The catalysis technology of propylene dimerization to form 4-methyl-1-pentene(4MP1)using a Cu-K/K_(2)CO_(3) solid base catalyst is a well-known heterogeneous catalytic reaction.In this study,the intrinsic kinetics of ...The catalysis technology of propylene dimerization to form 4-methyl-1-pentene(4MP1)using a Cu-K/K_(2)CO_(3) solid base catalyst is a well-known heterogeneous catalytic reaction.In this study,the intrinsic kinetics of propylene dimerization were studied in a fixed-bed continuous reactor.Internal and external diffusion during the dimerization reaction experiments were eliminated by adjusting the flow rate of the carrier gas and the particle size of the catalyst support.Then,the concentration changes of each substance at the outlet of the catalyst bed under different residence times were investigated.Moreover,the suitable reaction kinetics equations was derived using the Langmuir Hinshelwood-Hougen-Watson kinetic model.Finally,the activation energy for each reaction involved in the dimerization reaction was calculated.The activation energies of 4MP1,branched by-products,and 1-hexene were 115.0,150.8,and 177.4 kJ/mol,respectively.The effect of process conditions on propylene dimerization with solid base catalysts was studied through kinetic model simulation.By comparing the theoretical values obtained from the simulation with the experimental results,the applicability and accuracy of the kinetic model were verified.展开更多
In the process of dimerization of acetylene to produce monovinylacetylene （MVA）,the loss of active component CuCl in the Nieuwland catalyst due to the formation of a dark red precipitate was investigated.The formula...In the process of dimerization of acetylene to produce monovinylacetylene （MVA）,the loss of active component CuCl in the Nieuwland catalyst due to the formation of a dark red precipitate was investigated.The formula of the precipitate was CuCl·2C2H2·1/5NH 3,and it was presumed to be formed by the combination of NH 3,C2H2 and [Cu]-acetylene π-complex,which was an intermediate in the dimerization reaction.The addition of hydrochloric acid into the catalyst can reduce the formation of precipitate,whereas excessive H＋ is unfavorable to the dimerization reaction of acetylene.To balance between high acetylene conversion and low loss rate of CuCl,the optimum mass percentage of HCl in the added hydrochloric acid was determined.The result showed the optimum mass percentage of HCl decreased from 5.0% to 3.2% when the space velocity of acetylene was from 140 h-1 to 360 h-1.The result in this work also indicated the pH of the Nieuwland catalyst should be kept in the range of 5.80-5.97 during the reaction process,which was good for both catalyst life and acetylene conversion.展开更多
The production of monovinylacetylene （MVA） through Cu（I）-catalyzed acetylene dimerization reaction was performed in different reaction media. Based on the analyses of crystals precipitated from the catalyst soluti...The production of monovinylacetylene （MVA） through Cu（I）-catalyzed acetylene dimerization reaction was performed in different reaction media. Based on the analyses of crystals precipitated from the catalyst solution and UV-Vis spectra of the catalysts, the reaction mechanism and solvent dependence were studied. The highest yield of MVA can be obtained when dimethylformamide is used as solvent because of its strong coordination ability to Cu（I）. The activation of C=C bond is presumed to be improved when the catalytic metal ion is coordinated by a solvent with less steric hindrance and electron-rich coordination atom. The results of the present study provide a possible way to accelerate the metal-catalyzed homogeneous reaction of alkyne substrates through careful selection of a solvent.展开更多
Erythropoietin (EPO), a 34 kD glycopro-tein, is the principal growth factor regulating theproduction of circulating erythrocytes; EPO isessential for committed CFU - E erythroid pro-genitors to divide several times an...Erythropoietin (EPO), a 34 kD glycopro-tein, is the principal growth factor regulating theproduction of circulating erythrocytes; EPO isessential for committed CFU - E erythroid pro-genitors to divide several times and then to dif-ferentiate into erythrocytes. Like most receptorsfor hematopoietic growth factors, the erythro-poietin receptor (EPO - R) is a type I trans-membrane protein and a member of the cytokinereceptor superfamily. These receptors containfour conserved cysteines and a Trp - Ser - X -展开更多
Controlling catalytic activities through surface strain engineering remains a hot topic in electrocatalysis studies.Herein,ab initio molecular dynamics(AIMD)simulation associated with free energy sampling technology w...Controlling catalytic activities through surface strain engineering remains a hot topic in electrocatalysis studies.Herein,ab initio molecular dynamics(AIMD)simulation associated with free energy sampling technology were performed to study the energetics of the key step of producing C2 products in electrocatalytic reduction of CO or CO_(2),i.e.CO dimerization,on strained Cu(100)with an explicit aqueous solvent model.It is worth mentioning that when compressive strain reaches a certain extent,the surface of Cu(100)will undergo reconstruction.We showed that,from tensile to compressive strain,the free energy barrier of CO dimerization decreased,suggesting that the activity of CO dimerization increases.It was also found that some of the reconstructed surfaces showing the lowest free energy barriers but might be less stable can be stabilized in the presence of adsorbed O or CO.Upon detailed quantitative analysis on the charges of surface Cu atoms,we found that the free energy barriers were strongly correlated with the charge of Cu atoms where the OCCO intermediate adsorbs.When the surfaces structures of Cu(100)were altered under compressive strain,the electronic structure of surface Cu atoms was monitored and thus the activity of electrocatalytic CO dimerization can be tuned.展开更多
