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
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
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
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
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 limited chemical and dispersive stabilities of transition metal carbides and nitrides(MXenes)significantly hinder their practical applications despite the demonstrated excellent performances.In this study,colloida...The limited chemical and dispersive stabilities of transition metal carbides and nitrides(MXenes)significantly hinder their practical applications despite the demonstrated excellent performances.In this study,colloidally stable Ti_(2)CT_(x)-and Ti_(3)C_(2)T_(x)-MXene aqueous dispersions(0.1 mg.m L^(-1))were achieved through a corrosion inhibition strategy by incorporating sodium tartrate(ST).The addition of ST(0.3 mg.m L^(-1))effectively increased the activation energy and enthalpy for the degradation of Ti_(2)CT_(x)and Ti_(3)C_(2)T_(x)in aqueous solutions,largely extending their time constants to 565.5 h and 239.3 days,respectively.This strong oxidation inhibition effect of ST preserved the structural integrity and colloidal properties of both MXenes without compromising their electrical and electrochemical performances.The vacuum-filteredTi_(2)CT_(x)and Ti_(3)C_(2)T_(x)film electrodes demonstrated capacitance retentions of 96.7%and 88.5%after 96 h and 24 days of aging at 25°C,respectively.Multiscale simulations revealed that single-deprotonated ST-preferentially adsorbed onto edges and defect sites of MXene nanosheets via oxygen heteroatoms on the carbonyl moiety bonding to Ti vacancies.This work offers a promising and straightforward approach to stabilize the diluted MXene aqueous dispersions,fundamentally address their oxidation issues,and meet the requirements for temporary storage.展开更多
P2-type layered oxide cathode materials have attracted extensive attention due to their simple preparation,high specific capacity,adjustable voltage range,and high packing density.However,the harmful phase transitions...P2-type layered oxide cathode materials have attracted extensive attention due to their simple preparation,high specific capacity,adjustable voltage range,and high packing density.However,the harmful phase transitions that occur at high voltage severely limit their practical application.Herein,a novel high-valence tungsten doped P2-Na_(0.67)Ni_(0.33)Mn_(0.67)O_(2)cathode material was prepared using the sol–gel method.Through diffusion kinetics analysis and in situ X-ray diffraction(in situ XRD),it has been proven that W^(6+)not only enhances the Na^(+)diffusion coefficient but also reduces the P2–O2 phase transition.The optimized NNMO-W1%delivers a high discharge specific capacity of 163 mAh·g^(-1)at 0.1C,and the capacity retention rate is as high as 77.6%after 1000 cycles at 10C.This is mainly due to that W^(6+)enters the lattice,optimizing the arrangement of primary particles.This work sheds light on the design and construction of high-performance layered oxides cathode materials.展开更多
Metal oxide catalysts are widely employed in propane dehydrogenation(PDH)for propylene synthesis,requiring sequential reduction-reaction-regeneration cycles.However,the eff ect of water present in the inlet gas or rea...Metal oxide catalysts are widely employed in propane dehydrogenation(PDH)for propylene synthesis,requiring sequential reduction-reaction-regeneration cycles.However,the eff ect of water present in the inlet gas or reactor on the catalytic per-formance of various metal oxides remains insuffi ciently understood.This study examines the infl uence of water on supported metal oxide catalysts,specifi cally CoO x/Al_(2)O_(3),VO x/Al_(2)O_(3),and an industrial analog CrO x/Al_(2)O_(3) catalyst.By combining titration experiments,in situ Fourier transform infrared spectroscopy,kinetic analysis,and isotopic techniques,we demon-strate that even trace amounts of water can markedly suppress PDH performance via dissociative adsorption on the oxide surface.Methanol pretreatment eff ectively scavenges adsorbed water,recovering Lewis acid-base sites and consequently restoring PDH activity.This work underscores the profound inhibitory role of trace water in PDH over metal oxide catalysts and illustrates the potential of methanol pretreatment as an effective strategy to mitigate this limitation.展开更多
