OBJECTIVES Parkinson disease(PD)is the second most common neurodegener⁃ative disease,but none of the current treatments for PD could halt the progress of the disease due to the limited understanding of the pathogenesi...OBJECTIVES Parkinson disease(PD)is the second most common neurodegener⁃ative disease,but none of the current treatments for PD could halt the progress of the disease due to the limited understanding of the pathogenesis.Increasing evidence proves that the close com⁃munication between the brain and the gastroin⁃testinal system is influenced by gut microbiota in PD pathogenesis,known as microbiota-gut-brain axis.However,the explicit mechanisms of micro⁃biota dysbiosis in PD development have not been well elucidated yet.FLZ,a novel squamosamide derivative,has been proved to be effective in many PD models and is undergoing the phaseⅠclinical trial to treat PD in China.The aims of our study are to assess the neuroprotective effects of FLZ treatment on PD and to further explore the underlying microbiota-related mechanisms of PD by using FLZ as a tool.METHODS Chronic administration of rotenone(30 mg·kg-1 per day)was utilized to induce a mouse model to mimic the pathological process of PD.Behavioral tests and gastrointestinal function tests were conduct⁃ed to evaluate the PD symptoms.Gut microbiota alterations were analyzed by 16s rRNA sequenc⁃ing.The intestinal permeability and blood-brain barrier structures were assessed by various methods.The pro-inflammatory cytokines and LPS levels in the colon,serum,and brain were detected by ELISA.Furthermore,the levels of in⁃flammation and TLR4/MyD88/NF-κB pathway in the substantia nigra(SN)and colon were mea⁃sured.RESULTS Behavioral tests and gastroin⁃testinal function tests found that rotenone-in⁃duced mice showed gastrointestinal dysfunctions(week 3)prior to the motor deficits(week 4).However,FLZ treatment significantly alleviated these PD symptoms.16S rRNA sequencing illus⁃trated that PD-related microbiota alterations in⁃duced by rotenone were reversed by FLZ treatment at various taxa levels.Especially,we identified an increased genus Akkermansia in the Rotenone group(P=0.0006),which could be reversed by FLZ administration(P=0.0070).By reducing microbiota dysbiosis,qPCR results showed that FLZ treatment suppressed intestinal inflammation of rotenone-challenged mice.After⁃wards,transmission electron microscopy(TEM),in vivo FITC permeability assay,bacterial translocation assay,and Western blotting togeth⁃er suggested that FLZ treatment attenuated the intestinal barrier destruction induced by rote⁃none.Subsequently,ELISA results showed that FLZ administration inhibited the leakage of pro-inflammatory cytokines(TNF-α,IL-1β,and IL-6)and LPS into the serum,suggesting the atten⁃uation of systemic inflammation.Then,several experiments including TEM analysis found that FLZ treatment restored blood-brain barrier struc⁃ture.Consequently,the immunofluorescence staining demonstrated that neuroinflammation(increased Iba-1+and GFAP+cells)and dopami⁃nergic neuronal death(reduced TH+cells)in the SN caused by rotenone were remarkably attenu⁃ated.Further mechanistic research proved that the anti-inflammatory effects of FLZ administra⁃tion were mediated through the TLR4/MyD88/NF-κB pathway both in the SN and colon.CONCLU⁃SION FLZ treatment ameliorates microbiota dys⁃biosis to protect the PD model via inhibiting TLR4 pathway,which contributes to one of the underlying mechanisms beneath its neuroprotec⁃tive effects.Our research also supports the importance of microbiota-gut-brain axis in PD pathogenesis,suggesting its potential role as a novel therapeutic target for PD treatment.展开更多
A novel shrouded wind-solar hybrid renewable energy and rain water harvester with an omni-directional-guide-vane(ODGV) for urban high-rise application is introduced.The ODGV surrounds the vertical axis wind turbine(VA...A novel shrouded wind-solar hybrid renewable energy and rain water harvester with an omni-directional-guide-vane(ODGV) for urban high-rise application is introduced.The ODGV surrounds the vertical axis wind turbine(VAWT) and enhances the VAWT performance by increasing the on-coming wind speed and guiding it to an optimum flow angle before it interacts with the rotor blades.An ODGV scaled model was built and tested in the laboratory.The experimental results show that the rotational speed of the VAWT increases by about 2 times.Simulations show that the installation of the ODGV increases the torque output of a single-bladed VAWT by 206% for tip speed ratio of 0.4.The result also reveals that higher positive torque can be achieved when the blade tangential force at all radial positions is optimized.In conclusion,the ODGV improves the power output of a VAWT and this integrated design promotes the installation of wind energy systems in urban areas.展开更多
Collective pitch control and individual pitch control algorithms were present for straight-bladed vertical axis wind turbine to improve the self-starting capacity.Comparative analysis of straight-bladed vertical axis ...Collective pitch control and individual pitch control algorithms were present for straight-bladed vertical axis wind turbine to improve the self-starting capacity.Comparative analysis of straight-bladed vertical axis wind turbine(SB-VAWT)with or without pitch control was conducted from the aspects of aerodynamic force,flow structure and power coefficient.The computational fluid dynamics(CFD)prediction results show a significant increase in power coefficient for SB-VAWT with pitch control.According to the aerodynamic forces and total torque coefficient obtained at various tip speed ratios(TSRs),the results indicate that the blade pitch method can increase the power output and decrease the deformation of blade;especially,the total torque coefficient of blade pitch control at TSR 1.5 is about 2.5 times larger than that of fixed pitch case.Furthermore,experiment was carried out to verify the feasibility of pitch control methods.The results show that the present collective pitch control and individual pitch control methods can improve the self-starting capacity of SB-VAWT,and the former is much better and its proper operating TSRs ranges from 0.4 to 0.6.展开更多
