目的:基于miR-451a靶向磷酸甘油酸变位酶(PGAM5)-线粒体动力相关蛋白1(Drp1)轴调控线粒体动力学,探讨温肺降浊方对氧糖剥夺/复氧(OGD/R)诱导HT22模型的效应机制。方法:建立OGD/R诱导HT22细胞模型,设立正常对照组、OGD/R组、miR-451a过...目的:基于miR-451a靶向磷酸甘油酸变位酶(PGAM5)-线粒体动力相关蛋白1(Drp1)轴调控线粒体动力学,探讨温肺降浊方对氧糖剥夺/复氧(OGD/R)诱导HT22模型的效应机制。方法:建立OGD/R诱导HT22细胞模型,设立正常对照组、OGD/R组、miR-451a过表达组、miR-451a敲低组、温肺降浊方含药血清(WFJZF)组、miR-451a过表达+WFJZF组、miR-451a敲低+WFJZF组和miR-451a空载体组,双荧光素酶确定miR-451a和PGAM5的转录关系,免疫蛋白共沉淀确定PGAM5和Drp1的调控作用,慢病毒转染miR-451a于HT22细胞中,qRT-PCR确定转染效率,CCK-8测定缺糖缺氧状态下细胞活性的最佳时间点,qRT-PCR和Westem Blot检测HT22模型细胞内DGAM5-Drp1轴蛋白及mRNA的表达水平。结果:OGD/R诱导HT22细胞持续2 h为最佳时间点,miR-451a可以靶向调控PGAM5基因,PGAM5和Drp1具有相互调控作用。与正常对照组比较,OGD/R组细胞内PGAM5、Drp1和Fis1蛋白及mRNA表达上升,p-Drp1 Ser 616磷酸化表达上升(P<0.05),OPA1蛋白及mRNA表达下降,p-Drp1 Ser 637去磷酸化表达下降(P<0.05);与OGD/R组比较,miR-451a过表达+WFJZF组细胞内PGAM5、Drp1和Fis1蛋白及mRNA表达下降,p-Drp1 Ser 616磷酸化表达下降(P<0.05),OPA1蛋白及mRNA表达上升,p-Drp1 Ser 637去磷酸化表达上升(P<0.05)。结论:miR-451a可以靶向调控PGAM5-Drp1轴,miR-451a过表达+WFJZF组可以改善线粒体失衡状态,减少神经元过度损伤,发挥脑保护效应。展开更多
Osyris lanceolata is heavily and illegally exploited in East Africa for its essential oils, yet little is known about its population status and ecological requirements. This study examined its population structure and...Osyris lanceolata is heavily and illegally exploited in East Africa for its essential oils, yet little is known about its population status and ecological requirements. This study examined its population structure and environmental factors influencing its distribution in the semi-arid Karamoja sub-region, Uganda. We surveyed 388 plots (5 m radius) at different altitudes, recording life stages, stem diameters, and regeneration patterns, and analyzed soil samples. Multivariate analyses, including Canonical Correspondence Analysis (CCA), Detrended Correspondence Analysis (DCA), Non-metric Multidimensional Scaling (NMDS), and Multiple Regression Modeling (MRM), identified key environmental factors affecting its distribution. Findings show that O. lanceolata populations in Moroto, Nakapiripirit, and Amudat districts are severely degraded due to overexploitation. The species is primarily regenerating through coppicing rather than seedlings, with an exploitation intensity of 56.6%. Population densities are low, distribution is irregular, and sustainable harvesting is not viable. Soil properties, particularly Ca2+, N, P, K+, Na+, and organic matter, significantly influence its abundance. Conservation efforts should focus on identifying suitable provenances for genetic preservation and plantation establishment. Areas with at least 9 trees per hectare in Moroto, Nakapiripirit, and Amudat could serve as potential sites for ex-situ plantations. Further research should explore how biotic interactions, genetic diversity, and morphology affect oil yield and quality to support restoration, breeding, and domestication initiatives.展开更多
Intracellular redox homeostasis is of indispensable importance in pathophysiology.In order to maintain the balance of the redox state within the cell,reactive oxygen species(ROS)and reactive sulfur species(RSS)react a...Intracellular redox homeostasis is of indispensable importance in pathophysiology.In order to maintain the balance of the redox state within the cell,reactive oxygen species(ROS)and reactive sulfur species(RSS)react and transform with each other,and their levels also directly reflect the degree of oxidative stress and disease.Hypochlorous acid(HClO)and cysteine(Cys)usually co-exist in organisms,interacting with each