The importance of dissolved organic phosphorus(DOP) as a potential nutrient source for primary producers in marine systems has been recognized for up to eight decades, but currently, the understanding of the biogeoche...The importance of dissolved organic phosphorus(DOP) as a potential nutrient source for primary producers in marine systems has been recognized for up to eight decades, but currently, the understanding of the biogeochemistry of DOP is in its infancy. In the present study, monthly data between 2000 and 2014 were used to analyze the temporal and spatial distributions of DOP in the Mir Bay, the northern South China Sea. The DOP residence time(TDOP) was also investigated using a simple regression analysis in combination with chlorophyll a(Chl a) measurements while excess DOP(ΔDOP), produced by the biogeochemical processes of autotrophic production and heterotrophic removal, was determined using a two-component mixing mass-balance model in combination with salinity measurements. The results showed that the DOP concentration was(0.017±0.010) mg/L higher in the surface-water compared with the bottom-water and higher in the inner Tolo Harbour and waters adjacent to Shatoujiao compared with the main zone of the bay. Although seasonal changes and annual variability in the DOP were small, the surface DOP concentration was higher in the wet season(April–September)than in the dry season(October–March) due to the impacts of seaward discharges and atmospheric deposition into the bay. Measurement and regression results showed that the DOP release rate from phytoplankton production was about 1.83(gP)/(gChl a) and the TDOP was about 7 d, which implied that the DOP cycle in the bay was rapid. The ΔDOP was calculated from the model to be about 0.000 mg/L in the main zone of the bay and about 0.002 mg/L in the inner Tolo Harbour and waters adjacent to Shaotoujiao, suggesting that the autotrophic production of DOP was almost balanced by the heterotrophic removal in the main zone of the bay and dominated in the inner Tolo Harbour and waters adjacent to Shaotoujiao. In conclusion, the Mirs Bay is very productive and fairly heterotrophic.展开更多
Mirs Bay is a semi-enclosed bay neighboring the Zhujiang(Pearl)River estuary,one of the largest estuarine systems in the world.The long-term historical observational data(1994-2017)of temperature,salinity,dissolved ox...Mirs Bay is a semi-enclosed bay neighboring the Zhujiang(Pearl)River estuary,one of the largest estuarine systems in the world.The long-term historical observational data(1994-2017)of temperature,salinity,dissolved oxygen(DO),and biochemical parameters were used to examine the spatiotemporal distribution of hypoxia in Mirs Bay and adjacent coastal waters.Results show that bottom hypoxia varied seasonally and interannually.Hypoxia mainly occurred from June to September in Mirs Bay and the transition zone in the southern waters of Hong Kong,and the recorded hypoxia events have increased from 2007.The density difference between the bottom and surface layers was positively related to the bottom apparent oxygen utilization(AOU)(R=0.620,P<0.001)and negatively related to the bottom DO(R=0.616,P<0.001),indicating that water column stratification was an essential prerequisite for the formation of bottom hypoxia in summer.The bottom oxygen consumption and hypoxia had higher positive correlation with the seasonal thermocline(R=0.683,P<0.001)than the halocline(R=0.540,P<0.001),including in the area was affected by freshwater plume.The insignificant relationship between AOU and nutrients indicated that local eutrophication was not the only important factor in the formation of the hypoxic zone during summer.The decrease in phosphorous owing to the pollutant reduction policy and the increase in nitrate may have led to an increase in hypoxia events in the bay where waters therein are characterized by nitrogen-limitation.The increase in chemical oxygen demand in wastewater also promoted oxygen consumption.Compared to the adjacent coastal waters influenced by Zhujiang River plume water,the Mirs Bay experienced more hypoxia events.The high concentrations of ammonium and total Kjeldahl nitrogen in the sediment of Mirs Bay increased the oxygen depletion in the bottom water.The long residence time of the near-bottom water in Mirs Bay increased the risk of bottom hypoxia events,although the nutrient concentrations were lower than those in the transition zone.These factors lead to differences in hypoxia occurrence in Mirs Bay and adjacent coastal waters.展开更多
