Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we...Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we systematically investigated the effects of drug loading methods and physicochemical properties(lipophilicity and molecular weight)on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions.Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method,drug lipophilicity,drug molecular weight and exosome/drug proportions.Of note,we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes,which was attributed to the efficient loading capacity and sustained release behavior.Furthermore,milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs(octreotide,exendin-4 and salmon calcitonin).Collectively,our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.展开更多
Three cationic lipids with lysylated（1）, histidylated（2）, and arginylated（3） headgroups and cholesterol hydrophobic moiety were synthesized. The average sizes of liposomes and lipoplexes were around 100 and 160 ...Three cationic lipids with lysylated（1）, histidylated（2）, and arginylated（3） headgroups and cholesterol hydrophobic moiety were synthesized. The average sizes of liposomes and lipoplexes were around 100 and 160 nm, respectively. The gene transfection efficiency of the three lipoplexes loaded with pGL3 or pORF-LacZ was compared on 293T cells in the presence or the absence of serum. The transfection efficiency of the three lipoplexes in a serum-free medium was 2 to 3-fold higher than that of dioleoyl-trimethylammonium propane（DOTAP）. In the presence of serum, however, most of the lipoplexes showed lower transfection activities; only lipoplex 3 retained its high transfection efficiency.展开更多
Design and synthesis of a carbamate-linked cationic lipid DDCTMA (N-[1-(2,3-didodecylcarbamoyloxy)propyl]-N,N,N-trimethylammonium iodide)? as gene delivery carriers was described in this work. The transfection efficie...Design and synthesis of a carbamate-linked cationic lipid DDCTMA (N-[1-(2,3-didodecylcarbamoyloxy)propyl]-N,N,N-trimethylammonium iodide)? as gene delivery carriers was described in this work. The transfection efficiency of cationic liposome increased dramatically with the increase in the content of DOPE. In addition, the transfection efficiency of some of cationic lipoplexes was superior or parallel to that of two commercial transfection agents, Lipofectamine2000 and DOTAP. The carbamate-linked cationic lipid DDCTMA/DOPE may be a promising gene carrier that has high transfection efficiency as well as low cytotoxicity.展开更多
In this paper, the relatived mechanism between lipofectamine 2000 mediated transmembrane gene delivery and endocytic pathway were investigated. Clathrin and caveolae-mediated endocytic pathway contributions to transfe...In this paper, the relatived mechanism between lipofectamine 2000 mediated transmembrane gene delivery and endocytic pathway were investigated. Clathrin and caveolae-mediated endocytic pathway contributions to transfection efficiency were studied. The inhibitors of endocytosis were used to treat HEp-2 cells before lipofectamine 2000/pGFP-N2 transfection. Transfection efficiency was evaluated with green fluorescence protein (GFP) expression assays. Cell viability and cytotoxicity were evaluated with MTT method. The results indicated that inhibitors of clathrin (chlorpromazine or wortmannin) and caveolin (genistein) could reduce the cell transfection efficiency observably. Both clathrin and caveolae-mediated endocytic pathways play important roles in transmembrane gene delivery.展开更多
This study assessed six commercially available in-duct air cleaning devices which are designed to be mounted in the central ventilation system of offices or commercial buildings.The selected devices use different air ...This study assessed six commercially available in-duct air cleaning devices which are designed to be mounted in the central ventilation system of offices or commercial buildings.The selected devices use different air cleaning technologies:mechanical filtration,electrostatic precipitation,gas filtration,ionization/cold plasma,photocatalytic oxidation(PCO)and catalysis under UV light.They were tested against particles,a mixture of volatile organic compounds containing acetone,acetaldehyde,toluene,heptane and formaldehyde,and two bio-contaminants:Aspergillus brasiliensis(fungus)and Staphylococcus epidermidis(bacteria).Two different test rigs were used.The single pass efficiency of each device was determined for three airflow rates,corresponding to face velocities ranging from 0.9 to 2.7 m/s,and two sets of temperature and humidity that are representative of indoor air conditions in wintertime and summertime.The concentration of the chal-lenge volatile organic compounds was also varied in the 30 to 100μg/m^(3)range as a way to characterize their influence on efficiency at realistic concentration levels for non-industrial buildings.Measurements of ozone and formaldehyde concentration downstream of the air cleaners were carried out to determine