Selective-pivot sampling of radial distribution functions in asymmetric liquid mixtures

We present a Monte Carlo algorithm for selectively sampling radial distribution functions and effective interaction potentials in asymmetric liquid mixtures. We demonstrate its efficiency for hard-sphere mixtures, and for model systems with more general interactions, and compare our simulations with several analytical approximations. For interaction potentials containing a hard-sphere contribution, the algorithm yields the contact value of the radial distribution function.Comment: 5 pages, 5 figure

Chemical potential of quadrupolar two-centre Lennard-Jones fluids by gradual insertion

The gradual insertion method for direct calculation of the chemical potential by molecular simulation is applied in the NpT ensemble to different quadrupolar two-centre Lennard-Jones fluids at high density state points. The results agree well with Widom's test particle insertion but show at very high densities significantly smaller statistical uncertainties. The gradual insertion method, which is coupled here with preferential sampling, extends the density range where reliable information on the chemical potential can be obtained. Application details are reported

Use of EpiAlveolar Lung Model to Predict Fibrotic Potential of Multiwalled Carbon Nanotubes

Expansion in production and commercial use of nanomaterials increases the potential human exposure during the lifecycle of these materials (production, use, and disposal). Inhalation is a primary route of exposure to nanomaterials; therefore it is critical to assess their potential respiratory hazard. Herein, we developed a three-dimensional alveolar model (EpiAlveolar) consisting of human primary alveolar epithelial cells, fibroblasts, and endothelial cells, with or without macrophages for predicting long-term responses to aerosols. Following thorough characterization of the model, proinflammatory and profibrotic responses based on the adverse outcome pathway concept for lung fibrosis were assessed upon repeated subchronic exposures (up to 21 days) to two types of multiwalled carbon nanotubes (MWCNTs) and silica quartz particles. We simulate occupational exposure doses for the MWCNTs (1–30 μg/cm2) using an air–liquid interface exposure device (VITROCELL Cloud) with repeated exposures over 3 weeks. Specific key events leading to lung fibrosis, such as barrier integrity and release of proinflammatory and profibrotic markers, show the responsiveness of the model. Nanocyl induced, in general, a less pronounced reaction than Mitsui-7, and the cultures with human monocyte- derived macrophages (MDMs) showed the proinflammatory response at later time points than those without MDMs. In conclusion, we present a robust alveolar model to predict inflammatory and fibrotic responses upon exposure to MWCNTs

Use of EpiAlveolar Lung Model to Predict Fibrotic Potential of Multiwalled Carbon Nanotubes

Expansion in production and commercial use of nanomaterials increases the potential human exposure during the lifecycle of these materials (production, use, and disposal). Inhalation is a primary route of exposure to nanomaterials; therefore it is critical to assess their potential respiratory hazard. Herein, we developed a three-dimensional alveolar model (EpiAlveolar) consisting of human primary alveolar epithelial cells, fibroblasts, and endothelial cells, with or without macrophages for predicting long-term responses to aerosols. Following thorough characterization of the model, proinflammatory and profibrotic responses based on the adverse outcome pathway concept for lung fibrosis were assessed upon repeated subchronic exposures (up to 21 days) to two types of multiwalled carbon nanotubes (MWCNTs) and silica quartz particles. We simulate occupational exposure doses for the MWCNTs (1–30 μg/cm2) using an air–liquid interface exposure device (VITROCELL Cloud) with repeated exposures over 3 weeks. Specific key events leading to lung fibrosis, such as barrier integrity and release of proinflammatory and profibrotic markers, show the responsiveness of the model. Nanocyl induced, in general, a less pronounced reaction than Mitsui-7, and the cultures with human monocyte- derived macrophages (MDMs) showed the proinflammatory response at later time points than those without MDMs. In conclusion, we present a robust alveolar model to predict inflammatory and fibrotic responses upon exposure to MWCNTs

Single exposure to aerosolized graphene oxide and graphene nanoplatelets did not initiate an acute biological response in a 3D human lung model

