Machado-Joseph disease,or spinocerebellar ataxia type 3(SCA3),represents the most common autosomal dominant cerebellar ataxia worldwide.Despite its progressive and debilitating nature,disease-modifying therapies remai...Machado-Joseph disease,or spinocerebellar ataxia type 3(SCA3),represents the most common autosomal dominant cerebellar ataxia worldwide.Despite its progressive and debilitating nature,disease-modifying therapies remain elusive.Repetitive transcranial magnetic stimulation(rTMS)has emerged as a promising non-invasive intervention;however,its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding.A recent landmark study published in Brain Stimulation by Chen et al.addressed these challenges by combining a high-dose intermittent theta-burst stimulation(iTBS)protocol with concurrent transcranial magnetic stimulation-electroencephalography(TMS-EEG).This commentary provides an in-depth analysis of their findings,highlighting the restoration of cerebello-cortical inhibition(CBI)as a key therapeutic mechanism.Furthermore,we discuss the broader implications of this work,proposing that future translational research should integrate accelerated iTBS(aiTBS)paradigms,cortical response measurements(CRM),and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.展开更多
[Objectives]To evaluate the in vitro antibacterial,antioxidant,andα-glucosidase inhibitory activities of the ethanol total extract and four different polarity fractions(n-butanol,ethyl acetate,petroleum ether,and wat...[Objectives]To evaluate the in vitro antibacterial,antioxidant,andα-glucosidase inhibitory activities of the ethanol total extract and four different polarity fractions(n-butanol,ethyl acetate,petroleum ether,and water)of Pilea peltata Hance,so as to provide a reference for its further development and research.[Methods]The antibacterial activity of P.peltata was evaluated in vitro by determining the minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of its ethanol total extract and four different polarity fractions against seven test bacterial strains using the broth microdilution method.The in vitro antioxidant activity was investigated through DPPH radical,hydroxyl radical,and superoxide anion radical scavenging assays,with vitamin C(Vit C)as the positive control and the half maximal scavenging concentration(IC 50)as the evaluation indicator.The in vitroα-glucosidase inhibitory activity was assessed by measuring the peak area of p-nitrophenol(PNP),the hydrolysis product of 4-nitrophenylα-D-glucopyranoside(PNPG),via high-performance liquid chromatography(HPLC),using the half maximal inhibitory concentration(IC 50)as the evaluation indicator.[Results]Both the ethanol total extract and the four different polarity fractions of P.peltata exhibited significant in vitro anti-Streptococcus pneumoniae activity.The DPPH radical scavenging capacities of the ethanol total extract and the various fractions were all weaker than that of VitC,with the order of efficacy being:n-butanol fraction>ethanol total extract>ethyl acetate fraction>petroleum ether fraction>aqueous fraction.For hydroxyl radical scavenging activity,the efficacy order of P.peltata fractions was:n-butanol extract>ethyl acetate extract>ethanol total extract>petroleum ether extract>aqueous extract.Notably,the n-butanol fraction(IC 50=0.068±0.001)demonstrated stronger activity than VitC(IC 50=0.097±0.001).The activity of the ethyl acetate fraction(IC 50=0.096±0.004)was comparable to that of VitC(IC 50=0.097±0.001).The superoxide anion scavenging capacities of the ethanol total extract and different polarity fractions from P.peltata were all weaker than that of VitC,with the order of efficacy being:n-butanol fraction>ethyl acetate fraction>ethanol total extract>petroleum ether fraction>aqueous fraction.The ethanol total extract and aqueous fraction of Pilea peltata showed no significant in vitroα-glucosidase inhibitory activity.Compared with the acarbose group,the IC 50 values of the ethyl acetate fraction and the n-butanol fraction both showed highly significant differences(P<0.01).[Conclusions]This study provides an experimental basis for the pharmacodynamic study and active component study of P.peltata.展开更多
Two supramolecular organic frameworks(SOFs)have been constructed from the co-assembly of biimidazolium-derived octacationic components and cucurbit[8]uril in water.Dynamic light scattering and ^(1)H NMR experiments re...Two supramolecular organic frameworks(SOFs)have been constructed from the co-assembly of biimidazolium-derived octacationic components and cucurbit[8]uril in water.Dynamic light scattering and ^(1)H NMR experiments reveal that both SOFs can undergo reversible assembly and disassembly at room temperature.One of the SOFs displays unprecedently high maximum tolerated dose of 120 mg/kg with mice,which improves by 40%compared with the highest value of the reported SOFs.In vitro and in vivo tests show that the SOF can adsorb doxorubicin and overcome the resistance of multidrugresistant MDR A549/ADR tumor cells to realize intracellular delivery,leading to enhanced antitumor efficacy.Moreover,it can also completely inhibit the posttreatment phototoxicity of photofrin and fully neutralize the anticoagulation of both unfractionated heparin and low molecular weight heparins through efficient inclusion and elimination or sequestration mechanism.As the first examples that undergo roomtemperature reversible assembly and disassembly,the new SOFs in principle allow for quantitative analysis of the molecular components in the body that is prerequisite for preclinical evaluation in the future.展开更多
In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tum...In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tumors,or strokes,noting deficits,and inferring what functions certain brain regions may be responsible for.This approach exemplifies a deletion heuristic,where the absence of a specific function reveals insights about the underlying structures or mechanisms responsible for it.By observing what is lost when a particular brain region is damaged,throughout the history of the field,neurologists have pieced together the intricate relationship between anatomy and function.展开更多
Background:Neonatal-onset multisystem inflammatory disease is characterized by fever,urticarial rash,aseptic meningitis,deforming arthropathy,hearing loss,and mental retardation.Many patients have mutations in the col...Background:Neonatal-onset multisystem inflammatory disease is characterized by fever,urticarial rash,aseptic meningitis,deforming arthropathy,hearing loss,and mental retardation.Many patients have mutations in the cold-induced autoinflammatory syndrome 1(CIAS1)gene,encoding cryopyrin,a protein that regulates inflammation.展开更多
Rosa roxburghii seeds are by-products of R.roxburghii processing,and their protein hydrolysates(RTSPHs)were found to possess a variety of biological activities.This study aimed to rapidly identify pancreatic lipase(PL...Rosa roxburghii seeds are by-products of R.roxburghii processing,and their protein hydrolysates(RTSPHs)were found to possess a variety of biological activities.This study aimed to rapidly identify pancreatic lipase(PL)and cholesterol esterase(CE)inhibitory peptides in RTSPHs and to elucidate their molecular mechanisms by combining peptidomics and virtual screening.The simulated intestinal environment worsened the peptide’s inhibition of PL but catalyzed the inhibition of CE.The fraction less than 3 kDa in RTSPHs was found to have the highest PL/CE inhibitory activity,among which 17 promising inhibitory peptides were identified and screened by peptidomics and virtual screening.LFCMH,RIPAGSPF,and YFRPR showed good inhibitory abilities against both PL and CE.Molecular docking showed that peptides inhibited PL and CE mainly by hydrogen bonding and hydrophobic interactions with residues in the active site and surface loop.Inhibition kinetic revealed that the peptides were competitive and mixed-type inhibitors of PL/CE.Further,the three peptides,LFCMH,RIPAGSPF,and YFRPR,could effectively inhibit 3T3-L1 preadipocytes differentiation,increase high-density lipoprotein cholesterol content and decrease low-density lipoprotein cholesterol content.This study suggests that combining peptidomics with virtual screening is an effective strategy for rapid screening of PL/CE inhibitory peptides.展开更多
