A novel Zn-based metal–organic framework Zn(dobdc)(datz)[Zn_(2)(H2dobdc)(datz)2$1.5DMF]with plentiful hydrogen bond donors(HBD)groups was facilely synthesized from mixed ligands.The dual activation of metal Zn sites ...A novel Zn-based metal–organic framework Zn(dobdc)(datz)[Zn_(2)(H2dobdc)(datz)2$1.5DMF]with plentiful hydrogen bond donors(HBD)groups was facilely synthesized from mixed ligands.The dual activation of metal Zn sites and HBD groups for epoxides by forming Zn–O adduct and hydrogen bonds facilitated the ring-opening of epoxide substrate,which is critical for the subsequent CO_(2) fixation.Also,the existence of micropores and N-rich units in Zn(dobdc)(datz)afforded affinity towards CO_(2),which is beneficial to further improvement on catalytic CO_(2) conversion performance.Satisfactorily,Zn(dobdc)(datz)/Bu4NBr system was proved efficient heterogeneous catalyst for the CO_(2) cycloaddition with epoxides,and 98%propylene carbonate yield was obtained under mild conditions(80C,1.5 MPa and solvent-free).In addition,Zn(dobdc)(datz)/Bu4NBr exhibited remarkable versatility to different epoxides and could be completely recycled over six runs with high catalytic activity.The highly stable,easily recycle and solvent-free Zn-based MOF reported here displays eco-friendly and efficient performance to CO_(2)conversion.展开更多
Background:The Warburg effect is considered as a hallmark of various types of cancers,while the regulatory mechanism is poorly understood.Our previous study demonstrated that miR-194-5p directly targets and regulates ...Background:The Warburg effect is considered as a hallmark of various types of cancers,while the regulatory mechanism is poorly understood.Our previous study demonstrated that miR-194-5p directly targets and regulates insulin-like growth factor1 receptor(IGF1R).In this study,we aimed to investigate the role of miR-194-5p in the regulation of the Warburg effect in ovarian cancer cells.Methods:The stable ovarian cell lines with miR-194-5p overexpression or silencing IGF1R expression were established by lentivirus infection.ATP generation,glucose uptake,lactate production and extracellular acidification rate(ECAR)assay were used to analyze the effects of aerobic glycolysis in ovarian cancer cells.Gene expression was analyzed by quantitative polymerase chain reaction(qPCR)and western blot.Immunohistochemistry assays were performed to assess the expression of the IGF1R protein in ovarian cancer tissues.Results:Overexpression of miR-194-5p or silencing IGF1R expression in ovarian cancer cells decreases ATP generation,glucose uptake,lactate production,and ECAR and inhibits both the mRNA and protein expression of PKM2,LDHA,GLUT1,and GLUT3.While the knockdown of miR-194-5p expression led to opposite results.Overexpression of miR-194-5p or silencing IGF1R expression suppressed the phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)pathway,whose activation can sustain aerobic glycolysis in cancer cells,and the knockdown of miR-194-5p expression promoted the activation of the PI3K/AKT pathway.Conclusion:Our results suggest that miR-194-5p can inhibit the Warburg effect by negative regulation of IGF1R and further repression of the PI3K/AKT pathway,which provides a theoretical basis for further test of miR-194-5p as a target in the treatment of ovarian cancer.展开更多
Photoreforming hydrogen evolution(Pr-HE)of a water-pollutant system could simultaneously achieve efficient hydrogen production and pollutant degradation.It provides a new way to solve energy and environmental issues,b...Photoreforming hydrogen evolution(Pr-HE)of a water-pollutant system could simultaneously achieve efficient hydrogen production and pollutant degradation.It provides a new way to solve energy and environmental issues,but the poor internal charge separation still limits its performance.This work designed hetero-Janus nanofibers(HJNFs)with ordered electric field distribution and separated redox surfaces to promote Pr-HE of the water-pollutant system.Taking ZnO/NiO heterojunction as an example,the hetero-Janus structures were prepared via"Dual-channel"electrospinning and further confirmed by the element morphology analysis and asymmetric distribution of the XPS spectra.The theoretical simulation showed that Janus structures could effectively inhibit the electron trap and hole trap generation,then accelerate the directional carrier migration to the surface.Experimental investigations also confirmed that Janus structures could effectively suppress internal exciton luminescence and accelerate surface charge transfer.The Pr-HE amount and the corresponding propranolol(PRO)degradation rate of HJNFs were 7.9 and 1.5 times higher than hetero-mixed nanofibers(HMNFs).The enhancement factor of Pr-HE in water-PRO to pure water was about 3.1,but nearly zero for HMNFs.This prominent synergistic effect was due to the enhancement of charge separation and the inhibition of cascade side reaction from hetero-Janus structures.Furthermore,the synchronous Pr-HE and degradation reactions were significantly promoted by selective introducing Ag nanoparticles in one side of the HJNFs for enlarging the interfacial Fermi energy level difference.The hetero-Janus strategy offers a new perspective on designing efficient photoreforming photocatalysts for energy and environment applications.展开更多
