The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury.Ruxolitinib,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arth...The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury.Ruxolitinib,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arthritis,and managing inflammatory cytokine storms.Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma,the exact mechanism by which it enhances functional recovery after spinal cord injury,particularly its effect on astrocytes,remains unclear.To address this gap,we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury.Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury,restored EAAT2 expression,reduced glutamate levels,and alleviated excitatory toxicity.Furthermore,ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1β,interleukin-6,and tumor necrosis factor-α.Additionally,in glutamate-induced excitotoxicity astrocytes,ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3,thereby reducing glutamate-induced neurotoxicity,calcium influx,oxidative stress,and cell apoptosis,and increasing the complexity of dendritic branching.Collectively,these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes,reduces neurotoxicity,and effectively alleviates inflammatory and immune responses after spinal cord injury,thereby promoting functional recovery after spinal cord injury.展开更多
Inhibitors are important for flotation separation of quartz and feldspar.In this study,a novel combined inhibitor was used to separate quartz and feldspar in near-neutral pulp.Selective inhibition of the combined inhi...Inhibitors are important for flotation separation of quartz and feldspar.In this study,a novel combined inhibitor was used to separate quartz and feldspar in near-neutral pulp.Selective inhibition of the combined inhibitor was assessed by micro-flotation experiments.And a series of detection methods were used to detect differences in the surface properties of feldspars and quartz after flotation reagents and put forward the synergistic strengthening mechanism.The outcomes were pointed out that pre-mixing combined inhibitors were more effective than the addition of Ca^(2+)and SS in sequence under the optimal proportion of 1:5.A concentrate from artificial mixed minerals that was characterized by a high quartz grade and a high recovery was acquired,and was found to be 90.70wt% and 83.70%,respectively.It was demonstrated that the combined inhibitor selectively prevented the action of the collector and feldspar from Fourier-transform infrared(FT-IR)and adsorption capacity tests.The results of X-ray photoelectron spectroscopy(XPS)indicated that Ca^(2+)directly interacts with the surface of quartz to increase the adsorption of collectors.In contrast,the chemistry property of Al on the feldspar surface was altered by combined inhibitor due to Na^(+)and Ca^(2+)taking the place of K^(+),resulting in the composite inhibitor forms a hydrophilic structure,which prevents the adsorption of the collector on the surface of feldspar by interacting with the Al active site.The combination of Ca^(2+)and SS synergically strengthens the difference of collecting property between quartz and feldspar by collector,thus achieving the effect of efficient separation.A new strategy for flotation to separate quartz from feldspar in near-neutral pulp was provided.展开更多
Studies have suggested that aluminum, a neurotoxic metal, is involved in the progression of neurodegenerative diseases. Previous studies have confirmed that aluminum influences intracellular Ca^2＋ homeostasis. Howeve...Studies have suggested that aluminum, a neurotoxic metal, is involved in the progression of neurodegenerative diseases. Previous studies have confirmed that aluminum influences intracellular Ca^2＋ homeostasis. However, it remains unclear whether aluminum increases or decreases intracellular Ca^2＋ concentrations. The present study demonstrated that Al^3＋ competitively binds to calmodulin （CAM）, together with Ca^2＋, which resulted in loss of capacity of CaM to bind to Ca^2＋, leading to increased [Ca^2＋]i. Al^3＋ stimulated voltage-gated calcium channels on cell membranes, which allowed a small quantity of Ca^2＋ into the cells. Al^3＋ also promoted calcium release from organelles by stimulating L-Ca^2＋αlc to trigger calcium-induced calcium release. Although Al^3＋ upregulated expression of Na＋/Ca^2＋exchanger mRNA, increased levels of Ca^2＋ and Na＋/Ca^2＋ exchanger did not maintain a normal Ca^2＋ balance. Al^3＋ resulted in disordered intracellular calcium homeostasis by affecting calcium channels, calcium buffering, and calcium expulsion.展开更多
基金supported by the National Natural Science Foundation of China,No.82272484(to XC).
文摘The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury.Ruxolitinib,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arthritis,and managing inflammatory cytokine storms.Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma,the exact mechanism by which it enhances functional recovery after spinal cord injury,particularly its effect on astrocytes,remains unclear.To address this gap,we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury.Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury,restored EAAT2 expression,reduced glutamate levels,and alleviated excitatory toxicity.Furthermore,ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1β,interleukin-6,and tumor necrosis factor-α.Additionally,in glutamate-induced excitotoxicity astrocytes,ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3,thereby reducing glutamate-induced neurotoxicity,calcium influx,oxidative stress,and cell apoptosis,and increasing the complexity of dendritic branching.Collectively,these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes,reduces neurotoxicity,and effectively alleviates inflammatory and immune responses after spinal cord injury,thereby promoting functional recovery after spinal cord injury.
基金the financial support from the National Key Research and Development Program of China(No.2018YFC1903403)Young Elite Scientists Sponsorship Program by CAST(No.2022QNRC001).
文摘Inhibitors are important for flotation separation of quartz and feldspar.In this study,a novel combined inhibitor was used to separate quartz and feldspar in near-neutral pulp.Selective inhibition of the combined inhibitor was assessed by micro-flotation experiments.And a series of detection methods were used to detect differences in the surface properties of feldspars and quartz after flotation reagents and put forward the synergistic strengthening mechanism.The outcomes were pointed out that pre-mixing combined inhibitors were more effective than the addition of Ca^(2+)and SS in sequence under the optimal proportion of 1:5.A concentrate from artificial mixed minerals that was characterized by a high quartz grade and a high recovery was acquired,and was found to be 90.70wt% and 83.70%,respectively.It was demonstrated that the combined inhibitor selectively prevented the action of the collector and feldspar from Fourier-transform infrared(FT-IR)and adsorption capacity tests.The results of X-ray photoelectron spectroscopy(XPS)indicated that Ca^(2+)directly interacts with the surface of quartz to increase the adsorption of collectors.In contrast,the chemistry property of Al on the feldspar surface was altered by combined inhibitor due to Na^(+)and Ca^(2+)taking the place of K^(+),resulting in the composite inhibitor forms a hydrophilic structure,which prevents the adsorption of the collector on the surface of feldspar by interacting with the Al active site.The combination of Ca^(2+)and SS synergically strengthens the difference of collecting property between quartz and feldspar by collector,thus achieving the effect of efficient separation.A new strategy for flotation to separate quartz from feldspar in near-neutral pulp was provided.
基金supported by the Department of Hygienic Toxicology,Public Health College,Harbin Medical University,China
文摘Studies have suggested that aluminum, a neurotoxic metal, is involved in the progression of neurodegenerative diseases. Previous studies have confirmed that aluminum influences intracellular Ca^2＋ homeostasis. However, it remains unclear whether aluminum increases or decreases intracellular Ca^2＋ concentrations. The present study demonstrated that Al^3＋ competitively binds to calmodulin （CAM）, together with Ca^2＋, which resulted in loss of capacity of CaM to bind to Ca^2＋, leading to increased [Ca^2＋]i. Al^3＋ stimulated voltage-gated calcium channels on cell membranes, which allowed a small quantity of Ca^2＋ into the cells. Al^3＋ also promoted calcium release from organelles by stimulating L-Ca^2＋αlc to trigger calcium-induced calcium release. Although Al^3＋ upregulated expression of Na＋/Ca^2＋exchanger mRNA, increased levels of Ca^2＋ and Na＋/Ca^2＋ exchanger did not maintain a normal Ca^2＋ balance. Al^3＋ resulted in disordered intracellular calcium homeostasis by affecting calcium channels, calcium buffering, and calcium expulsion.
