Suchergebnisse

Wenpeng Liu,1,* Lei Kang,2,* Juqiang Han,3 Yadong Wang,1 Chuan Shen,1 Zhifeng Yan,4 Yanhong Tai,5 Caiyan Zhao1 1Department of Infectious Diseases, Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China; 2Department of Nuclear Medicine, Peking University First Hospital, Beijing, China; 3Institute of Liver Disease, Beijing Military General Hospital, Beijing, China; 4Department of Gynecology and Obstetrics, PLA General Hospital, Beijing, China; 5Department of Pathology, Hospital of PLA, Beijing, China *These authors contributed equally to this work Background: Insulin-like growth factor-1 receptor (IGF-1R) is a well-studied oncogenic factor that promotes cell proliferation and energy metabolism and is overexpressed in numerous cancers including hepatocellular carcinoma (HCC). Aerobic glycolysis is a hallmark of cancer, and drugs targeting its regulators, including IGF-1R, are being developed. However, the mechanisms of IGF-1R inhibition and the physiological significance of the IGF-1R inhibitors in cancer cells are unclear. Materials and methods: Cell proliferation was evaluated by cell counting Kit-8 and colony formation assay. Western blot and real-time PCR were accordingly used to detect the relevant proteins, miRNA and gene expression. Luciferase reporter assays were used to illustrate the interaction between miR-342-3p and IGF-1R. The effect of miR-342-3p on glycolysis was determined by glucose uptake, ATP concentration, lactate generation, extracellular acidification rate and oxygen consumption rate assays. In vivo, subcutaneous tumor formation assay and PET were performed in nude mice. Results: In this study, we demonstrate that by directly targeting the 3'-UTR (3'-untranslated regions) of IGF-1R, microRNA-342-3p (miR-342-3p) suppresses IGF-1R-mediated PI3K/AKT/GLUT1 signaling pathway both in vitro and in vivo. Through suppression of IGF-1R, miR-342-3p dampens glycolysis by decreasing glucose uptake, lactate generation, ATP production, and extracellular acidification rate (ECAR), and increasing oxygen consumption rate (OCR) in hepatoma cells. Importantly, glycolysis regulated by miR-342-3p is critical for its regulating HCC growth both in vitro and in vivo. Conclusion: Our findings provide clues regarding the role of miR-342-3p as a tumor suppressor in liver cancer mainly through the inhibition of IGF-1R. Targeting IGF-1R by miR-342-3p could be a potential therapeutic strategy in liver cancer. Keywords: miR-342-3p, IGF-1R, liver cancer, glycolysis, metabolism, PET

International audience ; The circum-Mediterranean region is the cradle of ancient civilizations that had their roots in the Holocene. Climate change has been considered a key element that contributed to their rise or fall. The Roman Warm Period (RWP), 200 B.C. to 400 A.D., was the warmest period in Europe during the last two thousand years. Hydroclimatic change at the end of the RWP has been suggested as a possible influence on the stability of the Roman political regime and the eventual collapse of the Roman Empire in 476 A.D. A lack of precise proxy records hampers our understanding of hydroclimatic variability over the RWP. Here we present a stalagmite-based climate record from 550 ± 10 B.C. to 950 ± 7 A.D. (2σ) from northern Italy, which reveals a climatic trend of warming and increased humidity throughout the RWP. By comparison with other proxy records in Europe and the circum-Mediterranean region, we argue that the warm, humid climate in southern Europe could be linked to the multi-centennial warming of the Mediterranean Sea. Our record further suggests a century-long rapid drying trend from the early-4th to early-5th century, followed by a 100-year-long drought event, which could have influenced the fall of the Roman Empire.

International audience ; The circum-Mediterranean region is the cradle of ancient civilizations that had their roots in the Holocene. Climate change has been considered a key element that contributed to their rise or fall. The Roman Warm Period (RWP), 200 B.C. to 400 A.D., was the warmest period in Europe during the last two thousand years. Hydroclimatic change at the end of the RWP has been suggested as a possible influence on the stability of the Roman political regime and the eventual collapse of the Roman Empire in 476 A.D. A lack of precise proxy records hampers our understanding of hydroclimatic variability over the RWP. Here we present a stalagmite-based climate record from 550 ± 10 B.C. to 950 ± 7 A.D. (2σ) from northern Italy, which reveals a climatic trend of warming and increased humidity throughout the RWP. By comparison with other proxy records in Europe and the circum-Mediterranean region, we argue that the warm, humid climate in southern Europe could be linked to the multi-centennial warming of the Mediterranean Sea. Our record further suggests a century-long rapid drying trend from the early-4th to early-5th century, followed by a 100-year-long drought event, which could have influenced the fall of the Roman Empire.

