On-column capping of poly dT media-tethered mRNA accomplishes high capping efficiency, enhanced mRNA recovery, and improved stability against RNase.

The messenger RNA (mRNA) 5'-cap structure is indispensable for mRNA translation initiation and stability. Despite its importance, large-scale production of capped mRNA through in vitro transcription (IVT) synthesis using vaccinia capping enzyme (VCE) is challenging, due to the requirement of tedious and multiple pre-and-post separation steps causing mRNA loss and degradation. Here in the present study, we found that the VCE together with 2'-O-methyltransferase can efficiently catalyze the capping of poly dT media-tethered mRNA to produce mRNA with cap-1 structure under an optimized condition. We have therefore designed an integrated purification and solid-based capping protocol, which involved capturing the mRNA from the IVT system by using poly dT media through its affinity binding for 3'-end poly-A in mRNA, in situ capping of mRNA 5'-end by supplying the enzymes, and subsequent eluting of the capped mRNA from the poly dT media. Using mRNA encoding the enhanced green fluorescent protein as a model system, we have demonstrated that the new strategy greatly simplified the mRNA manufacturing process and improved its overall recovery without sacrificing the capping efficiency, as compared with the conventional process, which involved at least mRNA preseparation from IVT, solution-based capping, and post-separation and recovering steps. Specifically, the new process accomplished a 1.76-fold (84.21% over 47.79%) increase in mRNA overall recovery, a twofold decrease in operation time (70 vs. 140 min), and similar high capping efficiency (both close to 100%). Furthermore, the solid-based capping process greatly improved mRNA stability, such that the integrity of the mRNA could be well kept during the capping process even in the presence of exogenously added RNase; in contrast, mRNA in the solution-based capping process degraded almost completely. Meanwhile, we showed that such a strategy can be operated both in a batch mode and in an on-column continuous mode. The results presented in this work demonstrated that the new on-column capping process developed here can accomplish high capping efficiency, enhanced mRNA recovery, and improved stability against RNase; therefore, can act as a simple, efficient, and cost-effective platform technology suitable for large-scale production of capped mRNA.

Numerical simulation of a mechanical flocculation process with multi-chambers in series.

A mechanical flocculation system with multi-chambers in series is commonly used as the advanced phosphorus removal technology for wastewater treatment. This work aims to numerically investigate the inner states and overall performance of industrial-scale mechanical flocculators in series. This is based on our previously developed computational fluid dynamics (CFD) flocculation model which is extended to consider the key chemical reactions of phosphorus removal. The effects of the number of flocculation chambers, locations, and sizes of the flocculation chamber connection as well as operational combinations of impeller speeds are investigated. With a decreasing number of flocculation chambers, the main vortexes and chemical reactions are weakened, while the small flocs form. Both the phosphorus removal efficiency η and the average floc size dp reduce as the number of flocculation chambers decreases. The connection location of flocculation chambers directly determines the turbulent flow, thus influencing the key performance indicators. However, the phosphorus removal efficiency η and average particle size dp are little affected by the size of the flocculation chamber connection. As the impeller speeds in series gradually increase, the gradient of floc size distribution in each chamber is enlarged and the chemical reaction is enhanced over the working volume.

Self-Assembly of Ir-Based Nanosheets with Ordered Interlayer Space for Enhanced Electrocatalytic Water Oxidation.

