Complement 5a （C5a） has been implicated in the pathogenesis of sepsis by inducing the functional impairment of neutrophils; however, the utility of C5a receptors （C5aRs; C5aR and C5L2） as biomarkers for the manage...Complement 5a （C5a） has been implicated in the pathogenesis of sepsis by inducing the functional impairment of neutrophils; however, the utility of C5a receptors （C5aRs; C5aR and C5L2） as biomarkers for the management of sepsis is uncertain. This study investigated the dynamic expression of C5aR and C5L2 on neutrophits and their effects on neutrophil function. We found that sepsis patients displayed low expression levels of C5aR and C5L2 on neutrophils compared to healthy and systemic inflammatory response syndrome （SIRS） subjects, and this expression pattern was correlated with disease severity. Additionally, the expression levels of C5aR and C5L2 were associated with the survival of sepsis patients. In vitro, the addition of C5a significantly reduced C5aR and C5L2 expression levels and IL-8 production in neutrophils from sepsis patients. Those findings suggest that the reduced expression of C5aRs was associated with the functional impairment of neutrophils and a poor prognosis for sepsis patients. Overall, these findings may help establish C5aRs expression levels as early markers to predict the severity of sepsis.展开更多
Granulocyte colony-stimulating factor(GM-CSF),produced by CD4^(+)T cells,has recently been implicated in the pathogenesis of inflammatory diseases,such as multiple sclerosis and juvenile arthritis.However,the role of ...Granulocyte colony-stimulating factor(GM-CSF),produced by CD4^(+)T cells,has recently been implicated in the pathogenesis of inflammatory diseases,such as multiple sclerosis and juvenile arthritis.However,the role of GM-CSF-producing CD4^(+)T cells in sepsis remains unknown.This study reports peripheral changes in GM-CSF-producing CD4^(+)T cells in septic patients and the possible underlying mechanism by which GM-CSF influences the outcome of sepsis.Forty-three septic patients,20 SIRS patients,and 20 healthy controls were enrolled in this study and followed for 28 days to assess mortality.We measured the peripheral frequency of GM-CSF^(+)CD4^(+)T cells and recorded their associated relationship with disease progression.Our data demonstrated that peripheral GM-CSF-producing CD4^(+)T cells were significantly higher in septic patients than in both SIRS patients and healthy controls.These cells exhibit a memory phenotype and impaired IFN-γ-secreting capacity in sepsis patients.Using a receiver operating curve analysis with 8.01%as a cut-off point,the percentage of GM-CSF^(+)CD4^(+)T cells could predict the outcome of septic patients.Combined with the increase in GM-CSF-producing CD4^(+)T cells,inflammatory cytokines IL-1βand IL-6 were also upregulated.Using an in vitro neutrophil model,we found that GM-CSF inhibited C3aR expression,while inducing IL-8 production.Furthermore,this effect was transferrable in plasma from sepsis patients and was attenuated by inhibition of GM-CSF using an anti-GM-CSF antibody.These results indicate that GM-CSF-producing CD4^(+)T cells may serve as a marker of sepsis severity.Thus,targeting GM-CSF overproduction may benefit sepsis patients.展开更多
The influence of Mg content on the microstructures and mechanical properties at room temperatures of A1-3.5Cu- （0.71-1.81）Mg alloys was studied. Precipitation phases in the alloys were identified by TEM and HRTEM. T...The influence of Mg content on the microstructures and mechanical properties at room temperatures of A1-3.5Cu- （0.71-1.81）Mg alloys was studied. Precipitation phases in the alloys were identified by TEM and HRTEM. The results show that when Mg contents increase from 0.71 to 1.81 wt%, the precipitates are transformed from S, S＂, 2, and 0 phases to S and St phases, and f2 phase is first observed in A1-3.48Cu-0.71 Mg alloy with Cu/Mg mass ratio of 5 during the conventional aging heat treatment （190 C/12 h）. Regard to aging hardness effect of the tested alloys, the hardness of the alloys improves with the increase of Mg content, but the increases become slow when Mg content is greater than 1.35 wt%.展开更多
