α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia,which play crucial roles in the management of type 2 diabetes.Protocatechuic acid(PCA)is one of phenolic acids existing not only in var...α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia,which play crucial roles in the management of type 2 diabetes.Protocatechuic acid(PCA)is one of phenolic acids existing not only in various plant foods but also as a major microbial metabolite of dietary anthocyanins in the large colon.The present study investigated the inhibitory mechanism of PCA on a-glucosidase in vitro and examined its effect on postprandial blood glucose levels in vivo.Results from in vitro experiments demonstrated that PCA was a mix-type inhibitor of a-glucosidase.Driven by hydrogen bonds and van der Waals interactions,PCA reversibly bound withα-glucosidase to form a stable a-glucosidase-PCA complex in a spontaneous manner.The computational simulation found that PCA could insert into the active cavity of a-glucosidase and establish hydrogen bonds with catalytic amino acid residues.PCA binding aroused the steric hindrance for substrates to enter active sites and caused the structural changes of interacted catalytic amino acid residues.PCA also exhibited postprandial hypoglycemic capacity in diabetic mice.This study may provide the theoretical basis for the application of PCA as an active ingredient of functional foods in dietary management of diabetes.展开更多
The additive manufacturing(AM)of Ni-based superalloys has attracted extensive interest from both academia and industry due to its unique capabilities to fabricate complex and high-performance components for use in hig...The additive manufacturing(AM)of Ni-based superalloys has attracted extensive interest from both academia and industry due to its unique capabilities to fabricate complex and high-performance components for use in high-end industrial systems.However,the intense temperature gradient induced by the rapid heating and cooling processes of AM can generate high levels of residual stress and metastable chemical and structural states,inevitably leading to severe metallurgical defects in Ni-based superalloys.Cracks are the greatest threat to these materials’integrity as they can rapidly propagate and thereby cause sudden and non-predictable failure.Consequently,there is a need for a deeper understanding of residual stress and cracking mechanisms in additively manufactured Ni-based superalloys and ways to potentially prevent cracking,as this knowledge will enable the wider application of these unique materials.To this end,this paper comprehensively reviews the residual stress and the various mechanisms of crack formation in Ni-based superalloys during AM.In addition,several common methods for inhibiting crack formation are presented to assist the research community to develop methods for the fabrication of crack-free additively manufactured components.展开更多
Glucosyltransferases(Gtfs)play critical roles in the etiology and pathogenesis of Streptococcus mutans(S.mutans)-mediated dental caries including early childhood caries.Gtfs enhance the biofilm formation and promotes ...Glucosyltransferases(Gtfs)play critical roles in the etiology and pathogenesis of Streptococcus mutans(S.mutans)-mediated dental caries including early childhood caries.Gtfs enhance the biofilm formation and promotes colonization of cariogenic bacteria by generating biofilm extracellular polysaccharides(EPSs),the key virulence property in the cariogenic process.Therefore,Gtfs have become an appealing target for effective therapeutic interventions that inhibit cariogenic biofilms.Importantly,targeting Gtfs selectively impairs the S.mutans virulence without affecting S.mutans existence or the existence of other species in the oral cavity.Over the past decade,numerous Gtfs inhibitory molecules have been identified,mainly including natural and synthetic compounds and their derivatives,antibodies,and metal ions.These therapeutic agents exert their inhibitory role in inhibiting the expression gtf genes and the activities and secretion of Gtfs enzymes with a wide range of sensitivity and effectiveness.Understanding molecular mechanisms of inhibiting Gtfs will contribute to instructing drug combination strategies,which is more effective for inhibiting Gtfs than one drug or class of drugs.This review highlights our current understanding of Gtfs activities and their potential utility,and discusses challenges and opportunities for future exploration of Gtfs as a therapeutic target.展开更多
Fusarium moniliforme(F.moniliforme) and its secondary metabolite fumonisin pose a severe threat to food safety,and searching for effective antimicrobial agents is a focus of current research.In this study,the secondar...Fusarium moniliforme(F.moniliforme) and its secondary metabolite fumonisin pose a severe threat to food safety,and searching for effective antimicrobial agents is a focus of current research.In this study,the secondary structure of Sub3 was analyzed by circular dichroism,meanwhile,the inhibition rate of Sub3 against spores,mycelia of F.moniliforme and infected maize was studied.To explore the possible inhibition mechanisms,morphological and structural changes of spores treated with Sub3 at0,1/2 MIC(minimum inhibitory concentration) and MIC were observed by scanning electron microscopy and transmission electron microscopy;the cell wall integrity,membrane integrity,reactive oxygen species,mitochondrial membrane potential,ATP synthase activity,redox reactions,and the nuclear damage of F.moniliforme were also investigated.The results showed that Sub3 was mostly in the state of random in deionized water,while mainly showed the β-sheet structure in the hydrophobic environment of 50% Trifluoroethanol(TFE) solution,indicating that Sub3 might generate partial structure deformation when acting on the cell membrane;and its MIC on F.moniliforme spores was 0.2 g/L.Under the 1/2 MIC and MIC,the inhibition rates of Sub3 against F.moniliforme infected maize were 34.3% and75.6%,respectively.The results of inhibition mechanisms revealed that the defective pathogenicity of F.moniliforme caused by Sub3 was attributed to damages on both the cell wall and the cell membrane,which might upset balance of intracellular redox system and mitochondrial energy metabolism and trigger nucleus damage,ultimately leading to cell death.Meanwhile,Sub3 could diminished ATP synthase enzyme activity in a dose-dependent manner.The results provided direct evidence for inhibition of F.moniliforme infection of maize by Sub3,and useful knowledge applicable for food preservation.展开更多
