Objectives:B-cell lymphoma 6(BCL6)is a transcriptional repressor whose overexpression is closely linked to the progression of diffuse large B-cell lymphoma(DLBCL),making it a promising therapeutic target.This study ai...Objectives:B-cell lymphoma 6(BCL6)is a transcriptional repressor whose overexpression is closely linked to the progression of diffuse large B-cell lymphoma(DLBCL),making it a promising therapeutic target.This study aims to identify a novel small molecule,synthesized via proteolysis-targeting chimeras(PROTACs),capable of degrading BCL6,thereby inhibiting DLBCL growth and providing a foundation for future preclinical studies.Methods:The expression of BCL6 in DLBCL was analyzed using The Cancer Genome Atlas(TCGA)database and the Human Protein Atlas.Western blotting assays confirmed BCL6 expression in tumor cell lines,leading to the identification of the small molecule compound DZ-865B.To evaluate DZ-865B’s in vitro efficacy,multiple assays were performed,including protein immunoblotting,immunofluorescence,reverse transcription quantitative PCR,EDU proliferation,and soft agar cloning assays.Results:TCGA analysis revealed significant overexpression of BCL6 in DLBCL(p<0.05),corroborated by immunohistological staining and western blotting.DZ-865B induced BCL6 degradation in DLBCL cell lines(OCI-LY-1 and SU-DHL-4)in a concentration-and time-dependent manner,and induced the degradation of nuclear BCL6 through the ubiquitin-proteasome pathway.Notably,DZ-865B did not alter BCL6 mRNA levels but modulated downstream gene expression,leading to the activation of apoptosis pathway proteins and inhibition of DNA synthesis,effectively suppressing DLBCL cell growth.Conclusion:This study demonstrates that the small molecule DZ-865B targets and degrades BCL6 in DLBCL cells,promoting apoptosis and inhibiting cellular proliferation.These findings highlight DZ-865B as a potential therapeutic agent for diffuse large B-cell lymphoma.展开更多
Metal halide perovskites are attractive for light-emitting diodes due to their superior optoelectronic properties such as tunable bandgaps,high photoluminescence quantum yields(PLQYs),high color purities and solution ...Metal halide perovskites are attractive for light-emitting diodes due to their superior optoelectronic properties such as tunable bandgaps,high photoluminescence quantum yields(PLQYs),high color purities and solution processability[1–6].In the past several years,impressive progress has been made in perovskite light-emitting diodes(PeLEDs)via microstructure engineering[7],charge balancing[8],surface defect passivation[9,10],metal ion doping[11,12]and dimensional engineering[13].As such,the green,red and near-infrared PeLEDs have achieved impressive external quantum efficiencies(EQEs)exceeding 20%[7,8,14,15].However,the performances of pure-blue PeLEDs,i.e.,brightness and EQEs,still lag largely behind those of the green and red counterparts,which severely impedes the PeLED application in full-color display and solid-state lighting.展开更多
Electrolytic MnO_(2)/Zn batteries have attracted extensive attention for use in large-scale energy storage applications due to their low cost,high output voltage,safety,and environmental friendliness.However,the poor ...Electrolytic MnO_(2)/Zn batteries have attracted extensive attention for use in large-scale energy storage applications due to their low cost,high output voltage,safety,and environmental friendliness.However,the poor electrical conductivity of MnO_(2)limits its deposition and dissolution at large capacities,which leads to sluggish reaction kinetics and drastic capacity decay.Here,we report a theory-guided design principle for an electrolytic MnO_(2)/Zn battery co-regulated with transition metal ions that has improved electrochemical performance in terms of deposition and stripping chemistries.We start with first-principles calculations to predict the electrolytic effects of regulating transition metal ions in the deposition/stripping chemistry of the MnO_(2)cathode.The results indicate that with the simultaneous incorporation of strongly electronegative Co and Ni,the MnO_(2)cathode tends to possess more active electron states,faster charge-transfer kinetics,and better electrical conductivity than either MnO_(2)regulated with Co or Ni on their own,or pristine MnO_(2);hence,this co-regulation is beneficial for the cathode solid/liquid MnO_(2)/Mn2t reactions.We then fabricate and demonstrate a novel Co2t and Ni2t coregulated