The use of carbon from waste biomass has the potential to eliminate the drawbacks of Li-S batteries and improve their overall performance.Chrome-tanned-leather-shavings(CTLS)are a readily available waste product that ...The use of carbon from waste biomass has the potential to eliminate the drawbacks of Li-S batteries and improve their overall performance.Chrome-tanned-leather-shavings(CTLS)are a readily available waste product that can be transformed into porous carbon.We prepared an ac-tivated carbon by microwave pyrolysis combined with KOH activator using the CTLS as starting materials.The carbon had a specific surface area of 556 m^(2)g^(-1) and a honeycomb-like structure.Two kinds of N-doped activated carbons were then synthesized by thermal decomposition of the activated carbon,either combined with urea,or impregnated with eth-anolamine.Both N-doped activated carbons have an in-creased number of nitrogen and amine surface groups.However,only the urea treatment was effective in improv-ing the initial capacity of the cell(1363 mAh g^(-1)),which is probably linked to the sorption of long-chain polysulfides.This investigation confirms that it is possible to use the thermal de-composition of urea to obtain carbon materials from CTLS for use as the sulfur-host cathode in Li-S batteries and improve their performance.A radial basis function neural network was fitted to provide statistical support for the experimental results,which confirmed the importance of the nitrogen content of the carbons in determining the discharge capacity of the cells.展开更多
Traditional selection of combustion catalysis is time-consuming and labor-intensive.Theoretical calculation is expected to resolve this problem.The adsorption energy of HMX and O atoms on 13 metal oxides was calculate...Traditional selection of combustion catalysis is time-consuming and labor-intensive.Theoretical calculation is expected to resolve this problem.The adsorption energy of HMX and O atoms on 13 metal oxides was calculated using DMol3,since HMX and O are key substances in decomposition process.And the relationship between the adsorption energy of HMX,O on metal oxides(TiO_(2),Al_(2)O_(3),PbO,CuO,Fe_(2)O_(3),Co_(3)O_(4),Bi_(2)O_(3),NiO)and experimental T30 values(time required for the decomposition depth of HMX to reach 30%)was depicted as volcano plot.Thus,the T30 values of other metal oxides was predicted based on their adsorption energy on volcano plot and validated by previous experimental data.Further,the adsorption energy of HMX on ZrO_(2)and MnO_(2)was predicted based on the linear relationship between surface energy and adsorption energy,and T30 values were estimated based on volcano plot.The apparent activation energy data of HMX/MgO,HMX/SnO_(2),HMX/ZrO_(2),and HMX/MnO_(2)obtained from DSC experiments are basically consistent with our predicted T30 values,indicating that it is feasible to predict the catalytic activity based on the adsorption calculation,and it is expected that these simple structural properties can predict adsorption energy to reduce the large quantities of computation and experiment cost.展开更多
OBJECTIVE To investigate whether aldo-keto reductases(AKRs)can act as a nitrore⁃ductase(NR)and bioactivate aristolochic acidⅠ(AA-Ⅰ)to produce AA-Ⅰ-DNA adducts.METHODS①Human-induced hepatocytes(hiHeps)and human bla...OBJECTIVE To investigate whether aldo-keto reductases(AKRs)can act as a nitrore⁃ductase(NR)and bioactivate aristolochic acidⅠ(AA-Ⅰ)to produce AA-Ⅰ-DNA adducts.METHODS①Human-induced hepatocytes(hiHeps)and human bladder RT4 cells were used as tool cells and treated with AA-Ⅰ0,0.5,1.0 and 2μmol·L^(-1)for 24 h.Cell viability was detected using the CCK-8 method,and the half maximal inhibition concentration(IC_(50))was calculated using the CCK-8 method and the level of DNA adduct production was calculated.②hiHeps and RT4 cells were treated with AKR inhibitor luteotin(0,5,10 and 25μmol·L^(-1))+AA-Ⅰ0.2 and 1.0μmol·L^(-1)for 24 h,respectively,and the levels of DNA adducts were detected by a liquid chromatography-tandem mass spectrometer(LC-MS/MS).③hiHeps cells were incubated with 80 nmol·L^(-1)small interfering RNAs(si-AKRs)for 48 h and treated with AA-Ⅰ1.0μmol·L^(-1)for 24 h.Real-time qualitative PCR(RT-qPCR)method was used to detect the mRNA expression of AKRs gene and LC-MS/MS technology was used to investigate the effect of specific AKR gene knockdown on DNA adduct levels.④500 nmol·L^(-1)human AKR recombinant proteins AKR1A1 and AA-Ⅰwere incubated in vitro under anaerobic conditions and the formation of AA-Ⅰ-DNA adducts was detected.RESULTS①The IC_(50)of AA-Ⅰto hiHeps and RT4 cells was 1.9 and 0.42μmol·L^(-1),respec⁃tively.The level of DNA adduct production of the two cell lines was significantly different(P<0.01).②Luteolin≥5μmol·L^(-1)significantly inhibited the production of AA-Ⅰ-DNA adducts in both cells(P<0.05),and there was a concentration-dependent effect in hiHeps cells(P<0.01,R=0.84).③In the AKR family,the knockdown of AKR1A1 gene up to 80%inhibited the generation of AA-Ⅰ-DNA adducts by 30%-40%.④The AA-Ⅰ-DNA adducts were detected in the incubation of recombinant protein AKR1A1 and AA-Ⅰunder anaerobic conditions in vitro,approximately 1 adduct per 107 nucleotides.CONCLU⁃SION AKR1A1 is involved in AA-Ⅰbioactivation,providing a reference for elucidation of the carcino⁃genic mechanism of AA-Ⅰ.展开更多
Dendritic cells (DCs) are the most potent antigen-presen ting cells that play crucial roles in the regulation of immune response. Triptol ide, an active component purified from the medicinal plant Tripterygium wilfor ...Dendritic cells (DCs) are the most potent antigen-presen ting cells that play crucial roles in the regulation of immune response. Triptol ide, an active component purified from the medicinal plant Tripterygium wilfor dii Hook F., has been demonstrated to act as a potent immunosuppressive drug c apab le of inhibiting T cell activation and proliferation. However, little is known a bout the effects of triptolide on DCs. The present study shows that triptolide d oes not affect phenotypic differentiation and LPS-induced maturation of murine DCs. But triptolide can dramatically reduce cell recovery by inducing apoptosis of DCs at concentration as low as 10 ng/ml, as demonstrated by phosphatidylserin e exposure, mitochondria potential decrease, and nuclear DNA condensation. Tript olide induces activation of p38 in DCs, which precedes the activation of caspase 3. SB203580, a specific kinase inhibitor for p38, can block the activation of caspase 3 and inhibit the resultant apoptosis of DCs. Our results suggest that t he anti-inflammatory and immunosuppressive activities of triptolide may be due, in part, to its apoptosis-inducing effects on DCs.展开更多
The effect of activation properties of the precursors of zeolite directly prepared from kaolin influenced by microwave field and conventional heating was investigated.XRD,TG-DSC,FT-IR,SEM,particle size analysis,specif...The effect of activation properties of the precursors of zeolite directly prepared from kaolin influenced by microwave field and conventional heating was investigated.XRD,TG-DSC,FT-IR,SEM,particle size analysis,specific surface area(BET),pore size distribution(BJH)and N2 adsorption-desorption were discussed to determine the optimal activation temperature.It is concluded that the conversion of kaolin to metakaolin in the microwave field is at 500°C holding for 30 min,which is 100°C lower than that in conventional calcination and 90 min shorter,and the phase transition process of kaolin under the effect of microwave field is the same as that of conventional heating method.SEM analysis indicates that the particle size is more uniform and agglomeration appears slightly in the microwave field.The N2 adsorption-desorption isotherm,BET and BJH of kaolin indicate that the pore properties are almost invariable regardless of calcination route during the process of calcining kaolin into metakaolin.It indicates that microwave calcination is superior to conventional calcination in the activation pathway of kaolin.It is attributed to microwave heating relying on objects to absorb microwave energy and convert it into thermal energy,which can simultaneously and uniformly heat the entire substance.展开更多
