The mammalian target of rapamycin （mTOR） pathway is essential for maintenance of the sensitivity of certain adult sensory neurons. Here, we investigated whether the mTOR cascade is involved in scorpion envenomation-...The mammalian target of rapamycin （mTOR） pathway is essential for maintenance of the sensitivity of certain adult sensory neurons. Here, we investigated whether the mTOR cascade is involved in scorpion envenomation-induced pain hypersensitivity in rats. The results showed that intraplantar injection of a neurotoxin from Buthus martensii Karsch, BmK I （10 pg）, induced the activation of mTOR, as well as its downstream molecules p70 ribosomal S6 protein kinase （p70 S6K） and eukaryotic initiation factor 4E-binding protein 1 （4E-BP1）, in lumbar 5-6 dorsal root ganglia neurons on both sides in rats. The activation peaked at 2 h and recovered 1 day after injection. Compared with the control group, the ratios of p-mTOR/p-p70 S6K/p-4E- BP1 in three types of neurons changed significantly. The cell typology of p-mTOR/p-p70 S6K/p-4E-BP1 immuno-reactive neurons also changed. Intrathecal administration of deforolimus, a specific inhibitor of mTOR, attenuated BmK I-induced pain responses （spontaneous flinching, paroxysmal pain-like behavior, and mechanical hypersensitivity）. Together, these results imply that the mTOR signaling pathway is mobilized by and contributes to experimental scorpion sting-induced pain.展开更多
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
Ultrafine silver fiber is an alternative to commercial indium tin oxide(ITO) as a new-generation flexible transparent conductor that can be used in flexible electronics.However,its primary limitation is the unrepeatab...Ultrafine silver fiber is an alternative to commercial indium tin oxide(ITO) as a new-generation flexible transparent conductor that can be used in flexible electronics.However,its primary limitation is the unrepeatable optoelectronic properties due to the disordered distribution of silver fibers.In this work,we report the in-situ direct writing of the silver microfiber pattern with high conductivity and transparency to attain a flexible transparent conductor.The silver network is composed of silver microfibers,which can be artificially designed and regularly patterned under the precise control of the fiber position and shape;this is crucial for regulating its optoelectronic properties.Herein,a high-performance conductor is achieved in the silver network with high stability.This novel conductor has a sheet resistance of 2 Ω sq-1at 90% transparency,which corre sponds to a high Figure of merit σdc/σopt=1742.The in-situ direct writing technique developed here is distinct from other fabrication methods because it requires no transfer steps,templates or heating.Further,this silver network is integrated into a light-printable rewritable device,and can be used as a wearable heater;this heater when driven by a 1.5 V battery attains a temperature of up to 55.6℃.Therefore,in-situ direct writing is expected to offer a new platform for facile,scalable,and ultralow-cost production of high-performance metal networks for flexible transparent conductors.展开更多
Voltage-gated sodium channels （VGSCs） in primary sensory neurons play a key role in transmitting pain signals to the central nervous system. BmK I, a site-3 sodium channel-specific toxin from scorpion Buthus martens...Voltage-gated sodium channels （VGSCs） in primary sensory neurons play a key role in transmitting pain signals to the central nervous system. BmK I, a site-3 sodium channel-specific toxin from scorpion Buthus martensi Karsch, induces pain behaviors in rats. How- ever, the subtypes of VGSCs targeted by BmK I were not entirely clear. We therefore investigated the effects of BmK I on the current amplitude, gating and kinetic properties of Nav1.8, which is associated with neuronal