Identification of a Novel Peptide with Alcohol Dehydrogenase Activating Ability from Ethanol-Induced Lactococcus lactis: A Combined In Silico Prediction and In Vivo Validation.

Alcohol dehydrogenase (ADH) is a crucial rate-limiting enzyme in alcohol metabolism. Our previous research found that ethanol-induced intracellular extracts of Lactococcus lactis (L. lactis) could enhance alcohol metabolism in mice, but the responsible compounds remain unidentified. The study aimed to screen potential ADH-activating peptides from ethanol-induced L. lactis using virtual screening and molecular docking calculation. Among them, the pentapeptide FAPEG might bind to ADH through hydrophobic interaction and hydrogen bonds, then enhancing ADH activity. Spectroscopy analysis further investigated the peptide-enzyme interaction between FAPEG and ADH, including changes in the amino acid residue microenvironment and secondary structural alterations. Furthermore, FAPEG could protect against alcoholic liver injury (ALI) in mice by reducing blood alcohol concentration, enhancing the activity of antioxidant and alcohol metabolism enzymes, and attenuating alcohol-induced hepatotoxicity, which was related to the activation of the Nrf2/keap1/HO-1 signaling pathway. The study provided preliminary evidence that the generation of ADH-activating peptides in ethanol-induced L. lactis has the potential in preventing ALI in mice using in silico prediction and in vivo validation approaches.

HIF-1α inhibition by MO-2097, a novel chiral-free benzofuran targeting hnRNPA2B1.

INTRODUCTION: Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator mediating adaptive responses to hypoxia. It is up-regulated in the tumor microenvironment and recognized as an effective anticancer drug target. Previously, we discovered that the natural compound moracin-O and its synthetic derivative MO-460 inhibited HIF-1α via hnRNPA2B1. OBJECTIVES: This study aimed to develop novel HIF-1 inhibitors for cancer chemotherapy by harnessing the potential of the natural products moracins-O and P. METHODS: In an ongoing search for novel HIF-1 inhibitors, a series of nature-inspired benzofurans with modifications on the chiral rings of moracins-O and P were synthesized. They showed improved chemical tractability and were evaluated for their inhibitory activity on HIF-1α accumulation under hypoxic conditions in HeLa CCL2 cells. The most potent derivative's chemical-based toxicities, binding affinities, and in vivo anti-tumorigenic effects were evaluated. Further, we examined whether our compound, MO-2097, exhibited anticancer effects in three-dimensional cultured organoids. RESULTS: Herein, we identified a novel synthetic chiral-free compound, MO-2097, with reduced structural complexity and increased efficiency. MO-2097 exhibited inhibitory effects on hypoxia-induced HIF-1α accumulation in HeLa CCL2 cells via inhibition of hnRNPA2B1 protein, whose binding affinities were confirmed by isothermal titration calorimetry analysis. In addition, MO-2097 demonstrated in vivo efficacy and biocompatibility in a BALB/c mice xenograft model. The immunohistochemistry staining of MO-2097-treated tissues showed decreased expression of HIF-1α and increased levels of apoptosis marker cleaved caspase 3, confirming in vivo efficacy. Furthermore, we confirmed that MO-2097 works effectively in cancer patient-based organoid models. CONCLUSION: MO-2097 represents a promising new generation of chemotherapeutic agents targeting HIF-1α inhibition via hnRNPA2B1, requiring further investigation.

Circ_0067717 promotes colorectal cancer cell growth, invasion and glutamine metabolism by serving as a miR-497-5p sponge to upregulate SLC7A5.

BACKGROUND: Circular RNAs (circRNAs) have been shown to exert vital functions in colorectal cancer (CRC) development. However, the role of circ_0067717 in CRC progression remains to be elucidated. METHODS: The expression of circ_0067717, microRNA (miR)-497-5p and solute carrier family 7 member 5 (SLC7A5) was analyzed by quantitative real-time PCR. Cell proliferation, apoptosis and invasion were determined by cell counting kit 8 assay, EdU assay, flow cytometry and transwell assay. Protein expression was examined using western blot analysis. Glutamine metabolism was assessed by measuring glutamine consumption, α-ketoglutarate production and glutamate production. The interaction between miR-497-5p and circ_0067717 or SLC7A5 was identified by dual-luciferase reporter assay. Xenograft tumor models were constructed to confirm the role of circ_0067717 in CRC tumorigenesis in vivo. RESULTS: Our data revealed that circ_0067717 was upregulated in CRC tissues and cells, and its knockdown restrained CRC cell proliferation, invasion, glutamine metabolism, and promoted apoptosis. MiR-497-5p was lowly expressed in CRC and it could be sponged by circ_0067717. MiR-497-5p inhibitor eliminated the regulation of circ_0067717 knockdown on CRC cell function. SLC7A5 was targeted by miR-497-5p and was positively regulated by circ_0067717. MiR-497-5p overexpression suppressed CRC cell growth, invasion and glutamine metabolism, and SLC7A5 was able to revoke this effect. Animal experiments showed that interference of circ_0067717 reduced CRC tumor growth. CONCLUSION: Our research pointed out that circ_0067717 facilitated CRC development depending on the regulation of the miR-497-5p/SLC7A5 axis, providing a novel insight into CRC treatment.