Iridium (Ir)-based electrocatalysts are widely explored as benchmarks for acidic oxygen evolution reactions (OERs). However, further enhancing their catalytic activity remains challenging due to the difficulty in identifying active species and unfavorable architectures. In this work, we synthesized ultrathin Ir-IrOx/C nanosheets with ordered interlayer space for enhanced OER by a nanoconfined self-assembly strategy, employing block copolymer formed stable end-merged lamellar micelles. The interlayer distance of the prepared Ir-IrOx/C nanosheets was well controlled at ∼20 nm and Ir-IrOx nanoparticles (∼2 nm) were uniformly distributed within the nanosheets. Importantly, the fabricated Ir-IrOx/C electrocatalysts display one of the lowest overpotential (η) of 198 mV at 10 mA cm-2geo during OER in an acid medium, benefiting from their features of mixed-valence states, rich electrophilic oxygen species (O(II-δ)-), and favorable mesostructured architectures. Both experimental and computational results reveal that the mixed valence and O(II-δ)- moieties of the 2D mesoporous Ir-IrOx/C catalysts with a shortened Ir-O(II-δ)- bond (1.91 Å) is the key active species for the enhancement of OER by balancing the adsorption free energy of oxygen-containing intermediates. This strategy thus opens an avenue for designing high performance 2D ordered mesoporous electrocatalysts through a nanoconfined self-assembly strategy for water oxidation and beyond.

In Vitro and In Silico Investigations on Drug Delivery in the Mouth-Throat Models with Handihaler®.

This work aimed to evaluate the relative inhalation parameters that affect the deposition of inhaled aerosols, including mouth-throat morphology, airflow rate, and initial condition of emitted particles. In vitro experiments were conducted using the US Pharmacopeia (USP) throat and a realistic mouth-throat (RMT) with Handihaler®. Then, in silico study of the gas-solid flow was performed by computational fluid dynamics and discrete phase method. Results indicated that aerosol deposition in RMT was higher compared to that in USP throat at an airflow rate of 30 L/min, with 33.16 ± 7.84% and 21.11 ± 7.1% lung deposition in USP throat and RMT models, respectively, which showed a better correlation with in vivo data from the literature. Increasing airflow rate resulted in better drug aerosolization, while the fine particle dose trend ascended before declining, with the peak value obtained at a flow rate of 40 L/min. Overall, the effect of geometrical variation was more significant. Additionally, in silico results demonstrated clearly that the initial conditions of the emitted particles from inhalers affected the subsequent deposition. Larger momentum possessed by the central aerosol jet entering the mouth directly led to stronger impaction, which resulted in the deposition in the front region of mouth-throat models. This study is beneficial to develop an in silico method to understand the underlying mechanisms of in vivo mouth-throat deposition.

Computational investigation of dust mite allergens in a realistic human nasal cavity.

Aim: Inhaled allergens from house dust mite (HDM) are a major source of allergic disease such as allergic rhinitis and asthma. It has been a challenge to properly evaluate health risks caused by HDM related allergens including mite bodies, eggs and fecal pellets. This paper presents a numerical study on particle deposition of dust mite allergens in a human nasal cavity. Materials and methods: A realistic nasal cavity model was reconstructed from CT scans and a Computational Fluid Dynamics analysis of steady airflow was simulated. The discrete phase model was used to trace particle trajectories of three dust mite related particles. Results: The flow and particle model were validated by comparing with nasal resistance measurement and previous literature respectively. Aerodynamic characteristics and deposition of dust mite allergens in the nasal cavity were analyzed under different breathing conditions including rest and exercising conditions. Conclusions: The numerical results revealed the roles of different nasal cavity regions in filtering various types of dust mite allergens with consideration of breathing conditions.

Dynamic modelling on the confined crystallization of mono-sized cubic particles under mechanical vibration.

The dynamic crystallization of cubic granular particles under three-dimensional mechanical vibration is numerically investigated by the discrete element method. The effects of operational conditions (vibration, container shape and system size) and particle properties (gravity and friction) on the formation of crystals and defects are discussed. The results show that the formation and growth of clusters with face-to-face aligned cubic particles can be easily realized under vibrations. Especially, a single crystal with both translational and orientational ordering can be reproduced in a rectangular container under appropriate vibrations. It is also found that the gravitational effect is beneficial for the ordering of a packing; the ordering of frictional particles can be improved significantly with an enlarged gravitational acceleration. The flat walls of a rectangular container facilitate the formation of orderly layered structures. The curved walls of a cylindrical container contribute to the formation of ring-like structures, whereas they also cause distortions and defects in the packing centers. Finally, it is shown that the crystallization of inelastic particles is basically accomplished by the pursuit of a better mechanical stability of the system, with decreasing kinetic and potential energies.