We report a hydrogen-evolution dimerization of styrenes via the synergistic merger of Acr＋-Mes photocatalyst and cobaloxime proton reduction catalysts. By utilizing this dual catalyst system, 1,2-dihydro-1-arylnaphth...We report a hydrogen-evolution dimerization of styrenes via the synergistic merger of Acr＋-Mes photocatalyst and cobaloxime proton reduction catalysts. By utilizing this dual catalyst system, 1,2-dihydro-1-arylnaphthalene derivatives can be directly constructed from commercially available styrenes. Our reaction proceeds smoothly under mild conditions without the need for oxidants or hydrogen atom transfer reagents, and the sole byproduct is hydrogen gas. Mechanistic investigation suggests that the reaction is initiated by photoinduced electron transfer under visible-light irradiation.展开更多
Density functional theory （DFT） calculations, at the B3LYP/6-311G＊＊ level of theory, were performed to study the reaction mechanism and potenti4the potential energy surface of the studied reactions was investigate...Density functional theory （DFT） calculations, at the B3LYP/6-311G＊＊ level of theory, were performed to study the reaction mechanism and potenti4the potential energy surface of the studied reactions was investigated. Our calculation results show that [2 ＋ 2] and [4 ＋ 4] reactions are concerted and synchronous processes; while [4 ＋ 2] reactions proceed via a concerted but asynchronous way in general. [2 ＋ 2] and [4 ＋ 2] reactions of germabenzenes and 1-germana- phthalene proceed much more easily than the corresponding [4 ＋ 4] reaction, both thermo- dynamically and kinetically; while most [4 ＋ 2] paths have lower activation barrier than the corres- ponding [2 ＋ 2] ones. As the number of six-membered aromatic rings in reactant molecules becomes larger, [2 ＋ 2], [4 ＋ 2] and [4 ＋ 4] reactions become easier to proceed. The influence of substituents at the Ge atom of germabenzenes on the potential energy surface of [2 ＋ 2] and [4 ＋ 2] reactions correlates with their electronic properties and volume. Solvent effect is not crucial for the potential energy surfaces of the studied reactions.展开更多
This work aims to investigate the intrinsic kinetics of thermal dimerization of C_5 fraction in the reactive distillation process. Experiments are conducted in an 1000-m L stainless steel autoclave under some selected...This work aims to investigate the intrinsic kinetics of thermal dimerization of C_5 fraction in the reactive distillation process. Experiments are conducted in an 1000-m L stainless steel autoclave under some selected design conditions. By means of the weighted least squares method, the intrinsic kinetics of thermal dimerization of C_5 fraction is established, and the corresponding pre-exponential factor as well as the activation energy are determined. For example, the pre-exponential factor A is equal to 4.39×105 and the activation energy E4 a is equal to 6.58×10J/mol for the cyclopentadiene dimerization reaction. The comparison between the experimental and calculated results shows that the kinetics model derived in this work is accurate and reliable, which can be used in the design of reactive distillation columns.展开更多
OBJECTIVE Hepatocellular carcinoma(HCC)is the fifth most common malignancy worldwide and the third cause of global cancer mortality.Activation of signal transducer and activator of transcription 3(STAT3)is commonly ob...OBJECTIVE Hepatocellular carcinoma(HCC)is the fifth most common malignancy worldwide and the third cause of global cancer mortality.Activation of signal transducer and activator of transcription 3(STAT3)is commonly observed in tumor cells and is a critical mediator of on cogenic signaling in HCC and controls the expression of several genes involved in proliferation,survival,metastasis and angiogenesis.Current drug-targeted therapies,besides being expensive,are associated with serious side effects and morbidity.Thus,novel agents that can suppress STAT3 activation have potential for both prevention and treatment of HCC.In the present report,we investigated whether the potent HAT/KAT inhibitor,garcinol,(apolyisoprenylatedbenzophenone),could suppress STAT3 activation in HCC cells and in nude mice model.METHODS The effect of garcinol on HCC cell lines wasdetermined by MTT assay,immunoblotting,DNA binding assays,immuno-fluorescenceand immune-histochemical analysis.The effect of garcinolon the inhibition of tumor growth in vivo was also investigated using HCCxenograft tumor modelin athymic nu/nu mice.RESULTS We found that garcinol could inhibit constitutive STAT3 activation in a dose-and time-dependent manner both by inhibiting STAT3 phosphorylation and acetylation in HCC cells.When investigated for molecular mechanism(s),we found that garcinol interferes with the dimer formation of STAT3 thereby inhibits its nuclear localization.Computational modeling showed that garcinol could bind to the SH2 domain of STAT3 and suppresses its dimerization in vitro.To understand the cellular mechanism(s)of inhibition of STAT3 function by garcinol,we observed that upon inhibition of STAT3 dimerization bygarcinol,STAT3 DNA binding ability gets repressed.The inhibition of STAT3 activation by garcinol led to the suppression of various gene products involved in proliferation,survival,and angiogenesis.Finally,when administered i.p.,garcinol inhibited the growth of human HCC xenograft tumors in athymic nu/nu mice.CONCLUSION Results frominvitroand in vivo studies suggest that garcinol exerts its anti-proliferative and pro-apoptotic effects through suppression of STAT3 signaling cascade in HCC by inhibiting its phosphorylation,acetylation and ultimately dimerization.展开更多