Taking the selection of coal-tar pitch as precursor and KOH as activated agent, the activated carbon electrode material was fabricated for supercapacitor.The surface area and the pore structure of activated carbon wer...Taking the selection of coal-tar pitch as precursor and KOH as activated agent, the activated carbon electrode material was fabricated for supercapacitor.The surface area and the pore structure of activated carbon were analyzed by Nitro adsorption method. The electrochemical properties of the activated carbons were determined using two-electrode capacitors in 6 mol/L KOH aqueous electrolytes. The influences of activated temperature and mass ratio of KOH to C on the pore structure and electrochemical property of porous activated carbon were investigated in detail. The reasons for the changes of pore structure and electrochemical performance of activated carbon prepared under different conditions were also discussed theoretically. The results indicate that the maximum specific capacitance of 240 F/g can be obtained in alkaline medium, and the surface area, the pore structure and the specific capacitance of activated carbon depend on the treatment methods; the capacitance variation of activated carbon cannot be interpreted only by the change of surface area and pore structure, the lattice order and the electrolyte wetting effect of the activated carbon should also be taken into account.展开更多
Based on physicochemical study of the reaction between scheelite and NaOH, a new decomposition process for scheelite and scheelitewolframite concentrate, i. e., mechenically activating caustic decomposition has bee...Based on physicochemical study of the reaction between scheelite and NaOH, a new decomposition process for scheelite and scheelitewolframite concentrate, i. e., mechenically activating caustic decomposition has been developed, and it has been successfu展开更多
Boron is a very promising and highly attractive fuel because of high calorific value. However, the practical applications in explosives and propellants of boron have been limited by long ignition delay time and low co...Boron is a very promising and highly attractive fuel because of high calorific value. However, the practical applications in explosives and propellants of boron have been limited by long ignition delay time and low combustion efficiency. Herein, nano-Al and graphene fluoride(GF) as surface activated materials are employed to coat boron(B) particles to improve ignition and combustion performance. The reaction heat of nano-Al coated B/KNO_(3)and GF coated B/KNO_(3)are 1116.83 J/g and 862.69 J/g, respectively, which are higher than that of pure B/KNO_(3)(823.39 J/g). The ignition delay time of B/KNO_(3)could be reduced through nano-Al coating. The shortest ignition delay time is only 75 ms for B coated with nano-Al of 8 wt%, which is much shorter than that of pure B/KNO_(3)(109 ms). However, the ignition delay time of B/KNOcoated with GF has been increased from 109 to 187 ms. B coated with GF and nano-Al shown significantly influence on the pressure output and flame structure of B/KNO_(3). Furthermore, the effects of B/O ratios on the pressure output and ignition delay time have been further fully studied. For B/KNO_(3)coated with nano-Al and GF, the highest pressures are 88 KPa and 59 KPa for B/O ratio of 4:6, and the minimum ignition delay time are 94 ms and 148 ms for B/O ratio of 7:3. Based on the above results, the reaction process of boron coated with GF and nano-Al has been proposed to understand combustion mechanism.展开更多
The preparation of activated carbon from Chinese fir sawdust by zinc chloride activation under both nitrogen atmosphere and vacuum conditions was carded out in a self-manufactured vacuum pyrolysis reactor. The effects...The preparation of activated carbon from Chinese fir sawdust by zinc chloride activation under both nitrogen atmosphere and vacuum conditions was carded out in a self-manufactured vacuum pyrolysis reactor. The effects of the system pressure and the activation condition （nitrogen or vacuum） on pore development were investigated. The results show that both high quality activated carbon and high added-value bio-oil can be obtained simultaneously via vacuum chemical activation. The characteristics of the activated carbons produced under vacuum conditions are better than those prepared under nitrogen atmosphere. The performance parameters of the activated carbon obtained under vacuum conditions are as follows： the pore size distribution is mainly microporous, the Brunauer-Emmett-Teller （BET） surface area is 1 070.59 m^2/g, the microporous volume is 0.502 4 cm^3/g, the average pore size is 2.085 nm, and the iodine adsorption value and the methylene blue adsorption value are 1 142.92 and 131.34 mg/g, respectively. The activated carbon from vacuum chemical activation has developed micropores, and the N2 adsorption equilibrium constant of the corresponding activated carbon gradually increases with the decrease of reaction system pressure.展开更多
A process was proposed based on the combination of chemical and physical activation for the production of activated carbons used as the electrode material for electric double layer capacitor (EDLC). By material charac...A process was proposed based on the combination of chemical and physical activation for the production of activated carbons used as the electrode material for electric double layer capacitor (EDLC). By material characterization and electrochemical methods, the influences of the activitation process on the specific surface area, pore structure and electrochemical properties of the activated carbons were investigated. The results show that specific surface area, the mesopore volume, and the specific capacitance increase with the increase of the mass ratio of KOH to char (m(KOH)/m(char)) and the activation time, respectively. When m(KOH)/m(char) is 4.0, the specific surface area and the mesopore volume reach the maximum values, i.e. 1 960 m2/g and 0.308 4 cm3/g, and the specific capacitance is 120.7 F/g synchronously. Compared with the chemical activation, the activated carbons prepared by chemical-physical activation show a larger mesopore volume, a higher ratio of mesopore and a larger specific capacitance.展开更多
Natural minerals receive growing attention as inexpensive, green, and efficient catalysts for degradation of organic pollutants. Mechanical activation of natural chalcopyrite was conducted for improving the catalytic ...Natural minerals receive growing attention as inexpensive, green, and efficient catalysts for degradation of organic pollutants. Mechanical activation of natural chalcopyrite was conducted for improving the catalytic performance.Tetracycline degradation was evaluated in the presence of hydrogen peroxide and mechanically activated chalcopyrite.Tetracycline degradation at 100 min is 55.52%(Chp10), 68.97%(Chp30), 77.79%(Chp60), and 86.43%(Chp120),respectively, and the rate constant of pseudo-first-order kinetics is 0.0079, 0.0109, 0.0137 and 0.0192 min^(-1), respectively.Chalcopyrite samples were examined by multiple characterizations. Mechanical activation of natural chalcopyrite induces the decline of particle size and slight increase of surface area, smaller grain size, lattice strain, and partial sulfur oxidation. The relationship between catalytic activity and property change manifests that the improved catalytic ability is mainly ascribed to the increase of surface area and surface oxidation induced by mechanical activation. This work provides novel insights into the improvement of catalytic performance of natural minerals by mechanical activation.展开更多
