Objective: To study the reversal effect of neferine on adriamycin (ADM) resistant human breast cancer cell line MCF-7/ADM. Methods: The cytotoxic effect of Nef or ADM was determined by 3-[4, 5-dimethylthiazol-2.-yl], ...Objective: To study the reversal effect of neferine on adriamycin (ADM) resistant human breast cancer cell line MCF-7/ADM. Methods: The cytotoxic effect of Nef or ADM was determined by 3-[4, 5-dimethylthiazol-2.-yl], 5-diphenyl tetraxolium bromid (MTT) assay. Apoptosis and the expression of P-glycoprotein (P-gp) were detected by flow cytometry (FCM). The intracellular ADM concentration was measured by HPLC. Results: Nef at 1, 5, 10 mol/L decreased the IC50 of ADM to MCF-7/ADM from 11.63 g/mL to 4.59, 2.44, 0.27 g/mL respectively. MCF-7/ADM could resist the apoptosis induced by ADM while Nef (1-10 mol/L) could augment ADR-mediated apoptosis. Nef (10 mol/L) increased the accumulation of ADM up to 2.88 fold in MCF-7/ADM but not in sensitive cells MCF-7/S and reduced the expression of P-gp in MCF-7/ADM cells. Conclusion: Nef can circumvent multidrug resistance (MDR) of MCF-7/ADM cells and the mechanism was associated with the increase of intracellular accumulation of ADM and the reduced expression of P-gp in MCF-7/ADM cells.展开更多
Human Immunodeficiency Virus Type 1 exists in vivo as quasispecies, and one of the genome's characteristics is its diversity. During the antiretroviral therapy, drug resistance is the main obstacle to effective vi...Human Immunodeficiency Virus Type 1 exists in vivo as quasispecies, and one of the genome's characteristics is its diversity. During the antiretroviral therapy, drug resistance is the main obstacle to effective viral prevention. Understanding the molecular evolution process is fundamental to analyze the mechanism of drug resistance and develop a strategy to minimize resistance. Objective: The molecular evolution of drug resistance of one patient who had received reverse transcriptase inhibitors for a long time and had treatment which replaced Nevirapine with Indinavir was analyzed, with the aim of observing the drug resistance evolution pathway. Methods: The patient, XLF, was followed-up for six successive times. The viral populations were amplified and sequenced by single-genome amplification. All the sequences were submitted to the Stanford HIV Drug Resistance Database for the analysis of genotypic drug resistance. Results: 149 entire protease and 171 entire reverse transcriptase sequences were obtained from these samples, and all sequences were identified as subtype B. Before the patient received Indinavir, the viral population only had some polymorphisms in the protease sequences. After the patient began Indinavir treatment, the variants carrying polymorphisms declined while variants carrying the secondary mutation G73S gained the advantage. As therapy was prolonged, G73S was combined with M46I/L90M to form a resistance pattern M46I/G73S/L90M, which then became the dominant population. 97.9% of variants had the M46I/G73S/L90M pattern at XLF6. During the emergence of protease inhibitors resistance, reverse transcriptase inhibitors resistance maintained high levels. Conclusion: Indinavirresistance evolution was observed by single-genome amplification. During the course of changing the regimen to incorporate Indinavir, the G73S mutation occurred and was combined with M46I/L90M.展开更多
The magnetic reversal mechanism has been determined within a micromagnetic model reliably for a two-phased magnetic nanosystem, with the formulae for nucleation fields derived analytically. It is found that the nuclea...The magnetic reversal mechanism has been determined within a micromagnetic model reliably for a two-phased magnetic nanosystem, with the formulae for nucleation fields derived analytically. It is found that the nucleation field HN decreases uni- formly as the size of the soft phase Ls increases whereas it increases with the size of the hard phase Lh. The analysis shows that whilst the effect of Lh could be ignored in most cases, where the nucleation field is dominated by the Ls and the calculation could be significantly simplified, the overly simple inverse square law between Hu and the soft layer thickness Ls adopted by the previous researchers is not a good approximation. While nucleation is the beginning of the magnetic reversal, pinning is the dominant coercivity mechanism in both two-phased and single-phased magnetic materials, where the crystalline defects exist. Comparison with the experimental data confirms this conclusion, indicating that Brown's paradox results from the much lower effective anisotropy in both single-phased and composite materials, as speculated in the literature.展开更多
This study is devoted to investigate the inherent irreversibility and thermal stability in a reactive electrically conducting fluid flowing steadily through a channel with isothermal walls under the influence of a tra...This study is devoted to investigate the inherent irreversibility and thermal stability in a reactive electrically conducting fluid flowing steadily through a channel with isothermal walls under the influence of a transversely imposed magnetic field.Using a perturbation method coupled with a special type of Hermite-Pade' approximation technique,the simplified governing non-linear equation is solved and the important properties of overall flow structure including velocity field,temperature field and thermal criticality conditions are derived which essentially expedite to obtain expressions for volumetric entropy generation numbers,irreversibility distribution ratio and the Bejan number in the flow field.展开更多
