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Secretase inhibition in Alzheimer's disease therapeutics reveals functional roles of amyloid-beta42
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作者 Timothy Daly Bruno P.Imbimbo 《Neural Regeneration Research》 2026年第5期2003-2004,共2页
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
关键词 infer brain functions secretase inhibition Alzheimers disease therapeutics king hammer deletion heuristic amyloid beta deletion heuristicwhere observing what l
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Correction to:Overexpression of Tau Rescues Nogo-66-Induced Neurite Outgrowth Inhibition In Vitro
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作者 Yu-Chao Zuo Hong-Lian Li +4 位作者 Nan-Xiang Xiong Jian-Ying Shen Yi-Zhi Huang Peng Fu Hong-Yang Zhao 《Neuroscience Bulletin》 2025年第9期1710-1710,共1页
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.
关键词 VITRO OVEREXPRESSION neurite outgrowth TAU NOGO inhibition
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Selective inhibition of acrylic acid-2-acrylamido-2-methylpropane sulfonic acid copolymer in the flotation separation of fluorite from dolomite
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作者 PENG Bin-bin ZHU Hai-ling +1 位作者 CHEN Jin-shan YANG Jia-jia 《Journal of Central South University》 2025年第10期3845-3856,共12页
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
关键词 FLUORITE DOLOMITE AA-AMPS flotation separation selective inhibition
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Inhibition mechanism of NaF on WE43 Mg alloy in NaCl solution
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作者 Yun-tian YANG Yu-xin ZHOU +3 位作者 Xiao-peng LU Ji-rui MA Jun-jie YANG Fu-hui WANG 《Transactions of Nonferrous Metals Society of China》 2025年第2期460-473,共14页
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
关键词 Mg alloy CORROSION corrosion film INHIBITOR inhibition mechanism
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Porcupine inhibition is a promising pharmacological treatment for severe sclerosteosis pathologies
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作者 Timothy J.Dreyer Jacob A.C.Keen +5 位作者 Leah M.Wells Mark Hopkinson Isabel R.Orriss Gill Holdsworth Andrew A.Pitsillides Scott J.Roberts 《Bone Research》 2025年第4期866-881,共16页
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
关键词 sost mutations suppresses osteogenesis wnt catenin signalling porcupine inhibition vitro vivo approacheswe sclerosteosis OSTEOGENESIS lgk
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Enhanced glutamine inhibition and photothermal therapy for breast cancer using Janus mesoporous organosilica-coated platinum nanomotors
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作者 Xiao-Feng Chen Zhi-Hui Chen +8 位作者 Nan Zhong Yang Liu Xuan Sha Yang Li Zi-Qing Xu Jie Zhang Shou-Ju Wang Cui-Ying Li Yu-Xia Tang 《Rare Metals》 2025年第10期7576-7586,共11页
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
关键词 Janus nanomotors Photothermal therapy Glutamine inhibition Drug delivery Ultrasound imaging
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Restoring dendritic cell interstitial motility via PDE5 inhibition for sustained antitumor immunity
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作者 Ruichen Zang Chen Zhang +1 位作者 Guoqing Ding Jie Zhang 《Journal of the National Cancer Center》 2025年第6期555-557,共3页
In a recent publication in Nature,Zhou and colleagues identified cyclic guanosine monophosphate(cGMP),a canonical phosphodiesterase 5(PDE5)substrate,as a key modulator of dendritic cell(DC)interstitial motility throug... In a recent publication in Nature,Zhou and colleagues identified cyclic guanosine monophosphate(cGMP),a canonical phosphodiesterase 5(PDE5)substrate,as a key modulator of dendritic cell(DC)interstitial motility through Rho kinase(ROCK)-dependent modulation of myosin-II activity. 展开更多
关键词 cyclic guanosine monophosphate cgmp pde inhibition rho kinase CGMP interstitial motility myosin ii activity antitumor immunity dendritic cell
