Spiropyran derivatives are prototype mechanophores with a promising application as molecular sensors because of their changeable structure under external force stimuli.However,the chemical structure evolution under ex...Spiropyran derivatives are prototype mechanophores with a promising application as molecular sensors because of their changeable structure under external force stimuli.However,the chemical structure evolution under external stimuli remains unclear due to the uncertainty and difficulty in distinguishing the structures of different ring-opened merocyanine isomers generated in the force-induced reaction.Here we identify the structure of isomers produced by the force-induced reaction of spiropyran derivatives using a single-molecule conductance measurement and an unsupervised clustering algorithm.We found that the original data from the single-molecule conductance measurement can be divided into four clusters through unsupervised clustering.By introducing a photoinduced reaction and theoretical calculation,we identified and attributed the four clusters of data to the multiple states of the molecular junctions.Our work demonstrates that a single-molecule break junction measurement can distinguish the isomers in the force-induced reaction,suggesting the great potential of single-molecule conductance measurement and unsupervised clustering approaches for structural analysis.展开更多
Osteoarthritis(OA)is a prevalent joint disease with no effective treatment strategies.Aberrant mechanical stimuli was demonstrated to be an essential factor for OA pathogenesis.Although multiple studies have detected ...Osteoarthritis(OA)is a prevalent joint disease with no effective treatment strategies.Aberrant mechanical stimuli was demonstrated to be an essential factor for OA pathogenesis.Although multiple studies have detected potential regulatory mechanisms underlying OA and have concentrated on developing novel treatment strategies,the epigenetic control of OA remains unclear.Histone demethylase JMJD3 has been reported to mediate multiple physiological and pathological processes,including cell differentiation,proliferation,autophagy,and apoptosis.However,the regulation of JMJD3 in aberrant force-related OA and its mediatory effect on disease progression are still unknown.In this work,we confirmed the upregulation of JMJD3 in aberrant forceinduced cartilage injury in vitro and in vivo.Functionally,inhibition of JMJD3 by its inhibitor,GSK-J4,or downregulation of JMJD3 by adenovirus infection of sh-JMJD3 could alleviate the aberrant force-induced chondrocyte injury.Mechanistic investigation illustrated that aberrant force induces JMJD3 expression and then demethylates H3K27me3 at the NR4A1 promoter to promote its expression.Further experiments indicated that NR4A1 can regulate chondrocyte apoptosis,cartilage degeneration,extracellular matrix degradation,and inflammatory responses.In vivo,anterior cruciate ligament transection(ACLT)was performed to construct an OA model,and the therapeutic effect of GSK-J4 was validated.More importantly,we adopted a peptide-si RNA nanoplatform to deliver si-JMJD3 into articular cartilage,and the severity of joint degeneration was remarkably mitigated.Taken together,our findings demonstrated that JMJD3 is flow-responsive and epigenetically regulates OA progression.Our work provides evidences for JMJD3 inhibition as an innovative epigenetic therapy approach for joint diseases by utilizing p5RHH-si RNA nanocomplexes.展开更多
