To develop suitable grouting materials for water conveyance tunnels in cold regions,firstly,this study investigated the performance evolution of ferrite-rich sulfoaluminate-based composite cement(FSAC grouting materia...To develop suitable grouting materials for water conveyance tunnels in cold regions,firstly,this study investigated the performance evolution of ferrite-rich sulfoaluminate-based composite cement(FSAC grouting material)at 20 and 3℃.The results show that low temperature only delays the strength development of FSAC grouting material within the first 3 d.Then,the effect of four typical early strength synergists on the early properties of FSAC grouting material was evaluated to optimize the early(£1 d)strength at 3℃.The most effective synergist,Ca(HCOO)_(2),which enhances the low-temperature early strength without compromising fluidity was selected based on strength and fluidity tests.Its micro-mechanism was analyzed by XRD,TG,and SEM methods.The results reveal that the most suitable dosage range is 0.3 wt%−0.5 wt%.Proper addition of Ca(HCOO)_(2)changed the crystal morphology of the hydration products,decreased the pore size and formed more compact hydration products by interlocking and overlapping.However,excessive addition of Ca(HCOO)_(2)inhibited the hydration reaction,resulting in a simple and loose structure of the hydration products.The research results have reference value for controlling surrounding rock deformation and preventing water and mud inrushes during the excavation in cold region tunnels.展开更多
Pseudomonas aeruginosa is an opportunistic pathogen that contributes to high morbidity and mortality. MexAB-OprM is the main efflux pump among the Resistance-Nodulation-Division family multi-drug effiux systems, which...Pseudomonas aeruginosa is an opportunistic pathogen that contributes to high morbidity and mortality. MexAB-OprM is the main efflux pump among the Resistance-Nodulation-Division family multi-drug effiux systems, which contribute greatly to the multidrug resistance of P. aeruginosa. Effiux pump inhibitors （EPIs） of MexAB-OprM could enhance the activity of the antibiotics effiuxed by MexAB-OprM, and thus they might be useful in the clinic as antibacterial synergistic agents. In this work, a new EPI of MexAB-OprM, KL-0153, was discovered by screening of a small molecular library. Its inhibition of MexAB-OprM was confirmed by assays of synergistic activity and EB accumulation. The activity of KL-0153 was shown to be synergistic with antibiotics effiuxed by MexAB-OprM when they were tested against strains expressing MexAB-OprM, especially so for the strains that express MexAB-OprM at high levels. KL-0153 showed more activity than the positive drug carbonyl cyanide m-chlorophenylhydrazone in the EB accumulation assay. It cannot be neglected that KL-0153 has significant liver and kidney toxicity. However, KL-0153 may be a lead comoound for the research and development of new tvoes of EPIs.展开更多
目的:探讨肌浆网钙泵(SERCA2a)/磷酸受纳蛋白(PLB)在电针干预对乌头碱改善心力衰竭增效/减毒作用中的机制。方法:将30只SPF级SD大鼠随机分为对照组、模型组、电针组、乌头碱组和电针+乌头碱组,每组6只。采用右股静脉输注大剂量盐酸普萘...目的:探讨肌浆网钙泵(SERCA2a)/磷酸受纳蛋白(PLB)在电针干预对乌头碱改善心力衰竭增效/减毒作用中的机制。方法:将30只SPF级SD大鼠随机分为对照组、模型组、电针组、乌头碱组和电针+乌头碱组,每组6只。采用右股静脉输注大剂量盐酸普萘洛尔溶液的方法制备大鼠急性心力衰竭模型。造模成功10 min后,电针组和电针+乌头碱组大鼠于"内关"行电针干预,予疏密波,频率2 Hz/15 Hz,电流强度3 mA,时间30 min;乌头碱组和电针+乌头碱组大鼠经左股静脉注射乌头碱溶液(10μg/kg)。检测各组大鼠血流动力学指标左心室收缩压(LVSP)、左心室内压最大上升/下降变化速率(±dp/dtmax);观察大鼠心律失常类型并进行评分;多重荧光Western blot法检测大鼠左心室心肌组织SERCA2a和PLB蛋白表达。结果:与对照组比较,模型组造模后、干预后各时点LVSP、±dp/dtmax均降低(P<0.01);与模型组比较,乌头碱组、电针组干预后1min±dp/dtmax升高(P<0.01,P<0.05),乌头碱组干预后10~60 min与电针组干预后20~60 min+dp/dtmax升高(P<0.01,P<0.05),电针组干预后1 min LVSP亦升高(P<0.01),电针+乌头碱组干预后1~60 min LVSP、±dp/dtmax均升高(P<0.01,P<0.05)。与乌头碱组比较,电针组干预后1 min LVSP和+dp/dtmax升高(P<0.01,P<0.05),电针+乌头碱组干预后1 min LVSP、±dp/dtmax与干预后20~60 min+dp/dtmax均升高(P<0.01,P<0.05)。与电针组比较,电针+乌头碱组干预后10~60 min+dp/dtmax升高(P<0.01)。与模型组比较,乌头碱组干预后心律失常评分升高(P<0.01);与乌头碱组比较,电针+乌头碱组与电针组心律失常评分降低(P<0.01)。与对照组比较,模型组左心室心肌组织SERCA2a蛋白表达降低(P<0.01),PLB蛋白表达增加(P<0.01);与模型组比较,电针组和电针+乌头碱组SERCA2a蛋白表达增加(P<0.05,P<0.01),各干预组PLB蛋白表达降低(P<0.01,P<0.05);与电针组、乌头碱组比较,电针+乌头碱组SERCA2a蛋白表达增加、PLB蛋白表达降低(P<0.05,P<0.01)。结论:电针干预可能是通过上调心肌组织SERCA2a蛋白表达、下调PLB蛋白表达实现对乌头碱改善心力衰竭的增效/减毒作用。展开更多