The influence of NaF on the microstructure,composition and corrosion performance of WE43 Mg alloy in 3.5 wt.%NaCl solution was systematically investigated by means of SEM,TEM,EPMA,XRD,XPS and electrochemical measureme...The influence of NaF on the microstructure,composition and corrosion performance of WE43 Mg alloy in 3.5 wt.%NaCl solution was systematically investigated by means of SEM,TEM,EPMA,XRD,XPS and electrochemical measurements.It was proved that NaF is an effective inhibitor for WE43 Mg alloy and the highest inhibition efficiency is 92.6%at its concentration of 40 mmol/L in neutral NaCl solution.The dissolution of WE43 alloy is inhibited by formation and deposition of a dense and protective double-layered corrosion film by chemical reaction between corrosion inhibitor and dissolved Mg^(2+).The microstructure and composition of this double-layered corrosion film were investigated by FIB and TEM.The outer layer of the corrosion film is found to be composed of NaMgF_(3),MgF_(2)and MgO,while the inner layer mainly consists of MgO and MgF_(2).展开更多
Ethyl-bis(octadecyl dipolyoxyethylene ammonium chloride)(E-BODAC)was a novel quaternary Gemini surfactant and was first found and identified as an excellent inhibitor with excellent surface activity and suitability.Th...Ethyl-bis(octadecyl dipolyoxyethylene ammonium chloride)(E-BODAC)was a novel quaternary Gemini surfactant and was first found and identified as an excellent inhibitor with excellent surface activity and suitability.The ethoxy group enhances its hydrophilicity,and facilitates a dense adsorption film on metal surface.The inhibitive action and mechanism of E-BODAC on cold rolled steel(CRS)in HCl and H_(2)SO_(4) solutions was studied in detail by theoretical and experimental methods.The surface activity and degree of polymerization of the surfactant are tightly related to the anti-corrosion properties.HCl has a lower critical micelle concentration(CMC)than H_(2)SO_(4) solutions.The hydrophilic group in E-BODAC is the pre-ferred site for donating and accepting electrons,with chemical interactions occurring among O,C,and Fe.The addition of E-BODAC obeys Langmuir isotherm,which can drastically reduce the diffusion of H_(3)O^(+),Cl^(-)/SO_(4)^(2-).E-BODAC has superior corrosion inhibition performance and lower dosage,and the inhibition efficiency for CRS reaches 92.9%in 1.0 M HCl with only 10 mg L^(-1) of E-BODAC and 91.5%in 0.50 M H_(2)SO_(4).The inhibition is through physical and chemical adsorption to form a protective film that covers the reaction site,blocking the corrosion reaction.CLSM,SEM,AFM,XPS,and time-of-flight secondary ion mass spectrometer(TOF-SIMS)provide evidence of the adsorption of E-BODAC,efficiently slowing down the corrosion of CRS surface.E-BODAC always shows higher efficiency in HCl than in H_(2)SO_(4),which is attributed to the re-dissolution of the adsorbed film in the H_(2)SO_(4) solution.Besides,SO42-ions are larger and migrate more slowly than Cl^(-)ions,resulting in weak adsorption on the metal surface.The assess-ment of E-BODAC's suitability and durability in different corrosive environments provides the opportunity to determine its optimum conditions and applicability to maximize its corrosion inhibition effect.展开更多
Wellbore instability is a critical challenge in drilling operations,especially in shale formations where interaction with water-based drilling fluids can result in significant operational risks and increased costs.To ...Wellbore instability is a critical challenge in drilling operations,especially in shale formations where interaction with water-based drilling fluids can result in significant operational risks and increased costs.To address these issues,shale chemical inhibitors have become a crucial component in drilling fluid formulations to ensure wellbore integrity.Although several researchers have published some reviews on shale inhibitors,the latest advancements in shale chemical inhibitors over the past five years still warrant further discussion and summary.This literature review provided a comprehensive examination of wellbore instability,focusing on the patterns of instability encountered in drilling and the various shale chemical inhibitors employed to mitigate these issues.The review explored the utilization of shale inhibitors in water-based drilling fluids,and the discussion highlights the timeline evolution of these inhibitors,from traditional salts and polymers to advanced ionic liquids and deep eutectic solvents.Additionally,the mechanisms of shale chemical inhibitors are summarized to guide their application.The objective of this paper is to provide a detailed review of the development of shale chemical inhibitors in water-based drilling fluids,aiming to fully appreciate shale hydration inhibition methods and to provide insights into the selection and optimization of shale inhibitors to improve wellbore stability in challengingdrilling environments.展开更多
Ionic liquids(ILs),recognized for their negligible vapor pressure,thermal stability,and structural tailorability,offer targeted inhibition of clay expansion.Compared to ILs,polyionic liquids(PILs)possess stronger mech...Ionic liquids(ILs),recognized for their negligible vapor pressure,thermal stability,and structural tailorability,offer targeted inhibition of clay expansion.Compared to ILs,polyionic liquids(PILs)possess stronger mechanical properties and adsorption capabilities,showing even greater potential in inhibiting clay swelling.In this work,we synthesized and characterized an imidazole-based ionic liquid(IL-NH_(2)),a polyionic liquid(PIL-ABHIm),and a PIL/IL combination.Their inhibitory performance was rigorously evaluated under simulated drilling conditions through immersion tests,linear swelling tests,among others.Additionally,the mechanisms underlying their interaction with clay minerals were elucidated through contact angle measurements,Fourier-transform infrared spectroscopy,X-ray diffraction(XRD),Zeta potential analysis,and molecular electrostatic potential(MEP)analysis.This work demonstrates that IL-NH_2inhibits osmotic hydration by altering the interlayer structure of the clay,while PIL-ABHIm reduces surface hydration by forming a hydrophobic barrier on the clay surface.PIL/IL combines both mechanisms,significantly enhancing the stability of clay through the dual mechanisms of cation exchange and hydrophobic barriers.These findings reveal an innovative mechanism by which PIL/IL combination inhibits clay hydration and swelling,providing a scientific foundation for their application in drilling fluids.展开更多
The inhibitory properties of rapeseed cake meal extract(RCME)on the corrosion of cold rolled steel(CRS)in trichloroacetic acid(TCA)were systematically investigated using gravimetric,electrochemical,surface characteriz...The inhibitory properties of rapeseed cake meal extract(RCME)on the corrosion of cold rolled steel(CRS)in trichloroacetic acid(TCA)were systematically investigated using gravimetric,electrochemical,surface characterizations and theoretical calculations.The results demonstrate that RCME exhibits excellent inhibitory performance with a maximum inhibition efficiency of 92.7%for 100 mg L−1 RCME at 20℃.The adsorption of RCME obeys Langmuir isotherm at 20 and 30℃,Temkin isotherm at 40℃,and Freundlich isotherm at 50℃.RCME acts as a cathodic inhibitor.The charge transfer resistance is increased with the addition of RCME,while the double-layer capacitance decreases.SEM,AFM,CLSM,XPS,XRD and TOF-SIMS analyses confirm that the active components in RCME adsorb onto the surface of CRS,forming a protective film that effectively inhibits the corrosion of CRS by TCA.Along with the increase in the concentration of RCME,the surface tension of the inhibited solution gradually decreases,while the electrical conductivity increases before stabilizing.HPLC-MS and FTIR analyses reveal rutin,linolenic acid,linoleic acid and adenine are the effective substances in RCME.Quantum chemical(QC)calculations and molecular dynamic(MD)simulations indicate that the active centers of the effective inhibitor molecules are predominantly located on benzene rings,O-or N-containing heterocyclic rings,and functional groups such as C=O and C=C.Additionally,their main chains adsorb onto the Fe(001)surface in an approximately flat manner,involving both chemical and physical adsorption processes.展开更多