The study investigated the effects of monetary rewards and punishments on the behavioral inhibition in children with attention deficit hyperactivity disorder(ADHD)tendencies.The present study adopted the signal stoppi...The study investigated the effects of monetary rewards and punishments on the behavioral inhibition in children with attention deficit hyperactivity disorder(ADHD)tendencies.The present study adopted the signal stopping task paradigm,with 66 children with ADHD tendencies as the research subjects.A mixed design of 2(reward and punishment type:reward,punishment)×2(stimulus type:monetary stimulus,social stimulus)was used.The analysis applied a between intervention group(with reward and punishment type variables)and within type of reward approach(by stimulus type as intra subject variables).The results showed that monetary punishment better promotes behavioral inhibition in children with an ADHD tendency than does reward.In addition,this study showed that monetary punishment and social rewards affected the speed–accuracy trade-off of inhibited behavior in children with an ADHD tendency.Thesefindings suggest that withdrawal of a material token resulted in more behavioural compliance in children with an ADHD tendency.展开更多
Sclerosteosis,an ultra-rare disorder characterised by high bone mass(HBM)and skeletal overgrowth,leads to facial paralysis,hearing loss and raised intracranial pressure,which is currently managed only through high-ris...Sclerosteosis,an ultra-rare disorder characterised by high bone mass(HBM)and skeletal overgrowth,leads to facial paralysis,hearing loss and raised intracranial pressure,which is currently managed only through high-risk surgery.Sclerosteosis is caused by SOST mutations and loss of functional sclerostin,a protein that suppresses osteogenesis by antagonising Wnt/β-catenin signalling.Herein,using in vitro and in vivo approaches,we explore whether LGK974,another potent Wnt inhibitor that targets porcupine(PORCN,Wnt-specific acyltransferase),is a promising sclerosteosis therapeutic.In vitro assays showed that 100 nmol/L LGK974 significantly reduced osteoblast alkaline phosphatase(ALP)activity/mineralisation,decreased Wnt/osteoblast marker(Axin2,Runx2 and Ocn)expression,and downregulated ossification and the Wnt signalling pathway,without affecting osteoclast numbers/resorption.To assess in vivo effects,6-week-old male and female Sost deficient(Sost-/-)mice received LGK974 for 4 weeks and right hindlimbs were subjected to 20 N peak loading to assess mechanoadaptive interactions.µCT revealed significant reductions in vertebral trabecular number and lower cortical bone volume in loaded and non-loaded tibiae in male and female LGK974-treated Sost-/-mice.Interestingly,the target engagement biomarker Axin2 was only significantly reduced in male vertebrae,which may indicate differences in male and female response to LGK974.This study also shows that PORCN inhibition may effectively limit characteristic HBM and skeletal overgrowth in sclerosteosis patients at sites with severe pathology.展开更多
The published article titled“MicroRNA-221-3p Plays an Oncogenic Role in Gastric Carcinoma by Inhibiting PTEN Expression”has been retracted from Oncology Research,Vol.25,No.4,2017,pp.523–536.DOI:10.3727/096504016X14...The published article titled“MicroRNA-221-3p Plays an Oncogenic Role in Gastric Carcinoma by Inhibiting PTEN Expression”has been retracted from Oncology Research,Vol.25,No.4,2017,pp.523–536.DOI:10.3727/096504016X14756282819385 URL:https://www.techscience.com/or/v25n4/56833 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.展开更多
A new type of corrosion-resistant alloyed-steel rebar,Cr10MoV,was researched using techniques such as corrosion electrochemistry,X-ray computed tomography,and zero resistance ammeter to systematically study the macro-...A new type of corrosion-resistant alloyed-steel rebar,Cr10MoV,was researched using techniques such as corrosion electrochemistry,X-ray computed tomography,and zero resistance ammeter to systematically study the macro-cell corrosion behavior and corrosion resistance of alloyed-steel rebar in mortar and concrete samples induced by chloride ion concentration in the marine environment.The macro-cell corrosion characteristics and development patterns induced by