Stent implantation has been proven to be safe and has become the first-line intervention for May-Thumer syndrome(MTS),with satisfactory mid-term patency rates and clinical outcomes.Recent research has demonstrated tha...Stent implantation has been proven to be safe and has become the first-line intervention for May-Thumer syndrome(MTS),with satisfactory mid-term patency rates and clinical outcomes.Recent research has demonstrated that catheter-directed thrombolysis is the preferred strategy when MTS is combined with deep vein thrombosis after self-expanding stent placement.However,the stent used for the venous system was developed based on the experience obtained in the treatment of arterial disease.Consequently,relatively common corresponding complications may come along later,which include stent displacement,deformation,and obstruction.Different measures such as adopting a stent with a larger diameter,improving stent flexibility,and increasing stent strength have been employed in order to prevent these complications.The ideal venous stent is presently being evaluated and will be introduced in detail in this review.展开更多
Reconstitution of complex multi-tissue organs is one of the most impressive feats of biology and is observed across regeneration-competent vertebrate species,including teleost fish(e.g.,zebrafish),urodeles(e.g.,axolot...Reconstitution of complex multi-tissue organs is one of the most impressive feats of biology and is observed across regeneration-competent vertebrate species,including teleost fish(e.g.,zebrafish),urodeles(e.g.,axolotls and newts),and some lizards.Regenerative ability within these species ranges from muscle(including cardiac),skeletal structures,to complex systems such as the brain,spinal cord and parts of the eye which are all capable of structural and functional repair following injury(Tanaka and Ferretti,2009).In stark contrast,re-establishment of multi-tissue structures is very rarely observed following embryogenesis in regeneration-incompetent mammals.Regrowth of digit tips is the most dramatic example of mammalian regeneration,but pales in comparison to other species in the animal kingdom.Undoubtedly,a complete recapitulation of complex organs or structures in mammals will remain out of reach for a considerable time;however,an improved understanding of regenerat i ve mechanisms would likely enhance the development of novel regenerative medicine strategies.Here we focus on the diversity and commonalities of stem cells,which could underlie complex tissue regeneration.展开更多
Homeostasis of dopamine,a classical neurotransmitter,is a key indicator of neuronal health.Dysfunction in the regulation of dopamine is implicated in a long list of neurological disorders,including addiction,depressio...Homeostasis of dopamine,a classical neurotransmitter,is a key indicator of neuronal health.Dysfunction in the regulation of dopamine is implicated in a long list of neurological disorders,including addiction,depression,and neurodegeneration.The existing methods used to evaluate dopamine homeostasis in vitro are inconvenient and do not allow for continuous non-destructive measurement.In response to this challenge,we introduce an integrated microfluidic system that combines dopaminergic cell culture and differentiation with electroanalytical measurements of extracellular dopamine in real-time at any point during an assay.We used the system to examine the behavior of differentiated SH-SY5Y cells upon exposure to four dopamine transporter ant/agonists(cocaine,ketamine,epigallocatechin gallate,and amphetamine)and study their pharmacokinetics.The IC_(50)values of cocaine,ketamine,and epigallocatechin gallate were determined to be(average±standard deviation)3.7±1.1μM,51.4±17.9μM,and 2.6±0.8μM,respectively.Furthermore,we used the new system to study amphetamine-mediated dopamine release to probe the related phenomena of dopamine transporter-mediated reverse-transport and dopamine release from vesicles.We propose that this platform,which is the first platform to simultaneously evaluate uptake and release,could be useful to screen for drugs and other agents that target dopaminergic neurons and the function of the dopamine transporter.More broadly,this platform should be adaptable for any application that could benefit from high-temporal resolution electroanalysis combined with multi-day cell culture using small numbers of cells.展开更多
Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells c...Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be changed.An exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.展开更多
