Objectives:The eukaryotic initiation factor 4F(eIF4F)translation initiation complex inhibitors(eIF4Fi)were recently found to hyperactivate extracellular signal-regulated kinases 1/2(ERK1/2)signals,which contribute to ...Objectives:The eukaryotic initiation factor 4F(eIF4F)translation initiation complex inhibitors(eIF4Fi)were recently found to hyperactivate extracellular signal-regulated kinases 1/2(ERK1/2)signals,which contribute to acquired resistance to BRAF(B-Raf proto-oncogene,serine/threonine kinase)inhibitors in melanoma.This present study aims to elucidate how to overcome the resistance of the eIF4Fi in BRAFV600E mutant melanoma cells and explore the underlying mechanisms.Methods:Melanoma A375(vemurafenib[VEM]-sensitive)and A375R(VEM-resistant)cells were exposed to eIF4Fi RocA at varying doses and durations in vitro.We investigated the impact of RocA on the activity of ERK1/2,AKT serine/threonine kinase 1(AKT1),eIF4E,and enhancer of zeste homolog 2(EZH2).We then examined the impact of RocA on pro-apoptotic BH3-only proteins and proliferative proteins.We subsequently determined the effect of combined eIF4Fi,AKT1 inhibitor,EZH2 inhibitor or VEM on tumor growth in vitro and in vivo.Results:RocA inhibited proliferation and induced apoptosis in A375 cells,but inhibited proliferation in A375R cells.RocA rapidly reactivated ERK1/2 at 3 h and returned to baseline levels at 48 h.However,eIF4E and AKT1 activation began at 12 h and peaked at 48 h.ERK1/2 positively regulated EZH2 and EZH2-dependent expression of c-Fos and EGR1,while AKT1 negatively regulated c-Myc,c-Jun,and BMF,but positively regulated eIF4E.RocA downregulated ERK1/2(or EZH2,AKT1,and eIF4E)independent bcl-2 and Mcl-1 expression.AKT1i enhanced RocA-induced cell apoptosis,while EZH2i reduced RocA-induced cell proliferation.Combined CR-1-31-B,EZH2i,and AKT1i effectively overcame resistance to RocA and VEM resistance both in vitro and in vivo.Conclusion:The eIF4F complex inhibitor reactivates ERK1/2-EZH2 and AKT1 signaling pathways,resulting in resistance to both eIF4Fi and VEM.Combined administration of an eIF4Fi with EZH2 and AKT1 inhibitors effectively enhances sensitivity to both eIF4F complex and BRAF inhibitors.展开更多
The copolymerization process of triphenylmethyl methacrylate (TrMA) and methylmethacrylate (MMA) using chiral anionic complex initiator (-) SP-FlLi (Scheme 1) has beenstudied in toluene and THF, respectively. The copo...The copolymerization process of triphenylmethyl methacrylate (TrMA) and methylmethacrylate (MMA) using chiral anionic complex initiator (-) SP-FlLi (Scheme 1) has beenstudied in toluene and THF, respectively. The copolymer obtained in toluene possessed muchhigher specific rotation than that in THF. These copolymers have shown a tendency to a random and a like alternating structure, respectively.展开更多
CIP （complex initial permeability） spectra of PF （polycrystalline ferrite） are studied both as intrinsic and extrinsic properties. In the former case, main steps of modeling, based on effects coming from polycryst...CIP （complex initial permeability） spectra of PF （polycrystalline ferrite） are studied both as intrinsic and extrinsic properties. In the former case, main steps of modeling, based on effects coming from polycrystal grain sizes distribution and defects, are described. The obtained relations work well in practice for PF with more or less normal MS （microstructure） and no size effects. Besides, fundamental connection between parameters of CIP and MS is found. Another case--PF with possible size effects （MnZn-ferrites） are studied experimentally for different sizes of cores, unveiling the dependence of phenomena on： dimensions of cross-section, number of turns, width of nonmagnetic gap.展开更多
Based on the asymmetric characteristic of skeleton curve obtained from dynamic tests on soils,a function with double asymptotes is proposed for describing the dynamic constitutive relations of soils.The hysteresis loo...Based on the asymmetric characteristic of skeleton curve obtained from dynamic tests on soils,a function with double asymptotes is proposed for describing the dynamic constitutive relations of soils.The hysteresis loops observed during unloading and reloading show the same form as the skeleton curve and are constructed by taking the ultimate stress as the corresponding asymptote.The coeffcient of initial unloading modulus is used to ensure that the constructed hysteresis loop fts well with the experimental data.Then,a new dynamic constitutive model considering the asymmetry of skeleton curve is elaborated.The verifcation tests on saturated Nanjing fne sand are performed using a hollow cylinder apparatus to verify the applicability of the UD model.It is found that the predicted curves by the UD model agree well with the test data.展开更多