chloride ion concentration in alloyed-steel rebar were preliminarily revealed.In the macro-cell corrosion system of rebar mortar samples induced by 29 times chloride ion concentration,the corrosion current density of the alloyed-steel rebar combination stabilizes at 1.6–2.4μA/cm^(2),which is only one-third of that of the carbon-steel rebar combination,while the dissimilar steel rebar combination stabilizes at 0–0.4μA/cm^(2).Alloyed-steel rebar and carbon-steel rebar are configured in high concentration and low concentration chlorine salt areas,respectively.With the help of high corrosion resistance,the long-term stable corrosion resistance of alloyed-steel rebar is ensured.The potential difference between carbon-steel rebar and alloyed-steel rebar is reduced to weaken the driving force of macro-cell corrosion.It is a useful way to inhibit the macro-cell corrosion of dissimilar steel rebar and ensure the high corrosion resistance and durability of marine reinforced concrete structures.展开更多
Neurofibromatosis type 1(NF1)is a genetic disorder affecting 1 in 3000 people due to heterozygous mutations in the NF1 gene.Patients with NF1 can develop multiple symptoms,such as neurofibromas,skin hyperpigmentation,...Neurofibromatosis type 1(NF1)is a genetic disorder affecting 1 in 3000 people due to heterozygous mutations in the NF1 gene.Patients with NF1 can develop multiple symptoms,such as neurofibromas,skin hyperpigmentation,and bone abnormalities,including tibial pseudarthrosis and spine deformity.Here,we aimed to elucidate the cellular origin and pathogenic mechanism of NF1 spine deformity.We explored the Prss56-Nf1 knockout(KO)mouse model that recapitulates neurofibromas and pseudarthrosis by carrying Nf1 gene inactivation in Prss56-expressing boundary cap cells,a neural crest subset,and their derivatives.Micro-CT analyses showed that Prss56-Nf1 KO mice exhibit spine deformity from 12 months of age,associated with vertebral anomalies reminiscent of patients with NF1.Fate mapping revealed a significant increase in OSX^(+)osteoblasts of the Prss56 lineage in vertebrae of Prss56-Nf1 KO mice.Increased traced Nf1-deficient cells correlated with increased vertebral bone volume and kyphosis spine curvature.Finally,we showed that treating Prss56-Nf1 KO mice with RAS-MAPK pathway inhibitors prevented spine deformity.Overall,the Prss56-Nf1 KO mouse model unravels the role of osteoblasts from the Prss56 lineage as the cellular origin of NF1 spine deformity and highlights RAS-MAPK pathway inhibition as a promising therapeutic strategy for preventing NF1 spine deformity.展开更多
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.
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 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.
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financially supported by the National Natural Science Foundation of China(No.21606005)Beijing Municipal Natural Science Foundation(No.2192016)。
文摘The limited chemical and dispersive stabilities of transition metal carbides and nitrides(MXenes)significantly hinder their practical applications despite the demonstrated excellent performances.In this study,colloidally stable Ti_(2)CT_(x)-and Ti_(3)C_(2)T_(x)-MXene aqueous dispersions(0.1 mg.m L^(-1))were achieved through a corrosion inhibition strategy by incorporating sodium tartrate(ST).The addition of ST(0.3 mg.m L^(-1))effectively increased the activation energy and enthalpy for the degradation of Ti_(2)CT_(x)and Ti_(3)C_(2)T_(x)in aqueous solutions,largely extending their time constants to 565.5 h and 239.3 days,respectively.This strong oxidation inhibition effect of ST preserved the structural integrity and colloidal properties of both MXenes without compromising their electrical and electrochemical performances.The vacuum-filteredTi_(2)CT_(x)and Ti_(3)C_(2)T_(x)film electrodes demonstrated capacitance retentions of 96.7%and 88.5%after 96 h and 24 days of aging at 25°C,respectively.Multiscale simulations revealed that single-deprotonated ST-preferentially adsorbed onto edges and defect sites of MXene nanosheets via oxygen heteroatoms on the carbonyl moiety bonding to Ti vacancies.This work offers a promising and straightforward approach to stabilize the diluted MXene aqueous dispersions,fundamentally address their oxidation issues,and meet the requirements for temporary storage.