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Achieving colloidal stability of diluted MXene dispersions through corrosion inhibition strategy with sodium tartrate
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作者 Hang Li Bao-Min Fan +1 位作者 Hua Tian Shi-Hao Wang 《Rare Metals》 2025年第6期3893-3908,共16页
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
关键词 Transition metal carbide Sodium tartrate Antioxidant Corrosion inhibition Density functional theory
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Monetary reward and punishment effects on behavioral inhibition in children with attention deficit hyperactivity disorder tendencies
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作者 Huifang Yang Peixuan Kuang 《Journal of Psychology in Africa》 2025年第4期535-540,共6页
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
关键词 REWARD PUNISHMENT behavioral inhibition attention deficit hyperactivity disorder children with ADHD tendency
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Chloride-induced macro-cell corrosion behavior of a novel alloyed-steel rebar and its inhibition strategy
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作者 Si-jie Zhang Qiu-yue Wang +4 位作者 Hao Guan Gong-nian Zou Guo-wei Wang Shu-guang Zhang Dan Song 《Journal of Iron and Steel Research International》 2025年第9期2995-3013,共19页
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
关键词 Alloyed-steel rebar Chloride ion concentration difference Macro-cell corrosion Corrosion electrochemistry Corrosion inhibition strategy
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Inhibition of KLK8 promotes pulmonary endothelial repair by restoring the VE-cadherin/Akt/FOXM1 pathway
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作者 Ying Zhao Hui Ji +10 位作者 Feng Han Qing-Feng Xu Hui Zhang Di Liu Juan Wei Dan-Hong Xu Lai Jiang Jian-Kui Du Ping-Bo Xu Yu-Jian Liu Xiao-Yan Zhu 《Journal of Pharmaceutical Analysis》 2025年第4期870-872,共3页
Repairing the endothelial barrier is essential for maintaining pulmonary fuid balance and regulating leukocyte infiltration during sepsis[1].Tissue kallikrein-related peptidases(KLKs)are secreted serine proteases invo... Repairing the endothelial barrier is essential for maintaining pulmonary fuid balance and regulating leukocyte infiltration during sepsis[1].Tissue kallikrein-related peptidases(KLKs)are secreted serine proteases involved in angiogenesis[2].However,their involvement in regulating endothelial regeneration remains largely unknown. 展开更多
关键词 repairing endothelial barrier regulating leukocyte infiltration pulmonary endothelial repair inhibition klk ve cadherin maintaining pulmonary fuid balance serine proteases
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Swelling inhibition and percolation promotion of PQ-10 on weathered crust elution-deposited rare earth ores
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作者 Aoyang Sha Huifang Yang +6 位作者 Meiling Jiang Zhengyan He Zhenhu Liu Zhigao Xu Yaguang Du Ming Wu Ru'an Chi 《Journal of Rare Earths》 2025年第7期1559-1570,共12页
Weathered crust elution-deposited rare earth ores(WREOs)are rich in medium and heavy rare earth.In order to improve the in-situ leaching process,which is prone to landslides and poor permeability,cationic hydroxyethyl... Weathered crust elution-deposited rare earth ores(WREOs)are rich in medium and heavy rare earth.In order to improve the in-situ leaching process,which is prone to landslides and poor permeability,cationic hydroxyethyl cellulose(PQ-10)was used as a novel green swelling inhibitor and percolation promoter and was mixed with conventional leaching agent ammonium sulfate((NH_(4))_(2)SO_(4))to form a composite leaching agent to study the performance and mechanism of swelling inhibition and percolation promotion.Adding PQ-10 can inhibit the hydration swelling of WREOs,promote the percolation effect of the leaching agent,improve the rare earth(RE)leaching efficiency,and reduce the im purity aluminum(Al)leaching efficiency.Compared with the conventional leaching agent 2 wt%(NH_(4))_(2)SO_(4),the percolation time is reduced by 50%by using the composite leaching agent(0.02 wt%PQ-10+2 