hyperexcitability in DRG neurons. It was found that BmK I dose-dependently increased Nav1.8 current in small- sized （〈25 μm） acutely dissociated DRG neurons, which correlated with its inhibition on both fast and slow in- activation. Moreover, voltage-dependent activation and steady-state inactivation curves of Nay1.8 were shifted in a hyperpolarized direction. Thus, BmK I reduced the threshold of neuronal excitability and increased action potential firing in DRG neurons. In conclusion, our data clearly demonstrated that BmK I modulated Nav1.8 re- markably, suggesting BmK I as a valuable probe for studying Nay1.8. And Navl.8 is an important target re- lated to BmK I-evoked pain.展开更多
Diverse subtypes of voltage-gated sodium channels(VGSCs)have been found throughout tissues of the brain,muscles and the heart.Neurotoxins extracted from the venom of the Asian scorpion Buthus martensi Karsch(BmK)act a...Diverse subtypes of voltage-gated sodium channels(VGSCs)have been found throughout tissues of the brain,muscles and the heart.Neurotoxins extracted from the venom of the Asian scorpion Buthus martensi Karsch(BmK)act as sodium channel-specific modulators and have therefore been widely used to study VGSCs.α-type neurotoxins,named BmK I,BmKαIV and BmK abT,bind to receptor site-3 on VGSCs and can strongly prolong the inactivation phase of VGSCs.In contrast,β-type neurotoxins,named BmK AS,BmK AS-1,BmK IT and BmK IT2,occupy receptor site-4 on VGSCs and can suppress peak currents and hyperpolarize the activation kinetics of sodium channels.Accumulating evidence from binding assays of scorpion neurotoxins on VGSCs,however,indicate that pharmacological sensitivity of VGSC subtypes to different modulators is much more complex than that suggested by the simpleα-type and β-type neurotoxin distinction.Exploring the mechanisms of possible dynamic interactions between site 3-/4-specific modulators and region-and/or speciesspecific subtypes of VGSCs would therefore greatly expand our understanding of the physiological and pharmacological properties of diverse VGSCs.In this review,we discuss the pharmacological and structural diversity of VGSCs as revealed by studies exploring the binding properties and cross-competitive binding of site 3-or site 4-specific modulators in VGSC subtypes in synaptosomes from distinct tissues of diverse species.展开更多
基金supported by grants from the National Basic Research Development Program of China(2010CB529806)the National Natural Science Foundation of China(31171064)+2 种基金the Shanghai Science and Technology CommissionChina(11JC140430010411956700 and 124119b0600)
文摘The mammalian target of rapamycin （mTOR） pathway is essential for maintenance of the sensitivity of certain adult sensory neurons. Here, we investigated whether the mTOR cascade is involved in scorpion envenomation-induced pain hypersensitivity in rats. The results showed that intraplantar injection of a neurotoxin from Buthus martensii Karsch, BmK I （10 pg）, induced the activation of mTOR, as well as its downstream molecules p70 ribosomal S6 protein kinase （p70 S6K） and eukaryotic initiation factor 4E-binding protein 1 （4E-BP1）, in lumbar 5-6 dorsal root ganglia neurons on both sides in rats. The activation peaked at 2 h and recovered 1 day after injection. Compared with the control group, the ratios of p-mTOR/p-p70 S6K/p-4E- BP1 in three types of neurons changed significantly. The cell typology of p-mTOR/p-p70 S6K/p-4E-BP1 immuno-reactive neurons also changed. Intrathecal administration of deforolimus, a specific inhibitor of mTOR, attenuated BmK I-induced pain responses （spontaneous flinching, paroxysmal pain-like behavior, and mechanical hypersensitivity）. Together, these results imply that the mTOR signaling pathway is mobilized by and contributes to experimental scorpion sting-induced pain.
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.
