3)are beneficial to the resumption of anti-tumor immunity...BACKGROUND Immune checkpoint inhibitors(ICIs)targeting programmed cell death protein 1(PD-1)and T cell immunoglobulin and mucin domain-containing protein 3(TIM-3)are beneficial to the resumption of anti-tumor immunity response and hold extreme potential as efficient therapies for certain malignancies.However,ICIs with a single target exhibit poor overall response rate in hepatocellular carcinoma(HCC)patients due to the complex pathological mechanisms of HCC.AIM To investigate the effects of combined TIM-3 and PD-1 blockade on tumor development in an HCC mouse model,aiming to identify more effective immunotherapies and provide more treatment options for HCC patients.METHODS The levels of PD-1 and TIM-3 on CD4+and CD8+T cells from tumor tissues,ascites,and matched adjacent tissues from HCC patients were determined with flow cytometry.An HCC xenograft mouse model was established and treated with anti-TIM-3 monoclonal antibody(mAb)and/or anti-PD-1 mAb.Tumor growth in each group was measured.Hematoxylin and eosin staining and immunohistochemical staining were used to evaluate T cell infiltration in tumors.The percentage of CD4+and CD8+T cells in tissue samples from mice was tested with flow cytometry.The percentages of PD-1+CD8+,TIM-3+CD8+,and PD-1+TIM-3+CD8+T cells was accessed by flow cytometry.The levels of the cytokines including tumor necrosis factor alpha(TNF-α),interferon-γ(IFN-γ),interleukin(IL)-6,and IL-10 in tumor tissues were gauged with enzyme-linked immunosorbent assay kits.RESULTS We confirmed that PD-1 and TIM-3 expression was substantially upregulated in CD4+and CD8+T cells isolated from tumor tissues and ascites of HCC patients.TIM-3 mAb and PD-1 mAb treatment both reduced tumor volume and weight,while combined blockade had more substantial anti-tumor effects than individual treatment.Then we showed that combined therapy increased T cell infiltration into tumor tissues,and downregulated PD-1 and TIM-3 expression on CD8+T cells in tumor tissues.Moreover,combined treatment facilitated the production of T cell effector cytokines TNF-α and IFN-γ,and reduced the production of immunosuppressive cytokines IL-10 and IL-6 in tumor tissues.Thus,we implicated that combined blockade could ameliorate T cell exhaustion in HCC mouse model.CONCLUSION Combined TIM-3 and PD-1 blockade restrains HCC development by facilitating CD4+ and CD8+T cell-mediated antitumor immune responses.展开更多
Spermatogenesis, maturation, capacitation and fertilization are precisely regulated by glycosylation. However, the relationship between altered glycosylation patterns and the onset and development of reproductive diso...Spermatogenesis, maturation, capacitation and fertilization are precisely regulated by glycosylation. However, the relationship between altered glycosylation patterns and the onset and development of reproductive disorders is unclear, mainly limited by the lack of in situ imaging techniques for spermatozoa glycosylation. We developed an efficient and highly specific spermatozoa glycan imaging technique based on the robust chemoselective labeling of sialic acid(Sia) and N-acetyl-D-galactosamine(Gal/GalNAc). We further proposed a “tandem glycan chemoselective labeling” strategy to achieve simultaneous imaging of two types of glycans on spermatozoa. We applied the developed method to the spermatozoa from oligozoospermic patients and diabetic mice and found that these spermatozoa showed higher levels of Sia and Gal/Gal NAc expression than the normal groups. Moreover, spermatozoa from diabetic mice showed a severe decrease in number, viability, and forward motility, suggesting that in vivo glucose metabolism disorders may lead to an elevated level of spermatozoa glycosylation and have a correlation with the development of oligoasthenotspermia. Our work provides a research tool to reveal the relationship between glycosylation modification and spermatozoa quality, and a promising clue for the development of glycan-based reproductive markers.展开更多
