Insects represent emerging sources of bioactive peptides and functional materials.Mantidis Oötheca(Sang-Piao-Xiao in Chinese,SPX)serves as an insect-derived medicine for treating kidney disease.This study demonst...Insects represent emerging sources of bioactive peptides and functional materials.Mantidis Oötheca(Sang-Piao-Xiao in Chinese,SPX)serves as an insect-derived medicine for treating kidney disease.This study demonstrated that supernatant(SPX)improved kidney function in adriamycin(ADR)-induced nephropathy mice model.Transcriptomic analysis revealed that SPX inhibited complement activation by targeting the MASP1-C3/C3a receptor(C3aR)pathway.Peptidomic analysis identified 304 peptides from SPX,with 49 peptides selected for evaluation using prediction tools and molecular docking with complement core protein C3.Three peptides(PMGFPFDR,FNDPK,AAQFFNR)exhibiting docking scores below-8.0 were synthesized to verify complement inhibition and anti-fibrotic activities.The synthetic peptide AAQFFNR demonstrated complement inhibitory activity,with an inhibitory complement hemolytic 50%(ICH_(50))value of 24.54μmol·L^(-1),and exhibited superior protective effects in ADR-induced HK-2 cells.Surface plasmon resonance(SPR)assay revealed direct interaction between AAQFFNR and complement C3 with K_(d)value of 16.8μmol·L^(-1).The reno-protective effect of AAQFFNR was subsequently verified in ADR-induced mice.This research provides initial evidence that complement C3-inhibiting peptides from insects demonstrate potential in preventing nephropathy through in silico and in vivo validation approaches.展开更多
Activation of spinal cord neural stem cells(NSCs)and subsequent neurogenesis holds a promising alternative for spinal cord injury(SCI)repair.Our previous study demonstrated that complement C3a,derived from reactive as...Activation of spinal cord neural stem cells(NSCs)and subsequent neurogenesis holds a promising alternative for spinal cord injury(SCI)repair.Our previous study demonstrated that complement C3a,derived from reactive astrocytes,inhibits NSC proliferation by suppressing protein aggregate clearance through the deubiquitinating enzyme ubiquitin carboxy-terminal hydrolase L1(UCHL1)-proteasome system post-SCI.However,the potential molecular mechanism by which C3a modulates NSC activation via this pathway remains unclear.Here,we revealed that C3a/C3a receptor(C3aR)signaling activated NF-κB p65,which in turn inhibited Nrf2 activity and UCHL1 expression,resulting in diminished proteasome activity and the accumulation of protein aggregates,and ultimately impaired NSC activation.Both knockdown of NF-κB p65 and Nrf2 upregulation restored UCHL1 expression and proteasome activity in vitro,promoting NSC activation by enhancing protein aggregate clearance.Mechanistically,we found that NF-κB p65 regulated Nrf2 activity through a dual mechanism:(1)promoting Keap1-dependent ubiquitination and proteasome degradation of Nrf2;(2)inhibiting protein kinase C-mediated Nrf2 phosphorylation and nuclear translocation.Using the dual-luciferase reporter assay and chromatin immunoprecipitation(ChIP)analysis,we further identified UCHL1 as a direct transcriptional target of Nrf2.Importantly,in vivo experiments using SCI mice confirmed that either C3aR blockade,NF-κB p65 knockdown,or Nrf2 overexpression could rescue SCI-induced UCHL1 downregulation.Together,this study uncovers the C3a-NF-κB p65-Nrf2-UCHL1-proteasome axis as a critical regulator of NSC activation after SCI.This may provide novel molecular targets and intervention strategies for SCI repair.展开更多
Objective:Triple-negative breast cancer(TNBC)is highly aggressive and lacks an effective targeted therapy.This study aimed to elucidate the functions and possible mechanisms of action of zinc finger miz-type containin...Objective:Triple-negative breast cancer(TNBC)is highly aggressive and lacks an effective targeted therapy.This study aimed to elucidate the functions and possible mechanisms of action of zinc finger miz-type containing 2(ZMIZ2)and minichromosome maintenance complex component 3(MCM3)in TNBC progression.Methods:The relationship between ZMIZ2 expression and clinical characteristics of TNBC was investigated.In vitro and in vivo experiments were performed to investigate the role of ZMIZ2 dysregulation in TNBC cell malignant behaviors.The regulatory relationship between ZMIZ2 and MCM3 was also explored.Transcriptome sequencing was performed to elucidate possible mechanisms underlying the ZMIZ2/MCM3 axis in TNBC.Results:High ZMIZ2 expression levels were associated with the malignant degree of TNBC.ZMIZ2 overexpression promoted TNBC cell proliferation,migration,and invasion;inhibited apoptosis;and