PI3 kinases are important for KIT signaling and KIT mutants mediated cell transformation.In order to know the difference of PI3 kinase isoforms p110αand p110δin the signaling of wild-type KIT and the often occurred ...PI3 kinases are important for KIT signaling and KIT mutants mediated cell transformation.In order to know the difference of PI3 kinase isoforms p110αand p110δin the signaling of wild-type KIT and the often occurred KIT mutation D816V in hematopoietic malignancy mastocytosis,the predominant PI3 kinase isoform p110δin hematopoietic tissues was knocked out in hematopoietic cells.We found that loss of p110δexpression dramatically inhibits PI3 kinase activation mediated by both wild-type KIT and KIT/D816V.By over expression of p110αin p110δknock out cells,wild-type KIT mediated PI3 kinase activation was not changed while over expression of p110δincreased PI3 kinase activation.Similarly,in KIT/D816V expressing cells without p110δexpression,over expression of p110δbut not p110αrestored PI3 kinase activation.In agreement with the signaling results,cell proliferation,cell survival and cell cycle assay further showed that over expression of p110δbut not p110αin p110δknock out cells increases both wild-type KIT and KIT/D816V mediated cell survival and proliferation.These results suggested that p110δplays a more important role than p110αin KIT signaling and KIT mutant mediated cell transformation in hematopoietic cells.展开更多
Saposhnikovia divaricata(SD)has high medicinal and edible value,but relatively little research has been done on its qual-ity markers(Q-markers).To further clarify the Q-markers of SD with their corresponding pharmacod...Saposhnikovia divaricata(SD)has high medicinal and edible value,but relatively little research has been done on its qual-ity markers(Q-markers).To further clarify the Q-markers of SD with their corresponding pharmacodynamic targets.In this experiment,14 batches of SD were identified and screened for Q-marker candidate components using a combination of HPLC fingerprint with similarity analysis,principal component analysis,hierarchical cluster analysis,and partial least squares discriminant analysis.Then,network pharmacology was used to predict Q-markers and core targets.The results showed that 5-O-methylvisammioside,cimifugin,and prim-O-glucosylcimifugin could be used as Q-markers of SD;while,MAPK1,MAPK3,PIK3CA,JUN,and MAPK8 were the core targets of SD for drug efficacy.To further evaluate the bind-ing efficiency of Q-markers,molecular docking of the main active ingredients of SD to the core targets was performed.The results showed that the compounds bind well to their targets,and binding energies were all less than-5 kcal/mol.The Q-markers obtained from the screening were closely related to the core target genes,which could achieve therapeutic effects by modulating the relevant signaling pathways.This study offers a reference for the establishment of a set of quality control evaluation system for SD potential Q-markers prediction analysis,and lays the foundation for elucidating the mechanism of actionunderlying itspharmacodynamic substance.展开更多
Interaction of the T cell receptor(TCR)with an MHC-antigenic peptide complex results in changes at the molecular and cellular levels in T cells.The outside environmental cues are translated into various signal transdu...Interaction of the T cell receptor(TCR)with an MHC-antigenic peptide complex results in changes at the molecular and cellular levels in T cells.The outside environmental cues are translated into various signal transduction pathways within the cell,which mediate the activation of various genes with the help of specific transcription factors.These signaling networks propagate with the help of various effector enzymes,such as kinases,phosphatases,and phospholipases.Integration of these disparate signal transduction pathways is done with the help of adaptor proteins that are non-enzymatic in function and that serve as a scaffold for various protein-protein interactions.This process aids in connecting the proximal to distal signaling pathways,thereby contributing to the full activation of T cells.This review provides a comprehensive snapshot of the various molecules involved in regulating T cell receptor signaling,covering both enzymes and adaptors,and will discuss their role in human disease.展开更多