Background:Gastric cancer(GC)remains a global health burden and is often characterized by heterogeneous molecular profiles and resistance to conventional therapies.The phosphoinositide 3-kinase and PI3K and Janus kina...Background:Gastric cancer(GC)remains a global health burden and is often characterized by heterogeneous molecular profiles and resistance to conventional therapies.The phosphoinositide 3-kinase and PI3K and Janus kinase(JAK)signal transducer and activator of transcription(JAK-STAT)pathways play pivotal roles in GC progression,making them attractive targets for therapeutic interventions.Methods:This study applied a computational and molecular dynamics simulation approach to identify and characterize SBL-JP-0004 as a potential dual inhibitor of JAK2 and PI3KCD kinases.KATOIII and SNU-5 GC cells were used for in vitro evaluation.Results:SBL-JP-0004 exhibited a robust binding affinity for JAK2 and PI3KCD kinases,as evidenced by molecular docking scores and molecular dynamics simulations.Binding interactions and Gibbs binding free energy estimates confirmed stable and favorable interactions with target proteins.SBL-JP-0004 displayed an half-maximal inhibitory concentration(IC_(50))value of 118.9 nM against JAK2 kinase and 200.9 nM against PI3KCD enzymes.SBL-JP-0004 exhibited potent inhibition of cell proliferation in KATOIII and SNU-5 cells,with half-maximal growth inhibitory concentration(GI50)values of 250.8 and 516.3 nM,respectively.A significant elevation in the early phase apoptosis(28.53%in KATOIII cells and 26.85%in SNU-5 cells)and late phase apoptosis(17.37%in KATOIII cells and 10.05%in SNU-5 cells)were observed with SBL-JP-0004 treatment compared to 2.1%and 2.83%in their respective controls.Conclusion:The results highlight SBL-JP-0004 as a promising dual inhibitor targeting JAK2 and PI3KCD kinases for treating GC and warrant further preclinical and clinical investigations to validate its utility in clinical settings.展开更多
Correction to:Neurosci.Bull.December,2016,32(6):577–584.https://doi.org/10.1007/s12264-016-0068-z In this article,in Fig 5A,the picture of the Vector+Nogo-66 group was incorrect and should have appeared as shown below.
Objective:To construct a pH-responsive paclitaxel(PTX)-exosome composite nanocarrier and investigate its inhibitory effect on the proliferation of endometrial cancer cells(HEC-1A).Methods:PTX was loaded into exosomes ...Objective:To construct a pH-responsive paclitaxel(PTX)-exosome composite nanocarrier and investigate its inhibitory effect on the proliferation of endometrial cancer cells(HEC-1A).Methods:PTX was loaded into exosomes derived from adipose mesenchymal stem cells using the thin-film hydration method,and modified with polyethylene glycol-polylactic-co-glycolic acid(PEG-PLGA)to form nanocarriers(PTX-Exo-NPs).The particle size and morphology were detected by nanoparticle size and Zeta potential analyzer;drug encapsulation efficiency and drug loading capacity were determined by high-performance liquid chromatography;drug release behavior was evaluated in vitro under simulated acidic(pH 5.5)and physiological(pH 7.4)conditions;MTT assay and flow cytometry were used to detect the effects of the carrier on the proliferation,apoptosis,and cell cycle distribution of HEC-1A cells.Results:PTX-Exo-NPs exhibited a uniform spherical shape with a particle size of(128.5±5.2)nm,PTX encapsulation efficiency of 92.3%±2.1%,and drug loading capacity of 15.6%±0.8%.Drug release rate in the acidic environment(85.3%±2.1%within 72 h)was significantly higher than that in the physiological environment(48.0%±1.7%).In vitro experiments demonstrated that the proliferation inhibition rate of PTX-Exo-NPs on HEC-1A cells was higher than that of free PTX,with a lower IC50(0.64μM vs 4.70μM),and could induce cell apoptosis(apoptosis rate:28.7%±2.1%vs 14.2%±1.5%)and promote cell cycle arrest(G_2/M rate:45.3%±3.2%).Conclusion:PTX-Exo-NPs exhibit pH-responsive characteristics,which can target drug release through the acidic microenvironment,enhance the proliferation inhibition and pro-apoptotic effect on endometrial cancer cells,thus serving as a potential strategy for targeted therapy of endometrial tumors.展开更多
The efficient recovery of fluorite is paid more and more attention with the increasing application especially in strategic emerging industries.In this study,acrylic acid-2-acrylamido-2-methylpropane sulfonic acid copo...The efficient recovery of fluorite is paid more and more attention with the increasing application especially in strategic emerging industries.In this study,acrylic acid-2-acrylamido-2-methylpropane sulfonic acid copolymer(AAAMPS)was first used as the depressant in fluorite flotation,and its effect on the flotation separation of fluorite and dolomite in sodium oleate(NaOL)system was investigated.The depression mechanism was analyzed by contact angle measurement,zeta potential test,FTIR and XPS analyses.The micro-flotation test results showed that dolomite can be inhibited in fluorite flotation system in the addition of 2 mg/L AA-AMPS and 20 mg/L NaOL at pH 10.The CaF_(2) grade increased from 49.85%in the artificial mixed mineral to 89.60%in the fluorite concentrate.The depression mechanism indicated that AA-AMPS could adsorb strongly on dolomite surface by the chelation with Ca and Mg active sites.Moreover,the further adsorption of NaOL on dolomite surface was prevented by the AA-AMPS adsorption,but that on fluorite surface was little affected,thereby increasing the difference in the hydrophobicity and floatability of the two minerals.展开更多
In the treatment of breast cancer,the combination of glutamine metabolism inhibition and photothermal therapy(PTT)is gaining increasing attention.This study developed a Janus nanomotor to enhance permeability in tumor...In the treatment of breast cancer,the combination of glutamine metabolism inhibition and photothermal therapy(PTT)is gaining increasing attention.This study developed a Janus nanomotor to enhance permeability in tumor tissues for nanomedicine applications by using mesoporous organic silica(PMO)anisotropic ally grown on the surface of the platinum(Pt)nanoparticles(PMO@Pt).The prepared PMO@Pt had unique Janus structure with an average size of approximately 236 nm.The loading capacity of V9302 was evaluated to be 44.37%when the mass ratio of V9302 to PMO@Pt was maintained at 2.0 and in vitro release studies demonstrated that acidic environments significantly enhanced the drug release.Then this nanomotor was loaded with perfluorohexane(PFH),a phase-change material,and the glutamine inhibitor V9302(denoted as Janus PMO@Pt@PFH@V9302,JPV).Janus PMO@Pt@PFH(JPP)nanomotors demonstrated enhanced fluorescence intensity and distribution within 3D tumor spheroids compared to Janus PMO@Pt nanomotors,attributed to the photothermal-induced phase change of PFH.The nanomotors exhibited high biocompatibility,with cell viability exceeding 98%at high concentrations.However,the incorporation of V9302 into the nanomotors(JPV)significantly reduced 4T1 cell viability under laser irradiation,indicating a cytotoxic effect resulting from the synergy between photothermal therapy and glutamine metabolism inhibition.In vivo,JPV nanomotors effectively inhibited tumor growth and induced apoptosis without causing significant systemic toxicity,showcasing their potential as a therapeutic agent for breast cancer.This integrated nanomotor offers a promising approach for enhanced ultrasound imaging and photothermal therapy in cancer treatment.展开更多
