Near-infrared fluorophores with absolute aggregation-caused quenching and negligible fluorescence re-illumination for in vivo bioimaging of nanocarriers

Environment-responsive fluorophores with aggregation-caused quenching(ACQ)properties have been applied to track nanocarriers with reduced artefacts caused by unbound or free fluorophores but suffer from incomplete fluorescence quenching and significant re-illumination,which undermine bioimaging accuracy.Herein,through structural modifications to reinforce the hydrophobicity,planarity and rigidity of fluorophores with an aza-BODIPY framework,probes featuring absolute ACQ(aACQ)and negligible re-illumination are developed and evaluated in various nanocarriers.aACQ probes,FD-B21 and FD-C7,exhibit near-infrared emission,high quantum yield,photostability,water sensitivity,and negligible re-illumination in blood,plasma and 1%Tween-80 in contrast to ACQ probe P2 and conventional probe DiR.All nanocarriers can be labeled efficiently by the tested fluorophores.Polymeric micelles(PMs)labeled by different aACQ probes manifest similar biodistribution patterns,which however differ from that of DiR-labeled PMs and could be ascribed to the appreciable re-illumination of DiR.Significantly lower re-illumination is also found in aACQ probes(2%-3%)than DiR(20%-40%)in Caco-2,Hela,and Raw264.7 cells.Molecular dynamics simulations unravel the molecular mechanisms behind aggregation and re-illumination,supporting the hypothesis of planarity dependency.It is concluded that aACQ fluorophores demonstrate excellent water sensitivity and negligible fluorescence re-illumination,making themselves useful tools for more accurate bioimaging of nanocarriers.

Permeation into but not across the cornea:Bioimaging of intact nanoemulsions and nanosuspensions using aggregation-caused quenching probes

Nanoemulsions(NEs) and nanosuspensions(NSs) show great potential in enhancing the ocular bioavailability of therapeutics through topical delivery. However, transocular fate of intact NEs and NSs is still inconclusive. In this study, an aggregation-caused quenching fluorescent probe is used to track precorneal retention and transocular transportation of intact NEs and NSs, while coumarin 6 is used to mimick the cargo. NEs show superior precorneal retention to NSs. Both the two types of nanocarriers can permeate into but not across the cornea. The smaller NEs(100 nm) permeate better into the cornea than the bigger ones(210 nm). Nanocarriers in the cornea serves as depots. The released cargo molecules can penetrate across the cornea and diffuse into the lens. Moreover, the conjunctiva-scleral route may be potential to deliver drugs to the back of the eye, In conclusion, the study provides useful tools and information in the field of transocular transportation of nanoparticles.

Insight into the in vivo fate of intravenous herpetrione amorphous nanosuspensions by aggregation-caused quenching probes

Intravenous nanosuspensions are attracted growing attention as a viable strategy for development of intravenous formulations of poorly water-soluble drugs.However,only few information about the biological fate of intravenous nanosuspensions is currently known,especially amorphous nanosuspensions are not reported yet.In this study,the in vivo fate of herpetrione(HPE)amorphous nanosuspensions following intravenous administration was explored by using an aggregation-caused quenching(ACQ)probe and HPLC methods.The ACQ probe is physically embedded into HPE nanoparticles via anti-solvent method to form HPE hybrid nanosuspensions(HPE-HNSs)for bioimaging.HPE-HNSs emit strong and stable fluorescence,but fluorescence quenches immediately upon the dissolution of HPE-HNSs,confirming the selfdiscrimination of HPE-HNSs.Following intravenous administration of HPE-HNSs,integral HPE-HNSs and HPE show similar degradation and biodistribution,with rapid clearance from blood circulation and obvious accumulation in liver and lung.Due to the slower dissolution and enhanced recognition by reticuloendothelial system,450 nm HPE-HNSs accumulate more in liver,lung and spleen than that of 200 nm HPE-HNSs.These results demonstrate that integral HPE-HNSs determine the in vivo performance of HPEHNSs.This study provides insight into the in vivo fate of intravenous amorphous nanosuspensions.