Synechocystis sp.PCC 6803(hereafter:Synechocystis)is a model organism for studying photosynthesis,energy metabolism,and environmental stress.Although known as the first fully sequenced phototrophic organism,Synechocys...Synechocystis sp.PCC 6803(hereafter:Synechocystis)is a model organism for studying photosynthesis,energy metabolism,and environmental stress.Although known as the first fully sequenced phototrophic organism,Synechocystis still has almost half of its proteome without functional annotations.In this study,by using co-fractionation coupled with liquid chromatographytandem mass spectrometry(LC-MS/MS),we define 291 multi-protein complexes,encompassing24,092 protein±protein interactions(PPIs)among 2062 distinct gene products.This information not only reveals the roles of photosynthesis in metabolism,cell motility,DNA repair,cell division,and other physiological processes,but also shows how protein functions vary from bacteria to higher plants due to changes in interaction partners.It also allows us to uncover the functions of hypothetical proteins,such as Sll0445,Sll0446,and Sll0447 involved in photosynthesis and cell motility,and Sll1334 involved in regulation of fatty acid biogenesis.Here we present the most extensive PPI data for Synechocystis so far,which provide critical insights into fundamental molecular mechanisms in cyanobacteria.展开更多
Correction to:Microsystems&Nanoengineering(2019)5:10 https://doi.org/10.1038/s41378-019-0049-2 published online:11 March 2019 The legend in Fig.4a in the previously published version of this article contained erro...Correction to:Microsystems&Nanoengineering(2019)5:10 https://doi.org/10.1038/s41378-019-0049-2 published online:11 March 2019 The legend in Fig.4a in the previously published version of this article contained erroneous units.The correct units are given in the caption–that is,1μM(black),500 nM(red),100 nM(blue),50 nM(cyan),10 nM(pink),and 0 nM(1×PBS solution,brown).展开更多
Optoelectronic tweezer(OET) is a useful optical micromanipulation technology that has been demonstrated for various applications in electrical engineering and most notably cell selection for biomedical engineering. In...Optoelectronic tweezer(OET) is a useful optical micromanipulation technology that has been demonstrated for various applications in electrical engineering and most notably cell selection for biomedical engineering. In this work, we studied the use of light patterns with different shapes and thicknesses to manipulate dielectric microparticles with OET. It was demonstrated that the maximum velocities of the microparticles increase to a peak and then gradually decrease as the light pattern’s thickness increases. Numerical simulations were run to clarify the underlying physical mechanisms, and it was found that the observed phenomenon is due to the co-influence of horizontal and vertical dielectrophoresis forces related to the light pattern’s thickness. Further experiments were run on light patterns with different shapes and objects with different sizes and structures. The experimental results indicate that the physical mechanism elucidated in this research is an important one that applies to different light pattern shapes and different objects, which is useful for enabling users to optimize OET settings for future micromanipulation applications.展开更多
Background:SOX transcription factors constitute an attractive target class for intervention with small molecules as they play a prominent role in the field of regenerative biomedicine and cancer biology.However,ration...Background:SOX transcription factors constitute an attractive target class for intervention with small molecules as they play a prominent role in the field of regenerative biomedicine and cancer biology.However,rationally engineering specific inhibitors that interfere with transcription factor DNA interfaces continues to be a monumental challenge in the field of transcription factor chemical biology.Polyoxometalates(POMs)are inorganic compounds that were previously shown to target the high-mobility group(HMG)of SOX proteins at nanomolar concentrations.In continuation of this work,we carried out an assessment of the selectivity of a panel of newly synthesized organo-polyoxometalate hybrids in targeting different transcription factor families to enable the usage of polyoxometalates as specific SOX transcription factor drugs.Results:The residual DNA-binding activities of 15 different transcription factors were measured after treatment with a panel of diverse polyoxometalates.Polyoxometalates belonging to the Dawson structural class were found to be more potent inhibitors than the Keggin class.Further,organically modified Dawson polyoxometalates were found to be the most potent in inhibiting transcription factor DNA binding activity.The size of the polyoxometalates and its derivitization were found to be the key determinants of their potency.Conclusion:Polyoxometalates are highly potent,nanomolar range inhibitors of the DNA binding activity of the Sox-HMG family.However,binding assays involving a limited subset of structurally diverse polyoxometalates revealed a low selectivity profile against different transcription factor families.Further progress in achieving selectivity and deciphering structure-activity relationship of POMs require the identification of POM binding sites on transcription factors using elaborate approaches like X-ray crystallography and multidimensional NMR.In summary,our report reaffirms that transcription factors are challenging molecular architectures and that future polyoxometalate chemistry must consider further modification strategies,to address the substantial challenges involved in achieving target selectivity.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81670512 and No.81101042)the Natural Science Foundation of Hubei Province,China(No.2016CFB378).