在北美和日本,无线集群系统迅速发展,其容量已远远不能满足人们的需求。各厂商纷纷投入力量开发新的系统,希望提高频谱利用率,增加系统容量。针对这种需求,MIRS(Motorola Integrated Radio System)应运而生。该系统是一种综合业务数字...在北美和日本,无线集群系统迅速发展,其容量已远远不能满足人们的需求。各厂商纷纷投入力量开发新的系统,希望提高频谱利用率,增加系统容量。针对这种需求,MIRS(Motorola Integrated Radio System)应运而生。该系统是一种综合业务数字移动通讯系统,集寻呼、集群、调度、移动电话和数据通讯多种业务于一身,工作在800MHz和1500MHz的集群频段,并且采用数字蜂窝技术。MIRS系统于1991年2月获得美国FCC批准,已在美国建网,发展前景较好,预计1995年底将覆盖美国洛杉矶、纽约、旧金山、芝加哥、达拉斯、休斯顿六大地区。展开更多
Despite aggressive therapy,glioblastoma(GBM)recurs in almost all patients and treatment options are very limited.Despite our growing understanding of how cellular transitions associate with relapse in GBM,critical gap...Despite aggressive therapy,glioblastoma(GBM)recurs in almost all patients and treatment options are very limited.Despite our growing understanding of how cellular transitions associate with relapse in GBM,critical gaps remain in our ability to block these molecular changes and treat recurrent disease.In this study we combine computational biology,forward-thinking understanding of miRNA biology and cutting-edge nucleic acid delivery vehicles to advance targeted therapeutics for GBM.Computational analysis of RNA sequencing from clinical GBM specimens identified TGFβ type Ⅱ receptor(TGFBR2)as a key player in the mesenchymal transition associated with worse outcome in GBM.Mechanistically,we show that elevated levels of TGFBR2 is conducive to reduced temozolomide(TMZ)sensitivity.This effect is,at least partially,induced by stem-cell driving events coordinated by the reprogramming transcription factors Oct4 and Sox2 that lead to open chromatin states.We show that blocking TGFBR2 via molecular and pharmacological approaches decreases stem cell capacity and sensitivity of clinical recurrent GBM(rGBM)isolates to TMZ in vitro.Network analysis uncovered miR-590-3p as a tumor suppressor that simultaneously inhibits multiple oncogenic nodes downstream of TGFBR2.We also developed novel biodegradable lipophilic poly(β-amino ester)nanoparticles(LiPBAEs)for in vivo microRNA(miRNAs)delivery.Following direct intra-tumoral infusion,these nanomiRs efficiently distribute through the tumors.Importantly,miR-590-3p nanomiRs inhibited the growth and extended survival of mice bearing orthotopic human rGBM xenografts,with an apparent 30% cure rate.These results show that miRNA-based targeted therapeutics provide new opportunities to treat rGBM and bypass the resistance to standard of care therapy.展开更多
基金The National Key Basic Research Special Foundation of China under contract No.2013CB965101the Marine Science and Technology Foundation of the South China Sea Sub-administration,SOA,China under contract No.1624
文摘The importance of dissolved organic phosphorus(DOP) as a potential nutrient source for primary producers in marine systems has been recognized for up to eight decades, but currently, the understanding of the biogeochemistry of DOP is in its infancy. In the present study, monthly data between 2000 and 2014 were used to analyze the temporal and spatial distributions of DOP in the Mir Bay, the northern South China Sea. The DOP residence time(TDOP) was also investigated using a simple regression analysis in combination with chlorophyll a(Chl a) measurements while excess DOP(ΔDOP), produced by the biogeochemical processes of autotrophic production and heterotrophic removal, was determined using a two-component mixing mass-balance model in combination with salinity measurements. The results showed that the DOP concentration was(0.017±0.010) mg/L higher in the surface-water compared with the bottom-water and higher in the inner Tolo Harbour and waters adjacent to Shatoujiao compared with the main zone of the bay. Although seasonal changes and annual variability in the DOP were small, the surface DOP concentration was higher in the wet season(April–September)than in the dry season(October–March) due to the impacts of seaward discharges and atmospheric deposition into the bay. Measurement and regression results showed that the DOP release rate from phytoplankton production was about 1.83(gP)/(gChl a) and the TDOP was about 7 d, which implied that the DOP cycle in the bay was rapid. The ΔDOP was calculated from the model to be about 0.000 mg/L in the main zone of the bay and about 0.002 mg/L in the inner Tolo Harbour and waters adjacent to Shaotoujiao, suggesting that the autotrophic production of DOP was almost balanced by the heterotrophic removal in the main zone of the bay and dominated in the inner Tolo Harbour and waters adjacent to Shaotoujiao. In conclusion, the Mirs Bay is very productive and fairly heterotrophic.