Recently we have synthesized a novel small retinoid molecule WYC-209 that can effectively inhibit proliferation of malignant murine melanoma tumor-repopulating cells(TRCs).The molecule can induce 100%TRCs apoptosis at...Recently we have synthesized a novel small retinoid molecule WYC-209 that can effectively inhibit proliferation of malignant murine melanoma tumor-repopulating cells(TRCs).The molecule can induce 100%TRCs apoptosis at 10μM concentration.However,how WYC-209 induces TRCs apoptosis is still elusive.Here we demonstrate that WYC-209 at>6μM concentration started to induce TRCs apoptosis primarily via the caspase 3 pathway by releasing cytochrome c from mitochondria.Interestingly,we found that at concentrations<6μM WYC-209 induced TRCs to elevate dormancy marker COUP TF1 but induced no changes in apoptosis marker P53.Furthermore,proliferation markers Ki67 and PCNA decreased with the increase of WYC-209 concentrations,suggesting that low concentrations of WYC-209 inhibit TRCs growth by inducing cell dormancy instead of causing apoptosis.In addition,TRC traction forces were almost abolished when WYC-209 concentration was at 5μM,preceding the initiation of apoptosis.Our findings demonstrate that inhibition of TRCs by anti-cancer molecule WYC-209 is concentration-dependent and WYC-209 inhibits cellular force generation of the tumor-repopulating cells before inducing apoptosis.展开更多
A new method of studying the corrosion inhibition mechanism of rare earth metal(REM) on LC4 Al alloy with the spilt cell technique was studied. The principle and experimental method of the spilt cell technique were ...A new method of studying the corrosion inhibition mechanism of rare earth metal(REM) on LC4 Al alloy with the spilt cell technique was studied. The principle and experimental method of the spilt cell technique were analyzed. By measuring the change of net-electric current between the two electrodes caused by the change of the amount of oxygen in the solution and the addition of CeCl3, the influence of corrosive performance of CeCl3 on LC4 super-power aluminum "alloy in the 0.1 mol· L^-1 NaCl solution was investigated. Meanwhile, the conditional changes of pH values, CeCl3 solution, additire and time of performance were also studied. Finally, the features of electrode surface were revealed by using SEM and X-ray energy-dispersive spectrometry (EDS). By combining these with other electric chemical techniques, such as potential-time curve, polarization curve et al.展开更多
A reduced mechanism for propane/air combustion and its flame inhibition by phosphorus-containing compounds (PCCs) is constructed with the level of importance (LOI) method. The analysis is performed on solutions of fre...A reduced mechanism for propane/air combustion and its flame inhibition by phosphorus-containing compounds (PCCs) is constructed with the level of importance (LOI) method. The analysis is performed on solutions of freely propagating premixed flames with detailed chemical kinetics involving 121 species and 682 reactions proposed by Jayaweera et al. For the non-homogeneous reaction-diffusion system, the chemical lifetime of each species is weighted by its diffusion timescale, and the characteristic flame timescale is used to normalize the chemical lifetime. The definition of sensitivity in LOI is extended so that multi-parameters can be used as sensitivity targets. Propane, oxygen, dimethyl methylphosphonate (DMMP), and flame speed are selected to be perturbed for sensitivity analysis, the species with low LOI index are removed, and reactions involving the redundant species are excluded from the mechanism. A skeletal mechanism is obtained, which consists of 57 species and 268 elementary reactions. Calculations for laminar flame speeds, key flame radicals and catalytic cycles using the skeletal mechanism are in good agreement with those by using the detailed mechanism over a wide range of equivalence ratio undoped and doped with DMMP.展开更多
Plant-derived essential oils have excellent antifungal effects and can be used for the preservation of fresh foods such as fruits and vegetables, but the detailed mechanism has not been fully elucidated. In this study...Plant-derived essential oils have excellent antifungal effects and can be used for the preservation of fresh foods such as fruits and vegetables, but the detailed mechanism has not been fully elucidated. In this study, we investigated the inhibitory effects of trans-cinnamaldehyde on Penicillium italicum, a common pollution fungus in citrus, and explored the antifungal mechanism of trans-cinnamaldehyde by detecting fungal oxidative damage, mitochondrial metabolism, and cell apoptosis. These results showed that transcinnamaldehyde made the carboxylic acid cycle deregulated by altering the related enzyme activities(succinate dehydrogenase, malate dehydrogenase) and mid product. Moreover, the level of reactive oxygen species rose sharply while the redox level was out of regulation. The mitochondrial membrane potential collapsed, leading to the leakage of cytochrome c, and then triggering the activation of apoptotic protease, which was further confirmed by the significant increase in caspase-3 activity from(3.6 ± 0.6) U to(8.8 ± 1.1) U(P < 0.05). The cytochrome c in mitochondria was detected by confocal Raman microspectroscopy, the characteristic intensity index(I750/I2944) was decreased, indicating that the cytochrome c in mitochondria was reduced and leakage. Besides, the strong negative correlation between Raman intensity and the amount of cytochrome c leakage was established with the correlation coefficient of-0.981 7. This study revealed that destroying the integrity of the mitochondrial membrane, activating the mitochondrial-mediated apoptosis pathway was the in-depth antifungal mechanism of trans-cinnamaldehyde;and Raman spectroscopy technology provided new ideas to study this process with high sensitivity determination of cytochrome c.展开更多
In order to analyze the complex chemical kinetic mechanism systematically and find out the redundant species and reactions, a numerical platform for mechanism analysis and simplification is established basing on Path ...In order to analyze the complex chemical kinetic mechanism systematically and find out the redundant species and reactions, a numerical platform for mechanism analysis and simplification is established basing on Path Flux Analysis (PFA). It is used to reduce a detailed mechanism for flame inhibited by phosphorus containing compounds, a reduced mechanism with 65 species and 335 reactions is obtained. The detailed and reduced mechanism are both used to calculate the freely-propagating premix C3H8/air flame with different dimethyl methylphosphonate doped over a wide range of equivalence ratios. The concentration distributions of free radicals and major species are compared, and the results under two different mechanisms agree well. The laminar flame speed obtained by the two mechanisms also matches well, with the maximum relative error introduces as a small value of 1.7%. On the basis of the reduced mechanism validation, the correlativity analysis is conducted between flame speed and flee radical concentrations, which can provide information for target species selection in the further mechanism reduction. By analyzing the species and reactions fluxes, the species and reaction paths which contribute the flame inhibition significantly are determined.展开更多
