HCV-Induced Immunometabolic Crosstalk in a Triple-Cell Co-Culture Model Capable of Simulating Systemic Iron Homeostasis

Iron is crucial to the regulation of the host innate immune system and the outcome of many infections. Hepatitis C virus (HCV), one of the major viral human pathogens that depends on iron to complete its life cycle, is highly skilled in evading the immune system. This study presents the construction and validation of a physiologically relevant triple-cell co-culture model that was used to investigate the input of iron in HCV infection and the interplay between HCV, iron, and determinants of host innate immunity. We recorded the expression patterns of key proteins of iron homeostasis involved in iron import, export and storage and examined their relation to the iron regulatory hormone hepcidin in hepatocytes, enterocytes and macrophages in the presence and absence of HCV. We then assessed the transcriptional profiles of pro-inflammatory cytokines Interleukin-6 (IL-6) and interleukin-15 (IL-15) and anti-inflammatory interleukin-10 (IL-10) under normal or iron-depleted conditions and determined how these were affected by infection. Our data suggest the presence of a link between iron homeostasis and innate immunity unfolding among liver, intestine, and macrophages, which could participate in the deregulation of innate immune responses observed in early HCV infection. Coupled with iron-assisted enhanced viral propagation, such a mechanism may be important for the establishment of viral persistence and the ensuing chronic liver disease.

Interactions of nasal epithelium with macrophages and dendritic cells variously alter urban PM-induced inflammation in healthy, asthma and COPD

Urban particulate matter (UPM) is an important trigger of airway inflammation. The cross-talk between the external and internal matrix in the respiratory tract occurs due to the transepithelial network of macrophages/dendritic cells. This study characterized the immune processes induced by the epithelium after UPM exposure in special regard to interactions with monocyte-derived dendritic cells (moDCs) and monocyte-derived macrophages (moMφs) in obstructive lung diseases. A triple-cell co-culture model (8 controls, 10 asthma, and 8 patients with COPD) utilized nasal epithelial cells, along with moMφs, and moDCs was exposed to UPM for 24 h. The inflammatory response of nasal epithelial cells to UPM stimulation is affected differently by cell–cell interactions in healthy people, asthma or COPD patients of which the interactions with DCs had the strongest impact on the inflammatory reaction of epithelial cells after UPM exposure. The epithelial remodeling and DCs dysfunction might accelerate the inflammation after air pollution exposure in asthma and COPD.

Investigation of mechanical properties for 2.5D woven composites with different weft-layer-numbers by a triple-cell model system

As a new type of textile composites with broad application prospects, it is essential to study the prediction method of the mechanical properties of 2.5 D woven composites (2.5DWC). Currently, the most popular prediction method is to use a representative volume cell (RVC) for numerical simulation, so the reasonableness of RVC determines the prediction accuracy. However, many practical factors are ignored in the traditional periodic unit-cell model (UCM), such as the weft-layer-number (WLN), resulting in low prediction accuracy; while the full-cell model (FCM) in which the surface extrusion effect (SEE) and WLN are considered has the problems of complex modeling and high computational cost. To solve these problems, a triple-cell model (TCM) system is proposed, which includes four RVCs that are applicable to different WLNs, each of which is composed of different sub-cells (surface-cell, transition-cell, and inner-cell) which are categorized according to the characteristics of the actual weft yarn cross-section. Based on the progressive damage method, the stiffness, strength, and damage behavior of 2.5DWC with different WLNs are predicted, and the TCM prediction results are compared with the results of the experiment, the UCM, and the FCM. Compared with the experimental results, the prediction accuracy of the TCM is more than 8% higher than that of the UCM, and the difference between the prediction results of the TCM and FCM is less than 5%. Therefore, the proposed TCM system has the characteristics of high prediction accuracy, relatively simple modeling, and the applicability of any WLN.

