BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in children and adolescents.NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis(N...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in children and adolescents.NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis(NASH),wherein hepatocellular inflammation and/or fibrosis coexist with steatosis.Circulating microRNA(miRNA)levels have been suggested to be altered in NAFLD,but the extent to which miRNA are related to NAFLD features remains unknown.This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents.AIM To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD.METHODS This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study.Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD.Plasma samples were collected during surgery for miRNA profiling.A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform.We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age,sex,race,and other key covariates.Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD.RESULTS We identified 16 upregulated plasma miRNAs,including miR-193a-5p and miR-193b-5p,and 22 downregulated plasma miRNAs,including miR-1282 and miR-6734-5p,in adolescents with NAFLD.Moreover,52,16,15,and 9 plasma miRNAs were associated with NASH,fibrosis,ballooning degeneration,and lobular inflammation,respectively.Collectively,16 miRNAs were associated with two or more histological features of NAFLD.Among those miRNAs,miR-411-5p was downregulated in NASH,ballooning,and fibrosis,while miR-122-5p,miR-1343-5p,miR-193a-5p,miR-193b-5p,and miR-7845-5p were consistently and positively associated with all histological features of NAFLD.Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression,while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B.CONCLUSION Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity.Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD.展开更多
It is well-known that the surface quality of the niobium microalloy profiled billet directly affects the comprehensive mechanical properties of the H-beam.The effects of chromium on theγ/αphase transformation and hi...It is well-known that the surface quality of the niobium microalloy profiled billet directly affects the comprehensive mechanical properties of the H-beam.The effects of chromium on theγ/αphase transformation and high-temperature mechanical properties of Nb-microalloyed steel were studied by Gleeble tensile and high-temperature in-situ observation experiments.Results indicated that the starting temperature of the γ→αphase transformation decreases with increasing Cr content.The hot ductility of Nb-microalloyed steel is improved by adding 0.12wt% Cr.Chromium atoms inhibit the diffusion of carbon atoms,which reduces the thickness of grain boundary ferrite.The number fractions of high-angle grain boundaries increase with increasing chromium content.In particular,the proportion is up to 48.7% when the Cr content is 0.12wt%.The high-angle grain boundaries hinder the crack propagation and improve the ductility of Nb-microalloyed steel.展开更多
Based on the solidification heat transfer model and CAFÉmodel,the solidification structure of GCr15 bloom alloy was studied.Using nail shooting and acid etching experiments,the solidification models were verified...Based on the solidification heat transfer model and CAFÉmodel,the solidification structure of GCr15 bloom alloy was studied.Using nail shooting and acid etching experiments,the solidification models were verified.The secondary dendrite arm spacing(SDAS)model of GCr15 was obtained by simulation calculation and metallographic observation.With the increase of casting speed,the SDAS,equiaxed crystal ratio(ECR)and average grain size increase.With the rise of superheat,the SDAS increases in the 20-70 mm of thickness and decreases in the 80-160 mm of thickness.The ECR decreases and the average grain size increases with the increase of superheat.With the increase of specific water flow,both the SDAS and ECR decrease.The minimum average grain size is obtained when the specific water flow is 0.20 L·kg^(-1).The central carbon segregation index is reduced from 1.11 to 1.075.展开更多
