To lay background for studying rejection mechanisms in xenotransplantation and developing the strategies for intervention, class I genes of swine leukocyte antigens (SLA) of three Chinese pig strains Bm, Gz and Yn wer...To lay background for studying rejection mechanisms in xenotransplantation and developing the strategies for intervention, class I genes of swine leukocyte antigens (SLA) of three Chinese pig strains Bm, Gz and Yn were cloned and sequenced. The cDNA of the class I loci P1 and P14 were amplified by RT-PCR and subjected to insert into sequencing vectors. All six allelic sequences we examined, each two for one Chinese strain, are not identical to those reported, which allows these novel sequences receiving their accession numbers AY102467- AY102472 from GenBank. This study further reveals that the homologies of MHC class I genes in their primary structures and the deduced amino acids between Chinese pigs (SLA) and human (HLA-A*0201) are better than those between pigs and mice (H-2Db/H-2Kb). The comparison also indicates that the amino acid residues critical for recognition by human KIRs are altered in the swine class I molecules. The amino acids responsible for binding human CD8 coreceptor are largely conserved although there are two critical residues substituted. A functional test indicated that the human T cells specific for the prokaryotically expressed SLA Plprotein could respond quite well in vitro to the class I-positive swine chon-drocytes and PBMCs in presence of human APCs. This implies that, due to the substitution of two critical residues, the inaccessibility of human CD8 coreceptor to swine class I molecule might be contributable to the indirect pathway that the human T cells have to use for recognizing the SLA class I xenogeneic antigens.展开更多
The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue regeneration.As the first i...The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue regeneration.As the first immune cells to be activated after an ischemic stroke,microglia play an important immunomodulatory role in the progression of the condition.After an ischemic stroke,peripheral blood immune cells(mainly T cells)are recruited to the central nervous system by chemokines secreted by immune cells in the brain,where they interact with central nervous system cells(mainly microglia)to trigger a secondary neuroimmune response.This review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic stroke.We found that,during ischemic stroke,T cells and microglia demonstrate a more pronounced synergistic effect.Th1,Th17,and M1 microglia can co-secrete proinflammatory factors,such as interferon-γ,tumor necrosis factor-α,and interleukin-1β,to promote neuroinflammation and exacerbate brain injury.Th2,Treg,and M2 microglia jointly secrete anti-inflammatory factors,such as interleukin-4,interleukin-10,and transforming growth factor-β,to inhibit the progression of neuroinflammation,as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain injury.Immune interactions between microglia and T cells influence the direction of the subsequent neuroinflammation,which in turn determines the prognosis of ischemic stroke patients.Clinical trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic stroke.However,such studies have been relatively infrequent,and clinical experience is still insufficient.In summary,in ischemic stroke,T cell subsets and activated microglia act synergistically to regulate inflamm展开更多
Duplexα/β-SiAlON ceramic cutting inserts(30α:70β)were synthesized by microwave sintering.The effects of solid solution parameters(m,n,z),synthesis temperature,and amount of excess Y_(2)O_(3) synthesis additive on ...Duplexα/β-SiAlON ceramic cutting inserts(30α:70β)were synthesized by microwave sintering.The effects of solid solution parameters(m,n,z),synthesis temperature,and amount of excess Y_(2)O_(3) synthesis additive on phase assemblage,microstructure,mechanical properties,and cutting performance were systematically investigated.It was found that increasing m value could improve the formation ofαphase while high z value over 1.0 resulted in the dissolution ofαphase intoβphase and intergranular phase.Increasing the amount of excess Y_(2)O_(3) could promote densification and elongatedβgrain growth;however,the excess Y_(2)O_(3) amount above 4 wt%resulted in substantial crystallization of M'SS phase,thus declining the mechanical properties and wear resistance.The microwave-synthesizedα/β-SiAlON cutting insert with modified parameters(m=1.7,n=1.0,z=0.7,and 3 wt%excess Y_(2)O_(3))was obtained with optimal comprehensive properties,whose tool life was found to increase by approximately 75%in high-speed milling of Inconel 718 superalloy compared to the commercialα/β-SiAlON cutting insert.展开更多
The mesencephalic astrocyte-derived neurotrophic factor(MANF)has been recently identified as a neurotrophic factor,but its role in hepatic fibrosis is unknown.Here,we found that MANF was upregulated in the fibrotic li...The mesencephalic astrocyte-derived neurotrophic factor(MANF)has been recently identified as a neurotrophic factor,but its role in hepatic fibrosis is unknown.Here,we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl4.MANF deficiency in either hepatocytes or hepatic mono-macrophages,particularly in hepatic mono-macrophages,clearly exacerbated hepatic fibrosis.Myeloid-specific MANF knockout increased the population of hepatic Ly6C^(high)macrophages and promoted HSCs activation.Furthermore,MANF-sufficient macrophages(from WT mice)transfusion ameliorated CCl4-induced hepatic fibrosis in myeloid cells-specific MANF knockout(MKO)mice.Mechanistically,MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation.Pharmacologically,systemic administration of recombinant human MANF significantly alleviated CCl_(4)-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout(HKO)mice.This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a“brake”on the upstream of NF-κB pathway,which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.展开更多
