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[Display omitted] • Use microfluidic device to study the dynamic mucopenetration of nanoparticles. • Quantitatively investigate the mucopenetrating behaviors of nanoparticles. • Confirm the factors that affect the mucopenetration of nanoparticles. • Mucus-on-Chip can study the barrier property of mucus with specific compositions. The mucus covering of epithelial tissues presents one significant biological barrier to the uptake and absorption of particulate carriers. Improved understanding of the mechanisms mediating the transport of nanoparticles across such mucus layers would accelerate their development as optimised mucosal drug delivery formulations (e.g. via oral and rectal routes). Herein, an in vitro mucus model ("Mucus-on-Chip") was developed to enable the interaction and transport of functionalised nanoparticles and reconstituted mucus to be quantitatively investigated in real-time. We verified that the diffusion of nanoparticles into mucus is highly dependent on their biointerfacial properties. Muco-inert modification (PEGylation) significantly enhanced the mucopenetration of 50 nm and 200 nm nanoparticles, whereas limited mucopenetration was observed for pectin coated mucoadhesive nanoparticles. Furthermore, this model can be easily adapted to mimic specific physiological mucus environments. Mucus pre-treated with a mucolytic agent displayed reduced barrier function and therefore significantly accelerated mucopenetration of nanoparticles, which was independent of their size and biointerfacial properties. This new "Mucus-on-Chip" methodology provides detailed insight into the dynamics of nanoparticle-mucus interaction, which can be applied to refine the design of particulate formulations for more efficient mucosal drug delivery. [ABSTRACT FROM AUTHOR]

Epithelial cells experience constant mechanical forces, including fluid shear stress (FSS) on their apical surface. These forces alter both structure and function. While precise recapitulation of the complex mechanobiology of organs remains challenging, better understanding of the effect of mechanical stimuli is necessary towards the development of biorelevant in vitro models. This is especially relevant to organs-on-chip models which allow for fine control of the culture environment. In this study, the effects of the FSS on Caco-2 cell monolayers were systematically determined using a microfluidic device based on Hele-Shaw geometry. This approach allowed for a physiologically relevant range of FSS (from ∼0 to 0.03 dyn/cm2) to be applied to the cells within a single device. Exposure to microfluidic FSS induced significant phenotypical and functional changes in Caco-2 cell monolayers as compared to cells grown in static conditions. The application of FSS significantly altered the production of mucus, expression of tight junctions, vacuolization, organization of cytoskeleton, formation of microvilli, mitochondrial activity and expression of cytochrome P450. In the context of the intestinal epithelium, this detailed understanding of the effects of the FSS will enable the realization of in vitro organs-on-chip models with well-defined and tailored characteristics to a specific purpose, including for drug and nanoparticle absorption studies. The Hele-Shaw approach used in this study could be readily applied to other cell types and adapted for a wide range of physiologically relevant FSS. [ABSTRACT FROM AUTHOR]

This study investigated the apoptosis pathway mediated by apoptosis-inducing factors (AIF) and internal factors that influence the release of AIF. The results indicated that the AIF expression was decreased in mitochondria and increased in nucleus ( P  < 0.05). However, no significant differences were observed in the AIF expression in mitochondria with caspase inhibitor treatment. The optical density of nucleus and mitochondrial swelling was significant increased ( P  < 0.05). Reactive oxygen species (ROS) fell gradually within the first 6 h and increased in the next 24 h. Calpain I activity was decreased, Ca 2+ concentration, cathepsin B and D activities was increased ( P  < 0.05). The results demonstrated that AIF-mediated caspase-dependent pathway was a new mitochondrial apoptosis pathway and that mitochondrial swelling, ROS content, Ca 2+ concentration, calpain I, cathepsin B and cathepsin D activities are the key influencing factors in apoptosis in postmortem bovine muscle. [ABSTRACT FROM AUTHOR]

[Display omitted] • Oxidative stress(OS) and protein S-nitrosylation(SNO) interaction regulates tenderness. • Interaction of OS with SNO impairs GSH and TRX response systems causing apoptosis. • Interaction between OS and SNO accelerates the Ca2+ release process causing apoptosis. • Interaction between OS and SNO positively regulates yak meat tenderization. To reveal the interaction of oxidative stress and protein S-nitrosylation on mitochondrial pathway apoptosis and tenderness development in postmortem yak meat. Herein, we selected yak longissimus dorsi muscle as the research object and treated hydrogen peroxide (H 2 O 2) with S-nitrosoglutathione agent (GSNO) as well as Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) in mixed injections with 0.9 % saline as a control group, followed by incubation at 4 °C for 12, 24, 72, 120 and 168 h. Results showed that this interaction significantly increased mitochondrial ROS and NO content (P < 0.05) while weakening the antioxidant capacity of GSH and TRX redox response systems or accelerating the Ca2+ release process, leading to mitochondrial functional impairment and increased apoptosis rate. Notably, the H 2 O 2 + L-NAME group showed more pronounced apoptosis. Hence, we suggest that the interaction between oxidative stress and protein S-nitrosylation could positively regulate yak meat tenderization. [ABSTRACT FROM AUTHOR]