induced G1 phase cell cycle arrest,whereas knockdown of ZMIZ2 had the opposite effect.ZMIZ2 directly targeted and positively regulated MCM3 expression.MCM3 knockdown reversed the effect of ZMIZ2 overexpression on TNBC tumor growth both in vitro and in vivo.High MCM3 expression levels were linked to the degree of malignancy and poor prognosis in TNBC.The differentially expressed genes associated with the ZMIZ2/MCM3 axis were significantly enriched in multiple pathways,such as the mitogen-activated protein kinase(MAPK),mechanistic target of rapamycin(mTOR),Wnt,and Ras signaling pathways,as verified by The Cancer Genome Atlas data.Conclusions:ZMIZ2 and MCM3 were highly expressed in TNBC.ZMIZ2 promoted the development by positively regulating MCM3 expression.Key pathways,such as the Ras/MAPK,phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mTOR,and Wnt signaling pathways,may be key downstreammechanisms.展开更多
BACKGROUND Complement-mediated thrombotic microangiopathy(TMA)is a rare endothelial injury syndrome caused by dysregulated activation of the alternative complement pathway,often linked to genetic abnormalities in comp...BACKGROUND Complement-mediated thrombotic microangiopathy(TMA)is a rare endothelial injury syndrome caused by dysregulated activation of the alternative complement pathway,often linked to genetic abnormalities in complement factor H(CFH),complement factor I,or complement factor H-related(CFHR)proteins.Both renal transplantation and pregnancy are independent triggers for recurrence.This case highlights a genetically high-risk patient who achieved a successful term pregnancy after renal transplantation without complement inhibition,emphasizing individualized risk stratification,close surveillance,and multidisciplinary management for favourable maternal and graft outcomes.CASE SUMMARY A 32-year-old woman with end-stage renal disease secondary to genetically confirmed complement-mediated TMA—homozygous CFH exon 17 deletion and CFHR3-CFHR1 duplication—was maintained on dialysis for 2.5 years before undergoing a successful live-donor kidney transplant from her mother.Post-transplant immunosuppression included tacrolimus,mycophenolate mofetil,and prednisolone,later modified to azathioprine during pregnancy planning.One-year post-transplant,she conceived spontaneously.Pregnancy was complicated by transient gestational hypertension,controlled with nifedipine,labetalol,and amlodipine.Proteinuria remained<150 mg/day;white blood cell counts 5.8-7.2×109/L without cytopenia.Serum creatinine ranged 0.9-1.1 mg/dL,and tacrolimus trough levels 5-7 ng/mL.At 36 weeks,she delivered a healthy 3 kg infant by elective caesarean section.Postpartum follow-up at three months confirmed stable maternal and graft function.CONCLUSION High-risk complement-mediated TMA patients can achieve successful pregnancy post-transplant through individualized care without mandatory complement blockade.展开更多
Aircraft digital flexible assembly fixture and technologies are widely used in developed countries, while the traditional jig-based assembly mode is still used in China. The application study of aircraft digital flexi...Aircraft digital flexible assembly fixture and technologies are widely used in developed countries, while the traditional jig-based assembly mode is still used in China. The application study of aircraft digital flexible assembly system is just beginning in our country recently. To meet the requirements of automated posture alignment and join in digital assembly system for large aircraft components, a novel fitting fixture called 3-axis actuator is developed. On the basis of the actuators, three kinds of posture alignment system for large aircraft components are proposed, including the non-redundant system, the redundant actuating system, and the redundant leg system, and their constitutions and properties are introduced. Through deriving the feeding transmission stiffness model of single actuator and analyzing the inverse kinematics of these systems, the relationship between the external force and the changes of position and orientation of large aircraft component is obtained, and then the postural alignment stiffness models are established. With the method mentioned above, the postural alignment stiffness of three systems is computed by using the algebraic formulate, and the results show that redundant properties can increase system＇s postural alignment stiffness. As an example, a optimized layout of the assembly system for a given model of aircraft is developed, the results of application show that the layout has many advantages, such as high accuracy, stiffness, stability, reliability, efficiency and flexible, which can satisfy the requirement of aircraft digital assembly system well. The proposed study of postural alignment stiffness for different systems can supply the theoretic support for the optimization layout design of aircraft digital assembly system, and contribute to evaluate the system working performance of systems.展开更多
Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures.Recent studies have shown that complement component 3(C3)aggravate the neuronal injury in epilepsy.And our previous studies revealed...Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures.Recent studies have shown that complement component 3(C3)aggravate the neuronal injury in epilepsy.And our previous studies revealed that TRPV1(transient receptor potential vanilloid type 1)is involved in epilepsy.Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood.We found that in a mouse model of status epilepticus(SE),complement C3 derived from astrocytes was increased and aggravated neuronal injury,and that TRPV 1-knockout rescued neurons from the injury induced by complement C3.Circular RNAs are abundant in the brain,and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV 1 and exacerbated neuronal injury.Mechanistically,disorders of neuron-glia interaction mediated by the C3-TRPV1 signaling pathway may be important for the induction of neuronal injury.This study provides support for the hypothesis that the C3-TRFV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.展开更多
Objective:Myeloma bone disease(MBD)is the most common complication of multiple myeloma(MM).Our previous study showed that the serum levels of C3/C4 in MM patients were significantly positively correlated with the seve...Objective:Myeloma bone disease(MBD)is the most common complication of multiple myeloma(MM).Our previous study showed that the serum levels of C3/C4 in MM patients were significantly positively correlated with the severity of bone disease.However,the mechanism of C3 a/C4 a in osteoclasts MM patients remains unclear.Methods:The formation and function of osteoclasts were analyzed after adding C3 a/C4 a in vitro.RNA-seq analysis was used to screen the potential pathways affecting osteoclasts,and the results were verified by Western blot,q RT-PCR,and pathway inhibitors.Results:The osteoclast area per view induced by 1μg/m L(mean±SD:50.828±12.984%)and 10μg/m L(53.663±12.685%)of C3 a was significantly increased compared to the control group(0μg/m L)(34.635±8.916%)(P<0.001 and P<0.001,respectively).The relative m RNA expressions of genes,OSCAR/TRAP/RANKL/cathepsin K,induced by 1μg/m L(median:5.041,3.726,1.638,and 4.752,respectively)and 10μg/m L(median:5.140,3.702,2.250,and 5.172,respectively)of C3 a was significantly increased compared to the control group(median:3.137,2.004,0.573,and 2.257,respectively)(1μg/m L P=0.001,P=0.003,P<0.001,and P=0.008,respectively;10μg/m L:P<0.001,P=0.019,P<0.001,and P=0.002,respectively).The absorption areas of the osteoclast resorption pits per view induced by 1μg/m L(mean±SD:51.464±11.983%)and 10μg/m L(50.219±12.067%)of C3 a was also significantly increased(33.845±8.331%)(P<0.001 and P<0.001,respectively)compared to the control.There was no difference between the C4 a and control groups.RNA-seq analysis showed that C3 a promoted the proliferation of osteoclasts using the phosphoinositide 3-kinase(PI3 K)signaling pathway.The relative expressions of PIK3 CA/phosphoinositide dependent kinase-1(PDK1)/serum and glucocorticoid inducible protein kinases(SGK3)genes and PI3 K/PDK1/p-SGK3 protein in the C3 a group were significantly higher than in the control group.The activation role of C3 a in osteoclasts of MM patients was reduced by the SGK inhibitor(EMD638683).Conclusions:C3 a activated osteoclasts by regulating the PI3 K/PDK1/SGK3 pathways in MM patients,which was reduced using a SGK inhibitor.Overall,our results identified potential therapeutic targets and strategies for MBD patients。展开更多
The current electromagnetic environment brings a growing demand for efficient microwave absorption(MA)materials.Ti_(3)C_(2)T_(x)MXene,one of the 2D transition-metal carbides,is considered to be a promising MA material...The current electromagnetic environment brings a growing demand for efficient microwave absorption(MA)materials.Ti_(3)C_(2)T_(x)MXene,one of the 2D transition-metal carbides,is considered to be a promising MA material owing to its superior dielectric properties and structural processability.In order to further improve the MA performance and environmental adaptability of Ti_(3)C_(2)T_(x)MXene,Ti_(3)C_(2)T_(x)MXene-based MA materials enhanced by composition and structure design have been extensively studied and the regu-lation ideas for its MA properties can be outlined as component optimization and structure manipulation strategies based on the microwave absorption mechanism.Herein,we briefly introduced the microwave absorption mechanism and focused on the design strategies of Ti_(3)C_(2)T_(x)MXene-based MA materials based on recent advances.In addition,the prospects of Ti_(3)C_(2)T_(x)MXene-based MA materials were also discussed.展开更多