Topologically close-packed characteristic of amorphous tantalum.

The structural evolution of tantalum (Ta) during rapid cooling was investigated by molecular dynamics simulation, in terms of the system energy, the pair distribution function and the largest standard cluster analysis. It was found that the critical cooling rate for vitrification was about R ≥ 0.25 K ps-1, two orders lower than other metals (such as Au, Ag, Al, Zr and Zn) and that the meta-stable σ phase (ß-Ta) not only appears on the pathway from liquid to the stable body-centred cubic crystal, but is also easily obtained at room temperature as a long-lived metastable phase with some probability. The most interesting point is that the liquid, amorphous and ß-Ta phases share a nontrivial structural homology; the intrinsic topologically close-packed (TCP) structures in liquids are inherited and developed in different ways, resulting in amorphous or crystalline solids, respectively. With highly local packing fractions and geometrical incompatibility with the global close-packed (such as hcp, fcc and bcc) crystals, TCP structures inevitably result in structural heterogeneity and favour vitrification. As a superset of icosahedrons, TCP structures are ubiquitous in metallic melts, and just before the onset of crystallization reach their maximal number, which is much bigger in Ta than in other poor-GFA metals; so we argue that the strong forming ability of TCP local structures significantly enhances the glass forming ability of pure metals. These findings open up a new perspective that could have a profound impact on the research into metallic glasses.

Superwettability Strategy: 1D Assembly of Binary Nanoparticles as Gas Sensors.

Binary 1D nanowires consisting of both SnO2 nanoparticles and Au nanorods are fabricated through a "substrate-particle solution template" assembling method, which shows highly enhanced gas sensitivity toward acetone under ambient conditions.

Seedless Synthesis of Monodispersed Gold Nanorods with Remarkably High Yield: Synergistic Effect of Template Modification and Growth Kinetics Regulation.

Gold nanorods (AuNRs) are versatile materials due to their broadly tunable optical properties associated with their anisotropic feature. Conventional seed-mediated synthesis is, however, not only limited by the operational complexity and over-sensitivity towards subtle changes of experimental conditions but also suffers from low yield (≈15 %). A facile seedless method is reported to overcome these challenges. Monodispersed AuNRs with high yield (≈100 %) and highly adjustable longitudinal surface plasmon resonance (LSPR) are reproducibly synthesized. The parameters that influence the AuNRs growth were thoroughly investigated in terms of growth kinetics and soft-template regulation, offering a better understanding of the template-based mechanism. The facile synthesis, broad tunability of LSRP, high reproducibility, high yield, and ease of scale-up make this method promising for the future mass production of monodispersed AuNRs for applications in catalysis, sensing, and biomedicine.

Direct Hydrothermal Synthesis of Carbonaceous Silver Nanocables for Electrocatalytic Applications.

This study demonstrates a facile but efficient hydrothermal method for the direct synthesis of both carbonaceous silver (Ag@C core-shell) nanocables and carbonaceous nanotubes under mild conditions (<180 °C). The carbonaceous tubes can be formed by removal of the silver cores via an etching process under temperature control (60-140 °C). The structure and composition are characterized using various advanced microscopic and spectroscopic techniques. The pertinent variables such as temperature, reaction time, and surfactants that can affect the formation and growth of the nanocables and nanotubes are investigated and optimized. It is found that cetyltrimethylammonium bromide plays multiple roles in the formation of Ag@C nanocables and carbonaceous nanotubes including: a shape controller for metallic Ag wires and Ag@C cables, a source of Br(-) ions to form insoluble AgBr and then Ag crystals, an etching agent of silver cores to form carbonaceous tubes, and an inducer to refill silver particles into the carbonaceous tubes to form core-shell structures. The formation mechanism of carbonaceous silver nanostructures depending upon temperature is also discussed. Finally, the electrocatalytic performance of the as-prepared Ag@C nanocables is assessed for the oxidation reduction reaction and found to be very active but much less costly than the commonly used platinum catalysts. The findings should be useful for designing and constructing carbonaceous-metal nanostructures with potential applications in conductive materials, catalysts, and biosensors.

