Background Azithromycin (Azm) is a macrolide recognized for its disease-modifying effects and reduction in exacerbation of chronic airway diseases. It is not clear whether the beneficial effects of Azm are due to its anti-microbial activity or other pharmacological actions. We have shown that Azm affects the integrity of the bronchial epithelial barrier measured by increased transepithelial electrical resistance. To better understand these effects of Azm on bronchial epithelia we have investigated global changes in gene expression. Methods VA10 bronchial epithelial cells were treated with Azm and cultivated in air-liquid interface conditions for up to 22 days. RNA was isolated at days 4, 10 and 22 and analyzed using high-throughput RNA sequencing. qPCR and immunostaining were used to confirm key findings from bioinformatic analyses. Detailed assessment of cellular changes was done using microscopy, followed by characterization of the lipidomic profiles of the multivesicular bodies present. Results Bioinformatic analysis revealed that after 10 days of treatment genes encoding effectors of sterol and cholesterol metabolism were prominent. Interestingly, expression of genes associated with epidermal barrier differentiation, KRT1, CRNN, SPINK5 and DSG1 , increased significantly at day 22. Together with immunostaining, these results suggest an epidermal differentiation pattern. We also found that Azm induced the formation of multivesicular and lamellar bodies in two different airway epithelial cell lines. Lipidomic analysis revealed that Azm was entrapped in multivesicular bodies linked to different types of lipids, most notably palmitate and stearate. Furthermore, targeted analysis of lipid species showed accumulation of phosphatidylcholines, as well as ceramide derivatives. Conclusions Taken together, we demonstrate how Azm might confer its barrier enhancing effects, via activation of epidermal characteristics and changes to intracellular lipid dynamics. These effects of Azm could explain the unexpected clinical benefit observed during Azm-treatment of patients with various lung diseases affecting barrier function. Electronic supplementary material The online version of this article (10.1186/s12931-019-1101-3) contains supplementary material, which is available to authorized users.

BackgroundDiatoms, which can accumulate large amounts of carotenoids, are a major group of microalgae and the dominant primary producer in marine environments. Phaeodactylum tricornutum, a model diatom species, acquires little silicon for its growth although silicon is known to contribute to gene regulation and play an important role in diatom intracellular metabolism. In this study, we explored the effects of artificial high-silicate medium (i.e. 3.0 mM sodium metasilicate) and LED illumination conditions on the growth rate and pigment accumulation in P. tricornutum, which is the only known species so far that can grow without silicate. It’s well known that light-emitting diodes (LEDs) as novel illuminants are emerging to be superior monochromatic light sources for algal cultivation with defined and efficient red and blue lights.ResultsFirstly, we cultivated P. tricornutum in a synthetic medium supplemented with either 0.3 mM or 3.0 mM silicate. The morphology and size of diatom cells were examined: the proportion of the oval and triradiate cells decreased while the fusiform cells increased with more silicate addition in high-silicate medium; the average length of fusiform cells also slightly changed from 14.33 µm in 0.3 mM silicate medium to 12.20 µm in 3.0 mM silicate medium. Then we cultivated P. tricornutum under various intensities of red light in combination with the two different levels of silicate in the medium. Higher biomass productivity also achieved in 3.0 mM silicate medium than in 0.3 mM silicate medium under red LED light irradiation at 128 μmol/m2/s or higher light intensity. Increasing silicate reversed the down-regulation of fucoxanthin and chlorophyll a under high red-light illumination (i.e. 255 μmol/m2/s). When doubling the light intensity, fucoxanthin content decreased under red light but increased under combined red and blue (50:50) lights while chlorophyll a content reduced under both conditions. Fucoxanthin accumulation and biomass productivity increased with enhanced red and blue (50:50) lights.ConclusionHigh-silicate medium and blue light increased biomass and fucoxanthin production in P. tricornutum under high light conditions and this strategy may be beneficial for large-scale production of fucoxanthin in diatoms.

with oxidative stress, may lead to activation of resident immune cells in the distal lungs to secrete inflammatory mediators resulting in edema and fibrosis, collectively referred to as biotrauma (Beitler et al., 2016).All mechanically ventilated patients are at risk for VILI, especially when it becomes challenging to ventilate the patient due to pathology in the lungs, as in acute respiratory distress syndrome (ARDS) (Carrasco Loza et al., 2015). VILI can cause, or augment substantially, damage of lung tissue in ARDS while being a necessary part of its treatment. The onset of ARDS is associated with the activation of the resident alveolar macrophages as a response to an insult or injury. The ensuing secretion of inflammatory mediators attracts neutrophils and monocytes from nearby capillaries, which secrete mediators harmful to endothelium and alveolar epithelium, causing increased permeability of the alveolar-capillary membrane, facilitating edema in the interstitium and air spaces. The following collapse of alveoli, increased dead space, worsening gas exchange and reduced lung compliance necessitate mechanical ventilation (Slutsky and Ranieri, 2013). AR-DS is a common and lethal or disabling syndrome that 10% of

Nanoplastics (NPs; <1 μm) have greater availability to marine organisms than microplastics (1–5000 μm). Understanding NP uptake and depuration in marine organisms intended for human consumption is imperative for food safety, but until now it has been limited due to analytical constraints. Oysters (Crassostrea gigas) were exposed to polystyrene NPs doped with palladium (Pd), allowing the measurements of their uptake into tissues by inductively coupled plasma mass spectrometry (ICP-MS) combined with electron microscopy. Oysters were exposed for 6 days (d) to “Smooth” or “Raspberry” NPs, followed by 30 d of depuration with the aim of assessing the NP concentration in C. gigas following exposure, inferring the accumulation and elimination rates, and understanding the clearance of Pd NPs during the depuration period. After 6 d, the most significant accumulation was found in the digestive gland (106.6 and 135.3 μg g–1 dw, for Smooth and Raspberry NPs, respectively) and showed the most evident depuration (elimination rate constant K Smooth = 2 d–1 and K Raspberry = 0.2 d–1). Almost complete depuration of the Raspberry NPs occurred after 30 d. While a post-harvesting depuration period of 24–48 h for oysters could potentially reduce the NP content by 75%, more research to validate these findings, including depuration studies of oysters from the field, is required to inform practices to reduce human exposure through consumption.

Organotin complexes are studied as promising alternatives to the anticancer drug cisplatin. We report two monoorganotin(IV) complexes based on a dibenzyl phosphinoyldithioformate (H-DBPTF) ligand, containing either bromide (Sn-DBPTF-1) or chloride...