The present exploration is conducted to describe the motion of viscous fluid embedded in squeezed channel under the applied magnetics effects.The processes of heat and mass transport incorporate the temperature-depend...The present exploration is conducted to describe the motion of viscous fluid embedded in squeezed channel under the applied magnetics effects.The processes of heat and mass transport incorporate the temperature-dependent binary chemical reaction with modified Arrhenius theory of activation energy function which is not yet disclosed for squeezing flow mechanism.The flow,heat and mass regime are exposed to be governed via dimensionless,highly non-linear,ordinary differential equations (ODEs) under no-slip walls boundary conditions.A well-tempered analytical convergent procedure is adopted for the solutions of boundary value problem.A detailed study is accounted through graphs in the form of flow velocity field,temperature and fluid concentration distributions for various emerging parameters of enormous interest.Skin-friction,Nusselt and Sherwood numbers have been acquired and disclosed through plots.The results indicate that fluid temperature follows an increasing trend with dominant dimensionless reaction rate σ and activation energy parameter E.However,an increment in σ and E parameters is found to decline in fluid concentration.The current study arises numerous engineering and industrial processes including polymer industry,compression and injection shaping,lubrication system,formation of paper sheets,thin fiber,molding of plastic sheets.In the area of chemical engineering,geothermal engineering,cooling of nuclear reacting,nuclear or chemical system,bimolecular reactions,biochemical process and electrically conducting polymeric flows can be controlled by utilizing magnetic fields.Motivated by such applications,the proposed study has been developed.展开更多
Conventional syntheses of organic chemicals rely mostly on reactions between various reactive functional groups and reagents. Mechanistically, they are dominated by the involvement of highly reactive intermediates suc...Conventional syntheses of organic chemicals rely mostly on reactions between various reactive functional groups and reagents. Mechanistically, they are dominated by the involvement of highly reactive intermediates such as carbocations, carbanions, radicals and carbenes.展开更多
Leaching of lowgrade refractory tungsten ore was carried out through mechanical activation. The effect of temperature, amount of Na2CO3, addition of NaOH, ratio of liquid to solid and leaching time on the recovery of ...Leaching of lowgrade refractory tungsten ore was carried out through mechanical activation. The effect of temperature, amount of Na2CO3, addition of NaOH, ratio of liquid to solid and leaching time on the recovery of WO3 was studied. The WO3 recovery upto 96%～99% has been achieved when the tungsten ore was digested by soda not more than three times stiochiometric amount at 185～195 ℃ for 10～20 h. The WO3 recovery can increase 10%～15% compared to that of conventional soda autoclave process.展开更多
The interactions on gold active and migratory quantities and rates between tuffaceous slate and solu tions with different compositions were experimentally studied at 200 ℃, 20 MPa, in a high pressure apparatus. After...The interactions on gold active and migratory quantities and rates between tuffaceous slate and solu tions with different compositions were experimentally studied at 200 ℃, 20 MPa, in a high pressure apparatus. After reaction, tuffaceous slate became light colored and soft, and its mass density reduced. The amount of gold extracted from tuffaceous slate ranges widely, from 0 027 to 0 234 μg/g. Chlorine solution may activate appreciable amount of gold, and the gold migratory rate is high enough, from 50 70% to 92 30%, which reveals that sulphur and chlorine work together in solutions to accelerate gold activation and migration, and to realize gold mineralization in favorable places.展开更多
Integrins are heterodimeric cell surface receptors that bind to ligands on another cell,e.g.intercellular adhesion molecule 1(ICAM-1),or the extracellular matrix.Integrins play an important role in immune system,and t...Integrins are heterodimeric cell surface receptors that bind to ligands on another cell,e.g.intercellular adhesion molecule 1(ICAM-1),or the extracellular matrix.Integrins play an important role in immune system,and they participate in inflammation,thrombosis,and proliferation,migration and apoptosis of tumor cells.They mediate adhesion and transduce signals across the membrane usually under the influence of forces.A recent study has shown that integrins bind and activate transforming growth factorβisoform(TGF-β)which is involved in tumor suppression and growth,and blocking the binding of TGF-βto integrin can inhibit tumor growth.RGD(arginine-glycine-aspartate)small peptide,which competitively inhibits ligand binding to integrins,has been approved as an injectable drug.However,when the RGD is used to block cancer-related extracellular signaling pathways,it will also cause activation of integrins for a period,and stimulate the transduction of intracellular signals constantly.Therefore,it is necessary to explore for new drugs that can selectively control conformational state of integrins without activating or blocking all of them.In this study,we selected two small peptides,KQAGDV and RTDLDSLRT,that combined with integrins and do not contain an RGD sequence.The non-RGD polypeptide RTDLDSLRT has been reported to have a binding site with integrins and the binding affinity is on nanomolar scale.For the motif of the fibrinogen y chain C-terminal KQAGDV,it can adhere to the head of the integrins.The micropipette aspiration technique and electron microscopy techniques were used to study the adhesion and activation of integrins by peptides,respectively.Micropipette aspiration technique was used to investigate the adhesion frequency of peptide and integrin on Jurkat cell.The pressure system was used to supply a controllable negative pression to the microtube,and two micropipettes were used to absorb red blood cells and Jurkat cells,respectively.The red blood cells were coated with small peptides and can serve as a force sensor after being sucked when two cells were connected.The binding kinetics of integrin and peptides interactions was determined by fitting the curves constructed using adhesion probability between two cells as a function of time.The curves were fitted using a small system probabilistic kinetic model to estimate a pair of kinetic parameters,including the zero force reverse rate kr0,and the cellular binding affinity Acmrm1Ka0.The adhesion frequency yielded P(t)=75%and 57%for RGD and KQAG DV peptides,respectively.We obtained Acmrm1Ka0=1.40 and kr0=0.32 s-1,for RGD,and Acmrm1Ka0=0.85 and kr0=0.54 s-1 for KQAGDV.The RGD peptide has a higher adhesion frequency and lower dissociation rate than the KQAGDV peptide.Electron microscopy techniques was used to observe the activation of integrins by peptides.Jurkat cell expressing integrins was bound to a magnetic bead and bottom plate which were coated with different integrin-binding peptides.Then,we manipulated the beads in a controlled direction by changing the magnetic field nearby,and the forces were applied to the cell.The target cells were fixed and then observed by scanning electron microscope or transmission electron microscope.Jurkat cells contain abundant flexible microvilli of which there are many parallel bundles of actin filaments inside.By electron microscopy analysis,the cell connected with magnetic bead coated with RGD were found to be protruded and the size of microvilli increased up to#-fold of the length of the KQAGDV sample.The microvilli exhibited a curved agglomerate structure under a force-free condition.Moreover,a higher proportion of cells were activated in the presence of RGD than KQAGDV.In conclusion,the binding affinity of KQAGDV to integrin is weaker than RGD,and KQAGDV can bind with integrins effectively with a lower activated proportion.Our results indicate the peptides may selectively bind to integrins without activating them.展开更多
