The terminal velocity of a liquid droplet settling in a sulfactant solution has been studied for the non-linear adsorption Langmuir frameworks accounting for monolayer saturation and non-ideal surfactant interactions....The terminal velocity of a liquid droplet settling in a sulfactant solution has been studied for the non-linear adsorption Langmuir frameworks accounting for monolayer saturation and non-ideal surfactant interactions. Most prior research uses a linear adsorption model which cannot capture these effects, The Maragoni migration of a liquid drop settling through a surfactant solution is examined by using Langmuir framework. The solution concentration Ceq is assumed large enough for the surfactant mass transfer to be adsorption-controlled. Langmuir model generates non-linear Marangoni stresses which diverge in the limit of approaching ∝, strongly retarding U'.展开更多
Background： Edaravone had been validated to effectively protect against ischemic injuries. In this study, we investigated the protective effect of edaravone by observing the effects on anti-apoptosis, regulation of B...Background： Edaravone had been validated to effectively protect against ischemic injuries. In this study, we investigated the protective effect of edaravone by observing the effects on anti-apoptosis, regulation of Bcl-2/Bax protein expression and recovering from damage to mitochondria after OGD （oxygen-glucose deprivation）-reperfusion. Methods： Viability of PC 12 cells which were injured at different time of OGD injury, was quantified by measuring MTT （2-（4,5-dimethylthia-zol-2-yl）-2,5-diphenyltetrazolium bromide） staining. In addition, PC 12 cells＇ viability was also quantified after their preincubation in different concentration of edaravone for 30 min followed by （OGD）. Furthermore, apoptotic population of PC 12 cells that reinsulted from OGD-reperfusion with or without preincubation with edaravone was determined by flow cytometer analysis, electron microscope and Hoechst/Pl staining. Finally, change of Bcl-2/Bax protein expression was detected by Western blot. Results： （1） The viability of PC12 cells decreased with time （1-12 h） after OGD. We regarded the model of OGD 2 h, then replacing DMEM （Dulbecco＇s Modified Eagle＇s Medium） for another 24 h as an OGD-reperfusion in this research. Furthermore, most PC 12 cells were in the state of apoptosis after OGD-reperfusion. （2） The viability of PC 12 cells preincubated with edaravone at high concentrations （1, 0.1, 0.01 μmol/L） increased significantly with edaravone protecting PC 12 cells from apoptosis after OGD-reperfusion injury. （3） Furthermore, edaravone attenuates the damage of OGD-reperfusion on mitochondria and regulated Bcl-2/Bax protein imbalance expression after OGD-reperfusion. Conclusion： Neuroprotective effects of edaravone on ischemic or other brain injuries may be partly mediated through inhibition of Bcl-2/Bax apoptotic pathways by recovering from the damage of mitochondria.展开更多
This paper deals with the existence and nonexistence of global positive solutions of the following quasilinear parabolic equations:u t=1m△u m-u n, x∈Ω,t>0 1m·u mv=u p,x∈Ω,t>0 u(x,0)=u 0(x)>0,x∈Ω-w...This paper deals with the existence and nonexistence of global positive solutions of the following quasilinear parabolic equations:u t=1m△u m-u n, x∈Ω,t>0 1m·u mv=u p,x∈Ω,t>0 u(x,0)=u 0(x)>0,x∈Ω-where Ω∈R N is a bounded domain with smooth boundary Ω,m,n,p are positive constants, γ is the outward normal vector. The necessary and sufficient conditions for the global existence of solutions are obtained.展开更多
Mitochondrion is a semi-autonomous organelle,important for cell energy metabolism,apoptosis,the production of reactive oxygen species(ROS),and Ca2+homeostasis.Mitochondrial DNA(mtDNA)mutation is one of the primary fac...Mitochondrion is a semi-autonomous organelle,important for cell energy metabolism,apoptosis,the production of reactive oxygen species(ROS),and Ca2+homeostasis.Mitochondrial DNA(mtDNA)mutation is one of the primary factors in mitochondrial disorders.Though much progress has been made,there remain many difficulties in constructing cell models for mitochondrial diseases.This seriously restricts studies related to targeted drug discovery and the mechanism and therapy for such diseases.Here we summarize the characteristics of patient-specific immortalized lymphoblastoid cells,fibroblastoid cells,cytoplasmic hybrid(cybrid)cell lines,and induced pluripotent stem cells(iPSCs)-derived differentiation cells in the study of mitochondrial disorders,as well as offering discussion of roles and advances of these cell models,particularly in the screening of drugs.展开更多
Target-mediated drug disposition (TMDD)model is one of the main modeling theories for studying nonlinear pharmacokinetics (PK)ofmonoclonal antibodies.However,there are too many parameters in full TMDD model to be esti...Target-mediated drug disposition (TMDD)model is one of the main modeling theories for studying nonlinear pharmacokinetics (PK)ofmonoclonal antibodies.However,there are too many parameters in full TMDD model to be estimated based on limited clinical data,leading to instability of the final model.In the present study,we analyzed the predictive ability and applicability of a simplified quasi-steady state (QSS)model with the assumption that the total target concentration was a constant parameter during treatment with monoelonal antibody in clinical data modeling.Based on the parameters of a published TMDD model of denosumab,simulations were performed at population and individual levels.Then,a simplified TMDD model,QSS model, was used to examine the effects of hypotheses,in which the total receptor concentration was constant or variable on model fit and stability of parameter estimation.Both simulations at the population level and model fit results of simulated individual data showed that at the therapeutic doses,the total receptor concentration had little influence on changes in drug concentration,and the model with constant total receptor concentration had the same predictive power.The validated hypothesis could be applied to clinical trial design and selection of the optimal PK model in the development of monoclonal antibodies.展开更多
文摘The terminal velocity of a liquid droplet settling in a sulfactant solution has been studied for the non-linear adsorption Langmuir frameworks accounting for monolayer saturation and non-ideal surfactant interactions. Most prior research uses a linear adsorption model which cannot capture these effects, The Maragoni migration of a liquid drop settling through a surfactant solution is examined by using Langmuir framework. The solution concentration Ceq is assumed large enough for the surfactant mass transfer to be adsorption-controlled. Langmuir model generates non-linear Marangoni stresses which diverge in the limit of approaching ∝, strongly retarding U'.