Multi-scale modelling of powder dispersion in a carrier-based inhalation system.

PURPOSE: Carrier-based dry powder inhalers (DPIs) are widely used for rapid and convenient delivery of drug to the site of action. This work aimed to predict powder aerosolisation in DPIs through numerical modelling. METHODS: A multi-scale modelling technique based on the combined computational fluid dynamics (CFD) and discrete element method (DEM) approach was developed. RESULTS: The simulation results of the detachments of the drug particles from single carrier under different impact velocities and angles were comparable with those measured in the experiments in terms of fine particle fraction FPF loaded . Empirical equations were developed to link the detachment performance with impact velocity and impact angle. Then the dynamics of the carrier particles in Aerolizer® was simulated. The results indicated that the carrier-wall impaction was the dominant mechanism for drug aerosolisation performance. By linking the empirical equations with the carrier-wall impact energy, the predictions showed that for a given formulation mass with a fixed carrier/drug ratio, the inhaler performance decreased with carrier size and increased with air flow rate. Device empty efficiency, however, was independent with carrier size and flow rate. CONCLUSIONS: The multi-scale model was able to provide quantitative information to better understand the aerosolisation mechanisms of carrier-based formulation.

Why have continuum theories previously failed to describe sandpile formation?

Granular piling may or may not induce a counterintuitive phenomenon of pressure dip at the center of a pile base. Understanding the behavior is a long-standing challenge in granular dynamics modeling. Here we show that the experimental observations of dip or nondip piles can be satisfactorily reproduced by the classic elastoplastic models. Our results demonstrate that (i) dynamic history is a critical factor in the successful description of a piling process and (ii) the dip phenomena are complicated, involving numerous variables associated not only with piling operation but also material properties. Our findings can explain why previous attempts failed to describe piling processes and may open up a new direction to describe granular materials in nature and many industrial processes.

Crystal plane-dependent gas-sensing properties of zinc oxide nanostructures: experimental and theoretical studies.

The sensitivity of a metal oxide gas sensor is strongly dependent on the nature of the crystal surface exposed to the gas species. In this study, two types of zinc oxide (ZnO) nanostructures: nanoplates and nanorods with exposed (0001) and (10̄10) crystal surfaces, respectively, were synthesized through facile solvothermal methods. The gas-sensing results show that sensitivity of the ZnO nanoplates toward ethanol is two times higher than that of the ZnO nanorods, at an optimum operating temperature of 300 °C. This could be attributed to the higher surface area and the exposed (0001) crystal surfaces. DFT (Density Functional Theory) simulations were carried out to study the adsorption of ethanol on the ZnO crystal planes such as (0001), (10̄10), and (11̄20) with adsorbed O(-) ions. The results reveal that the exposed (0001) planes of the ZnO nanoplates promote better ethanol adsorption by interacting with the surface oxygen p (O2p) orbitals and stretching the O-H bond to lower the adsorption energy, leading to the sensitivity enhancement of the nanoplates. These findings will be useful for the fabrication of metal oxide nanostructures with specifically exposed crystal surfaces for improved gas-sensing and/or catalytic performance.

Comparative Analysis of Micrometer-Sized Particle Deposition in the Olfactory Regions of Adult and Pediatric Nasal Cavities: A Computational Study.

Direct nose-to-brain drug delivery, a promising approach for treating neurological disorders, faces challenges due to anatomical variations between adults and children. This study aims to investigate the spatial particle deposition of micron-sized particles in the nasal cavity among adult and pediatric subjects. This study focuses on the olfactory region considering the effect of intrasubject parameters and particle properties. Two child and two adult nose models were developed based on computed tomography (CT) images, in which the olfactory region of the four nasal cavity models comprises 7% to 10% of the total nasal cavity area. Computational Fluid Dynamics (CFD) coupled with a discrete phase model (DPM) was implemented to simulate the particle transport and deposition. To study the deposition of micrometer-sized drugs in the human nasal cavity during a seated posture, particles with diameters ranging from 1 to 100 µm were considered under a flow rate of 15 LPM. The nasal cavity area of adults is approximately 1.2 to 2 times larger than that of children. The results show that the regional deposition fraction of the olfactory region in all subjects was meager for 1-100 µm particles, with the highest deposition fraction of 5.7%. The deposition fraction of the whole nasal cavity increased with the increasing particle size. Crucially, we identified a correlation between regional deposition distribution and nasal cavity geometry, offering valuable insights for optimizing intranasal drug delivery.