基金Supported by the Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)(Nos.GML2019ZD0302,GML2019ZD0303)the National Natural Science Foundation of China(No.31971480)the State Key Laboratory of Tropical Oceanology Independent Research Fund(No.LTOZZ2103)。
文摘Mirs Bay is a semi-enclosed bay neighboring the Zhujiang(Pearl)River estuary,one of the largest estuarine systems in the world.The long-term historical observational data(1994-2017)of temperature,salinity,dissolved oxygen(DO),and biochemical parameters were used to examine the spatiotemporal distribution of hypoxia in Mirs Bay and adjacent coastal waters.Results show that bottom hypoxia varied seasonally and interannually.Hypoxia mainly occurred from June to September in Mirs Bay and the transition zone in the southern waters of Hong Kong,and the recorded hypoxia events have increased from 2007.The density difference between the bottom and surface layers was positively related to the bottom apparent oxygen utilization(AOU)(R=0.620,P<0.001)and negatively related to the bottom DO(R=0.616,P<0.001),indicating that water column stratification was an essential prerequisite for the formation of bottom hypoxia in summer.The bottom oxygen consumption and hypoxia had higher positive correlation with the seasonal thermocline(R=0.683,P<0.001)than the halocline(R=0.540,P<0.001),including in the area was affected by freshwater plume.The insignificant relationship between AOU and nutrients indicated that local eutrophication was not the only important factor in the formation of the hypoxic zone during summer.The decrease in phosphorous owing to the pollutant reduction policy and the increase in nitrate may have led to an increase in hypoxia events in the bay where waters therein are characterized by nitrogen-limitation.The increase in chemical oxygen demand in wastewater also promoted oxygen consumption.Compared to the adjacent coastal waters influenced by Zhujiang River plume water,the Mirs Bay experienced more hypoxia events.The high concentrations of ammonium and total Kjeldahl nitrogen in the sediment of Mirs Bay increased the oxygen depletion in the bottom water.The long residence time of the near-bottom water in Mirs Bay increased the risk of bottom hypoxia events,although the nutrient concentrations were lower than those in the transition zone.These factors lead to differences in hypoxia occurrence in Mirs Bay and adjacent coastal waters.
文摘在北美和日本,无线集群系统迅速发展,其容量已远远不能满足人们的需求。各厂商纷纷投入力量开发新的系统,希望提高频谱利用率,增加系统容量。针对这种需求,MIRS(Motorola Integrated Radio System)应运而生。该系统是一种综合业务数字移动通讯系统,集寻呼、集群、调度、移动电话和数据通讯多种业务于一身,工作在800MHz和1500MHz的集群频段,并且采用数字蜂窝技术。MIRS系统于1991年2月获得美国FCC批准,已在美国建网,发展前景较好,预计1995年底将覆盖美国洛杉矶、纽约、旧金山、芝加哥、达拉斯、休斯顿六大地区。
基金supported by the United States NIH grants:R01NS073611(J.L.),R01NS096754(J.L.),R01CA228133(J.G.),P41EB028239(J.G.),R37CA246699(S.T.)and R01NS120949(H.L.B.)Summer Academic Research Experience and the Johns Hopkins Initiative for Careers in Science and Medicine(H.A.)+5 种基金Johns Hopkins University PURA(H.K.)Life Design Summer Experience Practicum(TC.T.and J.M.A)John Camp and Mindy Farber'74 Endowed Award(M.K.J.)and NCI F99 Fellowship F99CA284254(A.L.J.)The SKCCC(P30CA006973)Hugo W Moser institute IDDRC(5P50HD103538)Microscopy Core Grant(S10 OD016374).
文摘Despite aggressive therapy,glioblastoma(GBM)recurs in almost all patients and treatment options are very limited.Despite our growing understanding of how cellular transitions associate with relapse in GBM,critical gaps remain in our ability to block these molecular changes and treat recurrent disease.In this study we combine computational biology,forward-thinking understanding of miRNA biology and cutting-edge nucleic acid delivery vehicles to advance targeted therapeutics for GBM.Computational analysis of RNA sequencing from clinical GBM specimens identified TGFβ type Ⅱ receptor(TGFBR2)as a key player in the mesenchymal transition associated with worse outcome in GBM.Mechanistically,we show that elevated levels of TGFBR2 is conducive to reduced temozolomide(TMZ)sensitivity.This effect is,at least partially,induced by stem-cell driving events coordinated by the reprogramming transcription factors Oct4 and Sox2 that lead to open chromatin states.We show that blocking TGFBR2 via molecular and pharmacological approaches decreases stem cell capacity and sensitivity of clinical recurrent GBM(rGBM)isolates to TMZ in vitro.Network analysis uncovered miR-590-3p as a tumor suppressor that simultaneously inhibits multiple oncogenic nodes downstream of TGFBR2.We also developed novel biodegradable lipophilic poly(β-amino ester)nanoparticles(LiPBAEs)for in vivo microRNA(miRNAs)delivery.Following direct intra-tumoral infusion,these nanomiRs efficiently distribute through the tumors.Importantly,miR-590-3p nanomiRs inhibited the growth and extended survival of mice bearing orthotopic human rGBM xenografts,with an apparent 30% cure rate.These results show that miRNA-based targeted therapeutics provide new opportunities to treat rGBM and bypass the resistance to standard of care therapy.