文摘OBJECTIVES Parkinson disease(PD)is the second most common neurodegener⁃ative disease,but none of the current treatments for PD could halt the progress of the disease due to the limited understanding of the pathogenesis.Increasing evidence proves that the close com⁃munication between the brain and the gastroin⁃testinal system is influenced by gut microbiota in PD pathogenesis,known as microbiota-gut-brain axis.However,the explicit mechanisms of micro⁃biota dysbiosis in PD development have not been well elucidated yet.FLZ,a novel squamosamide derivative,has been proved to be effective in many PD models and is undergoing the phaseⅠclinical trial to treat PD in China.The aims of our study are to assess the neuroprotective effects of FLZ treatment on PD and to further explore the underlying microbiota-related mechanisms of PD by using FLZ as a tool.METHODS Chronic administration of rotenone(30 mg·kg-1 per day)was utilized to induce a mouse model to mimic the pathological process of PD.Behavioral tests and gastrointestinal function tests were conduct⁃ed to evaluate the PD symptoms.Gut microbiota alterations were analyzed by 16s rRNA sequenc⁃ing.The intestinal permeability and blood-brain barrier structures were assessed by various methods.The pro-inflammatory cytokines and LPS levels in the colon,serum,and brain were detected by ELISA.Furthermore,the levels of in⁃flammation and TLR4/MyD88/NF-κB pathway in the substantia nigra(SN)and colon were mea⁃sured.RESULTS Behavioral tests and gastroin⁃testinal function tests found that rotenone-in⁃duced mice showed gastrointestinal dysfunctions(week 3)prior to the motor deficits(week 4).However,FLZ treatment significantly alleviated these PD symptoms.16S rRNA sequencing illus⁃trated that PD-related microbiota alterations in⁃duced by rotenone were reversed by FLZ treatment at various taxa levels.Especially,we identified an increased genus Akkermansia in the Rotenone group(P=0.0006),which could be reversed by FLZ administration(P=0.0070).By reducing microbiota dysbiosis,qPCR results showed that FLZ treatment suppressed intestinal inflammation of rotenone-challenged mice.After⁃wards,transmission electron microscopy(TEM),in vivo FITC permeability assay,bacterial translocation assay,and Western blotting togeth⁃er suggested that FLZ treatment attenuated the intestinal barrier destruction induced by rote⁃none.Subsequently,ELISA results showed that FLZ administration inhibited the leakage of pro-inflammatory cytokines(TNF-α,IL-1β,and IL-6)and LPS into the serum,suggesting the atten⁃uation of systemic inflammation.Then,several experiments including TEM analysis found that FLZ treatment restored blood-brain barrier struc⁃ture.Consequently,the immunofluorescence staining demonstrated that neuroinflammation(increased Iba-1+and GFAP+cells)and dopami⁃nergic neuronal death(reduced TH+cells)in the SN caused by rotenone were remarkably attenu⁃ated.Further mechanistic research proved that the anti-inflammatory effects of FLZ administra⁃tion were mediated through the TLR4/MyD88/NF-κB pathway both in the SN and colon.CONCLU⁃SION FLZ treatment ameliorates microbiota dys⁃biosis to protect the PD model via inhibiting TLR4 pathway,which contributes to one of the underlying mechanisms beneath its neuroprotec⁃tive effects.Our research also supports the importance of microbiota-gut-brain axis in PD pathogenesis,suggesting its potential role as a novel therapeutic target for PD treatment.
基金Project (RG039-09AET) supported by University of Malaya, Malaysia
文摘A novel shrouded wind-solar hybrid renewable energy and rain water harvester with an omni-directional-guide-vane(ODGV) for urban high-rise application is introduced.The ODGV surrounds the vertical axis wind turbine(VAWT) and enhances the VAWT performance by increasing the on-coming wind speed and guiding it to an optimum flow angle before it interacts with the rotor blades.An ODGV scaled model was built and tested in the laboratory.The experimental results show that the rotational speed of the VAWT increases by about 2 times.Simulations show that the installation of the ODGV increases the torque output of a single-bladed VAWT by 206% for tip speed ratio of 0.4.The result also reveals that higher positive torque can be achieved when the blade tangential force at all radial positions is optimized.In conclusion,the ODGV improves the power output of a VAWT and this integrated design promotes the installation of wind energy systems in urban areas.
基金Project(E201216)supported by Heilongjiang Provincial Natural Science Foundation,China
文摘Collective pitch control and individual pitch control algorithms were present for straight-bladed vertical axis wind turbine to improve the self-starting capacity.Comparative analysis of straight-bladed vertical axis wind turbine(SB-VAWT)with or without pitch control was conducted from the aspects of aerodynamic force,flow structure and power coefficient.The computational fluid dynamics(CFD)prediction results show a significant increase in power coefficient for SB-VAWT with pitch control.According to the aerodynamic forces and total torque coefficient obtained at various tip speed ratios(TSRs),the results indicate that the blade pitch method can increase the power output and decrease the deformation of blade;especially,the total torque coefficient of blade pitch control at TSR 1.5 is about 2.5 times larger than that of fixed pitch case.Furthermore,experiment was carried out to verify the feasibility of pitch control methods.The results show that the present collective pitch control and individual pitch control methods can improve the self-starting capacity of SB-VAWT,and the former is much better and its proper operating TSRs ranges from 0.4 to 0.6.