Accurate and sensitive probing of onset of micellization based on absolute aggregation-caused quenching effect

Probing the onset of micellization,or determining the critical micelle concentration(CMC),is of crucial importance while remains to be challenged by growing demand for extraordinary sensitivity and accuracy.Although fluorometry has attracted wide attention owing to its superiority in simplicity and sensitivity over other methods,the presence and fluctuation of background fluorescence of conventional fluorescent probes undermine the accuracy of CMC determination.Herein,a series of novel fluorescent probes without background fluorescence at a concentration below CMC owing to absolute aggregation-caused quenching(aACQ)are utilized for sensitive and accurate measurement of CMC.The aACQ probes aggregate spontaneously and instantly in an aqueous environment owing to molecular π-π stacking with fluorescence quenching absolutely.Therefore,the absence of background fluorescence at a concentration below CMC clears relevant interference associated with conventional fluorophores.In this study,the new method is applied for versatile surfactants with CMCs ranging from nanomolar to millimolar concentrations,especially copolymers with ultralow CMC.The higher sensitivity and accuracy are highlighted by comparison with conventional probes.

An Experimental Artificial Neural Network Model:Investigating and Predicting Effects of Quenching Process on Residual Stresses of AISI 1035 Steel Alloy

The present study establishes a new estimation model using an artificial neural network(ANN) to predict the mechanical properties of the AISI 1035 alloy.The experiments were designed based on the L16 orthogonal array of the Taguchi method.A proposed numerical model for predicting the correlation of mechanical properties was supplemented with experimental data.The quenching process was conducted using a cooling medium called “nanofluids”.Nanoparticles were dissolved in a liquid phase at various concentrations(0.5%,1%,2.5%,and 5% vf) to prepare the nanofluids.Experimental investigations were done to assess the impact of temperature,base fluid,volume fraction,and soaking time on the mechanical properties.The outcomes showed that all conditions led to a noticeable improvement in the alloy's hardness which reached 100%,the grain size was refined about 80%,and unwanted residual stresses were removed from 50 to 150 MPa.Adding 5% of CuO nanoparticles to oil led to the best grain size refinement,while adding 2.5% of Al_(2)O_(3) nanoparticles to engine oil resulted in the greatest compressive residual stress.The experimental variables were used as the input data for the established numerical ANN model,and the mechanical properties were the output.Upwards of 99% of the training network's correlations seemed to be positive.The estimated result,nevertheless,matched the experimental dataset exactly.Thus,the ANN model is an effective tool for reflecting the effects of quenching conditions on the mechanical properties of AISI 1035.

Lanthanide-based bulky counterions against aggregation-caused quenching of dyes in fluorescent polymeric nanoparticles

Dye-loaded polymeric nanoparticles(NPs)are promising bioimaging agents because of their available surface chemistry,high brightness,and tunable optical properties.However,high dye loadings can cause the aggregation-caused quenching(ACQ)of the encapsulated fluorophores.Previously,we proposed to mitigate the ACQ inside polymeric NPs by insulating cationic dyes with bulky hydrophobic counterions.In order to implement new functionalities into dye-loaded NPs,here,we extend the concept of bulky counterions to anionic lanthanide-based complexes.We show that by employing Gd-based counterions with octadecyl rhodamine B loaded NPs at 30 wt% versus polymer,the fluorescence quantum yield can be increased to 10-fold(to 0.34).Moreover,Gd-anion provides NPs with enhanced contrast in electron microscopy.A combination of a luminescent Eu-based counterion with a far-red to near-infrared cyanine 5 dye(DiD)yields Forster resonance energy transfer NPs,where the UV-excited Eu-based counterion transfers energy to DiD,generating delayed fluorescence and large stokes shift of -340 nm.Cellular studies reveal low cytotoxicity of NPs and their capacity to internalize without detectable dye leakage,in contrast to leaky NPs with small counterions.Our findings show that the aggregation behavior of cationic dyes in the polymeric NPs can be controlled by bulky lanthanide anions,which will help in developing bright luminescent multifunctional nanomaterials.

Analysis of Quenching Resistor Effect to Improve Stability of TIA Circuit for APD-A Secondary Publication

In this paper,since the Avalanche Photo Diode(APD)for Light-to-Voltage LTV conversion uses a high voltage in the operating range unlike other Photo Diodes(PD),the quenching resistor must be connected in series to prevent overcurrent when using the Transimpedance Amplifier(TIA).In such a case,quenching resistance may affect the transfer function of the TIA circuit,resulting in serious stability.Therefore,in this paper,by analyzing the effect of APD quenching resistance on the voltage and current loop transfer function of TIA,we proposed a loop analysis and a method for determining the quenching resistance value to improve stability.A TIA circuit with quenching resistance was designed by the proposed method and its operational stability was verified through simulation and chip fabrication.