The spaceborne synthetic aperture radar(SAR)sparse flight 3-D imaging technology through multiple observations of the cross-track direction is designed to form the cross-track equivalent aperture,and achieve the third...The spaceborne synthetic aperture radar(SAR)sparse flight 3-D imaging technology through multiple observations of the cross-track direction is designed to form the cross-track equivalent aperture,and achieve the third dimensionality recognition.In this paper,combined with the actual triple star orbits,a sparse flight spaceborne SAR 3-D imaging method based on the sparse spectrum of interferometry and the principal component analysis(PCA)is presented.Firstly,interferometric processing is utilized to reach an effective sparse representation of radar images in the frequency domain.Secondly,as a method with simple principle and fast calculation,the PCA is introduced to extract the main features of the image spectrum according to its principal characteristics.Finally,the 3-D image can be obtained by inverse transformation of the reconstructed spectrum by the PCA.The simulation results of 4.84 km equivalent cross-track aperture and corresponding 1.78 m cross-track resolution verify the effective suppression of this method on high-frequency sidelobe noise introduced by sparse flight with a sparsity of 49%and random noise introduced by the receiver.Meanwhile,due to the influence of orbit distribution of the actual triple star orbits,the simulation results of the sparse flight with the 7-bit Barker code orbits are given as a comparison and reference to illuminate the significance of orbit distribution for this reconstruction results.This method has prospects for sparse flight 3-D imaging in high latitude areas for its short revisit period.展开更多
A sub-regular solution model SELF-SReM4 used to evaluate activity of the components in a homogeneous region of a quaternary system has been developed in Shanghai Enhanced Laboratory of Ferrometallurgy.The application ...A sub-regular solution model SELF-SReM4 used to evaluate activity of the components in a homogeneous region of a quaternary system has been developed in Shanghai Enhanced Laboratory of Ferrometallurgy.The application of SELF-SReM4 in C-Mn-Fe-Si system without the SiC formation has been introduced in previous paper.It’s application for molten slag of MnO-SiO2-Al2O3-CaO was introduced in this paper.They provide a basis for the prediction of the metal-slag equilibrium conditions.展开更多
Shifting the feeding time for fish from daytime to nighttime could alter their digestive behavior, disturb their metabolism, and may af fect immune-related genes. This study aimed to clone complement component C7 and ...Shifting the feeding time for fish from daytime to nighttime could alter their digestive behavior, disturb their metabolism, and may af fect immune-related genes. This study aimed to clone complement component C7 and analyze the different expression of C7 mRNA in fish fed during either the day or at night and then challenged with Aeromonas hydrophila infection. The P v-C7 cDNA of Pelteobagrus vachellii contained 2 647 bp with an open reading frame encoding a protein of 818 amino acids. Multiple sequences analysis indicated that P v-C7 included eight domains, which was similar to results for other species. Quantitative PCR analysis showed that P v-C7 was mainly expressed in the liver, spleen, intestine and head kidney tissues of healthy P. vachellii. Quantitative PCR analysis showed that C7 mRNA transcript in the liver, spleen and head kidney also increased significantly when the fish were fed at nighttime(20:00). In addition, the expression of Pv-C7 mRNA significantly increased with A. hydrophila challenge in the liver(48–96 h), spleen and head kidney(12–96 h) tissues of P. vachellii. Pv-C7 mRNA expression of the fish fed at nighttime showed significant higher than that in the fish fed at day time at 12–48 h in head kidney and 12–24 h in spleen. This study indicates that altering the feeding time from daytime to nighttime could increase P v-C7 mRNA expression, and feeding time may af fect the immune response involving C7.展开更多
基金supported by the National Natural Science Foundation of China(No.82104353)China Postdoctoral Science Foundation funded project(No.2022M711680).