other in many important physiological processes and synergistically maintaining the dynamic redox balance in the body.To understand the relevance and pathophysiological effects of these two signaling molecules in oxidative stress,unique fluorescence imaging tools are required.Herein,we designed and developed a dual-channel fluorescent probe HP,for the individual and continuous detection of HClO and Cys.This probe could simultaneously monitor the changes in the concentrations of HClO and Cys in cells,and was characterized by a fast response,high sensitivity and high selectivity,especially compared with glutathione(GSH)and homocysteine(Hcy),the probe had a good specificity for Cys.Importantly,probe HP successfully observed dynamic changes in HCl O-and Cys-mediated redox status in the oxygenglucose deprivation/reperfusion(OGD/R)model of HeLa cells and dynamically monitored fluctuations in endogenous HClO levels in lipopolysaccharides(LPS)-induced peritonitis mice.展开更多
Following the publication of Zeng et al.(2023),an inadvertent error was recently identified in Figure 1B and Supplementary Figure S3.To ensure the accuracy and integrity of our published work,we formally request a cor...Following the publication of Zeng et al.(2023),an inadvertent error was recently identified in Figure 1B and Supplementary Figure S3.To ensure the accuracy and integrity of our published work,we formally request a correction to address this issue and apologize for any confusion this error may have caused.For details,please refer to the modified Supplementary Materials.展开更多
Craniometaphyseal dysplasia(CMD),a rare craniotubular disorder,occurs in an autosomal dominant(AD)or autosomal recessive(AR)form.CMD is characterized by hyperostosis of craniofacial bones and metaphyseal flaring of lo...Craniometaphyseal dysplasia(CMD),a rare craniotubular disorder,occurs in an autosomal dominant(AD)or autosomal recessive(AR)form.CMD is characterized by hyperostosis of craniofacial bones and metaphyseal flaring of long bones.Many patients with CMD suffer from neurological symptoms.The pathogenesis of CMD is not fully understood.展开更多
Objective: To study the pharmacokinetics of native r SAK in rabbit's femoral artery thrombosis model, the “lytic circle' method was used to determine plasma levels of r SAK. Methods: Thirty New Zealand rabb...Objective: To study the pharmacokinetics of native r SAK in rabbit's femoral artery thrombosis model, the “lytic circle' method was used to determine plasma levels of r SAK. Methods: Thirty New Zealand rabbits were randomly assigned to the control (saline 10 ml, 30 min), r SAK low dose (0.25 mg/kg, 30 min), medial dose (0.50 mg/kg, 30 min), high dose (1.00 mg/kg, 30 min), single bolus (0.50 mg/kg, 2 min) and conjunctive therapy (initiated with heparin 200 U/kg, followed by infusion of r SAK 0.50 mg/kg for 30 min, and subsequently infused heparin 50 U/(kg·h) to endpoint) groups. The right femoral artery thrombosis model in rabbit was made by balloon injury, then the thrombolytic agents were infused through parallel ear vein and the blood samples were collected pre thrombolysis and at different time post thrombolysis to determine the plasma levels of r SAK by “lytic circle' method, the plasma levels of r SAK were processed by pharmacokinetic computing procedure to fit the model. Results: The plasma levels of r SAK and the diameters of lytic circles showed a pretty good linear correlation under