Expression of a phage-encoded Gp21 protein protects Pseudomonas aeruginosa against phage infection

There is a continuously expanding gap between predicted phage gene sequences and their corresponding functions, which largely hampered the development of phage therapy. Previous studies reported several phage proteins that could interfere with the intracellular processes of the host to obtain efficient infection. But few phage proteins that protect host against phage infection has been identified and characterized in detail. Here, we isolate a phage vB_Pae_QDWS capable of infecting Pseudomonas aeruginosa PAO1, and report its encoded Gp21 protein protects PAO1 against phage infection. Expressing of Gp21 regulate bacterial quorum sensing with an inhibitory effect in low cell density and activation effect in high cell density. By testing the TFPs-mediated twitching motility and transmission electron microscopy analysis, Gp21 was found decreased the pilus synthesis. Further constructing the TFPs synthesis gene pilB mutant and performing adsorption and phage resistance assay, we demonstrated Gp21 protein could block phage infection via decreasing the TFPs-mediated phage adsorption. Gp21 is a novel protein that inhibit phage efficacy against bacteria. The study deepens our understanding of phage-host interactions. Importance The majority of the annotated phage genes are currently deposited as “hypothetical protein” with unknown function. Researches revealed that some phage proteins serve to inhibit or redirect the host intracellular processes for phage infection. Differently, we report a phage encoded protein Gp21 that protect the host against phage infection. The pathways that Gp21 involved in anti-phage defense in Pseudomonas aeruginosa PAO1 are interfering with quorum sensing and decreasing the type IV pilus-mediated phage adsorption. Gp21 is a novel protein with a low sequence homology with other reported twitching inhibitory proteins. As a lytic phage derived protein, Gp21 expression protects P. aeruginosa PAO1 from reinfection by phage vB_Pae_QDWS, which may explain the well-known pseudolysogeny caused by virulent phages. Our discoveries provide valuable new insight into the phage-host evolutionary dynamics.

Study on Influence of Surface Plasma Activation of Quartz Fiber/Cyanate Ester Composite at Meter Range Working Distance

The surface of quartz fiber/cyanate ester composite at meter working distance was activated by plasma treatment technology. Influence of plasma treatment parameters on surface contact angle of the composite was investigated, as well as changes of surface morphology, intrinsic performance and membrane-based bonding strength. Results showed that surface contact angle of the composite decreased significantly after plasma treatment with nitrogen and argon. Moreover, activation effect of argon plasma was better than that of nitrogen plasma. With the increase of voltage, surface contact angle of composite became smaller and activation effect was better. After plasma treatment, glass transition temperature (Tg) and bending strength of the composite did not change, and intrinsic property of the composite was not damaged. After plasma treatment, surface roughness and specific surface area of the composite increased, and membrane-based bonding strength of the composite with Al coating increased significantly.

Functional Characterization of Melanocortin-3 Receptor in a Hibernating Cavefish Onychostoma macrolepis

Melanocortin-3 receptor (MC3R) plays an important role in the energy homeostasis of animals under different nutritional conditions. Onychostoma macrolepis is a hibernating cavefish found in the northern part of the Yangtze River, and its adaptation to a nutrient-poor environment has attracted growing interest. In this study, we characterized the protein structure of Onychostoma macrolepis Mc3r (omMc3r), examined its tissue distribution, and investigated its function in mediating cellular signaling. We showed that the CDS of omMc3r is 978 bp, encoding a putative protein of 325 amino acids. Homology and phylogenetic analyses indicated that omMc3r is evolutionary close to cyprinids. Real-time quantitative PCR (RT-qPCR) revealed that omMc3r was highly expressed in the liver and brain. The functions of omMc3r to mediate ligands activating downstream signaling have also been confirmed by using signal pathway-specific reporters. The four agonists α-MSH, β-MSH, NDP-MSH, and ACTH (1–24) can all activate the cAMP and MAPK/ERK signaling pathway, albeit with different potency orders. The “primitive” ligand ACTH (1–24) had the highest potency on the cAMP signaling pathway, while the synthetic ligand NDP-MSH had the highest activation effect on the MAPK/ERK signaling pathway. This research will lay the foundation for studying the energy regulation mechanism of cavefish in an oligotrophic environment.

