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Lipid nanoparticles are increasingly used for drug and gene delivery, including the delivery of small interfering RNA (siRNA). Pulmonary delivery of drug molecules carried by lipid ...nanoparticles directly into the lung may improve the treatment of certain lung diseases. The present study was designed to test the feasibility of engineering aerosolizable dry powder of lipid nanoparticles by thin-film freeze-drying (TFFD). Solid lipid nanoparticles (SLNs) comprised of lecithin, cholesterol, and a lipid-polyethylene glycol conjugate were prepared by solvent evaporation. Dry powders of the SLNs were prepared by TFFD, spray drying, or conventional shelf freeze-drying. The physical and aerosol properties of the dry powders as well as the physical properties of the SLNs reconstituted from the dry powders were evaluated. The particle size, polydispersity index, and the zeta potential of the SLNs were preserved after they were subjected to TFFD and reconstitution, but not after they were subjected to conventional shelf freeze-drying and reconstitution, and the dry powder prepared by TFFD showed better aerosol performance properties than that prepared by spray drying. SLNs encapsulated with siRNA can also be successfully transformed into aerosolizable dry powder by TFFD, and subjecting the siRNA-encapsulated SLNs to TFFD did not negatively affect the function of the siRNA. It is concluded that TFFD represents a promising method to prepare aerosolizable dry powder of lipid nanoparticles.
Vascular precursor cells with angiogenic potentials are important for tissue repair, which is impaired in diabetes mellitus. MicroRNAs are recently discovered key regulators of gene expression, but ...their role in vascular precursor cell-mediated angiogenesis in diabetes mellitus is unknown. We tested the hypothesis that the microRNA miR-27b rescues impaired bone marrow-derived angiogenic cell (BMAC) function in vitro and in vivo in type 2 diabetic mice.
BMACs from adult male type 2 diabetic db/db and from normal littermate db/+ mice were used. miR-27b expression was decreased in db/db BMACs. miR-27b mimic improved db/db BMAC function, including proliferation, adhesion, tube formation, and delayed apoptosis, but it did not affect migration. Elevated thrombospondin-1 (TSP-1) protein in db/db BMACs was suppressed on miR-27b mimic transfection. Inhibition of miR-27b in db/+ BMACs reduced angiogenesis, which was reversed by TSP-1 small interfering RNA (siRNA). miR-27b suppressed the pro-oxidant protein p66(shc) and mitochondrial oxidative stress, contributing to its protection of BMAC function. miR-27b also suppressed semaphorin 6A to improve BMAC function in diabetes mellitus. Luciferase binding assay suggested that miR-27b directly targeted TSP-1, TSP-2, p66(shc), and semaphorin 6A. miR-27b improved topical cell therapy of diabetic BMACs on diabetic skin wound closure, with a concomitant augmentation of wound perfusion and capillary formation. Normal BMAC therapy with miR-27b inhibition demonstrated reduced efficacy in wound closure, perfusion, and capillary formation. Local miR-27b delivery partly improved wound healing in diabetic mice.
miR-27b rescues impaired BMAC angiogenesis via TSP-1 suppression, semaphorin 6A expression, and p66shc-dependent mitochondrial oxidative stress and improves BMAC therapy in wound healing in type 2 diabetic mice.
Organic‐inorganic hybrid halides have attracted widespread attention in optics, electricity, magnetism. In particular, some of them can have a combination of luminescence and switching ...characteristics, providing a potential for a single device unit to meet multiple application requirements. Herein, we reported two novel organic‐inorganic hybrid single‐crystals (CTA)2ZnCl4 (1; CTA=3‐chloro‐2‐hydroxypropyltrimethylammonium) and (CTA)2InCl5(H2O) ⋅ H2O (2), exhibiting long lifetime blue emission upon UV excitation. Systematic characterizations of the compounds including crystal structure, phase transition, thermal, and photoluminescence properties were carried out. DSC tests detected that 1 had a reversible phase transition accompanied by obvious heat anomaly, at 411/391 K on the heating/cooling process, leading to its good switchable dielectric response with striking anisotropy along various crystallographic axis. This work offered a new example on the effective design of multifunctional response materials.
Two environmentally friendly hybrid organic‐inorganic hybrid halides (CTA)2ZnCl4 and (CTA)2InCl5(H2O) ⋅ H2O were successfully synthesized, both which have shown blue light emission with a long lifetime of 0.3 s, indicating a visible optical response. Notably, (CTA)2ZnCl4 also exhibits a sensitive switchable dielectric property, which allows it to be a good multifunctional response material.