In studies of ion channel systems,due to the huge computational cost of polarizable force elds,classical force elds remain the most widely used for a long time.In this work,we used the AMOEBA polarizable atomic multip...In studies of ion channel systems,due to the huge computational cost of polarizable force elds,classical force elds remain the most widely used for a long time.In this work,we used the AMOEBA polarizable atomic multipole force eld in enhanced sampling simula-tions of single-channel gramicidin A(gA)and double-channel gA systems and investigated its reliability in characterizing ion-transport properties of the gA ion channel under dimer-ization.The inuence of gA dimerization on the permeation of potassium and sodium ions through the channel was described in terms of conductance,di usion coeffcient,and free energy pro le.Results from the polarizable force eld simulations show that the conductance of potassium and sodium ions passing through the single-and double-channel agrees well with experimental values.Further data analysis reveals that the molecular mechanism of protein dimerization a ects the ion-transport properties of gA channels,i.e.,protein dimer-ization accelerates the permeation of potassium and sodium ions passing through the double-channel by adjusting the environment around gA protein(the distribution of phospholipid head groups,ions outside the channel,and bulk water),rather than directly adjusting the conformation of gA protein.展开更多
Penicillins are one type of the most important antibiotics used in the clinic.Control of drug impurity profiles is an important part of ensuring drug safety.This is particularly important in penicillins where polymeri...Penicillins are one type of the most important antibiotics used in the clinic.Control of drug impurity profiles is an important part of ensuring drug safety.This is particularly important in penicillins where polymerization can lead to polymers as elicitors of passive cutaneous anaphylaxis.The current understanding of penicillin polymerization is based on reactions with amino groups,but no comprehensive mechanistic understanding has been reported.Here,we used theoretical calculations and column switching-LC/MS techniques to study penicillin dimerization.Ampicillin and benzylpenicillin were selected as representative penicillins with or without amino groups in the side chain,respectively.We identified four pathways by which this may occur and the energy barrier graphs of each reaction process were given.For benzylpenicillin without an amino group in the 6-side chain,dimerization mode A is the dominant mode,where the 2-carboxyl group of one molecule reacts with the b-lactam of another molecule.However,ampicillin with an amino group in the 6-side chain favors dimerization mode C,where the amino group of one molecule attacks the b-lactam of another molecule.These findings can lead to a polymer control approach to maintaining penicillin antibiotics in an active formulation.展开更多
The effect of lattice dimerization on the magnetoresistance （MR） in organic spin valves is investigated based on the Su-Schrieffer-Heeger （SSH） model and the Green＇s function method. By comparing with the results...The effect of lattice dimerization on the magnetoresistance （MR） in organic spin valves is investigated based on the Su-Schrieffer-Heeger （SSH） model and the Green＇s function method. By comparing with the results for a uniform chain, we find that the dimerization of the molecular chain modifies the monotonic dependence of the MR on the bias to an oscillatory one. A sign inversion of the MR is observed when the amplitude of the dimerization is adjusted. The results also show that at a low bias, the MR through a dimerized chain decreases with the increasing bias as well as the increasing chain length, which is consistent with the experimental reports. A further understanding can be achieved by analyzing the electronic states and the spin-dependent transmission spectrum with the parallel and antiparallel magnetization orientations of the two ferromagnetic electrodes.展开更多
The catalytic property of propylene dimerization by several nickel (Ⅱ), cobalt (Ⅱ) complexes containing N-P bidentate ligands was studied in combination with organoaluminum co-catalysts. The effects of the type of a...The catalytic property of propylene dimerization by several nickel (Ⅱ), cobalt (Ⅱ) complexes containing N-P bidentate ligands was studied in combination with organoaluminum co-catalysts. The effects of the type of aluminum co-catalysts and its relative amount, the nature of precursors in terms of ligand backbone and metal center were investigated. The results indicated that precursor I (N,N-dimethyl-2-(diphenylphosphino)aniline nickel (Ⅱ) dichloride) exhibited high activity in propylene dimerization in the presence of the strong Lewis acid Et3Al2Cl3, whereas low productivity by its cobalt analogues was observed under identical reaction conditions.展开更多