The effects of aspartic acid on the crystal growth, morphology of hydroxyapatite(HAP) crystal were investigated, and the inhibition mechanism of aspartic acid on the crystal growth of hydroxyapatite was studied. The r...The effects of aspartic acid on the crystal growth, morphology of hydroxyapatite(HAP) crystal were investigated, and the inhibition mechanism of aspartic acid on the crystal growth of hydroxyapatite was studied. The results show that the crystal growth rate of HAP decreases with the increase of the aspartic acid concentration, and the HAP crystal is thinner significantly compared with that without amino acid, which is mainly due to the (1 010) surface of HAP crystal being inhibited by the aspartic acids. The calculation analysis indicates that the crystal growth mechanism of HAP, following surface diffusion controlled mechanism, is not changed due to the presence of aspartic acid. AFM result shows that the front of terrace on vicinal growth hillocks is pinned, which suggests that the aspartic acid is adsorbed onto the (1 010) surface of HAP and interacts with the Ca2+ ions of HAP surface, so as to block the growth active sites and result in retarding of the growth of HAP crystal.展开更多
The density functional theory at the B3LYP/6-311G(d, p) level was applied to exploring the inhibition mechanism of cholinesterases by carbamate. The results indicate that the inhibition reactions with or without the...The density functional theory at the B3LYP/6-311G(d, p) level was applied to exploring the inhibition mechanism of cholinesterases by carbamate. The results indicate that the inhibition reactions with or without the catalytic effect of the catalytic triad in eholinesterases underwent a two-step addition-elimination mechanism, which is in good agreement with the proposed mechanism. The solvent has a strong effect on the inhibition reactions and the reaction with the catalytic triad in the solvent phase is close to the real reaction under biological condition.展开更多
Pig Actinobacillus pleuropneumoniae(App) could induce chronic respiratory tract infection in pigs, which causes major economic losses on pig industry. Bacterial biofilm(BBF) is bacterial community adsorbed on the surf...Pig Actinobacillus pleuropneumoniae(App) could induce chronic respiratory tract infection in pigs, which causes major economic losses on pig industry. Bacterial biofilm(BBF) is bacterial community adsorbed on the surface of biomaterials or body cavity, to protect bacteria escape, and recurrent outbreaks of related infectious diseases and chronic infections resulting therefrom are called bacterial biofilm diseases. App BF belongs to polymers with spatial structure in vitro, and its formation is regulated by multiple genes. Among them, gene deletion of the key component TolC of multidrug efflux pumps and type I secretion systems causes that App BF adhesion weakens; gene deletion of catalytic core ClpP of Clp proteolytic complex induces the inhibition of BF formation; outer membrane lipoprotein VacJ of App promotes BF formation; gene deletion of active enzyme LuxS enhances the formation of App BF and decreases bacterial adhesion ability; gene deletion of Adh obviously declines bacterial accumulation, BF formation and adhesion to host cells. In this paper, BF formation or inhibition mechanism in App is elaborated from molecular level, which could provide reference basis for exploring the prevention of its biofilm diseases.展开更多
In order to study the inhibition mechanism of antifungal monomers DZP8 produced by streptomyces 702 strain against Rhizoctonia solani, the effects of DZP8 on mycelial morphology were investigated under light microscop...In order to study the inhibition mechanism of antifungal monomers DZP8 produced by streptomyces 702 strain against Rhizoctonia solani, the effects of DZP8 on mycelial morphology were investigated under light microscope, and the effects of DZP8 on mycelial inclusion leakage and cell membrane damage of myceli-um were determined. The results showed that DZP8 caused a series of changes in mycelial morphology of R. solani in liquid culture condition. DZP8 treatments with concentrations of 1.81 and 3.35 μg/mL for 24 h caused big vacuole, rough surface and more inclusions of mycelium. With the treatment time prolonging, the mycelium distorted and appeared irregular constriction. DZP8 treatment with concentration of 20.10 μg/mL led to the increase of conductivity of mycelium culture liquid, leakage of soluble sugar and protein, and the lipid peroxidation of mycelium membrane. It was found that DZP8 at a very low concentration could cause changes of mycelial morphology of R. solani, while only a certain concentration could cause significant damage to cell membrane. This indicated that cell membrane might be one of the action sites of DZP8, and it might have other action sites or mechanism.展开更多
Phosphorus-containing compounds are considered as the potential alternatives of traditional inhibitors for suppressing the formation of polychlorinated dibenzo-p-dioxins and dibenzofurans(PCDD/Fs),but the suppression ...Phosphorus-containing compounds are considered as the potential alternatives of traditional inhibitors for suppressing the formation of polychlorinated dibenzo-p-dioxins and dibenzofurans(PCDD/Fs),but the suppression characteristics are scarcely studied.In this study,ammonium dihydrogen phosphate(ADP)was selected as the inhibitor to inhibit the PCDD/F formation via de novo synthesis at 350℃.The influence of oxygen content and addition method on PCDD/F inhibition was systematically investigated by means of statistical analysis and morphological characterization.The results showed that oxygen enhanced the formation of PCDD/Fs from 1470 ng g^(−1)(9.78 ng I-TEQ g^(−1))to 2110 ng g^(−1)(14.8 ng I-TEQ g^(−1)).ADP significantly inhibited the PCDD/F formation,with inhibition efficiencies ranging from 82.0%to 97.7%.Herein,a higher oxygen content and the premixed way intensified the suppression effect.Dibenzo-p-dioxin(DD)/dibenzofuran(DF)chlorination was proven to be effectively suppressed while chlorophenol(CP)route was not obviously influenced.With the addition of ADP,Cl source was significantly reduced and the formation of organic Cl was effectively inhibited.Also,it decreased the proportion of C–O/C=N and C=O,revealing the efficient inhibition of carbon oxidation.Meanwhile,the formation of copper phosphate and copper pyrophosphate was observed in XPS(X-ray photoelectron spectroscopy)spectra,indicating that the catalytic metal Cu was chelated and passivated by ADP.The premixed way had a better effect on reducing Cl resources,inhibiting oxidation and chelating metals,due to the direct contact with inhibitor.However,the separation method could only depend on the decomposed gases,resulting in a lower inhibition efficiency.展开更多