wt%(NH_(4))_(2)SO_(4)).PQ-10 has positively charged quaternary ammonium groups and hydrophilic group hydroxyl groups,which makes it easy to adsorb on WREOs multiple sites through electrostatic interaction and hydrogen bonding,weakening the electrostatic repulsion between mineral particles,reducing the WREOs interlayer spacing,compressing the double electric layer thickness at the solid-liquid interface,weakening the mineral hydration swelling and increasing the percolation rate.The long carbon chains of the polymer entangle and link the fine mineral particles to agglomerate them,increasing their particle size and reduc ing their hydration dispersion,and preventing blockage of the pe rcolation pores caused by migration of the fine particles through the ore body with the solution.PQ-10 molecules also insert the mine ral interlayer and expulsion of the internal water,further inhibiting the swelling of WREOs.Adding PQ-10 reduces the surface tension of(NH_(4))_(2)SO_(4)solution,improving the spreading and spreading ability of the solution,reducing the adhesion work between molecules in the solid-liquid phase and the adhesion work reduction factor.It proves that PQ-10 promotes the percolation effect of the leaching process of WREOs.In addition,PQ-10 expands the leaching pore size and seepage channels,further improving the percolation rate. 展开更多
关键词 Weathered crust elution-deposited rare earth ores Swelling inhibition Percolation promotion Rare earth leaching Composite leaching agent
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Hole inhibition mechanisms of Mg/steel lap joint by pinless friction stir spot welding
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作者 Tao-tao Li Hong-de Ding +5 位作者 Rui-feng Li Kai Qi Zhen-guang Liu Xiao-qiang Zhang Yue Zhao Lei Qiao 《Journal of Iron and Steel Research International》 2025年第4期1085-1101,共17页
Pinless friction stir spot welding(P-FSSW)was performed to manufacture Mg/steel lap joints.Orthogonal tests for P-FSSW of Mg/steel were investigated,and the main factors affecting the properties of Mg/steel lap joints... Pinless friction stir spot welding(P-FSSW)was performed to manufacture Mg/steel lap joints.Orthogonal tests for P-FSSW of Mg/steel were investigated,and the main factors affecting the properties of Mg/steel lap joints were derived.The shear force of the Mg/steel lap joints gradually increased and then decreased as the welding time increased.Maximum shear force was 5.3 kN.Fe-Al intermetallic compound(IMC)was formed at the Mg/steel interface near the steel side,and Mg-Al IMCs were formed at the Mg/steel interface near the Mg alloy side.Mg/steel lap joint was transformed from an initial solid-state welding to fusion-brazing welding as the welding time increased.No hole defects were formed in Mg/steel solid-state welding joints,whereas hole defects appeared in Mg/steel fusion-brazing welding joints.The temperature field of Mg/steel lap joints was simulated to analyze hole defects generated during the welding process.Hole defects can be eliminated by changing the spindle deflection angle,and the shear force decreased.Excessive spindle deflection can also lead to failure to form a stable joint.Hole defects were removed because the spindle deflection angle reduced the interfacial reaction temperature,and a solid-state welding joint was formed,which resulted in an absence of fusion-brazing welding hole formation. 展开更多
关键词 Mg/steel Lap joint Pinless friction stir spot welding Hole inhibition SIMULATION
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Solidification cracking inhibition mechanism of 2024 Al alloy during oscillating laser-arc hybrid welding based on Zr-core-Al-shell wire
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作者 Jun Jin Shaoning Geng +3 位作者 Ping Jiang Liangyuan Ren Chu Han Yuantai Li 《Journal of Materials Science & Technology》 2025年第14期153-168,共16页
