An anisotropic nanocomposite hydrogel guides aligned orientation and enhances tenogenesis of human tendon stem/progenitor cells

The uniform and aligned arrangement of tendon cells is a marker of tendon tissue morphology and the embodiment of its biological anisotropy. However, most of the hydrogels used for tendon tissue engineering do not present anisotropic structures. In this work, a magnetically-responsive nanocomposite hydrogel composed of collagen type I (COL I) and aligned iron oxide nanoparticles (IOPs) was investigated for potential application in tendon tissue engineering. COL I with a mixture of remotely aligned IOPs (A/IOPs) and human tendon stem/progenitor cells (COL I-A/IOPs-hTSPCs) was prepared and the alignment of IOPs was induced under a remote magnetic field. Following the gelation of COL I, a stable and anisotropic nanocomposite COL I-A/IOPs hydrogel was formed. In addition, hTSPCs embedded in COL I with random IOPs (COL I-R/IOPs-hTSPCs) and in pure COL I (COL I-hTSPCs) were used as control groups. Cell viability, proliferation, morphology, cell row formation, and alignment of IOPs and hTSPCs were evaluated over time. In addition, a comprehensive gene expression profile of 48 different genes, including tendon-related genes and lineage/cross-linking genes, was obtained by implementing designer quantitative RT-PCR plates. The hTSPCs morphology followed the orientation of the anisotropic COL I-A/IOPs hydrogel with increased row formation in comparison to pristine COL I and COL-R/IOPs. Moreover, higher proliferation rate and significant upregulation of tendon gene markers were measured in comparison to hTSPCs cultivated in the COL I-R/IOPs and COL I. Thus, we suggest that providing the cells with aligned focal contact points, namely the aligned IOPs, is sufficient to provoke an immense effect on the formation of aligned cell rows. Taken together, we report a novel strategy for directing stem cell behavior without the use of exogenous growth factors or pre-aligned COL I fibers, and propose that anisotropic nanocomposite hydrogels hold great potential for tendon tissue engineering applications

TRIB3, as a robust prognostic biomarker for HNSC, is associated with poor immune infiltration and cancer cell immune evasion

ObjectiveAs a pseudokinase, Tribbles Pseudokinase 3 (TRIB3) is implicated in a wide array of biological processes, including cell signal transduction, metabolic regulation, stress responses, and immune regulation. While its significant role in the immune regulation of certain cancers is well-established, the specific functions and impact of TRIB3 in head and neck squamous cell carcinoma (HNSC) remain unclear.MethodsThe data of RNA-sequence was acquired from the TCGA database to analyze the expression patterns of TRIB3 and elucidate its prognostic value in HNSC patients. Furthermore, the correlation between TRIB3 and tumor mutation burden, clinical data, immune checkpoint genes, and immune cell infiltration was explored. Moreover, the TRIB3 location in tumor tissues and subcellular structures was identified via Tisch in the HPA database, and the potential protein interaction molecules for TRIB3 were elucidated in the STRING database. The potential TRIB3 gene function was assessed using gene set enrichment analysis (GSEA), whereas the TRIB3 expression levels in clinical HNSC samples were verified by RT-qPCR and immunohistochemistry. the role of TRIB3 in enhancing the malignant behavior of HNSC cells was validated in vitro through a series of methods including RT-qPCR, CCK8 assay, wound healing assay, and transwell assay.ResultsIt was revealed that TRIB3 was significantly overexpressed in the nucleus and cytoplasm of HNSC. Furthermore, this overexpression markedly enhanced the migration ability of tumor cells. As an independent prognostic factor, TRIB3 was associated with advanced tumor T stage and was significantly involved with tumor mutation burden and immune cell infiltration in HNSC. Moreover, it was observed that TRIB3 was not a predicted factor for PD1/PDL1 and ATL4 inhibitor treatment; however, it was substantially correlated with various immune evasion-related genes in HNSC.ConclusionTRIB3 could serve as a potential prognostic marker for HNSC and might be a key gene mediating HNSC immune evasion

Correlation between Fracture Morphology and Microstructural Evolution during Long-Term Aging of EK61 Superalloy

Microstructural evolutions of EK61 superalloy during long-term aging until 1000 h at 700°C and 750°C, respectively, are studied by combination of Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM). Impact fracture morphologies after aging for different time are observed by the SEM. The microstructure is found to be relatively stable during aging at 700°C, and the fracture morphologies are characterized by transgranular fracture. At 750°C, the coarsening of γ′ phase leads the reduction of the quantity of dimples, the chainization of carbides on grain boundaries leads to intergranular fracture, and the netting of η phases within grains leads to the formation of lamellar cleavage steps. It is obvious that the destabilization of precipitated phases affects fracture morphology significantly. The relationship between fracture morphology and the microstructure promotes the evaluation of service reliability of EK61 superalloy

