Objectives:Apatinib has been reported to be a promising treatment for sorafenib-resistant hepatocellular carcinoma(HCC)patients.However,the underlying mechanism remains ambiguous.The study aimed to explore the efficac...Objectives:Apatinib has been reported to be a promising treatment for sorafenib-resistant hepatocellular carcinoma(HCC)patients.However,the underlying mechanism remains ambiguous.The study aimed to explore the efficacy of apatinib in sorafenib-resistant HCC and the underlying mechanism both in vitro and in vivo.Methods:After observing epithelial-mesenchymal transformation(EMT)changes in HepG2 and HepG2/Sorafenib cells,we treated them with varying concentrations of apatinib to assess its impact on sorafenib-resistant HCC.Subsequently,specific inhibitors of c-Jun N-terminal kinase(JNK,SP600125)and extracellular signal-regulated kinase(ERK,PD98059)were introduced to investigate whether apatinib influenced sorafenib-resistant HCC via modulation of the epidermal growth factor receptor(EGFR)/JNK/ERK signaling pathway in vitro and in vivo.Biological behavior changes were assessed through cell counting kit-8(CCK-8),colony formation,transwell,and immunofluorescence tests.Simultaneously,Western blot analysis was conducted to elucidate the expression of proteins associated with EMT and the EGFR/JNK/ERK signaling pathway.Results:The HepG2/Sorafenib cells exhibited greater resistance to sorafenib compared to HepG2 cells,and sorafenib-resistant HCC was characterized by EMT changes.Apatinib demonstrated concentration-dependent inhibition of biological behaviors in HepG2/Sorafenib cells,with minimal impact on HepG2 cells.Additionally,apatinib had a pronounced effect on the expression of EMT-related proteins in sorafenib-resistant cells similar to that in sorafenib-sensitive cells.Furthermore,there was a dose-dependent reduction in the expression of proteins associated with the EGFR/JNK/ERK pathway in apatinib-treated groups.Notably,SP600125 and PD98059 contributed to the inhibition of EMT and EGFR/JNK/ERK pathway-related proteins by apatinib in sorafenib-resistant HCC.Conclusion:Apatinib potentially hindered the progression of sorafenib-resistant HCC by suppressing both EMT and the EGFR/JNK/ERK pathway.展开更多
Sex-specific neurons play pivotal roles in regulating sexually dimorphic behaviors.In insects,the sex determination gene doublesex(dsx)establishes major sexual dimorphism of the nervous system,in which male-specific d...Sex-specific neurons play pivotal roles in regulating sexually dimorphic behaviors.In insects,the sex determination gene doublesex(dsx)establishes major sexual dimorphism of the nervous system,in which male-specific dsx^(M)promotes neuronal development,while female-specific dsx^(F)inhibits neuronal development by promoting neuronal apoptosis.In this study,we find that dsx regulates the number of dsx-expressing central neurons in Drosophila in cell-specific manners.Although dsx^(M)overall promotes an increase in the number of dsx neurons,it inhibits the emergence of specific pC1 neurons.dsx^(F)reduces the number of different pC1/pC2 subtypes,but promotes the formation of pC1d.We also find that dsx^(M)and dsx^(F)barely affect the number of some pC2 neurons.Changes in the number of pC1/pC2 neurons alter their roles in regulating different behaviors,including courtship,aggression,and locomotion.Our results illustrate the multifaceted functions of dsx in sexually dimorphic neuronal development and behaviors.展开更多
To address the early separation problem in the Menter Shear-Stress Transport(SST)turbulence model,a correction for the Turbulent Kinetic Energy(TKE)production term,P_(k),is introduced to account for the effect of the ...To address the early separation problem in the Menter Shear-Stress Transport(SST)turbulence model,a correction for the Turbulent Kinetic Energy(TKE)production term,P_(k),is introduced to account for the effect of the Adverse Pressure Gradient(APG).The correction is determined based on the distribution of Pkin the APG region before separation.When the friction coefficient C_(f) is decomposed,its direct dependence on Pkis clearly observed.However,with the introduction of Bradshaw’s assumption,Pkin the SST turbulence model is over-suppressed,resulting in a lower inner peak or no significant inner peak distribution at all.To address this problem,this paper proposes a Gaussian function,HGauss,which corrects the numerical values of P_(k) involved in the calculation of the Menter SST model by focusing on the inner peak region of P_(k).The modified SST model is then applied to four cases with APGs.The modification leads to an increase in the wall friction coefficient C_(f)in the APG region and causes a downstream shift in the separation location,improving the model’s consistency with high-accuracy data and experimental results.It is demonstrated that this correction can improve the early separation problem in the Menter SST turbulence model.展开更多
