Background:Parkinson's disease(PD)is a progressive neurodegenerative disorder affecting a large number of elderly people worldwide.The current therapies for PD are symptom-based;they do not provide a cure but impr...Background:Parkinson's disease(PD)is a progressive neurodegenerative disorder affecting a large number of elderly people worldwide.The current therapies for PD are symptom-based;they do not provide a cure but improve the quality of life.Muscular dysfunction is the hallmark clinical feature of PD and oxidative stress and inflammation play a critical role in its pathogenesis.Epalrestat is used for the treatment of diabetic neuropathy and is known to improve antioxidative defense mechanisms in the CNS.Therefore,in this study,we investigated the role of Epalrestat in the reserpine induced mouse model of PD.Method:We used Swiss Albino mice for the PD model and tested for akinesia/bradykinesia,muscular rigidity,palpebral ptosis,and tremor,as well as conducting swim and open field tests.Brain samples were used to determine oxidative stress parameters and infiltration of immune cells.Results:Epalrestat treatment significantly improved akinesia and bradykinesia,muscular dysfunctions,tremor level,and gait functions compared to the reserpine group.It also improved the latency in the swim test.Eplarestat significantly reduced lipid peroxidation and NO concentration in different brain tissues and increased the activity of antioxidative enzymes,glutathione,catalase,and superoxide dismutase.Furthermore,Epalrestat reduced neuroinflammation by reducing the number of infiltrating immune cells.Conclusion:Eplarestat improves muscular dysfunction in PD by reducing oxidative stress and inflammation.展开更多
Serine integrases have been shown to be efficient tools for metabolic pathway assembly.To further improve the flexibility and efficiency of pathway engineering via serine integrases,we explored how multiple orthogonal...Serine integrases have been shown to be efficient tools for metabolic pathway assembly.To further improve the flexibility and efficiency of pathway engineering via serine integrases,we explored how multiple orthogonally active serine integrases can be applied for use in vitro for the heterologous expression of complex biosynthesis pathways in Streptomyces spp.,the major producers of useful bioactive natural products.The results show that multiple orthogonal serine integrases efficiently assemble the genes from a complex biosynthesis pathway in a single in vitro recombination reaction,potentially permitting a versatile combinatorial assembly approach.Furthermore,the assembly strategy also permitted the incorporation of a well-characterised promoter upstream of each gene for expression in a heterologous host.The results demonstrate how site-specific recombination based on orthogonal serine integrases can be applied in Streptomyces spp.展开更多
Silicon is a low price and high capacity ancxje material for lithium-ion batteries.The yolk-shell structure can effectively accommodate Si expansion to improve stability.However,the limited rate performance of Si anod...Silicon is a low price and high capacity ancxje material for lithium-ion batteries.The yolk-shell structure can effectively accommodate Si expansion to improve stability.However,the limited rate performance of Si anodes can't meet people's growing demand for high power density.Herein,the phosphorus-doped yolk-shell Si@C materials(P-doped Si@C)were prepared through carbon coating on P-doped Si/SiO_(x)matrix to obtain high power and stable devices.Therefore,the as-prepared P-doped Si@C electrodes delivered a rapid increase in Coulombic efficiency from 74.4%to 99.6%after only 6 cycles,high capacity retention of-95%over 800 cycles at 4 A·g^(-1),and great rate capability(510 mAh·g^(-1)at 35 A·g^(-1)).As a result,P-doped Si@C anodes paired with commercial activated carbon and LiFePO_(4)cathode to assemble lithium-ion capacitor(high power density of〜61,080 W·kg^(-1)at 20 A·g^(-1))and lithium-ion full cell(good rate performance with 68.3 mAh·g^(-1)at 5 C),respectively.This work can provide an effective way tofurther improve power density and stability for energy storage devices.展开更多
基金We thank Ms Fahmida Zaman for her initial intellectual support for this projectWe are grateful to Ms Noshin Noorjahan for her editorial support for our manuscript.Department of Pharmaceutical Sciences at North South University provided the Laboratory space,including the equipment and basic reagents necessary to conduct this project.