The monogamy relation of quantum states has limited the shareability properties of quantum resources in multiparty quantum systems. It plays a vital role in information distribution and ...transformation over many sites in quantum communications. Here, we focus on the monogamy relations of quantum correlations in the context of three-flavor neutrino oscillations, related to the squared entanglement of formation, the squared of quantum discord and its geometric variant. The monogamy relations in terms of the squared entanglement of formation work for the electron and muon antineutrino oscillations, suggesting that the bipartite entanglement measured by squared entanglement of formation of the three-flavor neutrino system set a limitation to the sum of pairwise squared entanglement of formation. Furthermore, we found that the squared quantum discord is also monogamous in three-flavor neutrino system. As a comparison, we test the monogamy of the quantum discord in neutrino oscillations with the result that the quantum discord is not monogamous. In addition, it is found that the bipartite geometric quantum discord of three-flavor systems is equal to the sum of the pairwise geometric quantum discord, i.e., the monogamy relation for geometric quantum discord is saturated for three-flavor neutrino system. These monogamy relations of quantum correlations provide a way for studying the distribution of quantum resources in neutrino oscillations, which is of significance to explore the further applications of neutrino oscillations in quantum communications.
In this paper, two design optimisation methods are evaluated using gradient-based optimisation for electric vehicle traction applications. A driving cycle-based approach is used to evaluate specific ...operational points for the design optimisation procedure. To determine the operational points, an energy centre of gravity (ECG) approach is used. Both optimisation methods are described, namely the point based method and the flux mapping method, with a focus on the flux mapping procedure. Within the flux mapping approach, an inner optimisation loop is defined in order to maintain the stability of gradient calculation for the gradient-based optimisation. An emphasis is placed on the importance of how the optimisation problem is defined, in terms of the objective function and constraints, and how it affects a gradient based optimisation. Based on a design case study conducted in the paper, it is found that the point-based strategy realised motor designs with a slightly lower overall cost (5.66% lower than that of the flux mapping strategy with 8 ECG points), whereas the flux mapping strategy found motor designs with a lower input energy (1.48% lower than that of the point-based strategy with 8 ECG points). This may be attributed to the difference in the definition and interpretation of constraints between these two methods. It is also shown that including more operational points from the driving cycle in the design optimisation leads to designs with reduced total input energy and thus better drive-cycle energy efficiency. This paper further illustrates the significant computational advantages of a gradient-based optimisation over a global optimisation method as it can be completed within a fraction of the time while still finding a global optimum, as long as the problem definition is correctly determined.
Metabolites from intestinal microbes modulate the mucosal immune system by regulating the polarization and expansion of T cells. Whether the microbial metabolites influence macrophage polarization, ...however, is poorly understood. Here, we show that the large bowel microbial fermentation product, butyrate, facilitates M2 macrophage polarization, in vitro and in vivo. The supernatant from butyrate-treated M2 macrophage increased the migration and enhanced the wound closure rate of MLE-12 cells. Butyrate attenuated intestinal inflammation in mice with dextran sulfate sodium (DSS)-induced colitis, with a significant increase in colonic expression of the M2 macrophage-associated protein, Arg1. M2 macrophage treated with butyrate, had increased activation of the H3K9/STAT6 signaling pathway, suggesting a mechanism for butyrate facilitated M2 macrophage polarization. Collectively, our study indicated that commensal microbe-derived butyrate is a novel activator of STAT6-mediated transcription through H3K9 acetylation driving M2 macrophage polarization, and delineated new insights into the immune interplay underlying inflammatory bowel disease.
A novel tropical cyclone (TC) intensity classification and estimation model (TCICENet) is proposed using infrared geostationary satellite images from the northwest Pacific Ocean basin in combination ...with a cascading deep convolutional neural network (CNN). The proposed model consists of two CNN network modules: a TC intensity classification (TCIC) module and a TC intensity estimation (TCIE) module. First, the TCIC module is utilized to divide TC intensity into three categories using infrared satellite images. Next, three TCIE models based on the CNN regression network that combine different intensity types of infrared satellite images with the TC best track data are presented. The three TCIE models consider classification error with the TCIC module in order to improve TCIE accuracy. A total of 1001 TCs from 1981-2019 were used to verify the proposed TCICENet model, with 844 TCs from 1981-2013 employed as training samples, 76 TCs from 2014-2016 used as validation samples, and 81 TCs from 2017-2019 used as testing samples. In order to reduce the computation burden of training the TCICENet model, various input image sizes were explored. An image size of 170 × 170 pixels achieved the best performance, with an overall root mean square error of 8.60 kt and a mean absolute error of 6.67 kt compared to the best track.
