Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related t...Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation.However,the effect of Spi1 on intracerebral hemorrhage remains unclear.In this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome.We showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained remyelination.Notably,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and coagulation.In conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage.This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.展开更多
The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to investigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial...The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to investigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar.We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation.Spatial transcriptomics(ST)analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods.During the early stage,sustained microglial depletion induced disorganized astrocytic scar,enhanced neutrophil infiltration,and impaired tissue repair.ST analysis indicated that microglia-derived insulin like growth factor 1(IGF1)modulated astrocytic scar formation via mechanistic target of rapamycin(mTOR)signaling activation.Moreover,repopulating microglia(RM)more strongly activated mTOR signaling,facilitating a more protective scar formation.The combination of IGF1 and osteopontin(OPN)was necessary and sufficient for RM function,rather than IGF1 or OPN alone.At the chronic stage of ICH,the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this.The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH.Inversely,early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy.This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes,and develop elaborate treatment strategies at precise time points after ICH.展开更多
The isomerization of n-pentane to generate high-quality blending components for clean gasoline was catalyzed by several amide-AlCl3-based ionic liquid(IL) analogs with various amides as donor molecules. The catalytic ...The isomerization of n-pentane to generate high-quality blending components for clean gasoline was catalyzed by several amide-AlCl3-based ionic liquid(IL) analogs with various amides as donor molecules. The catalytic performance of these IL analogs was evaluated in a magnetic agitated autoclave operated in batch mode.IL analog based n-methylacetamide(NMA)-AlCl3 with the amide/AlCl3 molar ratio of 0.65 showed excellent performance toward n-pentane isomerization because 0.65 NMA-1.0 AlCl3 had a low viscosity and bidentate coordination structure. The influences of reaction time, reaction temperature, and stirring speed on the catalytic performance were also investigated. Optimal reaction conditions comprised the reaction time of 1 h, the reaction temperature of 40 °C, and the stirring speed of 1500 r·min-1. Under optimal condition, the n-C5 conversion,research octane number(RON) increment, total liquids yield, and isoparaffin yield in isomerized oil were56.80%, 13.51, 89.90 wt%, and 44.32 wt%, respectively. A new mathematical model was constructed to predict the relationships among RON increment, RON increment/n-C5 conversion ratio, and n-C5 conversion. The new model indicated that an appropriate conversion per pass of n-C5 did not exceed 50%–55%. Various cycloparaffin additives were used to improve the catalytic performance of 0.65 NMA-1.0 AlCl3. The n-C5 conversion increased from 56.80% to 67.32%. The RON increment, total liquids yield, and isoparaffin yield reached 17.83, 97.36 wt%,and 63.74 wt%, respectively.展开更多
Background:China is undergoing a massive transition toward an urban and industrial economy.These changes will restructure the demographics and economy which will eventually influence the future patterns of disease.The...Background:China is undergoing a massive transition toward an urban and industrial economy.These changes will restructure the demographics and economy which will eventually influence the future patterns of disease.The risk factors of vision-impairing eye diseases remain ambiguous and poorly understood.Metabolomics is an ideal tool to understand and shed light on the ocular disease mechanisms for earlier treatment.This article aims to describe the design,methodology and baseline data of the Yueqing Ocular Diseases Investigation(YODI),a developed county population-based study to determine the prevalence and primary causes of visual impairment;also with metabonomics analysis we aimed to identify,predict and suggest some preventive biomarkers that cause blindness.Methods:A population-based,cross-sectional study.Randomized clustering sampling was used to identify adults aged 50 years and older in Xiangyang Town,Yueqing county-level City.The interviews covered demographic,behavioral,ocular risk factors and mental health state.The ocular examination included visual acuity,autorefraction,intraocular pressure,anterior and posterior segment examinations,fundus photography,retinal tomography and angiography,and visual field testing.Anthropometric measurements included height and weight,waist and hip circumference,blood pressure,pulse rate,electrocardiogram,and abdominal ultrasound scan.A venous blood sample was collected for laboratory tests and metabonomics studies.Results:Of the 5319 individuals recruited for the YODI,4769(89.7%)subjects were enrolled for analyses.The median age was 62.0 years,and 45.6%were male.The educational level of illiteracy or semi-illiteracy,primary,middle and high school or above was 29.8%,45.5%,20.1%,and 3.3%,respectively.Majority of the participants were female,younger,and less educated when compared with nonparticipants.The average body mass index and waist-hip ratios were 24.4±3.4 kg/m^(2) and 0.9±0.1 respectively.Blood sample collection reached a sample size of 1909(479 from subjects with selfreported diabetes and 1430 from one-third of the 4290 subjects without self-reported diabetes).Conclusions:The YODI provides population-based data with a high response rate(89.7%)on the prevalence and primary causes of major vision-impairing eye diseases in developed county areas in eastern China.Metabonomics analysis from YODI will provide further association of metabolic characteristics with the visual impairment eye diseases.The risk prediction model could be created and has the potential to be generalized to developed eastern areas in China for prevention.展开更多
基金supported by the National Natural Science Foundation of China,No.81971097(to JY)。
文摘Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation.However,the effect of Spi1 on intracerebral hemorrhage remains unclear.In this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome.We showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained remyelination.Notably,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and coagulation.In conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage.This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82071287,81870916)the National Natural Science Foundation of China(Grant No.:81971097)+3 种基金the Basic Public Interests Research Plan of Zhejiang Province,China(Grant No.:GF18H090006)the National Natural Science Foundation of China(Grant No.:81701214)the National Natural Science Foundation of China(Grant No.:82001299)the Natural Science Foundation of Zhejiang Province,China(Grant No.:TGD23C040017).
