Fibroblasts Close a Void in Free Space by a Purse-String Mechanism.

The mechanism by which stromal cells fill voids in injured tissue remains a fundamental question in regenerative medicine. While it is well-established that fibroblasts fill voids by depositing extracellular matrix (ECM) proteins as they migrate toward the wound site, little is known about their ability to adopt an epithelial-like purse-string behavior. To investigate fibroblast behavior during gap closure, we created an artificial wound with a large void space. We discovered that fibroblasts could form a free-standing bridge over deep microvoids, closing the void via purse-string contraction, a mechanism previously thought to be unique to epithelial wound closure. The findings also revealed that myosin II mediated contractility and intercellular adherent junctions were required for the closure of the fibroblast gap in our fabricated three-dimensional artificial wound. To fulfill their repair function under the specific microenvironmental conditions of wounds, fibroblasts appeared to acquire the structural features of epithelial cells, namely, contractile actin bundles that span over multiple cells along the boundary. These findings shed light on a novel mechanism by which stromal cells bridge the 3D gap during physiological processes such as morphogenesis and wound healing.

Deciphering Evolution Pathway of Supported NO3 • Enabled via Radical Transfer from •OH to Surface NO3 - Functionality for Oxidative Degradation of Aqueous Contaminants.

NO3 • can compete with omnipotent •OH/SO4 •- in decomposing aqueous pollutants because of its lengthy lifespan and significant tolerance to background scavengers present in H2O matrices, albeit with moderate oxidizing power. The generation of NO3 •, however, is of grand demand due to the need of NO2 •/O3, radioactive element, or NaNO3/HNO3 in the presence of highly energized electron/light. This study has pioneered a singular pathway used to radicalize surface NO3 - functionalities anchored on polymorphic α-/γ-MnO2 surfaces (α-/γ-MnO2-N), in which Lewis acidic Mn2+/3+ and NO3 - served to form •OH via H2O2 dissection and NO3 • via radical transfer from •OH to NO3 - (•OH → NO3 •), respectively. The elementary steps proposed for the •OH → NO3 • route could be energetically favorable and marginal except for two stages such as endothermic •OH desorption and exothermic •OH-mediated NO3 - radicalization, as verified by EPR spectroscopy experiments and DFT calculations. The Lewis acidic strength of the Mn2+/3+ species innate to α-MnO2-N was the smallest among those inherent to α-/ß-/γ-MnO2 and α-/γ-MnO2-N. Hence, α-MnO2-N prompted the rate-determining stage of the •OH → NO3 • route (•OH desorption) in the most efficient manner, as also evidenced by the analysis on the energy barrier required to proceed with the •OH → NO3 • route. Meanwhile, XANES and in situ DRIFT spectroscopy experiments corroborated that α-MnO2-N provided a larger concentration of surface NO3 - species with bi-dentate binding arrays than γ-MnO2-N. Hence, α-MnO2-N could outperform γ-MnO2-N in improving the collision frequency between •OH and NO3 - species and in facilitating the exothermic transition of NO3 - functionalities to surface NO3 • analogues per unit time. These were corroborated by a greater efficiency of α-MnO2-N in decomposing phenol, in addition to scavenging/filtration control runs and DFT calculations. Importantly, supported NO3 • species provided 5-7-fold greater efficiency in degrading textile wastewater than conventional •OH and supported SO4 •- analogues we discovered previously.

Lactobacillus and Pediococcus ameliorate progression of non-alcoholic fatty liver disease through modulation of the gut microbiome.