Discussion on the Free Quenching Heat Treatment Process of Automotive Leaf Springs

Free quenching of automotive leaf springs is a new technology that has gradually started to be applied in the industry in China in recent years.Only a few manufacturers are applying it in the industry.Through more than half a year of on-site practice,the changes in the hot forming of spring plates before free quenching have been explored,and finally a heat treatment process that meets the production requirements of our company has been developed,achieving normal production.

Influence of quenching medium on the dendrite morphology,hardness,and tribological behaviour of cast Cu-Ni-Sn spinodal alloy for defence application

Cu-Ni-Sn spinodal alloys(Spinodal bronze)are potential materials with robust applications in components associated with defence applications like bearings,propellers,bushes,and shafts of heavily loaded aircraft,off-road vehicles,and warships.This paper presents a comparative study using water,Brine solution,and SAE 40 oil as the quenching media in regular bronze(Cu-6Sn)and spinodal bronze(Cu-9Ni-6Sn)alloys.Morphological analysis was conducted by optical microscopy,transmission electron microscopy(TEM),and X-ray diffraction technique(XRD)on bronze and spinodal bronze samples immersed in the three different quenching media to understand the grain size and hardness values better.Tribological analysis was performed to analyze the effect of quenching media on the wear aspects of bronze and spinodal bronze samples.The hardness value of the brine-aged spinodal bronze samples was as high as 320 Hv,and the grain size was very low in the range of 60μm.A quantitative comparison between brine-aged regular bronze and brine-aged spinodal bronze showed that the hardness(Hv)was almost 80%higher for brine-aged spinodal bronze.Further,the grain size was approximately 30%finer for spinodal bronze when compared with regular bronze.When the load was increased in spinodal bronze samples,there was an initial dip in wear rate followed by a marginal increase.There was a steady increase in friction coefficient with a rise in load for brine-aged regular bronze and spinodal bronze samples.These results indicate that brine solution is the most effective quenching medium for cast Cu-Ni-Sn spinodal alloys.

Influence of two distinct quenching end-temperatures on phase development and mechanical properties in QP980 steel

Bainite microstructures have become increasingly attractive for the development of advanced high-strength steel owing to their balanced strength-plasticity properties.In this study, the final microstructure and mechanical properties of a quenching and partitioning(QP) steel sample after two distinct QP processes were analyzed.The results reveal that martensite transformation after quenching resulted in a lathed morphology with higher yield strength and hole expansion ratio.In contrast, bainite transformation after quenching resulted in the formation of a blocky microstructure composed of bainitic ferrite retained austenite and nanoscale precipitates during the subsequent phase transformation at a higher temperature.This kind of final microstructure is beneficial to the elongation of QP steel but detrimental to the hole expansion ratio.

Residual stress with asymmetric spray quenching for thick aluminum alloy plates

Solution and quenching heat treatments are generally carried out in a roller hearth furnace for large-scale thick aluminum alloy plates.However,the asymmetric or uneven spray water flow rate is inevitable under industrial production conditions,which leads to an asymmetric residual stress distribution.The spray quenching treatment was conducted on self-designed spray equipment,and the residual stress along the thickness direction was measured by a layer removal method based on deflections.Under the asymmetric spray quenching condition,the subsurface stress of the high-flow rate surface was lower than that of the low-flow rate surface,and the difference between the two subsurface stresses increased with the increase in the difference in water flow rates.The subsurface stress underneath the surface with a water flow rate of 0.60 m^(3)/h was 15.38 MPa less than that of 0.15 m^(3)/h.The simulated residual stress by finite element(FE)method of the high heat transfer coefficient(HTC)surface was less than that of the low HTC surface,which is consistent with the experimental results.The FE model can be used to analyze the strain and stress evolution and predict the quenched stress magnitude and distribution.

Effect of quenching and tempering processes on properties and microstructure of G115 steel

The novel martensitic heat-resistant steel G115 was designed for thick-section boiler components of ultra-supercritical(USC) power plants at 630-650 ℃.The impact of the quenching and tempering processes on the properties and microstructure of G115 steel was explored.The samples that were quenched and tempered twice had a higher tensile strength at room temperature and 650 ℃,and the impact energy was significantly improved.The strength and impact energy increased in proportion to the increase in the first quenching temperature.The microstructure differences between the single and double quenched and tempered samples were examined using metallographic microscopy and scanning electron microscopy.The grain size of the double quenched and tempered samples was finer than that of the single quenched and tempered samples, and the tempered martensite lath is more visible, as are the carbides and other precipitates, which are finer and more uniformly distributed.As the first quenching temperature increased, the grains became coarser but more uniform.