This work identified the important role of matrix mechanical plasticity in mediating fibroblast activation.Many existing studies have highlighted the important effects of biochemical cues(e.g.,transforming growth fact...This work identified the important role of matrix mechanical plasticity in mediating fibroblast activation.Many existing studies have highlighted the important effects of biochemical cues(e.g.,transforming growth factor-β1)and mechanicalstiffness on fibroblast activation.Our results indicated that self-assembled collagen hydrogels showed high plasticity and in which fibroblasts remain undifferentiated.However,when we decreased the plasticity of collagen hydrogels by increasing covalent crosslinking,fibroblasts showed a significant fibrotic response as reflected by the increasedα-SMA expression.Since the material systems we constructed have low and the same initial modulus,this process is stiffness independent.Although it has been reported that covalently crosslinked hydrogels are more difficult to degrade and matrix degradability has an important impact on cell behaviors,no significant changes of fibroblast activation were observed when proteases were broadly inhibited in our experiments.Importantly,the hydrogels we constructed showed similar plastic behaviors under creep and recovery tests compared to native normal and fibrotic tissues.These highlight the importance of matrix plasticity in mimicking the mechanical microenvironment of native fibrotic tissues.Mechanistically,we found that the enhanced fibroblast activation in low plastic matrix is mediated through integrin-actin pathway and nuclear localization of YAP.In high plastic collagen,matrix cannot provide effective resistance to actin contraction because of the rupture of weak crosslinks and the slippage of local fibers.On the contrary,in low plastic collagen,deformation energy can be stored in the network due to the existence of strong covalent crosslinks,thus enabling the build-up of cell traction and the formation of a robust cell-matrix interaction.Experiments of inhibiting or promoting cytoskeletal contractility and CGMD simulation both verified the above points.Our results clarify plasticity changes on the development of fibrotic diseases and highlight plasticity as an important mechanical cue in understanding cell-matrix interactions.展开更多
Inflammation and thrombosis usually occur together in many diseases,such as cardiovascular disease(CVD)and stroke,which remain to be the mostdetrimental human health killers.The crucial relevant cellular and molecular...Inflammation and thrombosis usually occur together in many diseases,such as cardiovascular disease(CVD)and stroke,which remain to be the mostdetrimental human health killers.The crucial relevant cellular and molecular events include platelet-leukocyte interaction,platelet P-selectin secretion of activated platelet and activation of leukocyte integrin Mac-1(also known asαMβ2 or CD11b/CD18),which has binding site of platelet receptor glycoprotein lbα(GPlboα). Circulating leukocytes tethered to,rolled on and firmly adhered at the activated platelets on vascular wall,through interaction of platelet P-selectin with leukocyte P-selectin glycoprotein ligand-1(PSGL-1)and Mac-1 with GPlbα.We assume that there is a rapid signaling pathway in PSGL-1 ligation-induced activation of Mac-1,for forming a stable gap junction intracellular communication between platelet and leukocyte.To test this assumption,we observed the tethering events and calcium bursting of neutrophils on immobilized P-selectin only or plus GPlbαwith use of the parallel plate flow chamber(PPFC)technique and intracellular calcium ion detector Fluo-4 AM at various wall shear stresses,and examined the dynamic force spectrum for interaction of Mac-1 plus Mn2+and GPlbαby single-molecule atomic force microscopy(AFM).In the PPFC experiments,the intracellular calcium flux of firmly adhered neutrophils on immobilized P-selectin only or plus GPlbαwas observed in real timeby fluorescence microscopy,and the tether events of neutrophils was recorded by an inverted microscope and a high speed CMOS acquisition system in 1280 pixels×1024 pixels at 100 frames per second(fps). Captured images were analyzed by Image Pro Plus.Our results indicated that force triggered,enhanced and quickened the cytoplasmic calcium bursting of neutrophils.Calcium bursting may be induced first by interaction of the activated neutrophil Integrin Mac-1 and GPlbα,but not by P-selectin ligation to its ligand PSGL-1.Being triggered and speeded up by wall shear stress,the P-selectin-induced activation of Mac-1 in neutrophils was a previous events of calcium bursting,and occurred within one second.The tether lifetime of neutrophils on immobilized P-selectin only or plus GPlbαincreased first and then decreased with wall shear stress,and the wall shear stress threshold is 0.3 dyn/cm2 for P-selectin only but 0.25 dyn/cm2 for P-selectin plus GPlbα.It suggested a mechanical regulation mechanism of'Catch-slip bond'transition for Mac-1/GPlbαcomplex,like P-selectin/PSGL-1 complex.It was also demonstrated through the single-molecule AFM data,which showed that force regulated binding of activated Mac-1 to GPlbαthrough the Catch bond mechanism for tensile force small than 31.25 pN,being matched with the PPFC experimental data.The tether lifetime of neutrophils on immobilized P-selectin plus GPlbαwas more long than that on P-selectin only,showing the P-selectin-induced activation of Mac-1 on neutrophils was a rapid but local events under flows.In summary,force rapidly triggers and promotes the PSGL-1 ligation-induced activation of Mac-1 on neutrophils,leading to formation of stable intercellular communication between leukocytes and platelets.This finding should be useful in understanding of platelet-leukocytes interaction-mediated biological process in cellular inflammation responses and thrombus formation.展开更多
As a key regulator of immune response,CD40 L is usually associated with chronic disease-related inflammation,autoimmune diseases and malignant diseases.Receptor recognition of platelet CD40 L is the initial event that...As a key regulator of immune response,CD40 L is usually associated with chronic disease-related inflammation,autoimmune diseases and malignant diseases.Receptor recognition of platelet CD40 L is the initial event that mediates platelet aggregation and leukocyte immune response.Unlike soluble CD40 L,the interaction between transmembrane platelet CD40 L and its receptors occurs within the cell junction surface,usually,in a physiological and pathological high blood flow shear stress environment.This two-dimensional reaction kinetics should be a mechano-chemical coupling process.In addition to its classical receptor CD40,CD40 L also binds to receptorα5β1,CD40 L can bind to the resting state of integrinα5β1,but the mechanical regulation mechanism of integrinα5β1 activation under fluid shear stress remains unclear.We assume that the force can promote CD40 L-inducedα5β1 activation.To check this hypothesis,we performed flow chamber experiment to investigate interaction of CD40 L andα5β1.In experiments,the bottom of the flow chamber is functionalized by a suitable concentration of CD40 L,and the fiber spheres of 6μm diameter was coated withα5β1.The selection of CD40 L concentration was based on the observation that as many tether events ofα5β1-coated spheres as possible were observed rather than stable adhesion events of these spheres.Theα5β1-coated sphere suspension was poured over the CD40 L-coated substrates in the flow chamber under different shear rates.A high-speed camera was used to observe and record tether events of fiber spheres at a rate of 100 frames per second.According to our affinity state transition model for integrin,the data were analyzed to obtain the rate of integrin activation and its mechanical regulation characteristics.Our results demonstrated that the interaction betweenα5β1 and CD40 L is biphasic force-dependent,showing mechano-chemical regulation mechanism of'Catch-slip bond'transition.The affinity jumping model was well fitted with the data obtained from flow chamber experiment at various wall shear stresses.We found that,CD40 L ligation-induced jumping ofα5β1 affinity state from low to medium(or high)one will occur within 0.5-1.0 second,resulting in prolonging of bond lifetimes.And,frequency distribution of the tether events number with tether lifetime under each force,exhibits obvious doublet peaks,one within 0.5-1 s and second within 1.5-2.5 s,indicating theα5β1 affinity state transform from low to high one.The probability distribution of the tether lifetime under different shear forces are not linear,and exists a turning point,which shows that the rate ofα5β1 dissociation from CD40 L is fast first,and then become slow,showing a force-induced conformation transformation of the integrinα5β1 from low affinity state to high affinity one.Our findings suggest that,the continuous force stimulation will quickly cause the affinity state change of integrinα5β1. The dissociation rate of theα5β1/CD40 L complex decreases first and then increases with wall shear stress,exhibiting a'Catch-slip bond'transformation of interaction betweenα5β1-CD40 L.This mechanical regulation mechanism exists in interaction of CD40 L not only toα5β1 at low affinity state but also to one at high affinity state.Our results should be useful in understanding the mechanical regulation mechanism of a5β1-CD40 L interaction-mediated cellular immune response and inflammatory processes.展开更多