Targeting the gut-liver axis by modulating the gut-microbiome can be a promising therapeutic approach in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the effects of single species and a combination of Lactobacillus and Pediococcus in NAFLD mice model. Six-week male C57BL/6J mice were divided into 9 groups (n = 10/group; normal, Western diet, and 7 Western diet-strains [109 CFU/g, 8 weeks]). The strains used were L. bulgaricus, L. casei, L. helveticus, P. pentosaceus KID7, and three combinations (1: L. casei+L. helveticus, 2: L. casei+L. helveticus+P. pentosaceus KID7, and 3: L. casei+L. helveticus+L. bulgaricus). Liver/Body weight ratio, serum and stool analysis, liver pathology, and metagenomics by 16S rRNA-sequencing were examined. In the liver/body ratio, L. bulgaricus (5.1 ± 0.5), L. helveticus (5.2 ± 0.4), P. pentosaceus KID7 (5.5 ± 0.5), and combination1 and 2 (4.2 ± 0.6 and 4.8 ± 0.7) showed significant reductions compared with Western (6.2 ± 0.6)(p < 0.001). In terms of cholesterol and steatosis/inflammation/NAFLD activity, all groups except for L. casei were associated with an improvement (p < .05). The elevated level of tumor necrosis factor-α/interleukin-1ß (pg/ml) in Western (65.8 ± 7.9/163.8 ± 12.2) was found to be significantly reduced in L. bulgaricus (24.2 ± 1.0/58.9 ± 15.3), L. casei (35.6 ± 2.1/62.9 ± 6.0), L. helveticus (43.4 ± 3.2/53.6 ± 7.5), and P. pentosaceus KID7 (22.9 ± 3.4/59.7 ± 12.2)(p < 0.01). Cytokines were improved in the combination groups. In metagenomics, each strains revealed a different composition and elevated Firmicutes/Bacteroidetes ratio in the western (47.1) was decreased in L. bulgaricus (14.5), L. helveticus (3.0), and P. pentosaceus KID7 (13.3). L. bulgaricus, L. casei, L. helveticus, and P. pentosaceus KID7 supplementation can improve NAFLD-progression by modulating gut-microbiome and inflammatory pathway.

Understanding dual precipitation strengthening in ultra-high strength low carbon steel containing nano-sized copper precipitates and carbides.

Low carbon ferritic steel alloyed with Ti, Mo and Cu was hot rolled and interrupt cooled to produce nano-sized precipitates of copper and (Ti,Mo)C carbides. The steel had a tensile strength of 840 MPa, an increase in yield strength of 380 MPa over that of the plain carbon steel and reasonable ductility. Transmission electron microscopy and small angle neutron scattering were used to characterize size and volume fraction of the precipitates in the steels designed to form only copper precipitates and only (Ti,Mo)C carbides. The individual and combined precipitation strengthening contributions was calculated using the size and volume fraction of precipitates and compared with the measured values.

Erratum to: Understanding dual precipitation strengthening in ultra-high strength low carbon steel containing nano-sized copper precipitates and carbides.

[This corrects the article DOI: 10.1186/s40580-017-0110-5.].

Proprotein convertase inhibition promotes ciliated cell differentiation - a potential mechanism for the inhibition of Notch1 signalling by decanoyl-RVKR-chloromethylketone.

Chronic repetitive rounds of injury and repair in the airway lead to airway remodelling, including ciliated cell loss and mucous cell hyperplasia. Airway remodelling is mediated by many growth and differentiation factors including Notch1, which are proteolytically processed by proprotein convertases (PCs). The present study evaluated a novel approach for controlling basal cell-type determination based on the inhibition of PCs. It was found that decanoyl-RVKR-chloromethylketone (CMK), a PC inhibitor, promotes ciliated cell differentiation and has no effect on the ciliary beat frequency in air-liquid interface (ALI) cultures of human nasal epithelial cells (HNECs). Comparative microarray analysis revealed that CMK considerably increases ciliogenesis-related gene expression. Use of cell-permeable and cell-impermeable PC inhibitors suggests that intracellular PCs regulate basal cell-type determination in ALI culture. Furthermore, CMK effect on ciliated cell differentiation was reversed by a Notch inhibitor N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT). CMK inhibited the processing of Notch1, a key regulator of basal cell differentiation toward secretory cell lineages in the airway epithelium, and down-regulated the expression of Notch1 target genes together with furin, a PC. Specific lentiviral shRNA-mediated knockdown of furin resulted in reduced Notch1 processing and increased numbers of ciliated cells in HNECs. Moreover, CMK inhibited Notch1 processing and promoted regeneration and ciliogenesis of the mouse nasal respiratory epithelium after ZnSO4 injury. These observations suggest that PC inhibition promotes airway ciliated cell differentiation, possibly through suppression of furin-mediated Notch1 processing. © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.