Nuclear bodies have long been noted in interphase nuclei of plant cells, but their structural component, origin and function are still unclear by now. The present work showed in onion cells the nuclear bodies appeared...Nuclear bodies have long been noted in interphase nuclei of plant cells, but their structural component, origin and function are still unclear by now. The present work showed in onion cells the nuclear bodies appeared as a spherical structure about 0.3 to 0.8 microm in diameter. They possibly were formed in nucleolus and subsequently released, and entered into nucleoplasm. Observation through cytochemical staining method at the ultrastructural level confirmed that nuclear bodies consisted of ribonucleoproteins (RNPs) and silver-stainable proteins. Immunocytochemical results revealed that nuclear bodies contained no DNA and ribosomal gene transcription factor (UBF). Based on these data, we suggested that nuclear bodies are not related to the ribosome or other gene transcription activities, instead they may act as subnuclear structures for RNPs transport from nucleolus to cytoplasm, and may also be involved in splicing of pre-mRNAs.展开更多
Polycrystalline xBa<sub>0.95</sub>Sr<sub>0.05</sub>TiO<sub>3</sub>-(1 - x)BiFe<sub>0.90</sub>Gd<sub>0.10</sub>O<sub>3</sub> ceramics were prepare...Polycrystalline xBa<sub>0.95</sub>Sr<sub>0.05</sub>TiO<sub>3</sub>-(1 - x)BiFe<sub>0.90</sub>Gd<sub>0.10</sub>O<sub>3</sub> ceramics were prepared by standard solid state reaction technique using the solid solution of BaCO<sub>3</sub>, SrCO<sub>3</sub>, TiO<sub>2</sub>, Bi<sub>2</sub>O<sub>3</sub>, Fe<sub>2</sub>O<sub>3</sub> and Gd<sub>2</sub>O<sub>3</sub>. The compound is a BiFeO<sub>3</sub> based multiferroic material which contains both magnetic and electric properties. The synthesized ceramics noticed better properties than xBaTiO<sub>3</sub>-(1 - x)BiFeO<sub>3</sub> because of adding rare earth element Gd which have higher magnetic moment than Fe. The prepared samples were sintered at 900<span style="font-size:12px;white-space:nowrap;"><span style="font-size:12px;white-space:nowrap;">˚</span></span>C, 950<span style="font-size:12px;white-space:nowrap;"><span style="font-size:12px;white-space:nowrap;">˚</span></span>C and 1000<span style="font-size:12px;white-space:nowrap;"><span style="font-size:12px;white-space:nowrap;">˚</span></span>C for 1 h. The effect of sintering temperature on density of the compound, complex initial permeability, dielectric properties and complex impedance analysis was reported in this article. Density of the ceramics was found to be enhanced with the rise in sintering temperature which implied porosity of the compound decreased when sintering temperature was increased. Enhanced complex initial permeability was noticed for the samples up to 950<span style="font-size:12px;white-space:nowrap;"><span style="font-size:12px;white-space:nowrap;">˚</span></span>C and this might be attributed to reducing the motion of domain wall when the ceramics were sintered above 950<span style="font-size:12px;white-space:nowrap;"><span style="font-size:12px;white-space:nowrap;">˚</span></span>C. Value of dielectric constant increased whereas dielectric loss decreased and these modifications might be expected because of changing density and grain size due to the variation of sintering temperature. Grain resistance (resistance due to grains) was determined from complex impedance analysis and it reduced with the rise in sintering temperature. The studied multiferroic material exhibited weak ferromagnetism but is an alternative product of environmental hazard lead (Pb) based multiferroic material and it is expected to be environment friendly.展开更多
