Both long-term environmental durability and high reflectance of protected-Al mirrors are of great importance for developing the optical instruments in the vacuum ultraviolet(VUV) applications. In this paper, the depen...Both long-term environmental durability and high reflectance of protected-Al mirrors are of great importance for developing the optical instruments in the vacuum ultraviolet(VUV) applications. In this paper, the dependence of spectral property and environmental durability of MgF2 over-coated Al mirrors using a 3-step method on deposition temperature of the outermost MgF2 layer are investigated in detail. Optics(reflectance), structure(surface morphology and crystalline), and environmental durability(humidity test) are characterized and discussed. The results show that both optical and moistureresistant properties of MgF2 over-coated Al mirrors are dependent on MgF2 deposition temperature, and the optimal deposition temperature for the outermost MgF2 layer should be between 250℃ and 300℃ for MgF2 over-coated Al mirrors to have both reasonably high reflectance in the VUV spectral range and high moisture resistance for long lifetime applications.展开更多
A convenient synthetic method of metal dendritic porphyrins through the convergent synthetic strategy is described. The porphyrin core were linked with the synthetic fragments by forming ether or ester bonds to give f...A convenient synthetic method of metal dendritic porphyrins through the convergent synthetic strategy is described. The porphyrin core were linked with the synthetic fragments by forming ether or ester bonds to give five target compounds were prepared.展开更多
In this work,high-manganese aluminium bronze CuMn_(13)Al_(7)samples were prepared by arc additive manufacturing technology.The phase composition,microstructure,and crystal structure of the high-manganese aluminium bro...In this work,high-manganese aluminium bronze CuMn_(13)Al_(7)samples were prepared by arc additive manufacturing technology.The phase composition,microstructure,and crystal structure of the high-manganese aluminium bronze CuMn_(13)Al_(7)arc additive manufactured samples were analysed using direct-reading spectrometer,metallographic microscope,scanning electron microscope,and transmission electron microscope.The micro-hardness tester,tensile tester,impact tester,and electrochemical workstation were also used to test the performance of the CuMn_(13)Al_(7)samples.By studying the microstructure and properties of the CuMn_(13)Al_(7)samples,it was found that preparation of the samples by the arc additive manufacturing technology ensured good forming quality,almost no defects,and good metallurgical bonding inside the sample.The metallographic structure(α+β+point phase)mainly comprises the following:the metallographic structure in the equiaxed grain region has an obvious grain boundaryα;the metallographic structure in the remelting region has no obvious grain boundaryα;the thermal influence on the metallographic structure produced a weaker grain boundaryαthan the equiaxed grain region.The transverse and longitudinal cross sections of the sample had uniform microhardness distributions,and the average microhardness values were 190.5 HV0.1 and 192.7 HV0.1,respectively.The sample also had excellent mechanical properties:yield strength of 301 MPa,tensile strength of 633 MPa,elongation of 43.5%,reduction of area by 58%,Charpy impact value of 68 J/cm^(2)at–20℃,and dynamic potential polarisation curve test results.Further,it was shown that the average corrosion potential of the sample was–284.5 mV,and the average corrosion current density was 4.1×10–3 mA/cm^(2).展开更多
Ischemic stroke is a major public health problem worldwide.Although the circadian clock is involved in the process of ischemic stroke,the exact mechanism of the circadian clock in regulating angiogenesis after cerebra...Ischemic stroke is a major public health problem worldwide.Although the circadian clock is involved in the process of ischemic stroke,the exact mechanism of the circadian clock in regulating angiogenesis after cerebral infarction remains unclear.In the present study,we determined that environmental circadian disruption(ECD)increased the stroke severity and impaired angiogenesis in the rat middle cerebral artery occlusion model,by measuring the infarct volume,neurological tests,and angiogenesis-related protein.We further report that Bmal1 plays an irreplaceable role in angiogenesis.Overexpression of Bmal1 promoted tube-forming,migration,and wound healing,and upregulated the vascular endothelial growth factor(VEGF)and Notch pathway protein levels.This promoting effect was reversed by the Notch pathway inhibitor DAPT,according to the results of angiogenesis capacity and VEGF pathway protein level.In conclusion,our study reveals the intervention of ECD in angiogenesis in ischemic stroke and further identifies the exact mechanism by which Bmal1 regulates angiogenesis through the VEGF-Notch1 pathway.展开更多
