Rapid Growth Cone Uptake and Dynein‐Mediated Axonal Retrograde Transport of Negatively Charged Nanoparticles in Neurons Is Dependent on Size and Cell Type

Nanoparticles (NPs) are now used in numerous technologies and serve as carriers for several new classes of therapeutics. Studies of the distribution of NPs in vivo demonstrate that they can be transported through biological barriers and are concentrated in specific tissues. Here, transport behavior, and final destination of polystyrene NPs are reported in primary mouse cortical neurons and SH‐SY5Y cells, cultured in two‐compartmental microfluidic devices. In both cell types, negative polystyrene NPs (PS(?)) smaller than 100 nm are taken up by the axons, undergo axonal retrograde transport, and accumulate in the somata. Examination of NP transport reveals different transport mechanisms depending on the cell type, particle charge, and particle internalization by the lysosomes. In cortical neurons, PS(?) inside lysosomes and 40 nm positive polystyrene NPs undergo slow axonal transport, whereas PS(?) outside lysosomes undergo fast axonal transport. Inhibition of dynein in cortical neurons decreases the transport velocity and cause a dose‐dependent reduction in the number of accumulated PS(?), suggesting that the fast axonal transport is dynein mediated. These results show that the axonal retrograde transport of NPs depends on the endosomal pathway taken and establishes a means for screening nanoparticle‐based therapeutics for diseases that involve neurons.     

Tolerogenic Iron Oxide Nanoparticles in Type 1 Diabetes: Biodistribution and Pharmacokinetics Studies in Nonobese Diabetic Mice

Nanoparticle (NP) administration is among the most attractive approaches to exploit the synergy of different copackaged molecules for the same target. In this work, iron oxide NPs are surface‐engineered for the copackaging of the autoantigen proinsulin, a major target of adaptive immunity in type 1 diabetes (T1D), and 2‐(1′H‐indole‐3′‐carbonyl)‐thiazole‐4‐carboxylic acid methylester (ITE), a small drug conditioning a tolerogenic environment. Magnetic resonance imaging (MRI) combined with magnetic quantification are used to investigate NP biokinetics in nonobese diabetic (NOD) mice and control mice in different organs. Different NP biodistribution, with in particular enhanced kidney elimination and a stronger accumulation in the pancreas for prediabetic NOD mice, is observed. This is related to preferential NP accumulation in the pancreatic inflammatory zone and to enhancement of renal elimination by diabetic nephropathy. For both mouse strains, an MRI T2 contrast enhancement at 72 h in the liver, pancreas, and kidneys, and indicating recirculating NPs, is also found. This unexpected result is confirmed by magnetic quantification at different time points as well as by histological evaluation. Besides, such NPs are potential MRI contrast agents for early diagnosis of T1D.     

Clinical Characteristics and Outcomes of Type 2 Diabetes Patients Infected with COVID-19: A Retrospective Study

Diabetes and its related metabolic disorders have been reported as the leading comorbidities in patients with coronavirus disease 2019 (COVID-19). This clinical study aims to investigate the clinical features, radiographic and laboratory tests, complications, treatments, and clinical outcomes in COVID-19 patients with or without diabetes. This retrospective study included 208 hospitalized patients (≥ 45 years old) with laboratory-confirmed COVID-19 during the period between 12 January and 25 March 2020. Information from the medical record, including clinical features, radiographic and laboratory tests, complications, treatments, and clinical outcomes, were extracted for the analysis. 96 (46.2%) patients had comorbidity with type 2 diabetes. In COVID-19 patients with type 2 diabetes, the coexistence of hypertension (58.3% vs 31.2%), coronary heart disease (17.1% vs 8.0%), and chronic kidney diseases (6.2% vs 0%) was significantly higher than in COVID-19 patients without type 2 diabetes. The frequency and degree of abnormalities in computed tomography (CT) chest scans in COVID-19 patients with type 2 diabetes were markedly increased, including ground-glass opacity (85.6% vs 64.9%, P < 0.001) and bilateral patchy shadowing (76.7% vs 37.8%, P < 0.001). In addition, the levels of blood glucose (7.23 mmol·L⁻¹ (interquartile range (IQR): 5.80–9.29) vs 5.46 mmol·L⁻¹ (IQR: 5.00–6.46)), blood low-density lipoprotein cholesterol (LDL-C) (2.21 mmol·L⁻¹ (IQR: 1.67–2.76) vs 1.75 mmol·L⁻¹ (IQR: 1.27–2.01)), and systolic pressure (130 mmHg (IQR: 120–142) vs 122 mmHg (IQR: 110–137)) (1 mmHg = 133.3 Pa) in COVID-19 patients with diabetes were significantly higher than in patients without diabetes (P < 0.001). The coexistence of type 2 diabetes and other metabolic disorders is common in patients with COVID-19, which may potentiate the morbidity and aggravate COVID-19 progression. Optimal management of the metabolic hemostasis of glucose and lipids is the key to ensuring better clinical outcomes. Increased clinical vigilance is warranted for COVID-19 patients with diabetes and other metabolic diseases that are fundamental and chronic conditions.     