基金supported by the National Natural Science Foundation of China Key Program(No.U22A20420)Changzhou Leading Innovative Talents Introduction and Cultivation Project(No.CQ20230109)the Key Project of Jiangsu Provincial Basic Research Program(No.BK20243032)。
文摘P2-type layered oxide cathode materials have attracted extensive attention due to their simple preparation,high specific capacity,adjustable voltage range,and high packing density.However,the harmful phase transitions that occur at high voltage severely limit their practical application.Herein,a novel high-valence tungsten doped P2-Na_(0.67)Ni_(0.33)Mn_(0.67)O_(2)cathode material was prepared using the sol–gel method.Through diffusion kinetics analysis and in situ X-ray diffraction(in situ XRD),it has been proven that W^(6+)not only enhances the Na^(+)diffusion coefficient but also reduces the P2–O2 phase transition.The optimized NNMO-W1%delivers a high discharge specific capacity of 163 mAh·g^(-1)at 0.1C,and the capacity retention rate is as high as 77.6%after 1000 cycles at 10C.This is mainly due to that W^(6+)enters the lattice,optimizing the arrangement of primary particles.This work sheds light on the design and construction of high-performance layered oxides cathode materials.
基金supported by the National Key R&D Program of China(No.2023YFA1507800)the National Science Foundation of China(Nos.22121004,22122808,22478279,and 22108201)+1 种基金the Haihe Laboratory of Sustainable Chemical Trans-formations,the Program of Introducing Talents of Discipline to Uni-versities(No.BP0618007)the XPLORER PRIZE.
文摘Metal oxide catalysts are widely employed in propane dehydrogenation(PDH)for propylene synthesis,requiring sequential reduction-reaction-regeneration cycles.However,the eff ect of water present in the inlet gas or reactor on the catalytic per-formance of various metal oxides remains insuffi ciently understood.This study examines the infl uence of water on supported metal oxide catalysts,specifi cally CoO x/Al_(2)O_(3),VO x/Al_(2)O_(3),and an industrial analog CrO x/Al_(2)O_(3) catalyst.By combining titration experiments,in situ Fourier transform infrared spectroscopy,kinetic analysis,and isotopic techniques,we demon-strate that even trace amounts of water can markedly suppress PDH performance via dissociative adsorption on the oxide surface.Methanol pretreatment eff ectively scavenges adsorbed water,recovering Lewis acid-base sites and consequently restoring PDH activity.This work underscores the profound inhibitory role of trace water in PDH over metal oxide catalysts and illustrates the potential of methanol pretreatment as an effective strategy to mitigate this limitation.
基金supported by the National General Projects in 2020 of the 13th Five Year Plan of National Education Science in China:A Study on Attention Training Interventions for ADHD Children in Regular Classes from the Perspective of Educational Neuroscience(BHA200123).
文摘The study investigated the effects of monetary rewards and punishments on the behavioral inhibition in children with attention deficit hyperactivity disorder(ADHD)tendencies.The present study adopted the signal stopping task paradigm,with 66 children with ADHD tendencies as the research subjects.A mixed design of 2(reward and punishment type:reward,punishment)×2(stimulus type:monetary stimulus,social stimulus)was used.The analysis applied a between intervention group(with reward and punishment type variables)and within type of reward approach(by stimulus type as intra subject variables).The results showed that monetary punishment better promotes behavioral inhibition in children with an ADHD tendency than does reward.In addition,this study showed that monetary punishment and social rewards affected the speed–accuracy trade-off of inhibited behavior in children with an ADHD tendency.Thesefindings suggest that withdrawal of a material token resulted in more behavioural compliance in children with an ADHD tendency.
文摘Sclerosteosis,an ultra-rare disorder characterised by high bone mass(HBM)and skeletal overgrowth,leads to facial paralysis,hearing loss and raised intracranial pressure,which is currently managed only through high-risk surgery.Sclerosteosis is caused by SOST mutations and loss of functional sclerostin,a protein that suppresses osteogenesis by antagonising Wnt/β-catenin signalling.Herein,using in vitro and in vivo approaches,we explore whether LGK974,another potent Wnt inhibitor that targets porcupine(PORCN,Wnt-specific acyltransferase),is a promising sclerosteosis therapeutic.In vitro assays showed that 100 nmol/L LGK974 significantly reduced osteoblast alkaline phosphatase(ALP)activity/mineralisation,decreased Wnt/osteoblast marker(Axin2,Runx2 and Ocn)expression,and downregulated ossification and the Wnt signalling pathway,without affecting osteoclast numbers/resorption.To assess in vivo effects,6-week-old male and female Sost deficient(Sost-/-)mice received LGK974 for 4 weeks and right hindlimbs were subjected to 20 N peak loading to assess mechanoadaptive interactions.µCT revealed significant reductions in vertebral trabecular number and lower cortical bone volume in loaded and non-loaded tibiae in male and female LGK974-treated Sost-/-mice.Interestingly,the target engagement biomarker Axin2 was only significantly reduced in male vertebrae,which may indicate differences in male and female response to LGK974.This study also shows that PORCN inhibition may effectively limit characteristic HBM and skeletal overgrowth in sclerosteosis patients at sites with severe pathology.