P2-Na_(0.67)Ni_(0.33)Mn_(0.67)O_(2)(NNMO)is promising cathode material for sodium-ion batteries(SIBs)due to its high specific capacity and fast Na+diffusion rate.Nonetheless,the irreversible P2-O_(2)phase transformati...P2-Na_(0.67)Ni_(0.33)Mn_(0.67)O_(2)(NNMO)is promising cathode material for sodium-ion batteries(SIBs)due to its high specific capacity and fast Na+diffusion rate.Nonetheless,the irreversible P2-O_(2)phase transformation,Na+/vacancy ordering,and transition metal(TM)dissolution seriously damage its cycling stability and restrict its commercialization process.Herein,Na occupation manipulation and interface stabilization are proposed to strengthen the phase structure of NNMO by synergistic Zn/Ti co-doping and introducing lithium difluorophosp(LiPO_(2)F_(2))film-forming electrolyte additive.The Zn/Ti co-doping regulates the occupancy ratio of Nae/Nafat Na sites and disorganizes the Na+/vacancy ordering,resulting in a faster Na+diffusion kinetics and reversible P2-Z phase transition for P2-Na_(0.67)Ni_(0.28)Zn_(0.05)Mn_(0.62)Ti_(0.05)O_(2)(NNZMTO).Meanwhile,the LiPO_(2)F_(2)additive can form homogeneous and ultrathin cathode-electrolyte interphase(CEI)on NNZMTO surface,which can stabilize the NNZMTO-electrolyte interface to prevent TM dissolution,surface structure transformation,and micro-crack generation.Combination studies of in situ and ex situ characterizations and theoretical calculations were used to elucidate the storage mechanism of NNZMTO with Li PO_(2)F_(2)additive.As a result,the NNZMTO displays outstanding capacity retention of 94.44%after 500 cycles at 1C with 0.3 wt%Li PO_(2)F_(2),excellent rate performance of 92.5 mA h g^(-1)at 8C with 0.1 wt%Li PO_(2)F_(2),and remarkable full cell capability.This work highlights the important role of manipulating Na occupation and constructing protective film in the design of layered materials,which provides a promising direction for developing high-performance cathodes for SIBs.展开更多
Microcystinase(MlrA)is a key endopeptidase that catalyzes microcystin degradation without generating harmful byproduct.However,the application of MlrA in the field is primarily impeded by its limited productivity and ...Microcystinase(MlrA)is a key endopeptidase that catalyzes microcystin degradation without generating harmful byproduct.However,the application of MlrA in the field is primarily impeded by its limited productivity and short lifespan.Therefore,the MlrA's function was studied by modelling its structure,which subsequently increased its heterologous expression and high-temperature stability.Results demonstrate that after the irregular sequence at the C-terminus of MlrA was removed,enzyme solubility was significantly decreased.In addition,three fusion tags,namely maltose-binding protein,glutathione S-transferase(GST),and N-utilization substance A(NusA)were used to enhance the overexpression of soluble recombinant MlrA,among which NusA-MlrA exhibited the highest solubility.Moreover,NusA-MlrA was active in pH 4-10 at 20-80℃;even at 80℃,approximately 35.8%of fusion protein remained active.NusA-MlrA retained 89%of MlrA's activity even after 7 d of storage at 50℃;and on day 7,the protein retained>90%of its activity at pH 7.Finally,a stable,soluble,and long-lasting heterologous MlrA was successfully constructed that could eliminate microcystins in Escherichia coli C43(DE3).This study enriched the comprehension of MlrA's structure and enzymatic properties,by particularly addressing the endopeptidase's low expression and short lifespan,which improved its suitability for future applications.展开更多
The Pt-free photocatalytic hydrogen evolution(PHE)has been the focus in the photocatalytic field.The catalytic system with the large accessible surface and good mass-transfer ability,as well as the intimate combinatio...The Pt-free photocatalytic hydrogen evolution(PHE)has been the focus in the photocatalytic field.The catalytic system with the large accessible surface and good mass-transfer ability,as well as the intimate combination of co-catalyst with semiconductor is promising for the promotion of the application.Here,we have reported the design of the two-dimensional(2D)porous C_(3)N_(4)nanosheets(PCN NS)intimately combined with few-layered MoS_(2)for the high-effective Pt-free PHE.The PCN NS were synthesized based on peeling the melamine–cyanuric acid precursor(MC precursor)by the triphenylphosphine(TP)molecular followed by the calcination,mainly due to the matched size of the(100)plane distance of the precursor(0.8 nm)and the height of TP molecular.The porous structure is favorable for the mass-transfer and the 2D structure having large accessible surface,both of which are positive to promote the photocatalytic ability.The few-layered MoS_(2)are grown on PCN to give 2D MoS_(2)/PCN composites based on anchoring phosphomolybdic acid(PMo_(12))cluster on polyetherimide(PEI)-modified PCN followed by the vulcanization.The few-layered MoS_(2)have abundant edge active sites,and its intimate combination with porous PCN NS is favorable for the faster transfer and separation of the electrons.The characterization together with the advantage of 2D porous structure can largely promote the photocatalytic ability.The MoS_(2)/PCN showed good PHE activity with the high hydrogen production activity of 4,270.8μmol·h^(−1)·g^(−1)under the simulated sunlight condition(AM1.5),which was 7.9 times of the corresponding MoS_(2)/bulk C_(3)N_(4)and 12.7 times of the 1 wt.%Pt/bulk C_(3)N_(4).The study is potentially meaningful for the synthesis of PCN-based catalytic systems.展开更多