文摘The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to investigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar.We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation.Spatial transcriptomics(ST)analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods.During the early stage,sustained microglial depletion induced disorganized astrocytic scar,enhanced neutrophil infiltration,and impaired tissue repair.ST analysis indicated that microglia-derived insulin like growth factor 1(IGF1)modulated astrocytic scar formation via mechanistic target of rapamycin(mTOR)signaling activation.Moreover,repopulating microglia(RM)more strongly activated mTOR signaling,facilitating a more protective scar formation.The combination of IGF1 and osteopontin(OPN)was necessary and sufficient for RM function,rather than IGF1 or OPN alone.At the chronic stage of ICH,the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this.The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH.Inversely,early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy.This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes,and develop elaborate treatment strategies at precise time points after ICH.
基金Supported by the National Natural Science Foundation of China(21802047)the Scientific Research Funds of Huaqiao University(600005-Z17Y0073).
文摘The isomerization of n-pentane to generate high-quality blending components for clean gasoline was catalyzed by several amide-AlCl3-based ionic liquid(IL) analogs with various amides as donor molecules. The catalytic performance of these IL analogs was evaluated in a magnetic agitated autoclave operated in batch mode.IL analog based n-methylacetamide(NMA)-AlCl3 with the amide/AlCl3 molar ratio of 0.65 showed excellent performance toward n-pentane isomerization because 0.65 NMA-1.0 AlCl3 had a low viscosity and bidentate coordination structure. The influences of reaction time, reaction temperature, and stirring speed on the catalytic performance were also investigated. Optimal reaction conditions comprised the reaction time of 1 h, the reaction temperature of 40 °C, and the stirring speed of 1500 r·min-1. Under optimal condition, the n-C5 conversion,research octane number(RON) increment, total liquids yield, and isoparaffin yield in isomerized oil were56.80%, 13.51, 89.90 wt%, and 44.32 wt%, respectively. A new mathematical model was constructed to predict the relationships among RON increment, RON increment/n-C5 conversion ratio, and n-C5 conversion. The new model indicated that an appropriate conversion per pass of n-C5 did not exceed 50%–55%. Various cycloparaffin additives were used to improve the catalytic performance of 0.65 NMA-1.0 AlCl3. The n-C5 conversion increased from 56.80% to 67.32%. The RON increment, total liquids yield, and isoparaffin yield reached 17.83, 97.36 wt%,and 63.74 wt%, respectively.
基金This study was supported by Yueqing Eye Health Project:Benefiting the People with Technology and Science,Grant 2014H01007 from the Science&Technology Department of the Zhejiang Province,China.
文摘Background:China is undergoing a massive transition toward an urban and industrial economy.These changes will restructure the demographics and economy which will eventually influence the future patterns of disease.The risk factors of vision-impairing eye diseases remain ambiguous and poorly understood.Metabolomics is an ideal tool to understand and shed light on the ocular disease mechanisms for earlier treatment.This article aims to describe the design,methodology and baseline data of the Yueqing Ocular Diseases Investigation(YODI),a developed county population-based study to determine the prevalence and primary causes of visual impairment;also with metabonomics analysis we aimed to identify,predict and suggest some preventive biomarkers that cause blindness.Methods:A population-based,cross-sectional study.Randomized clustering sampling was used to identify adults aged 50 years and older in Xiangyang Town,Yueqing county-level City.The interviews covered demographic,behavioral,ocular risk factors and mental health state.The ocular examination included visual acuity,autorefraction,intraocular pressure,anterior and posterior segment examinations,fundus photography,retinal tomography and angiography,and visual field testing.Anthropometric measurements included height and weight,waist and hip circumference,blood pressure,pulse rate,electrocardiogram,and abdominal ultrasound scan.A venous blood sample was collected for laboratory tests and metabonomics studies.Results:Of the 5319 individuals recruited for the YODI,4769(89.7%)subjects were enrolled for analyses.The median age was 62.0 years,and 45.6%were male.The educational level of illiteracy or semi-illiteracy,primary,middle and high school or above was 29.8%,45.5%,20.1%,and 3.3%,respectively.Majority of the participants were female,younger,and less educated when compared with nonparticipants.The average body mass index and waist-hip ratios were 24.4±3.4 kg/m^(2) and 0.9±0.1 respectively.Blood sample collection reached a sample size of 1909(479 from subjects with selfreported diabetes and 1430 from one-third of the 4290 subjects without self-reported diabetes).Conclusions:The YODI provides population-based data with a high response rate(89.7%)on the prevalence and primary causes of major vision-impairing eye diseases in developed county areas in eastern China.Metabonomics analysis from YODI will provide further association of metabolic characteristics with the visual impairment eye diseases.The risk prediction model could be created and has the potential to be generalized to developed eastern areas in China for prevention.