The polycrystalline Li<em><sub>x</sub></em>Ni<sub>0.2</sub>Zn<sub>0.8-2</sub><em><sub>x</sub></em>Fe<em><sub>x</sub></em>...The polycrystalline Li<em><sub>x</sub></em>Ni<sub>0.2</sub>Zn<sub>0.8-2</sub><em><sub>x</sub></em>Fe<em><sub>x</sub></em><sub>+2</sub>O<sub>4</sub> and Li<em><sub>x</sub></em>Ni<sub>0.1</sub>Cu<sub>0.1</sub>Zn<sub>0.8-2</sub><em><sub>x</sub></em>Fe<em><sub>x</sub></em><sub>+2</sub>O<sub>4</sub> (<em>x</em> = 0.0, 0.1, 0.2, and 0.3) ferrites were synthesized by the standard solid-state reaction method. The compound was sintered at 1150<span style="font-size:12px;white-space:nowrap;">˚</span>C for 5 hours. The effect of Cu substitution and its impact on the crystal structure, microstructure, complex initial permeability and magnetization of the Ni-Zn ferrites were studied. The effect of Li<sup>+</sup> incorporation on the properties mentioned above was also investigated. X-ray diffraction patterns of the samples indicated a single cubic spinel structure for both the compound. No effect of Cu addition on crystal structure was observed. The density of the ferrites was found to be enhanced because of adding Li whereas the porosity of the samples decreased with the content of Li ions. The average value of grain size increased with the addition of Li content. The samples having Cu ions formed bigger size grains. Frequency-dependent complex initial permeability, loss tangent, and relative quality factor were studied at room temperature using an Impedance analyzer in the range of 100 Hz - 120 MHz regions. In the low-frequency region, the prepared samples exhibited a high value of permeability and after a certain frequency, the permeability falls. The value of permeability enhanced with the increase in Li whereas loss tangent was found to be reduced. The relative quality factor graphs described that the compound has excellent frequency stability up to a certain frequency which is suitable to be used in inductors, resistors, capacitors, etc. Initial permeability for Li<em><sub>x</sub></em>Ni<sub>0.1</sub>Cu<sub>0.1</sub>Zn<sub>0.8-2</sub><em><sub>x</sub></em>Fe<em><sub>x</sub></em><sub>+2</sub>O<sub>4</sub> ferrites was found high than Li<em><sub>x</sub></em>Ni<sub>0.2</sub>Zn<sub>0.8-2</sub><em><sub>x</sub></em>Fe<em><sub>x</sub></em><sub>+2</sub>O<sub>4</sub> which might be attributed to having bigger size grains of Cu containing samples because of easy movement of domain wall in bigger size grains. The values of saturation magnetization (<em>M</em><sub>s</sub>) were calculated for both compounds from M-H hysteresis loops and it enhanced with the increase in Li content which might be related to the modification of predominant exchange interactions between the cations. The Cu-containing compound exhibited higher values of saturation magnetization. The cation distribution reflects this increment because ferromagnetic Ni<sup>2+</sup> and paramagnetic Cu<sup>2+</sup> ions occupied in the B-sites and the diamagnetic Zn and paramagnetic Li occupied in the A-sites;therefore, net magnetic moments increased gradually. The studied materials might be used as an alternative to Pb-based compounds and would be environment friendly.展开更多
文摘Objectives:The eukaryotic initiation factor 4F(eIF4F)translation initiation complex inhibitors(eIF4Fi)were recently found to hyperactivate extracellular signal-regulated kinases 1/2(ERK1/2)signals,which contribute to acquired resistance to BRAF(B-Raf proto-oncogene,serine/threonine kinase)inhibitors in melanoma.This present study aims to elucidate how to overcome the resistance of the eIF4Fi in BRAFV600E mutant melanoma cells and explore the underlying mechanisms.Methods:Melanoma A375(vemurafenib[VEM]-sensitive)and A375R(VEM-resistant)cells were exposed to eIF4Fi RocA at varying doses and durations in vitro.We investigated the impact of RocA on the activity of ERK1/2,AKT serine/threonine kinase 1(AKT1),eIF4E,and enhancer of zeste homolog 2(EZH2).We then examined the impact of RocA on pro-apoptotic BH3-only proteins and proliferative proteins.We subsequently determined the effect of combined eIF4Fi,AKT1 inhibitor,EZH2 inhibitor or VEM on tumor growth in vitro and in vivo.Results:RocA inhibited proliferation and induced apoptosis in A375 cells,but inhibited proliferation in A375R cells.RocA rapidly reactivated ERK1/2 at 3 h and returned to baseline levels at 48 h.However,eIF4E and AKT1 activation began at 12 h and peaked at 48 h.ERK1/2 positively regulated EZH2 and EZH2-dependent expression of c-Fos and EGR1,while AKT1 negatively regulated c-Myc,c-Jun,and BMF,but positively regulated eIF4E.RocA downregulated ERK1/2(or EZH2,AKT1,and eIF4E)independent bcl-2 and Mcl-1 expression.AKT1i enhanced RocA-induced cell apoptosis,while EZH2i reduced RocA-induced cell proliferation.Combined CR-1-31-B,EZH2i,and AKT1i effectively overcame resistance to RocA and VEM resistance both in vitro and in vivo.Conclusion:The eIF4F complex inhibitor reactivates ERK1/2-EZH2 and AKT1 signaling pathways,resulting in resistance to both eIF4Fi and VEM.Combined administration of an eIF4Fi with EZH2 and AKT1 inhibitors effectively enhances sensitivity to both eIF4F complex and BRAF inhibitors.