The development of organic materials with white-light emission and thermally activated delayed fluorescence(TADF)properties in the solid state remain a challenge.Herein,a series of white-light-emitting organic luminog...The development of organic materials with white-light emission and thermally activated delayed fluorescence(TADF)properties in the solid state remain a challenge.Herein,a series of white-light-emitting organic luminogens have been developed and are found to show aggregation-induced delayed fluorescence(AIDF)characteristics.The AIDF emitters present dual-emission consisted of prompt fluorescence and TADF in the crystalline state.Their white-light emissions can be easily tuned by altering the chemical structure and connecting position of the heterocyclic aromatic substituent.Under the stimuli of mechanical force and solvent vapor,the compounds exhibit remarkable and reversible mechanochromism,in which their emission colors are switchable between white and yellow.Upon grinding,they also display linearly tunable luminescence colors,as well as force-induced TADF enhancement,which may be associated with the more compact molecular packing and the restriction of intramolecular motions.The results from time-resolved emission scanning and theoretical calculation suggest that the dual-emission of the AIDF luminogens likely results from the twisted intramolecular charge transfer transitions of the molecules,and the reversible mechanochromism properties probably stem from the interconversion of the quasi-axial and the quasi-equatorial conformations.展开更多
A gate-to-body tunneling current model for silicon-on-insulator （SOl） devices is simulated. As verified by the mea- sured data, the model, considering both gate voltage and drain voltage dependence as well as image ...A gate-to-body tunneling current model for silicon-on-insulator （SOl） devices is simulated. As verified by the mea- sured data, the model, considering both gate voltage and drain voltage dependence as well as image force-induced barrier low effect, provides a better prediction of the tunneling current and gate-induced floating body effect than the BSIMSOI4 model. A delayed gate-induced floating body effect is also predicted by the model.展开更多
为了研究无刷直流电机(brushless DC motor,BLDCM)电枢电流对转子温升的影响,提出一种涡流电势分类估算法。将电枢电流分解为直流分量iDC和交流分量iAC,在空间上,运动的转子会在绕组直流分量iDC的磁动势作用下产生运动电势em;同时在时间...为了研究无刷直流电机(brushless DC motor,BLDCM)电枢电流对转子温升的影响,提出一种涡流电势分类估算法。将电枢电流分解为直流分量iDC和交流分量iAC,在空间上,运动的转子会在绕组直流分量iDC的磁动势作用下产生运动电势em;同时在时间上,绕组交流分量iAC的磁动势也会在转子中产生感应电势et。暂不考虑涡流反应,对11kW无刷直流电机典型工作点下,选择转子中最大闭合曲线和最大曲面分别计算运动电势em和感应电势et。在不考虑齿槽影响的前提下,得到运动电势远小于感应电势的结论,认为只要电枢电流连续,负载变化对转子温升影响不大。实验结果验证了上述观点。展开更多
基金supported by the National Natural Science Foundation of China(grant nos.22173075,21933012,61901402,31871877,and 21774106)the National Key R&D Program of China(grant no.2017YFA0204902)+1 种基金the Fundamental Research Funds for the Central Universities(grant nos.20720200068 and 20720190002)the Natural Science Foundation of Fujian Province(grant no.2018J06004).
文摘Spiropyran derivatives are prototype mechanophores with a promising application as molecular sensors because of their changeable structure under external force stimuli.However,the chemical structure evolution under external stimuli remains unclear due to the uncertainty and difficulty in distinguishing the structures of different ring-opened merocyanine isomers generated in the force-induced reaction.Here we identify the structure of isomers produced by the force-induced reaction of spiropyran derivatives using a single-molecule conductance measurement and an unsupervised clustering algorithm.We found that the original data from the single-molecule conductance measurement can be divided into four clusters through unsupervised clustering.By introducing a photoinduced reaction and theoretical calculation,we identified and attributed the four clusters of data to the multiple states of the molecular junctions.Our work demonstrates that a single-molecule break junction measurement can distinguish the isomers in the force-induced reaction,suggesting the great potential of single-molecule conductance measurement and unsupervised clustering approaches for structural analysis.