The increased mass production of graphene related materials (GRM), intended for a broad spectrum of applications, demands a thorough assessment of their potential hazard to humans and the environment. Particularly, the paramount concern has been expressed in regard to their interaction with the respiratory system in occupational exposure settings. It has been shown that GRM are easily respirable and can interact with lung cells resulting in the induction of oxidative stress or pulmonary inflammation. However, a comprehensive assessment of potential biological effects induced by GRM is currently hardly feasible to accomplish due to the lack of well-defined GRM materials and realistic exposure data. Herein, a 3D human lung model was combined with a commercial aerosolization system to study potential side effects of GRM. Two representative types of GRM were aerosolized onto the lung epithelial tissue surface. After 24 h post exposure, selected biological endpoints were evaluated, such as cell viability, morphology, barrier integrity, induction of (pro-)inflammation and oxidative stress reactions and compared with the reference material carbon black. Single exposure to all tested GRM at the two different exposure concentrations (∼300 and 1000 ng/cm2) did not initiate an observable adverse effect to the 3D lung model under acute exposure scenarios

Carbon nanodots: Opportunities and limitations to study their biodistribution at the human lung epithelial tissue barrier

Inhalation of combustion-derived ultrafine particles (≤0.1 μm) has been found to be associated with pulmonary and cardiovascular diseases. However, correlation of the physicochemical properties of carbon-based particles such as surface charge and agglomeration state with adverse health effects has not yet been established, mainly due to limitations related to the detection of carbon particles in biological environments. The authors have therefore applied model particles as mimics of simplified particles derived from incomplete combustion, namely, carbon nanodots (CNDs) with different surface modifications and fluorescent properties. Their possible adverse cellular effects and their biodistribution pattern were assessed in a three- dimensional (3D) lung epithelial tissue model. Three different CNDs, namely, nitrogen, sulfur codoped CNDs (N,S-CNDs) and nitrogen doped CNDs (N-CNDs-1 and N- CNDs-2), were prepared by microwave-assisted hydrothermal carbonization using different precursors or different microwave systems. These CNDs were found to possess different chemical and photophysical properties. The surfaces of nanodots N- CNDs-1 and N-CNDs-2 were positively charged or neutral, respectively, arguably due to the presence of amine and amide groups, while the surfaces of N,S-CNDs were negatively charged, as they bear carboxylic groups in addition to amine and amide groups. Photophysical measurements showed that these three types of CNDs displayed strong photon absorption in the UV range. Both N-CNDs-1 and N,S-CNDs showed weak fluorescence emission, whereas N-CNDs-2 showed intense emission. A 3D human lung model composed of alveolar epithelial cells (A549 cell line) and two primary immune cells, i.e., macrophages and dendritic cells, was exposed to CNDs via a pseudo-air-liquid interface at a concentration of 100 μg/ml. Exposure to these particles for 24 h induced no harmful effect on the cells as assessed by cytotoxicity, cell layer integrity, cell morphology, oxidative stress, and proinflammatory cytokines release. The distribution of the CNDs in the lung model was estimated by measuring the fluorescence intensity in three different fractions, e.g., apical, intracellular, and basal, after 1, 4, and 24 h of incubation, whereby reliable results were only obtained for N-CNDs-2. It was shown that N-CNDs-2 translocate rapidly, i.e., >40% in the basal fraction within 1 h and almost 100% after 4 h, while ca. 80% of the N-CNDs-1 and N,S-CNDs were still located on the apical surface of the lung cells after 1 h. This could be attributed to the agglomeration behavior of N-CNDs-1 or N,S-CNDs. The surface properties of the N-CNDs bearing amino and amide groups likely induce greater uptake as N-CNDs could be detected intracellularly. This was less evident for N,S- CNDs, which bear carboxylic acid groups on their surface. In conclusion, CNDs have been designed as model systems for carbon-based particles; however, their small size and agglomeration behavior made their quantification by fluorescence measurement challenging. Nevertheless, it was demonstrated that the surface properties and agglomeration affected the biodistribution of the particles at the lung epithelial barrier in vitro

Biological response of an in vitro human 3D lung cell model exposed to brake wear debris varies based on brake pad formulation