Dear Editor,The newly emerged severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron subvariants(XBB.1,EG.5 and JN.1)and sublineages have been circulating globally with superior growth advantages over othe...Dear Editor,The newly emerged severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron subvariants(XBB.1,EG.5 and JN.1)and sublineages have been circulating globally with superior growth advantages over other Omicron variants(Tamura et al.,2023).However,second-generation vaccines,including the BA.2 or BA.5 bivalent vaccine boosters,did not produce robust neutralization against the newly emerged XBB.1 or EG.5(Zou et al.,2023).Compared with variants BA.2 and BA.5,XBB.1 carries more mutations in the receptor binding domain(RBD)and exhibits significant immune evasion(Wang et al.,2023b).XBB.1 and its descendent lineages have rapidly become the dominant SARS-CoV-2 strain and are causing the next global wave of COVID-19.Therefore,it is essential to develop an updated vaccine against the newly emerged SARS-CoV-2 variants.展开更多
文摘Complement 5a （C5a） has been implicated in the pathogenesis of sepsis by inducing the functional impairment of neutrophils; however, the utility of C5a receptors （C5aRs; C5aR and C5L2） as biomarkers for the management of sepsis is uncertain. This study investigated the dynamic expression of C5aR and C5L2 on neutrophits and their effects on neutrophil function. We found that sepsis patients displayed low expression levels of C5aR and C5L2 on neutrophils compared to healthy and systemic inflammatory response syndrome （SIRS） subjects, and this expression pattern was correlated with disease severity. Additionally, the expression levels of C5aR and C5L2 were associated with the survival of sepsis patients. In vitro, the addition of C5a significantly reduced C5aR and C5L2 expression levels and IL-8 production in neutrophils from sepsis patients. Those findings suggest that the reduced expression of C5aRs was associated with the functional impairment of neutrophils and a poor prognosis for sepsis patients. Overall, these findings may help establish C5aRs expression levels as early markers to predict the severity of sepsis.
基金supported by the National Natural Science Foundation of China[grant number 81400626]the National Natural Science Foundation for innovation group[grant number 81721002].
文摘Granulocyte colony-stimulating factor(GM-CSF),produced by CD4^(+)T cells,has recently been implicated in the pathogenesis of inflammatory diseases,such as multiple sclerosis and juvenile arthritis.However,the role of GM-CSF-producing CD4^(+)T cells in sepsis remains unknown.This study reports peripheral changes in GM-CSF-producing CD4^(+)T cells in septic patients and the possible underlying mechanism by which GM-CSF influences the outcome of sepsis.Forty-three septic patients,20 SIRS patients,and 20 healthy controls were enrolled in this study and followed for 28 days to assess mortality.We measured the peripheral frequency of GM-CSF^(+)CD4^(+)T cells and recorded their associated relationship with disease progression.Our data demonstrated that peripheral GM-CSF-producing CD4^(+)T cells were significantly higher in septic patients than in both SIRS patients and healthy controls.These cells exhibit a memory phenotype and impaired IFN-γ-secreting capacity in sepsis patients.Using a receiver operating curve analysis with 8.01%as a cut-off point,the percentage of GM-CSF^(+)CD4^(+)T cells could predict the outcome of septic patients.Combined with the increase in GM-CSF-producing CD4^(+)T cells,inflammatory cytokines IL-1βand IL-6 were also upregulated.Using an in vitro neutrophil model,we found that GM-CSF inhibited C3aR expression,while inducing IL-8 production.Furthermore,this effect was transferrable in plasma from sepsis patients and was attenuated by inhibition of GM-CSF using an anti-GM-CSF antibody.These results indicate that GM-CSF-producing CD4^(+)T cells may serve as a marker of sepsis severity.Thus,targeting GM-CSF overproduction may benefit sepsis patients.