Aim Magnesium lithospermate B （MLB） is the most abundant hydrophilic active component of Salvia rniltiorrhiza Radix, a traditional Chinese herbal medicine mainly used to treat cardiovascular diseases. Studies have s...Aim Magnesium lithospermate B （MLB） is the most abundant hydrophilic active component of Salvia rniltiorrhiza Radix, a traditional Chinese herbal medicine mainly used to treat cardiovascular diseases. Studies have shown that endothelial activation contributes to the pathophysiology of cardiovascular diseases such as atherosclero- sis, diabetic vasculopathy, heart failure and hypertension. In the present study, the effects of MLB on endothelial activation were investigated. Lipopolysaccharide （LPS） 1 mg L^-1 was employed to induce endothelial activation, which was determined by relative gene expression and endothelial adhesion assay. Results showed that pretreatment with MLB attenuated LPS-induced ICAM1, VCAM1 and TNF-α upregulation in human dermal microvascular endo- thelial cells （HMEC-1） in dose-dependent manner, which contributed to the reduction of THP-1 adhesion to HMEC-1. Furthermore, it was revealed that 100 μmol · L^-1 MLB significantly decreased the nuclear translocation of NF-KB p65, a critical transcription factor in LPS-indueed inflammatory response, through the inhibition of IKBμ degradation. Besides, the transcriptional activity of NF-KB p65 was also inhibited by the pretreatment of MLB. Mo- reover, MLB pretreatment considerably inhibited LPS-induced p38 phosphorylation, which at least partly contribu- ted to the reduction of ICAM1 expression. In conclusion, these findings suggest that MLB inhibits LPS-induced nu- clear translocation and transcripitional activity of NF-KB, thus attenuates the increased expression of adhesion mole- cules and inflammatory factors, protects endothelial cells from LPS-induced activation.展开更多
文摘The use of carbon from waste biomass has the potential to eliminate the drawbacks of Li-S batteries and improve their overall performance.Chrome-tanned-leather-shavings(CTLS)are a readily available waste product that can be transformed into porous carbon.We prepared an ac-tivated carbon by microwave pyrolysis combined with KOH activator using the CTLS as starting materials.The carbon had a specific surface area of 556 m^(2)g^(-1) and a honeycomb-like structure.Two kinds of N-doped activated carbons were then synthesized by thermal decomposition of the activated carbon,either combined with urea,or impregnated with eth-anolamine.Both N-doped activated carbons have an in-creased number of nitrogen and amine surface groups.However,only the urea treatment was effective in improv-ing the initial capacity of the cell(1363 mAh g^(-1)),which is probably linked to the sorption of long-chain polysulfides.This investigation confirms that it is possible to use the thermal de-composition of urea to obtain carbon materials from CTLS for use as the sulfur-host cathode in Li-S batteries and improve their performance.A radial basis function neural network was fitted to provide statistical support for the experimental results,which confirmed the importance of the nitrogen content of the carbons in determining the discharge capacity of the cells.
基金supported by Key Science and Technology Innovation Team of Shaanxi Province(No.2022TD-33)National Natural Science Foundation of China(Grant Nos.21373161,21504067)。
文摘Traditional selection of combustion catalysis is time-consuming and labor-intensive.Theoretical calculation is expected to resolve this problem.The adsorption energy of HMX and O atoms on 13 metal oxides was calculated using DMol3,since HMX and O are key substances in decomposition process.And the relationship between the adsorption energy of HMX,O on metal oxides(TiO_(2),Al_(2)O_(3),PbO,CuO,Fe_(2)O_(3),Co_(3)O_(4),Bi_(2)O_(3),NiO)and experimental T30 values(time required for the decomposition depth of HMX to reach 30%)was depicted as volcano plot.Thus,the T30 values of other metal oxides was predicted based on their adsorption energy on volcano plot and validated by previous experimental data.Further,the adsorption energy of HMX on ZrO_(2)and MnO_(2)was predicted based on the linear relationship between surface energy and adsorption energy,and T30 values were estimated based on volcano plot.The apparent activation energy data of HMX/MgO,HMX/SnO_(2),HMX/ZrO_(2),and HMX/MnO_(2)obtained from DSC experiments are basically consistent with our predicted T30 values,indicating that it is feasible to predict the catalytic activity based on the adsorption calculation,and it is expected that these simple structural properties can predict adsorption energy to reduce the large quantities of computation and experiment cost.
文摘OBJECTIVE To investigate whether aldo-keto reductases(AKRs)can act as a nitrore⁃ductase(NR)and bioactivate aristolochic acidⅠ(AA-Ⅰ)to produce AA-Ⅰ-DNA adducts.METHODS①Human-induced hepatocytes(hiHeps)and human bladder RT4 cells were used as tool cells and treated with AA-Ⅰ0,0.5,1.0 and 2μmol·L^(-1)for 24 h.Cell viability was detected using the CCK-8 method,and the half maximal inhibition concentration(IC_(50))was calculated using the CCK-8 method and the level of DNA adduct production was calculated.②hiHeps and RT4 cells were treated with AKR inhibitor luteotin(0,5,10 and 25μmol·L^(-1))+AA-Ⅰ0.2 and 1.0μmol·L^(-1)for 24 h,respectively,and the levels of DNA adducts were detected by a liquid chromatography-tandem mass spectrometer(LC-MS/MS).③hiHeps cells were incubated with 80 nmol·L^(-1)small interfering RNAs(si-AKRs)for 48 h and treated with AA-Ⅰ1.0μmol·L^(-1)for 24 h.Real-time qualitative PCR(RT-qPCR)method was used to detect the mRNA expression of AKRs gene and LC-MS/MS technology was used to investigate the effect of specific AKR gene knockdown on DNA adduct levels.④500 nmol·L^(-1)human AKR recombinant proteins AKR1A1 and AA-Ⅰwere incubated in vitro under anaerobic conditions and the formation of AA-Ⅰ-DNA adducts was detected.RESULTS①The IC_(50)of AA-Ⅰto hiHeps and RT4 cells was 1.9 and 0.42μmol·L^(-1),respec⁃tively.The level of DNA adduct production of the two cell lines was significantly different(P<0.01).②Luteolin≥5μmol·L^(-1)significantly inhibited the production of AA-Ⅰ-DNA adducts in both cells(P<0.05),and there was a concentration-dependent effect in hiHeps cells(P<0.01,R=0.84).③In the AKR family,the knockdown of AKR1A1 gene up to 80%inhibited the generation of AA-Ⅰ-DNA adducts by 30%-40%.④The AA-Ⅰ-DNA adducts were detected in the incubation of recombinant protein AKR1A1 and AA-Ⅰunder anaerobic conditions in vitro,approximately 1 adduct per 107 nucleotides.CONCLU⁃SION AKR1A1 is involved in AA-Ⅰbioactivation,providing a reference for elucidation of the carcino⁃genic mechanism of AA-Ⅰ.
文摘Dendritic cells (DCs) are the most potent antigen-presen ting cells that play crucial roles in the regulation of immune response. Triptol ide, an active component purified from the medicinal plant Tripterygium wilfor dii Hook F., has been demonstrated to act as a potent immunosuppressive drug c apab le of inhibiting T cell activation and proliferation. However, little is known a bout the effects of triptolide on DCs. The present study shows that triptolide d oes not affect phenotypic differentiation and LPS-induced maturation of murine DCs. But triptolide can dramatically reduce cell recovery by inducing apoptosis of DCs at concentration as low as 10 ng/ml, as demonstrated by phosphatidylserin e exposure, mitochondria potential decrease, and nuclear DNA condensation. Tript olide induces activation of p38 in DCs, which precedes the activation of caspase 3. SB203580, a specific kinase inhibitor for p38, can block the activation of caspase 3 and inhibit the resultant apoptosis of DCs. Our results suggest that t he anti-inflammatory and immunosuppressive activities of triptolide may be due, in part, to its apoptosis-inducing effects on DCs.