A model of the irreversible regenerative Brayton refrigeration cycle working with paramagnetic materials is established,in which the regeneration problem in two constant-magnetic field processes and the irreversibilit...A model of the irreversible regenerative Brayton refrigeration cycle working with paramagnetic materials is established,in which the regeneration problem in two constant-magnetic field processes and the irreversibility in two adiabatic processes are considered synthetically.Expressions for the COP,cooling rate,power input,theminimum ratio of the two magnetic fields,etc.,are derived.It is found that the influence of the irreversibility and the regeneration on the main performance parameters of the magnetic Brayton refrigerator is remarkable.It is important that we have obtained several optimal criteria,which may provide some theoretical basis for the optimal design and operation of the Brayton refrigerator.The results obtained in the paper can provide some new theoretical information for the optimal design and performance improvement of real Brayton refrigerators.展开更多
A complex micelle as a hemoglobin functional model with the biaoactive function of reversible oxygen transfer has been constructed through the hierarchical assembly of the diblock copolymer poly(ethylene glycol)-blo...A complex micelle as a hemoglobin functional model with the biaoactive function of reversible oxygen transfer has been constructed through the hierarchical assembly of the diblock copolymer poly(ethylene glycol)-block- poly(4-vinylpyridine-co-N-heptyl-4-vinylpyridine) (PEG-b-P(4VP-co-4VPHep)), tetrakis(4-sulfonatophenyl)porphinato iron(II) (Fe(II)TPPS) and β-cyclodextrin (β-CD). The μ-oxo dimer of Fe(II)TPPS was successfully inhibited because the Fe(II)TPPS was included into the cavities of β-CDs through host-guest interaction. Fe(II)TPPS coordinated with pyridine groups functions as the active site to reversibly bind dioxygen. In adition, the host-guest inclusion (β-CD/Fe(II)TPPS) was encapsulated in the hydrophobic core of the complex micelle and tightly fixed by P4VP chains. The hydrophilic PEG blocks stretched in aqueous solution to constitute the shells which stabilize the structure of the complex micelle as well as endow the complex micelle with sufficient blood circulation time. Dioxygen can be bound to the Fe(II)TPPS located in the confined space and excellent reversibility of the binding-release process of dioxygen can be achieved. The quaternary amine N-heptyl-4-vinylpyridine can coerce abundant S2O4^2- ions into the core of the complex micelle to facilitate the self-reduction process. Dioxygen adducts (Fe(II)TPPS(O2)) were effectively protected by the double hydrophobic barriers constructed by the cavity of the cyclodextrin and the core of the complex micelle which enhances the ability to resist nucleophilic molecules. Therefore, the rationally designed amphiphilic structure can work as a promising artificial O2 carrier. Potentially, the complex micelle can be expected to improve the treatment of diseases linked with hypoxia.展开更多
文摘Objective: To study the reversal effect of neferine on adriamycin (ADM) resistant human breast cancer cell line MCF-7/ADM. Methods: The cytotoxic effect of Nef or ADM was determined by 3-[4, 5-dimethylthiazol-2.-yl], 5-diphenyl tetraxolium bromid (MTT) assay. Apoptosis and the expression of P-glycoprotein (P-gp) were detected by flow cytometry (FCM). The intracellular ADM concentration was measured by HPLC. Results: Nef at 1, 5, 10 mol/L decreased the IC50 of ADM to MCF-7/ADM from 11.63 g/mL to 4.59, 2.44, 0.27 g/mL respectively. MCF-7/ADM could resist the apoptosis induced by ADM while Nef (1-10 mol/L) could augment ADR-mediated apoptosis. Nef (10 mol/L) increased the accumulation of ADM up to 2.88 fold in MCF-7/ADM but not in sensitive cells MCF-7/S and reduced the expression of P-gp in MCF-7/ADM cells. Conclusion: Nef can circumvent multidrug resistance (MDR) of MCF-7/ADM cells and the mechanism was associated with the increase of intracellular accumulation of ADM and the reduced expression of P-gp in MCF-7/ADM cells.
基金National Natural Science Foundation of China (30830088 and 30800938)The National Key and Special Projects on Major Infectious Disease Grant (2008 ZX10001-004)
文摘Human Immunodeficiency Virus Type 1 exists in vivo as quasispecies, and one of the genome's characteristics is its diversity. During the antiretroviral therapy, drug resistance is the main obstacle to effective viral prevention. Understanding the molecular evolution process is fundamental to analyze the mechanism of drug resistance and develop a strategy to minimize resistance. Objective: The molecular evolution of drug resistance of one patient who had received reverse transcriptase inhibitors for a long time and had treatment which replaced Nevirapine with Indinavir was analyzed, with the aim of observing the drug resistance evolution pathway. Methods: The patient, XLF, was followed-up for six successive times. The viral populations were amplified and sequenced by single-genome amplification. All the sequences were submitted to the Stanford HIV Drug Resistance Database for the analysis of genotypic drug resistance. Results: 149 entire protease and 171 entire reverse transcriptase sequences were obtained from these samples, and all sequences were identified as subtype B. Before the patient received Indinavir, the viral population only had some polymorphisms in the protease sequences. After the patient began Indinavir treatment, the variants carrying polymorphisms declined while variants carrying the secondary mutation G73S gained the advantage. As therapy was prolonged, G73S was combined with M46I/L90M to form a resistance pattern M46I/G73S/L90M, which then became the dominant population. 97.9% of variants had the M46I/G73S/L90M pattern at XLF6. During the emergence of protease inhibitors resistance, reverse transcriptase inhibitors resistance maintained high levels. Conclusion: Indinavirresistance evolution was observed by single-genome amplification. During the course of changing the regimen to incorporate Indinavir, the G73S mutation occurred and was combined with M46I/L90M.