Chemical Imaging by Dissolution Analysis: Localized Kinetics of Dissolution Behavior to Provide Two-Dimensional Chemical Mapping and Tomographic Imaging on a Nanoscale.

A new approach to achieving chemical mapping on a nanoscale is described that can provide 2D and tomographic images of surface and near-surface structure. The method comprises dissolving material from the surface of the sample by applying a series of aliquots of solvent, then analyzing their contents after removing them; in between exposures, the surface is imaged with atomic force microscopy. This technique relies on being able to compensate for any drift between images by use of software. It was applied to a blend of two polymers, PMMA and PS. The analytical data identified the material that was dissolved, and the topography images enabled the location of the various materials to be determined by analyzing local dissolution kinetics. The prospects for generalizing the approach are discussed.

Numerical simulation of supersonic gap flow.

Various gaps in the surface of the supersonic aircraft have a significant effect on airflows. In order to predict the effects of attack angle, Mach number and width-to-depth ratio of gap on the local aerodynamic heating environment of supersonic flow, two-dimensional compressible Navier-Stokes equations are solved by the finite volume method, where convective flux of space term adopts the Roe format, and discretization of time term is achieved by 5-step Runge-Kutta algorithm. The numerical results reveal that the heat flux ratio is U-shaped distribution on the gap wall and maximum at the windward corner of the gap. The heat flux ratio decreases as the gap depth and Mach number increase, however, it increases as the attack angle increases. In addition, it is important to find that chamfer in the windward corner can effectively reduce gap effect coefficient. The study will be helpful for the design of the thermal protection system in reentry vehicles.

Game theory model of traffic participants within amber time at signalized intersection.

The traffic light scheme is composed of red, green, and amber lights, and it has been defined clearly for the traffic access of red and green lights; however, the definition of that for the amber light is indistinct, which leads to the appearance of uncertainty factors and serious traffic conflicts during the amber light. At present, the traffic administrations are faced with the decision of whether to forbid passing or not during the amber light in the cities of China. On one hand, it will go against the purpose of setting amber lights if forbidding passing; on the other hand, it may lead to a mess of traffic flow running if not. And meanwhile the drivers are faced with the decision of passing the intersection or stopping during the amber light as well. So the decision-making behavior of traffic administrations and drivers can be converted into a double game model. And through quantification of their earnings in different choice conditions, the optimum decision-making plan under specific conditions could be solved via the Nash equilibrium solution concept. Thus the results will provide a basis for the formulation of the traffic management strategy.

A simple route to enhance the interface between graphite oxide nanoplatelets and a semi-crystalline polymer for stress transfer.

This report shows that thermal treatment is a simple and effective approach to create a polymer crystalline layer on the surface of graphite oxide nanoplatelets (GONPs) in polycaprolactone (PCL) melts. It was found that the crystallization temperature of the PCL increased significantly by nearly 9 degrees C with the incorporation of 2 wt% GONPs. As the composite melts isothermally crystallized at the temperature that was 14 degrees C higher than the crystallization temperature, the polymer crystalline layer was optimized on the surface of the GONPs. At 2 wt% GONPs, the Young's modulus of the composite was nearly 1.5 times greater than for the pure PCL. In comparison with untreated composites, the improvement in the Young's modulus of treated composites nearly doubled. It confirmed that a non-covalent interface for stress transfer can be enhanced by the formation of the polymer crystalline layer bridging the GONPs and the polymer matrix.

The mechanical properties and morphology of a graphite oxide nanoplatelet/polyurethane composite.

Significant reinforcement of polyurethane (PU) using graphite oxide nanoplatelets (GONPs) is reported. Morphologic study shows that, due to the formation of chemical bonding, there is a strong interaction between the GONPs and the hard segment of the PU, which allows effective load transfer. The GONPs can prevent the formation of crystalline hard segments due to their two-dimensional structure. With the incorporation of 4.4 wt% of GONPs, the Young's modulus and hardness of the PU are significantly increased by approximately 900% and approximately 327%, respectively. The resultant high resistance to scratching indicates promise for application of these composite materials in surface coating.

Preparation and characterization of polyurethane-carbon nanotube composites.

Well-dispersed and long-term stable carbon nanotubes/polyol dispersions were prepared by a mechanochemical approach with the aid of dispersing agent. Polyurethane (PU)-carbon nanotube nanocomposites were prepared by further polymerization. Multi-walled carbon nanotubes (MWNT) can be dispersed individually. Fourier transform infrared (FTIR) spectra suggested that the addition of carbon nanotubes improved the degree of phase separation of polyurethane. Dynamic mechanical analysis (DMA) suggested that glass transition temperature () of polyurethane decreased with increasing carbon nanotube content slightly. Tensile test suggested that MWNT is more helpful to improve the modulus than single-walled carbon nanotube (SWNT), which is more favourable to improve the elongation of polyurethane. The different reinforcing effects of MWNT and SWNT on PU were correlated to the shearing thinning exponent and the shape factor of carbon nanotubes in polyol dispersion. Raman shift of SWNTs can reflect the dispersion state of SWNT in polyol or in PU, and the interaction between polymer and SWNT. Both SWNT and MWNT can improve the thermal stability of polyurethane and thermal conductivity.