Objective:To investigate the hepatorenoprotective effects of Origanum vulgare L.against finasteride-induced oxidative injury in the liver and kidney of mice.Methods:Liquid chromatography-electrospray ionization-tandem...Objective:To investigate the hepatorenoprotective effects of Origanum vulgare L.against finasteride-induced oxidative injury in the liver and kidney of mice.Methods:Liquid chromatography-electrospray ionization-tandem mass spectrometry(LC-ESI/MS)analysis was utilized to yield a fingerprint of Origanum vulgare polyphenolic constituents.Thirty BALB/c mice received 0.5 mL/day distilled water,finasteride(25 mg/kg/day for 10 d),and 100,200,or 400 mg/kg/day finasteride+Origanum vulgare extract with 6 mice per group for five weeks.On day 36,liver and kidney function as well as pro-and antiinflammatory(IFN-γ,IL-12,IL-6,TNF-α,IL-1β,and IL-10)cytokines were measured.The total antioxidant status,nitric oxide(NO),and malondialdehyde levels as well as the activities of NO synthase and catalase were also evaluated.Histopathological study was conducted to assess the effect of Origanum vulgare extract on finasteride-induced renal and hepatic toxicities.Results:Twenty-five major polyphenolic compounds were identified in the Origanum vulgare extract by LC-ESI/MS.Origanum vulgare extract,especially at 200 and 400 mg/kg/day doses,significantly improved liver and kidney biochemical indices,decreased inflammatory cytokines,increased total antioxidant status and NO synthase and catalase activities,as well as decreased plasma NO and malondialdehyde levels in a dose-dependent manner as compared to the finasteride group.Histopathological results further confirmed the protective effect of Origanum vulgare extract.Conclusions:Origanum vulgare extract ameliorates finasterideinduced hepatic and renal biochemical and histopathological alterations,and restores antioxidant/oxidant balance.展开更多
Ultrafine steel slag powder(shield powder)was prepared by grinding ordinary steel slag with a functional compound.As a substitute for aluminum hydroxide,the shield powder was combined with rubber to prepare flame-reta...Ultrafine steel slag powder(shield powder)was prepared by grinding ordinary steel slag with a functional compound.As a substitute for aluminum hydroxide,the shield powder was combined with rubber to prepare flame-retardant composites.Vulcanization tests showed that the incorporation of shield powder enhances the crosslinkage of the composite and speeds up the curing rate.The gaseous products formed in the pyrolysis process are mainly hydrocarbons.Mechanical and combustion tests revealed that the introduction of shield powder improves flame-retardant performance without sacrificing mechanical properties.Specifically,the optimum substitution ratio of shield powder for aluminum hydroxide is 50.0%.In this case,the composite has the highest degree of graphitization and exhibits excellent flame-retardant performance.展开更多
Background:The effect of short-segment decompression/fusion versus long-segment decompression/fusion and osteotomy for Lenke-Silva type Ⅵ adult degenerative scoliosis(ADS)has not been clarified.This study aimed to co...Background:The effect of short-segment decompression/fusion versus long-segment decompression/fusion and osteotomy for Lenke-Silva type Ⅵ adult degenerative scoliosis(ADS)has not been clarified.This study aimed to compare the clinical and radiographic results of short-segment fusion vs.long-segment fusion and osteotomy for patients with Lenke-Silva type Ⅵ ADS.Methods:Data of 28 patients who underwent spinal surgery for ADS from January 2012 to January 2014 in the General Hospital of Northern Theater Command were reviewed.Of the 28 patients,12 received long-segment fusion and osteotomy and 16 received short-segment fusion.Radiographic imaging parameters and clinical outcomes,including the sagittal vertical axis(SVA),lumbar lordosis(LL)angle,pelvic tilt(PT),sacral slope(SS),the visual analog scale(VAS),Japanese Orthopedic Association(JOA),Oswestry disability index(ODI),and lumbar stiffness disability index(LSDI)scores,were recorded.The difference between groups was compared using the dependent t test or Chi-squared test.Results:The Cobb and LL angles and SVA improved in both groups;however,PT and SS angles did not improve following short fusion.There were significant differences in the post-operative SVA(26.8±5.4mm vs.47.5±7.6 mm,t=–8.066,P<0.001),PT(14.7±1.8°vs.29.1±3.4°,t=–13.277,P<0.001),and SS(39.8±7.2°vs.26.1±3.3°,t=6.175,P<0.001)between the long and short fusion groups.All patients had improved ODI,JOA,and VAS scores post-operatively(all P<0.001),with no significant difference between the groups(all P>0.05).The post-operative LSDI score was 3.5±0.5 in the long fusion group,which was significantly higher than that of the short fusion group(1.4±0.7;P<0.001).Conclusions:The clinical outcomes of patients with Lenke-Silva type Ⅵ ADS who underwent short-segment decompression/fusion were comparable to those of patients who underwent long-segment decompression/fusion and osteotomy despite poor correction of sagittal imbalance.Moreover,short-segment decompression/fusion showed a short operation time and reduced surgical trauma.展开更多
