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Testing for acute inhalation hazards is conducted in animals; however, a number of robust in vitro human cell-based alternatives have been developed and tested. These models range in complexity from cultures of cell lines or primary cells in air-liquid interface on Transwells, to more complex and physiologically relevant flow- and mechanical stimulation-enabled tissue chips. Although the former models are relatively straightforward to establish and can be tested in medium/high throughput, the latter require specialized equipment and lack in throughput. In this study, we developed a device that can be easily manufactured while allowing for the production of a differentiated lung tissue. This multilayered microfluidic device enables coculture of primary human small airway epithelial cells and lung microvascular endothelial cells under physiological conditions for up to 18 days and recreates the parenchymal-vascular interface in the distal lung. To explore the potential of this airway on a chip for applications in inhalation toxicology, we also devised a system that allows for direct gas/aerosol exposures of the engineered airway epithelium to noxious stimuli known to cause adverse respiratory effects, including dry flowing air, lipopolysaccharide, particulate matter, and iodomethane. This study generated quantitative, high-content data that were indicative of aberrant changes in biochemical (lactate dehydrogenase), barrier (dextran permeability), functional (ciliary beating), and molecular (imaging for various markers) phenotypes of the small airway epithelium due to inhalational exposures. This study is significant because it established an in vitro model of human small airway on a chip that can be used in medium/high-throughput studies of subacute effects of inhalation toxicants. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated an array of stem cell–derived, self-organizing miniature organs, termed organoids, that replicate the key structural and functional characteristics of their in vivo counterparts. As organoid technology opens up new frontiers of research in biomedicine, there is an emerging need for innovative engineering approaches for the production, control, and analysis of organoids and their microenvironment. In this Review, we explore organ-on-a-chip technology as a platform to fulfill this need and examine how this technology may be leveraged to address major technical challenges in organoid research. We also discuss emerging opportunities and future obstacles for the development and application of organoid-on-a-chip technology. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study is to optimize the shape of a casing for a small wind turbine. The optimization is performed to augment the airflow in the active transversal circular section in which the turbine rotor will be mounted. The axial length of the case was constrained. To increase the volumetric flow through the casing, we equipped the casing with passive flow control devices (i.e., circular injection slots) that operate by the overlapping of multiple aerodynamic effects. This research was conducted using numerical simulations as an investigational tool, and experimental tests performed in the wind tunnel showed that the computed results are reasonably verified by the experimental data. Furthermore, the flow mechanism around the case is better understood via the numerical data post-processing. In this investigation, a total of 13 shapes of the casing were tested, and the results suggest that the optimal variant ensures a maximum axial velocity increase in the active transversal section of the casing by a factor of up to 3.25. [Copyright &y& Elsevier]

While IκB-kinase-ε (IKKε) induces immunomodulatory genes following viral stimuli, its upregulation by inflammatory cytokines remains under-explored. Since airway epithelial cells respond to airborne insults and potentiate inflammation, IKKε expression was characterized in pulmonary epithelial cell lines (A549, BEAS-2B) and primary human bronchial epithelial cells grown as submersion or differentiated air-liquid interface cultures. IKKε expression was up-regulated by the pro-inflammatory cytokines, interleukin-1β (IL-1β) and tumour necrosis factor-α (TNFα). Thus, mechanistic interrogations in A549 cells were used to demonstrate the NF-κB dependence of cytokine-induced IKKε. Furthermore, chromatin immunoprecipitation in A549 and BEAS-2B cells revealed robust recruitment of the NF-κB subunit, p65, to one 50 and two intronic regions within the IKKε locus (IKBKE). In addition, IL-1β and TNFα induced strong RNA polymerase 2 recruitment to the 50 region, the first intron, and the transcription start site. Stable transfection of the p65- binding regions into A549 cells revealed IL-1β- and TNFα-inducible reporter activity that required NF-κB, but was not repressed by glucocorticoid. While critical NF-κB motifs were identified in the 50 and downstream intronic regions, the first intronic region did not contain functional NF-κB motifs. Thus, IL-1β- and TNFα-induced IKKε expression involves three NF-κB-binding regions, containing multiple functional NF-κB motifs, and potentially other mechanisms of p65 binding through non-classical NF-κB binding motifs. By enhancing IKKε expression, IL-1β may prime, or potentiate, responses to alternative stimuli, as modelled by IKKε phosphorylation induced by phorbol 12-myristate 13- acetate. However, since IKKε expression was only partially repressed by glucocorticoid, IKKε-dependent responses could contribute to glucocorticoid-resistant disease. [ABSTRACT FROM AUTHOR]