This study investigates the effect of flexible tax enforcement on firms’excess goodwill using unique manually collected data on taxpaying credit rating in China from 2014 to 2021.We document that A-rated taxpayer fir...This study investigates the effect of flexible tax enforcement on firms’excess goodwill using unique manually collected data on taxpaying credit rating in China from 2014 to 2021.We document that A-rated taxpayer firms have less excess goodwill;A-rated firms reduce excess goodwill by 0.005 vis-a-vis non-Arated firms,which accounts for 100%of the mean value of excess goodwill.This finding holds after multiple robustness tests and an endogeneity analysis.Moreover,this negative effect is more pronounced in firms with low information transparency,that are non-state-owned and that are located in regions with low tax enforcement intensity.The channel test results suggest that taxpaying credit rating system as flexible tax enforcement reduces firms’excess goodwill through a reputation-based effect and not a governance-based effect.This study reveals that the taxpaying credit rating system in China as flexible tax enforcement can bring halo effect to A rating firms,thereby limiting irrational M&As and breaking goodwill bubble.展开更多
AbstracTthe blood-brain barrier(BBB)impairment plays a crucial role in the pathological processes of aging-accompanied neurological diseases(AAND).Meanwhile,circadian rhythms disruption and gut microbiota dysbiosis ar...AbstracTthe blood-brain barrier(BBB)impairment plays a crucial role in the pathological processes of aging-accompanied neurological diseases(AAND).Meanwhile,circadian rhythms disruption and gut microbiota dysbiosis are associated with increased morbidity of neurological diseases in the accelerated aging population.Importantly,circadian rhythms disruption and gut microbiota dysbiosis are also known to induce the generation of toxic metabolites and pro-inflammatory cytokines,resulting in disruption of BBB integrity.Collectively,this provides a new perspective for exploring the relationship among circadian rhythms,gut microbes,and the BBB in aging-accompanied neurological diseases.In this review,we focus on recent advances in the interplay between circadian rhythm disturbances and gut microbiota dysbiosis,and their potential roles in the BBB disruption that occurs in AAND.Based on existing literature,we discuss and propose potential mechanisms underlying BBB damage induced by dysregulated circadian rhythms and gut microbiota,which would serve as the basis for developing potential interventions to protect the BBB in the aging population through targeting the BBB by exploiting its links with gut microbiota and circadian rhythms for treating AAND.展开更多
Objective:The population density and diversity of Sinomenium acutum(Menispermaceae)have been greatly reduced recently by overharvesting for medicinal purposes in China.Therefore,it is urgent that the remaining populat...Objective:The population density and diversity of Sinomenium acutum(Menispermaceae)have been greatly reduced recently by overharvesting for medicinal purposes in China.Therefore,it is urgent that the remaining populations are investigated,and that strategies for the utilization and conservation of this species are developed.This study aimed to find the possible glacial refugia and define the genetic diversity of S.acutum for its proper utilization and conservation.Methods:A total of 77 S.acutum samples were collected from four locations,Qinling Mountains,Daba Mountains,Dalou Mountains,and Xuefeng Mountains,in subtropical China.Genetic diversity among and between these populations were phylogenetically analyzed using four chloroplast DNA molecular markers(atpI-atpH,trnQ-50 rps16,trnH-psbA and trnL-trnF).Results:A total of 14 haplotypes(C1 to C14)were found in collected samples.Haplotypes C1 and C3 were shared among all populations,with C3 as the ancestral haplotype.Haplotypes C11 and C12 diverged the most from C3 and other haplotypes.No obvious phylogeographic structure was found in four locations using the GST/NST test.There is no evidence of rapid demographic expansion in S.acutum based on the mismatch distribution,and the results of Tajima’s D test,and Fu’s FS test.Our analyses of molecular variance revealed a high level of genetic variation within populations.In contrast,the genetic differentiation among S.acutum populations was low,indicating frequent gene flow.Conclusion:Xuefeng,Dalou,and Daba Mountains were possible glacial refugia for the populations of S.acutum.C1,C3,C11 and C12 haplotypes of S.acutum should be carefully preserved and managed for their genetic value.展开更多
Systemic lupus erythematosus （SLE） is a prototypic autoimmune disease. Innate and adaptive immunity cooperatively contribute to the development of SLE. Antigen-presenting cells （APCs） have been suggested to link i...Systemic lupus erythematosus （SLE） is a prototypic autoimmune disease. Innate and adaptive immunity cooperatively contribute to the development of SLE. Antigen-presenting cells （APCs） have been suggested to link innate and adaptive immunity. T-cell immunoglobulin- and mucin-domain-containing molecule-4 （Tim-4; also known as Timd4）, expressed primarily on the surface of APCs, is a member of the TIM family, a recently described group of molecules that have received much attention as potential regulators of the immune system. In this study, we used quantitative real-time reverse transcription-polymerase chain reaction to examine the mRNA expression of Tim-4 in peripheral blood mononuclear cells （PBMCs） from SLE patients and further analyzed the correlation between the expression of Tim-4 and Tim- 1 （a potential l igand for Tim-4） in PB MCs and serum tumor necrosis factor （TNF）-a levels. The results showed that Tim-4 mRNA expression in PBMCs was significantly higher in SLE patients than in healthy controls, especially those patients in the active phase of disease. Moreover, Tim-4 mRNA levels were closely correlated with Tim- 1 mRNA levels in PBMCs and with serum TNF-a levels in SLE patients but not in the control group. Taken together, these results demonstrate that Tim-4 may be involved in the pathogenesis of SLE.展开更多