To the Editor:Ischemic stroke remains a major cause of death and disability worldwide and contributes to the rising costs of health care.Thrombolytic therapy with tissue plasminogen activator (tPA,alteplase)is benefic...To the Editor:Ischemic stroke remains a major cause of death and disability worldwide and contributes to the rising costs of health care.Thrombolytic therapy with tissue plasminogen activator (tPA,alteplase)is beneficial for the treatment of acute ischemic stroke.However,only 40%to 50%of stroke patients show a significant improvement after treatment.In addition,the use of alteplase is restricted because symptomatic intracranial hemorrhase (slCH)occurs in 1.7%to 6.4%of treated patients.[1] 25-hydroxyvitamin D (25(OH)D),which is the major circulating metabolite of vitamin D,has been confirmed to be closely related to cerebrovascular disease (CVD).A series of studies indicated that vitamin D deficiency was associated with an increased risk of ischemic stroke,high stroke severity and poor functional outcomes.展开更多
Background： Th9 cells are a newly discovered CD4＋ T helper cell subtype, characterized by high interleukin （IL）-9 secretion. Growing evidences suggest that Th9 cells are involved in the pathogenic mechanism of mul...Background： Th9 cells are a newly discovered CD4＋ T helper cell subtype, characterized by high interleukin （IL）-9 secretion. Growing evidences suggest that Th9 cells are involved in the pathogenic mechanism of multiple sclerosis （MS）. Mast cells are multifunctional innate imnmne cells, which are perhaps best known for their role as dominant effector cells in allergies and asthma. Several lines of evidence point to an important role lbr mast cells in MS and its animal models. Simultaneously, there is dynamic ＂＇cross-talk＂ between Th9 and mast cells. The aim of the present study was to examine the IL-9-mast cell axis in experimental autoimmune encephalomyelitis （EAE） and deternaine its interaction alter neutralizing anti-lL-9 antibody treatment. Methods： Female C57BL/6 mice were randomly divided into three groups （#1 = 5 in each group）： mice with myelin oligodendrocyte glycoprotein （MOG）-induced EAE （EAE group）, EAE mice treated with anti-lL-9 antibody （anti-lL-9 Abs group）, and EAE mice treated with IgG isotype control （lgG group）. EAE clinical score was evaluated. Mast cells from central nervous system （CNS） were detected by flow cytometry. The production of chemokine recruiting mast cells in the CNS was explored by reverse transcription-polymerase chain reaction （RT-PCR）. In mice with MOG-induced EAE, the expression of IL-9 receptor （IL-9R） complexes in CNS and spleen mast cells was also explored by RT-PCR, and then was repeating validated by immunocytochemistry. In vitro, spleen cells from EAE mice were cultured with anti-lL-9 antibody, and quantity of mast cells was counted by flow cytoinetry alter co-culture. Results： Compared with IgG group, IL-9 blockade delayed clinical disease onset and ameliorated EAE severity （t = -2.217, P- 0.031 ）, accompany with mast cells infiltration decreases （day 5： t = -8.005, P 〈 0.001; day 15： t = -11.857, P 〈 0.001; day 20： t- 5.243, P = 0.001 ） in anti-lL-9 Abs group. The messenger RNA expressions of C-C motif chemokine ligand 5 （t = -5.932, P = 0.003） and vascular cell adhesion molecule-I （t = -4.029, P 0.004） were significantly decreased alter 1L-9 neutralization in anti-lL-9 Abs group, compared with lgG group. In MOG-induced EAE, the 1L-9R complexes were expressed in CNS and spleen mast cells. 1#7 vitro, splenocyles cultured with anti-lL-9 antibody showed significantly lower levels of mast cells in a dose-dependent manner, compared with splenocytes cultured with anti-mouse lgG （5 μg/ml： t = -0.894, P = 0.397; 10 p-g/ml： t = -3.348, P - 0.019：20 μg/ml： I - -7.639, P 〈 0.001 ）.Conclusions： This study revealed that 1L-9 neutralization reduced mast cell infiltration in CNS and ameliorated EAE, which might be relate to the interaction between IL-9 and mast cells.展开更多