The advantages and disadvantages of organic antioxidant and inorganic salt on suppressing coal oxidation were analyzed on the basis of the theory that coal oxidation mechanisms can be attributed to the free radical ch...The advantages and disadvantages of organic antioxidant and inorganic salt on suppressing coal oxidation were analyzed on the basis of the theory that coal oxidation mechanisms can be attributed to the free radical chain-type reaction mechanism. The inhibition curves on suppressing coal oxidation of the different type and different concentration of organic antioxidant and inorganic salt were given through experimental study and data processing. Then some conclusions can be gained from the experimental study combining with theoretical analysis. First the inhibition mechanism of the organic antioxidant and inorganic salt is different. The former is that the chemical action is the dominant position. It can be called as the chain termination theory because the free radical is captured during coal oxidation. And the later is that the physical effect is the dominant position. It can be called as the decreasing-temperature theory because the liquid membrane which was formed by the inorganic salt can make coal body be the state of wetness and prevent oxygen from coal surface. Second the inhibition effect of the organic antioxidant is higher than the inorganic salt in the later period. But it is lower in the early period.展开更多
In comparing reference unification to reference linking,the authors found that reference linking yield similar result as that of reference unification.An investigative study was conducted by these authors at Chinese S...In comparing reference unification to reference linking,the authors found that reference linking yield similar result as that of reference unification.An investigative study was conducted by these authors at Chinese Science Citation Database(CSCD)of National Science Library(NSL)of the ChineseAcademy of Sciences(CAS),it was found that there were three inhibiting elements in invoking a reference unification solution and the same is true for a reference linking solution.Firstly,it was difficult to define a minimum set of data elements for matching.Secondly,it had a problem of data inaccuracy and/or data incompleteness.Thirdly,it was hard to determine an appropriate linking result that produced the desired document for the user.Thus these authors suggest that getting Digital Object Identifier(DOI)for each journal article is a good way to bring about reference unification and also to improve metadata quality simultaneously at the same time.Therefore,DOI has a pivotal role to play in terms of bringing about reference unification and/or a reference linking.展开更多
By analyzing the corrosion of phosphate completion fluid on the P110 steel at 170 °C, the high-temperature corrosion mechanism of phosphate completion fluid was revealed, and a corrosion inhibition method by memb...By analyzing the corrosion of phosphate completion fluid on the P110 steel at 170 °C, the high-temperature corrosion mechanism of phosphate completion fluid was revealed, and a corrosion inhibition method by membrane transformation was proposed and an efficient membrane-forming agent was selected. Scanning electron microscope (SEM) images, X-ray energy spectrum and X-ray diffraction results were used to characterize the microscopic morphology, elemental composition and phase composition of the precipitation membrane on the surface of the test piece. The effect and mechanism of corrosion inhibition by membrane transformation were clarified. The phosphate completion fluid eroded the test piece by high-temperature water vapor and its hydrolyzed products to form a membrane of iron phosphate corrosion product. By changing the corrosion reaction path, the Zn2+ membrane-forming agent could generate KZnPO4 precipitation membrane with high temperature resistance, uniform thickness and tight crystal packing on the surface of the test piece, which could inhibit the corrosion of the test piece, with efficiency up to 69.63%. The Cu2+ membrane-forming agent electrochemically reacted with Fe to precipitate trace elemental Cu on the surface of the test piece, thus forming a protective membrane, which could inhibit metal corrosion, with efficiency up to 96.64%, but the wear resistance was poor. After combining 0.05% Cu2+ and 0.25% Zn2+, a composite protective membrane of KZnPO4 crystal and elemental Cu was formed on the surface of the test piece. The corrosion inhibition efficiency reached 93.03%, which ensured the high corrosion inhibition efficiency and generated a precipitation membrane resistant to temperature and wear.展开更多
基金supported by the General Research Fund of Hong Kong (14105820)。
文摘α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia,which play crucial roles in the management of type 2 diabetes.Protocatechuic acid(PCA)is one of phenolic acids existing not only in various plant foods but also as a major microbial metabolite of dietary anthocyanins in the large colon.The present study investigated the inhibitory mechanism of PCA on a-glucosidase in vitro and examined its effect on postprandial blood glucose levels in vivo.Results from in vitro experiments demonstrated that PCA was a mix-type inhibitor of a-glucosidase.Driven by hydrogen bonds and van der Waals interactions,PCA reversibly bound withα-glucosidase to form a stable a-glucosidase-PCA complex in a spontaneous manner.The computational simulation found that PCA could insert into the active cavity of a-glucosidase and establish hydrogen bonds with catalytic amino acid residues.PCA binding aroused the steric hindrance for substrates to enter active sites and caused the structural changes of interacted catalytic amino acid residues.PCA also exhibited postprandial hypoglycemic capacity in diabetic mice.This study may provide the theoretical basis for the application of PCA as an active ingredient of functional foods in dietary management of diabetes.
