Multiple drug resistance(MDR)is the tumor’s way of escaping the cytotoxic effects of various unrelated chemotherapeutic drugs.It can be either innate or acquired.MDR represents the end of the therapeutic pathway,and ...Multiple drug resistance(MDR)is the tumor’s way of escaping the cytotoxic effects of various unrelated chemotherapeutic drugs.It can be either innate or acquired.MDR represents the end of the therapeutic pathway,and it practically leaves no treatment alternatives.Reversing MDR is an unfulfilled goal,despite the important recent advances in cancer research.MDR,the main cause of death in cancer patients,is a multi-factorial development,and most of its known causes have been thoroughly discussed in the literature.However,there is one aspect that has not received adequate consideration-intracellular alkalosis-which is part of wider pH deregulation where the pH gradient is inverted,meaning that extracellular pH is decreased and intracellular pH increased.This situation interacts with MDR and with the proteins involved,such as P-gp,breast cancer resistance protein,and multidrug associated resistance protein 1.However,there are also situations in which these proteins play no role at all,and where pH takes the lead.This is the case in ion trapping.Reversing the pH gradient to normal can be an important contribution to managing MDR.The drugs to manipulate pH exist,and most of them are FDA approved and in clinical use for other purposes.Furthermore,they have low or no toxicity and are inexpensive compared with any chemotherapeutic treatment.Repurposing these drugs and combining them in a reasonable fashion is one of the points proposed in this paper,which discusses the relationship between cancer’s peculiar pH and MDR.展开更多
A kind of PH gradient microfluidic chips through soft-lithography microfabrication for isoelectric focusing(IEF)and high performance liquid chromatography(HPLC)is introduced here.These pH gradient chips have the advan...A kind of PH gradient microfluidic chips through soft-lithography microfabrication for isoelectric focusing(IEF)and high performance liquid chromatography(HPLC)is introduced here.These pH gradient chips have the advan-tages such as easy fabrication,controllable pH range and precision,isoelectric focusing and separation at the same time,low voltage for isoelectric focusing,and time stable pH gradient.This method has potential application to sample preparation,separation and analysis of microfluidic chips.展开更多
The pH gradient caused by H^(+)/OH^(−)transport on an electrode surface is the key factor determining reaction performance,but its detailed impact on the electrode reaction kinetics has yet to be clarified.Here,the pH...The pH gradient caused by H^(+)/OH^(−)transport on an electrode surface is the key factor determining reaction performance,but its detailed impact on the electrode reaction kinetics has yet to be clarified.Here,the pH gradient effect was determined by developing electrode reaction equations,considering the overpotential assigned to the pH gradient called pH overpotential.The pH gradient effect was revealed to involve two aspects:(1)the Nernst pH overpotential,accounting for the common Nernst relationship with pH,and(2)the pH-dependent function of the electron-transfer coefficient(α_(pH)).Both parts were verified experimentally using oxygen reduction reaction and hydrogen evolution reaction,obviously,with differentα_(pH) functions.Detailedα_(pH) function effect was clarified based on numerical calculations of the electrode reaction equations.We found that the effect could be assessed suitably by an apparent constant(α_(app))and a nonlinear fitting method proposed forα_(app) value estimation.The results of this study provide the kinetic fundamentals of electrode reactions involving H^(+)/OH^(−)and contribute to the understanding and assessment of their performance with the H^(+)/OH^(−)transport effect.展开更多
Monolithic materials were prepared in capillaries by in situ polymerization of acrylamide, glycidyl methacrylate and N,N′-memylenebisacrylamid in the presence of trinary porogens, including 1,4-butanediol, dodecanol ...Monolithic materials were prepared in capillaries by in situ polymerization of acrylamide, glycidyl methacrylate and N,N′-memylenebisacrylamid in the presence of trinary porogens, including 1,4-butanediol, dodecanol and dimethyl sulphoxide. With Ampholine immobilized on the monolith by chemical bonding according to their p/s, the monolithic immobilized pH gradient (M-IPG) was prepared, and applied to the separation of four standard proteins. Compared with polyacrylate based M-IPG, the hydrophilicity of the new material was improved. It could not only avoid the adsorption of proteins, but also make the synthesized procedure simple, which showed great potential in the analysis of proteins.展开更多
The metal and nano-ceramic composite coatings were formed on gray cast iron surface by electrodepositon method.The Ni-Co was used as metal matrix,and the nano-Al2O3 was chosen as second-phase particulates.The gradient...The metal and nano-ceramic composite coatings were formed on gray cast iron surface by electrodepositon method.The Ni-Co was used as metal matrix,and the nano-Al2O3 was chosen as second-phase particulates.The gradient structure of biology material was the model to avoid bad interface bonding and stress distribution,therefore the gradient composite coating was prepared.The morphology of composite coatings was flatter and the microstructure was more com-pact than the pure Ni-Co coatings.Effect of pH value on surface morphology was analyzed,which some microcracks appeared when pH value was greater than 5.The content of codeposition na-no-Al2O3 reached a maximum value at pH value of 3-4,at the same time the properties including mi-crohardness and wear-resistance were analyzed.The result indicated that the mirohardness reached a maximum value and the wear loss volume was less at pH value 3-4.展开更多