International audience ; The circum-Mediterranean region is the cradle of ancient civilizations that had their roots in the Holocene. Climate change has been considered a key element that contributed to their rise or fall. The Roman Warm Period (RWP), 200 B.C. to 400 A.D., was the warmest period in Europe during the last two thousand years. Hydroclimatic change at the end of the RWP has been suggested as a possible influence on the stability of the Roman political regime and the eventual collapse of the Roman Empire in 476 A.D. A lack of precise proxy records hampers our understanding of hydroclimatic variability over the RWP. Here we present a stalagmite-based climate record from 550 ± 10 B.C. to 950 ± 7 A.D. (2σ) from northern Italy, which reveals a climatic trend of warming and increased humidity throughout the RWP. By comparison with other proxy records in Europe and the circum-Mediterranean region, we argue that the warm, humid climate in southern Europe could be linked to the multi-centennial warming of the Mediterranean Sea. Our record further suggests a century-long rapid drying trend from the early-4th to early-5th century, followed by a 100-year-long drought event, which could have influenced the fall of the Roman Empire.

International audience ; The circum-Mediterranean region is the cradle of ancient civilizations that had their roots in the Holocene. Climate change has been considered a key element that contributed to their rise or fall. The Roman Warm Period (RWP), 200 B.C. to 400 A.D., was the warmest period in Europe during the last two thousand years. Hydroclimatic change at the end of the RWP has been suggested as a possible influence on the stability of the Roman political regime and the eventual collapse of the Roman Empire in 476 A.D. A lack of precise proxy records hampers our understanding of hydroclimatic variability over the RWP. Here we present a stalagmite-based climate record from 550 ± 10 B.C. to 950 ± 7 A.D. (2σ) from northern Italy, which reveals a climatic trend of warming and increased humidity throughout the RWP. By comparison with other proxy records in Europe and the circum-Mediterranean region, we argue that the warm, humid climate in southern Europe could be linked to the multi-centennial warming of the Mediterranean Sea. Our record further suggests a century-long rapid drying trend from the early-4th to early-5th century, followed by a 100-year-long drought event, which could have influenced the fall of the Roman Empire.

International audience ; The circum-Mediterranean region is the cradle of ancient civilizations that had their roots in the Holocene. Climate change has been considered a key element that contributed to their rise or fall. The Roman Warm Period (RWP), 200 B.C. to 400 A.D., was the warmest period in Europe during the last two thousand years. Hydroclimatic change at the end of the RWP has been suggested as a possible influence on the stability of the Roman political regime and the eventual collapse of the Roman Empire in 476 A.D. A lack of precise proxy records hampers our understanding of hydroclimatic variability over the RWP. Here we present a stalagmite-based climate record from 550 ± 10 B.C. to 950 ± 7 A.D. (2σ) from northern Italy, which reveals a climatic trend of warming and increased humidity throughout the RWP. By comparison with other proxy records in Europe and the circum-Mediterranean region, we argue that the warm, humid climate in southern Europe could be linked to the multi-centennial warming of the Mediterranean Sea. Our record further suggests a century-long rapid drying trend from the early-4th to early-5th century, followed by a 100-year-long drought event, which could have influenced the fall of the Roman Empire.