基金Project (No. 2005C30059) supported by the Science and TechnologyProgram of Zhejiang Province, China
文摘Background： Edaravone had been validated to effectively protect against ischemic injuries. In this study, we investigated the protective effect of edaravone by observing the effects on anti-apoptosis, regulation of Bcl-2/Bax protein expression and recovering from damage to mitochondria after OGD （oxygen-glucose deprivation）-reperfusion. Methods： Viability of PC 12 cells which were injured at different time of OGD injury, was quantified by measuring MTT （2-（4,5-dimethylthia-zol-2-yl）-2,5-diphenyltetrazolium bromide） staining. In addition, PC 12 cells＇ viability was also quantified after their preincubation in different concentration of edaravone for 30 min followed by （OGD）. Furthermore, apoptotic population of PC 12 cells that reinsulted from OGD-reperfusion with or without preincubation with edaravone was determined by flow cytometer analysis, electron microscope and Hoechst/Pl staining. Finally, change of Bcl-2/Bax protein expression was detected by Western blot. Results： （1） The viability of PC12 cells decreased with time （1-12 h） after OGD. We regarded the model of OGD 2 h, then replacing DMEM （Dulbecco＇s Modified Eagle＇s Medium） for another 24 h as an OGD-reperfusion in this research. Furthermore, most PC 12 cells were in the state of apoptosis after OGD-reperfusion. （2） The viability of PC 12 cells preincubated with edaravone at high concentrations （1, 0.1, 0.01 μmol/L） increased significantly with edaravone protecting PC 12 cells from apoptosis after OGD-reperfusion injury. （3） Furthermore, edaravone attenuates the damage of OGD-reperfusion on mitochondria and regulated Bcl-2/Bax protein imbalance expression after OGD-reperfusion. Conclusion： Neuroprotective effects of edaravone on ischemic or other brain injuries may be partly mediated through inhibition of Bcl-2/Bax apoptotic pathways by recovering from the damage of mitochondria.
文摘This paper deals with the existence and nonexistence of global positive solutions of the following quasilinear parabolic equations:u t=1m△u m-u n, x∈Ω,t>0 1m·u mv=u p,x∈Ω,t>0 u(x,0)=u 0(x)>0,x∈Ω-where Ω∈R N is a bounded domain with smooth boundary Ω,m,n,p are positive constants, γ is the outward normal vector. The necessary and sufficient conditions for the global existence of solutions are obtained.
基金Project supported by the National Basic Research Program of China(No.2014CB943001)the National Natural Science Foundation of China(Nos.31771398 and 31571299)+1 种基金the Fundamental Research Funds for the Central Universities(No.2019QNA6001)the Zhejiang Provincial Natural Science Foundation of China(Nos.LZ19C060001 and LY14C060004)
文摘Mitochondrion is a semi-autonomous organelle,important for cell energy metabolism,apoptosis,the production of reactive oxygen species(ROS),and Ca2+homeostasis.Mitochondrial DNA(mtDNA)mutation is one of the primary factors in mitochondrial disorders.Though much progress has been made,there remain many difficulties in constructing cell models for mitochondrial diseases.This seriously restricts studies related to targeted drug discovery and the mechanism and therapy for such diseases.Here we summarize the characteristics of patient-specific immortalized lymphoblastoid cells,fibroblastoid cells,cytoplasmic hybrid(cybrid)cell lines,and induced pluripotent stem cells(iPSCs)-derived differentiation cells in the study of mitochondrial disorders,as well as offering discussion of roles and advances of these cell models,particularly in the screening of drugs.
文摘Target-mediated drug disposition (TMDD)model is one of the main modeling theories for studying nonlinear pharmacokinetics (PK)ofmonoclonal antibodies.However,there are too many parameters in full TMDD model to be estimated based on limited clinical data,leading to instability of the final model.In the present study,we analyzed the predictive ability and applicability of a simplified quasi-steady state (QSS)model with the assumption that the total target concentration was a constant parameter during treatment with monoelonal antibody in clinical data modeling.Based on the parameters of a published TMDD model of denosumab,simulations were performed at population and individual levels.Then,a simplified TMDD model,QSS model, was used to examine the effects of hypotheses,in which the total receptor concentration was constant or variable on model fit and stability of parameter estimation.Both simulations at the population level and model fit results of simulated individual data showed that at the therapeutic doses,the total receptor concentration had little influence on changes in drug concentration,and the model with constant total receptor concentration had the same predictive power.The validated hypothesis could be applied to clinical trial design and selection of the optimal PK model in the development of monoclonal antibodies.