Roles for the baculoviral inhibitor of apoptosis repeat-containing (BIRC) genes, BIRC2 and BIRC3, may include signaling to the inflammatory transcription factor, nuclear factor-κB (NF-κB) and protection from cell death. However, distinct functions for each BIRC are not well-delineated. Given roles for the epithelium in barrier function and host defence, BIRC2 and BIRC3 expression was characterized in pulmonary epithelial cell lines and primary human bronchial epithelial cells (pHBECs) grown as undifferentiated cells in submersion culture (SC) or as highly differentiated cells at air-liquid interface (ALI). In A549 cells, interleukin-1β (IL1B) and tumor necrosis factor α (TNF) induced BIRC3 mRNA (~20-50-fold), with maximal protein expression from 6–24 h. Similar effects occurred in BEAS-2B and Calu-3 cells, as well as SC and ALI pHBECs. BIRC2 protein was readily detected in unstimulated cells, but was not markedly modulated by IL1B or TNF. Glucocorticoids (dexamethasone, budesonide) modestly increased BIRC3 mRNA and protein, but showed little effect on BIRC2 expression. In A549 cells, BIRC3 mRNA induced by IL1B was unchanged by glucocorticoids and showed supra-additivity with TNF-plus-glucocorticoid. Supra-additivity was also evident for IL1B-plus-budesonide induced-BIRC3 in SC and ALI pHBECs. Using A549 cells, IL1B- and TNF-induced BIRC3 expression, and to a lesser extent, BIRC2, was prevented by NF-κB inhibition. Glucocorticoid-induced BIRC3 expression was prevented by silencing and antagonism of the glucocorticoid receptor. Whereas TNF, but not IL1B, induced degradation of basal BIRC2 and BIRC3 protein, IL1B- and TNF-induced BIRC3 protein remained stable. Differential regulation by cytokines and glucocorticoids shows BIRC2 protein expression to be consistent with roles in rapid signaling events, whereas cytokine-induced BIRC3 may be more important in later effects. While TNF-induced degradation of both BIRCs may restrict their activity, cytokine-enhanced BIRC3 expression could prime for its function. Finally, shielding from glucocorticoid repression, or further enhancement by glucocorticoid, may indicate a key protective role for BIRC3. [ABSTRACT FROM AUTHOR]

(1) Background: An open abdomen is a serious medical condition that requires prompt and effective treatment to prevent complications and improve patient outcomes. Negative pressure therapy (NPT) has emerged as a viable therapeutic option for temporary closure of the abdomen, offering several benefits over traditional methods. (2) Methods: We included 15 patients with pancreatitis who were hospitalized in the I–II Surgery Clinic of the Emergency County Hospital "St. Spiridon" from Iasi, Romania, between 2011–2018 and received NPT. (3) Results: Preoperatively, the mean IAP level was 28.62 mmHg, decreasing significantly postoperatively to 21.31 mmHg. The mean level of the highest IAP value recorded in pancreatitis patients treated with VAC did not differ significantly by lethality (30.31 vs. 28.50; p = 0.810). In vacuum-treated pancreatitis patients with a IAP level > 12, the probability of survival dropped below 50% during the first 7 days of stay in the ICU, so that after 20 days the probability of survival was approximately 20%. IAP enters the determinism of surgery with a sensitivity of 92.3% and a specificity of 99%, the cut-off value of IAP being 15 mmHg. (4) Conclusions: The timing of surgical decompression in abdominal compartment syndrome is very important. Consequently, it is vital to identify a parameter, easy to measure, within the reach of any clinician, so that the indication for surgical intervention can be made judiciously and without delay. [ABSTRACT FROM AUTHOR]

Seed‐mediated growth of core–shell nanoparticles, which is conventionally performed in a batch reactor, is successfully reproduced in a microfluidic reactor for a facile production of uniform metal core–shell nanoparticles. The proposed microfluidic design is based on the microstructure inversion for achieving multi‐scale homogeneous mixing with uniform nanoparticle residence time. Simulations demonstrate that among the staggered herringbone microstructures investigated in this study, the upper herringbone (UH) structure can rapidly and homogeneously mix multiple‐sized reagents and can also prevent both the irreversible trapping and long residence time of the nanoparticles inside the microfluidic channel. A wide variety of metal core–shell nanoparticles, namely Au@Ag, Au@Pd, and Au@Au with an interior nanogap, are synthesized by using the microfluidic reactor with built‐in UH microstructures. The proposed microfluidic synthesis produces a more uniform shell size than the conventional batch synthesis. This work could significantly expand the practical utility of metal core–shell nanoparticles in a multitude of applications ranging from catalysis to nanomedicine. [ABSTRACT FROM AUTHOR]