Syndecan-3 (N-syndecan) is a transmembrane heparan sulfate proteoglycan abundantly expressed in developing brain. In addition to acting as a coreceptor, syndecan-3 acts as a signaling receptor upon binding of its liga...Syndecan-3 (N-syndecan) is a transmembrane heparan sulfate proteoglycan abundantly expressed in developing brain. In addition to acting as a coreceptor, syndecan-3 acts as a signaling receptor upon binding of its ligand HB-GAM (heparin-binding growth-associated molecule;pleiotrophin), which activates the cortactin-src kinase signaling pathway. This leads to rapid neurite extension in neuronal cells, which makes syndecan-3 as an interesting transmembrane receptor in neuronal development and regeneration. However, little is known about the signaling mechanism of syndecan-3. Here we have analyzed formation of ligand-N-syndecan signaling complexes at the cell surface using fluorescence resonance energy transfer (FRET) and bioluminescence resonance energy transfer (BRET). We show that ligand binding leads to dimerization of syndecan-3 at the cell surface. The dimerized syndecan-3 colocalizes with actin in the filopodia of cells. Several amino acid residues (K383, G392 and G396) in the transmembrane domain are shown to be important for the ligand-induced dimerization, whereas the cytosolic domain is not required for the dimerization.展开更多
Objective:Dihydrotanshinone I(DHT)is a natural product with multiple bioactivities.In this study,we aimed to investigate its anti-infl ammatory effect and potential mechanisms.Methods and Results:Lipopolysaccharide(LP...Objective:Dihydrotanshinone I(DHT)is a natural product with multiple bioactivities.In this study,we aimed to investigate its anti-infl ammatory effect and potential mechanisms.Methods and Results:Lipopolysaccharide(LPS)was used to induce acute kidney injury(AKI)in mice and establish infl ammation in macrophage.In vivo experiment,pretreatment of mice with DHT effectively inhibited xylene-induced ear oedema and LPS-induced endotoxic death and protected against LPSinduced AKI.DHT suppressed COX-2,iNOS,TNF-α,IL-6 and IL-1βexpression.In vitro experiment,DHT attenuated LPS-induced transcriptional activity of NF-κB by decreasing levels of phosphorylated IκB-αand IKK and NF-κB/p65 nuclear translocation.In addition,DHT blocked LPS-induced TLR4 dimerization,resulting in the recruiting of MyD88 and TRIF.Conclusion:In summary,DHT blocks TLR4 dimerization to activate MyD88-TAK1-NF-Κb signalling cascades and TRIF pathway.Our data indicated that DHT is a potential lead compound for treatment of infl ammatory diseases.展开更多
Nanocrystals(NCs),a colloidal dispersion system formulated with stabilizers,have attracted widespread interest due to their ability to effectively improve the oral bioavailability of poorly water-soluble drugs.The sta...Nanocrystals(NCs),a colloidal dispersion system formulated with stabilizers,have attracted widespread interest due to their ability to effectively improve the oral bioavailability of poorly water-soluble drugs.The stabilizer plays a key role because it can affect the physical stability and even the oral bioavailability of NCs.However,how stabilizers affect the bioavailability of NCs remains unknown.In this study,F68,F127,HPMC,and PVP were each used as a stabilizer to formulate naringenin NCs.The NCs formulated with PVP exhibited excellent release behaviors,cellular uptake,permeability,oral bioavailability,and anti-inflammatory effects.The underlying mechanism is that PVP effectively inhibits the formation of naringenin dimer,which in turn improves the physical stability of the supersaturated solution generated when NC is dissolved.This finding provides insights into the effects of stabilizers on the in vivo performances of NCs and supplies valuable knowledge for the development of poorly water-soluble drugs.展开更多
ATP-binding cassette(ABC)transporters are integral membrane proteins that have evolved diverse func-tions fulfilled via the transport of various substrates.In Arabidopsis,the G subfamily of ABC proteins is particularl...ATP-binding cassette(ABC)transporters are integral membrane proteins that have evolved diverse func-tions fulfilled via the transport of various substrates.In Arabidopsis,the G subfamily of ABC proteins is particularly abundant and participates in multiple signaling pathways during plant development and stress responses.In this study,we revealed that two Arabidopsis ABCG transporters,ABCG16 and ABCG25,engage in ABA-mediated stress responses and early plant growth through endomembrane-specific dimerization-coupled transport of ABA and ABA-glucosyl ester(ABA-GE),respectively.We first revealed that ABCG16 contributes to osmotic stress tolerance via ABA signaling.More specifically,ABCG16 induces cellular ABA efflux in both yeast and plant cells.Using FRET analysis,we showed that ABCG16 forms oblig-atory homodimers for ABA export activity and that the plasma membrane-resident ABCG16 homodimers specifically respond to ABA,undergoing notable conformational changes.Furthermore,we demonstrated that ABCG16 heterodimerizes with ABCG25 at the endoplasmic reticulum(ER)membrane and facilitates the ER entry of ABA-GE in both Arabidopsis and tobacco cells.The specific responsiveness of the ABCG16-ABCG25 heterodimer to ABA-GE and the superior growth of their double mutant support an inhib-itory role of these twoABCGs in early seedling establishment via regulation of ABA-GE translocation across the ER membrane.Our endomembrane-specific analysis of the FRET signals derived from the homo-or heterodimerized ABcG complexes allowed us to link endomembrane-biased dimerization to the transloca-tion of distinct substrates by ABcG transporters,providing a prototypic framework for understanding the omnipotence of ABcG transporters in plant development and stress responses.展开更多
基金supported by the National Natural Science Foundation of China under agreement number 22378026the Project of Construction of Innovative Teams and Teacher Career Development for Universities and Colleges under Beijing Municipality(IDHT20180508).