This study develops and tests a full mediation model that examines the mediating role of job satisfaction in the Chinese context, based on a survey of 424 employees in three small and medium sized enterprises. Data an...This study develops and tests a full mediation model that examines the mediating role of job satisfaction in the Chinese context, based on a survey of 424 employees in three small and medium sized enterprises. Data analysis shows a good fit with the full mediation and all four classes of antecedents (i.e., perceived organizational support, procedural, distributive, and interactional justice). Particularly, procedural justice contributes to the prediction of satisfaction. Job satisfaction is also shown to mediate most antecedent- consequence relationships, except the two between perceived organizational support (POS)--turnover and procedural justice--consequences. Furthermore, there are only four direct links, including POS to citizenship behaviors directed at individuals, distributive justice to turnover intention, interactional justice to citizenship behaviors directed at organizations and turnover. These direct links suggest that job satisfaction does not fully mediate the relationships.展开更多
Summary of main observation and conclusion Atomistic dynamics of protonated polyglycine, glyn-H^+(n = 3, 5, and 7), colliding with a fluorinated octanethiol self-assembled monolayer (F-SAM) surface has been studied by...Summary of main observation and conclusion Atomistic dynamics of protonated polyglycine, glyn-H^+(n = 3, 5, and 7), colliding with a fluorinated octanethiol self-assembled monolayer (F-SAM) surface has been studied by trajectory calculations. The effects of peptide size on the collision processes and energy transfer efficiencies are emphasized and discussed in detail. The simulations show that the fraction of trapping, which is related to the soft-landing process, dramatically drops with the in crease in collisi on energy, but gently increases with the peptide size. The average energy transfer to the peptide ion's internal degrees of freedom, AEint, is compared with previous experiments. The limiting probability Po of energy transfer to the surface is given by fitting a function of Poexp(—b/&). Our results suggest that the efficiencies of energy transfer are less dependent on the masses, even the categories of the peptide ions, and are determined by the character of the surfaces.展开更多
Neuroblastoma(NB),a frequently occurring pediatric disease,is derived from the neural crest cells in the sympathetic ganglia and adrenal medulla.Notably,it is a heterogeneous tumor consisting of many affection factors...Neuroblastoma(NB),a frequently occurring pediatric disease,is derived from the neural crest cells in the sympathetic ganglia and adrenal medulla.Notably,it is a heterogeneous tumor consisting of many affection factors,such as the diagnosis time within the first year and the diversity of the histology and genetic features.Despite improved outcomes in NB patients,it remains a difficult clinical problem and requires new therapeutic targets and methods.The somatic acquired activation point mutations in the receptor tyrosine kinase anaplastic lymphoma kinase(ALK)represent potential targets for treating NB.Herein,we review the underlying mechanisms of ALK in NB development,the latest available strategies to block ALK constitutive activity to treat NB,and discuss the current clinical challenges of resistance to these therapies and the strategies to overcome them.展开更多
基金the National Natural Science Foundation of China(21972034,21673060)the State Key Lab of Urban Water Resource and Environment of Harbin Institute of Technology(HIT2019DX12).
文摘A novel Zn-based metal–organic framework Zn(dobdc)(datz)[Zn_(2)(H2dobdc)(datz)2$1.5DMF]with plentiful hydrogen bond donors(HBD)groups was facilely synthesized from mixed ligands.The dual activation of metal Zn sites and HBD groups for epoxides by forming Zn–O adduct and hydrogen bonds facilitated the ring-opening of epoxide substrate,which is critical for the subsequent CO_(2) fixation.Also,the existence of micropores and N-rich units in Zn(dobdc)(datz)afforded affinity towards CO_(2),which is beneficial to further improvement on catalytic CO_(2) conversion performance.Satisfactorily,Zn(dobdc)(datz)/Bu4NBr system was proved efficient heterogeneous catalyst for the CO_(2) cycloaddition with epoxides,and 98%propylene carbonate yield was obtained under mild conditions(80C,1.5 MPa and solvent-free).In addition,Zn(dobdc)(datz)/Bu4NBr exhibited remarkable versatility to different epoxides and could be completely recycled over six runs with high catalytic activity.The highly stable,easily recycle and solvent-free Zn-based MOF reported here displays eco-friendly and efficient performance to CO_(2)conversion.
基金supported by the Nature Science Foundation of Ningxia(2020AAC03162).