Background Polygalacturonase inhibiting proteins(PGIPs)play a pivotal role in plant defense against plant patho-gens by inhibiting polygalacturonase(PG),an enzyme produced by pathogens to degrade plant cell wall pecti...Background Polygalacturonase inhibiting proteins(PGIPs)play a pivotal role in plant defense against plant patho-gens by inhibiting polygalacturonase(PG),an enzyme produced by pathogens to degrade plant cell wall pectin.PGIPs,also known as leucine-rich repeat pathogenesis-related(PR)proteins,activate the host’s defense response upon interaction with PG,thereby reinforcing the host defense against plant pathogens attacks.In Egyptian or extra-long staple cotton(Gossypium barbadense),the interaction between PGIP and PG is one of the crucial steps in the defense mechanism against major pathogens such as Xanthomonas citri pv.malvacearum and Alternaria mac-rospora,which are responsible for bacterial leaf blight and leaf spot diseases,respectively.Results To unravel the molecular mechanisms underlying these PR proteins,we conducted a comprehensive study involving molecular modeling,protein-protein docking,site-specific double mutation(E169G and F242K),and molec-ular dynamics simulations.Both wild-type and mutated cotton PGIPs were examined in the interaction with the PG enzyme of a bacterial and fungal pathogen.Our findings revealed that changes in conformations of double-mutated residues in the active site of PGIP lead to the inhibition of PG binding.The molecular dynamics simulation studies provide insights into the dynamic behaviour and stability of the PGIP-PG complexes,shedding light on the intricate details of the inhibitory and exhibitory mechanism against the major fungal and bacterial pathogens of G.barbadense,respectively.Conclusions The findings of this study not only enhance our understanding of the molecular interactions between PGs of Xanthomonas citri pv.malvacearum and Alternaria macrospora and PGIP of G.barbadense but also pre-sent a potential strategy for developing the disease-resistant cotton varieties.By variations in the binding affinities of PGs through specific mutations in PGIP,this research offers promising avenues for the development of enhanced resistance to cotton plants against bacterial leaf blight and leaf spot diseases.展开更多
To address the critical need for safer and cleaner explosion suppression technologies in industrial settings,the suppression differences and mechanisms of the flame acceleration characteristics of CH_(4),LPG and H_(2)...To address the critical need for safer and cleaner explosion suppression technologies in industrial settings,the suppression differences and mechanisms of the flame acceleration characteristics of CH_(4),LPG and H_(2) explosions by N_(2)-water mist two-phase medium were investigated.The flame acceleration characteristics and suppression mechanism of methane,LPG and H_(2) explosions in N_(2)-water mist twophase medium were studied qualitatively and quantitatively from both experimental and simulation aspects.The experimental results show that compared with single N_(2) or water mist,the N_(2)-water mist two-phase medium is more effective in reducing the flame propagation speed and delaying the formation of flame hydrodynamic structure,thus slowing down the flame acceleration characteristics.The simulation results show that this two-phase medium exhibits a strong inhibitory effect on the thermal diffusion instability of CH_(4) and LPG,and significantly weakens the hydrodynamic instability of CH_(4),LPG,and H_(2) simultaneously.Mechanistic analysis confirms that the N_(2)-water mist two-phase medium has both chemical and physical inhibitory effects,among which the physical inhibition plays a dominant role.In addition,the study reveals a linear correlation between the concentration of H radicals in the three combustible gases and the laminar burning velocity.Moreover,this two-phase medium can significantly reduce the reaction rate of the H radical chain reaction,thereby effectively suppressing the laminar burning velocity.展开更多
Inflammation plays a crucial role in the initiation and progression of sepsis and induces alterations in brain neurotransmission, thereby contributing to the development of sepsis-associated encephalopathy(SAE).Parval...Inflammation plays a crucial role in the initiation and progression of sepsis and induces alterations in brain neurotransmission, thereby contributing to the development of sepsis-associated encephalopathy(SAE).Parvalbumin(PV) interneurons are pivotal contributors to cognitive processes and have been implicated in various central nervous system dysfunctions, including SAE. Oxytocin, known for its ability to augment the firing rate of gamma-aminobutyric acid(GABA)-ergic interneurons and directly stimulate inhibitory interneurons to enhance the tonic inhibition of pyramidal neurons, has prompted an investigation into its potential therapeutic effects on cognitive dysfunction in SAE. In the current study, we administered intranasal oxytocin to SAE mice induced by lipopolysaccharide. Behavioral assessments, including open field, Y-maze, and fear conditioning, were used to evaluate cognitive performance. Golgi staining revealed hippocampal synaptic deterioration, local field potential recordings showed weakened gamma oscillations, and immunofluorescence staining demonstrated decreased PV expression in the cornu ammonis 1(CA1) region of the hippocampus following lipopolysaccharide treatment, all of which were alleviated by oxytocin administration. Furthermore, immunofluorescence staining of PV co-localization with vesicular glutamate transporter 1 or vesicular GABA transporter indicated a balanced excitation/inhibition effect of neurotransmitters on PV interneurons after oxytocin administration in the SAE mice, leading to an improved cognitive function. In conclusion, oxytocin treatment improved cognitive function by increasing the number of PV^(+) neurons in the hippocampal CA1 region, restoring the balance of excitatory/inhibitory synaptic transmission on PV interneurons, and enhancing hippocampal CA1 local field potential gamma oscillations. These findings suggest a potential mechanism underlying the beneficial effects of oxytocin in SAE.展开更多
The rising prevalence of multidrug-resistant pathogens poses a substantial threat to global healthcare systems,demanding urgent therapeutic interventions.Microorganisms exhibit diverse resistance mechanisms against va...The rising prevalence of multidrug-resistant pathogens poses a substantial threat to global healthcare systems,demanding urgent therapeutic interventions.Microorganisms exhibit diverse resistance mechanisms against various classes of antibiotics,highlighting the urgent need to discover novel antimicrobial agents for combating bacterial infections.Anti-virulence therapy has emerged as a promising therapeutic strategy that neutralizes pathogens by targeting their virulence determinants.The strategies for screening virulence arresting drugs(VADs)in bacteria represent a multifaceted approach that involves elucidating molecular pathogenesis mechanisms of bacterial pathogenicity,identifying evolutionarily conserved virulence factors across different pathogens,and employing integrated approaches combining in silico prediction with experimental validation.Recent technological advancements have established standardized protocols for effective identification and validation of anti-virulence compounds.This review systematically examines contemporary screening methodologies,primarily focusing on quorum-sensing disruption and biofilm suppression strategies,including in silico screening,activity-based screening with bioassays,in vitro and in vivo models.Additionally,we emphasize the imperative for standardized preclinical validation through physiologically relevant animal models,while proposing framework recommendations for developing next-generation VAD screening platforms.This synthesis not only outlines current best practices but also proposes innovative avenues for future antimicrobial discovery research.展开更多
基金supported by grants from the Open Research Fund of the Zhejiang Key Laboratory of Precision Psychiatry(2025A2)the Natural Science Foundation of Zhejiang Province(LY23C090002)。
文摘Machado-Joseph disease,or spinocerebellar ataxia type 3(SCA3),represents the most common autosomal dominant cerebellar ataxia worldwide.Despite its progressive and debilitating nature,disease-modifying therapies remain elusive.Repetitive transcranial magnetic stimulation(rTMS)has emerged as a promising non-invasive intervention;however,its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding.A recent landmark study published in Brain Stimulation by Chen et al.addressed these challenges by combining a high-dose intermittent theta-burst stimulation(iTBS)protocol with concurrent transcranial magnetic stimulation-electroencephalography(TMS-EEG).This commentary provides an in-depth analysis of their findings,highlighting the restoration of cerebello-cortical inhibition(CBI)as a key therapeutic mechanism.Furthermore,we discuss the broader implications of this work,proposing that future translational research should integrate accelerated iTBS(aiTBS)paradigms,cortical response measurements(CRM),and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.