文摘Multiple drug resistance(MDR)is the tumor’s way of escaping the cytotoxic effects of various unrelated chemotherapeutic drugs.It can be either innate or acquired.MDR represents the end of the therapeutic pathway,and it practically leaves no treatment alternatives.Reversing MDR is an unfulfilled goal,despite the important recent advances in cancer research.MDR,the main cause of death in cancer patients,is a multi-factorial development,and most of its known causes have been thoroughly discussed in the literature.However,there is one aspect that has not received adequate consideration-intracellular alkalosis-which is part of wider pH deregulation where the pH gradient is inverted,meaning that extracellular pH is decreased and intracellular pH increased.This situation interacts with MDR and with the proteins involved,such as P-gp,breast cancer resistance protein,and multidrug associated resistance protein 1.However,there are also situations in which these proteins play no role at all,and where pH takes the lead.This is the case in ion trapping.Reversing the pH gradient to normal can be an important contribution to managing MDR.The drugs to manipulate pH exist,and most of them are FDA approved and in clinical use for other purposes.Furthermore,they have low or no toxicity and are inexpensive compared with any chemotherapeutic treatment.Repurposing these drugs and combining them in a reasonable fashion is one of the points proposed in this paper,which discusses the relationship between cancer’s peculiar pH and MDR.
文摘A kind of PH gradient microfluidic chips through soft-lithography microfabrication for isoelectric focusing(IEF)and high performance liquid chromatography(HPLC)is introduced here.These pH gradient chips have the advan-tages such as easy fabrication,controllable pH range and precision,isoelectric focusing and separation at the same time,low voltage for isoelectric focusing,and time stable pH gradient.This method has potential application to sample preparation,separation and analysis of microfluidic chips.
基金supported by the National Natural Science Foundation of China(grant nos.51525805,51727812,and 51808526).
文摘The pH gradient caused by H^(+)/OH^(−)transport on an electrode surface is the key factor determining reaction performance,but its detailed impact on the electrode reaction kinetics has yet to be clarified.Here,the pH gradient effect was determined by developing electrode reaction equations,considering the overpotential assigned to the pH gradient called pH overpotential.The pH gradient effect was revealed to involve two aspects:(1)the Nernst pH overpotential,accounting for the common Nernst relationship with pH,and(2)the pH-dependent function of the electron-transfer coefficient(α_(pH)).Both parts were verified experimentally using oxygen reduction reaction and hydrogen evolution reaction,obviously,with differentα_(pH) functions.Detailedα_(pH) function effect was clarified based on numerical calculations of the electrode reaction equations.We found that the effect could be assessed suitably by an apparent constant(α_(app))and a nonlinear fitting method proposed forα_(app) value estimation.The results of this study provide the kinetic fundamentals of electrode reactions involving H^(+)/OH^(−)and contribute to the understanding and assessment of their performance with the H^(+)/OH^(−)transport effect.
基金Supported by the State Key Fundamental Research Program (Grant No. 2001CB51020)National Natural Science Foundation of China (Grant Nos. 20405104 and 20435020) 100 Talents Project of Chinese Academy of Sciences
文摘Monolithic materials were prepared in capillaries by in situ polymerization of acrylamide, glycidyl methacrylate and N,N′-memylenebisacrylamid in the presence of trinary porogens, including 1,4-butanediol, dodecanol and dimethyl sulphoxide. With Ampholine immobilized on the monolith by chemical bonding according to their p/s, the monolithic immobilized pH gradient (M-IPG) was prepared, and applied to the separation of four standard proteins. Compared with polyacrylate based M-IPG, the hydrophilicity of the new material was improved. It could not only avoid the adsorption of proteins, but also make the synthesized procedure simple, which showed great potential in the analysis of proteins.
基金Funded by the National Natural Science Foundation of China(No.50635030)the National Basic Research of China (No.2007CB616913)
文摘The metal and nano-ceramic composite coatings were formed on gray cast iron surface by electrodepositon method.The Ni-Co was used as metal matrix,and the nano-Al2O3 was chosen as second-phase particulates.The gradient structure of biology material was the model to avoid bad interface bonding and stress distribution,therefore the gradient composite coating was prepared.The morphology of composite coatings was flatter and the microstructure was more com-pact than the pure Ni-Co coatings.Effect of pH value on surface morphology was analyzed,which some microcracks appeared when pH value was greater than 5.The content of codeposition na-no-Al2O3 reached a maximum value at pH value of 3-4,at the same time the properties including mi-crohardness and wear-resistance were analyzed.The result indicated that the mirohardness reached a maximum value and the wear loss volume was less at pH value 3-4.