Solidification cracking(SC)of 2024 high-strength aluminium alloy during fusion welding or additive manufacturing has been a long-term issue.In this work,crack-free weld could be obtained using a Zr-core-Alshell wire(Z... Solidification cracking(SC)of 2024 high-strength aluminium alloy during fusion welding or additive manufacturing has been a long-term issue.In this work,crack-free weld could be obtained using a Zr-core-Alshell wire(ZCASW filler material,a novel filler)coupled with an oscillating laser-arc hybrid welding process,and we investigated the solidification cracking susceptibility(SCS)and cracking behavior of AA2024 weld fabricated with different filler materials.The cracking inhibition mechanism of the weld fabricated with ZCASW filler material was elucidated by combined experiments and phase-field simulation.The results show that the effectiveness of filler materials in reducing the SC gradually improves in the order of ER2319 filler material<ER4043 filler material<ZCASW filler material.The main cracking(when using the ER2319 filler material)branches and the micro cracking branches interact with each other to produce cracking coalescence,which aggravates the cracking propagation.The formation of the Al_(3) Zr phase(when using the ZCASW filler material)promotes heterogeneous nucleation of α-Al,thereby resulting in finer and equiaxed non-dendrite structures,which shortens the liquid phase channels and decreases cracking susceptibility index|d T/d(f_(s))^(1/2)|(T is temperature and f_(s) is solidification fraction)at final solidification.A higher proportion(7.65%area fraction)of inter-dendrite phase with spherical distribution state,a shorter(8.6 mm liquid channel length)inter-dendrite phase coupled with round non-dendrite structure(6μm dendrite size)effectively inhibit the SC.The present study can be a useful database for welding and additive manufacturing of AA2024. 展开更多
关键词 2024 aluminium alloy Filler materials Solidification cracking susceptibility Cracking behavior Cracking inhibition mechanism
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Manganese-based nano-delivery system for sensitized anti-tumor immunotherapy via combined autophagy inhibition
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作者 Huijuan Zhang Chenglin Liang +3 位作者 Xinyi Ding Meng Zhang Siyu Lu Lin Hou 《Chinese Chemical Letters》 2025年第7期484-489,共6页
The stimulator of interferon genes(STING)agonists have been widely applied to active cyclic guanosine monophophate(GMP)-adenosine monophosphate(AMP)synthase(cGAS)-STING signaling for tumor immunotherapy.However,the th... The stimulator of interferon genes(STING)agonists have been widely applied to active cyclic guanosine monophophate(GMP)-adenosine monophosphate(AMP)synthase(cGAS)-STING signaling for tumor immunotherapy.However,the therapeutic effect will be limited by factors such as the rapid degradation of STING protein and the immunosuppressive tumor microenvironment(TME).In this study,we constructed a manganese-based nano drug delivery system(NDDS)loaded with hydroxychloroquine(HCQ)for synergistic autophagy inhibition and STING activation-based immunotherapy.Hyaluronic acid(HA)/MnOOH@HCQ system can be uptake by 4T1 tumor cells via the CD44 receptor-mediated endocytosis.Subsequently,it responded to the acidic and reducing lysosomal microenvironment degradation to release Mn^(2+)and HCQ simultaneously.As a kind of STING agonist,Mn^(2+)can bind to cGAS in tumor cells,activating the cGAS-STING pathway and generating typeⅠ-interferons(IFN-Ⅰ),which helped alleviate the immunosuppressive TME.Meanwhile,HCQ downregulated the autophagy level caused by cGAS-STING pathway to block STING degradation,further sensitizing the cGAS-STING signal.Benefiting from this synergistic mechanism,HA/MnOOH@HCQ demonstrated the best anti-tumor effect with the smallest tumor weight and volume after treatment.Moreover,HA/MnOOH@HCQ also exhibited a good inhibitory effect on lung metastasis.This study provided a new strategy for enhancing cGAS-STING pathway-mediated anti-tumor immunotherapy. 展开更多
关键词 Anti-tumor immunotherapy cGAS-STING signaling Mn2+and HCQ co-delivery Autophagy inhibition TME responsive
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Oxytocin ameliorates cognitive impairments by attenuating excitation/inhibition imbalance of neurotransmitters acting on parvalbumin interneurons in a mouse model of sepsisassociated encephalopathy