基金Supported by Scientific Research Project of the Guangxi Zhuang Autonomous Region Administration of Traditional Chinese Medicine(GXZYA20220105).
文摘[Objectives]To evaluate the in vitro antibacterial,antioxidant,andα-glucosidase inhibitory activities of the ethanol total extract and four different polarity fractions(n-butanol,ethyl acetate,petroleum ether,and water)of Pilea peltata Hance,so as to provide a reference for its further development and research.[Methods]The antibacterial activity of P.peltata was evaluated in vitro by determining the minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of its ethanol total extract and four different polarity fractions against seven test bacterial strains using the broth microdilution method.The in vitro antioxidant activity was investigated through DPPH radical,hydroxyl radical,and superoxide anion radical scavenging assays,with vitamin C(Vit C)as the positive control and the half maximal scavenging concentration(IC 50)as the evaluation indicator.The in vitroα-glucosidase inhibitory activity was assessed by measuring the peak area of p-nitrophenol(PNP),the hydrolysis product of 4-nitrophenylα-D-glucopyranoside(PNPG),via high-performance liquid chromatography(HPLC),using the half maximal inhibitory concentration(IC 50)as the evaluation indicator.[Results]Both the ethanol total extract and the four different polarity fractions of P.peltata exhibited significant in vitro anti-Streptococcus pneumoniae activity.The DPPH radical scavenging capacities of the ethanol total extract and the various fractions were all weaker than that of VitC,with the order of efficacy being:n-butanol fraction>ethanol total extract>ethyl acetate fraction>petroleum ether fraction>aqueous fraction.For hydroxyl radical scavenging activity,the efficacy order of P.peltata fractions was:n-butanol extract>ethyl acetate extract>ethanol total extract>petroleum ether extract>aqueous extract.Notably,the n-butanol fraction(IC 50=0.068±0.001)demonstrated stronger activity than VitC(IC 50=0.097±0.001).The activity of the ethyl acetate fraction(IC 50=0.096±0.004)was comparable to that of VitC(IC 50=0.097±0.001).The superoxide anion scavenging capacities of the ethanol total extract and different polarity fractions from P.peltata were all weaker than that of VitC,with the order of efficacy being:n-butanol fraction>ethyl acetate fraction>ethanol total extract>petroleum ether fraction>aqueous fraction.The ethanol total extract and aqueous fraction of Pilea peltata showed no significant in vitroα-glucosidase inhibitory activity.Compared with the acarbose group,the IC 50 values of the ethyl acetate fraction and the n-butanol fraction both showed highly significant differences(P<0.01).[Conclusions]This study provides an experimental basis for the pharmacodynamic study and active component study of P.peltata.
基金the National Natural Science Foundation of China(No.21921003 for Z.T.L.and 22201293 for S.B.Y.)Shanghai Sailing Program(No.22YF1458300 for S.B.Y.)for financial support。
文摘Two supramolecular organic frameworks(SOFs)have been constructed from the co-assembly of biimidazolium-derived octacationic components and cucurbit[8]uril in water.Dynamic light scattering and ^(1)H NMR experiments reveal that both SOFs can undergo reversible assembly and disassembly at room temperature.One of the SOFs displays unprecedently high maximum tolerated dose of 120 mg/kg with mice,which improves by 40%compared with the highest value of the reported SOFs.In vitro and in vivo tests show that the SOF can adsorb doxorubicin and overcome the resistance of multidrugresistant MDR A549/ADR tumor cells to realize intracellular delivery,leading to enhanced antitumor efficacy.Moreover,it can also completely inhibit the posttreatment phototoxicity of photofrin and fully neutralize the anticoagulation of both unfractionated heparin and low molecular weight heparins through efficient inclusion and elimination or sequestration mechanism.As the first examples that undergo roomtemperature reversible assembly and disassembly,the new SOFs in principle allow for quantitative analysis of the molecular components in the body that is prerequisite for preclinical evaluation in the future.
文摘In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tumors,or strokes,noting deficits,and inferring what functions certain brain regions may be responsible for.This approach exemplifies a deletion heuristic,where the absence of a specific function reveals insights about the underlying structures or mechanisms responsible for it.By observing what is lost when a particular brain region is damaged,throughout the history of the field,neurologists have pieced together the intricate relationship between anatomy and function.
文摘Background:Neonatal-onset multisystem inflammatory disease is characterized by fever,urticarial rash,aseptic meningitis,deforming arthropathy,hearing loss,and mental retardation.Many patients have mutations in the cold-induced autoinflammatory syndrome 1(CIAS1)gene,encoding cryopyrin,a protein that regulates inflammation.
基金supported by Yunnan Fundamental Research Project(202301AS070014)Science and Technology Plan Project in Guizhou Province([2020]1Y022).
文摘Rosa roxburghii seeds are by-products of R.roxburghii processing,and their protein hydrolysates(RTSPHs)were found to possess a variety of biological activities.This study aimed to rapidly identify pancreatic lipase(PL)and cholesterol esterase(CE)inhibitory peptides in RTSPHs and to elucidate their molecular mechanisms by combining peptidomics and virtual screening.The simulated intestinal environment worsened the peptide’s inhibition of PL but catalyzed the inhibition of CE.The fraction less than 3 kDa in RTSPHs was found to have the highest PL/CE inhibitory activity,among which 17 promising inhibitory peptides were identified and screened by peptidomics and virtual screening.LFCMH,RIPAGSPF,and YFRPR showed good inhibitory abilities against both PL and CE.Molecular docking showed that peptides inhibited PL and CE mainly by hydrogen bonding and hydrophobic interactions with residues in the active site and surface loop.Inhibition kinetic revealed that the peptides were competitive and mixed-type inhibitors of PL/CE.Further,the three peptides,LFCMH,RIPAGSPF,and YFRPR,could effectively inhibit 3T3-L1 preadipocytes differentiation,increase high-density lipoprotein cholesterol content and decrease low-density lipoprotein cholesterol content.This study suggests that combining peptidomics with virtual screening is an effective strategy for rapid screening of PL/CE inhibitory peptides.