Background:Xiaoqinglong decoction(XQLD)is a classic Chinese medicinal formula that is widely used to treat allergic asthma.Recently,the use of XQLD to treat allergic asthma has inspired research to determine its mecha...Background:Xiaoqinglong decoction(XQLD)is a classic Chinese medicinal formula that is widely used to treat allergic asthma.Recently,the use of XQLD to treat allergic asthma has inspired research to determine its mechanism of action.Because dendritic cells(DCs)and the T helper 1(Th1)/Th2 cytokine balance play important roles in allergic asthma,the present work aimed to assess how these immune system components are affected by XQLD.Methods:Thirty-six female BALB/C mice were randomly divided into three groups:an ovalbumin-based allergic asthma model group,a XQLD treatment group,and a control group.Histology was performed with haematoxylin and eosin staining and immunohistochemical staining.Bronchoalveolar lavage fluid and blood were collected from the animals and used to analyze the composition of inflammatory cells and expression levels of the cytokines interleukin(IL)-5 and IL-13.The thymic stromal lymphopoietin(TSLP)protein expression was assessed by western blot analysis,and the Gata3 and Tbx21 mRNA levels were assessed by polymerase chain reaction.Results:Compared with the OVA group,the levels of TSLP expression,IL-5,IL-13,and immunoglobulin E in the XQLD group were lower(all P<.01).The level of IL-4-expressing cells(Th2 cells)was lower(P=.0013),and the percentage of IFN-g-expressing cells(Th1 cells)was higher in the XQLD group compared with those in the OVA group(P=.0065).In addition,XQLD increased the expression of Tbx21 mRNA and decreased the expression of Gata3 mRNA in the lungs compared with the OVA group(both P<.01).Conclusion:These findings suggest that XQLD may ameliorate the course of allergic asthma by regulating the Gata3/Tbx21 balance and inhibiting TSLP expression,changes which are indicative of an altered Th1/Th2 balance.Thus,the clinical effectiveness of XQLD in treating allergic asthma may be due to its regulation of Th1/Th2 balance.展开更多
MAGED4B belongs to the melanoma-associated antigen family;originally found in melanoma,it is expressed in various types of cancer,and is especially enriched in glioblastoma.However,the functional role and molecular me...MAGED4B belongs to the melanoma-associated antigen family;originally found in melanoma,it is expressed in various types of cancer,and is especially enriched in glioblastoma.However,the functional role and molecular mechanisms of MAGED4B in glioma are still unclear.In this study,we found that the MAGED4B level was higher in glioma tissue than that in non-cancer tissue,and the level was positively correlated with glioma grade,tumor diameter,Ki-67 level,and patient age.The patients with higher levels had a worse prognosis than those with lower MAGED4B levels.In glioma cells,MAGED4B overexpression promoted proliferation,invasion,and migration,as well as decreasing apoptosis and the chemosensitivity to cisplatin and temozolomide.On the contrary,MAGED4B knockdown in glioma cells inhibited proliferation,invasion,and migration,as well as increasing apoptosis and the chemosensitivity to cisplatin and temozolomide.MAGED4B knockdown also inhibited the growth of gliomas implanted into the rat brain.The interaction between MAGED4B and tripartite motif-containing 27(TRIM27)in glioma cells was detected by co-immunoprecipitation assay,which showed that MAGED4B was co-localized with TRIM27.In addition,MAGED4B overexpression down-regulated the TRIM27 protein level,and this was blocked by carbobenzoxyl-L-leucyl-L-leucyl-L-leucine(MG132),an inhibitor of the proteasome.On the contrary,MAGED4B knockdown up-regulated the TRIM27 level.Furthermore,MAGED4B overexpression increased TRIM27 ubiquitination in the presence of MG132.Accordingly,MAGED4B down-regulated the protein levels of genes downstream of ubiquitin-specific protease 7(USP7)involved in the tumor necrosis factor-alpha(TNF-α)-induced apoptotic pathway.These findings indicate that MAGED4B promotes glioma growth via a TRIM27/USP7/receptor-interacting serine/threonine-protein kinase 1(RIP1)-dependent TNF-α-induced apoptotic pathway,which suggests that MAGED4B is a potential target for glioma diagnosis and treatment.展开更多
The aluminum alloy AlMn1Cu has been broadly applied for functional parts production because of its good properties. But few researches about the machining mechanism and the surface roughness were reported. The high-sp...The aluminum alloy AlMn1Cu has been broadly applied for functional parts production because of its good properties. But few researches about the machining mechanism and the surface roughness were reported. The high-speed milling experiments are carried out in order to improve the machining quality and reveal the machining mechanism. The typical topography features of machined surface are observed by scan electron microscope（SEM）. The results show that the milled surface topography is mainly characterized by the plastic shearing deformation surface and material piling zone. The material flows plastically along the end cutting edge of the flat-end milling tool and meanwhile is extruded by the end cutting edge, resulting in that materials partly adhere to the machined surface and form the material piling zone. As the depth of cut and the feed per tooth increase, the plastic flow of materials is strengthened and the machined surface becomes rougher. However, as the cutting speed increases, the plastic flow of materials is weakened and the milled surface becomes smoother. The cutting parameters （e.g. cutting speed, feed per tooth and depth of cut） influencing the surface roughness are analyzed. It can be concluded that the roughness of the machined surface formed by the end cutting edge is less than that by the cylindrical cutting edge when a cylindrical flat-end mill tool is used for milling. The proposed research provides the typical topography features of machined surface of the anti-rust aluminum alloy AlMn1Cu in high speed milling.展开更多