基金This work was supported by Shenzhen-Hong Kong Science and Technology Innovation Cooperation Zone Shenzhen Park Project:HZQB-KCZYB-2020030the National Natural Science Foundation of China(No.91860131and No.52074157)+2 种基金Guangdong Provincial Department of Science and Technology,Key-Area Research and Development Program of Guangdong Province(No.2020B090923002)the National Key Research and Development Program of China(No.2017YFB0702901)the Shenzhen Science and Technology Innovation Commission(No.JCYJ20170817111811303,No.KQTD20170328154443162and No.ZDSYS201703031748354).
文摘The additive manufacturing(AM)of Ni-based superalloys has attracted extensive interest from both academia and industry due to its unique capabilities to fabricate complex and high-performance components for use in high-end industrial systems.However,the intense temperature gradient induced by the rapid heating and cooling processes of AM can generate high levels of residual stress and metastable chemical and structural states,inevitably leading to severe metallurgical defects in Ni-based superalloys.Cracks are the greatest threat to these materials’integrity as they can rapidly propagate and thereby cause sudden and non-predictable failure.Consequently,there is a need for a deeper understanding of residual stress and cracking mechanisms in additively manufactured Ni-based superalloys and ways to potentially prevent cracking,as this knowledge will enable the wider application of these unique materials.To this end,this paper comprehensively reviews the residual stress and the various mechanisms of crack formation in Ni-based superalloys during AM.In addition,several common methods for inhibiting crack formation are presented to assist the research community to develop methods for the fabrication of crack-free additively manufactured components.
基金supported by the National Natural Science Foundation of China(82170947)the Applied Basic Research Project of Science and Technology Department of Sichuan Province(2020YJ0296)the Innovation and Collaborative Project of Science and Technology Department of Sichuan Province(2019YFH0025)。
文摘Glucosyltransferases(Gtfs)play critical roles in the etiology and pathogenesis of Streptococcus mutans(S.mutans)-mediated dental caries including early childhood caries.Gtfs enhance the biofilm formation and promotes colonization of cariogenic bacteria by generating biofilm extracellular polysaccharides(EPSs),the key virulence property in the cariogenic process.Therefore,Gtfs have become an appealing target for effective therapeutic interventions that inhibit cariogenic biofilms.Importantly,targeting Gtfs selectively impairs the S.mutans virulence without affecting S.mutans existence or the existence of other species in the oral cavity.Over the past decade,numerous Gtfs inhibitory molecules have been identified,mainly including natural and synthetic compounds and their derivatives,antibodies,and metal ions.These therapeutic agents exert their inhibitory role in inhibiting the expression gtf genes and the activities and secretion of Gtfs enzymes with a wide range of sensitivity and effectiveness.Understanding molecular mechanisms of inhibiting Gtfs will contribute to instructing drug combination strategies,which is more effective for inhibiting Gtfs than one drug or class of drugs.This review highlights our current understanding of Gtfs activities and their potential utility,and discusses challenges and opportunities for future exploration of Gtfs as a therapeutic target.
基金sponsored by grants from the Natural Science Foundation of China (31972176)the Cultivation Programme for Young Backbone Teachers in Henan University of Technology (21420114)+1 种基金the Innovative Funds Plan of Henan University of Technology (2020ZKCJ01)the National Key Research and Development Project of China(Project No.2019YFC1605303-04)
文摘Fusarium moniliforme(F.moniliforme) and its secondary metabolite fumonisin pose a severe threat to food safety,and searching for effective antimicrobial agents is a focus of current research.In this study,the secondary structure of Sub3 was analyzed by circular dichroism,meanwhile,the inhibition rate of Sub3 against spores,mycelia of F.moniliforme and infected maize was studied.To explore the possible inhibition mechanisms,morphological and structural changes of spores treated with Sub3 at0,1/2 MIC(minimum inhibitory concentration) and MIC were observed by scanning electron microscopy and transmission electron microscopy;the cell wall integrity,membrane integrity,reactive oxygen species,mitochondrial membrane potential,ATP synthase activity,redox reactions,and the nuclear damage of F.moniliforme were also investigated.The results showed that Sub3 was mostly in the state of random in deionized water,while mainly showed the β-sheet structure in the hydrophobic environment of 50% Trifluoroethanol(TFE) solution,indicating that Sub3 might generate partial structure deformation when acting on the cell membrane;and its MIC on F.moniliforme spores was 0.2 g/L.Under the 1/2 MIC and MIC,the inhibition rates of Sub3 against F.moniliforme infected maize were 34.3% and75.6%,respectively.The results of inhibition mechanisms revealed that the defective pathogenicity of F.moniliforme caused by Sub3 was attributed to damages on both the cell wall and the cell membrane,which might upset balance of intracellular redox system and mitochondrial energy metabolism and trigger nucleus damage,ultimately leading to cell death.Meanwhile,Sub3 could diminished ATP synthase enzyme activity in a dose-dependent manner.The results provided direct evidence for inhibition of F.moniliforme infection of maize by Sub3,and useful knowledge applicable for food preservation.