Crystal structure of conjugated molecules and polymers is fundamentally critical to understand their multilevel microstructures,carrier transport,and diverse functions.However,to determine the crystal structure of con...Crystal structure of conjugated molecules and polymers is fundamentally critical to understand their multilevel microstructures,carrier transport,and diverse functions.However,to determine the crystal structure of conjugated polymers is a significant challenge,mainly due to the poor crystallinity,weak diffraction,and instability under high-energy radiation.Here,we build the possible crystal structures of eight typical conjugated polymers,covering several widely used molecular segments in organic optoelectronics.We model the packing structures of these seed polymers based on synchrotron X-ray diffractions and molecular simulations.These crystal structures provide a new platform to predict the packing structures of more related polymer systems,extending the molecular scope.Based on this polymer crystal structure database,the multiscale microstructures and charge transport properties of conjugated polymers can be predicted before experiments.This study sets up a polymer crystal structure database to eliminate the current trial-and-error approaches and accelerating the design of high-performance conjugated polymers.展开更多
基金Supported by National Institute of Environmental Health,No.R01ES030691No.R01ES030364,No.R01ES029944,No.U01HG013288,No.T32-ES013678,No.P30ES007048,No.U2CES030859,No.R01ES032831,No.R01ES033688,No.P30ES023515,and No.P2CES033433+8 种基金National Human Genome Research Institute and National Institute of Environmental Health,No.U01HG013288California Environmental Protection Agency,No.20-E0017National Cancer Institute and National Institute of Environmental Health,No.P01CA196569Ministry of Science and Innovation and State Research Agency,No.CEX2018-000806-SEuropean Union(“NextGenerationEU/PRTR”),No.IJC2020-043630-IEuropean Union’s Horizon Europe Research And Innovation Programme Under the Marie Skłodowska-Curie Actions Postdoctoral Fellowships,No.101059245United States Department of Agriculture,No.6250-51000-053National Institutes of Health,No.R01DK128117-01A1The Teen-LABS Consortium:National Institute of Diabetes and Digestive and Kidney Diseases,No.UM1DK072493 and No.UM1DK095710.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in children and adolescents.NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis(NASH),wherein hepatocellular inflammation and/or fibrosis coexist with steatosis.Circulating microRNA(miRNA)levels have been suggested to be altered in NAFLD,but the extent to which miRNA are related to NAFLD features remains unknown.This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents.AIM To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD.METHODS This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study.Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD.Plasma samples were collected during surgery for miRNA profiling.A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform.We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age,sex,race,and other key covariates.Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD.RESULTS We identified 16 upregulated plasma miRNAs,including miR-193a-5p and miR-193b-5p,and 22 downregulated plasma miRNAs,including miR-1282 and miR-6734-5p,in adolescents with NAFLD.Moreover,52,16,15,and 9 plasma miRNAs were associated with NASH,fibrosis,ballooning degeneration,and lobular inflammation,respectively.Collectively,16 miRNAs were associated with two or more histological features of NAFLD.Among those miRNAs,miR-411-5p was downregulated in NASH,ballooning,and fibrosis,while miR-122-5p,miR-1343-5p,miR-193a-5p,miR-193b-5p,and miR-7845-5p were consistently and positively associated with all histological features of NAFLD.Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression,while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B.CONCLUSION Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity.Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD.