the scope of 2.0×10 4 2.0×10 6 U/L, and the averaged recycle rate was (96.05±11.35)%(RSD =±11.82%).All peak concentration time in each infusion group was 30 min, and the peak concentrations positively correlated with the doses administrated in infusion groups(r=0.999 98, P <0.000 1). In single bolus group, Peak concentration time was 2 min, and the peak concentration reached (5.16±1.02) mg/L, which was significant higher than that in the same dose r SAK infusion group ( P <0.01). In conjunctive therapy group, the peak concentration showed no significant difference from that in the same dose r SAK infusion group ( P >0.05). The plasma levels of r SAK fit in two compartment model as processed by pharmacokinetic computing procedure in each group. Conclusion: The “lytic circle' method is a simple, practical and reliable method to determine the plasma level of r SAK, and the pharmacokinetics of native r SAK infusion fits in two compartment model in rabbit's femoral artery thrombosis model.展开更多
文摘目的:基于miR-451a靶向磷酸甘油酸变位酶(PGAM5)-线粒体动力相关蛋白1(Drp1)轴调控线粒体动力学,探讨温肺降浊方对氧糖剥夺/复氧(OGD/R)诱导HT22模型的效应机制。方法:建立OGD/R诱导HT22细胞模型,设立正常对照组、OGD/R组、miR-451a过表达组、miR-451a敲低组、温肺降浊方含药血清(WFJZF)组、miR-451a过表达+WFJZF组、miR-451a敲低+WFJZF组和miR-451a空载体组,双荧光素酶确定miR-451a和PGAM5的转录关系,免疫蛋白共沉淀确定PGAM5和Drp1的调控作用,慢病毒转染miR-451a于HT22细胞中,qRT-PCR确定转染效率,CCK-8测定缺糖缺氧状态下细胞活性的最佳时间点,qRT-PCR和Westem Blot检测HT22模型细胞内DGAM5-Drp1轴蛋白及mRNA的表达水平。结果:OGD/R诱导HT22细胞持续2 h为最佳时间点,miR-451a可以靶向调控PGAM5基因,PGAM5和Drp1具有相互调控作用。与正常对照组比较,OGD/R组细胞内PGAM5、Drp1和Fis1蛋白及mRNA表达上升,p-Drp1 Ser 616磷酸化表达上升(P<0.05),OPA1蛋白及mRNA表达下降,p-Drp1 Ser 637去磷酸化表达下降(P<0.05);与OGD/R组比较,miR-451a过表达+WFJZF组细胞内PGAM5、Drp1和Fis1蛋白及mRNA表达下降,p-Drp1 Ser 616磷酸化表达下降(P<0.05),OPA1蛋白及mRNA表达上升,p-Drp1 Ser 637去磷酸化表达上升(P<0.05)。结论:miR-451a可以靶向调控PGAM5-Drp1轴,miR-451a过表达+WFJZF组可以改善线粒体失衡状态,减少神经元过度损伤,发挥脑保护效应。
文摘Osyris lanceolata is heavily and illegally exploited in East Africa for its essential oils, yet little is known about its population status and ecological requirements. This study examined its population structure and environmental factors influencing its distribution in the semi-arid Karamoja sub-region, Uganda. We surveyed 388 plots (5 m radius) at different altitudes, recording life stages, stem diameters, and regeneration patterns, and analyzed soil samples. Multivariate analyses, including Canonical Correspondence Analysis (CCA), Detrended Correspondence Analysis (DCA), Non-metric Multidimensional Scaling (NMDS), and Multiple Regression Modeling (MRM), identified key environmental factors affecting its distribution. Findings show that O. lanceolata populations in Moroto, Nakapiripirit, and Amudat districts are severely degraded due to overexploitation. The species is primarily regenerating through coppicing rather than seedlings, with an exploitation intensity of 56.6%. Population densities are low, distribution is irregular, and sustainable harvesting is not viable. Soil properties, particularly Ca2+, N, P, K+, Na+, and organic matter, significantly influence its abundance. Conservation efforts should focus on identifying suitable provenances for genetic preservation and plantation establishment. Areas with at least 9 trees per hectare in Moroto, Nakapiripirit, and Amudat could serve as potential sites for ex-situ plantations. Further research should explore how biotic interactions, genetic diversity, and morphology affect oil yield and quality to support restoration, breeding, and domestication initiatives.