文摘Insects represent emerging sources of bioactive peptides and functional materials.Mantidis Oötheca(Sang-Piao-Xiao in Chinese,SPX)serves as an insect-derived medicine for treating kidney disease.This study demonstrated that supernatant(SPX)improved kidney function in adriamycin(ADR)-induced nephropathy mice model.Transcriptomic analysis revealed that SPX inhibited complement activation by targeting the MASP1-C3/C3a receptor(C3aR)pathway.Peptidomic analysis identified 304 peptides from SPX,with 49 peptides selected for evaluation using prediction tools and molecular docking with complement core protein C3.Three peptides(PMGFPFDR,FNDPK,AAQFFNR)exhibiting docking scores below-8.0 were synthesized to verify complement inhibition and anti-fibrotic activities.The synthetic peptide AAQFFNR demonstrated complement inhibitory activity,with an inhibitory complement hemolytic 50%(ICH_(50))value of 24.54μmol·L^(-1),and exhibited superior protective effects in ADR-induced HK-2 cells.Surface plasmon resonance(SPR)assay revealed direct interaction between AAQFFNR and complement C3 with K_(d)value of 16.8μmol·L^(-1).The reno-protective effect of AAQFFNR was subsequently verified in ADR-induced mice.This research provides initial evidence that complement C3-inhibiting peptides from insects demonstrate potential in preventing nephropathy through in silico and in vivo validation approaches.
基金supported by the National Natural Science Foundation of China(82071362 and 82270669)Key Project of the Regional Joint Fund of Guangdong Province(2023B1515120077)+3 种基金Basic Research Program of Shenzhen Science and Technology Innovation Commission(JCYJ20210324123001003 and JCYJ20220530144801003)Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research(ZDSYS20230626091402006)the Innovation and Entrepreneurship Training Program for College Students,Sun Yat-sen University(20242150)the Leading Innovation and Entrepreneurship Team Program of Zhejiang Province,China(2023R01005).
文摘Activation of spinal cord neural stem cells(NSCs)and subsequent neurogenesis holds a promising alternative for spinal cord injury(SCI)repair.Our previous study demonstrated that complement C3a,derived from reactive astrocytes,inhibits NSC proliferation by suppressing protein aggregate clearance through the deubiquitinating enzyme ubiquitin carboxy-terminal hydrolase L1(UCHL1)-proteasome system post-SCI.However,the potential molecular mechanism by which C3a modulates NSC activation via this pathway remains unclear.Here,we revealed that C3a/C3a receptor(C3aR)signaling activated NF-κB p65,which in turn inhibited Nrf2 activity and UCHL1 expression,resulting in diminished proteasome activity and the accumulation of protein aggregates,and ultimately impaired NSC activation.Both knockdown of NF-κB p65 and Nrf2 upregulation restored UCHL1 expression and proteasome activity in vitro,promoting NSC activation by enhancing protein aggregate clearance.Mechanistically,we found that NF-κB p65 regulated Nrf2 activity through a dual mechanism:(1)promoting Keap1-dependent ubiquitination and proteasome degradation of Nrf2;(2)inhibiting protein kinase C-mediated Nrf2 phosphorylation and nuclear translocation.Using the dual-luciferase reporter assay and chromatin immunoprecipitation(ChIP)analysis,we further identified UCHL1 as a direct transcriptional target of Nrf2.Importantly,in vivo experiments using SCI mice confirmed that either C3aR blockade,NF-κB p65 knockdown,or Nrf2 overexpression could rescue SCI-induced UCHL1 downregulation.Together,this study uncovers the C3a-NF-κB p65-Nrf2-UCHL1-proteasome axis as a critical regulator of NSC activation after SCI.This may provide novel molecular targets and intervention strategies for SCI repair.
基金supported by the Jilin Province Health Science and Technology Ability Improvement Project(2023JL057).