Wear particles from automotive friction brake pads of various sizes, morphology, and chemical composition are significant contributors towards particulate matter. Knowledge concerning the potential adverse effects following inhalation exposure to brake wear debris is limited. Our aim was, therefore, to generate brake wear particles released from commercial low-metallic and non-asbestos organic automotive brake pads used in mid-size passenger cars by a full-scale brake dynamometer with an environmental chamber simulating urban driving and to deduce their potential hazard in vitro. The collected fractions were analysed using scanning electron microscopy via energy-dispersive X-ray spectroscopy (SEM-EDS) and Raman microspectroscopy. The biological impact of the samples was investigated using a human 3D multicellular model consisting of human epithelial cells (A549) and human primary immune cells (macrophages and dendritic cells) mimicking the human epithelial tissue barrier. The viability, morphology, oxidative stress, and (pro-)inflammatory response of the cells were assessed following 24 h exposure to similar to 12, similar to 24, and similar to 48 A mu g/cm(2) of non-airborne samples and to similar to 3.7 A mu g/cm(2) of different brake wear size fractions (2-4, 1-2, and 0.25-1 A mu m) applying a pseudo-air-liquid interface approach. Brake wear debris with low-metallic formula does not induce any adverse biological effects to the in vitro lung multicellular model. Brake wear particles from non-asbestos organic formulated pads, however, induced increased (pro-)inflammatory mediator release from the same in vitro system. The latter finding can be attributed to the different particle compositions, specifically the presence of anatase.Web of Science9272351233

Characteristics and properties of nano-LiCoO2 synthesized by pre-organized single source precursors: Li-ion diffusivity, electrochemistry and biological assessment

Background: LiCoO2 is one of the most used cathode materials in Li-ion batteries. Its conventional synthesis requires high temperature (>800 degrees C) and long heating time (>24 h) to obtain the micronscale rhombohedral layered high-temperature phase of LiCoO2 ( HT-LCO). Nanoscale HT-LCO is of interest to improve the battery performance as the lithium (Li+) ion pathway is expected to be shorter in nanoparticles as compared to micron sized ones. Since batteries typically get recycled, the exposure to nanoparticles during this process needs to be evaluated. Results: Several new single source precursors containing lithium (Li+) and cobalt (Co2+) ions, based on alkoxides and aryloxides have been structurally characterized and were thermally transformed into nanoscale HT-LCO at 450 degrees C within few hours. The size of the nanoparticles depends on the precursor, determining the electrochemical performance. The Li-ion diffusion coefficients of our - LiCoO2 nanoparticles improved at least by a factor of 10 compared to commercial one, while showing good reversibility upon charging and discharging. The hazard of occupational exposure to nanoparticles during battery recycling was investigated with an in vitro multicellular lung model. Conclusions: Our heterobimetallic single source precursors allow to dramatically reduce the production temperature and time for HT-LCO. The obtained nanoparticles of LiCoO2 have faster kinetics for Li+ insertion/extraction compared to microparticles. Overall, nano-sized - LiCoO2 particles indicate a lower cytotoxic and (pro-)inflammogenic potential in vitro compared to their micron-sized counterparts. However, nanoparticles aggregate in air and behave partially like microparticles

Sex-Based Differences in Bronchial Asthma: What Are the Mechanisms behind Them?

Sex-based differences in bronchial asthma can already be observed in childhood, at which time allergic atopic asthma is more frequently found in boys than in girls. In adulthood, higher prevalence of asthma is reported in women, especially for the more severe neutrophilic subtype associated with obesity, which responds poorly to corticosteroids. Sex-based differences seem to be attributable to changing levels of estrogens, progesterone, and testosterone, which may exert mainly pro-inflammatory (estrogens, progesterone) or anti-inflammatory effects (testosterone). Sex steroids differentially influence lung immune responses, airway reactivity, and pulmonary circulation and may thereby contribute to the higher susceptibility of females to more serious complications resulting from inflammatory lung diseases compared to males. However, other factors, such as anatomical and physiological differences in the lungs, differences in genetically conditioned factors, obesity and lifestyle, smoking, exposure to environmental and occupational factors, chronic stress, etc., may also contribute to the sex-based differences in asthma. Elucidation of the mechanisms behind these differences may contribute to more appropriate personalized therapy for asthma. For the review, articles in the English language from the PubMed database were used

Advances in the Use of <i>N</i>-Acetylcysteine in Chronic Respiratory Diseases

N-acetylcysteine (NAC) is widely used because of its mucolytic effects, taking part in the therapeutic protocols of cystic fibrosis. NAC is also administered as an antidote in acetaminophen (paracetamol) overdosing. Thanks to its wide antioxidative and anti-inflammatory effects, NAC may also be of benefit in other chronic inflammatory and fibrotizing respiratory diseases, such as chronic obstructive pulmonary disease, bronchial asthma, idiopathic lung fibrosis, or lung silicosis. In addition, NAC exerts low toxicity and rare adverse effects even in combination with other treatments, and it is cheap and easily accessible. This article brings a review of information on the mechanisms of inflammation and oxidative stress in selected chronic respiratory diseases and discusses the use of NAC in these disorders