Urolithin A(UA)is a natural metabolite produced from polyphenolics in foods such as pomegranates,berries,and nuts.UA is neuroprotective against Parkinson’s disease,Alzheimer’s disease,and cerebral hemorrhage.However...Urolithin A(UA)is a natural metabolite produced from polyphenolics in foods such as pomegranates,berries,and nuts.UA is neuroprotective against Parkinson’s disease,Alzheimer’s disease,and cerebral hemorrhage.However,its effect against traumatic brain injury remains unknown.In this study,we established adult C57BL/6J mouse models of traumatic brain injury by controlled cortical impact and then intraperitoneally administered UA.We found that UA greatly reduced brain edema;increased the expression of tight junction proteins in injured cortex;increased the immunopositivity of two neuronal autophagy markers,microtubule-associated protein 1A/B light chain 3A/B(LC3)and p62;downregulated protein kinase B(Akt)and mammalian target of rapamycin(mTOR),two regulators of the phosphatidylinositol 3-kinase(PI3K)/Akt/mTOR signaling pathway;decreased the phosphorylation levels of inhibitor of NFκB(IκB)kinase alpha(IKKα)and nuclear factor kappa B(NFκB),two regulators of the neuroinflammation-related Akt/IKK/NFκB signaling pathway;reduced blood-brain barrier permeability and neuronal apoptosis in injured cortex;and improved mouse neurological function.These findings suggest that UA may be a candidate drug for the treatment of traumatic brain injury,and its neuroprotective effects may be mediated by inhibition of the PI3K/Akt/mTOR and Akt/IKK/NFκB signaling pathways,thus reducing neuroinflammation and enhancing autophagy.展开更多
We report an electrochemically assisted mechanically controllable break junction （EC-MCBJ） approach to investigating single molecule conductance. Electrode pairs connected with a gold nanobridge were fabricated by e...We report an electrochemically assisted mechanically controllable break junction （EC-MCBJ） approach to investigating single molecule conductance. Electrode pairs connected with a gold nanobridge were fabricated by electrochemical deposition and then mounted on a homebuilt MCBJ platform. A large number of Au- molecule-Au junctions were produced sequentially by repeated breaking and reconnecting of the gold nanobridge. In order to measure their single molecule conductance, statistical conductance histograms were generated for benzene-l,4-dithiol （BDT） and 4,4＇-bipyridine （BPY）. The values extracted from these histograms were found to be in the same range as values previously reported in the literature. Our method is distinct from the ones used to acquire these previously reported literature values, however, in that it is faster, simpler, more cost-effective, and changing the electrode material is more convenient.展开更多
Stimuli-resp on sive release of drugs from a nano carrier in spatial-,temporal-,and dosage-controlled fashi ons is of great interest in the pharmaceutical industry.Paclitaxel is one of the most effective and popular c...Stimuli-resp on sive release of drugs from a nano carrier in spatial-,temporal-,and dosage-controlled fashi ons is of great interest in the pharmaceutical industry.Paclitaxel is one of the most effective and popular chemotherapeutic drugs against a number of cancers such as metastatic or non metastatic breast can cer,non-small cell lung can cer,refractory ovaria n cancer,AIDS-related Kaposi's sarcoma,and head and neck can cers.Here,by taki ng the adva ntage of RNA nanotechno logy in biomedical and material scie nee,we developed a three-dime nsional pyramid-shaped RNA nanocage for a photocontrolled release of cargo,using paclitaxel as a model drug.The light-triggered release of paclitaxel or fluorophore Cy5 was achieved by incorporation of photocleavable spacers into the RNA nanoparticles.Upon irradiation with ultraviolet light,cargos were rapidly released(within 5 min).In vitro treatment of breast can cer cells with the RNA nano particles harbori ng photocleavable paclitaxel showed higher cytotoxicity as compared to RNA nanoparticles without the photocleavable spacer.The methodology provides proof of con cept for the applicati on of the light-triggered con trolled release of drugs from RNA nano cages.展开更多