Programmed cell death 4 （Pdcd4） is a newly defined inhibitor of transcription and translation and a tumor suppressor. Recent studies have suggested that Pdcd4 may also be involved in some inflammatory diseases, Howe...Programmed cell death 4 （Pdcd4） is a newly defined inhibitor of transcription and translation and a tumor suppressor. Recent studies have suggested that Pdcd4 may also be involved in some inflammatory diseases, However, its role in atherosclerosis, a chronic inflammation of the arterial wall, remains to be investigated. Here, we found that Pdcd4 deficiency in mice increased the expression of IL-10 in macrophages and decreased the expression of IL-17 in T cells in the presence of an atherosclerosis-associated stimulator in vitro and in high fat-induced atherosclerotic plaques. Importantly, knocking out Pdcd4 led to a decrease in atherosclerotic lesions in Apoe-/- mice fed a high fat diet. This effect could be partly reversed by blocking IL-10 with a neutralizing antibody but not by the application of exogenous IL-17. Further mechanistic studies revealed that Pdcd4 negatively regulated the expression of IL-10 in an ERK1/2- and p38-dependent manner. These results demonstrate that Pdcd4 deficiency attenuates atherosclerosis in hyperlipidemic mice in part through the upregulation of the anti-inflammatory cytokine IL-10. This indicates that endogenous Pdcd4 promotes atherosclerosis and therefore represents a potential therapeutic target for patients with atherosclerosis.展开更多
Considerable evidence indicates that type 1 T helper （Th 1）- and Th 17-mediated immune responses promote the formation of atherosclerotic plaques while that CD4＋CD25＋Foxp3＋ regulatory T cells （Tregs） have a pro...Considerable evidence indicates that type 1 T helper （Th 1）- and Th 17-mediated immune responses promote the formation of atherosclerotic plaques while that CD4＋CD25＋Foxp3＋ regulatory T cells （Tregs） have a protective effect. However, the functions of diverse CD4＋ lymphocyte subsets in plaque rupture remain poorly understood because of a shortage of satisfactory plaque rupture models. Here, we established a murine model of atherosclerotic plaque rupture using a high-fat diet and collar placement on the carotid artery, and triggered plaque rupture by short-term stimulation with a combination of lipopolysaccharide, phenylephrine injection and cold in apolipoprotein E-knockout （ApoE-/-） mice. We investigated the associations between Thl cells, Th17 cells and Tregs and plaque rupture by PCR, flow cytometry, ELISA and immunohistochemistry. In total, 75% （18/24） of vulnerable plaques, but no stable plaques, showed rupture characteristics. The proportion of Th17 cells was increased among splenocytes after treatment, but the changes in the levels of Thl ceils and Tregs were not related to rupture. Furthermore, the treatment resulted in high levels of interleukin- 17 （IL-17） in the serum and in the region of plaque rupture, in vitro, IL-17 increased the level of apoptosis, a major factor associated with plaque rupture, in cultured murine vascular smooth muscle cells. Th17 cells and IL-17 may be involved in the disruption of vulnerable plaques triggered by short-term stimulation with lipopolysaccharide, phenylephrine injection and cold in ApoE-/-mice.展开更多
The solidification structure of a continuous casting large round billet was analyzed by a cellular-automaton-finite-element coupling model using the ProCAST software. The actual and simulated solidification structures...The solidification structure of a continuous casting large round billet was analyzed by a cellular-automaton-finite-element coupling model using the ProCAST software. The actual and simulated solidification structures were compared under mold electromagnetic stirring （MEMS） conditions （current of 300 A and frequency of 3 Hz）. Thereafter, the solidification structures of the large round billet were investigated under different superheats, casting speeds, and secondary cooling intensities. Finally, the effect of the MEMS current on the solidification structures was obtained under fixed superheat, casting speed, secondary cooling intensity, and MEMS frequency. The model accurately simulated the actual solidification structures of any steel, regardless of its size and the parameters used in the continuous casting process. The ratio of the central equiaxed grain zone was found to increase with decreasing superheat, increasing casting speed, decreasing secondary cooling intensity, and increasing MEMS current. The grain size obviously decreased with decreasing superheat and increasing MEMS current but was less sensitive to the casting speed and secondary cooling intensity.展开更多
