Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is...Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is typically accompanied by a poor prognosis.Exploring the synergistic potential of combining multiple chemotherapeutic agents may represent a promising avenue for optimizing treatment efficacy.Methods:This study investigated whether 3-Methyladenine(3-MA)could potentiated the effect of PTX and its potential molecular mechanism.Samples were divided into the following categories:Negative control(NC)with the solvent dimethyl sulfoxide(DMSO,0.5%v/v),PTX(400 nM),3-MA(4 mM),and PTX(400 nM)+3-MA(4 mM).The viability of NPC cells was assessed using both the cell counting kit-8(CCK-8)assay and the colony formation assay.Microscopic observation was performed to identify morphological cell changes.Flow cytometry was used to assess cell cycle status,mitochondrial membrane potential(MMP),and apoptotic cells.Western blotting was conducted to quantify the protein expression.Results:3-MA enhanced PTX-specific inhibition of NPC cell proliferation.PTX,either alone or in combination with 3-MA,caused cell cycle halt at the G2/M phase in the majority of NPC cells,and the combination treatment of PTX with 3-MA induced a higher rate of NPC cell death compared to PTX alone.Western blotting results revealed the combination of PTX with 3-MA heightened activation of cyclin-dependent kinase 1(CDK1),a key molecule in shifting cells from mitotic arrest to apoptosis,led to a reduction in Myeloid Cell Leukemia 1(MCL-1)expression and an increase in Poly(ADP-ribose)polymerase(PARP)cleavage.Conclusion:The concurrent administration of PTX with 3-MA effectively enhances PTX’s inhibitory impact on NPC and activates the apoptosis signal regulated by CDK1.展开更多
Background:Paclitaxel is a compound derived from Pacific yew bark that induces various cancer cell apoptosis.However,whether it also has anticancer activities in KOSC3 cells,an oral cancer cell line,is unclear.Methods:...Background:Paclitaxel is a compound derived from Pacific yew bark that induces various cancer cell apoptosis.However,whether it also has anticancer activities in KOSC3 cells,an oral cancer cell line,is unclear.Methods:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,flow cytometry,and western blotting assays were carried out to assess cell viability,subG1 phase of the cell cycle,and apoptosis-related protein expression,respectively.Results:Ourfindings indicate that paclitaxel could inhibit cell viability and increase the expression of apoptotic markers,including plasma membrane blebbing and the cleavage of poly ADP-ribose polymerase in KOSC3 cells.Also,the treatment with paclitaxel remarkably elevated the percentage of the subG1 phase in KOSC3 cells.In addition,treatment with a pan-caspase inhibitor could recover paclitaxel-inhibited cell viability.Moreover,caspase-8,caspase-9,caspase-7,and BH3 interacting domain death agonist(Bid)were activated in paclitaxel-treated KOSC3 cells.Conclusions:Paclitaxel induced apoptosis through caspase cascade in KOSC3 cells.展开更多
BACKGROUND The advanced first-line regimen for advanced gastric cancer is based on a combination of fluoropyrimidine and platinum and/or paclitaxel(PTX),forming a two-or three-drug regimen.Compared to conventional PTX...BACKGROUND The advanced first-line regimen for advanced gastric cancer is based on a combination of fluoropyrimidine and platinum and/or paclitaxel(PTX),forming a two-or three-drug regimen.Compared to conventional PTX,nanoparticle albumin-bound PTX(Nab-PTX)has better therapeutic effects and fewer adverse effects reported in studies.Nab-PTX is a great option for patients presenting with advanced gastric cancer.Herein,we highlight an adverse event(hemorrhagic cystitis)of Nab-PTX in advanced gastric cancer.CASE SUMMARY A 55-year-old male was diagnosed with lymph node metastasis after a laparo-scopic-assisted radical gastrectomy for gastric cancer that was treated by Nab-PTX and S-1(AS).On the 15th day after treatment with AS,he was diagnosed with hemorrhagic cystitis.CONCLUSION Physicians should be aware that hemorrhagic cystitis is a potential adverse event associated with Nab-PTX treatment.展开更多
