In this paper, a novel unsteady fluid network simulation method to compute the air system of jet engine was coded to predict the characteristics of pressure, temperature and mass flow rate of the flow and the temperat...In this paper, a novel unsteady fluid network simulation method to compute the air system of jet engine was coded to predict the characteristics of pressure, temperature and mass flow rate of the flow and the temperature of the solid in the gas turbine engine. The fluid and solid areas are divided into the network comprised of branches and nodes, and the method solves transient mass, energy conservation equations at each node and momentum conservation equation at each branch by a newly deduced numerical method. With this method, to simulate complicated fluid and solid system in short time becomes possible. To verify the code developed, it has been applied to simulate a gas turbine model against the widely used commercial software Flowmaster. And the comparisons show that the two are in good agreement. Then the verified program is applied to the prediction of the characteristics of a designed turbine disk and air-cooling system associated to it, and useful information is obtained.展开更多
1.Introduction Artificial intelligence(AI)has demonstrated remarkable advancements in ophthalmology,particularly in disease detection,grading,classification,and prediction with equal or even superior performance to ex...1.Introduction Artificial intelligence(AI)has demonstrated remarkable advancements in ophthalmology,particularly in disease detection,grading,classification,and prediction with equal or even superior performance to experienced ophthalmologists.1,2 These findings highlight the promising potential of AI in clinical application and its role as a powerful assistant for ophthalmologists.However,while the clinical utility of AI for ophthalmologists has been well documented,its application in pre-clinic settings to assist patients with eye diseases remains largely unexplored.Few studies evaluated the effectiveness of AI in providing eye health education to patients,which is vital,especially for patients with systemic diseases to prevent or attenuate ocular complications.Vision loss from diabetic retinopathy is largely preventable,but less than two-thirds of diabetic patients adhere to recommended annual eye examination,3 suggesting a huge insufficiency in vision self-management during diabetes course.By investigating and comparing the effectiveness of different AI tools in generating diabetic retinopathy guidelines,this study aimed to offer guidance in selecting AI platforms best suited to promote understanding and adherence to medical guidelines for vision protection.展开更多
Lens epithelium,a fundamental biological structure pivotal for maintaining normal vision,can be disrupted,leading to the development of cataracts.The epithelial-mesenchymal transition has been proven to be the key fac...Lens epithelium,a fundamental biological structure pivotal for maintaining normal vision,can be disrupted,leading to the development of cataracts.The epithelial-mesenchymal transition has been proven to be the key factor of secondary cataract progression.However,the underlying mechanism of epithelial-mesenchymal transition in lens epithelial cells remains unclear.In this study,we conducted a comprehensive analysis and classification annotation of single-cell transcriptomic sequencing(scRNA-seq)data.This data was derived from fetal eye tissues of ages ranging from 9 to 23 weeks,sourced from our previously published research.Trajectory analysis showed a differentiation trend from epithelial cell to fiber cell.Furthermore,an integrative analysis of accessible-chromatin sequencing(scATAC-seq)and single-cell RNA sequencing(scRNA-seq)data revealed that the transcription factor ATF6 may play a pivotal role in maintaining the homeostasis of lens epithelial cells.Subsequent in vitro experiments revealed that inhibition of ATF6 could alleviate epithelial-mesenchymal fibrosis by reducing STAT3 phosphorylation.Collectively,our study presents an atlas of lens epithelial cell development at the single-cell resolution,uncovering evidence that heightened ATF6 activity could potentially promote epithelial-mesenchymal transition in lens epithelial cells.展开更多
