IGFBP2 derived from PO-MSCs promote epithelial barrier destruction by activating FAK signaling in nasal polyps.

The nasal polyps (NPs) microenvironment comprises multiple cell types, including mesenchymal stromal cells (MSCs). Insulin-like growth factor binding protein 2 (IGFBP2) plays crucial roles in cell proliferation, differentiation and more. However, the role of NPs-derived MSCs (PO-MSCs) and IGFBP2 in NPs pathogenesis remains poorly defined. Herein, primary human nasal epithelial cells (pHNECs) and MSCs were extracted and cultured. Extracellular vesicles (EVs) and soluble proteins were isolated to investigate the role of PO-MSCs on epithelial-mesenchymal transition (EMT) and epithelial barrier function in NPs. Our data showed that IGFBP2, but not EVs from PO-MSCs (PO-MSCs-EVs), exhibited a crucial role in EMT and barrier destruction. Moreover, focal adhesion kinase (FAK) signaling pathway is necessary for IGFBP2 to exert its functions in human and mice nasal epithelial mucosa. Altogether, these findings may improve the current understanding of the role of PO-MSCs in NPs microenvironment and ultimately contribute to the prevention and treatment of NPs.

Contact Reactive Brazing of TC4 Alloy to Al7075 Alloy with Deposited Cu Interlayer.

The brazing of Titanium alloy to Aluminum alloy is of great significance for lightweight application, but the stable surface oxide film limits it. In our work, the surface oxide film was removed by the ion bombardment, the deposited Cu layer by magnetron sputtering was selected as an interlayer, and then the contact reactive brazing of TC4 alloy to Al7075 alloy was realized. The microstructure and joining properties of TC4/Al7075 joints obtained under different parameters were observed and tested, respectively. The results revealed that the intermetallic compounds in the brazing seam reduced with the increased brazing parameters, while the reaction layer adjacent to TC4 alloy continuously thickened. The shear strength improved first and then decreased with the changing of brazing parameters, and the maximum shear strength of ~201.45 ± 4.40 MPa was obtained at 600 °C for 30 min. The fracture path of TC4/Al7075 joints changed from brittle fracture to transgranular fracture, and the intergranular fracture occurred when the brazing temperature was higher than 600 °C and the holding time exceeded 30 min. Our work provides theoretical and technological analyses for brazing TC4/Al7075 and shows potential applications for large-area brazing of titanium/aluminum.

miR-30a-5p Inhibits Epithelial-to-Mesenchymal Transition by Targeting CDK6 in Nasal Polyps.

BACKGROUND: Epithelial-to-Mesenchymal Transition (EMT) is considered as a crucial event in disease development and dysregulation of microRNAs (miRNAs) is involved in the regulation of EMT in various human diseases. Emerging evidences congregated over the years have demonstrated that miR-30a-5p was decreased in diseases and its overexpression inhibited the process of diseases via attenuating EMT. Although aberrant expression of miRNAs and occurrence of EMT were previously reported in Nasal Polyps (NPs), the role of miR-30a-5p in EMT of NPs is still remains unclear. OBJECTIVE: The purpose of our present study was to explore the expression and potential function of miR-30a-5p in EMT of NPs. METHODS: The expression of miR-30a-5p and mRNA expression level were detected by quantitative real-time PCR (qRT-PCR) in transforming growth factor ß1 (TGF-ß1) - induced EMT model and NPs patients. Western Blot (WB) and immunohistochemistry (IHC) were performed to evaluate the protein expression level of EMT markers. The cells mobility was assessed by Wound-Healing assay. Luciferase reporter assay was utilized to verify the relationship between Cyclin-dependent kinase 6 (CDK6) and miR-30a-5p. RESULTS: Firstly, we observed that miR-30a-5p was down-regulated notably, accompanying with the alteration of EMT markers expression in NPs tissues and EMT model induced by TGF-ß1 in primary Human Nasal Epithelial Cells (pHNECs) and A549 cells in vitro. Moreover, the functional assays demonstrated that overexpression of miR-30a-5p significantly inhibited EMT and cells mobility. Subsequently, CDK6 was validated as a direct target of miR-30a-5p. Finally, we performed the rescue experiments indicating that overexpression of CDK6 eliminated the suppressive effects of miR-30a-5p in TGF-ß1-induced EMT in pHNECs and A549 cells. CONCLUSION: Taken together, our results suggested that EMT was involved in NPs, and overexpression of miR-30a-5p could attenuate EMT via repressing the expression of the CDK6 in pHNECs and A549 cells.

Exosomal miR-22-3p Derived from Chronic Rhinosinusitis with Nasal Polyps Regulates Vascular Permeability by Targeting VE-Cadherin.

BACKGROUND: The abnormal vascular permeability is associated with the formation of chronic rhinosinusitis with nasal polyps (CRSwNP). Previously, our study demonstrated that the nasal lavage fluid- (NLF-) derived exosomes from CRSwNP can promote the vascular permeability of human umbilical vein endothelial cells (HUVECs). miR-22-3p, a specific differentiated miRNA, is reported to regulate microvessels in some diseases. This study is purposed to explore the impact of exosomal miR-22-3p derived from CRSwNP on vascular permeability and identify the underlying targets. METHODS: Exosomes were extracted from NLF of 26 CRSwNP patients and 10 control patients. Quantitative real-time PCR (qRT- PCR) was applied to evaluate the relative level of exosomal miR-22-3p. The impact of exosomal miR-22-3p on HUVECs was assessed by permeability assays in vitro. The potential molecular targets of miR-22-3p were investigated by applying such technologies as dual-luciferase reporter assay and western blot. RESULTS: miR-22-3p was upregulated in NLF-derived exosomes from CRSwNP. Exosomal miR-22-3p derived from CRSwNP enhanced the tubule permeability of HUVECs. Vascular endothelial- (VE-) cadherin (CDH5) was identified as a direct target of miR-22-3p. miR-22-3p regulated the vascular permeability by targeting VE-cadherin in HUVECs. CONCLUSIONS: Exosomal miR-22-3p derived from NLF of CRSwNP plays an important role in regulating vascular permeability by targeting VE-cadherin.

Thermal management applied laminar composites with SiC nanowires enhanced interface bonding strength and thermal conductivity.

Design and fabrication of oriented thermal management materials has great significance in meeting the requirements of high-power heat dissipation device applications. To synchronously improve the structure stability and thermal management performance, in this study, large-scale silicon carbide (SiC) nanowires were deposited on the graphite film (GF) surface to reinforce the aluminum-based laminar composites. Highly thermally conductive SiCnws-GF multiscale architecture reinforced Al laminar composites with enhanced interlayer bonding strength were achieved by an innovative pressure infiltration strategy. The embedding of the silicon carbide nanowires not only improved the thermal conductivity of the laminar composites but also enhanced the interface bonding strength between the Al matrix and the SiCnws-GF multiscale structure robustly. The interlaminar shear strength of the SiCnws-GF reinforced Al laminar composites was 134.1 MPa, which was 2.4 times the value of GF reinforced Al composites. The in-plane thermal conductivity of the best-performing SiCnws-GF reinforced Al laminar composites was 868.9 W (m K)-1, which was 16.9% higher than the value of the GF reinforced Al laminar composites. The outstanding interlaminar shear strength and superior thermal conductivity of the SiCnws-GF reinforced Al laminar composites revealed that a potential and competitive thermal management material was obtained.