The Qinghai-Tibetan Plateau(QTP)is well known as the Roof of the World,the Third Pole and the Asian Water Tower.It spans a vast area from the Pamir Plateau in the west to the Longmenshan-Hengduan Mountains in the east...The Qinghai-Tibetan Plateau(QTP)is well known as the Roof of the World,the Third Pole and the Asian Water Tower.It spans a vast area from the Pamir Plateau in the west to the Longmenshan-Hengduan Mountains in the east,from the Himalaya Mountains in the south to the Kunlun-Qilian Mountains in the north.It stretches approximately 1,200 km from north to south and 2,500 km from east to west.When did the QTP start to uplift?This is still controversial between early and late Cenozoic scenarios.While some scholars advocated its uplift since the India-Asia continental collision at about 65 million years ago in the Paleogene(e.g.,Ding et al.,2017,2022),and the others suggested its uplift since the Miocene(Zheng and Wu,2018).展开更多
基金supported by the Second Tibetan Plateau Scientific Expedition and Research(Grant No.2019QZKK0705)the National Natural Science Foundation of China(Grant No.42002020)+1 种基金the Foundation of the State Key Laboratory of Paleobiology and Stratigraphy,Nanjing Institute of Geology and Paleontology,Chinese Academy of Sciences(Grant Nos.203127 and 193117)the West Light Project(Grant No.2020000023)。
文摘The Paleogene is a crucial period when terrestrial and marine ecosystems recovered from major disruptions and gradually approached their modern states.In the Qinghai-Tibetan Plateau and its surrounding regions,the Paleogene also represents a significant phase of tectonic evolution in the Qinghai-Tibetan Plateau-Himalaya orogeny,reorganization of Asian climates,and evolution of biodiversity.Due to limitations in research conditions and understanding,there are still many controversies regarding stratigraphic divisions in the Qinghai-Tibetan Plateau and its surrounding regions.In recent years,extensive studies on sedimentary petrology,magnetostratigraphy,and isotope dating have been conducted in the region.Numerous fossils have been discovered and reported,contributing to a more systematic understanding of biostratigraphy.These studies have laid a solid foundation for the comprehensive investigation of the stratigraphy,biotas and paleogeographic evolution of the Qinghai-Tibetan Plateau and its surrounding regions during the Paleogene.In this paper,we integrate recent research on fossils,isotopic dating,magnetostratigraphy,and geochemistry to refine the stratigraphic divisions and correlation framework of different tectonic units in the region,building upon previous studies.Since the Second Tibetan Plateau Scientific Expedition and Research,the knowledge of Paleogene floras has gradually expanded.This paper discusses the biostratigraphic significance of extinct and newly appeared taxa based on the latest dating results of these plant species.The new understanding of fossil species such as the“Eucalyptus”and Arecaceae establishes connections between the Paleogene flora of the Qinghai-Tibetan region and the biotas of Gondwana,specifically Oceania and South America.The evolutionary history of key taxa near the Yarlung Zangbo suture zone indicates that the collision between the Indian and Eurasian plates occurred approximately 65-54 Ma.Paleoelevation reconstructions,based on plant fossils,suggest that the Hengduan Mountain had already formed their current topographic pattern prior to the Early Oligocene.The warm and humid lowlands adjacent to the main suture zones in the Paleogene Qinghai-Tibetan Plateau served as the primary pathway for biota exchanges.The relatively low elevation of the Himalaya during the Paleogene did not effectively block the moisture from the Indian Ocean.
文摘化学事故具有突发性强、环境污染破坏严重、救援难度大等特点,对突发化学事故的影响范围、破坏程度进行快速评估,为事故抢险救援提供决策支持,是应对重特大突发化学事故、降低事故损失的重要手段。本文基于三维地理信息系统(Three-dimensional Geographic Information System,3D GIS),在充分考虑下垫面影响的前提下,研究了大气污染扩散模型,提出了扩散场快速构建技术及兼顾污染分区的救援力量调度方法,并以此为核心建立了系统总体框架,形成了集扩散模拟、危害分析、救援调度等功能于一体的突发化学事故危害评估与救援辅助决策支持系统,可为突发化学事故危害后果评估与辅助救援决策提供有效的技术支撑。
基金Supported by the First-Class Discipline Construction Founded Project of Ningxia Medical University and the School of Clinical Medicine,No.2020008.