基金Projects(51604135,51504116)supported by the National Natural Science Foundational of ChinaProject(YNWR-QNBJ-2018-323)supported by the Yunan Ten Thousand Talents Plan Young&Elite Talents Project,China。
文摘The effect of activation properties of the precursors of zeolite directly prepared from kaolin influenced by microwave field and conventional heating was investigated.XRD,TG-DSC,FT-IR,SEM,particle size analysis,specific surface area(BET),pore size distribution(BJH)and N2 adsorption-desorption were discussed to determine the optimal activation temperature.It is concluded that the conversion of kaolin to metakaolin in the microwave field is at 500°C holding for 30 min,which is 100°C lower than that in conventional calcination and 90 min shorter,and the phase transition process of kaolin under the effect of microwave field is the same as that of conventional heating method.SEM analysis indicates that the particle size is more uniform and agglomeration appears slightly in the microwave field.The N2 adsorption-desorption isotherm,BET and BJH of kaolin indicate that the pore properties are almost invariable regardless of calcination route during the process of calcining kaolin into metakaolin.It indicates that microwave calcination is superior to conventional calcination in the activation pathway of kaolin.It is attributed to microwave heating relying on objects to absorb microwave energy and convert it into thermal energy,which can simultaneously and uniformly heat the entire substance.
基金Project(2005CB623703) supported by the National Basic Research Program of China project(5JJ30103) supported bythe Natural Science Foundation of Hunan Province
文摘Taking the selection of coal-tar pitch as precursor and KOH as activated agent, the activated carbon electrode material was fabricated for supercapacitor.The surface area and the pore structure of activated carbon were analyzed by Nitro adsorption method. The electrochemical properties of the activated carbons were determined using two-electrode capacitors in 6 mol/L KOH aqueous electrolytes. The influences of activated temperature and mass ratio of KOH to C on the pore structure and electrochemical property of porous activated carbon were investigated in detail. The reasons for the changes of pore structure and electrochemical performance of activated carbon prepared under different conditions were also discussed theoretically. The results indicate that the maximum specific capacitance of 240 F/g can be obtained in alkaline medium, and the surface area, the pore structure and the specific capacitance of activated carbon depend on the treatment methods; the capacitance variation of activated carbon cannot be interpreted only by the change of surface area and pore structure, the lattice order and the electrolyte wetting effect of the activated carbon should also be taken into account.
文摘Based on physicochemical study of the reaction between scheelite and NaOH, a new decomposition process for scheelite and scheelitewolframite concentrate, i. e., mechenically activating caustic decomposition has been developed, and it has been successfu
基金supported by the National Natural Science Foundation of China (11872341 and 22075261)。
文摘Boron is a very promising and highly attractive fuel because of high calorific value. However, the practical applications in explosives and propellants of boron have been limited by long ignition delay time and low combustion efficiency. Herein, nano-Al and graphene fluoride(GF) as surface activated materials are employed to coat boron(B) particles to improve ignition and combustion performance. The reaction heat of nano-Al coated B/KNO_(3)and GF coated B/KNO_(3)are 1116.83 J/g and 862.69 J/g, respectively, which are higher than that of pure B/KNO_(3)(823.39 J/g). The ignition delay time of B/KNO_(3)could be reduced through nano-Al coating. The shortest ignition delay time is only 75 ms for B coated with nano-Al of 8 wt%, which is much shorter than that of pure B/KNO_(3)(109 ms). However, the ignition delay time of B/KNOcoated with GF has been increased from 109 to 187 ms. B coated with GF and nano-Al shown significantly influence on the pressure output and flame structure of B/KNO_(3). Furthermore, the effects of B/O ratios on the pressure output and ignition delay time have been further fully studied. For B/KNO_(3)coated with nano-Al and GF, the highest pressures are 88 KPa and 59 KPa for B/O ratio of 4:6, and the minimum ignition delay time are 94 ms and 148 ms for B/O ratio of 7:3. Based on the above results, the reaction process of boron coated with GF and nano-Al has been proposed to understand combustion mechanism.
文摘The preparation of activated carbon from Chinese fir sawdust by zinc chloride activation under both nitrogen atmosphere and vacuum conditions was carded out in a self-manufactured vacuum pyrolysis reactor. The effects of the system pressure and the activation condition （nitrogen or vacuum） on pore development were investigated. The results show that both high quality activated carbon and high added-value bio-oil can be obtained simultaneously via vacuum chemical activation. The characteristics of the activated carbons produced under vacuum conditions are better than those prepared under nitrogen atmosphere. The performance parameters of the activated carbon obtained under vacuum conditions are as follows： the pore size distribution is mainly microporous, the Brunauer-Emmett-Teller （BET） surface area is 1 070.59 m^2/g, the microporous volume is 0.502 4 cm^3/g, the average pore size is 2.085 nm, and the iodine adsorption value and the methylene blue adsorption value are 1 142.92 and 131.34 mg/g, respectively. The activated carbon from vacuum chemical activation has developed micropores, and the N2 adsorption equilibrium constant of the corresponding activated carbon gradually increases with the decrease of reaction system pressure.
基金Project(2007BAE12B01) supported by the National Key Technology Research and Development Program of China
文摘A process was proposed based on the combination of chemical and physical activation for the production of activated carbons used as the electrode material for electric double layer capacitor (EDLC). By material characterization and electrochemical methods, the influences of the activitation process on the specific surface area, pore structure and electrochemical properties of the activated carbons were investigated. The results show that specific surface area, the mesopore volume, and the specific capacitance increase with the increase of the mass ratio of KOH to char (m(KOH)/m(char)) and the activation time, respectively. When m(KOH)/m(char) is 4.0, the specific surface area and the mesopore volume reach the maximum values, i.e. 1 960 m2/g and 0.308 4 cm3/g, and the specific capacitance is 120.7 F/g synchronously. Compared with the chemical activation, the activated carbons prepared by chemical-physical activation show a larger mesopore volume, a higher ratio of mesopore and a larger specific capacitance.
基金Project(2020YFC1908802) supported by the National Key Research and Development Project of China。
文摘Natural minerals receive growing attention as inexpensive, green, and efficient catalysts for degradation of organic pollutants. Mechanical activation of natural chalcopyrite was conducted for improving the catalytic performance.Tetracycline degradation was evaluated in the presence of hydrogen peroxide and mechanically activated chalcopyrite.Tetracycline degradation at 100 min is 55.52%(Chp10), 68.97%(Chp30), 77.79%(Chp60), and 86.43%(Chp120),respectively, and the rate constant of pseudo-first-order kinetics is 0.0079, 0.0109, 0.0137 and 0.0192 min^(-1), respectively.Chalcopyrite samples were examined by multiple characterizations. Mechanical activation of natural chalcopyrite induces the decline of particle size and slight increase of surface area, smaller grain size, lattice strain, and partial sulfur oxidation. The relationship between catalytic activity and property change manifests that the improved catalytic ability is mainly ascribed to the increase of surface area and surface oxidation induced by mechanical activation. This work provides novel insights into the improvement of catalytic performance of natural minerals by mechanical activation.
文摘The present exploration is conducted to describe the motion of viscous fluid embedded in squeezed channel under the applied magnetics effects.The processes of heat and mass transport incorporate the temperature-dependent binary chemical reaction with modified Arrhenius theory of activation energy function which is not yet disclosed for squeezing flow mechanism.The flow,heat and mass regime are exposed to be governed via dimensionless,highly non-linear,ordinary differential equations (ODEs) under no-slip walls boundary conditions.A well-tempered analytical convergent procedure is adopted for the solutions of boundary value problem.A detailed study is accounted through graphs in the form of flow velocity field,temperature and fluid concentration distributions for various emerging parameters of enormous interest.Skin-friction,Nusselt and Sherwood numbers have been acquired and disclosed through plots.The results indicate that fluid temperature follows an increasing trend with dominant dimensionless reaction rate σ and activation energy parameter E.However,an increment in σ and E parameters is found to decline in fluid concentration.The current study arises numerous engineering and industrial processes including polymer industry,compression and injection shaping,lubrication system,formation of paper sheets,thin fiber,molding of plastic sheets.In the area of chemical engineering,geothermal engineering,cooling of nuclear reacting,nuclear or chemical system,bimolecular reactions,biochemical process and electrically conducting polymeric flows can be controlled by utilizing magnetic fields.Motivated by such applications,the proposed study has been developed.