基金the National Natural Science Foundation of China(Nos.22207069,22325703,22377071,22074084)Research Project Supported by Shanxi Scholarship Council of China(No.2022-002)+2 种基金the Shanxi Province Science Foundation(Nos.20210302124012,202203021221009)Key R&D and transformation plan of Qinghai Province(No.2020-GX-101)2023 Graduate Innovation Project of Shanxi University。
文摘Intracellular redox homeostasis is of indispensable importance in pathophysiology.In order to maintain the balance of the redox state within the cell,reactive oxygen species(ROS)and reactive sulfur species(RSS)react and transform with each other,and their levels also directly reflect the degree of oxidative stress and disease.Hypochlorous acid(HClO)and cysteine(Cys)usually co-exist in organisms,interacting with each other in many important physiological processes and synergistically maintaining the dynamic redox balance in the body.To understand the relevance and pathophysiological effects of these two signaling molecules in oxidative stress,unique fluorescence imaging tools are required.Herein,we designed and developed a dual-channel fluorescent probe HP,for the individual and continuous detection of HClO and Cys.This probe could simultaneously monitor the changes in the concentrations of HClO and Cys in cells,and was characterized by a fast response,high sensitivity and high selectivity,especially compared with glutathione(GSH)and homocysteine(Hcy),the probe had a good specificity for Cys.Importantly,probe HP successfully observed dynamic changes in HCl O-and Cys-mediated redox status in the oxygenglucose deprivation/reperfusion(OGD/R)model of HeLa cells and dynamically monitored fluctuations in endogenous HClO levels in lipopolysaccharides(LPS)-induced peritonitis mice.
文摘Following the publication of Zeng et al.(2023),an inadvertent error was recently identified in Figure 1B and Supplementary Figure S3.To ensure the accuracy and integrity of our published work,we formally request a correction to address this issue and apologize for any confusion this error may have caused.For details,please refer to the modified Supplementary Materials.
基金supported by NIH/NIDCR grant R01DE025664 to IPC.
文摘Craniometaphyseal dysplasia(CMD),a rare craniotubular disorder,occurs in an autosomal dominant(AD)or autosomal recessive(AR)form.CMD is characterized by hyperostosis of craniofacial bones and metaphyseal flaring of long bones.Many patients with CMD suffer from neurological symptoms.The pathogenesis of CMD is not fully understood.
文摘Objective: To study the pharmacokinetics of native r SAK in rabbit's femoral artery thrombosis model, the “lytic circle' method was used to determine plasma levels of r SAK. Methods: Thirty New Zealand rabbits were randomly assigned to the control (saline 10 ml, 30 min), r SAK low dose (0.25 mg/kg, 30 min), medial dose (0.50 mg/kg, 30 min), high dose (1.00 mg/kg, 30 min), single bolus (0.50 mg/kg, 2 min) and conjunctive therapy (initiated with heparin 200 U/kg, followed by infusion of r SAK 0.50 mg/kg for 30 min, and subsequently infused heparin 50 U/(kg·h) to endpoint) groups. The right femoral artery thrombosis model in rabbit was made by balloon injury, then the thrombolytic agents were infused through parallel ear vein and the blood samples were collected pre thrombolysis and at different time post thrombolysis to determine the plasma levels of r SAK by “lytic circle' method, the plasma levels of r SAK were processed by pharmacokinetic computing procedure to fit the model. Results: The plasma levels of r SAK and the diameters of lytic circles showed a pretty good linear correlation under the scope of 2.0×10 4 2.0×10 6 U/L, and the averaged recycle rate was (96.05±11.35)%(RSD =±11.82%).All peak concentration time in each infusion group was 30 min, and the peak concentrations positively correlated with the doses administrated in infusion groups(r=0.999 98, P <0.000 1). In single bolus group, Peak concentration time was 2 min, and the peak concentration reached (5.16±1.02) mg/L, which was significant higher than that in the same dose r SAK infusion group ( P <0.01). In conjunctive therapy group, the peak concentration showed no significant difference from that in the same dose r SAK infusion group ( P >0.05). The plasma levels of r SAK fit in two compartment model as processed by pharmacokinetic computing procedure in each group. Conclusion: The “lytic circle' method is a simple, practical and reliable method to determine the plasma level of r SAK, and the pharmacokinetics of native r SAK infusion fits in two compartment model in rabbit's femoral artery thrombosis model.