文摘Background:The Warburg effect is considered as a hallmark of various types of cancers,while the regulatory mechanism is poorly understood.Our previous study demonstrated that miR-194-5p directly targets and regulates insulin-like growth factor1 receptor(IGF1R).In this study,we aimed to investigate the role of miR-194-5p in the regulation of the Warburg effect in ovarian cancer cells.Methods:The stable ovarian cell lines with miR-194-5p overexpression or silencing IGF1R expression were established by lentivirus infection.ATP generation,glucose uptake,lactate production and extracellular acidification rate(ECAR)assay were used to analyze the effects of aerobic glycolysis in ovarian cancer cells.Gene expression was analyzed by quantitative polymerase chain reaction(qPCR)and western blot.Immunohistochemistry assays were performed to assess the expression of the IGF1R protein in ovarian cancer tissues.Results:Overexpression of miR-194-5p or silencing IGF1R expression in ovarian cancer cells decreases ATP generation,glucose uptake,lactate production,and ECAR and inhibits both the mRNA and protein expression of PKM2,LDHA,GLUT1,and GLUT3.While the knockdown of miR-194-5p expression led to opposite results.Overexpression of miR-194-5p or silencing IGF1R expression suppressed the phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)pathway,whose activation can sustain aerobic glycolysis in cancer cells,and the knockdown of miR-194-5p expression promoted the activation of the PI3K/AKT pathway.Conclusion:Our results suggest that miR-194-5p can inhibit the Warburg effect by negative regulation of IGF1R and further repression of the PI3K/AKT pathway,which provides a theoretical basis for further test of miR-194-5p as a target in the treatment of ovarian cancer.
基金supported by the National Natural Science Foundation of China(Nos.52072064,51972051,62171115,and 51732003)the 111 Project(No.B13013).
文摘Photoreforming hydrogen evolution(Pr-HE)of a water-pollutant system could simultaneously achieve efficient hydrogen production and pollutant degradation.It provides a new way to solve energy and environmental issues,but the poor internal charge separation still limits its performance.This work designed hetero-Janus nanofibers(HJNFs)with ordered electric field distribution and separated redox surfaces to promote Pr-HE of the water-pollutant system.Taking ZnO/NiO heterojunction as an example,the hetero-Janus structures were prepared via"Dual-channel"electrospinning and further confirmed by the element morphology analysis and asymmetric distribution of the XPS spectra.The theoretical simulation showed that Janus structures could effectively inhibit the electron trap and hole trap generation,then accelerate the directional carrier migration to the surface.Experimental investigations also confirmed that Janus structures could effectively suppress internal exciton luminescence and accelerate surface charge transfer.The Pr-HE amount and the corresponding propranolol(PRO)degradation rate of HJNFs were 7.9 and 1.5 times higher than hetero-mixed nanofibers(HMNFs).The enhancement factor of Pr-HE in water-PRO to pure water was about 3.1,but nearly zero for HMNFs.This prominent synergistic effect was due to the enhancement of charge separation and the inhibition of cascade side reaction from hetero-Janus structures.Furthermore,the synchronous Pr-HE and degradation reactions were significantly promoted by selective introducing Ag nanoparticles in one side of the HJNFs for enlarging the interfacial Fermi energy level difference.The hetero-Janus strategy offers a new perspective on designing efficient photoreforming photocatalysts for energy and environment applications.
基金This work is supported by National Natural Science Foundation of China(82160521)Natural Science Foundation of Ningxia Province(2018A0089)Key Research and Development Program of Ningxia Province(2019BEH03003).
文摘PI3 kinases are important for KIT signaling and KIT mutants mediated cell transformation.In order to know the difference of PI3 kinase isoforms p110αand p110δin the signaling of wild-type KIT and the often occurred KIT mutation D816V in hematopoietic malignancy mastocytosis,the predominant PI3 kinase isoform p110δin hematopoietic tissues was knocked out in hematopoietic cells.We found that loss of p110δexpression dramatically inhibits PI3 kinase activation mediated by both wild-type KIT and KIT/D816V.By over expression of p110αin p110δknock out cells,wild-type KIT mediated PI3 kinase activation was not changed while over expression of p110δincreased PI3 kinase activation.Similarly,in KIT/D816V expressing cells without p110δexpression,over expression of p110δbut not p110αrestored PI3 kinase activation.In agreement with the signaling results,cell proliferation,cell survival and cell cycle assay further showed that over expression of p110δbut not p110αin p110δknock out cells increases both wild-type KIT and KIT/D816V mediated cell survival and proliferation.These results suggested that p110δplays a more important role than p110αin KIT signaling and KIT mutant mediated cell transformation in hematopoietic cells.
基金funded by Fundamental Research Funds for the Central Universities(2572022DJ01)Natural Science Foundation of Heilongjiang Province(LH2022B004)+1 种基金111 Project(B20088)Heilongjiang Touyan Innovation Team Program(Tree Genetics and Breeding Innovation Team).