文摘Stent implantation has been proven to be safe and has become the first-line intervention for May-Thumer syndrome(MTS),with satisfactory mid-term patency rates and clinical outcomes.Recent research has demonstrated that catheter-directed thrombolysis is the preferred strategy when MTS is combined with deep vein thrombosis after self-expanding stent placement.However,the stent used for the venous system was developed based on the experience obtained in the treatment of arterial disease.Consequently,relatively common corresponding complications may come along later,which include stent displacement,deformation,and obstruction.Different measures such as adopting a stent with a larger diameter,improving stent flexibility,and increasing stent strength have been employed in order to prevent these complications.The ideal venous stent is presently being evaluated and will be introduced in detail in this review.
文摘Reconstitution of complex multi-tissue organs is one of the most impressive feats of biology and is observed across regeneration-competent vertebrate species,including teleost fish(e.g.,zebrafish),urodeles(e.g.,axolotls and newts),and some lizards.Regenerative ability within these species ranges from muscle(including cardiac),skeletal structures,to complex systems such as the brain,spinal cord and parts of the eye which are all capable of structural and functional repair following injury(Tanaka and Ferretti,2009).In stark contrast,re-establishment of multi-tissue structures is very rarely observed following embryogenesis in regeneration-incompetent mammals.Regrowth of digit tips is the most dramatic example of mammalian regeneration,but pales in comparison to other species in the animal kingdom.Undoubtedly,a complete recapitulation of complex organs or structures in mammals will remain out of reach for a considerable time;however,an improved understanding of regenerat i ve mechanisms would likely enhance the development of novel regenerative medicine strategies.Here we focus on the diversity and commonalities of stem cells,which could underlie complex tissue regeneration.
基金which is supported by the Canada First Research Excellence Fund(CFREF)for funding。
文摘Homeostasis of dopamine,a classical neurotransmitter,is a key indicator of neuronal health.Dysfunction in the regulation of dopamine is implicated in a long list of neurological disorders,including addiction,depression,and neurodegeneration.The existing methods used to evaluate dopamine homeostasis in vitro are inconvenient and do not allow for continuous non-destructive measurement.In response to this challenge,we introduce an integrated microfluidic system that combines dopaminergic cell culture and differentiation with electroanalytical measurements of extracellular dopamine in real-time at any point during an assay.We used the system to examine the behavior of differentiated SH-SY5Y cells upon exposure to four dopamine transporter ant/agonists(cocaine,ketamine,epigallocatechin gallate,and amphetamine)and study their pharmacokinetics.The IC_(50)values of cocaine,ketamine,and epigallocatechin gallate were determined to be(average±standard deviation)3.7±1.1μM,51.4±17.9μM,and 2.6±0.8μM,respectively.Furthermore,we used the new system to study amphetamine-mediated dopamine release to probe the related phenomena of dopamine transporter-mediated reverse-transport and dopamine release from vesicles.We propose that this platform,which is the first platform to simultaneously evaluate uptake and release,could be useful to screen for drugs and other agents that target dopaminergic neurons and the function of the dopamine transporter.More broadly,this platform should be adaptable for any application that could benefit from high-temporal resolution electroanalysis combined with multi-day cell culture using small numbers of cells.
基金supported by Canada First Research Excellence Fund,Medicine by Design(to CMM)。
文摘Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be changed.An exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.