基金supported by funds from Huazhong University of Science and Technology
文摘Recently we have synthesized a novel small retinoid molecule WYC-209 that can effectively inhibit proliferation of malignant murine melanoma tumor-repopulating cells(TRCs).The molecule can induce 100%TRCs apoptosis at 10μM concentration.However,how WYC-209 induces TRCs apoptosis is still elusive.Here we demonstrate that WYC-209 at>6μM concentration started to induce TRCs apoptosis primarily via the caspase 3 pathway by releasing cytochrome c from mitochondria.Interestingly,we found that at concentrations<6μM WYC-209 induced TRCs to elevate dormancy marker COUP TF1 but induced no changes in apoptosis marker P53.Furthermore,proliferation markers Ki67 and PCNA decreased with the increase of WYC-209 concentrations,suggesting that low concentrations of WYC-209 inhibit TRCs growth by inducing cell dormancy instead of causing apoptosis.In addition,TRC traction forces were almost abolished when WYC-209 concentration was at 5μM,preceding the initiation of apoptosis.Our findings demonstrate that inhibition of TRCs by anti-cancer molecule WYC-209 is concentration-dependent and WYC-209 inhibits cellular force generation of the tumor-repopulating cells before inducing apoptosis.
文摘A new method of studying the corrosion inhibition mechanism of rare earth metal(REM) on LC4 Al alloy with the spilt cell technique was studied. The principle and experimental method of the spilt cell technique were analyzed. By measuring the change of net-electric current between the two electrodes caused by the change of the amount of oxygen in the solution and the addition of CeCl3, the influence of corrosive performance of CeCl3 on LC4 super-power aluminum "alloy in the 0.1 mol· L^-1 NaCl solution was investigated. Meanwhile, the conditional changes of pH values, CeCl3 solution, additire and time of performance were also studied. Finally, the features of electrode surface were revealed by using SEM and X-ray energy-dispersive spectrometry (EDS). By combining these with other electric chemical techniques, such as potential-time curve, polarization curve et al.
基金Supported by the National Natural Science Foundation of China (50876097) the Program for New Century Excellent Talents in University of China (NCET-06-0546)
文摘A reduced mechanism for propane/air combustion and its flame inhibition by phosphorus-containing compounds (PCCs) is constructed with the level of importance (LOI) method. The analysis is performed on solutions of freely propagating premixed flames with detailed chemical kinetics involving 121 species and 682 reactions proposed by Jayaweera et al. For the non-homogeneous reaction-diffusion system, the chemical lifetime of each species is weighted by its diffusion timescale, and the characteristic flame timescale is used to normalize the chemical lifetime. The definition of sensitivity in LOI is extended so that multi-parameters can be used as sensitivity targets. Propane, oxygen, dimethyl methylphosphonate (DMMP), and flame speed are selected to be perturbed for sensitivity analysis, the species with low LOI index are removed, and reactions involving the redundant species are excluded from the mechanism. A skeletal mechanism is obtained, which consists of 57 species and 268 elementary reactions. Calculations for laminar flame speeds, key flame radicals and catalytic cycles using the skeletal mechanism are in good agreement with those by using the detailed mechanism over a wide range of equivalence ratio undoped and doped with DMMP.
基金supported by China Postdoctoral Science Foundation (2020M680064)National Natural Science Foundation of China (32172326)the Postdoctoral Research Startup Fee of Jiangnan University (1025219032200190)。
文摘Plant-derived essential oils have excellent antifungal effects and can be used for the preservation of fresh foods such as fruits and vegetables, but the detailed mechanism has not been fully elucidated. In this study, we investigated the inhibitory effects of trans-cinnamaldehyde on Penicillium italicum, a common pollution fungus in citrus, and explored the antifungal mechanism of trans-cinnamaldehyde by detecting fungal oxidative damage, mitochondrial metabolism, and cell apoptosis. These results showed that transcinnamaldehyde made the carboxylic acid cycle deregulated by altering the related enzyme activities(succinate dehydrogenase, malate dehydrogenase) and mid product. Moreover, the level of reactive oxygen species rose sharply while the redox level was out of regulation. The mitochondrial membrane potential collapsed, leading to the leakage of cytochrome c, and then triggering the activation of apoptotic protease, which was further confirmed by the significant increase in caspase-3 activity from(3.6 ± 0.6) U to(8.8 ± 1.1) U(P < 0.05). The cytochrome c in mitochondria was detected by confocal Raman microspectroscopy, the characteristic intensity index(I750/I2944) was decreased, indicating that the cytochrome c in mitochondria was reduced and leakage. Besides, the strong negative correlation between Raman intensity and the amount of cytochrome c leakage was established with the correlation coefficient of-0.981 7. This study revealed that destroying the integrity of the mitochondrial membrane, activating the mitochondrial-mediated apoptosis pathway was the in-depth antifungal mechanism of trans-cinnamaldehyde;and Raman spectroscopy technology provided new ideas to study this process with high sensitivity determination of cytochrome c.