Development and Application of Multi-phase Nitrides Bonded Silicon Carbide Lintel Blocks for Dry Quenching Furnaces

Multi-phase nitrides bonded silicon carbide lintel blocks were prepared using industrial SiC(SiC≥98 mass%,3-0.5,≤0.5 and≤0.044 mm),Si powder(Si≥98 mass%,≤0.044 mm),and SiO2 micropowder(SiO2≥96 mass%,d50=0.15 pm)as raw materials,and calcium lignosulfonate as the additive,batching,mixing,and molding on a vibration pressure molding machine,drying and then firing at 1420℃for 10 h in high-purity N2.The apparent porosity,the bulk density,the cold modulus of rupture,the hot modulus of rupture,and the linear expansion coefficient of the samples were tested.The phase composition and the microstructure of the samples at different nitriding depths(50,100,and 150 mm)were analyzed by XRD and SEM.The field application effects of the blocks were studied.The results show that:(1)the multi-phase nitrides bonded silicon carbide refractories can dynamically adjust their own phase composition and minimize structural and thermal stresses,improving the service life of key parts of dry quenching furnaces;(2)calcium lignosulfonate can improve the nitriding micro-environment of multi-phase nitrides bonded silicon carbide lintel blocks,successfully increasing the effective nitriding thickness of the blocks to 300 mm;(3)Sinosteel LI RR provides a unique concept in the design of materials and block types as well as the stable and scientific overall structure,promoting the industrialization process of dry quenching furnaces with long service life in China.

Dynamical nonlinear excitations induced by interaction quench in a two-dimensional box-trapped Bose-Einstein condensate

Manipulating nonlinear excitations,including solitons and vortices,is an essential topic in quantum many-body physics.A new progress in this direction is a protocol proposed in[Phys.Rev.Res.2043256(2020)]to produce dark solitons in a one-dimensional atomic Bose–Einstein condensate(BEC)by quenching inter-atomic interaction.Motivated by this work,we generalize the protocol to a two-dimensional BEC and investigate the generic scenario of its post-quench dynamics.For an isotropic disk trap with a hard-wall boundary,we find that successive inward-moving ring dark solitons(RDSs)can be induced from the edge,and the number of RDSs can be controlled by tuning the ratio of the after-and before-quench interaction strength across different critical values.The role of the quench played on the profiles of the density,phase,and sound velocity is also investigated.Due to the snake instability,the RDSs then become vortex–antivortex pairs with peculiar dynamics managed by the initial density and the after-quench interaction.By tuning the geometry of the box traps,demonstrated as polygonal ones,more subtle dynamics of solitons and vortices are enabled.Our proposed protocol and the discovered rich dynamical effects on nonlinear excitations can be realized in near future cold-atom experiments.

Phase diagram and quench dynamics of a periodically drivenHaldane model

We investigate a periodically driven Haldane model subjected to a two-stage driving scheme in the form of a step function.By using the Floquet theory,we obtain the topological phase diagram of the system.We also find that anomalous Floquet topological phases exist in the system.Focusing on examining the quench dynamics among topological phases,we analyze the site distribution of the 0-mode and p-mode edge states in long-period evolution after a quench.The results demonstrate that,under certain conditions,the site distribution of the 0-mode can be confined at the edge even in long-period evolution.Additionally,both the 0-mode and p-mode can recover and become confined at the edge in long-period evolution when the post-quench parameters(T,M_(2) /M_(1))in the phase diagram cross away from the phase boundary (M_(2)/ M_(1))=(6√3t2)/ M_(1)−1.Furthermore,we conclude that whether the edge state is confined at the edge in the long-period evolution after a quench depends on the similarity of the edge states before and after the quench.Our findings reveal some new characteristics of quench dynamics in a periodically driven system.