The effect of Ultra-violet light on the structure and motion of the polyvinyl alcohol (PVA) chains was studied by H NMR, spin-lattice relaxation and IR spectroscopy. 1 The results indicated that with the increase of i...The effect of Ultra-violet light on the structure and motion of the polyvinyl alcohol (PVA) chains was studied by H NMR, spin-lattice relaxation and IR spectroscopy. 1 The results indicated that with the increase of irradiation time, the intensity of the polymer hydroxyl proton peaks decreased and finally vanished, which suggested the self-condensation between the hydroxyl groups proceeded. No methyl proton peaks appeared in the spectra after irradiation shows that there is no cleavage of polymer chain. The longer the irradiation time is, the wider the proton peak of the residual water of the solvent is and it shifted toward low field. This result implies that the hydrogen bonds formed between the polymer and the residual water. The absorption peak of hydroxyl group of the polymer moves toward the lower wave number in the IR spectrum that showed the existence of the hydrogen bonds between the PVA macromolecules.展开更多
Using the first-principles calculations, we studied the geometric structures, electronic structures and optical properties of the single-walled (n, 0) ZnO nanotubes (NTs). The calculated results show that all the bind...Using the first-principles calculations, we studied the geometric structures, electronic structures and optical properties of the single-walled (n, 0) ZnO nanotubes (NTs). The calculated results show that all the bind energies of the single-walled (n,0) ZnO NTs are of negative values, which indicate that the ZnO NTs can exist stably as single-walled NTs. While the calculated results of electronic structure indicate that the single-walled (n,0) ZnO NTs are a type of direct wide band-gap semiconductor materials, the whole valence bands are spread and drift to low-energy direction with the increase of the NT diameter. The defect energy levels caused by quantum size and surface effects emerge on the top of the valence bands. Furthermore, the calculated results of optical properties reveal that the dielectric peaks have a blue shift and the edge of absorption band corresponds to ultraviolet band with the decrease of the NT diameter. The single-walled (n, 0) ZnO NTs can be applied to ultraviolet semiconductor systems.展开更多
In this study, powder mixtures containing(Ti, W)C additions(10, 20, 30 and 40 wt%) were prepared and then consolidated at 1200, 1250, 1300 and 1350 °C by spark plasma sintering. The effect of(Ti, W)C additions on...In this study, powder mixtures containing(Ti, W)C additions(10, 20, 30 and 40 wt%) were prepared and then consolidated at 1200, 1250, 1300 and 1350 °C by spark plasma sintering. The effect of(Ti, W)C additions on the microstructure and mechanical properties of ultrafine WC–Co materials was investigated. The results demonstrate that the(Ti, W)C not only retards the sintering densification but also increases the porosity of sintered samples. The increasing sintering temperature is beneficial to the densification but results in the grain coarsening and the dissolution of W in(Ti, W)C. Moreover, there are no(Ti, W)C grains with obvious core/rim structure in the microstructure. With the(Ti, W)C increasing from 10 to 20 wt%, the hardness increases and fracture toughness changes hardly. However, the hardness and fracture toughness decrease slightly as the(Ti, W)C further increases. The transgranular fracture of(Ti, W)C phases is responsible for the slight reduction in fracture toughness. The sample with 20 wt%(Ti, W)C has high hardness and fracture toughness( HV : 21.3 GPa, KIC: 9.8 MPa m1/2).展开更多
Memristor is introduced as the fourth basic circuit element.Memristor exhibits great potential for numerous applications,such as emulating synapse,while the mathematical model of the memristor is still an open subject...Memristor is introduced as the fourth basic circuit element.Memristor exhibits great potential for numerous applications,such as emulating synapse,while the mathematical model of the memristor is still an open subject.In the linear-drift model,the boundary condition of the device is not considered.This paper proposes an extended linear-drift model of the memristor.The extended linear-drift model keeps the linear characteristic and simplicity of the linear-drift model and considers the boundary condition of the device.A piecewise linear approximation model of the extended linear-drift model is given.Both models are suitable for describing the memristor.展开更多
Spark plasma sintering(SPS)is a highly efficient method for the preparation ofα/β-SiAlON ceramics.However,the rapid preparation of large-scaleα/β-SiAlON ceramic components with reliable mechanical properties is di...Spark plasma sintering(SPS)is a highly efficient method for the preparation ofα/β-SiAlON ceramics.However,the rapid preparation of large-scaleα/β-SiAlON ceramic components with reliable mechanical properties is difficult via SPS due to their near-insulating properties.In this study,high-performanceα/β-SiAlON ceramic end mill rods with large aspect ratios were successfully prepared via SPS.Two different types of sintering processes(namely vertical-round-rod(VRR)and horizontal-square-rod(HSR)processes)were developed,and their effects on the phase composition,microstructure,mechanical properties,and machining performance of theα/β-SiAlON ceramic end mill rods were studied.The electric and temperature field distributions during sintering were studied through an electro–thermal simulation.The simulated and experimental temperature distributions are in good agreement.In contrast to VRR samples,HSR samples with a small axial size show a uniform temperature distribution and satisfactory microstructures within a certain range of dimensions as well as the expected phase composition;furthermore,elongatedβ-SiAlON grains are preferentially oriented in the direction perpendicular to the sintering pressure direction.As a result,the HSR samples exhibit better mechanical properties and machining performance than the VRR samples.展开更多