基金This work was financially supported by the National Natural Science Foundation of China(Nos.U1860104 and 51774030).
文摘It is well-known that the surface quality of the niobium microalloy profiled billet directly affects the comprehensive mechanical properties of the H-beam.The effects of chromium on theγ/αphase transformation and high-temperature mechanical properties of Nb-microalloyed steel were studied by Gleeble tensile and high-temperature in-situ observation experiments.Results indicated that the starting temperature of the γ→αphase transformation decreases with increasing Cr content.The hot ductility of Nb-microalloyed steel is improved by adding 0.12wt% Cr.Chromium atoms inhibit the diffusion of carbon atoms,which reduces the thickness of grain boundary ferrite.The number fractions of high-angle grain boundaries increase with increasing chromium content.In particular,the proportion is up to 48.7% when the Cr content is 0.12wt%.The high-angle grain boundaries hinder the crack propagation and improve the ductility of Nb-microalloyed steel.
基金financially supported by the National Natural Science Foundation of China(Grant Nos.51774030 and U1860104)the Fundamental Research Funds for the Central Universities(FRF-TP-20-029A1)。
文摘Based on the solidification heat transfer model and CAFÉmodel,the solidification structure of GCr15 bloom alloy was studied.Using nail shooting and acid etching experiments,the solidification models were verified.The secondary dendrite arm spacing(SDAS)model of GCr15 was obtained by simulation calculation and metallographic observation.With the increase of casting speed,the SDAS,equiaxed crystal ratio(ECR)and average grain size increase.With the rise of superheat,the SDAS increases in the 20-70 mm of thickness and decreases in the 80-160 mm of thickness.The ECR decreases and the average grain size increases with the increase of superheat.With the increase of specific water flow,both the SDAS and ECR decrease.The minimum average grain size is obtained when the specific water flow is 0.20 L·kg^(-1).The central carbon segregation index is reduced from 1.11 to 1.075.
基金supported by King Khalid University,Abha,KSA through Research Group Project under grant number R.G.P.2/80/41 and Wuxi Municipal Health and Family Planning Commission(WXQ201832).
文摘Objective:To investigate the hepatorenoprotective effects of Origanum vulgare L.against finasteride-induced oxidative injury in the liver and kidney of mice.Methods:Liquid chromatography-electrospray ionization-tandem mass spectrometry(LC-ESI/MS)analysis was utilized to yield a fingerprint of Origanum vulgare polyphenolic constituents.Thirty BALB/c mice received 0.5 mL/day distilled water,finasteride(25 mg/kg/day for 10 d),and 100,200,or 400 mg/kg/day finasteride+Origanum vulgare extract with 6 mice per group for five weeks.On day 36,liver and kidney function as well as pro-and antiinflammatory(IFN-γ,IL-12,IL-6,TNF-α,IL-1β,and IL-10)cytokines were measured.The total antioxidant status,nitric oxide(NO),and malondialdehyde levels as well as the activities of NO synthase and catalase were also evaluated.Histopathological study was conducted to assess the effect of Origanum vulgare extract on finasteride-induced renal and hepatic toxicities.Results:Twenty-five major polyphenolic compounds were identified in the Origanum vulgare extract by LC-ESI/MS.Origanum vulgare extract,especially at 200 and 400 mg/kg/day doses,significantly improved liver and kidney biochemical indices,decreased inflammatory cytokines,increased total antioxidant status and NO synthase and catalase activities,as well as decreased plasma NO and malondialdehyde levels in a dose-dependent manner as compared to the finasteride group.Histopathological results further confirmed the protective effect of Origanum vulgare extract.Conclusions:Origanum vulgare extract ameliorates finasterideinduced hepatic and renal biochemical and histopathological alterations,and restores antioxidant/oxidant balance.