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作者 Renqi Li Qiuting Zeng +5 位作者 Muhuo Ji Yue Zhang Mingjie Mao Shanwu Feng Manlin Duan Zhiqiang Zhou 《Journal of Biomedical Research》 2025年第2期132-145,共14页
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
关键词 excitation/inhibition balance OXYTOCIN cognitive sepsis-associated encephalopathy
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Fluorescence sensor based on IFE between AEP@UCNPs and oxTMB for the determination of Cd^(2+)in paddy rice combined with HRP enzyme inhibition mechanism
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作者 Haizhen Ding Shuai Hou +6 位作者 Siqi Zhao Liping Guo Ao Sun Qiuhui Hu Leiqing Pan Qiang Liu Chao Ding 《Food Science and Human Wellness》 2025年第1期154-160,共7页
Cadmium ion(Cd^(2+))detection technology plays a prominent role in food safety and human health.Herein,we designed and constructed an 2-aminoethyl dihydrogen phosphate(AEP)@upconversion nanoparticles(UCNPs)fluorescenc... Cadmium ion(Cd^(2+))detection technology plays a prominent role in food safety and human health.Herein,we designed and constructed an 2-aminoethyl dihydrogen phosphate(AEP)@upconversion nanoparticles(UCNPs)fluorescence sensor for quantitative detection of Cd^(2+)in paddy rice based on inner filter effect(IFE)combined with enzyme inhibition mechanism.The AEP modification UCNPs can offer a stable fluorescence donor at 658 nm and be quenched by the oxidized tetramethylbenzidine(oxTMB)catalyzed by horseradish peroxidase(HRP)enzymes.Without addition of Cd^(2+),the fluorescence of AEP@UCNPs fluorescence sensor was weaken due to the IFE between AEP@UCNPs and oxTMB.With addition of Cd^(2+),HRP enzyme activity was inhibited by Cd^(2+),leading to the decreased oxTMB,resulting in the enhance upconversion fluorescence intensity.As a result,the fluorescence intensity signal at 658 nm of the IFE-based AEP@UCNPs fluorescence sensor increased linearly with the increase in Cd^(2+)in a wide range from 0.5μmol/L to 6μmol/L and the limit of detection(LOD)was 24.6 n mol/L.In addition,our proposed IFE-based AEP@UCNPs fluorescence sensor can achieve Cd^(2+)detection in paddy rice in 30 min. 展开更多
关键词 Paddy rice Cd^(2+) Enzyme inhibition Upconversion nanoparticles(UCNPs) Inner filter effect(IFE)
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COX-2 inhibition synergizes with radioimmunotherapy by promoting TCF1+CD8+T cell infiltration in NSCLC
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作者 Lin Ma Menglin Bai +3 位作者 Yao Wang Xueying Zhai Jinming Yu Xiangjiao Meng 《Cancer Biology & Medicine》 2025年第12期1537-1543,共7页
Non-small cell lung cancer(NSCLC)is a leading cause of cancer-related mortality worldwide1-3.While radioimmuno-therapy shows promise in boosting antitumor immunity,the clinical outcomes have been inconsistent4 and are... Non-small cell lung cancer(NSCLC)is a leading cause of cancer-related mortality worldwide1-3.While radioimmuno-therapy shows promise in boosting antitumor immunity,the clinical outcomes have been inconsistent4 and are often lim-ited by the immunosuppressive tumor microenvironment(TME).Cyclooxygenase(COX)-2 and the COX-2 downstream product,prostaglandin E2(PGE2),are increasingly implicated in immune escape5,6 but the impact on radioimmunother-apy efficacy has not been explored.TCF1-expressing CD8+T cells demonstrate defining functional properties of progeni-tor-exhausted T cells,including clonal expansion through self-renewal capacity and multipotent differentiation toward terminal effector phenotypes,while maintaining long-term persistence critical for sustaining antitumor immunity7-9.Given the central role in anti-tumor immune maintenance,TCF1+CD8+T cells are likely critical to radioimmunotherapy efficacy10.The role of COX-2 inhibition in enhancing the effi-cacy of radioimmunotherapy efficacy in NSCLC was investi-gated in the current study. 展开更多
关键词 boosting antitumor immunitythe prostaglandin E non small cell lung cancer immune escape TCF CD T cells cox inhibition tumor microenvironment tme cyclooxygenase cox RADIOIMMUNOTHERAPY