Visualization of Vapor Film Collapse Behavior with Complexity on Quenching Process by Cellular Automaton

The vapor film collapse that occurs in the quenching process is complicated and affects the heat treatment quality and its distortion.In order to incorporate it into the MBD(Model Based Development)technology required these days,it is necessary to predict the quality of heat treatment by CAE(Computer Added Engineering),shorten the product development period.The calculation of the vapor film collapses in a simple and practical time in order to improve the product performance.However,in the past,in order to formulate the vapor film collapse on a simulation,it was necessary to perform a very large amount of computational calculation CFD(computational fluid dynamics),which was a problem in terms of computer resources and the model of vapor film collapse.In addition,this phenomenon has a complexity behavior of the phenomenon in iterative processing,which also complicates the calculation.In this study,the vapor film collapse phenomenon is easily visualized using self-organized cellular automaton simulation which includes the phenomena of“vapor film thickness and its fluctuation”,“flow disturbance”,“surface step of workpiece”,and“decrease of cooling due to r shape of surface”.The average cooling state and repeated fluctuations of the cooling state were reproduced by this method.

Critical current degradation in an epoxy-impregnated rare-earth Ba_(2)Cu_(3)O_(7-x)coated conductor caused by damage during a quench

High-temperature superconducting(HTS)rare-earth Ba_(2)Cu_(3)O_(7-x)(REBCO)coated conductors(CCs)have significant potential in high-current and high-field applications.However,owing to the weak interface strength of the laminated composite REBCO CCs,the damage induced by the thermal mismatch stress under a combination of epoxy impregnation,cooling,and quenching can cause premature degradation of the critical current.In this study,a three-dimensional(3D)electromagnetic-thermal-mechanical model based on the H-formulation and cohesive zone model(CZM)is developed to study the critical current degradation characteristics in an epoxy-impregnated REBCO CC caused by the damage during a quench.The temperature variation,critical current degradation of the REBCO CC,and its degradation onset temperature calculated by the numerical model are in agreement with the experimental data taken from the literature.The delamination of the REBCO CC predicted by the numerical model is consistent with the experimental result.The numerical results also indicate that the shear stress is the main contributor to the damage propagation inside the REBCO CC.The premature degradation of the critical current during a quench is closely related to the interface shear strength inside the REBCO CC.Finally,the effects of the coefficient of thermal expansion(CTE)of the epoxy resin,thickness of the substrate,and substrate material on the critical current degradation characteristics of the epoxy-impregnated REBCO CC during a quench are also discussed.These results help us understand the relationship between the current-carrying degradation and damage in the HTS applications.

Simulation of temperature and stress in 6061 aluminum alloy during online quenching process

The cooling curves of 6061 aluminum alloy were acquired through water quenching experiment. The heat transfer coefficient was accurately calculated based on the cooling curves and the law of cooling. The online quenching process of complex cross-section profile was dynamically simulated by the ABAQUS software. The results suggest that the heat transfer coefficient changes during online quenching process. Different parts of the profile have different cooling velocity, and it was verified by water quenching experiment. The maximum residual stress of the profile was predicted using FEM simulation based on ABAQUS software The relations between the temperature and stress were presented by analyzing the data of key points.

Optimum design of flow distribution in quenching tank for heat treatment of A357 aluminum alloy large complicated thin-wall workpieces by CFD simulation and ANN approach

Based on the computational fluid dynamics （CFD） method, a quenching tank with two agitator systems and two flow-equilibrating devices was selected to simulate flow distribution using Fluent software. A numerical example was used to testify the validity of the quenching tank model. In order to take tank parameters （agitation speed, position of directional flow baffle and coordinate position in quench zone） into account, an approach that combines the artificial neural network （ANN） with CFD method was developed to study the flow distribution in the quenching tank. The flow rate of the quenching medium shows a very good agreement between the ANN predicted results and the Fluent simulated data. Methods for the optimal design of the quenching tank can be used as technical support for industrial production.

遏止(Quenching)及其在分析RTD逻辑电路中的应用

在深入分析共振隧穿二极管(RTD)开关前后内阻变化和RTD串联组合中不同RTD电压分布随总偏压变化的基础上,深化了“遏止(Q uench ing)”的概念。并进一步以此概念说明了RTD/HEM T电路中,单-双稳转换逻辑单元(M OB ILE)、多值逻辑(M VL)文字(L itera l)逻辑门、三态反相器(T ernary inverter)等逻辑单元的工作原理。通过此种分析,证实了“遏止”概念是解释和分析复杂RTD电路原理的强有力工具。以上论证也适用于由其它负阻器件构成的逻辑电路。