为了解决软击穿导致的压控磁各向异性磁隧道结(voltage-controlled magnetic anisotropy magnetic tunnel junction,VCMA-MTJ)及其读电路性能下降的问题,在对VCMA-MTJ软击穿机理深入分析的基础上,修正了VCMA-MTJ的电学模型,设计了一种...为了解决软击穿导致的压控磁各向异性磁隧道结(voltage-controlled magnetic anisotropy magnetic tunnel junction,VCMA-MTJ)及其读电路性能下降的问题,在对VCMA-MTJ软击穿机理深入分析的基础上,修正了VCMA-MTJ的电学模型,设计了一种具有固定参考电阻的VCMA-MTJ读电路和一种具有参考电阻调控单元的VCMA-MTJ读电路,研究了软击穿对VCMA-MTJ电阻R_(t)、隧穿磁阻比率M、软击穿时间T_(s)以及VCMA-MTJ读电路读错误率的影响。结果表明:软击穿的出现会导致R_(t)和M均随应力时间t的增加而降低,T_(s)随氧化层厚度t_(ox)的增大而缓慢增加,却随脉冲电压V_(b)的增大而迅速减少,与反平行态相比,平行态的T_(s)更短且M降低50%所需时间更少;具有固定参考电阻的VCMA-MTJ读电路可有效避免读“0”错误率的产生,但读“1”错误率却随t的增加而上升,而具有参考电阻调控单元的VCMA-MTJ读电路可在保持读“0”正确率的同时,对读“1”错误率改善达54%,在一定程度上削弱了软击穿对VCMA-MTJ读电路的影响。展开更多
Plasmonic optical manipulation has emerged as an affordable alternative to manipulate single chemical and biological molecules in nanoscience.Although the theoretical models of sub-5 nm single-molecule trapping have b...Plasmonic optical manipulation has emerged as an affordable alternative to manipulate single chemical and biological molecules in nanoscience.Although the theoretical models of sub-5 nm single-molecule trapping have been considered promising,the experimental strategies remain a challenge due to the Brownian motions and weak optical gradient forces with significantly reduced molecular polarizability.Herein,we address direct trapping and in situ sensing of single molecules with unprecedented size,down to∼5Åin solution,by employing an adjustable plasmonic optical nanogap and single-molecule conductance measurement.The theoretical simulations demonstrate that local fields with a high enhancement factor,over 103,were generated at such small nanogaps,resulting in optical forces as large as several piconewtons to suppress the Brownian motion and trap a molecule of length sub-1 nm.This work demonstrates a strategy for directly manipulating the small molecule units,promising a vast multitude of applications in chemical,biological,and materials sciences at the single-molecule level.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81974189(to HLT),81801236(to QYG and LC),82001310(to DXY).
文摘Urolithin A(UA)is a natural metabolite produced from polyphenolics in foods such as pomegranates,berries,and nuts.UA is neuroprotective against Parkinson’s disease,Alzheimer’s disease,and cerebral hemorrhage.However,its effect against traumatic brain injury remains unknown.In this study,we established adult C57BL/6J mouse models of traumatic brain injury by controlled cortical impact and then intraperitoneally administered UA.We found that UA greatly reduced brain edema;increased the expression of tight junction proteins in injured cortex;increased the immunopositivity of two neuronal autophagy markers,microtubule-associated protein 1A/B light chain 3A/B(LC3)and p62;downregulated protein kinase B(Akt)and mammalian target of rapamycin(mTOR),two regulators of the phosphatidylinositol 3-kinase(PI3K)/Akt/mTOR signaling pathway;decreased the phosphorylation levels of inhibitor of NFκB(IκB)kinase alpha(IKKα)and nuclear factor kappa B(NFκB),two regulators of the neuroinflammation-related Akt/IKK/NFκB signaling pathway;reduced blood-brain barrier permeability and neuronal apoptosis in injured cortex;and improved mouse neurological function.These findings suggest that UA may be a candidate drug for the treatment of traumatic brain injury,and its neuroprotective effects may be mediated by inhibition of the PI3K/Akt/mTOR and Akt/IKK/NFκB signaling pathways,thus reducing neuroinflammation and enhancing autophagy.