Objective： Lung cancer has emerged as a leading cause of cancer death in the world. Eyes Absent （EYA） is an important and conserved transcriptional regulator of development. The aim of the present study was to iden...Objective： Lung cancer has emerged as a leading cause of cancer death in the world. Eyes Absent （EYA） is an important and conserved transcriptional regulator of development. The aim of the present study was to identify the expression of Drosophila Eyes Absent Hemologue 2 （EYA2） in non-small cell lung cancer （NSCLC） and to investigate their correlation with clinical parameters. Methods： Fresh, paired lung samples （n = 59） of NSCLC were obtained by surgical resection at the Department of Thoracic Surgery of the People＇s Liberation Army General Hospital. Expression of EYA2 were examined by Western blot and immunohistochemical analysis in specimens of NSCLC and paired normal lung tissue. Clinical data, pathologic result and Ki67 expression were collected and subsequent correlation with EYA2 expression was analyzed. Results： EYA2 expression was found located in cytoplasm and nucleus, but mostly in cytoplasm. The expression of EYA2 increased in NSCLC by Western blot and immunohistochemistry, which was correlated with histology type, but not correlated with gender, age, pTNM stage, histological differentiation and lymph node metastasis. Compared with normal lung tissue, the expression of EYA2 significantly was up-regulated in lung adenocarcinoma, while no significant difference in lung squamous cell carcinoma. Expression of EYA2 was uncorrelated with expression of Ki67 in NSCLC. Conclusion： Expression of EYA2 was augmented in lung adenocarcinoma. EYA2 is likely participating in tumorigenesis and development of lung adenocarcinoma as transcriptional activator.展开更多
Two new metabolites, namely bisline lactone and isolinecic acid lactone, were isolated from the resultant incubates after a scale-up incubation of isoline with rat liver microsomes. Their structures were determined by...Two new metabolites, namely bisline lactone and isolinecic acid lactone, were isolated from the resultant incubates after a scale-up incubation of isoline with rat liver microsomes. Their structures were determined by spectroscopic data, especially those from 1D and 2D NMR experiments.展开更多
Objective： To investigate the alternations of proteins in the colonic mucosa of chronic slow transit constipation （STC） rats with a 2-DE-based proteomic method and analyze the function of these down-regulated prote...Objective： To investigate the alternations of proteins in the colonic mucosa of chronic slow transit constipation （STC） rats with a 2-DE-based proteomic method and analyze the function of these down-regulated proteins so as to provide theoretical basis for the pathogenesis of intestinal mucosa of chronic STC rats. Methods： STC model was established by feeding rats with 8 mg/（kg＇d） diphenoxylate for 120 d. An experimental model of chronic STC rat was used for separation of proteomics from colonic mucosa using two-dimensional electrophoresis （2-DE）. Proteins altered in expressional level were identified by Image Master 2DElite, mass spectrometry, and bibliometrics were applied to identify the differential protein expression and their clinical s observed in the pathogenesis lgn of ificance and function were analyzed. Results： Obvious differential protein expression was STC, including mast cell protease （A1）, non-specific dipeptidase （A2） and chondrosome succinate dehydrogenase precursor （A3）. The expressions of A1, A2 and A3 were down-regulated in the gel graph of STC rats Conclusion： The down-regulation of chondrosome succinate dehydrogenase, mast cell protease as well as non-specific dipeptidase in rat colon suggests the functional impairment of the oxidoreduction of mitochondrion is very important in the genesis and development of STC. The immunological reaction of STC rats is weakened, and the function of digesting and absorbing protein may be damaged to some extent.展开更多
AIM: To determine the role of p38 MAP kinase signal transduction pathways in diallyl disulfide (DADS)-induced G2/M arrest in human gastric cancer MGC803 cells.METHODS: MGC803 cell growth inhibition was measured by MTT...AIM: To determine the role of p38 MAP kinase signal transduction pathways in diallyl disulfide (DADS)-induced G2/M arrest in human gastric cancer MGC803 cells.METHODS: MGC803 cell growth inhibition was measured by MTT assay. Phase distribution of cell cyde was analyzed by flow cytometry. Expression of Cdc25C, p38, phosphorylation of p38 (pp38) were determined by Western blotting.RESULTS: MT1- assay showed that SB203580, a specific p38 MAPK inhibitor blocked DADS-induced growth inhibition.Flow cytometry analysis revealed that treatment of MGC803 cells with 30 mg/L DADS increased the percentage of cells in the G2/M phase from 9.3% to 39.4% (P<0.05), whereas inhibition of p38 activity by SB203580 abolished induction of G2/M arrest by DADS. Western blotting showed that phosphorylation of p38 was increased 3.52-fold following treatment of MGC803 cells with 30 mg/L DADS for 20 min(P<0.05), whereas Cdc25C was decreased 68% following treatment of MGCS03 cells with 30 mg/L DADS for 24 h(P<0.05). Decreased Cdc25C protein expression by DADS was attenuated by SB203580 (P<0.05).CONCLUSION: DADS-induced G2/M arrest of MGC803 cells involves activation of p38 MAP kinase pathways.Decreased Cdc25C protein expression by p38 MAPK played a crucial role in G2/M arrest after treatment with DADS.展开更多
基金supported by the grants from National Natural Science Foundation of China(No.39993430-2,30000157)
