The Indonesian Throughflow(ITF), which connects the tropical Pacific and Indian oceans, plays important roles in the inter-ocean water exchange and regional or even global climate variability. The Makassar Strait is t...The Indonesian Throughflow(ITF), which connects the tropical Pacific and Indian oceans, plays important roles in the inter-ocean water exchange and regional or even global climate variability. The Makassar Strait is the main inflow passage of the ITF, carrying about 77% of the total ITF volume transport. In this study, we analyze the simulated ITF in the Makassar Strait in the Simple Ocean Data Assimilation version 3(SODA3) datasets. A total of nine ensemble members of the SODA3 datasets, of which are driven by different surface forcings and bulk formulas, and with or without data assimilation, are used in this study. The annual mean water transports(i.e.,volume, heat and freshwater) are related to the combination of surface forcing and bulk formula, as well as whether data assimilation is employed. The phases of the seasonal and interannual variability in water transports cross the Makassar Strait, are basically consistent with each other among the SODA3 ensemble members. The interannual variability in Makassar Strait volume and heat transports are significantly correlated with El Ni?oSouthern Oscillation(ENSO) at time lags of-6 to 7 months. There is no statistically significant correlation between the freshwater transport and the ENSO. The Makassar Strait water transports are not significantly correlated with the Indian Ocean Dipole(IOD), which may attribute to model deficiency in simulating the propagation of semiannual Kelvin waves from the Indian Ocean to the Makassar Strait.展开更多
The tumor microenvironment is a complex network of cells,extracellular matrix,and signaling molecules that plays a critical role in tumor progression and metastasis.Lymphatic and blood vessels are major routes for sol...The tumor microenvironment is a complex network of cells,extracellular matrix,and signaling molecules that plays a critical role in tumor progression and metastasis.Lymphatic and blood vessels are major routes for solid tumor metastasis and essential parts of tumor drainage conduits.However,recent studies have shown that lymphatic endothelial cells(LECs)and blood endothelial cells(BECs)also play multifaceted roles in the tumor microenvironment beyond their structural functions,particularly in hepatocellular carcinoma(HCC).This comprehensive review summarizes the diverse roles played by LECs and BECs in HCC,including their involvement in angiogenesis,immune modulation,lymphangiogenesis,and metastasis.By providing a detailed account of the complex interplay between LECs,BECs,and tumor cells,this review aims to shed light on future research directions regarding the immune regulatory function of LECs and potential therapeutic targets for HCC.展开更多
Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential b...Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-^(89)(^(89)Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[^(89)Zr]Zr-desferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,>99%)and specific activity(24.15±1.34 GBq/mmol),and was stable in 5%human serum albumin,and phosphate buffer saline(>85%RCP at 96 h).The EC_(50) values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P>0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[^(89)Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2().The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16%ID/g)than BGC823 mice(0.69±0.02%ID/g)and blocking group(0.72±0.02%ID/g).A dosimetry estimation study showed that the effective dose of[^(89)Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these results suggest that Good Manufacturing Practices produced by this immuno-positron emission tomography probe can detect CLDN18.2-overexpressing tumors.展开更多
基金supported by the National Natural Science Foundation of China (Nos.52274295,52104291,51874079)the Natural Science Foundation of Hebei Province,China (Nos.E2022501028,E2022501029,E2021501029,A2021501007,E2018501091,E2020501001,E2022501030)+4 种基金the Hebei Province Key Research and Development Plan Project,China (No.19211302D)Performance Subsidy Fund for Key Laboratory of Dielectric and Electrolyte Functional Material Hebei Province,China (No.22567627H)the Fundamental Research Funds for the Central Universities,China (Nos.N2223009,N2223010,N2123035,N2023040)the Science and Technology Project of Hebei Education Department,China (No.ZD2022158)the Central Guided Local Science and Technology Development Fund Project of Hebei Province,China (No.226Z4401G).