文摘The catalysis technology of propylene dimerization to form 4-methyl-1-pentene(4MP1)using a Cu-K/K_(2)CO_(3) solid base catalyst is a well-known heterogeneous catalytic reaction.In this study,the intrinsic kinetics of propylene dimerization were studied in a fixed-bed continuous reactor.Internal and external diffusion during the dimerization reaction experiments were eliminated by adjusting the flow rate of the carrier gas and the particle size of the catalyst support.Then,the concentration changes of each substance at the outlet of the catalyst bed under different residence times were investigated.Moreover,the suitable reaction kinetics equations was derived using the Langmuir Hinshelwood-Hougen-Watson kinetic model.Finally,the activation energy for each reaction involved in the dimerization reaction was calculated.The activation energies of 4MP1,branched by-products,and 1-hexene were 115.0,150.8,and 177.4 kJ/mol,respectively.The effect of process conditions on propylene dimerization with solid base catalysts was studied through kinetic model simulation.By comparing the theoretical values obtained from the simulation with the experimental results,the applicability and accuracy of the kinetic model were verified.
基金supported by the National Basic Research Program of China (No. 2009CB219901)
文摘In the process of dimerization of acetylene to produce monovinylacetylene （MVA）,the loss of active component CuCl in the Nieuwland catalyst due to the formation of a dark red precipitate was investigated.The formula of the precipitate was CuCl·2C2H2·1/5NH 3,and it was presumed to be formed by the combination of NH 3,C2H2 and [Cu]-acetylene π-complex,which was an intermediate in the dimerization reaction.The addition of hydrochloric acid into the catalyst can reduce the formation of precipitate,whereas excessive H＋ is unfavorable to the dimerization reaction of acetylene.To balance between high acetylene conversion and low loss rate of CuCl,the optimum mass percentage of HCl in the added hydrochloric acid was determined.The result showed the optimum mass percentage of HCl decreased from 5.0% to 3.2% when the space velocity of acetylene was from 140 h-1 to 360 h-1.The result in this work also indicated the pH of the Nieuwland catalyst should be kept in the range of 5.80-5.97 during the reaction process,which was good for both catalyst life and acetylene conversion.
基金supported by the National Basic Research Program of China (No. 2009CB219901)
文摘The production of monovinylacetylene （MVA） through Cu（I）-catalyzed acetylene dimerization reaction was performed in different reaction media. Based on the analyses of crystals precipitated from the catalyst solution and UV-Vis spectra of the catalysts, the reaction mechanism and solvent dependence were studied. The highest yield of MVA can be obtained when dimethylformamide is used as solvent because of its strong coordination ability to Cu（I）. The activation of C=C bond is presumed to be improved when the catalytic metal ion is coordinated by a solvent with less steric hindrance and electron-rich coordination atom. The results of the present study provide a possible way to accelerate the metal-catalyzed homogeneous reaction of alkyne substrates through careful selection of a solvent.
文摘Erythropoietin (EPO), a 34 kD glycopro-tein, is the principal growth factor regulating theproduction of circulating erythrocytes; EPO isessential for committed CFU - E erythroid pro-genitors to divide several times and then to dif-ferentiate into erythrocytes. Like most receptorsfor hematopoietic growth factors, the erythro-poietin receptor (EPO - R) is a type I trans-membrane protein and a member of the cytokinereceptor superfamily. These receptors containfour conserved cysteines and a Trp - Ser - X -
文摘Controlling catalytic activities through surface strain engineering remains a hot topic in electrocatalysis studies.Herein,ab initio molecular dynamics(AIMD)simulation associated with free energy sampling technology were performed to study the energetics of the key step of producing C2 products in electrocatalytic reduction of CO or CO_(2),i.e.CO dimerization,on strained Cu(100)with an explicit aqueous solvent model.It is worth mentioning that when compressive strain reaches a certain extent,the surface of Cu(100)will undergo reconstruction.We showed that,from tensile to compressive strain,the free energy barrier of CO dimerization decreased,suggesting that the activity of CO dimerization increases.It was also found that some of the reconstructed surfaces showing the lowest free energy barriers but might be less stable can be stabilized in the presence of adsorbed O or CO.Upon detailed quantitative analysis on the charges of surface Cu atoms,we found that the free energy barriers were strongly correlated with the charge of Cu atoms where the OCCO intermediate adsorbs.When the surfaces structures of Cu(100)were altered under compressive strain,the electronic structure of surface Cu atoms was monitored and thus the activity of electrocatalytic CO dimerization can be tuned.
