No effective drug treatments are available for coronavirus disease 2019(COVID-19).Host-directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage,death,or long-term functi...No effective drug treatments are available for coronavirus disease 2019(COVID-19).Host-directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage,death,or long-term functional disability in survivors require clinical evaluation.We performed a parallel assigned controlled,non-randomized,phase 1 clinical trial to evaluate the safety of human umbilical cord-derived mesenchymal stem cells(UC-MSCs)infusions in the treatment of patients with moderate and severe COVID-19 pulmonary disease.The study enrolled 18 hospitalized patients with COVID-19(n=9 for each group).The treatment group received three cycles of intravenous infusion of UC-MSCs(3×107 cells per infusion)on days 0,3,and 6.Both groups received standard COVID-treatment regimens.Adverse events,duration of clinical symptoms,laboratory parameters,length of hospitalization,serial chest computed tomography(CT)images,the PaO2/FiO2 ratio,dynamics of cytokines,and IgG and IgM anti-SARS-CoV-2 antibodies were analyzed.No serious UC-MSCs infusion-associated adverse events were observed.Two patients receiving UC-MSCs developed transient facial flushing and fever,and one patient developed transient hypoxia at 12 h post UC-MSCs transfusion.Mechanical ventilation was required in one patient in the treatment group compared with four in the control group.All patients recovered and were discharged.Our data show that intravenous UC-MSCs infusion in patients with moderate and severe COVID-19 is safe and well tolerated.Phase 2/3 randomized,controlled,double-blinded trials with long-term follow-up are needed to evaluate the therapeutic use of UC-MSCs to reduce deaths and improve long-term treatment outcomes in patients with serious COVID-19.展开更多
Treatment of severe Coronavirus Disease 2019(COVID-19)is challenging.We performed a phase 2 trial to assess the efficacy andsafety of human umbilical cord-mesenchymal stem cells(UC-MScs)to treat severe coViD-19 patien...Treatment of severe Coronavirus Disease 2019(COVID-19)is challenging.We performed a phase 2 trial to assess the efficacy andsafety of human umbilical cord-mesenchymal stem cells(UC-MScs)to treat severe coViD-19 patients with lung damage,based onour phase 1 data.In this randomized,double-blind,and placebo-controlled trial,we recruited 101 severe coVID-19 patients withlung damage.They were randomly assigned at a 2:1 ratio to receive either UC-MSCs(4×10^(7)cells per infusion)or placebo on day 0,3,and 6.The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28.Other imagingoutcomes,6-minute walk test(6-MWT),maximum vital capacity,diffusing capacity,and adverse events were recorded and analyzed.In all,100 COVID-19 patients were finally received either UC-MSCs in=65)or placebo(n=35).UC-MSCs administrationexerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo(the mediandifference was-13.31%,95%Cl-29.14%,2.13%,P=0.08).UC-MSCs significanty reduced the proportions of solid componentlesion volume compared with the placebo(median difference:-15.45%;95%CI-30.82%,-0.39%;P=0.043).The 6-MWT showedan increased distance in patients treated with UC-MSCs(difference:27.00 m;95%CI 0.00,57.00;P=0.057).The incidence of adverseevents was similar in the two groups.These results suggest that UC-MSCs treatment is a safe and potentially effective therapeuticapproach for COVID-19 patients with lung damage.A phase 3 trial is required to evaluate effects on reducing mortality andpreventing long-term pulmonary disability.展开更多