文摘The published article titled“MicroRNA-221-3p Plays an Oncogenic Role in Gastric Carcinoma by Inhibiting PTEN Expression”has been retracted from Oncology Research,Vol.25,No.4,2017,pp.523–536.DOI:10.3727/096504016X14756282819385 URL:https://www.techscience.com/or/v25n4/56833 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.
基金the financial support from National Natural Science Foundation of China(Grant Nos.52278255 and 51878246)Postgraduate Research&Practice Innovation Program of Jiangsu Province(SJCX24_0195).
文摘A new type of corrosion-resistant alloyed-steel rebar,Cr10MoV,was researched using techniques such as corrosion electrochemistry,X-ray computed tomography,and zero resistance ammeter to systematically study the macro-cell corrosion behavior and corrosion resistance of alloyed-steel rebar in mortar and concrete samples induced by chloride ion concentration in the marine environment.The macro-cell corrosion characteristics and development patterns induced by chloride ion concentration in alloyed-steel rebar were preliminarily revealed.In the macro-cell corrosion system of rebar mortar samples induced by 29 times chloride ion concentration,the corrosion current density of the alloyed-steel rebar combination stabilizes at 1.6–2.4μA/cm^(2),which is only one-third of that of the carbon-steel rebar combination,while the dissimilar steel rebar combination stabilizes at 0–0.4μA/cm^(2).Alloyed-steel rebar and carbon-steel rebar are configured in high concentration and low concentration chlorine salt areas,respectively.With the help of high corrosion resistance,the long-term stable corrosion resistance of alloyed-steel rebar is ensured.The potential difference between carbon-steel rebar and alloyed-steel rebar is reduced to weaken the driving force of macro-cell corrosion.It is a useful way to inhibit the macro-cell corrosion of dissimilar steel rebar and ensure the high corrosion resistance and durability of marine reinforced concrete structures.
基金Association Neurofibromatoses et Recklinghausen(C.C)Agence Nationale de la Recherche-18-CE14-0033(C.C.,P.T.)+2 种基金Agence Nationale de la Recherche-21-CE18-007-01(C.C.,P.T.)US Department of the Army NF220019(C.C.)supported by a PhD fellowship from the University Paris-Est Créteil and the Fondation pour la Recherche Médicale(FRM)(FDT202304016600 to FK and ECO202306017399 to CG)。
文摘Neurofibromatosis type 1(NF1)is a genetic disorder affecting 1 in 3000 people due to heterozygous mutations in the NF1 gene.Patients with NF1 can develop multiple symptoms,such as neurofibromas,skin hyperpigmentation,and bone abnormalities,including tibial pseudarthrosis and spine deformity.Here,we aimed to elucidate the cellular origin and pathogenic mechanism of NF1 spine deformity.We explored the Prss56-Nf1 knockout(KO)mouse model that recapitulates neurofibromas and pseudarthrosis by carrying Nf1 gene inactivation in Prss56-expressing boundary cap cells,a neural crest subset,and their derivatives.Micro-CT analyses showed that Prss56-Nf1 KO mice exhibit spine deformity from 12 months of age,associated with vertebral anomalies reminiscent of patients with NF1.Fate mapping revealed a significant increase in OSX^(+)osteoblasts of the Prss56 lineage in vertebrae of Prss56-Nf1 KO mice.Increased traced Nf1-deficient cells correlated with increased vertebral bone volume and kyphosis spine curvature.Finally,we showed that treating Prss56-Nf1 KO mice with RAS-MAPK pathway inhibitors prevented spine deformity.Overall,the Prss56-Nf1 KO mouse model unravels the role of osteoblasts from the Prss56 lineage as the cellular origin of NF1 spine deformity and highlights RAS-MAPK pathway inhibition as a promising therapeutic strategy for preventing NF1 spine deformity.