基金supported by the Ministry of Science and Technology of China (2014CB239402, 2017YFA0206903)the National Natural Science foundation of China (21390404)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Science (XDB17000000)the Key Research Pro-gram of Frontier Sciences, the Chinese Academy of Sciences (QYZDY-SSW-JSC029)~~
文摘We report a hydrogen-evolution dimerization of styrenes via the synergistic merger of Acr＋-Mes photocatalyst and cobaloxime proton reduction catalysts. By utilizing this dual catalyst system, 1,2-dihydro-1-arylnaphthalene derivatives can be directly constructed from commercially available styrenes. Our reaction proceeds smoothly under mild conditions without the need for oxidants or hydrogen atom transfer reagents, and the sole byproduct is hydrogen gas. Mechanistic investigation suggests that the reaction is initiated by photoinduced electron transfer under visible-light irradiation.
基金Henan Provincial Fundamental and Frontier Technological Research Program (No. 092300410207)
文摘Density functional theory （DFT） calculations, at the B3LYP/6-311G＊＊ level of theory, were performed to study the reaction mechanism and potenti4the potential energy surface of the studied reactions was investigated. Our calculation results show that [2 ＋ 2] and [4 ＋ 4] reactions are concerted and synchronous processes; while [4 ＋ 2] reactions proceed via a concerted but asynchronous way in general. [2 ＋ 2] and [4 ＋ 2] reactions of germabenzenes and 1-germana- phthalene proceed much more easily than the corresponding [4 ＋ 4] reaction, both thermo- dynamically and kinetically; while most [4 ＋ 2] paths have lower activation barrier than the corres- ponding [2 ＋ 2] ones. As the number of six-membered aromatic rings in reactant molecules becomes larger, [2 ＋ 2], [4 ＋ 2] and [4 ＋ 4] reactions become easier to proceed. The influence of substituents at the Ge atom of germabenzenes on the potential energy surface of [2 ＋ 2] and [4 ＋ 2] reactions correlates with their electronic properties and volume. Solvent effect is not crucial for the potential energy surfaces of the studied reactions.
文摘This work aims to investigate the intrinsic kinetics of thermal dimerization of C_5 fraction in the reactive distillation process. Experiments are conducted in an 1000-m L stainless steel autoclave under some selected design conditions. By means of the weighted least squares method, the intrinsic kinetics of thermal dimerization of C_5 fraction is established, and the corresponding pre-exponential factor as well as the activation energy are determined. For example, the pre-exponential factor A is equal to 4.39×105 and the activation energy E4 a is equal to 6.58×10J/mol for the cyclopentadiene dimerization reaction. The comparison between the experimental and calculated results shows that the kinetics model derived in this work is accurate and reliable, which can be used in the design of reactive distillation columns.
基金The project supported in part by agrant from National Medical Research Council of Singapore
文摘OBJECTIVE Hepatocellular carcinoma(HCC)is the fifth most common malignancy worldwide and the third cause of global cancer mortality.Activation of signal transducer and activator of transcription 3(STAT3)is commonly observed in tumor cells and is a critical mediator of on cogenic signaling in HCC and controls the expression of several genes involved in proliferation,survival,metastasis and angiogenesis.Current drug-targeted therapies,besides being expensive,are associated with serious side effects and morbidity.Thus,novel agents that can suppress STAT3 activation have potential for both prevention and treatment of HCC.In the present report,we investigated whether the potent HAT/KAT inhibitor,garcinol,(apolyisoprenylatedbenzophenone),could suppress STAT3 activation in HCC cells and in nude mice model.METHODS The effect of garcinol on HCC cell lines wasdetermined by MTT assay,immunoblotting,DNA binding assays,immuno-fluorescenceand immune-histochemical analysis.The effect of garcinolon the inhibition of tumor growth in vivo was also investigated using HCCxenograft tumor modelin athymic nu/nu mice.RESULTS We found that garcinol could inhibit constitutive STAT3 activation in a dose-and time-dependent manner both by inhibiting STAT3 phosphorylation and acetylation in HCC cells.When investigated for molecular mechanism(s),we found that garcinol interferes with the dimer formation of STAT3 thereby inhibits its nuclear localization.Computational modeling showed that garcinol could bind to the SH2 domain of STAT3 and suppresses its dimerization in vitro.To understand the cellular mechanism(s)of inhibition of STAT3 function by garcinol,we observed that upon inhibition of STAT3 dimerization bygarcinol,STAT3 DNA binding ability gets repressed.The inhibition of STAT3 activation by garcinol led to the suppression of various gene products involved in proliferation,survival,and angiogenesis.Finally,when administered i.p.,garcinol inhibited the growth of human HCC xenograft tumors in athymic nu/nu mice.CONCLUSION Results frominvitroand in vivo studies suggest that garcinol exerts its anti-proliferative and pro-apoptotic effects through suppression of STAT3 signaling cascade in HCC by inhibiting its phosphorylation,acetylation and ultimately dimerization.