•MDG-1 lowers TC contents in obese mice via affecting bile acids metabolic profile.•The lipid-control effect of MDG-1 is mediated by promoting cholesterol catabolism.•MDG-1 affects gene expression ...related to the negative feedback control of bile acids.
Hyperlipidemia is a chronic metabolic disorder with systemic complications that is prevalent worldwide. MDG-1, a water-soluble β-d-fructan polysaccharide from Ophiopogon japonicas has potent hypolipidemic and weight-control effects. The present study aimed to investigate the effects of MDG-1 on lipid metabolic disorders in diet-induced obese mice based on the metabolic profile of bile acids. C57BL/6 mice were treated with a low-fat diet, high-fat diet or high fat mixed with 1‰ (w/w) MDG-1 diet for 12 weeks. The results showed that MDG-1 inhibited body weight gain and lowered serum and liver total cholesterol contents in obese mice. In addition, MDG-1 could adsorb bile acids in the gut lumen and reduce their reabsorption, thus promoting cholesterol catabolism. Furthermore, MDG-1 inhibited the expression of the farnesoid X receptor, but activated the liver X receptor. Our findings shed new light on the mechanism of MDG-1 in the control of lipids.
We present a molecular line study towards 31 extended green object (EGO) clumps in the southern sky using data from MALT90 (Millimetre Astronomy Legacy Team 90 GHz). According to previous ...multiwavelength observations, we divide our sample into two groups: massive young stellar objects (MYSOs) and H ii regions. The most detected lines are N2H+ (J = 1 − 0), HCO+ (J = 1 − 0), HNC (J = 1 − 0), HCN (J = 1 − 0), HC3N (J = 10 − 9), H13CO+ (J = 1 − 0), C2H (N = 1 − 0) and SiO (J = 2 − 1), indicating that most EGOs are indeed associated with dense clumps and recent outflow activities. The velocity widths of the N2H+ (J = 1 − 0), H13CO+ (J = 1 − 0), C2H (N = 1 − 0) and HC3N (J = 10 − 9) lines are comparable to each other in MYSOs. However, in H ii regions the velocity widths of the N2H+ (J = 1 − 0) and C2H (N = 1 − 0) lines tend to be narrower than those of H13CO+ (J = 1 − 0) and HC3N (J = 10 − 9). Our results seem to support that N2H+ and C2H emissions mainly come from the gas inside quiescent clumps. In addition, we also find that the N2H+/H13CO+ and C2H/H13CO+ relative abundance ratios decrease from MYSOs to H ii regions. These results suggest depletion of N2H+ and C2H in the late stages of massive-star formation, probably caused by the formation of H ii regions inside. N2H+ and C2H might be used as chemical clocks for massive-star formation by comparing with other molecules such as H13CO+ and HC3N.
A coal-based direct reduction process was used to recover the ferronickel from low-grade nickel laterite ore. The effects of basicity on the compressive strength, metallization rate, microstructure, ...and reduction characteristics of carbon-bearing nickel laterite ore pellets were investigated. The results show that the metallization rate of iron and the compressive strength of metallized pellets follow a parabolic function with increasing basicity. The optimal reduction temperature of the rotary kiln should be controlled at 1150 °C to 1250 °C with pellet basicity of 0.56 to prevent the ring-forming phenomenon. Under optimum process conditions, the metallized pellets mainly consist of ferronickel (Fe,Ni), forsterite ferroan (Mg1.38Fe0.61Ca0.01SiO4), and pigeonite ((Ca0.06Mg0.68Fe0.26)SiO3). The particle size of ferronickel can reach to 30 μm with a high nickel‑chromium concentrations. The compressive strength of metallized pellets is 5220 to 7223 N·Pellet−1, and the metallization rates of iron and nickel are 95.28% to 98.45%, 94.75 to 96.33%, respectively.
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•Producing a high value-added Fe-Ni-Cr alloy is a new idea for the utilization of low-grade nickel laterite ore.•The high basicity is negative to reduction of iron, but can promote the reduction of nickel.•The reduction temperature and pellet basicity are the main factors contributing to the Ni and Cr contents in ferronickel.•The coal-based direct reduction process is a feasible method to obtain the ferronickel from low-grade nickel laterite ore.