文摘Conventional syntheses of organic chemicals rely mostly on reactions between various reactive functional groups and reagents. Mechanistically, they are dominated by the involvement of highly reactive intermediates such as carbocations, carbanions, radicals and carbenes.
基金the Key+7 种基金 Programof the 8th Five-year Plan of China
文摘Leaching of lowgrade refractory tungsten ore was carried out through mechanical activation. The effect of temperature, amount of Na2CO3, addition of NaOH, ratio of liquid to solid and leaching time on the recovery of WO3 was studied. The WO3 recovery upto 96%～99% has been achieved when the tungsten ore was digested by soda not more than three times stiochiometric amount at 185～195 ℃ for 10～20 h. The WO3 recovery can increase 10%～15% compared to that of conventional soda autoclave process.
文摘The interactions on gold active and migratory quantities and rates between tuffaceous slate and solu tions with different compositions were experimentally studied at 200 ℃, 20 MPa, in a high pressure apparatus. After reaction, tuffaceous slate became light colored and soft, and its mass density reduced. The amount of gold extracted from tuffaceous slate ranges widely, from 0 027 to 0 234 μg/g. Chlorine solution may activate appreciable amount of gold, and the gold migratory rate is high enough, from 50 70% to 92 30%, which reveals that sulphur and chlorine work together in solutions to accelerate gold activation and migration, and to realize gold mineralization in favorable places.
基金supported by the National Science Foundation of China ( 11772133, 11372116)
文摘Integrins are heterodimeric cell surface receptors that bind to ligands on another cell,e.g.intercellular adhesion molecule 1(ICAM-1),or the extracellular matrix.Integrins play an important role in immune system,and they participate in inflammation,thrombosis,and proliferation,migration and apoptosis of tumor cells.They mediate adhesion and transduce signals across the membrane usually under the influence of forces.A recent study has shown that integrins bind and activate transforming growth factorβisoform(TGF-β)which is involved in tumor suppression and growth,and blocking the binding of TGF-βto integrin can inhibit tumor growth.RGD(arginine-glycine-aspartate)small peptide,which competitively inhibits ligand binding to integrins,has been approved as an injectable drug.However,when the RGD is used to block cancer-related extracellular signaling pathways,it will also cause activation of integrins for a period,and stimulate the transduction of intracellular signals constantly.Therefore,it is necessary to explore for new drugs that can selectively control conformational state of integrins without activating or blocking all of them.In this study,we selected two small peptides,KQAGDV and RTDLDSLRT,that combined with integrins and do not contain an RGD sequence.The non-RGD polypeptide RTDLDSLRT has been reported to have a binding site with integrins and the binding affinity is on nanomolar scale.For the motif of the fibrinogen y chain C-terminal KQAGDV,it can adhere to the head of the integrins.The micropipette aspiration technique and electron microscopy techniques were used to study the adhesion and activation of integrins by peptides,respectively.Micropipette aspiration technique was used to investigate the adhesion frequency of peptide and integrin on Jurkat cell.The pressure system was used to supply a controllable negative pression to the microtube,and two micropipettes were used to absorb red blood cells and Jurkat cells,respectively.The red blood cells were coated with small peptides and can serve as a force sensor after being sucked when two cells were connected.The binding kinetics of integrin and peptides interactions was determined by fitting the curves constructed using adhesion probability between two cells as a function of time.The curves were fitted using a small system probabilistic kinetic model to estimate a pair of kinetic parameters,including the zero force reverse rate kr0,and the cellular binding affinity Acmrm1Ka0.The adhesion frequency yielded P(t)=75%and 57%for RGD and KQAG DV peptides,respectively.We obtained Acmrm1Ka0=1.40 and kr0=0.32 s-1,for RGD,and Acmrm1Ka0=0.85 and kr0=0.54 s-1 for KQAGDV.The RGD peptide has a higher adhesion frequency and lower dissociation rate than the KQAGDV peptide.Electron microscopy techniques was used to observe the activation of integrins by peptides.Jurkat cell expressing integrins was bound to a magnetic bead and bottom plate which were coated with different integrin-binding peptides.Then,we manipulated the beads in a controlled direction by changing the magnetic field nearby,and the forces were applied to the cell.The target cells were fixed and then observed by scanning electron microscope or transmission electron microscope.Jurkat cells contain abundant flexible microvilli of which there are many parallel bundles of actin filaments inside.By electron microscopy analysis,the cell connected with magnetic bead coated with RGD were found to be protruded and the size of microvilli increased up to#-fold of the length of the KQAGDV sample.The microvilli exhibited a curved agglomerate structure under a force-free condition.Moreover,a higher proportion of cells were activated in the presence of RGD than KQAGDV.In conclusion,the binding affinity of KQAGDV to integrin is weaker than RGD,and KQAGDV can bind with integrins effectively with a lower activated proportion.Our results indicate the peptides may selectively bind to integrins without activating them.
基金financially supported by the National Natural Science Foundation of China ( 11872298, 11602191,11532009,11621062)the China Postdoctoral Science Foundation ( 2018M631141)the Fundamental Research Funds for the Central Universities ( Z201811336)
文摘This work identified the important role of matrix mechanical plasticity in mediating fibroblast activation.Many existing studies have highlighted the important effects of biochemical cues(e.g.,transforming growth factor-β1)and mechanicalstiffness on fibroblast activation.Our results indicated that self-assembled collagen hydrogels showed high plasticity and in which fibroblasts remain undifferentiated.However,when we decreased the plasticity of collagen hydrogels by increasing covalent crosslinking,fibroblasts showed a significant fibrotic response as reflected by the increasedα-SMA expression.Since the material systems we constructed have low and the same initial modulus,this process is stiffness independent.Although it has been reported that covalently crosslinked hydrogels are more difficult to degrade and matrix degradability has an important impact on cell behaviors,no significant changes of fibroblast activation were observed when proteases were broadly inhibited in our experiments.Importantly,the hydrogels we constructed showed similar plastic behaviors under creep and recovery tests compared to native normal and fibrotic tissues.These highlight the importance of matrix plasticity in mimicking the mechanical microenvironment of native fibrotic tissues.Mechanistically,we found that the enhanced fibroblast activation in low plastic matrix is mediated through integrin-actin pathway and nuclear localization of YAP.In high plastic collagen,matrix cannot provide effective resistance to actin contraction because of the rupture of weak crosslinks and the slippage of local fibers.On the contrary,in low plastic collagen,deformation energy can be stored in the network due to the existence of strong covalent crosslinks,thus enabling the build-up of cell traction and the formation of a robust cell-matrix interaction.Experiments of inhibiting or promoting cytoskeletal contractility and CGMD simulation both verified the above points.Our results clarify plasticity changes on the development of fibrotic diseases and highlight plasticity as an important mechanical cue in understanding cell-matrix interactions.