Numerical modelling of the interaction between dialysis catheter, vascular vessel and blood considering elastic structural deformation.

The dialysis catheter indwelling in human bodies has a high risk of inducing thrombus and stenosis. Biomechanical research showed that such physiological complications are triggered by the wall shear stress of the vascular vessel. This study aimed to assess the impact of CVC implantation on central venous haemodynamics and the potential alterations in the haemodynamic environment related to thrombus development. The SVC structure was built from the images from computed tomography. The blood flow was calculated using the Carreau model, and the fluid domain was determined by CFD. The vascular wall and the CVC were computed using FEA. The elastic interaction between the vessel wall and the flow field was considered using FSI simulation. With consideration of the effect of coupling, it was shown that the catheter vibrated in the vascular systems due to the periodic variation of blood pressure, with an amplitude of up to 10% of the vessel width. Spiral flow was observed along the catheter after CVC indwelling, and recirculation flow appeared near the catheter tip. High OSI and WSS regions occurred at the catheter tip and the vascular junction. The arterial lumen tip had a larger effect on the WSS and OSI values on the vascular wall. Considering FSI simulation, the movement of the catheter inside the blood flow was simulated in the deformable vessel. After CVC indwelling, spiral flow and recirculation flow were observed near the regions with high WSS and OSI values.

Tailored interface engineering of Co3Fe7/Fe3C heterojunctions for enhancing oxygen reduction reaction in zinc-air batteries.

The rational construction of highly active and robust non-precious metal oxygen reduction electrocatalysts is a vital factor to facilitate commercial applications of Zn-air batteries. In this study, a precise and stable heterostructure, comprised of a coupling of Co3Fe7 and Fe3C, was constructed through an interface engineering-induced strategy. The coordination polymerization of the resin with the bimetallic components was meticulously regulated to control the interfacial characteristics of the heterostructure. The synergistic interfacial effects of the heterostructure successfully facilitated electron coupling and rapid charge transfer. Consequently, the optimized CST-FeCo displayed superb oxygen reduction catalytic activity with a positive half-wave potential of 0.855 V vs. RHE. Furthermore, the CST-FeCo air electrode of the liquid zinc-air battery revealed a large specific capacity of 805.6 mAh gZn-1, corresponding to a remarkable peak power density of 162.7 mW cm-2, and a long charge/discharge cycle stability of 220 h, surpassing that of the commercial Pt/C catalyst.

Calculation of noncontact forces between silica nanospheres.

Quantification of the interactions between nanoparticles is important in understanding their dynamic behaviors and many related phenomena. In this study, molecular dynamics simulation is used to calculate the interaction potentials (i.e., van der Waals attraction, Born repulsion, and electrostatic interaction) between two silica nanospheres of equal radius in the range of 0.975 to 5.137 nm. The results are compared with those obtained from the conventional Hamaker approach, leading to the development of modified formulas to calculate the van der Waals attraction and Born repulsion between nanospheres, respectively. Moreover, Coulomb's law is found to be valid for calculating the electrostatic potential between nanospheres. The developed formulas should be useful in the study of the dynamic behaviors of nanoparticle systems under different conditions.

Bimetallic Ag-Au nanowires: synthesis, growth mechanism, and catalytic properties.