基金financially supported by the National Basic Research Program of China(Nos.2012CB619500 and 2010CB731700)the National Natural Science Foundation of China(No.51375503)
文摘The influence of Mg content on the microstructures and mechanical properties at room temperatures of A1-3.5Cu- （0.71-1.81）Mg alloys was studied. Precipitation phases in the alloys were identified by TEM and HRTEM. The results show that when Mg contents increase from 0.71 to 1.81 wt%, the precipitates are transformed from S, S＂, 2, and 0 phases to S and St phases, and f2 phase is first observed in A1-3.48Cu-0.71 Mg alloy with Cu/Mg mass ratio of 5 during the conventional aging heat treatment （190 C/12 h）. Regard to aging hardness effect of the tested alloys, the hardness of the alloys improves with the increase of Mg content, but the increases become slow when Mg content is greater than 1.35 wt%.
基金supported by the Natural Science Foundation of Shandong Province (ZR2023MB017,ZR2021QB055,ZR2020QB014,ZR2022JQ10)the National Natural Science Foundation of China (21901146,220781792,52007110)the Taishan Scholar Foundation (tsqn201812063)。
文摘P2-Na_(0.67)Ni_(0.33)Mn_(0.67)O_(2)(NNMO)is promising cathode material for sodium-ion batteries(SIBs)due to its high specific capacity and fast Na+diffusion rate.Nonetheless,the irreversible P2-O_(2)phase transformation,Na+/vacancy ordering,and transition metal(TM)dissolution seriously damage its cycling stability and restrict its commercialization process.Herein,Na occupation manipulation and interface stabilization are proposed to strengthen the phase structure of NNMO by synergistic Zn/Ti co-doping and introducing lithium difluorophosp(LiPO_(2)F_(2))film-forming electrolyte additive.The Zn/Ti co-doping regulates the occupancy ratio of Nae/Nafat Na sites and disorganizes the Na+/vacancy ordering,resulting in a faster Na+diffusion kinetics and reversible P2-Z phase transition for P2-Na_(0.67)Ni_(0.28)Zn_(0.05)Mn_(0.62)Ti_(0.05)O_(2)(NNZMTO).Meanwhile,the LiPO_(2)F_(2)additive can form homogeneous and ultrathin cathode-electrolyte interphase(CEI)on NNZMTO surface,which can stabilize the NNZMTO-electrolyte interface to prevent TM dissolution,surface structure transformation,and micro-crack generation.Combination studies of in situ and ex situ characterizations and theoretical calculations were used to elucidate the storage mechanism of NNZMTO with Li PO_(2)F_(2)additive.As a result,the NNZMTO displays outstanding capacity retention of 94.44%after 500 cycles at 1C with 0.3 wt%Li PO_(2)F_(2),excellent rate performance of 92.5 mA h g^(-1)at 8C with 0.1 wt%Li PO_(2)F_(2),and remarkable full cell capability.This work highlights the important role of manipulating Na occupation and constructing protective film in the design of layered materials,which provides a promising direction for developing high-performance cathodes for SIBs.
基金Supported by the National Key R&D Program of China(No.2018YFA0903100)the National Natural Science Foundation of China(No.32071601)。
文摘Microcystinase(MlrA)is a key endopeptidase that catalyzes microcystin degradation without generating harmful byproduct.However,the application of MlrA in the field is primarily impeded by its limited productivity and short lifespan.Therefore,the MlrA's function was studied by modelling its structure,which subsequently increased its heterologous expression and high-temperature stability.Results demonstrate that after the irregular sequence at the C-terminus of MlrA was removed,enzyme solubility was significantly decreased.In addition,three fusion tags,namely maltose-binding protein,glutathione S-transferase(GST),and N-utilization substance A(NusA)were used to enhance the overexpression of soluble recombinant MlrA,among which NusA-MlrA exhibited the highest solubility.Moreover,NusA-MlrA was active in pH 4-10 at 20-80℃;even at 80℃,approximately 35.8%of fusion protein remained active.NusA-MlrA retained 89%of MlrA's activity even after 7 d of storage at 50℃;and on day 7,the protein retained>90%of its activity at pH 7.Finally,a stable,soluble,and long-lasting heterologous MlrA was successfully constructed that could eliminate microcystins in Escherichia coli C43(DE3).This study enriched the comprehension of MlrA's structure and enzymatic properties,by particularly addressing the endopeptidase's low expression and short lifespan,which improved its suitability for future applications.
基金supported by the National Key R&D Program of China(No.2018YFB1502401)the National Natural Science Foundation of China(Nos.91961111,U20A20250,and 21901064)+3 种基金the Natural Science Foundation of Heilongjiang Province(No.ZD2021B003)the University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province(No.UNPYSCT-2020004)the Basic Research Fund of Heilongjiang University in Heilongjiang Province(No.2021-KYYWF-0039)Open Project of Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education.