基金Projcet(52279119)supported by the National Natural Science Foundation of ChinaProject(XZ202201ZY0021G)supported by the Science and Technology Planning Project of Xizang Autonomous Region,China+1 种基金Project(2019QZKK0904)supported by the Second Xizang Plateau Scientific Expedition and Research Program of ChinaProject(51922104)supported by the National Natural Science Foundation for Distinguished Young Scholars of China。
文摘To develop suitable grouting materials for water conveyance tunnels in cold regions,firstly,this study investigated the performance evolution of ferrite-rich sulfoaluminate-based composite cement(FSAC grouting material)at 20 and 3℃.The results show that low temperature only delays the strength development of FSAC grouting material within the first 3 d.Then,the effect of four typical early strength synergists on the early properties of FSAC grouting material was evaluated to optimize the early(£1 d)strength at 3℃.The most effective synergist,Ca(HCOO)_(2),which enhances the low-temperature early strength without compromising fluidity was selected based on strength and fluidity tests.Its micro-mechanism was analyzed by XRD,TG,and SEM methods.The results reveal that the most suitable dosage range is 0.3 wt%−0.5 wt%.Proper addition of Ca(HCOO)_(2)changed the crystal morphology of the hydration products,decreased the pore size and formed more compact hydration products by interlocking and overlapping.However,excessive addition of Ca(HCOO)_(2)inhibited the hydration reaction,resulting in a simple and loose structure of the hydration products.The research results have reference value for controlling surrounding rock deformation and preventing water and mud inrushes during the excavation in cold region tunnels.
文摘Pseudomonas aeruginosa is an opportunistic pathogen that contributes to high morbidity and mortality. MexAB-OprM is the main efflux pump among the Resistance-Nodulation-Division family multi-drug effiux systems, which contribute greatly to the multidrug resistance of P. aeruginosa. Effiux pump inhibitors （EPIs） of MexAB-OprM could enhance the activity of the antibiotics effiuxed by MexAB-OprM, and thus they might be useful in the clinic as antibacterial synergistic agents. In this work, a new EPI of MexAB-OprM, KL-0153, was discovered by screening of a small molecular library. Its inhibition of MexAB-OprM was confirmed by assays of synergistic activity and EB accumulation. The activity of KL-0153 was shown to be synergistic with antibiotics effiuxed by MexAB-OprM when they were tested against strains expressing MexAB-OprM, especially so for the strains that express MexAB-OprM at high levels. KL-0153 showed more activity than the positive drug carbonyl cyanide m-chlorophenylhydrazone in the EB accumulation assay. It cannot be neglected that KL-0153 has significant liver and kidney toxicity. However, KL-0153 may be a lead comoound for the research and development of new tvoes of EPIs.
文摘目的:探讨肌浆网钙泵(SERCA2a)/磷酸受纳蛋白(PLB)在电针干预对乌头碱改善心力衰竭增效/减毒作用中的机制。方法:将30只SPF级SD大鼠随机分为对照组、模型组、电针组、乌头碱组和电针+乌头碱组,每组6只。采用右股静脉输注大剂量盐酸普萘洛尔溶液的方法制备大鼠急性心力衰竭模型。造模成功10 min后,电针组和电针+乌头碱组大鼠于"内关"行电针干预,予疏密波,频率2 Hz/15 Hz,电流强度3 mA,时间30 min;乌头碱组和电针+乌头碱组大鼠经左股静脉注射乌头碱溶液(10μg/kg)。检测各组大鼠血流动力学指标左心室收缩压(LVSP)、左心室内压最大上升/下降变化速率(±dp/dtmax);观察大鼠心律失常类型并进行评分;多重荧光Western blot法检测大鼠左心室心肌组织SERCA2a和PLB蛋白表达。结果:与对照组比较,模型组造模后、干预后各时点LVSP、±dp/dtmax均降低(P<0.01);与模型组比较,乌头碱组、电针组干预后1min±dp/dtmax升高(P<0.01,P<0.05),乌头碱组干预后10~60 min与电针组干预后20~60 min+dp/dtmax升高(P<0.01,P<0.05),电针组干预后1 min LVSP亦升高(P<0.01),电针+乌头碱组干预后1~60 min LVSP、±dp/dtmax均升高(P<0.01,P<0.05)。与乌头碱组比较,电针组干预后1 min LVSP和+dp/dtmax升高(P<0.01,P<0.05),电针+乌头碱组干预后1 min LVSP、±dp/dtmax与干预后20~60 min+dp/dtmax均升高(P<0.01,P<0.05)。与电针组比较,电针+乌头碱组干预后10~60 min+dp/dtmax升高(P<0.01)。与模型组比较,乌头碱组干预后心律失常评分升高(P<0.01);与乌头碱组比较,电针+乌头碱组与电针组心律失常评分降低(P<0.01)。与对照组比较,模型组左心室心肌组织SERCA2a蛋白表达降低(P<0.01),PLB蛋白表达增加(P<0.01);与模型组比较,电针组和电针+乌头碱组SERCA2a蛋白表达增加(P<0.05,P<0.01),各干预组PLB蛋白表达降低(P<0.01,P<0.05);与电针组、乌头碱组比较,电针+乌头碱组SERCA2a蛋白表达增加、PLB蛋白表达降低(P<0.05,P<0.01)。结论:电针干预可能是通过上调心肌组织SERCA2a蛋白表达、下调PLB蛋白表达实现对乌头碱改善心力衰竭的增效/减毒作用。