Probe molecule Eu(DBM)3 phen is made up of europium oxide(EuO),dibenzoylmethane(DBM) and1,10-phenanthroline(phen). The temperature sensitive paint(TSP) was compounded by the polymerization of the probe molecule, methy...Probe molecule Eu(DBM)3 phen is made up of europium oxide(EuO),dibenzoylmethane(DBM) and1,10-phenanthroline(phen). The temperature sensitive paint(TSP) was compounded by the polymerization of the probe molecule, methyl methacrylate(MMA) and the initiator of benzoyl peroxide(BPO).The structure, morphology, luminescence property of probe molecule and the temperature quenching property of the temperature sensitive paint(TSP) were characterized by infrared spectrometer, UV-vis spectrometer, scanning electron microscopy and fluorescence spectrometer respectively. The infrared spectrum and UV-vis spectra show that Eu and DBM form six membered rings, and Eu-O coordinate bonds form. The nanocrystals are in sphere-like morphology with an average size of approximately100 nm. Fluorescence spectra present that the performance of temperature quenching is excellent,what’s more, TSP sample has different temperature sensitivity in various temperature scope. Particularly,under excitation of 286 nm, TSP has a highest temperature sensitivity between 50 and 60 ℃, and the strongest fluorescence emission reaches a peak(615 nm). It indicated that probe molecule(Eu(DBM)phen) has strong luminescent intensity and the temperature quenching properties of Eu(DBM)phen/PMMA is good.展开更多
East Asian dust（EAD） exerts considerable impacts on the energy balance and climate/climate change of the earth system through its influence on solar and terrestrial radiation, cloud properties, and precipitation eff...East Asian dust（EAD） exerts considerable impacts on the energy balance and climate/climate change of the earth system through its influence on solar and terrestrial radiation, cloud properties, and precipitation efficiency. Providing an accurate description of the life cycle and climate effects of EAD is therefore critical to better understanding of climate change and socioeconomic development in East Asia and even worldwide. Dust modeling has undergone substantial development since the late 1990 s, associated with improved understanding of the role of EAD in the earth system. Here, we review the achievements and progress made in recent decades in terms of dust modeling research,including dust emissions, long-range transport, radiative forcing（RF）, and climate effects of dust particles over East Asia. Numerous efforts in dust/EAD modeling have been directed towards furnishing more sophisticated physical and chemical processes into the models on higher spatial resolutions. Meanwhile, more systematic observations and more advanced retrieval methods for instruments that address EAD related science issues have made it possible to evaluate model results and quantify the role of EAD in the earth system, and to further reduce the uncertainties in EAD simulations. Though much progress has been made, large discrepancies and knowledge gaps still exist among EAD simulations. The deficiencies and limitations that pertain to the performance of the EAD simulations referred to in the present study are also discussed.展开更多
The Jiangmen Underground Neutrino Observatory(JUNO)is a large liquid scintillator detector designed to explore many topics in fundamental physics.In this study,the potential of searching for proton decay in the p→νK...The Jiangmen Underground Neutrino Observatory(JUNO)is a large liquid scintillator detector designed to explore many topics in fundamental physics.In this study,the potential of searching for proton decay in the p→νK^(+)mode with JUNO is investigated.The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification.Moreover,the excellent energy resolution of JUNO permits suppression of the sizable background caused by other delayed signals.Based on these advantages,the detection efficiency for the proton decay via p→νK^(+)is 36.9%±4.9%with a background level of 0.2±0.05(syst)±0.2(stat)events after 10 years of data collection.The estimated sensitivity based on 200 kton-years of exposure is 9.6×1033 years,which is competitive with the current best limits on the proton lifetime in this channel and complements the use of different detection technologies.展开更多
基金supported by The National Key R&D Program of China(2020YFC0841900,2020YFC0844000)The Innovation Groups of the National Natural Science Foundation of China(81721002)+2 种基金The National Science and Technology Major Project(2017YFA0105703)The Military Emergency Research Project for COVID-19(BWS20J006)The Project for Innovation of Military Medicine of China(16CXZ045).