基金National Natural Science Foundation of China(No.52071067)Liaoning Revitalization Talents Program,China(No.XLYC2403026)+6 种基金Shenyang Young and Middle-aged Science and Technology Innovation Talent Support Program of China(No.RC231178)Natural Scienceof Liaoning Province,China(No.2022-YGJC-16)Fundamental Research Funds for the Central Universities,China(No.N2302019)financial supports by the National Natural Science Foundation of China(No.52101084)Guangdong Basic and Applied Basic Research Foundation,China(No.2023A1515011579)Guangzhou Basic and Applied Basic Research Foundation,China(No.2024A04J9889)National Key Research and Development Project of China(No.2023YFB3408200)。
文摘The influence of NaF on the microstructure,composition and corrosion performance of WE43 Mg alloy in 3.5 wt.%NaCl solution was systematically investigated by means of SEM,TEM,EPMA,XRD,XPS and electrochemical measurements.It was proved that NaF is an effective inhibitor for WE43 Mg alloy and the highest inhibition efficiency is 92.6%at its concentration of 40 mmol/L in neutral NaCl solution.The dissolution of WE43 alloy is inhibited by formation and deposition of a dense and protective double-layered corrosion film by chemical reaction between corrosion inhibitor and dissolved Mg^(2+).The microstructure and composition of this double-layered corrosion film were investigated by FIB and TEM.The outer layer of the corrosion film is found to be composed of NaMgF_(3),MgF_(2)and MgO,while the inner layer mainly consists of MgO and MgF_(2).
基金supported by the National Natural Science Foundation of China(No.52161016)the Joint Key Project of Agricultural Fundamental Research in Yunnan Province(No.202101BD070001-017)+1 种基金the Yunnan Provincial Academician Work-station(No.202305AF150009)the Special Project of"Leading Talents of Industrial Technology"of Yunnan Ten Thousand Talents Plan(No.80201408).
文摘Ethyl-bis(octadecyl dipolyoxyethylene ammonium chloride)(E-BODAC)was a novel quaternary Gemini surfactant and was first found and identified as an excellent inhibitor with excellent surface activity and suitability.The ethoxy group enhances its hydrophilicity,and facilitates a dense adsorption film on metal surface.The inhibitive action and mechanism of E-BODAC on cold rolled steel(CRS)in HCl and H_(2)SO_(4) solutions was studied in detail by theoretical and experimental methods.The surface activity and degree of polymerization of the surfactant are tightly related to the anti-corrosion properties.HCl has a lower critical micelle concentration(CMC)than H_(2)SO_(4) solutions.The hydrophilic group in E-BODAC is the pre-ferred site for donating and accepting electrons,with chemical interactions occurring among O,C,and Fe.The addition of E-BODAC obeys Langmuir isotherm,which can drastically reduce the diffusion of H_(3)O^(+),Cl^(-)/SO_(4)^(2-).E-BODAC has superior corrosion inhibition performance and lower dosage,and the inhibition efficiency for CRS reaches 92.9%in 1.0 M HCl with only 10 mg L^(-1) of E-BODAC and 91.5%in 0.50 M H_(2)SO_(4).The inhibition is through physical and chemical adsorption to form a protective film that covers the reaction site,blocking the corrosion reaction.CLSM,SEM,AFM,XPS,and time-of-flight secondary ion mass spectrometer(TOF-SIMS)provide evidence of the adsorption of E-BODAC,efficiently slowing down the corrosion of CRS surface.E-BODAC always shows higher efficiency in HCl than in H_(2)SO_(4),which is attributed to the re-dissolution of the adsorbed film in the H_(2)SO_(4) solution.Besides,SO42-ions are larger and migrate more slowly than Cl^(-)ions,resulting in weak adsorption on the metal surface.The assess-ment of E-BODAC's suitability and durability in different corrosive environments provides the opportunity to determine its optimum conditions and applicability to maximize its corrosion inhibition effect.
基金supported by the Research Foundation of China University of Petroleum-Beijing at Karamay(No.XQZX20250032)the Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2022D01A250)the Basic Research Foundation of Xinjiang Uygur Autonomous Region(No.XQZX20250003)。
文摘Wellbore instability is a critical challenge in drilling operations,especially in shale formations where interaction with water-based drilling fluids can result in significant operational risks and increased costs.To address these issues,shale chemical inhibitors have become a crucial component in drilling fluid formulations to ensure wellbore integrity.Although several researchers have published some reviews on shale inhibitors,the latest advancements in shale chemical inhibitors over the past five years still warrant further discussion and summary.This literature review provided a comprehensive examination of wellbore instability,focusing on the patterns of instability encountered in drilling and the various shale chemical inhibitors employed to mitigate these issues.The review explored the utilization of shale inhibitors in water-based drilling fluids,and the discussion highlights the timeline evolution of these inhibitors,from traditional salts and polymers to advanced ionic liquids and deep eutectic solvents.Additionally,the mechanisms of shale chemical inhibitors are summarized to guide their application.The objective of this paper is to provide a detailed review of the development of shale chemical inhibitors in water-based drilling fluids,aiming to fully appreciate shale hydration inhibition methods and to provide insights into the selection and optimization of shale inhibitors to improve wellbore stability in challengingdrilling environments.
基金funding from the National Natural Science Foundation of China(Nos.51991361 and 52288101)the Young Scientists Fund of the National Natural Science Foundation(No.52204023)。
文摘Ionic liquids(ILs),recognized for their negligible vapor pressure,thermal stability,and structural tailorability,offer targeted inhibition of clay expansion.Compared to ILs,polyionic liquids(PILs)possess stronger mechanical properties and adsorption capabilities,showing even greater potential in inhibiting clay swelling.In this work,we synthesized and characterized an imidazole-based ionic liquid(IL-NH_(2)),a polyionic liquid(PIL-ABHIm),and a PIL/IL combination.Their inhibitory performance was rigorously evaluated under simulated drilling conditions through immersion tests,linear swelling tests,among others.Additionally,the mechanisms underlying their interaction with clay minerals were elucidated through contact angle measurements,Fourier-transform infrared spectroscopy,X-ray diffraction(XRD),Zeta potential analysis,and molecular electrostatic potential(MEP)analysis.This work demonstrates that IL-NH_2inhibits osmotic hydration by altering the interlayer structure of the clay,while PIL-ABHIm reduces surface hydration by forming a hydrophobic barrier on the clay surface.PIL/IL combines both mechanisms,significantly enhancing the stability of clay through the dual mechanisms of cation exchange and hydrophobic barriers.These findings reveal an innovative mechanism by which PIL/IL combination inhibits clay hydration and swelling,providing a scientific foundation for their application in drilling fluids.
基金financially supported by the National Natural Science Foundation of China(No.52161016)Joint Key Project of Agricultural Fundamental Research in Yunnan Provinceg(No.202101BD070001-017)+3 种基金Yunnan Provincial Academician Workstation(No.202305AF150009)Yunnan Province Natural Science Key Foundation(No.202201AS070152)Special Project of“Top Young Talents”of Yunnan Ten Thousand Talents Plan(No.51900109)Special Project of"Leading Talents of Industrial Technology"of Yunnan Ten Thousand Talents Plan(No.80201408).