基金support from the National Natural Science Foundation of China (Grant Nos. 10747007 and 11074179)the Scientific Research Foundation for the Returned Overseas Chinese Scholars, the Ministry of Education
文摘The magnetic reversal mechanism has been determined within a micromagnetic model reliably for a two-phased magnetic nanosystem, with the formulae for nucleation fields derived analytically. It is found that the nucleation field HN decreases uni- formly as the size of the soft phase Ls increases whereas it increases with the size of the hard phase Lh. The analysis shows that whilst the effect of Lh could be ignored in most cases, where the nucleation field is dominated by the Ls and the calculation could be significantly simplified, the overly simple inverse square law between Hu and the soft layer thickness Ls adopted by the previous researchers is not a good approximation. While nucleation is the beginning of the magnetic reversal, pinning is the dominant coercivity mechanism in both two-phased and single-phased magnetic materials, where the crystalline defects exist. Comparison with the experimental data confirms this conclusion, indicating that Brown's paradox results from the much lower effective anisotropy in both single-phased and composite materials, as speculated in the literature.
文摘This study is devoted to investigate the inherent irreversibility and thermal stability in a reactive electrically conducting fluid flowing steadily through a channel with isothermal walls under the influence of a transversely imposed magnetic field.Using a perturbation method coupled with a special type of Hermite-Pade' approximation technique,the simplified governing non-linear equation is solved and the important properties of overall flow structure including velocity field,temperature field and thermal criticality conditions are derived which essentially expedite to obtain expressions for volumetric entropy generation numbers,irreversibility distribution ratio and the Bejan number in the flow field.
基金supported by the Program for Excellent Young Teachers of Shanghai,China (Grant No.thc-20100036)
文摘A model of the irreversible regenerative Brayton refrigeration cycle working with paramagnetic materials is established,in which the regeneration problem in two constant-magnetic field processes and the irreversibility in two adiabatic processes are considered synthetically.Expressions for the COP,cooling rate,power input,theminimum ratio of the two magnetic fields,etc.,are derived.It is found that the influence of the irreversibility and the regeneration on the main performance parameters of the magnetic Brayton refrigerator is remarkable.It is important that we have obtained several optimal criteria,which may provide some theoretical basis for the optimal design and operation of the Brayton refrigerator.The results obtained in the paper can provide some new theoretical information for the optimal design and performance improvement of real Brayton refrigerators.
文摘A complex micelle as a hemoglobin functional model with the biaoactive function of reversible oxygen transfer has been constructed through the hierarchical assembly of the diblock copolymer poly(ethylene glycol)-block- poly(4-vinylpyridine-co-N-heptyl-4-vinylpyridine) (PEG-b-P(4VP-co-4VPHep)), tetrakis(4-sulfonatophenyl)porphinato iron(II) (Fe(II)TPPS) and β-cyclodextrin (β-CD). The μ-oxo dimer of Fe(II)TPPS was successfully inhibited because the Fe(II)TPPS was included into the cavities of β-CDs through host-guest interaction. Fe(II)TPPS coordinated with pyridine groups functions as the active site to reversibly bind dioxygen. In adition, the host-guest inclusion (β-CD/Fe(II)TPPS) was encapsulated in the hydrophobic core of the complex micelle and tightly fixed by P4VP chains. The hydrophilic PEG blocks stretched in aqueous solution to constitute the shells which stabilize the structure of the complex micelle as well as endow the complex micelle with sufficient blood circulation time. Dioxygen can be bound to the Fe(II)TPPS located in the confined space and excellent reversibility of the binding-release process of dioxygen can be achieved. The quaternary amine N-heptyl-4-vinylpyridine can coerce abundant S2O4^2- ions into the core of the complex micelle to facilitate the self-reduction process. Dioxygen adducts (Fe(II)TPPS(O2)) were effectively protected by the double hydrophobic barriers constructed by the cavity of the cyclodextrin and the core of the complex micelle which enhances the ability to resist nucleophilic molecules. Therefore, the rationally designed amphiphilic structure can work as a promising artificial O2 carrier. Potentially, the complex micelle can be expected to improve the treatment of diseases linked with hypoxia.