Spoof LSP (Localized Surface Plasmon) is a great advance in metamaterials, expanding the LSP resonance from optical band into microwave band. It will yield amazing outcomes by integration with flexible electronics, wearable electronics and nanophotonics. Here, an ultrathin and flexible spoof LSP prepeared by layer-by-layer (LBL) assembly of gold nanoparticles was demonstrated. The LSPR effects in microwave band was assembly-induced and the electric resonance component disappeared, which is significantly different from that of the spoof LSPs by bulk metal. It was thought and proved by simulation to be relative with the special micro-structure of the gold nanoparticle assemblies. Furthermore, the spoof LSP by gold nanoparticles was flexible and showed a strong relationship between the resonance frequency and the curvature degree of the spoof LSP, meaning that the LSP resonance can be modulated by the deformation of the spoof LSP. We believed that these results could deepen understanding about the spoof LSPs and widen the application in multiple areas. [Display omitted] • Ultrathin and flexible spoof localized surface plasmon is fabricated by LBL assembly of gold nanoparticles. • The spoof localized surface plasmon exhibits assembly-induced LSPR resonance in microwave band. • Disappearance of electric resonance component resulting in high surface impedance. • Strong relationship between resonance frequency and curvature degree was observed. [ABSTRACT FROM AUTHOR]

Pancreatic β-cells have been reported to be mechanosensitive to cellular microenvironments, and subjecting the cells to more physiologically relevant microenvironments can produce better results than when subjecting them to the conventional two-dimensional (2D) cell-culture conditions. In this work, we propose a novel three-dimensional (3D) strategy for inducing multicellular spheroid formation based on hydrogels with tunable mechanical and interfacial properties. The results indicate that MIN6 cells can sense the substrates and form tightly clustered monolayers or multicellular spheroids on hydrogels with tunable physical properties. Compared to the conventional 2D cell-culture system, the glucose sensitivities of the MIN6 cells cultured in the 3D culture model is enhanced greatly and their insulin content (relative to the amount of protein) is increased 7.3–7.9 folds. Moreover, the relative gene and protein expression levels of some key factors such as Pdx1, NeuroD1, Piezo1, and Rac1 in the MIN6 cells are significantly higher on the 3D platform, compared to the 2D control group. We believe that this 3D cell-culture system developed for the generation of multicellular spheroids will be a promising platform for diabetes treatment in clinical islet transplantation. [ABSTRACT FROM AUTHOR]

The objective of this study was to compare the effects of two oxidation systems on the biochemical properties of yak myofibrillar protein (MP). Oxidation was induced by incubating MP with either an iron-catalyzed oxidizing system (IOS) or a metmyoglobin-oxidizing system (MOS). The following indicators of protein oxidation and protein degradation were analyzed. The carbonyl, disulfide bonds, dityrosine, and β-sheet content increased markedly with oxidant concentration in both systems(P <.05), whereas the total sulfhydryl, surface hydrophobicity and α-helix content decreased significantly(P <.05). Furthermore, the MOS carbonyl formation rate was significantly faster than the IOS rate, and the MOS significantly affected the formation of disulfide bonds and inhibited the exposure of hydrophobic amino acids. Both oxidative systems promoted cross-linking of myosin heavy chains (MHCs) and action, but the degree of cross-linking in IOS was greater than that in MOS. MOS also promoted cross-linking of myosin light chains (MLCs). IOS and MOS produced mainly 20–25-kDa and 20–17-kDa MLC degradation products, respectively. In conclusion, oxidation caused cross-linking in MHCs or MLCs through disulfide bonds, but the extent of such cross-linking was oxidant dose-dependent and specific to each oxidizing system. • The metmyoglobin oxidizing system carbonyl formation rate was faster than the iron-catalyzed oxidizing system. • The metmyoglobin oxidizing system significantly affected the formation of disulfide bonds and inhibited the exposure of hydrophobic amino acids (P <.05). • The degree of cross-linking of myofibrillar protein in metmyoglobin oxidizing system was greater than that in iron-catalyzed oxidizing system. [ABSTRACT FROM AUTHOR]