Neuroblast Differentiation-Associated Protein Derived Polypeptides: AHNAK(5758-5775) Induced Inflammatory Reaction in Skin By Mast Cells Activation

Psoriasis is a chronic inflammatory skin disease. Mast cells significantly increase and activate in the lesions and are involved in psoriatic inflammation. Neuroblast differentiation-associated protein (AHNAK) mainly express in skin, esophagus and kidney, which participates in the differentiation of neurons, the formation of cytoskeletal structure muscular regeneration and the calcium homeostasis process. Whether AHNAK is involved in mast cell activation is unclear, and the mechanisms of AHNAK induced skin inflammation also needs investigation. To investigate whether Neuroblast differentiation-associated protein derived polypeptides: AHNAK(5758-5775) activates mast cells and induces skin inflammation contributing to psoriasis, wild-type mice were treated with AHNAK(5758-5775) to observe inflammatory cells infiltrated in skin and cytokines release in vivo. Release of inflammatory mediators by mouse primary mast cells, LAD2 cells and human neutrophils were measured in vitro. Neutrophils and mast cells were co-cultured to verify AHNAK(5758-5775)’ role in inflammation. Molecular docking analysis, molecular dynamics simulation and siRNA transfection were used to prove the receptor of AHNAK(5758-5775). AHNAK(5758-5775) caused skin inflammation in WT mice by recruitment of neutrophils and cytokines release. Moreover, AHNAK(5758-5775) does not directly activate neutrophils PPD, while it is via mast cells. ST2 seems to be a key receptor meditating the activation effect of AHNAK(5758-5775) on mast cells and lead to cytokines release. Altogether, we proposed the novel polypeptide: AHNAK(5758-5775), which might induce inflammation and participated in the occurrence and development of psoriasis by activating mast cells.

Comparison of the activation capabilities of hemosorbents by adhesion rate of blood cells in vitro

Background: The relevance of the work lies in the search for new hemocontact drugs with hemocompatibility and a pronounced activation effect on the cellular and humoral blood systems for their possible use in clinical practice during low-volume hemoperfusion.The aim of this work was to assess the activation capabilities of three granular hemosorbents by the rate of adhesion of blood cellular elements to the surface of granules in vitro.Materials and methods. When using the method of low-volume hemoperfusion (LVH) in the clinic it is important to take into account the activation properties of solid-phase granular drugs. Blood-contact interaction was carried out in bench conditions with the use of donated blood in rotary mode. Blood samples were taken before the experiment and after 5, 20, 40 and 60 minutes. Changes in blood cell and subcellular populations were evaluated using the Sysmex XT 1800i hematological analyzer (26 parameters), which made it possible to indirectly judge the activation of blood cells. 30 experiments were conducted. To analyze the activation functions of the hemocontact preparations the speed-time adhesive profile of blood cells on the sorbent was used.Results. The effect of using the preparations Silochrome S-120 and SPS in comparison with SСT-6A HP as contact hemoactivators can be more pronounced, since the activation potential of these sorbents for blood cells is much higher. Silochrome S-120 has the highest activation capabilities compared to SPS and SKT-6A HP.Conclusion. Adhesion rate indicators can be indicators of the activation of blood cells upon contact with foreign surfaces and serve as a criterion for assessing the activation capabilities of these surfaces when using the LVH method in the clinic.