Aluminum alloys are the potential materials in the automobile and aerospace sectors due to their lower density,easy forming and excellent corrosion resistance.The demand of high strength-to-weight ratio materials in s...Aluminum alloys are the potential materials in the automobile and aerospace sectors due to their lower density,easy forming and excellent corrosion resistance.The demand of high strength-to-weight ratio materials in structural applications needs the engineering industries to seek aluminum alloy with new versions of hard and brittle ceramic particles.The microstructure,hardness,wear and corrosion behaviors of AA7075 composites with 2.5wt.%and 5wt.%TiC particles were studied.Microscopic analysis is evident that the transformation of the strong dendritic morphology to non-dendritic morphology on the incorporation of TiC into AA7075.Furthermore,the precipitation of the second-phase compounds such as Al_(2)CuMg,Al_(2)Cu andFe-rich Al_6(Cu,Fe)/Al_(7)Cu_(2)Fe)is promoted by TiC particles at inter-and intra-dendritic regions.Accordingly,the hardness of composites is improved by grain boundary strengthening and particulate strengthening mechanisms.Both coefficient of friction and wear rate have an inverse relation with TiC concentration.The base alloy without TiC shows adhesive-type wear-induced deformation due to the formation of an oxide film,while composite samples exhibit a mechanically mixed layer and abrasive-type wear behavior.Composite samples shows a higher corrosion rate due to the presence of numerous precipitates which promote pitting corrosion.展开更多
Considering their affordability and high strength-to-weight ratio,lightweight aluminium alloys are the subject of intensive research aimed at improving their properties for use in the aerospace industry.This research ...Considering their affordability and high strength-to-weight ratio,lightweight aluminium alloys are the subject of intensive research aimed at improving their properties for use in the aerospace industry.This research effort aims to develop novel hybrid composites based on AA 2014 alloy through the use of liquid metallurgy stir casting to reinforce dual ceramic particles of Zirconium Diboride(ZrB_(2))and Boron Carbide(B4C).The weight percentage(wt%)of ZrB_(2) was varied(0,5,10,and 15),while a constant 5 wt%of B4C was maintained during this fabrication.The as-cast samples have been assessed using an Optical Microscope(OM)and a Scanning Electron Microscope(SEM)with Energy Dispersive Spectroscopy(EDS).The properties such as hardness,tensile strength,and wear characteristics of stir cast specimens were assessed to examine the impact of varying weight percentages of reinforcements in AA 2014 alloy.In particular,dry sliding wear behaviour was evaluated considering varied loads using a pin-on-disc tribotester.As the weight%of ZrB_(2) grew and B4C was incorporated,hybrid composites showed higher hardness,tensile strength,and wear resistance.Notably,the incorporation of a cumulative reinforcement consisting of 15 wt%ZrB_(2) and 5 wt%B4C resulted in a significant 31.86%increase in hardness and a 44.1%increase in tensile strength compared to AA 2014 alloy.In addition,it has been detected that wear resistance of hybrid composite pin(containing 20 wt%cumulative reinforcement)is higher than that of other stir cast wear test pins during the whole range of applied loads.Fractured surfaces of tensile specimens showed ductile fracture in the AA 2014 matrix and mixed mode for hybrid composites.Worn surfaces obtained employing higher applied load indicated abrasive wear with little plastic deformation for hybrid composites and dominant adhesive wear for matrix alloy.Hence,the superior mechanical and tribological performance of hybrid composites can be attributed to dual reinforcement particles being dispersed well and the effective transmission of load at this specific composition.展开更多
