Suppression of the inner energy dissipation,related to the lattice phonons and inner defects,in lanthanide doped upco nversion luminescent materials remains a formidable challenge.Herein,we reveal an energy cycling st...Suppression of the inner energy dissipation,related to the lattice phonons and inner defects,in lanthanide doped upco nversion luminescent materials remains a formidable challenge.Herein,we reveal an energy cycling strategy capable of suppressing the inner energy dissipation in lanthanide doped upconversion nanocrystals.Yb^(3+)ions were introduced in Er^(3+)heavily doped nanocrystals as an energy reservoir to compete with the inner energy dissipation.The detailed energy cycling processes between Er^(3+)activator and Yb^(3+)reservoir,responsible for the enhancement of Er^(3+)upconversion intensity,are proposed and further verified on the basis of spectral observations.The energy cycling strategy,with unique merits like facile and cost-effective preparation as well as broad scope of application,is highly valuable in lanthanide luminescent nano materials.展开更多
Objective:B-cell antigen receptor(BCR)signaling is required to maintain the physiological functions of normal B cells and plays an important pathogenic role in B-cell malignancies.Bruton tyrosine kinase(BTK),a critica...Objective:B-cell antigen receptor(BCR)signaling is required to maintain the physiological functions of normal B cells and plays an important pathogenic role in B-cell malignancies.Bruton tyrosine kinase(BTK),a critical mediator of BCR signaling,is an attractive target for the treatment of B-cell malignancies.This study aimed to identify a highly potent and selective BTK inhibitor.Methods:Homogeneous time-resolved fluorescence assays were used to screen BTK inhibitors.Typhoon fluorescence imaging and Western blot analysis were used to confirm the effects of SY-1530 on the BCR signaling pathway.Additionally,the anti-tumor activities of SY-1530 were evaluated in TMD8 xenografts and spontaneous canine B-cell lymphoma.Results:We found a novel irreversible and non-competitive inhibitor of BTK,SY-1530,which provided dose-dependent and timedependent inhibition.SY-1530 selectively bound to BTK rather than inducible T-cell kinase;consequently,it did not significantly affect T-cell receptor signaling and caused limited off-target effects.SY-1530 blocked the BCR signaling pathway through downregulation of BTK activity,thus leading to impaired phosphorylation of BTK and its downstream kinases.Moreover,SY-1530 induced apoptosis in a caspase-dependent manner and efficaciously inhibited tumor growth in mouse xenograft models of B-cell malignancy(P<0.001).SY-1530 also induced positive clinical responses in spontaneous canine B-cell lymphoma.Conclusions:SY-1530 is an irreversible and selective BTK inhibitor that shows inhibitory effects on B-cell malignancies by blocking the BCR signaling pathway.Therefore,it may be a promising therapeutic approach for the treatment of B-cell malignancies.展开更多
基金Project supported by Fundamental Research Funds for the Central Universities(3072021CF2502)Natural Science Foundation of Heilongjiang Province(LH2020A008)+1 种基金Science and Technology Research Program of Chongqing Education Commission of China(KJQN202001420)National College Student Innovation and Entrepreneurship Training Program(202110217224)。
文摘Suppression of the inner energy dissipation,related to the lattice phonons and inner defects,in lanthanide doped upco nversion luminescent materials remains a formidable challenge.Herein,we reveal an energy cycling strategy capable of suppressing the inner energy dissipation in lanthanide doped upconversion nanocrystals.Yb^(3+)ions were introduced in Er^(3+)heavily doped nanocrystals as an energy reservoir to compete with the inner energy dissipation.The detailed energy cycling processes between Er^(3+)activator and Yb^(3+)reservoir,responsible for the enhancement of Er^(3+)upconversion intensity,are proposed and further verified on the basis of spectral observations.The energy cycling strategy,with unique merits like facile and cost-effective preparation as well as broad scope of application,is highly valuable in lanthanide luminescent nano materials.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.81622037,81672762,and 81372185)and the Beijing Natural Science Foundation(Grant No.5194023).
文摘Objective:B-cell antigen receptor(BCR)signaling is required to maintain the physiological functions of normal B cells and plays an important pathogenic role in B-cell malignancies.Bruton tyrosine kinase(BTK),a critical mediator of BCR signaling,is an attractive target for the treatment of B-cell malignancies.This study aimed to identify a highly potent and selective BTK inhibitor.Methods:Homogeneous time-resolved fluorescence assays were used to screen BTK inhibitors.Typhoon fluorescence imaging and Western blot analysis were used to confirm the effects of SY-1530 on the BCR signaling pathway.Additionally,the anti-tumor activities of SY-1530 were evaluated in TMD8 xenografts and spontaneous canine B-cell lymphoma.Results:We found a novel irreversible and non-competitive inhibitor of BTK,SY-1530,which provided dose-dependent and timedependent inhibition.SY-1530 selectively bound to BTK rather than inducible T-cell kinase;consequently,it did not significantly affect T-cell receptor signaling and caused limited off-target effects.SY-1530 blocked the BCR signaling pathway through downregulation of BTK activity,thus leading to impaired phosphorylation of BTK and its downstream kinases.Moreover,SY-1530 induced apoptosis in a caspase-dependent manner and efficaciously inhibited tumor growth in mouse xenograft models of B-cell malignancy(P<0.001).SY-1530 also induced positive clinical responses in spontaneous canine B-cell lymphoma.Conclusions:SY-1530 is an irreversible and selective BTK inhibitor that shows inhibitory effects on B-cell malignancies by blocking the BCR signaling pathway.Therefore,it may be a promising therapeutic approach for the treatment of B-cell malignancies.