This study was supported by the NERC project, ID NE/M003752/1 to D.A.H. The sampling surveys were supported by the Water Resources and Environmental Geology Research Group (University of Almería). S.F.M.B., F.G. and D.A.H. acknowledge support from the European Union's Horizon 2020 Research and Innovation programme for project "QUEST" (Marie Sklodowska-Curie grant agreement No. 691037). Usingle bondTh dating was supported by grants from Taiwan ROC MOST (104-2119-M-002-003, 105-2119-M-002-001 to C.-C.S.) and the Research Center for Future Earth, National Taiwan University (107L901001 to C.-C.S.). ; Here we track the water-table position and temperature of the Mount San Giovanni aquifer (Iglesiente-Sulcis mining district, SW Sardinia, Italy) during the past 600 ka by determining the ages (UTh dating) and stable isotope compositions (δ18O, δ13C and Δ47) of a variety of subaqueous carbonate speleothems (e.g. calcite spars, dogtooth calcite crystals and calcite coatings). Clumped isotopes (Δ47) provide quantitative estimates of carbonate formation temperatures (and thus water temperatures) that are independent of the oxygen isotope composition of water (δ18Ow). Then, the δ18Ow of the paleo-water has been reconstructed from the clumped isotope temperature (TΔ47) and the δ18O of the carbonate (δ18Oc). We find that high-temperature calcite spars formed already before 600 ka at temperatures above ~120 °C. Lower-temperature spars (~70 °C) precipitated at ~400 ka, and cold-water subaqueous speleothems (~10–20 °C) formed in perched ponds at different levels of the karst systems between 410 ka and 110 ka, while coeval precipitation of subaerial flowstones occurred in the upper levels of the shallower caves until 82 ka. We infer that the groundwater level dropped by ~120 m from ~400 to ~250 ka, with a relatively rapid rate of ~0.8 mm/y. Considering the tectonic stability of Sardinia during the Quaternary, this high rate derives from climate driven geomorphological processes at the surface rather than tectonic uplifting. The δ18O values of the paleo-aquifer water range from −6.0 ± 0.7‰ during MIS 5c, and similar to modern cave water values (−5.1‰), to −7.7± 0.4‰ during the colder MIS 8. These values indicate that the groundwater reflected the δ18O signal of meteoric water, with no significant contributions from metasomatism and metamorphic waters. The observed δ18Ow variability can be explained by glacial/interglacial paleoclimate changes affecting rainfall δ18O (and thus groundwater δ18O). We conclude that clumped isotope thermometry on subaqueous carbonate speleothems is a powerful tool for tracking paleo-aquifer temperatures and δ18Ow reconstructions. ; Publisher PDF ; Peer reviewed

Copper-based materials are promising electrocatalysts for CO2 reduction. Prior studies show that the mixture of copper (I) and copper (0) at the catalyst surface enhances multi-carbon products from CO2 reduction; however, the stable presence of copper (I) remains the subject of debate. Here we report a copper on copper (I) composite that stabilizes copper (I) during CO2 reduction through the use of copper nitride as an underlying copper (I) species. We synthesize a copper-on-nitride catalyst that exhibits a Faradaic efficiency of 64 ± 2% for C2+ products. We achieve a 40-fold enhancement in the ratio of C2+ to the competing CH4 compared to the case of pure copper. We further show that the copper-on-nitride catalyst performs stable CO2 reduction over 30 h. Mechanistic studies suggest that the use of copper nitride contributes to reducing the CO dimerization energy barrier-a rate-limiting step in CO2 reduction to multi-carbon products. ; This work was supported financially by the Ontario Research Fund Research-Excellence Program, the Natural Sciences and Engineering Research Council (NSERC) of Canada, and the CIFAR Bio-Inspired Solar Energy program. Computations were performed on the SOSCIP Consortium's Blue Gene/Q computing platform. SOSCIP is funded by the Federal Economic Development Agency of Southern Ontario, the Province of Ontario, IBM Canada Ltd., Ontario Centres of Excellence, Mitacs and 15 Ontario academic member institutions. X-ray absorption spectra were performed on SXRMB beamlines at the Canadian Light Source (CLS), which is supported by the Canada Foundation for Innovation, Natural Sciences and Engineering Research Council of Canada, the University of Saskatchewan, the Government of Saskatchewan, Western Economic Diversification Canada, the National Research Council Canada, and the Canadian Institutes of Health Research. Z.L. acknowledges a scholarship from the China Scholarship Council (CSC) (201607090041) and Basic and Innovation Program, Beijing Jiaotong University (KSJB17016536). A.S. acknowledges Fonds de Recherche du Quebec-Nature et Technologies (FRQNT) for the postdoctoral fellowship award. P.D.L. acknowledges support from NSERC in the form of the Canada Graduate Scholarship. H.T. acknowledges the Netherlands Organisation for Scientific Research (NWO) for a Rubicon grant (680-50-1511) to support his postdoctoral research at University of Toronto. The authors thank C. Q. Zou, M. X. Liu, F. F. Fan, J. Xing and L. Gao from University of Toronto for fruitful discussions.