The Expressions of TSLP, IL-33, and IL-17A in Monocyte Derived Dendritic Cells from Asthma and COPD Patients are Related to Epithelial–Macrophage Interactions

Background. The cross-talk between the external and internal environment in the respiratory tract involves macrophage/dendritic cell (DC) transepithelial network. Epithelium triggers dendritic cell-mediated inflammation by producing thymic stromal lymphopoietin (TSLP), IL-33, and IL-17A. The study aimed to evaluate the expression of TSLP, IL-33, and IL-17A in human monocyte derived dendritic cells (moDCs) co-cultured with respiratory epithelium and monocyte derived macrophages (moMφs) in asthma, chronic obstructive pulmonary disease (COPD) and healthy controls. Methods. The study used a triple-cell co-culture model, utilizing nasal epithelial cells, along with moMφs and moDCs. Cells were cultured in mono-, di-, and triple-co-cultures for 24 h. Results. Co-culture with epithelium and moMφs significantly increased TSLP in asthma and did not change IL-33 and IL-17A mRNA expression in moDCs. moDCs from asthmatics were characterized by the highest TSLP mRNA expression and the richest population of TSLPR, ST2, and IL17RA expressed cells. A high number of positive correlations between the assessed cytokines and CHI3L1, IL-12p40, IL-1β, IL-6, IL-8, TNF in moDCs was observed in asthma and COPD. Conclusion. TSLP, IL-33, and IL-17A expression in moDCs are differently regulated by epithelium in asthma, COPD, and healthy subjects. These complex cell–cell interactions may impact airway inflammation and be an important factor in the pathobiology of asthma and COPD.

Triple-Cell Origami Structure for Multistable Transition Sequences

With the infinite design space and the excellent folding-induced deformability, origami has been recognized as an effective tool for developing reconfigurable structures. Particularly, the multistable origami structure, which possesses more than one stable configuration that is distinct in shape and mechanical properties, has received wide research attention. Generally, the origami structure reaches a kinematic singularity point when switching among different stable configurations. At this critical state, multiple switching sequences are possible, and the actual transition is generally hard to predict. In this paper, evolving from the conventional bistable Miura-ori unit, a triple-cell origami structure with eight potential stable configurations is proposed, which serves as a platform for investigating the transition sequences among different stable configurations. To quantify the overall elastic potential of the structure, besides the conventional elastic energy originating from the rigid folding creases, extra elastic potential induced by the mismatch among the cells are introduced, so that folding of the triple-cell structure is no longer a strict single degree-of-freedom mechanism. Instead, the three cells can deform asynchronously to avoid reaching the kinematic singularity point. Hence, under displacement loading, the transition sequence of the multistable structure is predicted by performing optimization on the elastic potential energy. It shows that sequences with multifarious characteristics are possible, including reversible and irreversible transitions, and transitions with symmetric and asymmetric energy barriers. Considering that the fundamental transition mechanisms are of great significance in understanding the quasi-static and dynamic behaviors of multistable structures, the results could be potentially employed for developing morphing structures, adaptive metamaterials, and mechanical logic gates.

Equivalent substitution criteria of aluminum for steel and its application in automobile structures

Lightweight automobile body structure, made of aluminum, can extend the endurance mileage of electric automobile. However, the mechanisms for the application of aluminum in automobile body structure are not clear until now. The main contribution of this work is to propose a method of equivalent substitution criteria of aluminum for steel. This method researches small deformation and large deformation under bending mode. First, formulations of cross-sectional properties, including open, single-cell, double-cell, three-cell, and four-cell sections, are derived, and equivalent substitution criteria in the case of small deformation, which include equal stiffness design and equal strength design, are initially proposed. Second, in the case of large deformation, the steel circular tube and channel tube are substituted by aluminum tube under equivalent stiffness. The bending resistance of five types of tubes, including rectangular hollow section, rectangular hollow section with double-cell, rectangular hollow section with triple-cell, mild steel, and high-strength steel tube, are, respectively, compared considering crashworthiness under equal mass. Third, the side frame and chassis frame examples verify the effectiveness of the proposed method, which is universal and can also be applied in aerospace structures.