基金supported by the University Synergy Innovation Program of Anhui Province(GXXT-2020-072)Anhui Province Science Foundation for Excellent Young Scholars(2208085J19).
文摘Ultrafine steel slag powder(shield powder)was prepared by grinding ordinary steel slag with a functional compound.As a substitute for aluminum hydroxide,the shield powder was combined with rubber to prepare flame-retardant composites.Vulcanization tests showed that the incorporation of shield powder enhances the crosslinkage of the composite and speeds up the curing rate.The gaseous products formed in the pyrolysis process are mainly hydrocarbons.Mechanical and combustion tests revealed that the introduction of shield powder improves flame-retardant performance without sacrificing mechanical properties.Specifically,the optimum substitution ratio of shield powder for aluminum hydroxide is 50.0%.In this case,the composite has the highest degree of graphitization and exhibits excellent flame-retardant performance.
文摘Background:The effect of short-segment decompression/fusion versus long-segment decompression/fusion and osteotomy for Lenke-Silva type Ⅵ adult degenerative scoliosis(ADS)has not been clarified.This study aimed to compare the clinical and radiographic results of short-segment fusion vs.long-segment fusion and osteotomy for patients with Lenke-Silva type Ⅵ ADS.Methods:Data of 28 patients who underwent spinal surgery for ADS from January 2012 to January 2014 in the General Hospital of Northern Theater Command were reviewed.Of the 28 patients,12 received long-segment fusion and osteotomy and 16 received short-segment fusion.Radiographic imaging parameters and clinical outcomes,including the sagittal vertical axis(SVA),lumbar lordosis(LL)angle,pelvic tilt(PT),sacral slope(SS),the visual analog scale(VAS),Japanese Orthopedic Association(JOA),Oswestry disability index(ODI),and lumbar stiffness disability index(LSDI)scores,were recorded.The difference between groups was compared using the dependent t test or Chi-squared test.Results:The Cobb and LL angles and SVA improved in both groups;however,PT and SS angles did not improve following short fusion.There were significant differences in the post-operative SVA(26.8±5.4mm vs.47.5±7.6 mm,t=–8.066,P<0.001),PT(14.7±1.8°vs.29.1±3.4°,t=–13.277,P<0.001),and SS(39.8±7.2°vs.26.1±3.3°,t=6.175,P<0.001)between the long and short fusion groups.All patients had improved ODI,JOA,and VAS scores post-operatively(all P<0.001),with no significant difference between the groups(all P>0.05).The post-operative LSDI score was 3.5±0.5 in the long fusion group,which was significantly higher than that of the short fusion group(1.4±0.7;P<0.001).Conclusions:The clinical outcomes of patients with Lenke-Silva type Ⅵ ADS who underwent short-segment decompression/fusion were comparable to those of patients who underwent long-segment decompression/fusion and osteotomy despite poor correction of sagittal imbalance.Moreover,short-segment decompression/fusion showed a short operation time and reduced surgical trauma.
文摘To the Editor:Ischemic stroke remains a major cause of death and disability worldwide and contributes to the rising costs of health care.Thrombolytic therapy with tissue plasminogen activator (tPA,alteplase)is beneficial for the treatment of acute ischemic stroke.However,only 40%to 50%of stroke patients show a significant improvement after treatment.In addition,the use of alteplase is restricted because symptomatic intracranial hemorrhase (slCH)occurs in 1.7%to 6.4%of treated patients.[1] 25-hydroxyvitamin D (25(OH)D),which is the major circulating metabolite of vitamin D,has been confirmed to be closely related to cerebrovascular disease (CVD).A series of studies indicated that vitamin D deficiency was associated with an increased risk of ischemic stroke,high stroke severity and poor functional outcomes.