Silver-gold (Ag-Au) bimetallic nanowires were controllably synthesized by a newly developed wet-chemical method at room temperature. The Ag nanowires and Au nanoparticles were sequentially formed by reduction with vanadium oxide (V2O3) nanoparticles so as to form Ag-Au bimetal, in which the Ag nanowires show a diameter of ~20 nm and length up to 10 µm. A few unique features were noted in our new approach: it was rapid (within a few minutes), controllable in shape and size, reproducible, and there was no need for any surface modifiers. The formation and growth mechanisms of these Ag-Au bimetallic nanostructures driven by lattice match and a unique reducing agent (V2O3) have been proposed in this study. Moreover, the application of such bimetallic nanoparticles for catalytic reduction of 4-nitrophenol to 4-aminophenol was performed, and they exhibit catalytic properties superior to those of the Ag nanowires, Au nanoparticles, and Ag-Pd bimetallic nanostructures prepared under the reported conditions. These Ag-Au bimetallic nanoparticles have potential to be highly efficient catalysts for the reduction of 4-nitrophenol. This study may lead to new path for the generation of other bimetallic nanostructures with excellent catalytic efficiency.

Calculation of normal contact forces between silica nanospheres.

In this work, interaction forces between two silica nanospheres after contact, including the van der Waals (vdW) attraction, Born repulsion, and mechanical contact forces are studied by molecular dynamics (MD) simulations. The effects of interaction path (approach or departure), initial relative velocity, and relative orientations of two nanospheres are first examined. The results show that the interparticle forces are, to a large degree, independent of these variables. Then, emphasis is given to other important variables. At a small contact deformation, the size dependence of the vdW attraction and Born repulsion qualitatively agrees with the prediction based on the conventional theories, but this becomes vague upon further deformation due to the gradually flattened shape of deformed particles. An alternative approach is provided to calculate the interparticle vdW attraction and Born repulsion forces. Moreover, the MD simulations show that the Hertz model still holds to describe the mechanical contact force at low compression, which is obtained by subtracting the vdW attraction and Born repulsion forces from the total normal force. Comparisons with the Johnson-Kendall-Roberts (JKR) and Derjaguin-Muller-Toporov (DMT) models, in terms of force-displacement relationships and contact radius, show that the two models can be used to provide the first approximation, but there is some deviation from the MD simulated results. The origins of the quantitative difference are analyzed. New equations are formulated to estimate the interaction forces between silica nanospheres, which should be useful in the dynamic simulation of silica nanoparticle systems.

Experimental Study on Coaxial Waterjet-Assisted Laser Scanning Machining of Nickel-Based Special Alloy.

The problems of the recast layer, oxide layer, and heat-affected zone (HAZ) in conventional laser machining seriously impact material properties. Coaxial waterjet-assisted laser scanning machining (CWALSM) can reduce the conduction and accumulation of heat in laser machining by the high specific heat capacity of water and can realize the machining of nickel-based special alloy with almost no thermal damage. With the developed experimental setup, the laser ablation threshold and drilling experiments of the K4002 nickel-based special alloy were carried out. The effects of various factors on the thermal damage thickness were studied with an orthogonal experiment. Experimental results have indicated that the ablation threshold of K4002 nickel-based special alloy by a single pulse is 4.15 J/cm2. The orthogonal experiment results have shown that the effects of each factor on the thermal damage thickness are in the order of laser pulse frequency, waterjet speed, pulse overlap rate, laser pulse energy, and focal plane position. When the laser pulse energy is 0.21 mJ, the laser pulse frequency is 1 kHz, the pulse overlap is 55%, the focal plane position is 1 mm, and the waterjet speed is 6.98 m/s, no thermal damage machining can be achieved. In addition, a comparative experiment with laser drilling in the air was carried out under the same conditions. The results have shown that compared with laser machining in the air, the thermal damage thickness of CWALSM is smaller than 1 µm, and the hole taper is reduced by 106%. There is no accumulation and burr around the hole entrance, and the thermal damage thickness range is 0-0.996 µm. Furthermore, the thermal damage thickness range of laser machining in the air is 0.499-2.394 µm. It has also been found that the thermal damage thickness is greatest at the entrance to the hole, decreasing as the distance from the entrance increases.