文摘Background:Parkinson's disease(PD)is a progressive neurodegenerative disorder affecting a large number of elderly people worldwide.The current therapies for PD are symptom-based;they do not provide a cure but improve the quality of life.Muscular dysfunction is the hallmark clinical feature of PD and oxidative stress and inflammation play a critical role in its pathogenesis.Epalrestat is used for the treatment of diabetic neuropathy and is known to improve antioxidative defense mechanisms in the CNS.Therefore,in this study,we investigated the role of Epalrestat in the reserpine induced mouse model of PD.Method:We used Swiss Albino mice for the PD model and tested for akinesia/bradykinesia,muscular rigidity,palpebral ptosis,and tremor,as well as conducting swim and open field tests.Brain samples were used to determine oxidative stress parameters and infiltration of immune cells.Results:Epalrestat treatment significantly improved akinesia and bradykinesia,muscular dysfunctions,tremor level,and gait functions compared to the reserpine group.It also improved the latency in the swim test.Eplarestat significantly reduced lipid peroxidation and NO concentration in different brain tissues and increased the activity of antioxidative enzymes,glutathione,catalase,and superoxide dismutase.Furthermore,Epalrestat reduced neuroinflammation by reducing the number of infiltrating immune cells.Conclusion:Eplarestat improves muscular dysfunction in PD by reducing oxidative stress and inflammation.
基金This work was supported by the Biotechnology and Biological Sciences Research Council project grant BB/K003356/1.HPLC-MS analysis was performed on equipment within the Centre of Excellence in Mass Spectrometry(University of York),funded by Science City York(Yorkshire Forward,EP/K039660/1,EP/M028127/1).
文摘Serine integrases have been shown to be efficient tools for metabolic pathway assembly.To further improve the flexibility and efficiency of pathway engineering via serine integrases,we explored how multiple orthogonally active serine integrases can be applied for use in vitro for the heterologous expression of complex biosynthesis pathways in Streptomyces spp.,the major producers of useful bioactive natural products.The results show that multiple orthogonal serine integrases efficiently assemble the genes from a complex biosynthesis pathway in a single in vitro recombination reaction,potentially permitting a versatile combinatorial assembly approach.Furthermore,the assembly strategy also permitted the incorporation of a well-characterised promoter upstream of each gene for expression in a heterologous host.The results demonstrate how site-specific recombination based on orthogonal serine integrases can be applied in Streptomyces spp.
基金Science and Technology Commission of Shanghai Municipality(Nos.20520710400,18230743400,18QA1402400)the National Natural Science Foundation of China(No.21771124)+1 种基金Oceanic Interdisciplinary Program of Shanghai Jiao Tong University(No.SL2020MS020)SJTU-Warwick Joint Seed Fund(2019/20).
文摘Silicon is a low price and high capacity ancxje material for lithium-ion batteries.The yolk-shell structure can effectively accommodate Si expansion to improve stability.However,the limited rate performance of Si anodes can't meet people's growing demand for high power density.Herein,the phosphorus-doped yolk-shell Si@C materials(P-doped Si@C)were prepared through carbon coating on P-doped Si/SiO_(x)matrix to obtain high power and stable devices.Therefore,the as-prepared P-doped Si@C electrodes delivered a rapid increase in Coulombic efficiency from 74.4%to 99.6%after only 6 cycles,high capacity retention of-95%over 800 cycles at 4 A·g^(-1),and great rate capability(510 mAh·g^(-1)at 35 A·g^(-1)).As a result,P-doped Si@C anodes paired with commercial activated carbon and LiFePO_(4)cathode to assemble lithium-ion capacitor(high power density of〜61,080 W·kg^(-1)at 20 A·g^(-1))and lithium-ion full cell(good rate performance with 68.3 mAh·g^(-1)at 5 C),respectively.This work can provide an effective way tofurther improve power density and stability for energy storage devices.