基金Supported by the National Natural Science Foundation of China (51176181), the National Basic Research Program of China (2012CB719704), and the Research Fund for the Doctoral Program of Higher Education (20123402110047).
文摘In order to analyze the complex chemical kinetic mechanism systematically and find out the redundant species and reactions, a numerical platform for mechanism analysis and simplification is established basing on Path Flux Analysis (PFA). It is used to reduce a detailed mechanism for flame inhibited by phosphorus containing compounds, a reduced mechanism with 65 species and 335 reactions is obtained. The detailed and reduced mechanism are both used to calculate the freely-propagating premix C3H8/air flame with different dimethyl methylphosphonate doped over a wide range of equivalence ratios. The concentration distributions of free radicals and major species are compared, and the results under two different mechanisms agree well. The laminar flame speed obtained by the two mechanisms also matches well, with the maximum relative error introduces as a small value of 1.7%. On the basis of the reduced mechanism validation, the correlativity analysis is conducted between flame speed and flee radical concentrations, which can provide information for target species selection in the further mechanism reduction. By analyzing the species and reactions fluxes, the species and reaction paths which contribute the flame inhibition significantly are determined.
基金Project(2003AA302210) support by the National High-Tech Research and Development Program of ChinaProject(05JJ20014) supported by the Natural Science Foundation of Hunan Province, China
文摘The effects of aspartic acid on the crystal growth, morphology of hydroxyapatite(HAP) crystal were investigated, and the inhibition mechanism of aspartic acid on the crystal growth of hydroxyapatite was studied. The results show that the crystal growth rate of HAP decreases with the increase of the aspartic acid concentration, and the HAP crystal is thinner significantly compared with that without amino acid, which is mainly due to the (1 010) surface of HAP crystal being inhibited by the aspartic acids. The calculation analysis indicates that the crystal growth mechanism of HAP, following surface diffusion controlled mechanism, is not changed due to the presence of aspartic acid. AFM result shows that the front of terrace on vicinal growth hillocks is pinned, which suggests that the aspartic acid is adsorbed onto the (1 010) surface of HAP and interacts with the Ca2+ ions of HAP surface, so as to block the growth active sites and result in retarding of the growth of HAP crystal.
基金Supported by the National Natural Science Foundation of China(Nos.20333050 and 20673044), PCSIRT(No.IRT0625) Key Subject of Science and Technology by Jilin Province, China
文摘The density functional theory at the B3LYP/6-311G(d, p) level was applied to exploring the inhibition mechanism of cholinesterases by carbamate. The results indicate that the inhibition reactions with or without the catalytic effect of the catalytic triad in eholinesterases underwent a two-step addition-elimination mechanism, which is in good agreement with the proposed mechanism. The solvent has a strong effect on the inhibition reactions and the reaction with the catalytic triad in the solvent phase is close to the real reaction under biological condition.
基金Supported by Tianjin Natural Science Foundation Project(07JCYBJC16000)Key Technologies Integration and Students' Comprehensive Ability Improvement Project of Animal Hospital Affiliated to Tianjin Agricultural University(ZH004901)
文摘Pig Actinobacillus pleuropneumoniae(App) could induce chronic respiratory tract infection in pigs, which causes major economic losses on pig industry. Bacterial biofilm(BBF) is bacterial community adsorbed on the surface of biomaterials or body cavity, to protect bacteria escape, and recurrent outbreaks of related infectious diseases and chronic infections resulting therefrom are called bacterial biofilm diseases. App BF belongs to polymers with spatial structure in vitro, and its formation is regulated by multiple genes. Among them, gene deletion of the key component TolC of multidrug efflux pumps and type I secretion systems causes that App BF adhesion weakens; gene deletion of catalytic core ClpP of Clp proteolytic complex induces the inhibition of BF formation; outer membrane lipoprotein VacJ of App promotes BF formation; gene deletion of active enzyme LuxS enhances the formation of App BF and decreases bacterial adhesion ability; gene deletion of Adh obviously declines bacterial accumulation, BF formation and adhesion to host cells. In this paper, BF formation or inhibition mechanism in App is elaborated from molecular level, which could provide reference basis for exploring the prevention of its biofilm diseases.
基金Supported by General Program of National Natural Science Foundation of China(31071724)Natural Science Foundation of Jiangxi Province(2010GZN0037)
文摘In order to study the inhibition mechanism of antifungal monomers DZP8 produced by streptomyces 702 strain against Rhizoctonia solani, the effects of DZP8 on mycelial morphology were investigated under light microscope, and the effects of DZP8 on mycelial inclusion leakage and cell membrane damage of myceli-um were determined. The results showed that DZP8 caused a series of changes in mycelial morphology of R. solani in liquid culture condition. DZP8 treatments with concentrations of 1.81 and 3.35 μg/mL for 24 h caused big vacuole, rough surface and more inclusions of mycelium. With the treatment time prolonging, the mycelium distorted and appeared irregular constriction. DZP8 treatment with concentration of 20.10 μg/mL led to the increase of conductivity of mycelium culture liquid, leakage of soluble sugar and protein, and the lipid peroxidation of mycelium membrane. It was found that DZP8 at a very low concentration could cause changes of mycelial morphology of R. solani, while only a certain concentration could cause significant damage to cell membrane. This indicated that cell membrane might be one of the action sites of DZP8, and it might have other action sites or mechanism.