基金The Fund of Laoshan Laboratory under contract No. LSKJ202202700the National Natural Science Foundation of China under contract Nos 42076023, 42076024 and 41876027the Global Change and Air-Sea Interaction Ⅱ Project under contract No.GASI-01-AIP-STwin。
文摘The Indonesian Throughflow(ITF), which connects the tropical Pacific and Indian oceans, plays important roles in the inter-ocean water exchange and regional or even global climate variability. The Makassar Strait is the main inflow passage of the ITF, carrying about 77% of the total ITF volume transport. In this study, we analyze the simulated ITF in the Makassar Strait in the Simple Ocean Data Assimilation version 3(SODA3) datasets. A total of nine ensemble members of the SODA3 datasets, of which are driven by different surface forcings and bulk formulas, and with or without data assimilation, are used in this study. The annual mean water transports(i.e.,volume, heat and freshwater) are related to the combination of surface forcing and bulk formula, as well as whether data assimilation is employed. The phases of the seasonal and interannual variability in water transports cross the Makassar Strait, are basically consistent with each other among the SODA3 ensemble members. The interannual variability in Makassar Strait volume and heat transports are significantly correlated with El Ni?oSouthern Oscillation(ENSO) at time lags of-6 to 7 months. There is no statistically significant correlation between the freshwater transport and the ENSO. The Makassar Strait water transports are not significantly correlated with the Indian Ocean Dipole(IOD), which may attribute to model deficiency in simulating the propagation of semiannual Kelvin waves from the Indian Ocean to the Makassar Strait.
基金Supported by National Natural Science Foundation of China,No.81702923,and No.81971503Open Project of State Key Laboratory of Medical Immunology,No.NKLMI2023K03+1 种基金Shanghai Shen Kang Hospital Development Center Clinical Science and Technology Innovation Project,No.SHDC12020104Basic Medical Research Project of Naval Medical University,No.2022QN072.
文摘The tumor microenvironment is a complex network of cells,extracellular matrix,and signaling molecules that plays a critical role in tumor progression and metastasis.Lymphatic and blood vessels are major routes for solid tumor metastasis and essential parts of tumor drainage conduits.However,recent studies have shown that lymphatic endothelial cells(LECs)and blood endothelial cells(BECs)also play multifaceted roles in the tumor microenvironment beyond their structural functions,particularly in hepatocellular carcinoma(HCC).This comprehensive review summarizes the diverse roles played by LECs and BECs in HCC,including their involvement in angiogenesis,immune modulation,lymphangiogenesis,and metastasis.By providing a detailed account of the complex interplay between LECs,BECs,and tumor cells,this review aims to shed light on future research directions regarding the immune regulatory function of LECs and potential therapeutic targets for HCC.
基金The research was funded by the National Natural Science Foundation of China(Grant Nos.:82171973,82171980,and 82102092)Beijing Millions of Talent Projects A Level Funding(Grant No.:2019A38)+2 种基金The study was also supported by Beijing Hospitals Authority Dengfeng Project(Grant No.:DFL20191102)the Pilot Project(4th Round)to Reform Public Development of Beijing Municipal Medical Research Institute(20211)the Third Foster Plan in 2019“Molecular Imaging Probe Preparation and Characterization of Key Technologies and Equipment”for the Development of Key Technologies and Equipment in Major Science and Technology Infrastructure in Shenzhen,China.
文摘Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-^(89)(^(89)Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[^(89)Zr]Zr-desferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,>99%)and specific activity(24.15±1.34 GBq/mmol),and was stable in 5%human serum albumin,and phosphate buffer saline(>85%RCP at 96 h).The EC_(50) values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P>0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[^(89)Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2().The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16%ID/g)than BGC823 mice(0.69±0.02%ID/g)and blocking group(0.72±0.02%ID/g).A dosimetry estimation study showed that the effective dose of[^(89)Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these results suggest that Good Manufacturing Practices produced by this immuno-positron emission tomography probe can detect CLDN18.2-overexpressing tumors.