Summary of main observation and conclusion Benzofuran has antifungal activity as the inhibitor of N-myristoyltransferase.Twenty-nine novel benzofuran-semicarbazide hybrids were designed and synthesized by principle of...Summary of main observation and conclusion Benzofuran has antifungal activity as the inhibitor of N-myristoyltransferase.Twenty-nine novel benzofuran-semicarbazide hybrids were designed and synthesized by principle of drug combinationatory.On this basis,the benzofuran ring was simplified to a resorcinol structure,and sixteen novel 1,3-dialkoxybenzene-semicarbazide hybrids were designed and synthesized.All structures of the target compounds were characterized by HRMS and NMR.The in vitro antifungal activity of target compounds was evaluated using the microdilution broth method against eight strains of pathogenic fungi with fluconazole as positive control.According to the results of the target compounds,structure-activity relationship(SAR)is summarized.The inhibitory activity against the tested strains of simplified compounds(K01-K16)has different levels improvement compared with compounds Z01-Z29.K01-K16 showed significant antifungal activities against A.fumigatus,C.kruseii,and sensitive C.albicans 5314.Notably,compounds Z20,Z22,K10,K11 and K16 also displayed different activities against two fluconazole-resistance strains that were isolated from AIDS patients.The minimal inhibitory concentration(MIC)values against fluconazole-resistant strains were in the range of 2-8μg/mL and 4-32μg/mL,respectively.Furthermore,molecular docking was performed to investigate the binding affinities and interaction modes between the target compound and N-myristoyltransferase.展开更多
Purpose： To investigate the influence of the same mechanical loading on osteogenesis and osteoclastogenesis in vitro. Methods： Primary osteoblasts, bone marrow-derived mesenchymal stem cells （BMSCs, cultured in ost...Purpose： To investigate the influence of the same mechanical loading on osteogenesis and osteoclastogenesis in vitro. Methods： Primary osteoblasts, bone marrow-derived mesenchymal stem cells （BMSCs, cultured in osteoinductive medium） and RAW264.7 cells cultured in osteoclast inductive medium were all subjected to a 1000μstrain （μs） at 1 Hz cyclic mechanical stretch for 30 min （twice a day）. Results： After mechanical stimulation, the alkaline phosphatase （ALP） activity, osteocalcin protein level of the osteoblasts and BMSCs were all enhanced, and the mRNA levels of ALP and collagen type I increased. Additionally, extracellular-deposited calcium of both osteoblasts and BMSCs increased. At the same time, the activity of secreted tartrate-resistant acid phosphatase, the number of tartrate-resistant acid phosphatase-positive multinucleated cells, matrix metalloproteinase-9 protein levels of RAW264.7 cells and the extracellular calcium solvency all decreased. Conclusion： The results demonstrated that 1000 μs cyclic mechanical loading enhanced osteoblasts activity, promoted osteoblastic differentiation of BMSCs and restrained osteoclastogenesis of RAW264.7 cells in vitro.展开更多
BACKGROUND： Nearly 15% of acute myeloid leukemia （AML） cases are caused by aberrant expression of AML 1-ETO, a fusion protein generated by the t（8;21） chromosomal translocation. Since its discovery, AML 1-ETO has...BACKGROUND： Nearly 15% of acute myeloid leukemia （AML） cases are caused by aberrant expression of AML 1-ETO, a fusion protein generated by the t（8;21） chromosomal translocation. Since its discovery, AML 1-ETO has served as a prototype to understand how leukemia fusion proteins deregulate transcription to promote leukemogenesis. Another leukemia fusion protein, E2A-Pbx 1, generated by the t（1; 19） translocation, is involved in acute lymphoblastic leukemias （ALLs）. While AML 1 - ETO and E2A-Pbxl are structurally unrelated fusion proteins, we have recently shown that a common axis, the ETO/E-protein interaction, is involved in the regulation of both fusion proteins, underscoring the importance of studying protein-protein interactions in elucidating the mechanisms of leukemia fusion proteins. OBJECTIVE： In this review, we aim to summarize these new developments while also providing a historic overview of the related early studies. METHODS： A total of 218 publications were reviewed in this article, a majority of which were published after 2004. We also downloaded 3D structures of AML1-ETO domains from Protein Data Bank and provided a systematic summary of their structures. RESULTS： By reviewing the literature, we summarized early and recent findings on AML 1-ETO, including its protein-protein interactions, transcriptional and lenkemogenic mechanisms, as well as the recently reported involvement of ETO family corepressors in regulating the function of E2A-Pbxl. CONCLUSION： While the recent development in genomic and structural studies has clearly demonstrated that the fusion proteins function by directly regulating transcription, a further understanding of the underlying mechanisms, including crosstalk with other transcription factors and cofactors, and the protein-protein interactions in the context of native proteins, may be necessary for the development of highly targeted drugs for leukemia therapy.展开更多
基金Project supported by the West Light Foundation of the Chinese Academy of Sciencesthe National Natural Science Foundation of China(Grant No.61805247)
文摘Both long-term environmental durability and high reflectance of protected-Al mirrors are of great importance for developing the optical instruments in the vacuum ultraviolet(VUV) applications. In this paper, the dependence of spectral property and environmental durability of MgF2 over-coated Al mirrors using a 3-step method on deposition temperature of the outermost MgF2 layer are investigated in detail. Optics(reflectance), structure(surface morphology and crystalline), and environmental durability(humidity test) are characterized and discussed. The results show that both optical and moistureresistant properties of MgF2 over-coated Al mirrors are dependent on MgF2 deposition temperature, and the optimal deposition temperature for the outermost MgF2 layer should be between 250℃ and 300℃ for MgF2 over-coated Al mirrors to have both reasonably high reflectance in the VUV spectral range and high moisture resistance for long lifetime applications.