文摘The copolymerization process of triphenylmethyl methacrylate (TrMA) and methylmethacrylate (MMA) using chiral anionic complex initiator (-) SP-FlLi (Scheme 1) has beenstudied in toluene and THF, respectively. The copolymer obtained in toluene possessed muchhigher specific rotation than that in THF. These copolymers have shown a tendency to a random and a like alternating structure, respectively.
文摘CIP （complex initial permeability） spectra of PF （polycrystalline ferrite） are studied both as intrinsic and extrinsic properties. In the former case, main steps of modeling, based on effects coming from polycrystal grain sizes distribution and defects, are described. The obtained relations work well in practice for PF with more or less normal MS （microstructure） and no size effects. Besides, fundamental connection between parameters of CIP and MS is found. Another case--PF with possible size effects （MnZn-ferrites） are studied experimentally for different sizes of cores, unveiling the dependence of phenomena on： dimensions of cross-section, number of turns, width of nonmagnetic gap.
基金the fnancial support by the Major Research Plan Integration Project of the National Natural Science Foundation of China under Grant No.91215301by the National Basic Research Program of China under Grant No.2011CB013601
文摘Based on the asymmetric characteristic of skeleton curve obtained from dynamic tests on soils,a function with double asymptotes is proposed for describing the dynamic constitutive relations of soils.The hysteresis loops observed during unloading and reloading show the same form as the skeleton curve and are constructed by taking the ultimate stress as the corresponding asymptote.The coeffcient of initial unloading modulus is used to ensure that the constructed hysteresis loop fts well with the experimental data.Then,a new dynamic constitutive model considering the asymmetry of skeleton curve is elaborated.The verifcation tests on saturated Nanjing fne sand are performed using a hollow cylinder apparatus to verify the applicability of the UD model.It is found that the predicted curves by the UD model agree well with the test data.
文摘Nuclear bodies have long been noted in interphase nuclei of plant cells, but their structural component, origin and function are still unclear by now. The present work showed in onion cells the nuclear bodies appeared as a spherical structure about 0.3 to 0.8 microm in diameter. They possibly were formed in nucleolus and subsequently released, and entered into nucleoplasm. Observation through cytochemical staining method at the ultrastructural level confirmed that nuclear bodies consisted of ribonucleoproteins (RNPs) and silver-stainable proteins. Immunocytochemical results revealed that nuclear bodies contained no DNA and ribosomal gene transcription factor (UBF). Based on these data, we suggested that nuclear bodies are not related to the ribosome or other gene transcription activities, instead they may act as subnuclear structures for RNPs transport from nucleolus to cytoplasm, and may also be involved in splicing of pre-mRNAs.