文摘Objective:Triple-negative breast cancer(TNBC)is highly aggressive and lacks an effective targeted therapy.This study aimed to elucidate the functions and possible mechanisms of action of zinc finger miz-type containing 2(ZMIZ2)and minichromosome maintenance complex component 3(MCM3)in TNBC progression.Methods:The relationship between ZMIZ2 expression and clinical characteristics of TNBC was investigated.In vitro and in vivo experiments were performed to investigate the role of ZMIZ2 dysregulation in TNBC cell malignant behaviors.The regulatory relationship between ZMIZ2 and MCM3 was also explored.Transcriptome sequencing was performed to elucidate possible mechanisms underlying the ZMIZ2/MCM3 axis in TNBC.Results:High ZMIZ2 expression levels were associated with the malignant degree of TNBC.ZMIZ2 overexpression promoted TNBC cell proliferation,migration,and invasion;inhibited apoptosis;and induced G1 phase cell cycle arrest,whereas knockdown of ZMIZ2 had the opposite effect.ZMIZ2 directly targeted and positively regulated MCM3 expression.MCM3 knockdown reversed the effect of ZMIZ2 overexpression on TNBC tumor growth both in vitro and in vivo.High MCM3 expression levels were linked to the degree of malignancy and poor prognosis in TNBC.The differentially expressed genes associated with the ZMIZ2/MCM3 axis were significantly enriched in multiple pathways,such as the mitogen-activated protein kinase(MAPK),mechanistic target of rapamycin(mTOR),Wnt,and Ras signaling pathways,as verified by The Cancer Genome Atlas data.Conclusions:ZMIZ2 and MCM3 were highly expressed in TNBC.ZMIZ2 promoted the development by positively regulating MCM3 expression.Key pathways,such as the Ras/MAPK,phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mTOR,and Wnt signaling pathways,may be key downstreammechanisms.
文摘BACKGROUND Complement-mediated thrombotic microangiopathy(TMA)is a rare endothelial injury syndrome caused by dysregulated activation of the alternative complement pathway,often linked to genetic abnormalities in complement factor H(CFH),complement factor I,or complement factor H-related(CFHR)proteins.Both renal transplantation and pregnancy are independent triggers for recurrence.This case highlights a genetically high-risk patient who achieved a successful term pregnancy after renal transplantation without complement inhibition,emphasizing individualized risk stratification,close surveillance,and multidisciplinary management for favourable maternal and graft outcomes.CASE SUMMARY A 32-year-old woman with end-stage renal disease secondary to genetically confirmed complement-mediated TMA—homozygous CFH exon 17 deletion and CFHR3-CFHR1 duplication—was maintained on dialysis for 2.5 years before undergoing a successful live-donor kidney transplant from her mother.Post-transplant immunosuppression included tacrolimus,mycophenolate mofetil,and prednisolone,later modified to azathioprine during pregnancy planning.One-year post-transplant,she conceived spontaneously.Pregnancy was complicated by transient gestational hypertension,controlled with nifedipine,labetalol,and amlodipine.Proteinuria remained<150 mg/day;white blood cell counts 5.8-7.2×109/L without cytopenia.Serum creatinine ranged 0.9-1.1 mg/dL,and tacrolimus trough levels 5-7 ng/mL.At 36 weeks,she delivered a healthy 3 kg infant by elective caesarean section.Postpartum follow-up at three months confirmed stable maternal and graft function.CONCLUSION High-risk complement-mediated TMA patients can achieve successful pregnancy post-transplant through individualized care without mandatory complement blockade.
文摘Aircraft digital flexible assembly fixture and technologies are widely used in developed countries, while the traditional jig-based assembly mode is still used in China. The application study of aircraft digital flexible assembly system is just beginning in our country recently. To meet the requirements of automated posture alignment and join in digital assembly system for large aircraft components, a novel fitting fixture called 3-axis actuator is developed. On the basis of the actuators, three kinds of posture alignment system for large aircraft components are proposed, including the non-redundant system, the redundant actuating system, and the redundant leg system, and their constitutions and properties are introduced. Through deriving the feeding transmission stiffness model of single actuator and analyzing the inverse kinematics of these systems, the relationship between the external force and the changes of position and orientation of large aircraft component is obtained, and then the postural alignment stiffness models are established. With the method mentioned above, the postural alignment stiffness of three systems is computed by using the algebraic formulate, and the results show that redundant properties can increase system＇s postural alignment stiffness. As an example, a optimized layout of the assembly system for a given model of aircraft is developed, the results of application show that the layout has many advantages, such as high accuracy, stiffness, stability, reliability, efficiency and flexible, which can satisfy the requirement of aircraft digital assembly system well. The proposed study of postural alignment stiffness for different systems can supply the theoretic support for the optimization layout design of aircraft digital assembly system, and contribute to evaluate the system working performance of systems.