基金supported by National MCF Energy R&D Program(No.2018YFE0313300)Young Elite Scientists Sponsorship Program by CAST(No.2017QNRC001)+2 种基金the National Natural Science Foundation of China(No.51402116)the Fundamental Research Funds for the Central Universities(Nos.2018KFYYXJJ028and 2019KFYXMBZ045)the Analytical and Testing Center of Huazhong University of Science and Technology for support。
文摘Ultrafine silver fiber is an alternative to commercial indium tin oxide(ITO) as a new-generation flexible transparent conductor that can be used in flexible electronics.However,its primary limitation is the unrepeatable optoelectronic properties due to the disordered distribution of silver fibers.In this work,we report the in-situ direct writing of the silver microfiber pattern with high conductivity and transparency to attain a flexible transparent conductor.The silver network is composed of silver microfibers,which can be artificially designed and regularly patterned under the precise control of the fiber position and shape;this is crucial for regulating its optoelectronic properties.Herein,a high-performance conductor is achieved in the silver network with high stability.This novel conductor has a sheet resistance of 2 Ω sq-1at 90% transparency,which corre sponds to a high Figure of merit σdc/σopt=1742.The in-situ direct writing technique developed here is distinct from other fabrication methods because it requires no transfer steps,templates or heating.Further,this silver network is integrated into a light-printable rewritable device,and can be used as a wearable heater;this heater when driven by a 1.5 V battery attains a temperature of up to 55.6℃.Therefore,in-situ direct writing is expected to offer a new platform for facile,scalable,and ultralow-cost production of high-performance metal networks for flexible transparent conductors.
基金J.Y.H was supported by the National Basic Research Program （973 Program） （No. 2010CB529806）, partially by grants from National Nat- ural Science Foundation of China （Grant Nos. 31171064 and 81402903） and Key Research Program of Science and Technology Commissions of Shanghai Municipality （11JC1404300, 13DJ 1400300）. L.T. was supported by grants from National Natural Science Foundation of China （Grant Nos. 31371179 and 81300968） and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Voltage-gated sodium channels （VGSCs） in primary sensory neurons play a key role in transmitting pain signals to the central nervous system. BmK I, a site-3 sodium channel-specific toxin from scorpion Buthus martensi Karsch, induces pain behaviors in rats. How- ever, the subtypes of VGSCs targeted by BmK I were not entirely clear. We therefore investigated the effects of BmK I on the current amplitude, gating and kinetic properties of Nav1.8, which is associated with neuronal hyperexcitability in DRG neurons. It was found that BmK I dose-dependently increased Nav1.8 current in small- sized （〈25 μm） acutely dissociated DRG neurons, which correlated with its inhibition on both fast and slow in- activation. Moreover, voltage-dependent activation and steady-state inactivation curves of Nay1.8 were shifted in a hyperpolarized direction. Thus, BmK I reduced the threshold of neuronal excitability and increased action potential firing in DRG neurons. In conclusion, our data clearly demonstrated that BmK I modulated Nav1.8 re- markably, suggesting BmK I as a valuable probe for studying Nay1.8. And Navl.8 is an important target re- lated to BmK I-evoked pain.
基金supported by the National Basic Research Program of China(Grant Nos.1999054001,2006CB500801,and 2010CB529806)partially by grants from Key discipline“Molecular Physiology”of Shanghai Education Committee.
文摘Diverse subtypes of voltage-gated sodium channels(VGSCs)have been found throughout tissues of the brain,muscles and the heart.Neurotoxins extracted from the venom of the Asian scorpion Buthus martensi Karsch(BmK)act as sodium channel-specific modulators and have therefore been widely used to study VGSCs.α-type neurotoxins,named BmK I,BmKαIV and BmK abT,bind to receptor site-3 on VGSCs and can strongly prolong the inactivation phase of VGSCs.In contrast,β-type neurotoxins,named BmK AS,BmK AS-1,BmK IT and BmK IT2,occupy receptor site-4 on VGSCs and can suppress peak currents and hyperpolarize the activation kinetics of sodium channels.Accumulating evidence from binding assays of scorpion neurotoxins on VGSCs,however,indicate that pharmacological sensitivity of VGSC subtypes to different modulators is much more complex than that suggested by the simpleα-type and β-type neurotoxin distinction.Exploring the mechanisms of possible dynamic interactions between site 3-/4-specific modulators and region-and/or speciesspecific subtypes of VGSCs would therefore greatly expand our understanding of the physiological and pharmacological properties of diverse VGSCs.In this review,we discuss the pharmacological and structural diversity of VGSCs as revealed by studies exploring the binding properties and cross-competitive binding of site 3-or site 4-specific modulators in VGSC subtypes in synaptosomes from distinct tissues of diverse species.