基金supported by the National Natural Science Foundation of China ( 116272109,11432006)
文摘Inflammation and thrombosis usually occur together in many diseases,such as cardiovascular disease(CVD)and stroke,which remain to be the mostdetrimental human health killers.The crucial relevant cellular and molecular events include platelet-leukocyte interaction,platelet P-selectin secretion of activated platelet and activation of leukocyte integrin Mac-1(also known asαMβ2 or CD11b/CD18),which has binding site of platelet receptor glycoprotein lbα(GPlboα). Circulating leukocytes tethered to,rolled on and firmly adhered at the activated platelets on vascular wall,through interaction of platelet P-selectin with leukocyte P-selectin glycoprotein ligand-1(PSGL-1)and Mac-1 with GPlbα.We assume that there is a rapid signaling pathway in PSGL-1 ligation-induced activation of Mac-1,for forming a stable gap junction intracellular communication between platelet and leukocyte.To test this assumption,we observed the tethering events and calcium bursting of neutrophils on immobilized P-selectin only or plus GPlbαwith use of the parallel plate flow chamber(PPFC)technique and intracellular calcium ion detector Fluo-4 AM at various wall shear stresses,and examined the dynamic force spectrum for interaction of Mac-1 plus Mn2+and GPlbαby single-molecule atomic force microscopy(AFM).In the PPFC experiments,the intracellular calcium flux of firmly adhered neutrophils on immobilized P-selectin only or plus GPlbαwas observed in real timeby fluorescence microscopy,and the tether events of neutrophils was recorded by an inverted microscope and a high speed CMOS acquisition system in 1280 pixels×1024 pixels at 100 frames per second(fps). Captured images were analyzed by Image Pro Plus.Our results indicated that force triggered,enhanced and quickened the cytoplasmic calcium bursting of neutrophils.Calcium bursting may be induced first by interaction of the activated neutrophil Integrin Mac-1 and GPlbα,but not by P-selectin ligation to its ligand PSGL-1.Being triggered and speeded up by wall shear stress,the P-selectin-induced activation of Mac-1 in neutrophils was a previous events of calcium bursting,and occurred within one second.The tether lifetime of neutrophils on immobilized P-selectin only or plus GPlbαincreased first and then decreased with wall shear stress,and the wall shear stress threshold is 0.3 dyn/cm2 for P-selectin only but 0.25 dyn/cm2 for P-selectin plus GPlbα.It suggested a mechanical regulation mechanism of'Catch-slip bond'transition for Mac-1/GPlbαcomplex,like P-selectin/PSGL-1 complex.It was also demonstrated through the single-molecule AFM data,which showed that force regulated binding of activated Mac-1 to GPlbαthrough the Catch bond mechanism for tensile force small than 31.25 pN,being matched with the PPFC experimental data.The tether lifetime of neutrophils on immobilized P-selectin plus GPlbαwas more long than that on P-selectin only,showing the P-selectin-induced activation of Mac-1 on neutrophils was a rapid but local events under flows.In summary,force rapidly triggers and promotes the PSGL-1 ligation-induced activation of Mac-1 on neutrophils,leading to formation of stable intercellular communication between leukocytes and platelets.This finding should be useful in understanding of platelet-leukocytes interaction-mediated biological process in cellular inflammation responses and thrombus formation.
基金supported by the National Natural Science Foundation of China ( 116272109, 11432006)
文摘As a key regulator of immune response,CD40 L is usually associated with chronic disease-related inflammation,autoimmune diseases and malignant diseases.Receptor recognition of platelet CD40 L is the initial event that mediates platelet aggregation and leukocyte immune response.Unlike soluble CD40 L,the interaction between transmembrane platelet CD40 L and its receptors occurs within the cell junction surface,usually,in a physiological and pathological high blood flow shear stress environment.This two-dimensional reaction kinetics should be a mechano-chemical coupling process.In addition to its classical receptor CD40,CD40 L also binds to receptorα5β1,CD40 L can bind to the resting state of integrinα5β1,but the mechanical regulation mechanism of integrinα5β1 activation under fluid shear stress remains unclear.We assume that the force can promote CD40 L-inducedα5β1 activation.To check this hypothesis,we performed flow chamber experiment to investigate interaction of CD40 L andα5β1.In experiments,the bottom of the flow chamber is functionalized by a suitable concentration of CD40 L,and the fiber spheres of 6μm diameter was coated withα5β1.The selection of CD40 L concentration was based on the observation that as many tether events ofα5β1-coated spheres as possible were observed rather than stable adhesion events of these spheres.Theα5β1-coated sphere suspension was poured over the CD40 L-coated substrates in the flow chamber under different shear rates.A high-speed camera was used to observe and record tether events of fiber spheres at a rate of 100 frames per second.According to our affinity state transition model for integrin,the data were analyzed to obtain the rate of integrin activation and its mechanical regulation characteristics.Our results demonstrated that the interaction betweenα5β1 and CD40 L is biphasic force-dependent,showing mechano-chemical regulation mechanism of'Catch-slip bond'transition.The affinity jumping model was well fitted with the data obtained from flow chamber experiment at various wall shear stresses.We found that,CD40 L ligation-induced jumping ofα5β1 affinity state from low to medium(or high)one will occur within 0.5-1.0 second,resulting in prolonging of bond lifetimes.And,frequency distribution of the tether events number with tether lifetime under each force,exhibits obvious doublet peaks,one within 0.5-1 s and second within 1.5-2.5 s,indicating theα5β1 affinity state transform from low to high one.The probability distribution of the tether lifetime under different shear forces are not linear,and exists a turning point,which shows that the rate ofα5β1 dissociation from CD40 L is fast first,and then become slow,showing a force-induced conformation transformation of the integrinα5β1 from low affinity state to high affinity one.Our findings suggest that,the continuous force stimulation will quickly cause the affinity state change of integrinα5β1. The dissociation rate of theα5β1/CD40 L complex decreases first and then increases with wall shear stress,exhibiting a'Catch-slip bond'transformation of interaction betweenα5β1-CD40 L.This mechanical regulation mechanism exists in interaction of CD40 L not only toα5β1 at low affinity state but also to one at high affinity state.Our results should be useful in understanding the mechanical regulation mechanism of a5β1-CD40 L interaction-mediated cellular immune response and inflammatory processes.
文摘Aim Magnesium lithospermate B （MLB） is the most abundant hydrophilic active component of Salvia rniltiorrhiza Radix, a traditional Chinese herbal medicine mainly used to treat cardiovascular diseases. Studies have shown that endothelial activation contributes to the pathophysiology of cardiovascular diseases such as atherosclero- sis, diabetic vasculopathy, heart failure and hypertension. In the present study, the effects of MLB on endothelial activation were investigated. Lipopolysaccharide （LPS） 1 mg L^-1 was employed to induce endothelial activation, which was determined by relative gene expression and endothelial adhesion assay. Results showed that pretreatment with MLB attenuated LPS-induced ICAM1, VCAM1 and TNF-α upregulation in human dermal microvascular endo- thelial cells （HMEC-1） in dose-dependent manner, which contributed to the reduction of THP-1 adhesion to HMEC-1. Furthermore, it was revealed that 100 μmol · L^-1 MLB significantly decreased the nuclear translocation of NF-KB p65, a critical transcription factor in LPS-indueed inflammatory response, through the inhibition of IKBμ degradation. Besides, the transcriptional activity of NF-KB p65 was also inhibited by the pretreatment of MLB. Mo- reover, MLB pretreatment considerably inhibited LPS-induced p38 phosphorylation, which at least partly contribu- ted to the reduction of ICAM1 expression. In conclusion, these findings suggest that MLB inhibits LPS-induced nu- clear translocation and transcripitional activity of NF-KB, thus attenuates the increased expression of adhesion mole- cules and inflammatory factors, protects endothelial cells from LPS-induced activation.