文摘BACKGROUND Immune checkpoint inhibitors(ICIs)targeting programmed cell death protein 1(PD-1)and T cell immunoglobulin and mucin domain-containing protein 3(TIM-3)are beneficial to the resumption of anti-tumor immunity response and hold extreme potential as efficient therapies for certain malignancies.However,ICIs with a single target exhibit poor overall response rate in hepatocellular carcinoma(HCC)patients due to the complex pathological mechanisms of HCC.AIM To investigate the effects of combined TIM-3 and PD-1 blockade on tumor development in an HCC mouse model,aiming to identify more effective immunotherapies and provide more treatment options for HCC patients.METHODS The levels of PD-1 and TIM-3 on CD4+and CD8+T cells from tumor tissues,ascites,and matched adjacent tissues from HCC patients were determined with flow cytometry.An HCC xenograft mouse model was established and treated with anti-TIM-3 monoclonal antibody(mAb)and/or anti-PD-1 mAb.Tumor growth in each group was measured.Hematoxylin and eosin staining and immunohistochemical staining were used to evaluate T cell infiltration in tumors.The percentage of CD4+and CD8+T cells in tissue samples from mice was tested with flow cytometry.The percentages of PD-1+CD8+,TIM-3+CD8+,and PD-1+TIM-3+CD8+T cells was accessed by flow cytometry.The levels of the cytokines including tumor necrosis factor alpha(TNF-α),interferon-γ(IFN-γ),interleukin(IL)-6,and IL-10 in tumor tissues were gauged with enzyme-linked immunosorbent assay kits.RESULTS We confirmed that PD-1 and TIM-3 expression was substantially upregulated in CD4+and CD8+T cells isolated from tumor tissues and ascites of HCC patients.TIM-3 mAb and PD-1 mAb treatment both reduced tumor volume and weight,while combined blockade had more substantial anti-tumor effects than individual treatment.Then we showed that combined therapy increased T cell infiltration into tumor tissues,and downregulated PD-1 and TIM-3 expression on CD8+T cells in tumor tissues.Moreover,combined treatment facilitated the production of T cell effector cytokines TNF-α and IFN-γ,and reduced the production of immunosuppressive cytokines IL-10 and IL-6 in tumor tissues.Thus,we implicated that combined blockade could ameliorate T cell exhaustion in HCC mouse model.CONCLUSION Combined TIM-3 and PD-1 blockade restrains HCC development by facilitating CD4+ and CD8+T cell-mediated antitumor immune responses.
基金the support from the National Natural Science Foundation of China (Nos.21974067, 22274073, 81971373 and 82001535)the National Key Research and Development Program of China (No.2018YFC1004700)+1 种基金Fundamental Research Funds for the Central Universities (Nos.020514380309,021414380502 and 2022300324)the State Key Laboratory of Analytical Chemistry for Life Science (Nos.5431ZZXM2305 and 5431ZZXM2204)。
文摘Spermatogenesis, maturation, capacitation and fertilization are precisely regulated by glycosylation. However, the relationship between altered glycosylation patterns and the onset and development of reproductive disorders is unclear, mainly limited by the lack of in situ imaging techniques for spermatozoa glycosylation. We developed an efficient and highly specific spermatozoa glycan imaging technique based on the robust chemoselective labeling of sialic acid(Sia) and N-acetyl-D-galactosamine(Gal/GalNAc). We further proposed a “tandem glycan chemoselective labeling” strategy to achieve simultaneous imaging of two types of glycans on spermatozoa. We applied the developed method to the spermatozoa from oligozoospermic patients and diabetic mice and found that these spermatozoa showed higher levels of Sia and Gal/Gal NAc expression than the normal groups. Moreover, spermatozoa from diabetic mice showed a severe decrease in number, viability, and forward motility, suggesting that in vivo glucose metabolism disorders may lead to an elevated level of spermatozoa glycosylation and have a correlation with the development of oligoasthenotspermia. Our work provides a research tool to reveal the relationship between glycosylation modification and spermatozoa quality, and a promising clue for the development of glycan-based reproductive markers.
基金supported by the Second Expedition of QTP Project(Grant No.2019QZKK0706)the National Natural Science Foundation of China(Grant No.42293280)。
文摘The Qinghai-Tibetan Plateau(QTP)is well known as the Roof of the World,the Third Pole and the Asian Water Tower.It spans a vast area from the Pamir Plateau in the west to the Longmenshan-Hengduan Mountains in the east,from the Himalaya Mountains in the south to the Kunlun-Qilian Mountains in the north.It stretches approximately 1,200 km from north to south and 2,500 km from east to west.When did the QTP start to uplift?This is still controversial between early and late Cenozoic scenarios.While some scholars advocated its uplift since the India-Asia continental collision at about 65 million years ago in the Paleogene(e.g.,Ding et al.,2017,2022),and the others suggested its uplift since the Miocene(Zheng and Wu,2018).