Hard carbon(HC)as an anode material for sodium-ion batteries(SIBs)suffers from poor rate capability,low firstcycle coulombic efficiency,and insufficient cycle stability.To address these issues,HC is commonly modified ...Hard carbon(HC)as an anode material for sodium-ion batteries(SIBs)suffers from poor rate capability,low firstcycle coulombic efficiency,and insufficient cycle stability.To address these issues,HC is commonly modified via hightemperature sintering,hydrothermal synthesis,or gas-phase deposition;however,these methods often introduce impurities due to the use of additives.In this work,dielectric barrier discharge(DBD)plasma,a“clean modification”technique employing energetic particles,is utilized to simultaneously etch the carbon skeleton and dope nitrogen atoms onto the HC surface.By adjusting the modification time,the size of pseudo-graphitic microcrystals can be precisely controlled,while the energetic species generated by the DBD plasma facilitate the formation of nitrogen defects(N-defects).This strategy effectively tailors the pore structure and interfacial wettability of HC,thereby creating additional Na^(+)active sites and enhancing Na^(+)transport kinetics.As a result,the optimized HC-6 sample delivers a reversible capacity of 326.8 mAh g^(-1)at 0.02 A g^(-1),along with a capacity retention rate of 92.73%after 800 cycles under high-rate conditions(3 A g^(-1)).Compared with pristine HC,HC-6 exhibits a 14%increase in capacity and a 50%longer cycle life.This study provides valuable insights into the strategic design of HC surface architectures via plasma engineering and promotes the advancement of plasma-modified SIB materials.展开更多
Vogt–Koyanagi–Harada(VKH)disease is a leading cause of blindness in young and middle-aged people.However,the etiology of VKH disease remains unclear.Here,we performed the first trio-based whole-exome sequencing stud...Vogt–Koyanagi–Harada(VKH)disease is a leading cause of blindness in young and middle-aged people.However,the etiology of VKH disease remains unclear.Here,we performed the first trio-based whole-exome sequencing study,which enrolled 25 VKH patients and 50 controls,followed by a study of 2081 VKH patients from a Han Chinese population to uncover detrimental mutations.A total of 15 de novo mutations in VKH patients were identified,with one of the most important being the membrane palmitoylated protein 2(MPP2)p.K315N(MPP2-N315)mutation.The MPP2-N315 mutation was highly deleterious according to bioinformatic predictions.Additionally,this mutation appears rare,being absent from the 1000 Genome Project and Genome Aggregation Database,and it is highly conserved in 10 species,including humans and mice.Subsequent studies showed that pathological phenotypes and retinal vascular leakage were aggravated in MPP2-N315 mutation knock-in or MPP2-N315 adeno-associated virus-treated mice with experimental autoimmune uveitis(EAU).In vitro,we used clustered regularly interspaced short palindromic repeats(CRISPR‒Cas9)gene editing technology to delete intrinsic MPP2 before overexpressing wild-type MPP2 or MPP2-N315.Levels of cytokines,such as IL-1β,IL-17E,and vascular endothelial growth factor A,were increased,and barrier function was destroyed in the MPP2-N315 mutant ARPE19 cells.Mechanistically,the MPP2-N315 mutation had a stronger ability to directly bind to ANXA2 than MPP2-K315,as shown by LC‒MS/MS and Co-IP,and resulted in activation of the ERK3/IL-17E pathway.Overall,our results demonstrated that the MPP2-K315N mutation may increase susceptibility to VKH disease.展开更多
Uveitis,a vision-threatening inflammatory disease worldwide,is closely related to resident microglia.Retinal microglia are the main immune effector cells with strong plasticity,but their role in uveitis remains unclea...Uveitis,a vision-threatening inflammatory disease worldwide,is closely related to resident microglia.Retinal microglia are the main immune effector cells with strong plasticity,but their role in uveitis remains unclear.N6-methyladenosine(m^(6)A)modification has been proven to be involved in the immune response.Therefore,we in this work aimed to identify the potentially crucial m^(6)A regulators of microglia in uveitis.Through the single-cell sequencing(scRNA-seq)analysis and experimental verification,we found a significant decrease in the expression of fat mass and obesity-associated protein(FTO)in retinal microglia of uveitis mice and human microglia clone 3(HMC3)cells with inflammation.Additionally,FTO knockdown was found to aggravate the secretion of inflammatory factors and the mobility/chemotaxis of microglia.Mechanistically,the RNA-seq data and rescue experiments showed that glypican 4(GPC4)was the target of FTO,which regulated microglial inflammation mediated by the TLR4/NF-κB pathway.Moreover,RNA stability assays indicated that GPC4 upregulation was mainly regulated by the downregulation of the m^(6)A“reader”YTH domain family protein 3(YTHDF3).Finally,the FTO inhibitor FB23-2 further exacerbated experimental autoimmune uveitis(EAU)inflammation by promoting the GPC4/TLR4/NF-κB signaling axis,and this could be attenuated by the TLR4 inhibitor TAK-242.Collectively,a decreased FTO could facilitate microglial inflammation in EAU,suggesting that the restoration or activation of FTO function may be a potential therapeutic strategy for uveitis.展开更多