文摘Polycrystalline xBa<sub>0.95</sub>Sr<sub>0.05</sub>TiO<sub>3</sub>-(1 - x)BiFe<sub>0.90</sub>Gd<sub>0.10</sub>O<sub>3</sub> ceramics were prepared by standard solid state reaction technique using the solid solution of BaCO<sub>3</sub>, SrCO<sub>3</sub>, TiO<sub>2</sub>, Bi<sub>2</sub>O<sub>3</sub>, Fe<sub>2</sub>O<sub>3</sub> and Gd<sub>2</sub>O<sub>3</sub>. The compound is a BiFeO<sub>3</sub> based multiferroic material which contains both magnetic and electric properties. The synthesized ceramics noticed better properties than xBaTiO<sub>3</sub>-(1 - x)BiFeO<sub>3</sub> because of adding rare earth element Gd which have higher magnetic moment than Fe. The prepared samples were sintered at 900<span style="font-size:12px;white-space:nowrap;"><span style="font-size:12px;white-space:nowrap;">˚</span></span>C, 950<span style="font-size:12px;white-space:nowrap;"><span style="font-size:12px;white-space:nowrap;">˚</span></span>C and 1000<span style="font-size:12px;white-space:nowrap;"><span style="font-size:12px;white-space:nowrap;">˚</span></span>C for 1 h. The effect of sintering temperature on density of the compound, complex initial permeability, dielectric properties and complex impedance analysis was reported in this article. Density of the ceramics was found to be enhanced with the rise in sintering temperature which implied porosity of the compound decreased when sintering temperature was increased. Enhanced complex initial permeability was noticed for the samples up to 950<span style="font-size:12px;white-space:nowrap;"><span style="font-size:12px;white-space:nowrap;">˚</span></span>C and this might be attributed to reducing the motion of domain wall when the ceramics were sintered above 950<span style="font-size:12px;white-space:nowrap;"><span style="font-size:12px;white-space:nowrap;">˚</span></span>C. Value of dielectric constant increased whereas dielectric loss decreased and these modifications might be expected because of changing density and grain size due to the variation of sintering temperature. Grain resistance (resistance due to grains) was determined from complex impedance analysis and it reduced with the rise in sintering temperature. The studied multiferroic material exhibited weak ferromagnetism but is an alternative product of environmental hazard lead (Pb) based multiferroic material and it is expected to be environment friendly.
文摘The polycrystalline Li<em><sub>x</sub></em>Ni<sub>0.2</sub>Zn<sub>0.8-2</sub><em><sub>x</sub></em>Fe<em><sub>x</sub></em><sub>+2</sub>O<sub>4</sub> and Li<em><sub>x</sub></em>Ni<sub>0.1</sub>Cu<sub>0.1</sub>Zn<sub>0.8-2</sub><em><sub>x</sub></em>Fe<em><sub>x</sub></em><sub>+2</sub>O<sub>4</sub> (<em>x</em> = 0.0, 0.1, 0.2, and 0.3) ferrites were synthesized by the standard solid-state reaction method. The compound was sintered at 1150<span style="font-size:12px;white-space:nowrap;">˚</span>C for 5 hours. The effect of Cu substitution and its impact on the crystal structure, microstructure, complex initial permeability and magnetization of the Ni-Zn ferrites were studied. The effect of Li<sup>+</sup> incorporation on the properties mentioned above was also investigated. X-ray diffraction patterns of the samples indicated a single cubic spinel structure for both the compound. No effect of Cu addition on crystal structure was observed. The density of the ferrites was found to be enhanced because of adding Li whereas the porosity of the samples decreased with the content of Li ions. The average value of grain size increased with the addition of Li content. The samples having Cu ions formed bigger size grains. Frequency-dependent complex initial permeability, loss tangent, and relative quality factor were studied at room temperature using an Impedance analyzer in the range of 100 Hz - 120 MHz regions. In the low-frequency region, the prepared samples exhibited a high value of permeability and after a certain frequency, the permeability falls. The value of permeability enhanced with the increase in Li whereas loss tangent was found to be reduced. The relative quality factor graphs described that the compound has excellent frequency stability up to a certain frequency which is suitable to be used in inductors, resistors, capacitors, etc. Initial permeability for Li<em><sub>x</sub></em>Ni<sub>0.1</sub>Cu<sub>0.1</sub>Zn<sub>0.8-2</sub><em><sub>x</sub></em>Fe<em><sub>x</sub></em><sub>+2</sub>O<sub>4</sub> ferrites was found high than Li<em><sub>x</sub></em>Ni<sub>0.2</sub>Zn<sub>0.8-2</sub><em><sub>x</sub></em>Fe<em><sub>x</sub></em><sub>+2</sub>O<sub>4</sub> which might be attributed to having bigger size grains of Cu containing samples because of easy movement of domain wall in bigger size grains. The values of saturation magnetization (<em>M</em><sub>s</sub>) were calculated for both compounds from M-H hysteresis loops and it enhanced with the increase in Li content which might be related to the modification of predominant exchange interactions between the cations. The Cu-containing compound exhibited higher values of saturation magnetization. The cation distribution reflects this increment because ferromagnetic Ni<sup>2+</sup> and paramagnetic Cu<sup>2+</sup> ions occupied in the B-sites and the diamagnetic Zn and paramagnetic Li occupied in the A-sites;therefore, net magnetic moments increased gradually. The studied materials might be used as an alternative to Pb-based compounds and would be environment friendly.