文摘A convenient synthetic method of metal dendritic porphyrins through the convergent synthetic strategy is described. The porphyrin core were linked with the synthetic fragments by forming ether or ester bonds to give five target compounds were prepared.
基金University Synergy Innovation Program of Anhui Province(Grant No.GXXT-2019-022)Anhui Provincial Natural Science Foundation of China(Grant No.1908085QE174)the Talent Program of Anhui Science and Technology University(Grant No.RCYJ201905).
文摘In this work,high-manganese aluminium bronze CuMn_(13)Al_(7)samples were prepared by arc additive manufacturing technology.The phase composition,microstructure,and crystal structure of the high-manganese aluminium bronze CuMn_(13)Al_(7)arc additive manufactured samples were analysed using direct-reading spectrometer,metallographic microscope,scanning electron microscope,and transmission electron microscope.The micro-hardness tester,tensile tester,impact tester,and electrochemical workstation were also used to test the performance of the CuMn_(13)Al_(7)samples.By studying the microstructure and properties of the CuMn_(13)Al_(7)samples,it was found that preparation of the samples by the arc additive manufacturing technology ensured good forming quality,almost no defects,and good metallurgical bonding inside the sample.The metallographic structure(α+β+point phase)mainly comprises the following:the metallographic structure in the equiaxed grain region has an obvious grain boundaryα;the metallographic structure in the remelting region has no obvious grain boundaryα;the thermal influence on the metallographic structure produced a weaker grain boundaryαthan the equiaxed grain region.The transverse and longitudinal cross sections of the sample had uniform microhardness distributions,and the average microhardness values were 190.5 HV0.1 and 192.7 HV0.1,respectively.The sample also had excellent mechanical properties:yield strength of 301 MPa,tensile strength of 633 MPa,elongation of 43.5%,reduction of area by 58%,Charpy impact value of 68 J/cm^(2)at–20℃,and dynamic potential polarisation curve test results.Further,it was shown that the average corrosion potential of the sample was–284.5 mV,and the average corrosion current density was 4.1×10–3 mA/cm^(2).
基金This work was supported by the National Natural Science Foundation for Young Scholars of China(82004346 and 82104766)the Natural Science Foundation of Hunan Province(2021JJ30521 and 2021JJ40424)+2 种基金the Open Fund for the First-class Discipline of Integrated Traditional Chinese and Western Medicine of Hunan University of Chinese Medicine(2020ZXYJH38 and 2020ZXYJH39)Natural Science Foundation of Changsha(kq2208202)the University-level Fund Project of Hunan University of Chinese Medicine(2021XJJJ039).
文摘Ischemic stroke is a major public health problem worldwide.Although the circadian clock is involved in the process of ischemic stroke,the exact mechanism of the circadian clock in regulating angiogenesis after cerebral infarction remains unclear.In the present study,we determined that environmental circadian disruption(ECD)increased the stroke severity and impaired angiogenesis in the rat middle cerebral artery occlusion model,by measuring the infarct volume,neurological tests,and angiogenesis-related protein.We further report that Bmal1 plays an irreplaceable role in angiogenesis.Overexpression of Bmal1 promoted tube-forming,migration,and wound healing,and upregulated the vascular endothelial growth factor(VEGF)and Notch pathway protein levels.This promoting effect was reversed by the Notch pathway inhibitor DAPT,according to the results of angiogenesis capacity and VEGF pathway protein level.In conclusion,our study reveals the intervention of ECD in angiogenesis in ischemic stroke and further identifies the exact mechanism by which Bmal1 regulates angiogenesis through the VEGF-Notch1 pathway.