文摘To lay background for studying rejection mechanisms in xenotransplantation and developing the strategies for intervention, class I genes of swine leukocyte antigens (SLA) of three Chinese pig strains Bm, Gz and Yn were cloned and sequenced. The cDNA of the class I loci P1 and P14 were amplified by RT-PCR and subjected to insert into sequencing vectors. All six allelic sequences we examined, each two for one Chinese strain, are not identical to those reported, which allows these novel sequences receiving their accession numbers AY102467- AY102472 from GenBank. This study further reveals that the homologies of MHC class I genes in their primary structures and the deduced amino acids between Chinese pigs (SLA) and human (HLA-A*0201) are better than those between pigs and mice (H-2Db/H-2Kb). The comparison also indicates that the amino acid residues critical for recognition by human KIRs are altered in the swine class I molecules. The amino acids responsible for binding human CD8 coreceptor are largely conserved although there are two critical residues substituted. A functional test indicated that the human T cells specific for the prokaryotically expressed SLA Plprotein could respond quite well in vitro to the class I-positive swine chon-drocytes and PBMCs in presence of human APCs. This implies that, due to the substitution of two critical residues, the inaccessibility of human CD8 coreceptor to swine class I molecule might be contributable to the indirect pathway that the human T cells have to use for recognizing the SLA class I xenogeneic antigens.
基金supported by the National Natural Science Foundation of China,Nos.82104560(to CL),U21A20400(to QW)the Natural Science Foundation of Beijing,No.7232279(to XW)the Project of Beijing University of Chinese Medicine,No.2022-JYB-JBZR-004(to XW)。
文摘The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue regeneration.As the first immune cells to be activated after an ischemic stroke,microglia play an important immunomodulatory role in the progression of the condition.After an ischemic stroke,peripheral blood immune cells(mainly T cells)are recruited to the central nervous system by chemokines secreted by immune cells in the brain,where they interact with central nervous system cells(mainly microglia)to trigger a secondary neuroimmune response.This review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic stroke.We found that,during ischemic stroke,T cells and microglia demonstrate a more pronounced synergistic effect.Th1,Th17,and M1 microglia can co-secrete proinflammatory factors,such as interferon-γ,tumor necrosis factor-α,and interleukin-1β,to promote neuroinflammation and exacerbate brain injury.Th2,Treg,and M2 microglia jointly secrete anti-inflammatory factors,such as interleukin-4,interleukin-10,and transforming growth factor-β,to inhibit the progression of neuroinflammation,as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain injury.Immune interactions between microglia and T cells influence the direction of the subsequent neuroinflammation,which in turn determines the prognosis of ischemic stroke patients.Clinical trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic stroke.However,such studies have been relatively infrequent,and clinical experience is still insufficient.In summary,in ischemic stroke,T cell subsets and activated microglia act synergistically to regulate inflamm
基金The work is supported by the National Natural Science Foundation of China(Nos.51875291 and 52075266)the Excellent Youth Fund of Jiangsu Province(No.BK20190070)the Fundamental Research Funds for the Central Universities(No.30920032206).
文摘Duplexα/β-SiAlON ceramic cutting inserts(30α:70β)were synthesized by microwave sintering.The effects of solid solution parameters(m,n,z),synthesis temperature,and amount of excess Y_(2)O_(3) synthesis additive on phase assemblage,microstructure,mechanical properties,and cutting performance were systematically investigated.It was found that increasing m value could improve the formation ofαphase while high z value over 1.0 resulted in the dissolution ofαphase intoβphase and intergranular phase.Increasing the amount of excess Y_(2)O_(3) could promote densification and elongatedβgrain growth;however,the excess Y_(2)O_(3) amount above 4 wt%resulted in substantial crystallization of M'SS phase,thus declining the mechanical properties and wear resistance.The microwave-synthesizedα/β-SiAlON cutting insert with modified parameters(m=1.7,n=1.0,z=0.7,and 3 wt%excess Y_(2)O_(3))was obtained with optimal comprehensive properties,whose tool life was found to increase by approximately 75%in high-speed milling of Inconel 718 superalloy compared to the commercialα/β-SiAlON cutting insert.
基金supported by the National Natural Science Foundation of China(81973336)the Joint Fund of the National Natural Science Foundation of China(U21A20345)。
文摘The mesencephalic astrocyte-derived neurotrophic factor(MANF)has been recently identified as a neurotrophic factor,but its role in hepatic fibrosis is unknown.Here,we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl4.MANF deficiency in either hepatocytes or hepatic mono-macrophages,particularly in hepatic mono-macrophages,clearly exacerbated hepatic fibrosis.Myeloid-specific MANF knockout increased the population of hepatic Ly6C^(high)macrophages and promoted HSCs activation.Furthermore,MANF-sufficient macrophages(from WT mice)transfusion ameliorated CCl4-induced hepatic fibrosis in myeloid cells-specific MANF knockout(MKO)mice.Mechanistically,MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation.Pharmacologically,systemic administration of recombinant human MANF significantly alleviated CCl_(4)-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout(HKO)mice.This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a“brake”on the upstream of NF-κB pathway,which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.