文摘No effective drug treatments are available for coronavirus disease 2019(COVID-19).Host-directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage,death,or long-term functional disability in survivors require clinical evaluation.We performed a parallel assigned controlled,non-randomized,phase 1 clinical trial to evaluate the safety of human umbilical cord-derived mesenchymal stem cells(UC-MSCs)infusions in the treatment of patients with moderate and severe COVID-19 pulmonary disease.The study enrolled 18 hospitalized patients with COVID-19(n=9 for each group).The treatment group received three cycles of intravenous infusion of UC-MSCs(3×107 cells per infusion)on days 0,3,and 6.Both groups received standard COVID-treatment regimens.Adverse events,duration of clinical symptoms,laboratory parameters,length of hospitalization,serial chest computed tomography(CT)images,the PaO2/FiO2 ratio,dynamics of cytokines,and IgG and IgM anti-SARS-CoV-2 antibodies were analyzed.No serious UC-MSCs infusion-associated adverse events were observed.Two patients receiving UC-MSCs developed transient facial flushing and fever,and one patient developed transient hypoxia at 12 h post UC-MSCs transfusion.Mechanical ventilation was required in one patient in the treatment group compared with four in the control group.All patients recovered and were discharged.Our data show that intravenous UC-MSCs infusion in patients with moderate and severe COVID-19 is safe and well tolerated.Phase 2/3 randomized,controlled,double-blinded trials with long-term follow-up are needed to evaluate the therapeutic use of UC-MSCs to reduce deaths and improve long-term treatment outcomes in patients with serious COVID-19.
基金Funded by The National Key R&D Program of China and others.ClinicalTrials.gov number,NCT04288102supported by The National Key R&D Program of China(2020YFC0841900,2020YFC0844000,2020YFC08860900)+1 种基金The Innovation Groups of the National Natural Science Foundation of China(81721002)The National Science and Technology Major Project(2017YFA0105703).
文摘Treatment of severe Coronavirus Disease 2019(COVID-19)is challenging.We performed a phase 2 trial to assess the efficacy andsafety of human umbilical cord-mesenchymal stem cells(UC-MScs)to treat severe coViD-19 patients with lung damage,based onour phase 1 data.In this randomized,double-blind,and placebo-controlled trial,we recruited 101 severe coVID-19 patients withlung damage.They were randomly assigned at a 2:1 ratio to receive either UC-MSCs(4×10^(7)cells per infusion)or placebo on day 0,3,and 6.The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28.Other imagingoutcomes,6-minute walk test(6-MWT),maximum vital capacity,diffusing capacity,and adverse events were recorded and analyzed.In all,100 COVID-19 patients were finally received either UC-MSCs in=65)or placebo(n=35).UC-MSCs administrationexerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo(the mediandifference was-13.31%,95%Cl-29.14%,2.13%,P=0.08).UC-MSCs significanty reduced the proportions of solid componentlesion volume compared with the placebo(median difference:-15.45%;95%CI-30.82%,-0.39%;P=0.043).The 6-MWT showedan increased distance in patients treated with UC-MSCs(difference:27.00 m;95%CI 0.00,57.00;P=0.057).The incidence of adverseevents was similar in the two groups.These results suggest that UC-MSCs treatment is a safe and potentially effective therapeuticapproach for COVID-19 patients with lung damage.A phase 3 trial is required to evaluate effects on reducing mortality andpreventing long-term pulmonary disability.
基金supported by the Pre-Research Fund Project(BQ0302)
文摘Probe molecule Eu(DBM)3 phen is made up of europium oxide(EuO),dibenzoylmethane(DBM) and1,10-phenanthroline(phen). The temperature sensitive paint(TSP) was compounded by the polymerization of the probe molecule, methyl methacrylate(MMA) and the initiator of benzoyl peroxide(BPO).The structure, morphology, luminescence property of probe molecule and the temperature quenching property of the temperature sensitive paint(TSP) were characterized by infrared spectrometer, UV-vis spectrometer, scanning electron microscopy and fluorescence spectrometer respectively. The infrared spectrum and UV-vis spectra show that Eu and DBM form six membered rings, and Eu-O coordinate bonds form. The nanocrystals are in sphere-like morphology with an average size of approximately100 nm. Fluorescence spectra present that the performance of temperature quenching is excellent,what’s more, TSP sample has different temperature sensitivity in various temperature scope. Particularly,under excitation of 286 nm, TSP has a highest temperature sensitivity between 50 and 60 ℃, and the strongest fluorescence emission reaches a peak(615 nm). It indicated that probe molecule(Eu(DBM)phen) has strong luminescent intensity and the temperature quenching properties of Eu(DBM)phen/PMMA is good.