基金by the National Natural Science Foundation of China(81571481 and 82060588)the Natural Science Foundation of Hubei Province,China(2017CFA017)+1 种基金the Wuhan Science and Technology Project(2019020701011444)the Medical Science Advancement Program of Wuhan University(TFJC2018001 and TFLC2018001).
文摘Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures.Recent studies have shown that complement component 3(C3)aggravate the neuronal injury in epilepsy.And our previous studies revealed that TRPV1(transient receptor potential vanilloid type 1)is involved in epilepsy.Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood.We found that in a mouse model of status epilepticus(SE),complement C3 derived from astrocytes was increased and aggravated neuronal injury,and that TRPV 1-knockout rescued neurons from the injury induced by complement C3.Circular RNAs are abundant in the brain,and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV 1 and exacerbated neuronal injury.Mechanistically,disorders of neuron-glia interaction mediated by the C3-TRPV1 signaling pathway may be important for the induction of neuronal injury.This study provides support for the hypothesis that the C3-TRFV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.
基金supported by the National Natural Science Foundation of China(Grant Nos.81770110,81900131,and 82000219)the Anticancer Major Special Project of Tianjin(Grant No.12ZCDZSY18000)+4 种基金the Tianjin Municipal Natural Science Foundation(Grant Nos.18JCYBJC27200 and 18JCQNJC80400)the Tianjin Education Commission Research Project(Grant Nos.2018KJ043 and 2018KJ045)the Tianjin Health and Family Planning Commission(Grant No.15KG150)the Youth Incubation Fund of Tianjin Medical University General Hospital(Grant No.ZYYFY2019020)the Tianjin Science and Technology Planning Project(Grant No.20YFZCSY00060)。
文摘Objective:Myeloma bone disease(MBD)is the most common complication of multiple myeloma(MM).Our previous study showed that the serum levels of C3/C4 in MM patients were significantly positively correlated with the severity of bone disease.However,the mechanism of C3 a/C4 a in osteoclasts MM patients remains unclear.Methods:The formation and function of osteoclasts were analyzed after adding C3 a/C4 a in vitro.RNA-seq analysis was used to screen the potential pathways affecting osteoclasts,and the results were verified by Western blot,q RT-PCR,and pathway inhibitors.Results:The osteoclast area per view induced by 1μg/m L(mean±SD:50.828±12.984%)and 10μg/m L(53.663±12.685%)of C3 a was significantly increased compared to the control group(0μg/m L)(34.635±8.916%)(P<0.001 and P<0.001,respectively).The relative m RNA expressions of genes,OSCAR/TRAP/RANKL/cathepsin K,induced by 1μg/m L(median:5.041,3.726,1.638,and 4.752,respectively)and 10μg/m L(median:5.140,3.702,2.250,and 5.172,respectively)of C3 a was significantly increased compared to the control group(median:3.137,2.004,0.573,and 2.257,respectively)(1μg/m L P=0.001,P=0.003,P<0.001,and P=0.008,respectively;10μg/m L:P<0.001,P=0.019,P<0.001,and P=0.002,respectively).The absorption areas of the osteoclast resorption pits per view induced by 1μg/m L(mean±SD:51.464±11.983%)and 10μg/m L(50.219±12.067%)of C3 a was also significantly increased(33.845±8.331%)(P<0.001 and P<0.001,respectively)compared to the control.There was no difference between the C4 a and control groups.RNA-seq analysis showed that C3 a promoted the proliferation of osteoclasts using the phosphoinositide 3-kinase(PI3 K)signaling pathway.The relative expressions of PIK3 CA/phosphoinositide dependent kinase-1(PDK1)/serum and glucocorticoid inducible protein kinases(SGK3)genes and PI3 K/PDK1/p-SGK3 protein in the C3 a group were significantly higher than in the control group.The activation role of C3 a in osteoclasts of MM patients was reduced by the SGK inhibitor(EMD638683).Conclusions:C3 a activated osteoclasts by regulating the PI3 K/PDK1/SGK3 pathways in MM patients,which was reduced using a SGK inhibitor.Overall,our results identified potential therapeutic targets and strategies for MBD patients。
基金financially supported by the Natural Science Foundation of Shandong Province(No.ZR2019YQ24)the Taishan Scholars and Young Experts Program of Shandong Province(No.tsqn202103057)the Qingchuang Talents Induction Program of Shandong Higher Education Institution(Research and Inno-vation Team of Structural-Functional Polymer Composites),and the Special Financial of Shandong Province(Structural Design of High-efficiency Electromagnetic Wave-absorbing Composite Mate-rials and Construction of Shandong Provincial Talent Teams(No.37000022P990304116449)).