基金the National Natural Science Foundation of China(816015085).
文摘Background:Xiaoqinglong decoction(XQLD)is a classic Chinese medicinal formula that is widely used to treat allergic asthma.Recently,the use of XQLD to treat allergic asthma has inspired research to determine its mechanism of action.Because dendritic cells(DCs)and the T helper 1(Th1)/Th2 cytokine balance play important roles in allergic asthma,the present work aimed to assess how these immune system components are affected by XQLD.Methods:Thirty-six female BALB/C mice were randomly divided into three groups:an ovalbumin-based allergic asthma model group,a XQLD treatment group,and a control group.Histology was performed with haematoxylin and eosin staining and immunohistochemical staining.Bronchoalveolar lavage fluid and blood were collected from the animals and used to analyze the composition of inflammatory cells and expression levels of the cytokines interleukin(IL)-5 and IL-13.The thymic stromal lymphopoietin(TSLP)protein expression was assessed by western blot analysis,and the Gata3 and Tbx21 mRNA levels were assessed by polymerase chain reaction.Results:Compared with the OVA group,the levels of TSLP expression,IL-5,IL-13,and immunoglobulin E in the XQLD group were lower(all P<.01).The level of IL-4-expressing cells(Th2 cells)was lower(P=.0013),and the percentage of IFN-g-expressing cells(Th1 cells)was higher in the XQLD group compared with those in the OVA group(P=.0065).In addition,XQLD increased the expression of Tbx21 mRNA and decreased the expression of Gata3 mRNA in the lungs compared with the OVA group(both P<.01).Conclusion:These findings suggest that XQLD may ameliorate the course of allergic asthma by regulating the Gata3/Tbx21 balance and inhibiting TSLP expression,changes which are indicative of an altered Th1/Th2 balance.Thus,the clinical effectiveness of XQLD in treating allergic asthma may be due to its regulation of Th1/Th2 balance.
基金supported by the National Natural Science Foundation of China(81801679,81571308).
文摘MAGED4B belongs to the melanoma-associated antigen family;originally found in melanoma,it is expressed in various types of cancer,and is especially enriched in glioblastoma.However,the functional role and molecular mechanisms of MAGED4B in glioma are still unclear.In this study,we found that the MAGED4B level was higher in glioma tissue than that in non-cancer tissue,and the level was positively correlated with glioma grade,tumor diameter,Ki-67 level,and patient age.The patients with higher levels had a worse prognosis than those with lower MAGED4B levels.In glioma cells,MAGED4B overexpression promoted proliferation,invasion,and migration,as well as decreasing apoptosis and the chemosensitivity to cisplatin and temozolomide.On the contrary,MAGED4B knockdown in glioma cells inhibited proliferation,invasion,and migration,as well as increasing apoptosis and the chemosensitivity to cisplatin and temozolomide.MAGED4B knockdown also inhibited the growth of gliomas implanted into the rat brain.The interaction between MAGED4B and tripartite motif-containing 27(TRIM27)in glioma cells was detected by co-immunoprecipitation assay,which showed that MAGED4B was co-localized with TRIM27.In addition,MAGED4B overexpression down-regulated the TRIM27 protein level,and this was blocked by carbobenzoxyl-L-leucyl-L-leucyl-L-leucine(MG132),an inhibitor of the proteasome.On the contrary,MAGED4B knockdown up-regulated the TRIM27 level.Furthermore,MAGED4B overexpression increased TRIM27 ubiquitination in the presence of MG132.Accordingly,MAGED4B down-regulated the protein levels of genes downstream of ubiquitin-specific protease 7(USP7)involved in the tumor necrosis factor-alpha(TNF-α)-induced apoptotic pathway.These findings indicate that MAGED4B promotes glioma growth via a TRIM27/USP7/receptor-interacting serine/threonine-protein kinase 1(RIP1)-dependent TNF-α-induced apoptotic pathway,which suggests that MAGED4B is a potential target for glioma diagnosis and treatment.
基金Supported by Jiangsu Provincial Natural Science Foundation of China(Grant No.BK20141400)National Natural Science Foundation of China(Grant No.51105207)Priority Academic Program Development of Jiangsu Higher Education Institutions of China
文摘The aluminum alloy AlMn1Cu has been broadly applied for functional parts production because of its good properties. But few researches about the machining mechanism and the surface roughness were reported. The high-speed milling experiments are carried out in order to improve the machining quality and reveal the machining mechanism. The typical topography features of machined surface are observed by scan electron microscope（SEM）. The results show that the milled surface topography is mainly characterized by the plastic shearing deformation surface and material piling zone. The material flows plastically along the end cutting edge of the flat-end milling tool and meanwhile is extruded by the end cutting edge, resulting in that materials partly adhere to the machined surface and form the material piling zone. As the depth of cut and the feed per tooth increase, the plastic flow of materials is strengthened and the machined surface becomes rougher. However, as the cutting speed increases, the plastic flow of materials is weakened and the milled surface becomes smoother. The cutting parameters （e.g. cutting speed, feed per tooth and depth of cut） influencing the surface roughness are analyzed. It can be concluded that the roughness of the machined surface formed by the end cutting edge is less than that by the cylindrical cutting edge when a cylindrical flat-end mill tool is used for milling. The proposed research provides the typical topography features of machined surface of the anti-rust aluminum alloy AlMn1Cu in high speed milling.