Behcet’s disease is defined as a multisystemic inflammatory disease.Although the precise pathogenesis and etiology is still a mystery,accumulating evidence shows that genetic variants of immune-related genes have a p...Behcet’s disease is defined as a multisystemic inflammatory disease.Although the precise pathogenesis and etiology is still a mystery,accumulating evidence shows that genetic variants of immune-related genes have a profound influence on the development of Behcet’s disease.To explore the genetic factors for Behcet’s disease,our group investigated the association of Behcet’s disease with multiple immune response genes and has identified multiple Behcet’s disease-related immunoregulatory pathways in the Chinese Han population.A large number of gene polymorphisms were studied including STAT4,IL23R,CD40,CCR1/CCR3,STAT3,OPN,IL17,JAK2,MCP-1,CTLA4,PD-1,PD-L1,PD-L2,TGRBR3,CCR6,PTPN22,FCRL3,IRF5,SUMO4 and UBAC2.Significant associations were found between Behcet’s disease and STAT4,IL23R,CD40,CCR1/CCR3,STAT3,MCP-1,TGFBR3,FCRL3,SUMO4,UBAC2.These genetic predisposition studies support an important role for both lymphocyte differentiation as well as ubiquitination pathways.These findings are helpful in elucidating the pathogenesis of Behcet’s disease and hopefully will allow the development of novel treatment regimes.展开更多
文摘In this paper, a novel unsteady fluid network simulation method to compute the air system of jet engine was coded to predict the characteristics of pressure, temperature and mass flow rate of the flow and the temperature of the solid in the gas turbine engine. The fluid and solid areas are divided into the network comprised of branches and nodes, and the method solves transient mass, energy conservation equations at each node and momentum conservation equation at each branch by a newly deduced numerical method. With this method, to simulate complicated fluid and solid system in short time becomes possible. To verify the code developed, it has been applied to simulate a gas turbine model against the widely used commercial software Flowmaster. And the comparisons show that the two are in good agreement. Then the verified program is applied to the prediction of the characteristics of a designed turbine disk and air-cooling system associated to it, and useful information is obtained.
基金supported by the National Natural Science Foundation Project of China(82271078)the Project of Youth Beijing Scholar(No.076)Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(PWD&RPP-MRI,JYY2023-6).
文摘1.Introduction Artificial intelligence(AI)has demonstrated remarkable advancements in ophthalmology,particularly in disease detection,grading,classification,and prediction with equal or even superior performance to experienced ophthalmologists.1,2 These findings highlight the promising potential of AI in clinical application and its role as a powerful assistant for ophthalmologists.However,while the clinical utility of AI for ophthalmologists has been well documented,its application in pre-clinic settings to assist patients with eye diseases remains largely unexplored.Few studies evaluated the effectiveness of AI in providing eye health education to patients,which is vital,especially for patients with systemic diseases to prevent or attenuate ocular complications.Vision loss from diabetic retinopathy is largely preventable,but less than two-thirds of diabetic patients adhere to recommended annual eye examination,3 suggesting a huge insufficiency in vision self-management during diabetes course.By investigating and comparing the effectiveness of different AI tools in generating diabetic retinopathy guidelines,this study aimed to offer guidance in selecting AI platforms best suited to promote understanding and adherence to medical guidelines for vision protection.
基金support by the National Natural Science Foundation Project of China(No.82271078)Youth Beijing Scholar(No.076)Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(No.PWD&RPP-MRI,JYY2023-6).