基金This work is supported by the National Natural Sci-ence Foundation of China(No.21933010).
文摘In studies of ion channel systems,due to the huge computational cost of polarizable force elds,classical force elds remain the most widely used for a long time.In this work,we used the AMOEBA polarizable atomic multipole force eld in enhanced sampling simula-tions of single-channel gramicidin A(gA)and double-channel gA systems and investigated its reliability in characterizing ion-transport properties of the gA ion channel under dimer-ization.The inuence of gA dimerization on the permeation of potassium and sodium ions through the channel was described in terms of conductance,di usion coeffcient,and free energy pro le.Results from the polarizable force eld simulations show that the conductance of potassium and sodium ions passing through the single-and double-channel agrees well with experimental values.Further data analysis reveals that the molecular mechanism of protein dimerization a ects the ion-transport properties of gA channels,i.e.,protein dimer-ization accelerates the permeation of potassium and sodium ions passing through the double-channel by adjusting the environment around gA protein(the distribution of phospholipid head groups,ions outside the channel,and bulk water),rather than directly adjusting the conformation of gA protein.
基金supported by the National Major Scientific and Technological Special Project for“Significant New Drugs Development”(Grant No.:2017ZX09101001-007).
文摘Penicillins are one type of the most important antibiotics used in the clinic.Control of drug impurity profiles is an important part of ensuring drug safety.This is particularly important in penicillins where polymerization can lead to polymers as elicitors of passive cutaneous anaphylaxis.The current understanding of penicillin polymerization is based on reactions with amino groups,but no comprehensive mechanistic understanding has been reported.Here,we used theoretical calculations and column switching-LC/MS techniques to study penicillin dimerization.Ampicillin and benzylpenicillin were selected as representative penicillins with or without amino groups in the side chain,respectively.We identified four pathways by which this may occur and the energy barrier graphs of each reaction process were given.For benzylpenicillin without an amino group in the 6-side chain,dimerization mode A is the dominant mode,where the 2-carboxyl group of one molecule reacts with the b-lactam of another molecule.However,ampicillin with an amino group in the 6-side chain favors dimerization mode C,where the amino group of one molecule attacks the b-lactam of another molecule.These findings can lead to a polymer control approach to maintaining penicillin antibiotics in an active formulation.
基金Project supported by the National Natural Science Foundation of China (Grant Nos. 10904084 and 10904083)the Shandong Provincial Middle-Aged and Young Scientists Research Awards Foundation, China (Grant No. 2009BS01009)
文摘The effect of lattice dimerization on the magnetoresistance （MR） in organic spin valves is investigated based on the Su-Schrieffer-Heeger （SSH） model and the Green＇s function method. By comparing with the results for a uniform chain, we find that the dimerization of the molecular chain modifies the monotonic dependence of the MR on the bias to an oscillatory one. A sign inversion of the MR is observed when the amplitude of the dimerization is adjusted. The results also show that at a low bias, the MR through a dimerized chain decreases with the increasing bias as well as the increasing chain length, which is consistent with the experimental reports. A further understanding can be achieved by analyzing the electronic states and the spin-dependent transmission spectrum with the parallel and antiparallel magnetization orientations of the two ferromagnetic electrodes.
文摘The catalytic property of propylene dimerization by several nickel (Ⅱ), cobalt (Ⅱ) complexes containing N-P bidentate ligands was studied in combination with organoaluminum co-catalysts. The effects of the type of aluminum co-catalysts and its relative amount, the nature of precursors in terms of ligand backbone and metal center were investigated. The results indicated that precursor I (N,N-dimethyl-2-(diphenylphosphino)aniline nickel (Ⅱ) dichloride) exhibited high activity in propylene dimerization in the presence of the strong Lewis acid Et3Al2Cl3, whereas low productivity by its cobalt analogues was observed under identical reaction conditions.
文摘Syndecan-3 (N-syndecan) is a transmembrane heparan sulfate proteoglycan abundantly expressed in developing brain. In addition to acting as a coreceptor, syndecan-3 acts as a signaling receptor upon binding of its ligand HB-GAM (heparin-binding growth-associated molecule;pleiotrophin), which activates the cortactin-src kinase signaling pathway. This leads to rapid neurite extension in neuronal cells, which makes syndecan-3 as an interesting transmembrane receptor in neuronal development and regeneration. However, little is known about the signaling mechanism of syndecan-3. Here we have analyzed formation of ligand-N-syndecan signaling complexes at the cell surface using fluorescence resonance energy transfer (FRET) and bioluminescence resonance energy transfer (BRET). We show that ligand binding leads to dimerization of syndecan-3 at the cell surface. The dimerized syndecan-3 colocalizes with actin in the filopodia of cells. Several amino acid residues (K383, G392 and G396) in the transmembrane domain are shown to be important for the ligand-induced dimerization, whereas the cytosolic domain is not required for the dimerization.