文摘Background： Th9 cells are a newly discovered CD4＋ T helper cell subtype, characterized by high interleukin （IL）-9 secretion. Growing evidences suggest that Th9 cells are involved in the pathogenic mechanism of multiple sclerosis （MS）. Mast cells are multifunctional innate imnmne cells, which are perhaps best known for their role as dominant effector cells in allergies and asthma. Several lines of evidence point to an important role lbr mast cells in MS and its animal models. Simultaneously, there is dynamic ＂＇cross-talk＂ between Th9 and mast cells. The aim of the present study was to examine the IL-9-mast cell axis in experimental autoimmune encephalomyelitis （EAE） and deternaine its interaction alter neutralizing anti-lL-9 antibody treatment. Methods： Female C57BL/6 mice were randomly divided into three groups （#1 = 5 in each group）： mice with myelin oligodendrocyte glycoprotein （MOG）-induced EAE （EAE group）, EAE mice treated with anti-lL-9 antibody （anti-lL-9 Abs group）, and EAE mice treated with IgG isotype control （lgG group）. EAE clinical score was evaluated. Mast cells from central nervous system （CNS） were detected by flow cytometry. The production of chemokine recruiting mast cells in the CNS was explored by reverse transcription-polymerase chain reaction （RT-PCR）. In mice with MOG-induced EAE, the expression of IL-9 receptor （IL-9R） complexes in CNS and spleen mast cells was also explored by RT-PCR, and then was repeating validated by immunocytochemistry. In vitro, spleen cells from EAE mice were cultured with anti-lL-9 antibody, and quantity of mast cells was counted by flow cytoinetry alter co-culture. Results： Compared with IgG group, IL-9 blockade delayed clinical disease onset and ameliorated EAE severity （t = -2.217, P- 0.031 ）, accompany with mast cells infiltration decreases （day 5： t = -8.005, P 〈 0.001; day 15： t = -11.857, P 〈 0.001; day 20： t- 5.243, P = 0.001 ） in anti-lL-9 Abs group. The messenger RNA expressions of C-C motif chemokine ligand 5 （t = -5.932, P = 0.003） and vascular cell adhesion molecule-I （t = -4.029, P 0.004） were significantly decreased alter 1L-9 neutralization in anti-lL-9 Abs group, compared with lgG group. In MOG-induced EAE, the 1L-9R complexes were expressed in CNS and spleen mast cells. 1#7 vitro, splenocyles cultured with anti-lL-9 antibody showed significantly lower levels of mast cells in a dose-dependent manner, compared with splenocytes cultured with anti-mouse lgG （5 μg/ml： t = -0.894, P = 0.397; 10 p-g/ml： t = -3.348, P - 0.019：20 μg/ml： I - -7.639, P 〈 0.001 ）.Conclusions： This study revealed that 1L-9 neutralization reduced mast cell infiltration in CNS and ameliorated EAE, which might be relate to the interaction between IL-9 and mast cells.
基金supported by National Key R&D Program of China(2017YFA0204701)National Natural Science Foundation of China(21420102005,21790360,21722201)Beijing Outstanding Young Scientist Program(BJJWZYJH01201910001001).
文摘Crystal structure of conjugated molecules and polymers is fundamentally critical to understand their multilevel microstructures,carrier transport,and diverse functions.However,to determine the crystal structure of conjugated polymers is a significant challenge,mainly due to the poor crystallinity,weak diffraction,and instability under high-energy radiation.Here,we build the possible crystal structures of eight typical conjugated polymers,covering several widely used molecular segments in organic optoelectronics.We model the packing structures of these seed polymers based on synchrotron X-ray diffractions and molecular simulations.These crystal structures provide a new platform to predict the packing structures of more related polymer systems,extending the molecular scope.Based on this polymer crystal structure database,the multiscale microstructures and charge transport properties of conjugated polymers can be predicted before experiments.This study sets up a polymer crystal structure database to eliminate the current trial-and-error approaches and accelerating the design of high-performance conjugated polymers.