文摘Lens epithelium,a fundamental biological structure pivotal for maintaining normal vision,can be disrupted,leading to the development of cataracts.The epithelial-mesenchymal transition has been proven to be the key factor of secondary cataract progression.However,the underlying mechanism of epithelial-mesenchymal transition in lens epithelial cells remains unclear.In this study,we conducted a comprehensive analysis and classification annotation of single-cell transcriptomic sequencing(scRNA-seq)data.This data was derived from fetal eye tissues of ages ranging from 9 to 23 weeks,sourced from our previously published research.Trajectory analysis showed a differentiation trend from epithelial cell to fiber cell.Furthermore,an integrative analysis of accessible-chromatin sequencing(scATAC-seq)and single-cell RNA sequencing(scRNA-seq)data revealed that the transcription factor ATF6 may play a pivotal role in maintaining the homeostasis of lens epithelial cells.Subsequent in vitro experiments revealed that inhibition of ATF6 could alleviate epithelial-mesenchymal fibrosis by reducing STAT3 phosphorylation.Collectively,our study presents an atlas of lens epithelial cell development at the single-cell resolution,uncovering evidence that heightened ATF6 activity could potentially promote epithelial-mesenchymal transition in lens epithelial cells.
基金financially supported by the National Natural Science Foundation of China(Grant Nos.12175089,12205127)the Applied Basic Research Programs of Yunnan Provincial Science and Technology Department(Grant Nos.202401AV070008,202301AS070051,202401AT070329,202301BE070001-052,202301AU070064)the“Xingdian Talent Support Plan”Programs of Yunnan Province(Grant Nos.KKXY202252001,KKXX202452067)。
文摘Hard carbon(HC)as an anode material for sodium-ion batteries(SIBs)suffers from poor rate capability,low firstcycle coulombic efficiency,and insufficient cycle stability.To address these issues,HC is commonly modified via hightemperature sintering,hydrothermal synthesis,or gas-phase deposition;however,these methods often introduce impurities due to the use of additives.In this work,dielectric barrier discharge(DBD)plasma,a“clean modification”technique employing energetic particles,is utilized to simultaneously etch the carbon skeleton and dope nitrogen atoms onto the HC surface.By adjusting the modification time,the size of pseudo-graphitic microcrystals can be precisely controlled,while the energetic species generated by the DBD plasma facilitate the formation of nitrogen defects(N-defects).This strategy effectively tailors the pore structure and interfacial wettability of HC,thereby creating additional Na^(+)active sites and enhancing Na^(+)transport kinetics.As a result,the optimized HC-6 sample delivers a reversible capacity of 326.8 mAh g^(-1)at 0.02 A g^(-1),along with a capacity retention rate of 92.73%after 800 cycles under high-rate conditions(3 A g^(-1)).Compared with pristine HC,HC-6 exhibits a 14%increase in capacity and a 50%longer cycle life.This study provides valuable insights into the strategic design of HC surface architectures via plasma engineering and promotes the advancement of plasma-modified SIB materials.
基金We thank the families for participation in this study,and we thank Novogene Technology Co.,Ltd.,for the WES sequencing and analysis.This work was supported by the National Natural Science Foundation Project of China(82070951,82271078)the National Natural Science Foundation Key Program(81930023)+3 种基金The Innovative Research Group Project of Chongqing Education Commission(CXQT19015)the Innovation Supporting Plan of Overseas Study of Chongqing(cx2018010)the National Key Clinical Specialties Construction Program of China,the Chongqing Branch of the National Clinical Research Center for Ocular Diseases,the Chongqing Key Laboratory of Ophthalmology(CSTC,2008CA5003)the Program for Youth Innovation in Future Medicine,Chongqing Medical University(w0047).
文摘Vogt–Koyanagi–Harada(VKH)disease is a leading cause of blindness in young and middle-aged people.However,the etiology of VKH disease remains unclear.Here,we performed the first trio-based whole-exome sequencing study,which enrolled 25 VKH patients and 50 controls,followed by a study of 2081 VKH patients from a Han Chinese population to uncover detrimental mutations.A total of 15 de novo mutations in VKH patients were identified,with one of the most important being the membrane palmitoylated protein 2(MPP2)p.K315N(MPP2-N315)mutation.The MPP2-N315 mutation was highly deleterious according to bioinformatic predictions.Additionally,this mutation appears rare,being absent from the 1000 Genome Project and Genome Aggregation Database,and it is highly conserved in 10 species,including humans and mice.Subsequent studies showed that pathological phenotypes and retinal vascular leakage were aggravated in MPP2-N315 mutation knock-in or MPP2-N315 adeno-associated virus-treated mice with experimental autoimmune uveitis(EAU).In vitro,we used clustered regularly interspaced short palindromic repeats(CRISPR‒Cas9)gene editing technology to delete intrinsic MPP2 before overexpressing wild-type MPP2 or MPP2-N315.Levels of cytokines,such as IL-1β,IL-17E,and vascular endothelial growth factor A,were increased,and barrier function was destroyed in the MPP2-N315 mutant ARPE19 cells.Mechanistically,the MPP2-N315 mutation had a stronger ability to directly bind to ANXA2 than MPP2-K315,as shown by LC‒MS/MS and Co-IP,and resulted in activation of the ERK3/IL-17E pathway.Overall,our results demonstrated that the MPP2-K315N mutation may increase susceptibility to VKH disease.