Large Eddy Simulation of Base Drag Reduction with Jet Boat-tail Passive Flow Control

A Large Eddy Simulation (LES) of base drag reduction for automotive side view mirrors using passive Jet Boat-Tail (JBT) passive flow control is conducted. The JBT passive flow control technique is to introduce a strong jet by opening an inlet in the front of a bluff body, accelerate the jet via a converging duct and eject the jet at an angle toward the center of the base surface. The high speed jet flow entrains the free stream flow to energize the base flow and increase base flow pressure. The LES investigation of flow over a JBT mirror and baseline mirror model is conducted with a low diffusion E-CUSP scheme with fifth order WENO scheme for the inviscid term and fourth order central differencing for the viscous term. The LES calculation indicates that strong passive flow jet enhances the flow entrainment, which mixes with the main flow and transfers the energy from the main stream to the base flow by increasing base flow pressure, thus reducing pressure drag. The preliminary analysis of the flow structures with wake and jet interaction is presented

典型光学窗口流场的气动光学效应数值模拟

Delayed detached eddy simulation (DDES) is used to simulate the flow field around the conformal optical window turret and the flat optical window turret. The aero-optical effect and the far-field diffraction result of the two optical windows at 0°, 90° and 180° angles are quantitatively analyzed based on the flow field around the turret. Zernike polynomial is applied to fit the wavefront distortion, and the adaptive optics is used to analyze the propagation performance of the two optical windows. The results show that the beam transmission performance of the flat optical window is better than that of the conformal one at the angles of 0° and 180° without adaptive optical correction, while the beam transmission performance of the conformal window at 90° angle is better than that of the flat one. When the adaptive optics correct these low-order terms including piston, tilt, defocus and astigmatism, the beam transmission performance of the conformal optical window is better than that of the flat one at the angles of 90° and 180°. At the angle of 0°, the beam transmission performance of the two optical windows is similar. With the increase of the angle, the high-order terms of the two windows decrease continuously. It is worth noting that the peak intensity of the distorted beam after diffraction in the far field may be larger than that of the undistorted beam in the far field. Meanwhile, the location of the peak intensity will be seriously offset.Aerodynamic

Rapamycin Enhances the Anti-Cancer Effect of Dasatinib by Suppressing Src/PI3K/mTOR Pathway in NSCLC Cells.

Src and the mammalian target of rapamycin (mTOR) signaling are commonly activated in non-small cell lung cancer (NSCLC) and hence potential targets for chemotherapy. Although the combined use of Src inhibitor Dasatinib with other chemotherapeutic agents has shown superior efficacy for cancer treatment, the mechanisms that lead to enhanced sensitivity of Dasatinib are not completely understood. In this study, we found that Rapamycin dramatically enhanced Dasatinib-induced cell growth inhibition and cell cycle G1 arrest in human lung adenocarcinoma A549 cells without affecting apoptosis. The synergistic effects were consistently correlated with the up-regulation of cyclin-dependent kinases inhibitor proteins, including p16, p19, p21, and p27, as well as the repression of Cdk4 expression and nuclear translocation. Mechanistic investigations demonstrated that FoxO1/FoxO3a and p70S6K/4E-BP1, the molecules at downstream of Src-PI3K-Akt and mTOR signaling, were significantly suppressed by the combined use of Dasatinib and Rapamycin. Restraining Src and mTOR with small interfering RNA in A549 cells further confirmed that the Src/PI3K/mTOR Pathway played a crucial role in enhancing the anticancer effect of Dasatinib. In addition, this finding was also validated by a series of assays using another two NSCLC cell lines, NCI-H1706 and NCI-H460. Conclusively, our results suggested that the combinatory application of Src and mTOR inhibitors might be a promising therapeutic strategy for NSCLC treatment

Facile Synthesis of P25@Pd Core-Shell Catalyst with Ultrathin Pd Shell and Improved Catalytic Performance in Heterogeneous Enantioselective Hydrogenation of Acetophenone

Heterogeneous enantioselective hydrogenation is an ideal method for synthesizing important chiral compounds in pesticides and pharmaceuticals. Up to the present, supported noble-metal catalysts are most widely studied in heterogeneous enantioselective hydrogenations. However, it is found that the weak interactions existing on the surface of support may have negative effects on the enantioselectivity. Herein, a new category of TiO2 (Aeroxide® P25) supported Pd catalyst with ultrathin Pd shell was successfully prepared via a simple strategy based on the reduction of PdI carbonyl complex. Characterization results show that a well-dispersed ultrathin Pd shell with an average thickness of ~1.0 nm and a Pd loading of 36 wt.% was formed over the surface of P25 support. By excluding the negative weak interactions from the support, the P25@Pd core-shell catalyst with unique electronic properties of Pd exhibits higher activity and enantioselectivity than that of Pd/P25 catalyst prepared by the impregnation method and unsupported Pd black catalyst in the enantioselective hydrogenation of acetophenone