Metal phosphides have shown great application potential as anode for sodium-ion batteries(NIBs)owing to high theoretical capacity,suitable operation voltage and abundant resource.Unfortunately,the application of NiP_(...Metal phosphides have shown great application potential as anode for sodium-ion batteries(NIBs)owing to high theoretical capacity,suitable operation voltage and abundant resource.Unfortunately,the application of NiP_(2) anode is severely impeded by low practical capacity and fast capacity decay due to the huge volume variation and low reactivity of internal phosphorus(P)component towards Na^(+).Herein,electronic structure modulation of NiP_(2) via heteroatoms doping and introducing vacancies defects to enhance Na+adsorption sites and diffusion kinetics is successfully attempted.The as-synthesized three-dimensional(3D)bicontinuous carbon matrix decorated with well-dispersed fluorine(F)-doped NiP_(2) nanoparticles(F-NiP_(2)@carbon nanosheets)delivers a high reversible capacity(585 mAh·g^(−1) at 0.1 A·g^(−1))and excellent long cycling stability(244 mAh·g^(−1) over 1,000 cycles at 2 A·g^(−1))when tested as anode in NIBs.Density functional theory(DFT)calculations reveal that F doping in NiP_(2) induces the formation of P vacancies with increased Na+adsorption energy and accelerates the alloying of internal P component.The F-NiP_(2)@carbon nanosheets//Na_(3)V_(2)(PO_(4))_(3) full cell is evaluated showing stable long cycling life.The heteroatoms doping-induced dual defects strategy opens up a new way of metal phosphides for sodium storage.展开更多
Sodium-ion battery(SIB),one of most promising battery technologies,offers an alternative low-cost solution for scalable energy storage.Developing advanced electrode materials with superior electrochemical performance ...Sodium-ion battery(SIB),one of most promising battery technologies,offers an alternative low-cost solution for scalable energy storage.Developing advanced electrode materials with superior electrochemical performance is of great significance for SIBs.Transition metal sulfides that emerge as promising anode materials have advantageous features particularly for electrochemical redox reaction,including high theoretical capacity,good cycling stability,easily-controlled structure and modifiable chemical composition.In this review,recent progress of transition metal sulfides based materials for SIBs is summarized by discussing the materials properties,advanced design strategies,electrochemical reaction mechanism and their applications in sodium-ion full batteries.Moreover,we propose several promising strategies to overcome the challenges of transition metal sulfides for SIBs,paving the way to explore and construct advanced electrode materials for SIBs and other energy storage devices.展开更多
基金supported by Natural Science Foundation of Shandong Province,No.ZR2021QH186National Natural Science Foundation of China,No.81870205+3 种基金Foundation Research Project of Qinghai Province,2021-ZJ-719National Natural Science Foundation of China,No.82000579Qinghai Provincial Health System Key Project No.2021-wjzd-06Foundation Research Project of Qinghai Province,2023-ZJ-786.
文摘Objectives:Apatinib has been reported to be a promising treatment for sorafenib-resistant hepatocellular carcinoma(HCC)patients.However,the underlying mechanism remains ambiguous.The study aimed to explore the efficacy of apatinib in sorafenib-resistant HCC and the underlying mechanism both in vitro and in vivo.Methods:After observing epithelial-mesenchymal transformation(EMT)changes in HepG2 and HepG2/Sorafenib cells,we treated them with varying concentrations of apatinib to assess its impact on sorafenib-resistant HCC.Subsequently,specific inhibitors of c-Jun N-terminal kinase(JNK,SP600125)and extracellular signal-regulated kinase(ERK,PD98059)were introduced to investigate whether apatinib influenced sorafenib-resistant HCC via modulation of the epidermal growth factor receptor(EGFR)/JNK/ERK signaling pathway in vitro and in vivo.Biological behavior changes were assessed through cell counting kit-8(CCK-8),colony formation,transwell,and immunofluorescence tests.Simultaneously,Western blot analysis was conducted to elucidate the expression of proteins associated with EMT and the EGFR/JNK/ERK signaling pathway.Results:The HepG2/Sorafenib cells exhibited greater resistance to sorafenib compared to HepG2 cells,and sorafenib-resistant HCC was characterized by EMT changes.Apatinib demonstrated concentration-dependent inhibition of biological behaviors in HepG2/Sorafenib cells,with minimal impact on HepG2 cells.Additionally,apatinib had a pronounced effect on the expression of EMT-related proteins in sorafenib-resistant cells similar to that in sorafenib-sensitive cells.Furthermore,there was a dose-dependent reduction in the expression of proteins associated with the EGFR/JNK/ERK pathway in apatinib-treated groups.Notably,SP600125 and PD98059 contributed to the inhibition of EMT and EGFR/JNK/ERK pathway-related proteins by apatinib in sorafenib-resistant HCC.Conclusion:Apatinib potentially hindered the progression of sorafenib-resistant HCC by suppressing both EMT and the EGFR/JNK/ERK pathway.
基金supported by the National Key R&D Program of China(2021YFA1101300)the National Natural Science Foundation of China(32371067 to Y.P.)+1 种基金the Natural Science Foundation from Jiangsu Province(BK20231418 to Q.P.)the Fundamental Research Funds for the Central Universities(2242023R40054 to Q.P.).