基金supported by the National Natural Science Foundation Project of China(No.82070951,82271078 and 81873678)the Innovative Research Group Project of Chongqing Education Commission(China)(No.CXQT19015)+5 种基金the Natural Science Foundation Project of Chongqing,China(No.cstc2019jcyjmsxmx0120)the Innovation Supporting Plan of Overseas Study of Chongqing,China(No.cx2018010)the Chongqing Education Commission(China)(No.KJQN202000406)the National Key Clinical Specialties Construction Program of China,Chongqing Branch of National Clinical Research Center for Ocular Diseasesthe Chongqing Key Laboratory of Ophthalmology(China)(CSTC,No.2008CA5003)Natural Science Foundation Project of Chongqing Medical University(China)(No.W0047).
文摘Uveitis,a vision-threatening inflammatory disease worldwide,is closely related to resident microglia.Retinal microglia are the main immune effector cells with strong plasticity,but their role in uveitis remains unclear.N6-methyladenosine(m^(6)A)modification has been proven to be involved in the immune response.Therefore,we in this work aimed to identify the potentially crucial m^(6)A regulators of microglia in uveitis.Through the single-cell sequencing(scRNA-seq)analysis and experimental verification,we found a significant decrease in the expression of fat mass and obesity-associated protein(FTO)in retinal microglia of uveitis mice and human microglia clone 3(HMC3)cells with inflammation.Additionally,FTO knockdown was found to aggravate the secretion of inflammatory factors and the mobility/chemotaxis of microglia.Mechanistically,the RNA-seq data and rescue experiments showed that glypican 4(GPC4)was the target of FTO,which regulated microglial inflammation mediated by the TLR4/NF-κB pathway.Moreover,RNA stability assays indicated that GPC4 upregulation was mainly regulated by the downregulation of the m^(6)A“reader”YTH domain family protein 3(YTHDF3).Finally,the FTO inhibitor FB23-2 further exacerbated experimental autoimmune uveitis(EAU)inflammation by promoting the GPC4/TLR4/NF-κB signaling axis,and this could be attenuated by the TLR4 inhibitor TAK-242.Collectively,a decreased FTO could facilitate microglial inflammation in EAU,suggesting that the restoration or activation of FTO function may be a potential therapeutic strategy for uveitis.
文摘Behcet’s disease is defined as a multisystemic inflammatory disease.Although the precise pathogenesis and etiology is still a mystery,accumulating evidence shows that genetic variants of immune-related genes have a profound influence on the development of Behcet’s disease.To explore the genetic factors for Behcet’s disease,our group investigated the association of Behcet’s disease with multiple immune response genes and has identified multiple Behcet’s disease-related immunoregulatory pathways in the Chinese Han population.A large number of gene polymorphisms were studied including STAT4,IL23R,CD40,CCR1/CCR3,STAT3,OPN,IL17,JAK2,MCP-1,CTLA4,PD-1,PD-L1,PD-L2,TGRBR3,CCR6,PTPN22,FCRL3,IRF5,SUMO4 and UBAC2.Significant associations were found between Behcet’s disease and STAT4,IL23R,CD40,CCR1/CCR3,STAT3,MCP-1,TGFBR3,FCRL3,SUMO4,UBAC2.These genetic predisposition studies support an important role for both lymphocyte differentiation as well as ubiquitination pathways.These findings are helpful in elucidating the pathogenesis of Behcet’s disease and hopefully will allow the development of novel treatment regimes.