基金supported by the Fundamental Research Funds for the Central Universities(No.K20220145).
文摘Phosphorus-containing compounds are considered as the potential alternatives of traditional inhibitors for suppressing the formation of polychlorinated dibenzo-p-dioxins and dibenzofurans(PCDD/Fs),but the suppression characteristics are scarcely studied.In this study,ammonium dihydrogen phosphate(ADP)was selected as the inhibitor to inhibit the PCDD/F formation via de novo synthesis at 350℃.The influence of oxygen content and addition method on PCDD/F inhibition was systematically investigated by means of statistical analysis and morphological characterization.The results showed that oxygen enhanced the formation of PCDD/Fs from 1470 ng g^(−1)(9.78 ng I-TEQ g^(−1))to 2110 ng g^(−1)(14.8 ng I-TEQ g^(−1)).ADP significantly inhibited the PCDD/F formation,with inhibition efficiencies ranging from 82.0%to 97.7%.Herein,a higher oxygen content and the premixed way intensified the suppression effect.Dibenzo-p-dioxin(DD)/dibenzofuran(DF)chlorination was proven to be effectively suppressed while chlorophenol(CP)route was not obviously influenced.With the addition of ADP,Cl source was significantly reduced and the formation of organic Cl was effectively inhibited.Also,it decreased the proportion of C–O/C=N and C=O,revealing the efficient inhibition of carbon oxidation.Meanwhile,the formation of copper phosphate and copper pyrophosphate was observed in XPS(X-ray photoelectron spectroscopy)spectra,indicating that the catalytic metal Cu was chelated and passivated by ADP.The premixed way had a better effect on reducing Cl resources,inhibiting oxidation and chelating metals,due to the direct contact with inhibitor.However,the separation method could only depend on the decomposed gases,resulting in a lower inhibition efficiency.
文摘The advantages and disadvantages of organic antioxidant and inorganic salt on suppressing coal oxidation were analyzed on the basis of the theory that coal oxidation mechanisms can be attributed to the free radical chain-type reaction mechanism. The inhibition curves on suppressing coal oxidation of the different type and different concentration of organic antioxidant and inorganic salt were given through experimental study and data processing. Then some conclusions can be gained from the experimental study combining with theoretical analysis. First the inhibition mechanism of the organic antioxidant and inorganic salt is different. The former is that the chemical action is the dominant position. It can be called as the chain termination theory because the free radical is captured during coal oxidation. And the later is that the physical effect is the dominant position. It can be called as the decreasing-temperature theory because the liquid membrane which was formed by the inorganic salt can make coal body be the state of wetness and prevent oxygen from coal surface. Second the inhibition effect of the organic antioxidant is higher than the inorganic salt in the later period. But it is lower in the early period.
文摘In comparing reference unification to reference linking,the authors found that reference linking yield similar result as that of reference unification.An investigative study was conducted by these authors at Chinese Science Citation Database(CSCD)of National Science Library(NSL)of the ChineseAcademy of Sciences(CAS),it was found that there were three inhibiting elements in invoking a reference unification solution and the same is true for a reference linking solution.Firstly,it was difficult to define a minimum set of data elements for matching.Secondly,it had a problem of data inaccuracy and/or data incompleteness.Thirdly,it was hard to determine an appropriate linking result that produced the desired document for the user.Thus these authors suggest that getting Digital Object Identifier(DOI)for each journal article is a good way to bring about reference unification and also to improve metadata quality simultaneously at the same time.Therefore,DOI has a pivotal role to play in terms of bringing about reference unification and/or a reference linking.
基金Supported by the National Natural Science Foundation of China(5215000105)Huo Yingdong Education Foundation(171043).
文摘By analyzing the corrosion of phosphate completion fluid on the P110 steel at 170 °C, the high-temperature corrosion mechanism of phosphate completion fluid was revealed, and a corrosion inhibition method by membrane transformation was proposed and an efficient membrane-forming agent was selected. Scanning electron microscope (SEM) images, X-ray energy spectrum and X-ray diffraction results were used to characterize the microscopic morphology, elemental composition and phase composition of the precipitation membrane on the surface of the test piece. The effect and mechanism of corrosion inhibition by membrane transformation were clarified. The phosphate completion fluid eroded the test piece by high-temperature water vapor and its hydrolyzed products to form a membrane of iron phosphate corrosion product. By changing the corrosion reaction path, the Zn2+ membrane-forming agent could generate KZnPO4 precipitation membrane with high temperature resistance, uniform thickness and tight crystal packing on the surface of the test piece, which could inhibit the corrosion of the test piece, with efficiency up to 69.63%. The Cu2+ membrane-forming agent electrochemically reacted with Fe to precipitate trace elemental Cu on the surface of the test piece, thus forming a protective membrane, which could inhibit metal corrosion, with efficiency up to 96.64%, but the wear resistance was poor. After combining 0.05% Cu2+ and 0.25% Zn2+, a composite protective membrane of KZnPO4 crystal and elemental Cu was formed on the surface of the test piece. The corrosion inhibition efficiency reached 93.03%, which ensured the high corrosion inhibition efficiency and generated a precipitation membrane resistant to temperature and wear.