TiCl4/MgCl2/MCM-41 Bi-Supported Ziegler–Natta Catalyst: Effects of Catalyst Composition on Ethylene/1-Hexene Copolymerization

TiCl4/MgCl2/MCM-41 type bi-supported Ziegler-Natta catalysts with different MgCl2/MCM-41 ratios were synthesized by adsorbing TiCl4 onto MgCl2 crystallites anchored in mesopores of MCM-41 (mesoporous silica with 3.4 nm pore size). Ethylene/1-hexene copolymerization with the catalysts was conducted at different 1-hexene concentrations and ethylene pressures. MgCl2/MCM-41 composite supports and the catalysts were characterized by X-ray diffraction (XRD), nitrogen adsorption analysis (BET), and elemental analysis. The copolymers were fractionated by extraction with boiling n-heptane, and comonomer contents of the fractions were determined. Under 4 bar ethylene pressure, the bi-supported catalysts showed higher activity and a stronger comonomer activation effect than the TiCl4/MgCl2 catalyst. In comparison with the TiCl4/MgCl2 catalyst, the bi-supported catalysts produced much less copolymer fraction of low molecular weight and high 1-hexene content, meaning that the active center distribution of the catalyst was significantly changed by introducing MCM-41 in the support. The copolymer produced by the bi-supported catalysts showed similar melting temperature to that produced by TiCl4/MgCl2 under the same polymerization conditions. The space confinement effect of the mesopores of MCM-41 on the size and structure of MgCl2 crystallites is proposed as the main reason for the special active center distribution of the bi-supported catalysts.

The Research Progress of PD-1/PD-L1 Inhibitors Enhancing Radiotherapy Efficacy

Approximately 60%–70% of patients with malignant tumours require radiotherapy. The clinical application of immune checkpoint inhibitors (ICIs), such as anti-PD-1/PD-L1, has revolutionized cancer treatment and greatly improved the outcome of a variety of cancers by boosting host immunity.However, radiotherapy is a double-edged sword for PD-1/PD-L immunotherapy. Research on how to improve radiotherapy efficacy using PD-1/PD-L1 inhibitor is gaining momentum. Various studies have reported the survival benefits of the combined application of radiotherapy and PD-1/PD-L1 inhibitor. To fully exerts the immune activation effect of radiotherapy, while avoiding the immunosuppressive effect of radiotherapy as much as possible, the dose selection, segmentation mode, treatment timing and the number of treatment sites of radiotherapy play a role. Therefore, we aim to review the effect of radiotherapy combined with anti-PD-1/PD-L1 on the immune system and its optimization.

Influence of Mechanochemical Activation of Concrete Components on the Properties of Vibro-Centrifugated Heavy Concrete

One of the crucial problems in current construction is energy, resource, and material efficient technologies in both industrial and civil engineering, associated with new material manufacturing and building construction. This article is devoted to developing comprehensive technology for activation effects on concrete made by various production techniques: vibration, centrifugation, and vibro-centrifugation. The possibility of a significant improvement in the microstructure of concrete and obtaining materials with increased specified characteristics, depending on its manufacturing technology, were studied during the complex activation effect exposed to this concrete and its components. Chemical activation of water and mechanical activation of cement were considered. The urgency and prospects of double, complex mechanochemical activation of concrete mixture components were substantiated. It was proven that the complex mechanochemical activation of the concrete mixture components gives a synergistic effect in obtaining concrete composition with an improved structure and improved characteristics. Furthermore, the relationship between concrete production technology and the technology of activation of its components was established. It was revealed that the most effective is the complex mechanochemical activation of vibro-centrifuged concrete, which gives an increase in strength up to 30%. The study results indicate a further direction of development associated with an increase in variatropic characteristics using both prescription and technological factors.

Effect of mechanical activation on the properties of Portland cement

The paper deals with the mechanical activation of cement by grinding in a high-speed mill, and compares the parameters found with the commonly used grinding method in cement production, which uses grinding of cement by means of a ball mill. The aim is to verify the influence of the aging time of the ground material on the preservation of the mechanical activation effect and on the properties of the final product at different stages of hydration. It evaluates the physical-mechanical properties, the compressive and tensile strength after 1, 2, 7, 14 and 28 days, as well as the course of the hydration process. The evaluated results suggest the existence of mechanical activation, but this effect is very difficult to achieve and depends on many other factors.