基金National Natural Science Foundation of China(41405003 and 41521004)supported by the Office of Science,U.S.Department of Energy(DOE),as part of its Regional and Global Climate Modeling ProgramThe Pacific Northwest National Laboratory is operated for the DOE by the Battelle Memorial Institute under contract DE-AC05-76RL01830
文摘East Asian dust（EAD） exerts considerable impacts on the energy balance and climate/climate change of the earth system through its influence on solar and terrestrial radiation, cloud properties, and precipitation efficiency. Providing an accurate description of the life cycle and climate effects of EAD is therefore critical to better understanding of climate change and socioeconomic development in East Asia and even worldwide. Dust modeling has undergone substantial development since the late 1990 s, associated with improved understanding of the role of EAD in the earth system. Here, we review the achievements and progress made in recent decades in terms of dust modeling research,including dust emissions, long-range transport, radiative forcing（RF）, and climate effects of dust particles over East Asia. Numerous efforts in dust/EAD modeling have been directed towards furnishing more sophisticated physical and chemical processes into the models on higher spatial resolutions. Meanwhile, more systematic observations and more advanced retrieval methods for instruments that address EAD related science issues have made it possible to evaluate model results and quantify the role of EAD in the earth system, and to further reduce the uncertainties in EAD simulations. Though much progress has been made, large discrepancies and knowledge gaps still exist among EAD simulations. The deficiencies and limitations that pertain to the performance of the EAD simulations referred to in the present study are also discussed.
基金supported by the Chinese Academy of Sciencesthe National Key R&D Program of China+22 种基金the CAS Center for Excellence in Particle PhysicsWuyi Universitythe Tsung-Dao Lee Institute of Shanghai Jiao Tong University in Chinathe Institut National de Physique Nucléaire et de Physique de Particules (IN2P3) in Francethe Istituto Nazionale di Fisica Nucleare (INFN) in Italythe Italian-Chinese collaborative research program MAECI-NSFCthe Fond de la Recherche Scientifique (F.R.S-FNRS)FWO under the "Excellence of Science-EOS" in Belgiumthe Conselho Nacional de Desenvolvimento Científico e Tecnològico in Brazilthe Agencia Nacional de Investigacion y Desarrollo in Chilethe Charles University Research Centrethe Ministry of Education,Youth,and Sports in Czech Republicthe Deutsche Forschungsgemeinschaft (DFG)the Helmholtz Associationthe Cluster of Excellence PRISMA+ in Germanythe Joint Institute of Nuclear Research (JINR)Lomonosov Moscow State University in Russiathe joint Russian Science Foundation (RSF)National Natural Science Foundation of China (NSFC) research programthe MOST and MOE in Taiwan,Chinathe Chulalongkorn UniversitySuranaree University of Technology in Thailandthe University of California at Irvine in USA
文摘The Jiangmen Underground Neutrino Observatory(JUNO)is a large liquid scintillator detector designed to explore many topics in fundamental physics.In this study,the potential of searching for proton decay in the p→νK^(+)mode with JUNO is investigated.The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification.Moreover,the excellent energy resolution of JUNO permits suppression of the sizable background caused by other delayed signals.Based on these advantages,the detection efficiency for the proton decay via p→νK^(+)is 36.9%±4.9%with a background level of 0.2±0.05(syst)±0.2(stat)events after 10 years of data collection.The estimated sensitivity based on 200 kton-years of exposure is 9.6×1033 years,which is competitive with the current best limits on the proton lifetime in this channel and complements the use of different detection technologies.