MnO_(2)/Zn(Co-Ni-MnO_(2)/Zn)battery that yields significantly better electrochemical performance,finding that the synergistic regulation of Co and Ni on MnO_(2)can significantly increase its intrinsic conductivity and achieve high rates and Coulombic efficiencies at large capacities.The aqueous Co-Ni-MnO_(2)/Zn battery exhibits a high rate(10C,100 mA cm^(-2)),high Coulombic efficiency(91.89%),and excellent cycling stability(600 cycles without decay)at a large areal capacity of 10 mAh cm^(-2).Our proposed strategy of co-regulation with transition metal ions offers a versatile approach for improving the electrochemical performance of aqueous electrolytic MnO_(2)/Zn batteries in large-scale energy storage applications.展开更多
The roasting process of pyrogallol,a polyphenol compound distributed in coffee beverages,significantly enhanced itsα-glucosidase inhibitory activity.In this study,a bioassay-guided isolation of the thermal reaction p...The roasting process of pyrogallol,a polyphenol compound distributed in coffee beverages,significantly enhanced itsα-glucosidase inhibitory activity.In this study,a bioassay-guided isolation of the thermal reaction products of pyrogallol led to the identification of two potentα-glucosidase inhibitors,4-4′dimer of pyrogallol(4,4′-DP)and 4-5′dimer of pyrogallol(4,5′-DP).Theirα-glucosidase inhibitory activity was higher than that of pyrogallol,as evidenced by comparing the IC_(50)values(206.2±1.2μM for 4,4′-DP,187.6±2.6μM for 4,5′-DP,2660±60.1μM for pyrogallol).And the roasting products were more potentα-glucosidase inhibitors compared to acarbose(IC_(50)=695±12.7μM).Enzyme kinetics demonstrated that 4,4′-DP and 4,5′-DP inhibitedα-glucosidase in an uncompetitive and a non-competitive manner,respectively.Docking simulations revealed that the main interaction forces between these two compounds andα-glucosidase were hydrogen bonding and hydrophobic effect.These results suggested that a simple roasting process might increase theα-glucosidase inhibitory activity of pyrogallol-containing foods such as coffee beverages.展开更多
基金supported by the National Natural Science Foundation of China(82260716)the Key Research and Development Program of Ningxia(2023BEG02010).
文摘Objectives:B-cell lymphoma 6(BCL6)is a transcriptional repressor whose overexpression is closely linked to the progression of diffuse large B-cell lymphoma(DLBCL),making it a promising therapeutic target.This study aims to identify a novel small molecule,synthesized via proteolysis-targeting chimeras(PROTACs),capable of degrading BCL6,thereby inhibiting DLBCL growth and providing a foundation for future preclinical studies.Methods:The expression of BCL6 in DLBCL was analyzed using The Cancer Genome Atlas(TCGA)database and the Human Protein Atlas.Western blotting assays confirmed BCL6 expression in tumor cell lines,leading to the identification of the small molecule compound DZ-865B.To evaluate DZ-865B’s in vitro efficacy,multiple assays were performed,including protein immunoblotting,immunofluorescence,reverse transcription quantitative PCR,EDU proliferation,and soft agar cloning assays.Results:TCGA analysis revealed significant overexpression of BCL6 in DLBCL(p<0.05),corroborated by immunohistological staining and western blotting.DZ-865B induced BCL6 degradation in DLBCL cell lines(OCI-LY-1 and SU-DHL-4)in a concentration-and time-dependent manner,and induced the degradation of nuclear BCL6 through the ubiquitin-proteasome pathway.Notably,DZ-865B did not alter BCL6 mRNA levels but modulated downstream gene expression,leading to the activation of apoptosis pathway proteins and inhibition of DNA synthesis,effectively suppressing DLBCL cell growth.Conclusion:This study demonstrates that the small molecule DZ-865B targets and degrades BCL6 in DLBCL cells,promoting apoptosis and inhibiting cellular proliferation.These findings highlight DZ-865B as a potential therapeutic agent for diffuse large B-cell lymphoma.
基金We acknowledge the financial support from the National Natural Science Foundation of China(51571184,21501165,21875236,21573211,21633007)the National Key R&D Program on Nano Science and Technology(2016YFA0200602,2018YFA0208702)+3 种基金the Fundamental Research Funds for the Central Universities(WK2060190085)the Joint Funds from Hefei National Synchrotron Radiation Laboratory(KY2060000111)the Anhui Initiative in Quantum Information Technologies(AHY090200)We also thank the support from the USTC Center for Micro and Nanoscale Research and Fabrication.