文摘The effect of Ultra-violet light on the structure and motion of the polyvinyl alcohol (PVA) chains was studied by H NMR, spin-lattice relaxation and IR spectroscopy. 1 The results indicated that with the increase of irradiation time, the intensity of the polymer hydroxyl proton peaks decreased and finally vanished, which suggested the self-condensation between the hydroxyl groups proceeded. No methyl proton peaks appeared in the spectra after irradiation shows that there is no cleavage of polymer chain. The longer the irradiation time is, the wider the proton peak of the residual water of the solvent is and it shifted toward low field. This result implies that the hydrogen bonds formed between the polymer and the residual water. The absorption peak of hydroxyl group of the polymer moves toward the lower wave number in the IR spectrum that showed the existence of the hydrogen bonds between the PVA macromolecules.
基金supported by the National Natural Science Foundation of China (Grant No. 60976069)the Scientific Research Program of the Educational Committee of Shaanxi Province, China (Grant No. 11JK0846)+1 种基金the Scientific Research Foundation for Doctors of Yanan University (GrantNos. YD2009-01 and YDZD2011-03)the Scientific and Technology Research and Development Program of Yanan Municipal (Grant No.2011ks-24)
文摘Using the first-principles calculations, we studied the geometric structures, electronic structures and optical properties of the single-walled (n, 0) ZnO nanotubes (NTs). The calculated results show that all the bind energies of the single-walled (n,0) ZnO NTs are of negative values, which indicate that the ZnO NTs can exist stably as single-walled NTs. While the calculated results of electronic structure indicate that the single-walled (n,0) ZnO NTs are a type of direct wide band-gap semiconductor materials, the whole valence bands are spread and drift to low-energy direction with the increase of the NT diameter. The defect energy levels caused by quantum size and surface effects emerge on the top of the valence bands. Furthermore, the calculated results of optical properties reveal that the dielectric peaks have a blue shift and the edge of absorption band corresponds to ultraviolet band with the decrease of the NT diameter. The single-walled (n, 0) ZnO NTs can be applied to ultraviolet semiconductor systems.
基金the National Natural Science Foundation of China(Nos.51775280 and 51675285)the Six Talent Peaks Project in Jiangsu Province(No.2016-HKHT-019)。
文摘In this study, powder mixtures containing(Ti, W)C additions(10, 20, 30 and 40 wt%) were prepared and then consolidated at 1200, 1250, 1300 and 1350 °C by spark plasma sintering. The effect of(Ti, W)C additions on the microstructure and mechanical properties of ultrafine WC–Co materials was investigated. The results demonstrate that the(Ti, W)C not only retards the sintering densification but also increases the porosity of sintered samples. The increasing sintering temperature is beneficial to the densification but results in the grain coarsening and the dissolution of W in(Ti, W)C. Moreover, there are no(Ti, W)C grains with obvious core/rim structure in the microstructure. With the(Ti, W)C increasing from 10 to 20 wt%, the hardness increases and fracture toughness changes hardly. However, the hardness and fracture toughness decrease slightly as the(Ti, W)C further increases. The transgranular fracture of(Ti, W)C phases is responsible for the slight reduction in fracture toughness. The sample with 20 wt%(Ti, W)C has high hardness and fracture toughness( HV : 21.3 GPa, KIC: 9.8 MPa m1/2).
基金supported by the National Natural Science Foundation of China (Nos. 61074118 and 61134012)the National Key Basic Research and Development (973) Program of China (No. 2012CB720505)
文摘Memristor is introduced as the fourth basic circuit element.Memristor exhibits great potential for numerous applications,such as emulating synapse,while the mathematical model of the memristor is still an open subject.In the linear-drift model,the boundary condition of the device is not considered.This paper proposes an extended linear-drift model of the memristor.The extended linear-drift model keeps the linear characteristic and simplicity of the linear-drift model and considers the boundary condition of the device.A piecewise linear approximation model of the extended linear-drift model is given.Both models are suitable for describing the memristor.
基金supported by the National Natural Science Foundation of China(Nos.52075266,51875291)Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.KYCX22_0402).
文摘Spark plasma sintering(SPS)is a highly efficient method for the preparation ofα/β-SiAlON ceramics.However,the rapid preparation of large-scaleα/β-SiAlON ceramic components with reliable mechanical properties is difficult via SPS due to their near-insulating properties.In this study,high-performanceα/β-SiAlON ceramic end mill rods with large aspect ratios were successfully prepared via SPS.Two different types of sintering processes(namely vertical-round-rod(VRR)and horizontal-square-rod(HSR)processes)were developed,and their effects on the phase composition,microstructure,mechanical properties,and machining performance of theα/β-SiAlON ceramic end mill rods were studied.The electric and temperature field distributions during sintering were studied through an electro–thermal simulation.The simulated and experimental temperature distributions are in good agreement.In contrast to VRR samples,HSR samples with a small axial size show a uniform temperature distribution and satisfactory microstructures within a certain range of dimensions as well as the expected phase composition;furthermore,elongatedβ-SiAlON grains are preferentially oriented in the direction perpendicular to the sintering pressure direction.As a result,the HSR samples exhibit better mechanical properties and machining performance than the VRR samples.