the emission rate of by-products into the air stream.Finally,the energy issue was addressed by measuring the electric power drawn and pressure loss of the devices.The results showed that two devices,namely a radiant catalytic ionizer and a plasma ionizer,had a very low single pass efficiency against all the challenge pollutants.The association of the plasma ionizer and the electrostatic precipitator did not produce a synergetic effect between the two technologies either,contrary to what their manufacturer claims.Finally,three of the six devices tested were effective in terms of pollutant removal,but only two had an acceptable energy effectiveness in view of their use in low or zero energy buildings.Their energy effectiveness ranged from a few thousand m^(3)/kWh for VOCs at the 展开更多
Many states have implemented an Energy Efficiency Resource Standard (EERS) or target to curtail greenhouse gas (GHG) emissions. California alone has set a target of doubling energy efficiency savings in existing build...Many states have implemented an Energy Efficiency Resource Standard (EERS) or target to curtail greenhouse gas (GHG) emissions. California alone has set a target of doubling energy efficiency savings in existing buildings by 2030. As more states rely on energy efficiency to reduce GHG emissions, programs designed to support the planning and implementation of energy efficiency projects will become more important. Identifying energy efficiency projects has traditionally been the focus of these programs, however delivering savings remains a key challenge. Strategies to address procurement are often overlooked as program resources focus more on technical resources, such as audits and monetary incentives. Then once identified, specialized energy efficiency projects are often folded in with standard maintenance or capital improvement projects, putting them at risk of compromising the expected performance. This paper focuses on procurement as a key component of program implementation and success and outlines key issues and challenges specifically faced by the public sector. Furthermore, the paper shares a procurement strategy implemented through the Southern California Regional Energy Network (SoCalREN) Public Agency Program that addresses these problems in order to assure intended project performance. The strategy includes engaging procurement stakeholders early in the project process, exploring the different types of procurement pathways and following an implementation checklist to enhance project success. With this systematic approach to procurement, there will be fewer barriers and energy efficiency will be easy and enticing, which will further enable states to achieve their GHG emission reduction targets.展开更多
基金The authors gratefully acknowledge financial support from National Natural Science Foundation of China(81872818)National Key R&D Program of China(2021YFE0115200).
文摘Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we systematically investigated the effects of drug loading methods and physicochemical properties(lipophilicity and molecular weight)on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions.Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method,drug lipophilicity,drug molecular weight and exosome/drug proportions.Of note,we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes,which was attributed to the efficient loading capacity and sustained release behavior.Furthermore,milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs(octreotide,exendin-4 and salmon calcitonin).Collectively,our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.
基金Supported by the National Basic Research Program of China(No.2005CB623903).
文摘Three cationic lipids with lysylated（1）, histidylated（2）, and arginylated（3） headgroups and cholesterol hydrophobic moiety were synthesized. The average sizes of liposomes and lipoplexes were around 100 and 160 nm, respectively. The gene transfection efficiency of the three lipoplexes loaded with pGL3 or pORF-LacZ was compared on 293T cells in the presence or the absence of serum. The transfection efficiency of the three lipoplexes in a serum-free medium was 2 to 3-fold higher than that of dioleoyl-trimethylammonium propane（DOTAP）. In the presence of serum, however, most of the lipoplexes showed lower transfection activities; only lipoplex 3 retained its high transfection efficiency.
文摘Design and synthesis of a carbamate-linked cationic lipid DDCTMA (N-[1-(2,3-didodecylcarbamoyloxy)propyl]-N,N,N-trimethylammonium iodide)? as gene delivery carriers was described in this work. The transfection efficiency of cationic liposome increased dramatically with the increase in the content of DOPE. In addition, the transfection efficiency of some of cationic lipoplexes was superior or parallel to that of two commercial transfection agents, Lipofectamine2000 and DOTAP. The carbamate-linked cationic lipid DDCTMA/DOPE may be a promising gene carrier that has high transfection efficiency as well as low cytotoxicity.