The AA5052 aluminum alloy is widely used in automobile and aerospace manufacturing,and with the development of light-weight alloys,it is required that these materials exhibit better mechanical properties.Previous stud...The AA5052 aluminum alloy is widely used in automobile and aerospace manufacturing,and with the development of light-weight alloys,it is required that these materials exhibit better mechanical properties.Previous studies have demonstrated that the addition of Sc to aluminum alloys can improve both the microstructure and properties of the alloys.In this study,the effect of Sc on the Fe-rich phase and properties of the AA5052 aluminum alloy was studied by adding 0%,0.05%,0.2%,and 0.3%Sc.The results show that with the increase of Sc,the coarse needle-like Fe-rich phase gradually transforms into Chinese-script and then nearly spherical particles,reduce the size of Fe-rich phase,and refine the grain with increase of high angle grain boundaries(HAGBs).These microstructure changes enhance the strength of the AA5052 alloy through Sc addition.The ductility of the alloy is obviously improved because the addition of a lower amount of Sc changes the morphology of Fe-rich phase from needle-like into a Chinese-script,and it is subsequently reduced as a result of significant increase in HAGBs with increasing Sc content.展开更多
TA1 P-Ti/AA6061 composite plate was produced by oxidizing the surface of the titanium plate and adopting a cold roll bonding process.The results revealed that the oxide film(Ti6O)prepared on the surface of TA1 pure ti...TA1 P-Ti/AA6061 composite plate was produced by oxidizing the surface of the titanium plate and adopting a cold roll bonding process.The results revealed that the oxide film(Ti6O)prepared on the surface of TA1 pure titanium was easy to crack during the cold roll bonding,thereby promoting the formation of an effective mechanical interlock at the interface,which can effectively reduce the minimum reduction rate of the composite plates produced by cold rolling of titanium and aluminium plates.Moreover,the composite plate subjected to oxidation treatment exhibited high shear strength,particularly at a 43%reduction rate,achieving a commendable value of 117 MPa.Based on oxidation treatment and different reduction rates,the annealed composite plates at temperatures of 400,450,and 500°C displayed favorable resistance to interface delamination,highlighting their remarkable strength-plasticity compatibility as evidenced by a maximum elongation of 31.845%.展开更多
基金supported by the Science and Technology Innovation Program of Hunan Province(Grant Numbers:2021SK1014 and 2022WZ1027)the Colleges and Universities of Hunan Province(Grant Number:HNJG 20200440)+1 种基金the Scientific Research Fund of Hunan Provincial Education Department(Grant Number:21B0411)the Scientific Research Project of Changsha Central Hospital(Number:YNKY202201).
文摘Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is typically accompanied by a poor prognosis.Exploring the synergistic potential of combining multiple chemotherapeutic agents may represent a promising avenue for optimizing treatment efficacy.Methods:This study investigated whether 3-Methyladenine(3-MA)could potentiated the effect of PTX and its potential molecular mechanism.Samples were divided into the following categories:Negative control(NC)with the solvent dimethyl sulfoxide(DMSO,0.5%v/v),PTX(400 nM),3-MA(4 mM),and PTX(400 nM)+3-MA(4 mM).The viability of NPC cells was assessed using both the cell counting kit-8(CCK-8)assay and the colony formation assay.Microscopic observation was performed to identify morphological cell changes.Flow cytometry was used to assess cell cycle status,mitochondrial membrane potential(MMP),and apoptotic cells.Western blotting was conducted to quantify the protein expression.Results:3-MA enhanced PTX-specific inhibition of NPC cell proliferation.PTX,either alone or in combination with 3-MA,caused cell cycle halt at the G2/M phase in the majority of NPC cells,and the combination treatment of PTX with 3-MA induced a higher rate of NPC cell death compared to PTX alone.Western blotting results revealed the combination of PTX with 3-MA heightened activation of cyclin-dependent kinase 1(CDK1),a key molecule in shifting cells from mitotic arrest to apoptosis,led to a reduction in Myeloid Cell Leukemia 1(MCL-1)expression and an increase in Poly(ADP-ribose)polymerase(PARP)cleavage.Conclusion:The concurrent administration of PTX with 3-MA effectively enhances PTX’s inhibitory impact on NPC and activates the apoptosis signal regulated by CDK1.