文摘Synechocystis sp.PCC 6803(hereafter:Synechocystis)is a model organism for studying photosynthesis,energy metabolism,and environmental stress.Although known as the first fully sequenced phototrophic organism,Synechocystis still has almost half of its proteome without functional annotations.In this study,by using co-fractionation coupled with liquid chromatographytandem mass spectrometry(LC-MS/MS),we define 291 multi-protein complexes,encompassing24,092 protein±protein interactions(PPIs)among 2062 distinct gene products.This information not only reveals the roles of photosynthesis in metabolism,cell motility,DNA repair,cell division,and other physiological processes,but also shows how protein functions vary from bacteria to higher plants due to changes in interaction partners.It also allows us to uncover the functions of hypothetical proteins,such as Sll0445,Sll0446,and Sll0447 involved in photosynthesis and cell motility,and Sll1334 involved in regulation of fatty acid biogenesis.Here we present the most extensive PPI data for Synechocystis so far,which provide critical insights into fundamental molecular mechanisms in cyanobacteria.
文摘Correction to:Microsystems&Nanoengineering(2019)5:10 https://doi.org/10.1038/s41378-019-0049-2 published online:11 March 2019 The legend in Fig.4a in the previously published version of this article contained erroneous units.The correct units are given in the caption–that is,1μM(black),500 nM(red),100 nM(blue),50 nM(cyan),10 nM(pink),and 0 nM(1×PBS solution,brown).
基金National Natural Science Foundation of China(11774437, 61975243, 62103050)Natural Sciences and Engineering Research Council of Canada (ALLRP 548593-19,CREATE 482073-16, RGPIN 2019-04867, RTI-2019-00300)。
文摘Optoelectronic tweezer(OET) is a useful optical micromanipulation technology that has been demonstrated for various applications in electrical engineering and most notably cell selection for biomedical engineering. In this work, we studied the use of light patterns with different shapes and thicknesses to manipulate dielectric microparticles with OET. It was demonstrated that the maximum velocities of the microparticles increase to a peak and then gradually decrease as the light pattern’s thickness increases. Numerical simulations were run to clarify the underlying physical mechanisms, and it was found that the observed phenomenon is due to the co-influence of horizontal and vertical dielectrophoresis forces related to the light pattern’s thickness. Further experiments were run on light patterns with different shapes and objects with different sizes and structures. The experimental results indicate that the physical mechanism elucidated in this research is an important one that applies to different light pattern shapes and different objects, which is useful for enabling users to optimize OET settings for future micromanipulation applications.
基金Work was supported by the Agency for Science,Technology and Research(A*STAR)Singapore.R.J.is supported by the people’s government of Guangzhou municipality Science&Technology Project 2011Y2-00026We also thank ANR(grant 08-PCVI-0005),UPMC and CNRS for fundingThe code number of Institut Parisien de Chimie Moléculaire was UMR7201 when K.M.and E.L.were present.
文摘Background:SOX transcription factors constitute an attractive target class for intervention with small molecules as they play a prominent role in the field of regenerative biomedicine and cancer biology.However,rationally engineering specific inhibitors that interfere with transcription factor DNA interfaces continues to be a monumental challenge in the field of transcription factor chemical biology.Polyoxometalates(POMs)are inorganic compounds that were previously shown to target the high-mobility group(HMG)of SOX proteins at nanomolar concentrations.In continuation of this work,we carried out an assessment of the selectivity of a panel of newly synthesized organo-polyoxometalate hybrids in targeting different transcription factor families to enable the usage of polyoxometalates as specific SOX transcription factor drugs.Results:The residual DNA-binding activities of 15 different transcription factors were measured after treatment with a panel of diverse polyoxometalates.Polyoxometalates belonging to the Dawson structural class were found to be more potent inhibitors than the Keggin class.Further,organically modified Dawson polyoxometalates were found to be the most potent in inhibiting transcription factor DNA binding activity.The size of the polyoxometalates and its derivitization were found to be the key determinants of their potency.Conclusion:Polyoxometalates are highly potent,nanomolar range inhibitors of the DNA binding activity of the Sox-HMG family.However,binding assays involving a limited subset of structurally diverse polyoxometalates revealed a low selectivity profile against different transcription factor families.Further progress in achieving selectivity and deciphering structure-activity relationship of POMs require the identification of POM binding sites on transcription factors using elaborate approaches like X-ray crystallography and multidimensional NMR.In summary,our report reaffirms that transcription factors are challenging molecular architectures and that future polyoxometalate chemistry must consider further modification strategies,to address the substantial challenges involved in achieving target selectivity.