文摘Objective:Dihydrotanshinone I(DHT)is a natural product with multiple bioactivities.In this study,we aimed to investigate its anti-infl ammatory effect and potential mechanisms.Methods and Results:Lipopolysaccharide(LPS)was used to induce acute kidney injury(AKI)in mice and establish infl ammation in macrophage.In vivo experiment,pretreatment of mice with DHT effectively inhibited xylene-induced ear oedema and LPS-induced endotoxic death and protected against LPSinduced AKI.DHT suppressed COX-2,iNOS,TNF-α,IL-6 and IL-1βexpression.In vitro experiment,DHT attenuated LPS-induced transcriptional activity of NF-κB by decreasing levels of phosphorylated IκB-αand IKK and NF-κB/p65 nuclear translocation.In addition,DHT blocked LPS-induced TLR4 dimerization,resulting in the recruiting of MyD88 and TRIF.Conclusion:In summary,DHT blocks TLR4 dimerization to activate MyD88-TAK1-NF-Κb signalling cascades and TRIF pathway.Our data indicated that DHT is a potential lead compound for treatment of infl ammatory diseases.
基金by the National Natural Science Foundation of China(No.82173765)the Science Foundation for Outstanding Youth of Liaoning Province(2021-YQ-08)+5 种基金Ningxia Key Research and Invention Program(No.2021BEG02039)Basic Research Projects of Liaoning Provincial Department of Education(2020LFW01)the Career Development Program for Young Teachers in Shenyang Pharmaceutical University(ZQN2019003)the Outstanding Youth Lifting Program in Shenyang Pharmaceutical University(YQ202115)the Natural Science Foundation of Liaoning Province(2020-MS-074)Open Fund of Key Laboratory of Biotechnology and Bioresources Utilization(Dalian Minzu University),Ministry of Education(KF2022005),China.
文摘Nanocrystals(NCs),a colloidal dispersion system formulated with stabilizers,have attracted widespread interest due to their ability to effectively improve the oral bioavailability of poorly water-soluble drugs.The stabilizer plays a key role because it can affect the physical stability and even the oral bioavailability of NCs.However,how stabilizers affect the bioavailability of NCs remains unknown.In this study,F68,F127,HPMC,and PVP were each used as a stabilizer to formulate naringenin NCs.The NCs formulated with PVP exhibited excellent release behaviors,cellular uptake,permeability,oral bioavailability,and anti-inflammatory effects.The underlying mechanism is that PVP effectively inhibits the formation of naringenin dimer,which in turn improves the physical stability of the supersaturated solution generated when NC is dissolved.This finding provides insights into the effects of stabilizers on the in vivo performances of NCs and supplies valuable knowledge for the development of poorly water-soluble drugs.
基金supported by the National Natural Science Foundation of China(grant 32070292)the Shenzhen Science and Technology Program (grant KQTD20190929173906742)+2 种基金the Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes(grant 2019KSYS006)Shenzhen government for fundamental research(grant JCYJ20170817104523456)Scientific research funding for postdoctoral researchers staying at Shenzhen(grant K20227507).
文摘ATP-binding cassette(ABC)transporters are integral membrane proteins that have evolved diverse func-tions fulfilled via the transport of various substrates.In Arabidopsis,the G subfamily of ABC proteins is particularly abundant and participates in multiple signaling pathways during plant development and stress responses.In this study,we revealed that two Arabidopsis ABCG transporters,ABCG16 and ABCG25,engage in ABA-mediated stress responses and early plant growth through endomembrane-specific dimerization-coupled transport of ABA and ABA-glucosyl ester(ABA-GE),respectively.We first revealed that ABCG16 contributes to osmotic stress tolerance via ABA signaling.More specifically,ABCG16 induces cellular ABA efflux in both yeast and plant cells.Using FRET analysis,we showed that ABCG16 forms oblig-atory homodimers for ABA export activity and that the plasma membrane-resident ABCG16 homodimers specifically respond to ABA,undergoing notable conformational changes.Furthermore,we demonstrated that ABCG16 heterodimerizes with ABCG25 at the endoplasmic reticulum(ER)membrane and facilitates the ER entry of ABA-GE in both Arabidopsis and tobacco cells.The specific responsiveness of the ABCG16-ABCG25 heterodimer to ABA-GE and the superior growth of their double mutant support an inhib-itory role of these twoABCGs in early seedling establishment via regulation of ABA-GE translocation across the ER membrane.Our endomembrane-specific analysis of the FRET signals derived from the homo-or heterodimerized ABcG complexes allowed us to link endomembrane-biased dimerization to the transloca-tion of distinct substrates by ABcG transporters,providing a prototypic framework for understanding the omnipotence of ABcG transporters in plant development and stress responses.