文摘We report an electrochemically assisted mechanically controllable break junction （EC-MCBJ） approach to investigating single molecule conductance. Electrode pairs connected with a gold nanobridge were fabricated by electrochemical deposition and then mounted on a homebuilt MCBJ platform. A large number of Au- molecule-Au junctions were produced sequentially by repeated breaking and reconnecting of the gold nanobridge. In order to measure their single molecule conductance, statistical conductance histograms were generated for benzene-l,4-dithiol （BDT） and 4,4＇-bipyridine （BPY）. The values extracted from these histograms were found to be in the same range as values previously reported in the literature. Our method is distinct from the ones used to acquire these previously reported literature values, however, in that it is faster, simpler, more cost-effective, and changing the electrode material is more convenient.
文摘Stimuli-resp on sive release of drugs from a nano carrier in spatial-,temporal-,and dosage-controlled fashi ons is of great interest in the pharmaceutical industry.Paclitaxel is one of the most effective and popular chemotherapeutic drugs against a number of cancers such as metastatic or non metastatic breast can cer,non-small cell lung can cer,refractory ovaria n cancer,AIDS-related Kaposi's sarcoma,and head and neck can cers.Here,by taki ng the adva ntage of RNA nanotechno logy in biomedical and material scie nee,we developed a three-dime nsional pyramid-shaped RNA nanocage for a photocontrolled release of cargo,using paclitaxel as a model drug.The light-triggered release of paclitaxel or fluorophore Cy5 was achieved by incorporation of photocleavable spacers into the RNA nanoparticles.Upon irradiation with ultraviolet light,cargos were rapidly released(within 5 min).In vitro treatment of breast can cer cells with the RNA nano particles harbori ng photocleavable paclitaxel showed higher cytotoxicity as compared to RNA nanoparticles without the photocleavable spacer.The methodology provides proof of con cept for the applicati on of the light-triggered con trolled release of drugs from RNA nano cages.
文摘为了解决软击穿导致的压控磁各向异性磁隧道结(voltage-controlled magnetic anisotropy magnetic tunnel junction,VCMA-MTJ)及其读电路性能下降的问题,在对VCMA-MTJ软击穿机理深入分析的基础上,修正了VCMA-MTJ的电学模型,设计了一种具有固定参考电阻的VCMA-MTJ读电路和一种具有参考电阻调控单元的VCMA-MTJ读电路,研究了软击穿对VCMA-MTJ电阻R_(t)、隧穿磁阻比率M、软击穿时间T_(s)以及VCMA-MTJ读电路读错误率的影响。结果表明:软击穿的出现会导致R_(t)和M均随应力时间t的增加而降低,T_(s)随氧化层厚度t_(ox)的增大而缓慢增加,却随脉冲电压V_(b)的增大而迅速减少,与反平行态相比,平行态的T_(s)更短且M降低50%所需时间更少;具有固定参考电阻的VCMA-MTJ读电路可有效避免读“0”错误率的产生,但读“1”错误率却随t的增加而上升,而具有参考电阻调控单元的VCMA-MTJ读电路可在保持读“0”正确率的同时,对读“1”错误率改善达54%,在一定程度上削弱了软击穿对VCMA-MTJ读电路的影响。
基金supported by the National Natural Science Foundation of China(grant nos.T2222002,21973079,22032004,92161118,12174324,21991130,and 21905238)the Ministry of Science and Technology of the People’s Republic of China(grant no.2021YFA1201502)the Natural Science Foundation of Fujian Province(grant no.2021J06008).
文摘Plasmonic optical manipulation has emerged as an affordable alternative to manipulate single chemical and biological molecules in nanoscience.Although the theoretical models of sub-5 nm single-molecule trapping have been considered promising,the experimental strategies remain a challenge due to the Brownian motions and weak optical gradient forces with significantly reduced molecular polarizability.Herein,we address direct trapping and in situ sensing of single molecules with unprecedented size,down to∼5Åin solution,by employing an adjustable plasmonic optical nanogap and single-molecule conductance measurement.The theoretical simulations demonstrate that local fields with a high enhancement factor,over 103,were generated at such small nanogaps,resulting in optical forces as large as several piconewtons to suppress the Brownian motion and trap a molecule of length sub-1 nm.This work demonstrates a strategy for directly manipulating the small molecule units,promising a vast multitude of applications in chemical,biological,and materials sciences at the single-molecule level.