文摘The inhibitory properties of rapeseed cake meal extract(RCME)on the corrosion of cold rolled steel(CRS)in trichloroacetic acid(TCA)were systematically investigated using gravimetric,electrochemical,surface characterizations and theoretical calculations.The results demonstrate that RCME exhibits excellent inhibitory performance with a maximum inhibition efficiency of 92.7%for 100 mg L−1 RCME at 20℃.The adsorption of RCME obeys Langmuir isotherm at 20 and 30℃,Temkin isotherm at 40℃,and Freundlich isotherm at 50℃.RCME acts as a cathodic inhibitor.The charge transfer resistance is increased with the addition of RCME,while the double-layer capacitance decreases.SEM,AFM,CLSM,XPS,XRD and TOF-SIMS analyses confirm that the active components in RCME adsorb onto the surface of CRS,forming a protective film that effectively inhibits the corrosion of CRS by TCA.Along with the increase in the concentration of RCME,the surface tension of the inhibited solution gradually decreases,while the electrical conductivity increases before stabilizing.HPLC-MS and FTIR analyses reveal rutin,linolenic acid,linoleic acid and adenine are the effective substances in RCME.Quantum chemical(QC)calculations and molecular dynamic(MD)simulations indicate that the active centers of the effective inhibitor molecules are predominantly located on benzene rings,O-or N-containing heterocyclic rings,and functional groups such as C=O and C=C.Additionally,their main chains adsorb onto the Fe(001)surface in an approximately flat manner,involving both chemical and physical adsorption processes.
文摘Background:Gastric cancer(GC)remains a global health burden and is often characterized by heterogeneous molecular profiles and resistance to conventional therapies.The phosphoinositide 3-kinase and PI3K and Janus kinase(JAK)signal transducer and activator of transcription(JAK-STAT)pathways play pivotal roles in GC progression,making them attractive targets for therapeutic interventions.Methods:This study applied a computational and molecular dynamics simulation approach to identify and characterize SBL-JP-0004 as a potential dual inhibitor of JAK2 and PI3KCD kinases.KATOIII and SNU-5 GC cells were used for in vitro evaluation.Results:SBL-JP-0004 exhibited a robust binding affinity for JAK2 and PI3KCD kinases,as evidenced by molecular docking scores and molecular dynamics simulations.Binding interactions and Gibbs binding free energy estimates confirmed stable and favorable interactions with target proteins.SBL-JP-0004 displayed an half-maximal inhibitory concentration(IC_(50))value of 118.9 nM against JAK2 kinase and 200.9 nM against PI3KCD enzymes.SBL-JP-0004 exhibited potent inhibition of cell proliferation in KATOIII and SNU-5 cells,with half-maximal growth inhibitory concentration(GI50)values of 250.8 and 516.3 nM,respectively.A significant elevation in the early phase apoptosis(28.53%in KATOIII cells and 26.85%in SNU-5 cells)and late phase apoptosis(17.37%in KATOIII cells and 10.05%in SNU-5 cells)were observed with SBL-JP-0004 treatment compared to 2.1%and 2.83%in their respective controls.Conclusion:The results highlight SBL-JP-0004 as a promising dual inhibitor targeting JAK2 and PI3KCD kinases for treating GC and warrant further preclinical and clinical investigations to validate its utility in clinical settings.
文摘Correction to:Neurosci.Bull.December,2016,32(6):577–584.https://doi.org/10.1007/s12264-016-0068-z In this article,in Fig 5A,the picture of the Vector+Nogo-66 group was incorrect and should have appeared as shown below.
文摘Objective:To construct a pH-responsive paclitaxel(PTX)-exosome composite nanocarrier and investigate its inhibitory effect on the proliferation of endometrial cancer cells(HEC-1A).Methods:PTX was loaded into exosomes derived from adipose mesenchymal stem cells using the thin-film hydration method,and modified with polyethylene glycol-polylactic-co-glycolic acid(PEG-PLGA)to form nanocarriers(PTX-Exo-NPs).The particle size and morphology were detected by nanoparticle size and Zeta potential analyzer;drug encapsulation efficiency and drug loading capacity were determined by high-performance liquid chromatography;drug release behavior was evaluated in vitro under simulated acidic(pH 5.5)and physiological(pH 7.4)conditions;MTT assay and flow cytometry were used to detect the effects of the carrier on the proliferation,apoptosis,and cell cycle distribution of HEC-1A cells.Results:PTX-Exo-NPs exhibited a uniform spherical shape with a particle size of(128.5±5.2)nm,PTX encapsulation efficiency of 92.3%±2.1%,and drug loading capacity of 15.6%±0.8%.Drug release rate in the acidic environment(85.3%±2.1%within 72 h)was significantly higher than that in the physiological environment(48.0%±1.7%).In vitro experiments demonstrated that the proliferation inhibition rate of PTX-Exo-NPs on HEC-1A cells was higher than that of free PTX,with a lower IC50(0.64μM vs 4.70μM),and could induce cell apoptosis(apoptosis rate:28.7%±2.1%vs 14.2%±1.5%)and promote cell cycle arrest(G_2/M rate:45.3%±3.2%).Conclusion:PTX-Exo-NPs exhibit pH-responsive characteristics,which can target drug release through the acidic microenvironment,enhance the proliferation inhibition and pro-apoptotic effect on endometrial cancer cells,thus serving as a potential strategy for targeted therapy of endometrial tumors.
基金Project(52004333)supported by the National Science Foundation of ChinaProject(2021CB1002)supported by Hunan International Joint Research Center for Efficient and Clean Utilization of Critical Metal Mineral Resources,China。
文摘The efficient recovery of fluorite is paid more and more attention with the increasing application especially in strategic emerging industries.In this study,acrylic acid-2-acrylamido-2-methylpropane sulfonic acid copolymer(AAAMPS)was first used as the depressant in fluorite flotation,and its effect on the flotation separation of fluorite and dolomite in sodium oleate(NaOL)system was investigated.The depression mechanism was analyzed by contact angle measurement,zeta potential test,FTIR and XPS analyses.The micro-flotation test results showed that dolomite can be inhibited in fluorite flotation system in the addition of 2 mg/L AA-AMPS and 20 mg/L NaOL at pH 10.The CaF_(2) grade increased from 49.85%in the artificial mixed mineral to 89.60%in the fluorite concentrate.The depression mechanism indicated that AA-AMPS could adsorb strongly on dolomite surface by the chelation with Ca and Mg active sites.Moreover,the further adsorption of NaOL on dolomite surface was prevented by the AA-AMPS adsorption,but that on fluorite surface was little affected,thereby increasing the difference in the hydrophobicity and floatability of the two minerals.
基金financially supported by the Major Basic Research Fund of Jiangsu Province Hospital(No.TS202401)Jiangsu Province Hospital High-level Talent Cultivation Program(PhaseⅠ)(No.CZ0121002010039)
文摘In the treatment of breast cancer,the combination of glutamine metabolism inhibition and photothermal therapy(PTT)is gaining increasing attention.This study developed a Janus nanomotor to enhance permeability in tumor tissues for nanomedicine applications by using mesoporous organic silica(PMO)anisotropic ally grown on the surface of the platinum(Pt)nanoparticles(PMO@Pt).The prepared PMO@Pt had unique Janus structure with an average size of approximately 236 nm.The loading capacity of V9302 was evaluated to be 44.37%when the mass ratio of V9302 to PMO@Pt was maintained at 2.0 and in vitro release studies demonstrated that acidic environments significantly enhanced the drug release.Then this nanomotor was loaded with perfluorohexane(PFH),a phase-change material,and the glutamine inhibitor V9302(denoted as Janus PMO@Pt@PFH@V9302,JPV).Janus PMO@Pt@PFH(JPP)nanomotors demonstrated enhanced fluorescence intensity and distribution within 3D tumor spheroids compared to Janus PMO@Pt nanomotors,attributed to the photothermal-induced phase change of PFH.The nanomotors exhibited high biocompatibility,with cell viability exceeding 98%at high concentrations.However,the incorporation of V9302 into the nanomotors(JPV)significantly reduced 4T1 cell viability under laser irradiation,indicating a cytotoxic effect resulting from the synergy between photothermal therapy and glutamine metabolism inhibition.In vivo,JPV nanomotors effectively inhibited tumor growth and induced apoptosis without causing significant systemic toxicity,showcasing their potential as a therapeutic agent for breast cancer.This integrated nanomotor offers a promising approach for enhanced ultrasound imaging and photothermal therapy in cancer treatment.