A High‐Throughput Automated Confocal Microscopy Platform for Quantitative Phenotyping of Nanoparticle Uptake and Transport in Spheroids

There is a high demand for advanced, image‐based, automated high‐content screening (HCS) approaches to facilitate phenotypic screening in 3D cell culture models. A major challenge lies in retaining the resolution of fine cellular detail but at the same time imaging multicellular structures at a large scale. In this study, a confocal microscopy‐based HCS platform in optical multiwell plates that enables the quantitative morphological profiling of populations of nonuniform spheroids obtained from HT‐29 human colorectal cancer cells is described. This platform is then utilized to demonstrate a quantitative dissection of the penetration of synthetic nanoparticles (NP) in multicellular 3D spheroids at multiple levels of scale. A pilot RNA interference‐based screening validates this methodology and identifies a subset of RAB GTPases that regulate NP trafficking in these spheroids. This technology is suitable for high‐content phenotyping in 3D cell‐based screening, providing a framework for nanomedicine drug development as applied to translational oncology.     

Type Inversion and Certain Physical Properties of Spray Pyrolysed SnO::A1Films for Novel Transparent Electronics Applications

Aluminium doped tin oxide films have been deposited onto glass substrates by using a simplified and low cost spray pyrolysis technique.The Al doping level varies between 0 and 30 at.%in the step of 5 at.%.The resistivity(ρ) is the minimum(0.38 Ω cm) for 20 at.%of Al doping.The possible mechanism behind the phenomenal zig-zag variation in resistivity with respect to Al doping is discussed in detail.The nature of conductivity changes from n-type to p-type when the Al doping level is 10 at.%.The results show that20 at.%is the optimum doping level for good quality p-type SnO_2:AI films suitable for transparent electronic devices.     

A novel Z-scheme CeO2/g-C3N4 heterojunction photocatalyst for degradation of Bisphenol A and hydrogen evolution and insight of the photocatalysis mechanism

CeO2/g-C3N4 heterojunction photocatalyst had been successfully fabricated through a one-step in-situ pyrolysis formation of 3D hollow CeO2 mesoporous nanospheres and 2D g-C3N4 nanosheets together with simultaneous removal of carbon sphere templates after heat treatment.The sample shows high catalytic performances for photocatalytic hydrogen generation and photocatalytic oxidation of Bisphe-nol A(BPA)under visible light irradiation,and the catalytic degradation route of BPA was suggested by the degradation products determined by GC-MS.The enhancing catalytic activity was attributed to the effective interfacial charge migration and separation.Finally,it was proposed that the CeO2/g-C3N4 het-erojunction photocatalyst could follow a more appropriate Z-scheme charge transfer mechanism,which was confirmed by the analysis of experiment and theoretical calculation results.     

HL-2A装置直流辉光自动调节控制系统

直流辉光放电清洗的主要作用是去除HL-2A装置内的低Z杂质C、O,以及放电期间所产生的残余气体和杂质。介绍了直流辉光放电自动调节控制系统。在辉光放电过程中,实现了真空室工作气体气压和放电电压的自动调节和信号采集。本文描述了系统的设计原理,控制方案和系统实现后的具体应用效果。直流辉光放电系统的性能得到了提高,放电电流稳定性得到了显著提高,放电电压的控制精度改善为1%FS,系统从启动到稳定运行状态的时间小于40 s,HL-2A装置的清洗效率也明显获得改善。     

A Novel Approach for FMEA: Combination of Interval 2‐Tuple Linguistic Variables and Gray Relational Analysis

Failure mode and effect analysis (FMEA) is a powerful tool for defining, identifying, and eliminating potential failures from the system, design, process, or service before they reach the customer. Since its appearance, FMEA has been extensively used in a wide range of industries. However, the conventional risk priority number (RPN) method has been criticized for having a number of drawbacks. In addition, FMEA is a group decision behavior and generally performed by a cross‐functional team. Multiple experts tend to express their judgments on the failure modes by using multigranularity linguistic term sets, and there usually exists uncertain and incomplete assessment information. In this paper, we present a novel FMEA approach combining interval 2‐tuple linguistic variables with gray relational analysis to capture FMEA team members’ diversity opinions and improve the effectiveness of the traditional FMEA. An empirical example of a C‐arm X‐ray machine is given to illustrate the potential applications and benefits of the proposed approach. Copyright © 2014 John Wiley & Sons, Ltd.     

A Novel and Facile Route to Synthesize Atomic‐Layered MoS2 Film for Large‐Area Electronics

High‐quality and large‐area molybdenum disulfide (MoS₂) thin film is highly desirable for applications in large‐area electronics. However, there remains a challenge in attaining MoS₂ film of reasonable crystallinity due to the absence of appropriate choice and control of precursors, as well as choice of suitable growth substrates. Herein, a novel and facile route is reported for synthesizing few‐layered MoS₂ film with new precursors via chemical vapor deposition. Prior to growth, an aqueous solution of sodium molybdate as the molybdenum precursor is spun onto the growth substrate and dimethyl disulfide as the liquid sulfur precursor is supplied with a bubbling system during growth. To supplement the limiting effect of Mo (sodium molybdate), a supplementary Mo is supplied by dissolving molybdenum hexacarbonyl (Mo(CO)₆) in the liquid sulfur precursor delivered by the bubbler. By precisely controlling the amounts of precursors and hydrogen flow, full coverage of MoS₂ film is readily achievable in 20 min. Large‐area MoS₂ field effect transistors (FETs) fabricated with a conventional photolithography have a carrier mobility as high as 18.9 cm² V^?1 s^?1, which is the highest reported for bottom‐gated MoS₂‐FETs fabricated via photolithography with an on/off ratio of ≈10⁵ at room temperature.