文摘The Pt-free photocatalytic hydrogen evolution(PHE)has been the focus in the photocatalytic field.The catalytic system with the large accessible surface and good mass-transfer ability,as well as the intimate combination of co-catalyst with semiconductor is promising for the promotion of the application.Here,we have reported the design of the two-dimensional(2D)porous C_(3)N_(4)nanosheets(PCN NS)intimately combined with few-layered MoS_(2)for the high-effective Pt-free PHE.The PCN NS were synthesized based on peeling the melamine–cyanuric acid precursor(MC precursor)by the triphenylphosphine(TP)molecular followed by the calcination,mainly due to the matched size of the(100)plane distance of the precursor(0.8 nm)and the height of TP molecular.The porous structure is favorable for the mass-transfer and the 2D structure having large accessible surface,both of which are positive to promote the photocatalytic ability.The few-layered MoS_(2)are grown on PCN to give 2D MoS_(2)/PCN composites based on anchoring phosphomolybdic acid(PMo_(12))cluster on polyetherimide(PEI)-modified PCN followed by the vulcanization.The few-layered MoS_(2)have abundant edge active sites,and its intimate combination with porous PCN NS is favorable for the faster transfer and separation of the electrons.The characterization together with the advantage of 2D porous structure can largely promote the photocatalytic ability.The MoS_(2)/PCN showed good PHE activity with the high hydrogen production activity of 4,270.8μmol·h^(−1)·g^(−1)under the simulated sunlight condition(AM1.5),which was 7.9 times of the corresponding MoS_(2)/bulk C_(3)N_(4)and 12.7 times of the 1 wt.%Pt/bulk C_(3)N_(4).The study is potentially meaningful for the synthesis of PCN-based catalytic systems.
基金supported by a grant from the National Key R&D Program of China(2023YFC3041600 YW,the National Natural Science Foundation of China(82025001 JZ,92369113 YW,82172240 YW)Guangdong Basic and Applied Research Projects(2023B1515020040 YW,2021B1515130005 JZ,2021B1212030016 JD,2021A1111100009 JD)+7 种基金Science and Technology Planning Project of Guangzhou City(2023A04J1279 LZ)ZhongNanShan Medical Foundation of Guangdong Province(ZNSA-2020013 JZ)the Science and Technology Project of General Administration of Customs,P.R.China(2023HK065 LZ)State Key Laboratory of Respiratory Disease(SKLRD-Z-202214,SKLRD-OP-202309 YW,SKLRD-Z-202411 LZ)the Self-supporting Program of Guangzhou Laboratory(GZNL2023A01006,SRPG22-001)Guangzhou Medical University(YP2022005 YW)Korea Institute of Planning and Evaluation for Technology in Food,Agriculture and Forestry(IPET)through Animal Disease Management Technology Advancement Support Program,funded by the Ministry of Agriculture,Food and Rural Affairs(MAFRA)(122012-2,122060-2 JZ)the National Clinical Research Center for Respiratory Disease(BRD-NCRCRD,Guangzhou,Southern China).Patronus Biotech is a company researching virus-like particle display technology and vaccines.Yu Zhou and Jing Jin are named inventors on a patent invention relating to the described novel SARS-CoV-2 virus-like particle vaccine.All BALB/c mouse experiments complied with relevant ethical regulations for animal research and were approved by the LUYE PHARMA Animal Experimentation Ethics Committee.The K18-hACE2 mouse experiment was reviewed and approved by the Institutional Animal Care and Use Committees of Guangzhou Medical University(2023-0451).All authors declare that they have no conflict of interests.
文摘Dear Editor,The newly emerged severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron subvariants(XBB.1,EG.5 and JN.1)and sublineages have been circulating globally with superior growth advantages over other Omicron variants(Tamura et al.,2023).However,second-generation vaccines,including the BA.2 or BA.5 bivalent vaccine boosters,did not produce robust neutralization against the newly emerged XBB.1 or EG.5(Zou et al.,2023).Compared with variants BA.2 and BA.5,XBB.1 carries more mutations in the receptor binding domain(RBD)and exhibits significant immune evasion(Wang et al.,2023b).XBB.1 and its descendent lineages have rapidly become the dominant SARS-CoV-2 strain and are causing the next global wave of COVID-19.Therefore,it is essential to develop an updated vaccine against the newly emerged SARS-CoV-2 variants.