文摘Sex-specific neurons play pivotal roles in regulating sexually dimorphic behaviors.In insects,the sex determination gene doublesex(dsx)establishes major sexual dimorphism of the nervous system,in which male-specific dsx^(M)promotes neuronal development,while female-specific dsx^(F)inhibits neuronal development by promoting neuronal apoptosis.In this study,we find that dsx regulates the number of dsx-expressing central neurons in Drosophila in cell-specific manners.Although dsx^(M)overall promotes an increase in the number of dsx neurons,it inhibits the emergence of specific pC1 neurons.dsx^(F)reduces the number of different pC1/pC2 subtypes,but promotes the formation of pC1d.We also find that dsx^(M)and dsx^(F)barely affect the number of some pC2 neurons.Changes in the number of pC1/pC2 neurons alter their roles in regulating different behaviors,including courtship,aggression,and locomotion.Our results illustrate the multifaceted functions of dsx in sexually dimorphic neuronal development and behaviors.
基金supported by the National Natural Science Foundation of China(No.92252201)。
文摘To address the early separation problem in the Menter Shear-Stress Transport(SST)turbulence model,a correction for the Turbulent Kinetic Energy(TKE)production term,P_(k),is introduced to account for the effect of the Adverse Pressure Gradient(APG).The correction is determined based on the distribution of Pkin the APG region before separation.When the friction coefficient C_(f) is decomposed,its direct dependence on Pkis clearly observed.However,with the introduction of Bradshaw’s assumption,Pkin the SST turbulence model is over-suppressed,resulting in a lower inner peak or no significant inner peak distribution at all.To address this problem,this paper proposes a Gaussian function,HGauss,which corrects the numerical values of P_(k) involved in the calculation of the Menter SST model by focusing on the inner peak region of P_(k).The modified SST model is then applied to four cases with APGs.The modification leads to an increase in the wall friction coefficient C_(f)in the APG region and causes a downstream shift in the separation location,improving the model’s consistency with high-accuracy data and experimental results.It is demonstrated that this correction can improve the early separation problem in the Menter SST turbulence model.
基金the National Natural Science Foundation of China(Nos.22005201 and 22005292)the Natural Science Foundation of Guangdong(No.2020A1515010840)Shenzhen Government’s Plan of Science and Technology(Nos.JCYJ20200109105803806 and RCYX20200714114535052).
文摘Metal phosphides have shown great application potential as anode for sodium-ion batteries(NIBs)owing to high theoretical capacity,suitable operation voltage and abundant resource.Unfortunately,the application of NiP_(2) anode is severely impeded by low practical capacity and fast capacity decay due to the huge volume variation and low reactivity of internal phosphorus(P)component towards Na^(+).Herein,electronic structure modulation of NiP_(2) via heteroatoms doping and introducing vacancies defects to enhance Na+adsorption sites and diffusion kinetics is successfully attempted.The as-synthesized three-dimensional(3D)bicontinuous carbon matrix decorated with well-dispersed fluorine(F)-doped NiP_(2) nanoparticles(F-NiP_(2)@carbon nanosheets)delivers a high reversible capacity(585 mAh·g^(−1) at 0.1 A·g^(−1))and excellent long cycling stability(244 mAh·g^(−1) over 1,000 cycles at 2 A·g^(−1))when tested as anode in NIBs.Density functional theory(DFT)calculations reveal that F doping in NiP_(2) induces the formation of P vacancies with increased Na+adsorption energy and accelerates the alloying of internal P component.The F-NiP_(2)@carbon nanosheets//Na_(3)V_(2)(PO_(4))_(3) full cell is evaluated showing stable long cycling life.The heteroatoms doping-induced dual defects strategy opens up a new way of metal phosphides for sodium storage.
基金supported by the National Key R&D Research Program of China(No.2018YFB0905400,2017YFA0206301)the National Natural Science Foundation of China(Nos.51925207,U1910210,21605136,and 51872277)+1 种基金Dalian National Laboratory For Clean Energy(DNL)Cooperation Fund,the CAS(DNL 180310)the Fundamental Research Funds for the Central Universities(WK2060140026,WK2060000009).
文摘Sodium-ion battery(SIB),one of most promising battery technologies,offers an alternative low-cost solution for scalable energy storage.Developing advanced electrode materials with superior electrochemical performance is of great significance for SIBs.Transition metal sulfides that emerge as promising anode materials have advantageous features particularly for electrochemical redox reaction,including high theoretical capacity,good cycling stability,easily-controlled structure and modifiable chemical composition.In this review,recent progress of transition metal sulfides based materials for SIBs is summarized by discussing the materials properties,advanced design strategies,electrochemical reaction mechanism and their applications in sodium-ion full batteries.Moreover,we propose several promising strategies to overcome the challenges of transition metal sulfides for SIBs,paving the way to explore and construct advanced electrode materials for SIBs and other energy storage devices.