文摘The current electromagnetic environment brings a growing demand for efficient microwave absorption(MA)materials.Ti_(3)C_(2)T_(x)MXene,one of the 2D transition-metal carbides,is considered to be a promising MA material owing to its superior dielectric properties and structural processability.In order to further improve the MA performance and environmental adaptability of Ti_(3)C_(2)T_(x)MXene,Ti_(3)C_(2)T_(x)MXene-based MA materials enhanced by composition and structure design have been extensively studied and the regu-lation ideas for its MA properties can be outlined as component optimization and structure manipulation strategies based on the microwave absorption mechanism.Herein,we briefly introduced the microwave absorption mechanism and focused on the design strategies of Ti_(3)C_(2)T_(x)MXene-based MA materials based on recent advances.In addition,the prospects of Ti_(3)C_(2)T_(x)MXene-based MA materials were also discussed.
基金This work was supported by the General Design Department,China Academy of Space Technology(10377).
文摘The spaceborne synthetic aperture radar(SAR)sparse flight 3-D imaging technology through multiple observations of the cross-track direction is designed to form the cross-track equivalent aperture,and achieve the third dimensionality recognition.In this paper,combined with the actual triple star orbits,a sparse flight spaceborne SAR 3-D imaging method based on the sparse spectrum of interferometry and the principal component analysis(PCA)is presented.Firstly,interferometric processing is utilized to reach an effective sparse representation of radar images in the frequency domain.Secondly,as a method with simple principle and fast calculation,the PCA is introduced to extract the main features of the image spectrum according to its principal characteristics.Finally,the 3-D image can be obtained by inverse transformation of the reconstructed spectrum by the PCA.The simulation results of 4.84 km equivalent cross-track aperture and corresponding 1.78 m cross-track resolution verify the effective suppression of this method on high-frequency sidelobe noise introduced by sparse flight with a sparsity of 49%and random noise introduced by the receiver.Meanwhile,due to the influence of orbit distribution of the actual triple star orbits,the simulation results of the sparse flight with the 7-bit Barker code orbits are given as a comparison and reference to illuminate the significance of orbit distribution for this reconstruction results.This method has prospects for sparse flight 3-D imaging in high latitude areas for its short revisit period.
文摘A sub-regular solution model SELF-SReM4 used to evaluate activity of the components in a homogeneous region of a quaternary system has been developed in Shanghai Enhanced Laboratory of Ferrometallurgy.The application of SELF-SReM4 in C-Mn-Fe-Si system without the SiC formation has been introduced in previous paper.It’s application for molten slag of MnO-SiO2-Al2O3-CaO was introduced in this paper.They provide a basis for the prediction of the metal-slag equilibrium conditions.
基金Supported by the National Natural Science Foundation of China(No.31402305)the Natural Science Foundation of Sichuan Province(No.2017JY0161)the Educational Commission of Sichuan Province of China(No.14ZA0249)
文摘Shifting the feeding time for fish from daytime to nighttime could alter their digestive behavior, disturb their metabolism, and may af fect immune-related genes. This study aimed to clone complement component C7 and analyze the different expression of C7 mRNA in fish fed during either the day or at night and then challenged with Aeromonas hydrophila infection. The P v-C7 cDNA of Pelteobagrus vachellii contained 2 647 bp with an open reading frame encoding a protein of 818 amino acids. Multiple sequences analysis indicated that P v-C7 included eight domains, which was similar to results for other species. Quantitative PCR analysis showed that P v-C7 was mainly expressed in the liver, spleen, intestine and head kidney tissues of healthy P. vachellii. Quantitative PCR analysis showed that C7 mRNA transcript in the liver, spleen and head kidney also increased significantly when the fish were fed at nighttime(20:00). In addition, the expression of Pv-C7 mRNA significantly increased with A. hydrophila challenge in the liver(48–96 h), spleen and head kidney(12–96 h) tissues of P. vachellii. Pv-C7 mRNA expression of the fish fed at nighttime showed significant higher than that in the fish fed at day time at 12–48 h in head kidney and 12–24 h in spleen. This study indicates that altering the feeding time from daytime to nighttime could increase P v-C7 mRNA expression, and feeding time may af fect the immune response involving C7.