基金funded by a grant from the Natural Science Foundation of China(No.71762014)Soft Science Foundation in Gansu(No.23JRZA374).
文摘This study investigates the effect of flexible tax enforcement on firms’excess goodwill using unique manually collected data on taxpaying credit rating in China from 2014 to 2021.We document that A-rated taxpayer firms have less excess goodwill;A-rated firms reduce excess goodwill by 0.005 vis-a-vis non-Arated firms,which accounts for 100%of the mean value of excess goodwill.This finding holds after multiple robustness tests and an endogeneity analysis.Moreover,this negative effect is more pronounced in firms with low information transparency,that are non-state-owned and that are located in regions with low tax enforcement intensity.The channel test results suggest that taxpaying credit rating system as flexible tax enforcement reduces firms’excess goodwill through a reputation-based effect and not a governance-based effect.This study reveals that the taxpaying credit rating system in China as flexible tax enforcement can bring halo effect to A rating firms,thereby limiting irrational M&As and breaking goodwill bubble.
基金supported by Jiaxing Plan of Science and Technology(2022AY30028),Chinasupported by the National Natural Science Foundation of China(81870973,81671145).
文摘AbstracTthe blood-brain barrier(BBB)impairment plays a crucial role in the pathological processes of aging-accompanied neurological diseases(AAND).Meanwhile,circadian rhythms disruption and gut microbiota dysbiosis are associated with increased morbidity of neurological diseases in the accelerated aging population.Importantly,circadian rhythms disruption and gut microbiota dysbiosis are also known to induce the generation of toxic metabolites and pro-inflammatory cytokines,resulting in disruption of BBB integrity.Collectively,this provides a new perspective for exploring the relationship among circadian rhythms,gut microbes,and the BBB in aging-accompanied neurological diseases.In this review,we focus on recent advances in the interplay between circadian rhythm disturbances and gut microbiota dysbiosis,and their potential roles in the BBB disruption that occurs in AAND.Based on existing literature,we discuss and propose potential mechanisms underlying BBB damage induced by dysregulated circadian rhythms and gut microbiota,which would serve as the basis for developing potential interventions to protect the BBB in the aging population through targeting the BBB by exploiting its links with gut microbiota and circadian rhythms for treating AAND.
基金supported by the Hunan Provincial Major Science and Technology Project(2015SK1001)Changsha Science and Technology Plan(kq1801015)+1 种基金Project of Hunan Administration of Traditional Chinese Medicine(2021212)Hunan Provincial Key Laboratory for Synthetic Biology of Traditional Chinese Medicine(HCSW2020-01).
文摘Objective:The population density and diversity of Sinomenium acutum(Menispermaceae)have been greatly reduced recently by overharvesting for medicinal purposes in China.Therefore,it is urgent that the remaining populations are investigated,and that strategies for the utilization and conservation of this species are developed.This study aimed to find the possible glacial refugia and define the genetic diversity of S.acutum for its proper utilization and conservation.Methods:A total of 77 S.acutum samples were collected from four locations,Qinling Mountains,Daba Mountains,Dalou Mountains,and Xuefeng Mountains,in subtropical China.Genetic diversity among and between these populations were phylogenetically analyzed using four chloroplast DNA molecular markers(atpI-atpH,trnQ-50 rps16,trnH-psbA and trnL-trnF).Results:A total of 14 haplotypes(C1 to C14)were found in collected samples.Haplotypes C1 and C3 were shared among all populations,with C3 as the ancestral haplotype.Haplotypes C11 and C12 diverged the most from C3 and other haplotypes.No obvious phylogeographic structure was found in four locations using the GST/NST test.There is no evidence of rapid demographic expansion in S.acutum based on the mismatch distribution,and the results of Tajima’s D test,and Fu’s FS test.Our analyses of molecular variance revealed a high level of genetic variation within populations.In contrast,the genetic differentiation among S.acutum populations was low,indicating frequent gene flow.Conclusion:Xuefeng,Dalou,and Daba Mountains were possible glacial refugia for the populations of S.acutum.C1,C3,C11 and C12 haplotypes of S.acutum should be carefully preserved and managed for their genetic value.
文摘Systemic lupus erythematosus （SLE） is a prototypic autoimmune disease. Innate and adaptive immunity cooperatively contribute to the development of SLE. Antigen-presenting cells （APCs） have been suggested to link innate and adaptive immunity. T-cell immunoglobulin- and mucin-domain-containing molecule-4 （Tim-4; also known as Timd4）, expressed primarily on the surface of APCs, is a member of the TIM family, a recently described group of molecules that have received much attention as potential regulators of the immune system. In this study, we used quantitative real-time reverse transcription-polymerase chain reaction to examine the mRNA expression of Tim-4 in peripheral blood mononuclear cells （PBMCs） from SLE patients and further analyzed the correlation between the expression of Tim-4 and Tim- 1 （a potential l igand for Tim-4） in PB MCs and serum tumor necrosis factor （TNF）-a levels. The results showed that Tim-4 mRNA expression in PBMCs was significantly higher in SLE patients than in healthy controls, especially those patients in the active phase of disease. Moreover, Tim-4 mRNA levels were closely correlated with Tim- 1 mRNA levels in PBMCs and with serum TNF-a levels in SLE patients but not in the control group. Taken together, these results demonstrate that Tim-4 may be involved in the pathogenesis of SLE.