基金CABin grant(F.no.Agril.Edn.4-1/2013-A&P)Indian Council of Agricul-tural Research,Ministry of Agriculture and Farmers’Welfare,Govt.of India and Department of Biotechnology,Govt.of India for BIC project grant(BT/PR40161/BTIS/137/32/2021)。
文摘Background Polygalacturonase inhibiting proteins(PGIPs)play a pivotal role in plant defense against plant patho-gens by inhibiting polygalacturonase(PG),an enzyme produced by pathogens to degrade plant cell wall pectin.PGIPs,also known as leucine-rich repeat pathogenesis-related(PR)proteins,activate the host’s defense response upon interaction with PG,thereby reinforcing the host defense against plant pathogens attacks.In Egyptian or extra-long staple cotton(Gossypium barbadense),the interaction between PGIP and PG is one of the crucial steps in the defense mechanism against major pathogens such as Xanthomonas citri pv.malvacearum and Alternaria mac-rospora,which are responsible for bacterial leaf blight and leaf spot diseases,respectively.Results To unravel the molecular mechanisms underlying these PR proteins,we conducted a comprehensive study involving molecular modeling,protein-protein docking,site-specific double mutation(E169G and F242K),and molec-ular dynamics simulations.Both wild-type and mutated cotton PGIPs were examined in the interaction with the PG enzyme of a bacterial and fungal pathogen.Our findings revealed that changes in conformations of double-mutated residues in the active site of PGIP lead to the inhibition of PG binding.The molecular dynamics simulation studies provide insights into the dynamic behaviour and stability of the PGIP-PG complexes,shedding light on the intricate details of the inhibitory and exhibitory mechanism against the major fungal and bacterial pathogens of G.barbadense,respectively.Conclusions The findings of this study not only enhance our understanding of the molecular interactions between PGs of Xanthomonas citri pv.malvacearum and Alternaria macrospora and PGIP of G.barbadense but also pre-sent a potential strategy for developing the disease-resistant cotton varieties.By variations in the binding affinities of PGs through specific mutations in PGIP,this research offers promising avenues for the development of enhanced resistance to cotton plants against bacterial leaf blight and leaf spot diseases.
基金financially supported by the National Natural Science Foundation of China (52474216 and 52374197)the Science&Technology Innovation Talents in Universities of Henan Province(22HASTIT027)the Scientific and Technological Key Project of Henan Province (222102320142)。
文摘To address the critical need for safer and cleaner explosion suppression technologies in industrial settings,the suppression differences and mechanisms of the flame acceleration characteristics of CH_(4),LPG and H_(2) explosions by N_(2)-water mist two-phase medium were investigated.The flame acceleration characteristics and suppression mechanism of methane,LPG and H_(2) explosions in N_(2)-water mist twophase medium were studied qualitatively and quantitatively from both experimental and simulation aspects.The experimental results show that compared with single N_(2) or water mist,the N_(2)-water mist two-phase medium is more effective in reducing the flame propagation speed and delaying the formation of flame hydrodynamic structure,thus slowing down the flame acceleration characteristics.The simulation results show that this two-phase medium exhibits a strong inhibitory effect on the thermal diffusion instability of CH_(4) and LPG,and significantly weakens the hydrodynamic instability of CH_(4),LPG,and H_(2) simultaneously.Mechanistic analysis confirms that the N_(2)-water mist two-phase medium has both chemical and physical inhibitory effects,among which the physical inhibition plays a dominant role.In addition,the study reveals a linear correlation between the concentration of H radicals in the three combustible gases and the laminar burning velocity.Moreover,this two-phase medium can significantly reduce the reaction rate of the H radical chain reaction,thereby effectively suppressing the laminar burning velocity.
基金supported by grants from the general project of Nanjing Medical University Science and Technology Development Foundation (Grant No.NMUB20210112)。
文摘Inflammation plays a crucial role in the initiation and progression of sepsis and induces alterations in brain neurotransmission, thereby contributing to the development of sepsis-associated encephalopathy(SAE).Parvalbumin(PV) interneurons are pivotal contributors to cognitive processes and have been implicated in various central nervous system dysfunctions, including SAE. Oxytocin, known for its ability to augment the firing rate of gamma-aminobutyric acid(GABA)-ergic interneurons and directly stimulate inhibitory interneurons to enhance the tonic inhibition of pyramidal neurons, has prompted an investigation into its potential therapeutic effects on cognitive dysfunction in SAE. In the current study, we administered intranasal oxytocin to SAE mice induced by lipopolysaccharide. Behavioral assessments, including open field, Y-maze, and fear conditioning, were used to evaluate cognitive performance. Golgi staining revealed hippocampal synaptic deterioration, local field potential recordings showed weakened gamma oscillations, and immunofluorescence staining demonstrated decreased PV expression in the cornu ammonis 1(CA1) region of the hippocampus following lipopolysaccharide treatment, all of which were alleviated by oxytocin administration. Furthermore, immunofluorescence staining of PV co-localization with vesicular glutamate transporter 1 or vesicular GABA transporter indicated a balanced excitation/inhibition effect of neurotransmitters on PV interneurons after oxytocin administration in the SAE mice, leading to an improved cognitive function. In conclusion, oxytocin treatment improved cognitive function by increasing the number of PV^(+) neurons in the hippocampal CA1 region, restoring the balance of excitatory/inhibitory synaptic transmission on PV interneurons, and enhancing hippocampal CA1 local field potential gamma oscillations. These findings suggest a potential mechanism underlying the beneficial effects of oxytocin in SAE.
基金supported by the National Natural Science Foundation of China(Grant No:82474158)the Natural Science Foundation of Sichuan Province,China(Grant No.:2024NSFSC0708).
文摘The rising prevalence of multidrug-resistant pathogens poses a substantial threat to global healthcare systems,demanding urgent therapeutic interventions.Microorganisms exhibit diverse resistance mechanisms against various classes of antibiotics,highlighting the urgent need to discover novel antimicrobial agents for combating bacterial infections.Anti-virulence therapy has emerged as a promising therapeutic strategy that neutralizes pathogens by targeting their virulence determinants.The strategies for screening virulence arresting drugs(VADs)in bacteria represent a multifaceted approach that involves elucidating molecular pathogenesis mechanisms of bacterial pathogenicity,identifying evolutionarily conserved virulence factors across different pathogens,and employing integrated approaches combining in silico prediction with experimental validation.Recent technological advancements have established standardized protocols for effective identification and validation of anti-virulence compounds.This review systematically examines contemporary screening methodologies,primarily focusing on quorum-sensing disruption and biofilm suppression strategies,including in silico screening,activity-based screening with bioassays,in vitro and in vivo models.Additionally,we emphasize the imperative for standardized preclinical validation through physiologically relevant animal models,while proposing framework recommendations for developing next-generation VAD screening platforms.This synthesis not only outlines current best practices but also proposes innovative avenues for future antimicrobial discovery research.