基金supported by National Natural Science Foundation of China(11932012,81870790 and 31801233)Science and Technology Commission of Shanghai Municipality(18441903600)+1 种基金Clinical Research Plan of SHDC(No.SHDC2020CR3009A)Innovative Research Team of High-level Local Universities in Shanghai(SSMU-ZDCX20180902)。
文摘Osteoarthritis(OA)is a prevalent joint disease with no effective treatment strategies.Aberrant mechanical stimuli was demonstrated to be an essential factor for OA pathogenesis.Although multiple studies have detected potential regulatory mechanisms underlying OA and have concentrated on developing novel treatment strategies,the epigenetic control of OA remains unclear.Histone demethylase JMJD3 has been reported to mediate multiple physiological and pathological processes,including cell differentiation,proliferation,autophagy,and apoptosis.However,the regulation of JMJD3 in aberrant force-related OA and its mediatory effect on disease progression are still unknown.In this work,we confirmed the upregulation of JMJD3 in aberrant forceinduced cartilage injury in vitro and in vivo.Functionally,inhibition of JMJD3 by its inhibitor,GSK-J4,or downregulation of JMJD3 by adenovirus infection of sh-JMJD3 could alleviate the aberrant force-induced chondrocyte injury.Mechanistic investigation illustrated that aberrant force induces JMJD3 expression and then demethylates H3K27me3 at the NR4A1 promoter to promote its expression.Further experiments indicated that NR4A1 can regulate chondrocyte apoptosis,cartilage degeneration,extracellular matrix degradation,and inflammatory responses.In vivo,anterior cruciate ligament transection(ACLT)was performed to construct an OA model,and the therapeutic effect of GSK-J4 was validated.More importantly,we adopted a peptide-si RNA nanoplatform to deliver si-JMJD3 into articular cartilage,and the severity of joint degeneration was remarkably mitigated.Taken together,our findings demonstrated that JMJD3 is flow-responsive and epigenetically regulates OA progression.Our work provides evidences for JMJD3 inhibition as an innovative epigenetic therapy approach for joint diseases by utilizing p5RHH-si RNA nanocomplexes.
基金supported by the National Natural Science Foundation of China(No.51603233)the Natural Science Foundation of Guangdong Province of China(Nos.2019A1515010550,2020A1515010439,2019A1515011389)the GDUPS(2019)the Opening Foundation of Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education(Sun Yat-sen University,No.PCFM-2019-05)。
文摘The development of organic materials with white-light emission and thermally activated delayed fluorescence(TADF)properties in the solid state remain a challenge.Herein,a series of white-light-emitting organic luminogens have been developed and are found to show aggregation-induced delayed fluorescence(AIDF)characteristics.The AIDF emitters present dual-emission consisted of prompt fluorescence and TADF in the crystalline state.Their white-light emissions can be easily tuned by altering the chemical structure and connecting position of the heterocyclic aromatic substituent.Under the stimuli of mechanical force and solvent vapor,the compounds exhibit remarkable and reversible mechanochromism,in which their emission colors are switchable between white and yellow.Upon grinding,they also display linearly tunable luminescence colors,as well as force-induced TADF enhancement,which may be associated with the more compact molecular packing and the restriction of intramolecular motions.The results from time-resolved emission scanning and theoretical calculation suggest that the dual-emission of the AIDF luminogens likely results from the twisted intramolecular charge transfer transitions of the molecules,and the reversible mechanochromism properties probably stem from the interconversion of the quasi-axial and the quasi-equatorial conformations.
文摘A gate-to-body tunneling current model for silicon-on-insulator （SOl） devices is simulated. As verified by the mea- sured data, the model, considering both gate voltage and drain voltage dependence as well as image force-induced barrier low effect, provides a better prediction of the tunneling current and gate-induced floating body effect than the BSIMSOI4 model. A delayed gate-induced floating body effect is also predicted by the model.
文摘为了研究无刷直流电机(brushless DC motor,BLDCM)电枢电流对转子温升的影响,提出一种涡流电势分类估算法。将电枢电流分解为直流分量iDC和交流分量iAC,在空间上,运动的转子会在绕组直流分量iDC的磁动势作用下产生运动电势em;同时在时间上,绕组交流分量iAC的磁动势也会在转子中产生感应电势et。暂不考虑涡流反应,对11kW无刷直流电机典型工作点下,选择转子中最大闭合曲线和最大曲面分别计算运动电势em和感应电势et。在不考虑齿槽影响的前提下,得到运动电势远小于感应电势的结论,认为只要电枢电流连续,负载变化对转子温升影响不大。实验结果验证了上述观点。