文摘Objective： Lung cancer has emerged as a leading cause of cancer death in the world. Eyes Absent （EYA） is an important and conserved transcriptional regulator of development. The aim of the present study was to identify the expression of Drosophila Eyes Absent Hemologue 2 （EYA2） in non-small cell lung cancer （NSCLC） and to investigate their correlation with clinical parameters. Methods： Fresh, paired lung samples （n = 59） of NSCLC were obtained by surgical resection at the Department of Thoracic Surgery of the People＇s Liberation Army General Hospital. Expression of EYA2 were examined by Western blot and immunohistochemical analysis in specimens of NSCLC and paired normal lung tissue. Clinical data, pathologic result and Ki67 expression were collected and subsequent correlation with EYA2 expression was analyzed. Results： EYA2 expression was found located in cytoplasm and nucleus, but mostly in cytoplasm. The expression of EYA2 increased in NSCLC by Western blot and immunohistochemistry, which was correlated with histology type, but not correlated with gender, age, pTNM stage, histological differentiation and lymph node metastasis. Compared with normal lung tissue, the expression of EYA2 significantly was up-regulated in lung adenocarcinoma, while no significant difference in lung squamous cell carcinoma. Expression of EYA2 was uncorrelated with expression of Ki67 in NSCLC. Conclusion： Expression of EYA2 was augmented in lung adenocarcinoma. EYA2 is likely participating in tumorigenesis and development of lung adenocarcinoma as transcriptional activator.
基金supported by the National Natural Science Foundation of China(NNSFC)for outstanding young scientists for Dr.Zheng-tao Wang(No.39825129).
文摘Two new metabolites, namely bisline lactone and isolinecic acid lactone, were isolated from the resultant incubates after a scale-up incubation of isoline with rat liver microsomes. Their structures were determined by spectroscopic data, especially those from 1D and 2D NMR experiments.
基金Supported by the Science Research Foundation of Janssen Pharmaceutical Ltd.(JRC14)
文摘Objective： To investigate the alternations of proteins in the colonic mucosa of chronic slow transit constipation （STC） rats with a 2-DE-based proteomic method and analyze the function of these down-regulated proteins so as to provide theoretical basis for the pathogenesis of intestinal mucosa of chronic STC rats. Methods： STC model was established by feeding rats with 8 mg/（kg＇d） diphenoxylate for 120 d. An experimental model of chronic STC rat was used for separation of proteomics from colonic mucosa using two-dimensional electrophoresis （2-DE）. Proteins altered in expressional level were identified by Image Master 2DElite, mass spectrometry, and bibliometrics were applied to identify the differential protein expression and their clinical s observed in the pathogenesis lgn of ificance and function were analyzed. Results： Obvious differential protein expression was STC, including mast cell protease （A1）, non-specific dipeptidase （A2） and chondrosome succinate dehydrogenase precursor （A3）. The expressions of A1, A2 and A3 were down-regulated in the gel graph of STC rats Conclusion： The down-regulation of chondrosome succinate dehydrogenase, mast cell protease as well as non-specific dipeptidase in rat colon suggests the functional impairment of the oxidoreduction of mitochondrion is very important in the genesis and development of STC. The immunological reaction of STC rats is weakened, and the function of digesting and absorbing protein may be damaged to some extent.
基金Supported by the Natural Science Foundation of Hunan Province,No.02JJY2026,01JJY2146 and the Foundation of Hunan ProvinceEducation Department,No.01A016
文摘AIM: To determine the role of p38 MAP kinase signal transduction pathways in diallyl disulfide (DADS)-induced G2/M arrest in human gastric cancer MGC803 cells.METHODS: MGC803 cell growth inhibition was measured by MTT assay. Phase distribution of cell cyde was analyzed by flow cytometry. Expression of Cdc25C, p38, phosphorylation of p38 (pp38) were determined by Western blotting.RESULTS: MT1- assay showed that SB203580, a specific p38 MAPK inhibitor blocked DADS-induced growth inhibition.Flow cytometry analysis revealed that treatment of MGC803 cells with 30 mg/L DADS increased the percentage of cells in the G2/M phase from 9.3% to 39.4% (P<0.05), whereas inhibition of p38 activity by SB203580 abolished induction of G2/M arrest by DADS. Western blotting showed that phosphorylation of p38 was increased 3.52-fold following treatment of MGC803 cells with 30 mg/L DADS for 20 min(P<0.05), whereas Cdc25C was decreased 68% following treatment of MGCS03 cells with 30 mg/L DADS for 24 h(P<0.05). Decreased Cdc25C protein expression by DADS was attenuated by SB203580 (P<0.05).CONCLUSION: DADS-induced G2/M arrest of MGC803 cells involves activation of p38 MAP kinase pathways.Decreased Cdc25C protein expression by p38 MAPK played a crucial role in G2/M arrest after treatment with DADS.