基金The present study was supported by the National Science and Technology Council,Taiwan(MOST-107-2320-B-471-001 to YYL and MOST-110-2320-B-006-025-MY3 to BMH)by An Nan Hospital(ANHRF111-55 to TCC and BMH).
文摘Background:Paclitaxel is a compound derived from Pacific yew bark that induces various cancer cell apoptosis.However,whether it also has anticancer activities in KOSC3 cells,an oral cancer cell line,is unclear.Methods:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,flow cytometry,and western blotting assays were carried out to assess cell viability,subG1 phase of the cell cycle,and apoptosis-related protein expression,respectively.Results:Ourfindings indicate that paclitaxel could inhibit cell viability and increase the expression of apoptotic markers,including plasma membrane blebbing and the cleavage of poly ADP-ribose polymerase in KOSC3 cells.Also,the treatment with paclitaxel remarkably elevated the percentage of the subG1 phase in KOSC3 cells.In addition,treatment with a pan-caspase inhibitor could recover paclitaxel-inhibited cell viability.Moreover,caspase-8,caspase-9,caspase-7,and BH3 interacting domain death agonist(Bid)were activated in paclitaxel-treated KOSC3 cells.Conclusions:Paclitaxel induced apoptosis through caspase cascade in KOSC3 cells.
文摘BACKGROUND The advanced first-line regimen for advanced gastric cancer is based on a combination of fluoropyrimidine and platinum and/or paclitaxel(PTX),forming a two-or three-drug regimen.Compared to conventional PTX,nanoparticle albumin-bound PTX(Nab-PTX)has better therapeutic effects and fewer adverse effects reported in studies.Nab-PTX is a great option for patients presenting with advanced gastric cancer.Herein,we highlight an adverse event(hemorrhagic cystitis)of Nab-PTX in advanced gastric cancer.CASE SUMMARY A 55-year-old male was diagnosed with lymph node metastasis after a laparo-scopic-assisted radical gastrectomy for gastric cancer that was treated by Nab-PTX and S-1(AS).On the 15th day after treatment with AS,he was diagnosed with hemorrhagic cystitis.CONCLUSION Physicians should be aware that hemorrhagic cystitis is a potential adverse event associated with Nab-PTX treatment.
文摘Aluminum alloys are the potential materials in the automobile and aerospace sectors due to their lower density,easy forming and excellent corrosion resistance.The demand of high strength-to-weight ratio materials in structural applications needs the engineering industries to seek aluminum alloy with new versions of hard and brittle ceramic particles.The microstructure,hardness,wear and corrosion behaviors of AA7075 composites with 2.5wt.%and 5wt.%TiC particles were studied.Microscopic analysis is evident that the transformation of the strong dendritic morphology to non-dendritic morphology on the incorporation of TiC into AA7075.Furthermore,the precipitation of the second-phase compounds such as Al_(2)CuMg,Al_(2)Cu andFe-rich Al_6(Cu,Fe)/Al_(7)Cu_(2)Fe)is promoted by TiC particles at inter-and intra-dendritic regions.Accordingly,the hardness of composites is improved by grain boundary strengthening and particulate strengthening mechanisms.Both coefficient of friction and wear rate have an inverse relation with TiC concentration.The base alloy without TiC shows adhesive-type wear-induced deformation due to the formation of an oxide film,while composite samples exhibit a mechanically mixed layer and abrasive-type wear behavior.Composite samples shows a higher corrosion rate due to the presence of numerous precipitates which promote pitting corrosion.