基金We are grateful to the Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University for expert technical assistance. This work was supported by the National 973 Basic Research Program of China （Nos. 2011CB503906, 2012CB518603）, grants from the National Natural Science Foundation of China （81172863, 31470856 and 91439124） and the Natural Science Foundation of Shandong （Z2008C02）, and a grant from the China Postdoctoral Science Foundation （2014 M551912）.
文摘Programmed cell death 4 （Pdcd4） is a newly defined inhibitor of transcription and translation and a tumor suppressor. Recent studies have suggested that Pdcd4 may also be involved in some inflammatory diseases, However, its role in atherosclerosis, a chronic inflammation of the arterial wall, remains to be investigated. Here, we found that Pdcd4 deficiency in mice increased the expression of IL-10 in macrophages and decreased the expression of IL-17 in T cells in the presence of an atherosclerosis-associated stimulator in vitro and in high fat-induced atherosclerotic plaques. Importantly, knocking out Pdcd4 led to a decrease in atherosclerotic lesions in Apoe-/- mice fed a high fat diet. This effect could be partly reversed by blocking IL-10 with a neutralizing antibody but not by the application of exogenous IL-17. Further mechanistic studies revealed that Pdcd4 negatively regulated the expression of IL-10 in an ERK1/2- and p38-dependent manner. These results demonstrate that Pdcd4 deficiency attenuates atherosclerosis in hyperlipidemic mice in part through the upregulation of the anti-inflammatory cytokine IL-10. This indicates that endogenous Pdcd4 promotes atherosclerosis and therefore represents a potential therapeutic target for patients with atherosclerosis.
基金Our study was supported by the National ＇973＇ Program of China （2011CB503900）, the National Natural Science Foundation of China （30628015, 30700729, and 30872309） and Natural Science foundation of Shandong （Z2008C02）.
文摘Considerable evidence indicates that type 1 T helper （Th 1）- and Th 17-mediated immune responses promote the formation of atherosclerotic plaques while that CD4＋CD25＋Foxp3＋ regulatory T cells （Tregs） have a protective effect. However, the functions of diverse CD4＋ lymphocyte subsets in plaque rupture remain poorly understood because of a shortage of satisfactory plaque rupture models. Here, we established a murine model of atherosclerotic plaque rupture using a high-fat diet and collar placement on the carotid artery, and triggered plaque rupture by short-term stimulation with a combination of lipopolysaccharide, phenylephrine injection and cold in apolipoprotein E-knockout （ApoE-/-） mice. We investigated the associations between Thl cells, Th17 cells and Tregs and plaque rupture by PCR, flow cytometry, ELISA and immunohistochemistry. In total, 75% （18/24） of vulnerable plaques, but no stable plaques, showed rupture characteristics. The proportion of Th17 cells was increased among splenocytes after treatment, but the changes in the levels of Thl ceils and Tregs were not related to rupture. Furthermore, the treatment resulted in high levels of interleukin- 17 （IL-17） in the serum and in the region of plaque rupture, in vitro, IL-17 increased the level of apoptosis, a major factor associated with plaque rupture, in cultured murine vascular smooth muscle cells. Th17 cells and IL-17 may be involved in the disruption of vulnerable plaques triggered by short-term stimulation with lipopolysaccharide, phenylephrine injection and cold in ApoE-/-mice.
文摘The solidification structure of a continuous casting large round billet was analyzed by a cellular-automaton-finite-element coupling model using the ProCAST software. The actual and simulated solidification structures were compared under mold electromagnetic stirring （MEMS） conditions （current of 300 A and frequency of 3 Hz）. Thereafter, the solidification structures of the large round billet were investigated under different superheats, casting speeds, and secondary cooling intensities. Finally, the effect of the MEMS current on the solidification structures was obtained under fixed superheat, casting speed, secondary cooling intensity, and MEMS frequency. The model accurately simulated the actual solidification structures of any steel, regardless of its size and the parameters used in the continuous casting process. The ratio of the central equiaxed grain zone was found to increase with decreasing superheat, increasing casting speed, decreasing secondary cooling intensity, and increasing MEMS current. The grain size obviously decreased with decreasing superheat and increasing MEMS current but was less sensitive to the casting speed and secondary cooling intensity.