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Chemical Constituents of Pu-erh Tea and Its Inhibition Effect on α-amylase in vitro 被引量:21
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作者 张冬英 邵宛芳 +2 位作者 刘仲华 黄业伟 施兆鹏 《Agricultural Science & Technology》 CAS 2010年第1期130-132,共3页
[Objective]The aim was to clarify the chemical substance basis of hypoglycemic and lipid-lowering effects of Pu-erh Tea. [Method]Pu-erh Tea was extracted with 95% ethanol,followed by petroleum ether,chloroform,ethyl a... [Objective]The aim was to clarify the chemical substance basis of hypoglycemic and lipid-lowering effects of Pu-erh Tea. [Method]Pu-erh Tea was extracted with 95% ethanol,followed by petroleum ether,chloroform,ethyl acetate and n-butanol extraction,after the further purification and through the NKA-9 macroporous resin and many times of Sephadex column chromatography,two compounds were isolated,in the same time,the effect of Uracil and Gallic acid on α-amylase was studied. [Result]The Uracil and Gallic acid were isolated and identified respectively from Pu-erh Tea and the Uracil was firstly isolated from Pu-erh Tea; Gallic acid had strong inhibition on α-amylase. [Conclusion]It could provide some theories on the hypoglycemic and lipid-lowering effects of Pu-erh Tea. 展开更多
关键词 Pu-erh Tea URACIL Gallic acid Α-AMYLASE inhibition
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Inhibition of Chlamydospore Germination and Mycelial Growth of Trichoderma spp. by Chemical Fungicides 被引量:2
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作者 张林 蒋细良 +2 位作者 杨晓燕 李梅 陈书华 《Agricultural Science & Technology》 CAS 2015年第7期1494-1499,共6页
For exploring the influences of application and residue of chemical fungi- cides on chlamydospore preparations of Trichoderma spp., the effects of seven chemical fungicides on chlamydospore germination and mycelia gro... For exploring the influences of application and residue of chemical fungi- cides on chlamydospore preparations of Trichoderma spp., the effects of seven chemical fungicides on chlamydospore germination and mycelia growth of two bio- control fungi T. harzianum 610 and T. Iongibrachiatum 758 were studied. Carben- dazim, tebuconazole and difenoconazole showed strong toxicities, thiram and car- bexin showed moderate toxicities, and metalaxyl showed Mycelia growth of the two strains was more sensitive to most tested fungicides than those of chlamydospore germination. Chlamydospore germination of 610 was more sensitive to tested fungicides than those of 758, and mycelia growth of 758 was more sensitive to most tested fungi- cides than those of 610. Among the seven fungicides, 98% carbendazim had the strongest effects (ECru values were 1.64 and 0.05μpg/ml), and 70% pentachloroni- trobenzene had the weakest effects (EC50 values were 1.64 and 0,05 μg/ml) for chlamydospore germination and mycelia growth of 610. As for 758, 98% carbendaz- im had the strongest inhibitory effects and 95% metalaxyl had the weakest inhibitory for chlamydospore germination of 756 (EC50 values were 0.62 and 1 108.61 μg/ml respectively), whereas 96.2% tebuconazole showed the strongest inhibitory effects for mycelia growth of 758 (EC= value was 0.32μg/ml), and 95% metalaxyl was the weakest (EC= value was 1 206.29 μg/ml). According to the applied concentration of different fungicides in practice, we concluded that chlamydospore preparations of 610 and 758 could not be combined with carbendazim, tebuconazole, thiram and carboxin for controlling plant diseases, and the pesticide residues to the biocontrol effects should be kept in mind. Chlamydospore preparations of 610 and 758 can be and difenoconazole for controlling plant dis- eases, 758 chlamydospore preparations and germinated chlamydospore of 610 can be combined with metalaxyl for controlling plant diseases, and pesticide residue risk was not serious. 展开更多
关键词 Chemical fungicide inhibition Trichoderma spp: Chlamydospore germi- nation Mycelia growth
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