文摘Metal halide perovskites are attractive for light-emitting diodes due to their superior optoelectronic properties such as tunable bandgaps,high photoluminescence quantum yields(PLQYs),high color purities and solution processability[1–6].In the past several years,impressive progress has been made in perovskite light-emitting diodes(PeLEDs)via microstructure engineering[7],charge balancing[8],surface defect passivation[9,10],metal ion doping[11,12]and dimensional engineering[13].As such,the green,red and near-infrared PeLEDs have achieved impressive external quantum efficiencies(EQEs)exceeding 20%[7,8,14,15].However,the performances of pure-blue PeLEDs,i.e.,brightness and EQEs,still lag largely behind those of the green and red counterparts,which severely impedes the PeLED application in full-color display and solid-state lighting.
基金This work was financially supported by the USTC(No.KY2060000150)Natural Science Foundation of Guangdong Province(No.2021A1515010144)National Natural Science Foundation of China(No.51602009).
文摘Electrolytic MnO_(2)/Zn batteries have attracted extensive attention for use in large-scale energy storage applications due to their low cost,high output voltage,safety,and environmental friendliness.However,the poor electrical conductivity of MnO_(2)limits its deposition and dissolution at large capacities,which leads to sluggish reaction kinetics and drastic capacity decay.Here,we report a theory-guided design principle for an electrolytic MnO_(2)/Zn battery co-regulated with transition metal ions that has improved electrochemical performance in terms of deposition and stripping chemistries.We start with first-principles calculations to predict the electrolytic effects of regulating transition metal ions in the deposition/stripping chemistry of the MnO_(2)cathode.The results indicate that with the simultaneous incorporation of strongly electronegative Co and Ni,the MnO_(2)cathode tends to possess more active electron states,faster charge-transfer kinetics,and better electrical conductivity than either MnO_(2)regulated with Co or Ni on their own,or pristine MnO_(2);hence,this co-regulation is beneficial for the cathode solid/liquid MnO_(2)/Mn2t reactions.We then fabricate and demonstrate a novel Co2t and Ni2t coregulated MnO_(2)/Zn(Co-Ni-MnO_(2)/Zn)battery that yields significantly better electrochemical performance,finding that the synergistic regulation of Co and Ni on MnO_(2)can significantly increase its intrinsic conductivity and achieve high rates and Coulombic efficiencies at large capacities.The aqueous Co-Ni-MnO_(2)/Zn battery exhibits a high rate(10C,100 mA cm^(-2)),high Coulombic efficiency(91.89%),and excellent cycling stability(600 cycles without decay)at a large areal capacity of 10 mAh cm^(-2).Our proposed strategy of co-regulation with transition metal ions offers a versatile approach for improving the electrochemical performance of aqueous electrolytic MnO_(2)/Zn batteries in large-scale energy storage applications.
基金This work was supported by the National Natural Science Foundation of China[grant number 82003650]TCM Science and Technology Project of Shandong Province,China[grant number 2020Q050].
文摘The roasting process of pyrogallol,a polyphenol compound distributed in coffee beverages,significantly enhanced itsα-glucosidase inhibitory activity.In this study,a bioassay-guided isolation of the thermal reaction products of pyrogallol led to the identification of two potentα-glucosidase inhibitors,4-4′dimer of pyrogallol(4,4′-DP)and 4-5′dimer of pyrogallol(4,5′-DP).Theirα-glucosidase inhibitory activity was higher than that of pyrogallol,as evidenced by comparing the IC_(50)values(206.2±1.2μM for 4,4′-DP,187.6±2.6μM for 4,5′-DP,2660±60.1μM for pyrogallol).And the roasting products were more potentα-glucosidase inhibitors compared to acarbose(IC_(50)=695±12.7μM).Enzyme kinetics demonstrated that 4,4′-DP and 4,5′-DP inhibitedα-glucosidase in an uncompetitive and a non-competitive manner,respectively.Docking simulations revealed that the main interaction forces between these two compounds andα-glucosidase were hydrogen bonding and hydrophobic effect.These results suggested that a simple roasting process might increase theα-glucosidase inhibitory activity of pyrogallol-containing foods such as coffee beverages.