文摘Considering their affordability and high strength-to-weight ratio,lightweight aluminium alloys are the subject of intensive research aimed at improving their properties for use in the aerospace industry.This research effort aims to develop novel hybrid composites based on AA 2014 alloy through the use of liquid metallurgy stir casting to reinforce dual ceramic particles of Zirconium Diboride(ZrB_(2))and Boron Carbide(B4C).The weight percentage(wt%)of ZrB_(2) was varied(0,5,10,and 15),while a constant 5 wt%of B4C was maintained during this fabrication.The as-cast samples have been assessed using an Optical Microscope(OM)and a Scanning Electron Microscope(SEM)with Energy Dispersive Spectroscopy(EDS).The properties such as hardness,tensile strength,and wear characteristics of stir cast specimens were assessed to examine the impact of varying weight percentages of reinforcements in AA 2014 alloy.In particular,dry sliding wear behaviour was evaluated considering varied loads using a pin-on-disc tribotester.As the weight%of ZrB_(2) grew and B4C was incorporated,hybrid composites showed higher hardness,tensile strength,and wear resistance.Notably,the incorporation of a cumulative reinforcement consisting of 15 wt%ZrB_(2) and 5 wt%B4C resulted in a significant 31.86%increase in hardness and a 44.1%increase in tensile strength compared to AA 2014 alloy.In addition,it has been detected that wear resistance of hybrid composite pin(containing 20 wt%cumulative reinforcement)is higher than that of other stir cast wear test pins during the whole range of applied loads.Fractured surfaces of tensile specimens showed ductile fracture in the AA 2014 matrix and mixed mode for hybrid composites.Worn surfaces obtained employing higher applied load indicated abrasive wear with little plastic deformation for hybrid composites and dominant adhesive wear for matrix alloy.Hence,the superior mechanical and tribological performance of hybrid composites can be attributed to dual reinforcement particles being dispersed well and the effective transmission of load at this specific composition.
基金supported by the Key Research&Development Program of Yunnan Province(Grant numbers 202103AA080017,202203AE140011).
文摘The AA5052 aluminum alloy is widely used in automobile and aerospace manufacturing,and with the development of light-weight alloys,it is required that these materials exhibit better mechanical properties.Previous studies have demonstrated that the addition of Sc to aluminum alloys can improve both the microstructure and properties of the alloys.In this study,the effect of Sc on the Fe-rich phase and properties of the AA5052 aluminum alloy was studied by adding 0%,0.05%,0.2%,and 0.3%Sc.The results show that with the increase of Sc,the coarse needle-like Fe-rich phase gradually transforms into Chinese-script and then nearly spherical particles,reduce the size of Fe-rich phase,and refine the grain with increase of high angle grain boundaries(HAGBs).These microstructure changes enhance the strength of the AA5052 alloy through Sc addition.The ductility of the alloy is obviously improved because the addition of a lower amount of Sc changes the morphology of Fe-rich phase from needle-like into a Chinese-script,and it is subsequently reduced as a result of significant increase in HAGBs with increasing Sc content.
基金supports from the National Natural Science Foundation of China(Nos.52075472,52004242)the National Key Research and Development Program of China(No.2018YFA0707300)the Natural Science Foundation of Hebei Province,China(No.E2020203001)。
文摘TA1 P-Ti/AA6061 composite plate was produced by oxidizing the surface of the titanium plate and adopting a cold roll bonding process.The results revealed that the oxide film(Ti6O)prepared on the surface of TA1 pure titanium was easy to crack during the cold roll bonding,thereby promoting the formation of an effective mechanical interlock at the interface,which can effectively reduce the minimum reduction rate of the composite plates produced by cold rolling of titanium and aluminium plates.Moreover,the composite plate subjected to oxidation treatment exhibited high shear strength,particularly at a 43%reduction rate,achieving a commendable value of 117 MPa.Based on oxidation treatment and different reduction rates,the annealed composite plates at temperatures of 400,450,and 500°C displayed favorable resistance to interface delamination,highlighting their remarkable strength-plasticity compatibility as evidenced by a maximum elongation of 31.845%.