基金The authors appreciate the financial supports from the National Natural Science Foundation of China(Nos.81573292 and 81903463)Department of Education of Liaoning Province(2017LQN03)Department of Science and Technology of Liaoning Province(20180540032).
文摘Summary of main observation and conclusion Benzofuran has antifungal activity as the inhibitor of N-myristoyltransferase.Twenty-nine novel benzofuran-semicarbazide hybrids were designed and synthesized by principle of drug combinationatory.On this basis,the benzofuran ring was simplified to a resorcinol structure,and sixteen novel 1,3-dialkoxybenzene-semicarbazide hybrids were designed and synthesized.All structures of the target compounds were characterized by HRMS and NMR.The in vitro antifungal activity of target compounds was evaluated using the microdilution broth method against eight strains of pathogenic fungi with fluconazole as positive control.According to the results of the target compounds,structure-activity relationship(SAR)is summarized.The inhibitory activity against the tested strains of simplified compounds(K01-K16)has different levels improvement compared with compounds Z01-Z29.K01-K16 showed significant antifungal activities against A.fumigatus,C.kruseii,and sensitive C.albicans 5314.Notably,compounds Z20,Z22,K10,K11 and K16 also displayed different activities against two fluconazole-resistance strains that were isolated from AIDS patients.The minimal inhibitory concentration(MIC)values against fluconazole-resistant strains were in the range of 2-8μg/mL and 4-32μg/mL,respectively.Furthermore,molecular docking was performed to investigate the binding affinities and interaction modes between the target compound and N-myristoyltransferase.
基金This work was financially supported by the National Natural Science Foundation of China （No.11372351, No.31370942, No.81160223）, and Scientific Research Foundation of Guangxi Higher Education （No.KY2015LX241）.
文摘Purpose： To investigate the influence of the same mechanical loading on osteogenesis and osteoclastogenesis in vitro. Methods： Primary osteoblasts, bone marrow-derived mesenchymal stem cells （BMSCs, cultured in osteoinductive medium） and RAW264.7 cells cultured in osteoclast inductive medium were all subjected to a 1000μstrain （μs） at 1 Hz cyclic mechanical stretch for 30 min （twice a day）. Results： After mechanical stimulation, the alkaline phosphatase （ALP） activity, osteocalcin protein level of the osteoblasts and BMSCs were all enhanced, and the mRNA levels of ALP and collagen type I increased. Additionally, extracellular-deposited calcium of both osteoblasts and BMSCs increased. At the same time, the activity of secreted tartrate-resistant acid phosphatase, the number of tartrate-resistant acid phosphatase-positive multinucleated cells, matrix metalloproteinase-9 protein levels of RAW264.7 cells and the extracellular calcium solvency all decreased. Conclusion： The results demonstrated that 1000 μs cyclic mechanical loading enhanced osteoblasts activity, promoted osteoblastic differentiation of BMSCs and restrained osteoclastogenesis of RAW264.7 cells in vitro.
文摘BACKGROUND： Nearly 15% of acute myeloid leukemia （AML） cases are caused by aberrant expression of AML 1-ETO, a fusion protein generated by the t（8;21） chromosomal translocation. Since its discovery, AML 1-ETO has served as a prototype to understand how leukemia fusion proteins deregulate transcription to promote leukemogenesis. Another leukemia fusion protein, E2A-Pbx 1, generated by the t（1; 19） translocation, is involved in acute lymphoblastic leukemias （ALLs）. While AML 1 - ETO and E2A-Pbxl are structurally unrelated fusion proteins, we have recently shown that a common axis, the ETO/E-protein interaction, is involved in the regulation of both fusion proteins, underscoring the importance of studying protein-protein interactions in elucidating the mechanisms of leukemia fusion proteins. OBJECTIVE： In this review, we aim to summarize these new developments while also providing a historic overview of the related early studies. METHODS： A total of 218 publications were reviewed in this article, a majority of which were published after 2004. We also downloaded 3D structures of AML1-ETO domains from Protein Data Bank and provided a systematic summary of their structures. RESULTS： By reviewing the literature, we summarized early and recent findings on AML 1-ETO, including its protein-protein interactions, transcriptional and lenkemogenic mechanisms, as well as the recently reported involvement of ETO family corepressors in regulating the function of E2A-Pbxl. CONCLUSION： While the recent development in genomic and structural studies has clearly demonstrated that the fusion proteins function by directly regulating transcription, a further understanding of the underlying mechanisms, including crosstalk with other transcription factors and cofactors, and the protein-protein interactions in the context of native proteins, may be necessary for the development of highly targeted drugs for leukemia therapy.