文摘Saposhnikovia divaricata(SD)has high medicinal and edible value,but relatively little research has been done on its qual-ity markers(Q-markers).To further clarify the Q-markers of SD with their corresponding pharmacodynamic targets.In this experiment,14 batches of SD were identified and screened for Q-marker candidate components using a combination of HPLC fingerprint with similarity analysis,principal component analysis,hierarchical cluster analysis,and partial least squares discriminant analysis.Then,network pharmacology was used to predict Q-markers and core targets.The results showed that 5-O-methylvisammioside,cimifugin,and prim-O-glucosylcimifugin could be used as Q-markers of SD;while,MAPK1,MAPK3,PIK3CA,JUN,and MAPK8 were the core targets of SD for drug efficacy.To further evaluate the bind-ing efficiency of Q-markers,molecular docking of the main active ingredients of SD to the core targets was performed.The results showed that the compounds bind well to their targets,and binding energies were all less than-5 kcal/mol.The Q-markers obtained from the screening were closely related to the core target genes,which could achieve therapeutic effects by modulating the relevant signaling pathways.This study offers a reference for the establishment of a set of quality control evaluation system for SD potential Q-markers prediction analysis,and lays the foundation for elucidating the mechanism of actionunderlying itspharmacodynamic substance.
基金This research was supported by the Crafoord Foundationthe Swedish Cancer Societythe Swedish Childhood Cancer Foundation.
文摘Interaction of the T cell receptor(TCR)with an MHC-antigenic peptide complex results in changes at the molecular and cellular levels in T cells.The outside environmental cues are translated into various signal transduction pathways within the cell,which mediate the activation of various genes with the help of specific transcription factors.These signaling networks propagate with the help of various effector enzymes,such as kinases,phosphatases,and phospholipases.Integration of these disparate signal transduction pathways is done with the help of adaptor proteins that are non-enzymatic in function and that serve as a scaffold for various protein-protein interactions.This process aids in connecting the proximal to distal signaling pathways,thereby contributing to the full activation of T cells.This review provides a comprehensive snapshot of the various molecules involved in regulating T cell receptor signaling,covering both enzymes and adaptors,and will discuss their role in human disease.
文摘This study develops and tests a full mediation model that examines the mediating role of job satisfaction in the Chinese context, based on a survey of 424 employees in three small and medium sized enterprises. Data analysis shows a good fit with the full mediation and all four classes of antecedents (i.e., perceived organizational support, procedural, distributive, and interactional justice). Particularly, procedural justice contributes to the prediction of satisfaction. Job satisfaction is also shown to mediate most antecedent- consequence relationships, except the two between perceived organizational support (POS)--turnover and procedural justice--consequences. Furthermore, there are only four direct links, including POS to citizenship behaviors directed at individuals, distributive justice to turnover intention, interactional justice to citizenship behaviors directed at organizations and turnover. These direct links suggest that job satisfaction does not fully mediate the relationships.
文摘Summary of main observation and conclusion Atomistic dynamics of protonated polyglycine, glyn-H^+(n = 3, 5, and 7), colliding with a fluorinated octanethiol self-assembled monolayer (F-SAM) surface has been studied by trajectory calculations. The effects of peptide size on the collision processes and energy transfer efficiencies are emphasized and discussed in detail. The simulations show that the fraction of trapping, which is related to the soft-landing process, dramatically drops with the in crease in collisi on energy, but gently increases with the peptide size. The average energy transfer to the peptide ion's internal degrees of freedom, AEint, is compared with previous experiments. The limiting probability Po of energy transfer to the surface is given by fitting a function of Poexp(—b/&). Our results suggest that the efficiencies of energy transfer are less dependent on the masses, even the categories of the peptide ions, and are determined by the character of the surfaces.
基金This work is supported by grants from the National Natural Science Foundation of China(82002633)Medical Scientific Research Foundation of Guangdong Province of China(A2019433)+1 种基金Shenzhen Health Family Planning System Research Project(SZBC2018012)to Tianfeng LiThe Science,Technology and Innovation Commission of Shenzhen(JCYJ20220531093213030)to Zhenjian Zhuo.
文摘Neuroblastoma(NB),a frequently occurring pediatric disease,is derived from the neural crest cells in the sympathetic ganglia and adrenal medulla.Notably,it is a heterogeneous tumor consisting of many affection factors,such as the diagnosis time within the first year and the diversity of the histology and genetic features.Despite improved outcomes in NB patients,it remains a difficult clinical problem and requires new therapeutic targets and methods.The somatic acquired activation point mutations in the receptor tyrosine kinase anaplastic lymphoma kinase(ALK)represent potential targets for treating NB.Herein,we review the underlying mechanisms of ALK in NB development,the latest available strategies to block ALK constitutive activity to treat NB,and discuss the current clinical challenges of resistance to these therapies and the strategies to overcome them.