文摘In this paper, the relatived mechanism between lipofectamine 2000 mediated transmembrane gene delivery and endocytic pathway were investigated. Clathrin and caveolae-mediated endocytic pathway contributions to transfection efficiency were studied. The inhibitors of endocytosis were used to treat HEp-2 cells before lipofectamine 2000/pGFP-N2 transfection. Transfection efficiency was evaluated with green fluorescence protein (GFP) expression assays. Cell viability and cytotoxicity were evaluated with MTT method. The results indicated that inhibitors of clathrin (chlorpromazine or wortmannin) and caveolin (genistein) could reduce the cell transfection efficiency observably. Both clathrin and caveolae-mediated endocytic pathways play important roles in transmembrane gene delivery.
文摘This study assessed six commercially available in-duct air cleaning devices which are designed to be mounted in the central ventilation system of offices or commercial buildings.The selected devices use different air cleaning technologies:mechanical filtration,electrostatic precipitation,gas filtration,ionization/cold plasma,photocatalytic oxidation(PCO)and catalysis under UV light.They were tested against particles,a mixture of volatile organic compounds containing acetone,acetaldehyde,toluene,heptane and formaldehyde,and two bio-contaminants:Aspergillus brasiliensis(fungus)and Staphylococcus epidermidis(bacteria).Two different test rigs were used.The single pass efficiency of each device was determined for three airflow rates,corresponding to face velocities ranging from 0.9 to 2.7 m/s,and two sets of temperature and humidity that are representative of indoor air conditions in wintertime and summertime.The concentration of the chal-lenge volatile organic compounds was also varied in the 30 to 100μg/m^(3)range as a way to characterize their influence on efficiency at realistic concentration levels for non-industrial buildings.Measurements of ozone and formaldehyde concentration downstream of the air cleaners were carried out to determine the emission rate of by-products into the air stream.Finally,the energy issue was addressed by measuring the electric power drawn and pressure loss of the devices.The results showed that two devices,namely a radiant catalytic ionizer and a plasma ionizer,had a very low single pass efficiency against all the challenge pollutants.The association of the plasma ionizer and the electrostatic precipitator did not produce a synergetic effect between the two technologies either,contrary to what their manufacturer claims.Finally,three of the six devices tested were effective in terms of pollutant removal,but only two had an acceptable energy effectiveness in view of their use in low or zero energy buildings.Their energy effectiveness ranged from a few thousand m^(3)/kWh for VOCs at the
文摘Many states have implemented an Energy Efficiency Resource Standard (EERS) or target to curtail greenhouse gas (GHG) emissions. California alone has set a target of doubling energy efficiency savings in existing buildings by 2030. As more states rely on energy efficiency to reduce GHG emissions, programs designed to support the planning and implementation of energy efficiency projects will become more important. Identifying energy efficiency projects has traditionally been the focus of these programs, however delivering savings remains a key challenge. Strategies to address procurement are often overlooked as program resources focus more on technical resources, such as audits and monetary incentives. Then once identified, specialized energy efficiency projects are often folded in with standard maintenance or capital improvement projects, putting them at risk of compromising the expected performance. This paper focuses on procurement as a key component of program implementation and success and outlines key issues and challenges specifically faced by the public sector. Furthermore, the paper shares a procurement strategy implemented through the Southern California Regional Energy Network (SoCalREN) Public Agency Program that addresses these problems in order to assure intended project performance. The strategy includes engaging procurement stakeholders early in the project process, exploring the different types of procurement pathways and following an implementation checklist to enhance project success. With this systematic approach to procurement, there will be fewer barriers and energy efficiency will be easy and enticing, which will further enable states to achieve their GHG emission reduction targets.
