Synergy of Immunostimulatory Genetherapy with Immune Checkpoint Blockade Motivates Immune Response to Eliminate Cancer

Normalizing the tumor-induced immune deficiency in the immunosuppressive tumor microenvironment (TME) through increasing the efficient infiltration and activation of antitumoral immunity in TME is the core of promising immunotherapy. Herein, a Cyclo(Arg-Gly-Asp-d -Phe-Lys) (RGD) peptides-modified combinatorial immunotherapy system based on the self-assembly of the nanoparticles named RGD-DMA composed of RGD-PEG-PLA, methoxy poly(ethylene glycol)-poly(lactide) (MPEG-PLA) and 1,2-Dioleoyl-3-trimethylammonium-propane (DOTAP) is used to codeliver the immunostimulatory chemokine CCL19-encoding plasmid DNA (CCL19 pDNA) and immune checkpoint ligand PD-L1 inhibitor (BMS-1). The RGD-DMA/pCCL19-BMS-1 system not only exhibited significant inhibition of tumor progression but also induced locally high concentrations of immunostimulatory cytokines at tumor sites without causing an obviously systemic inflammatory response. The immunosuppressive TME is efficaciously reshaped by the coadministration of RGD-DMA/pCCL19 and BMS-1, as indicated by the activated T lymphocytes, increased intratumoral-infiltration of mature dendritic cells (DCs), and the repolarization of macrophages from pro-tumoral M2-phenotype toward tumoricidal M1-phenotype. The upregulated PD-L1 expression at tumor sites caused by the increased IFN-γ levels after immunostimulatory gene therapy further demonstrated the synergistic effects of BMS-1 in counteracting the inhibitory role of PD-L1 expression in antitumor immunity. Therefore, the combination of immunostimulating therapy and immune checkpoint inhibitor that synergistically target multiple immune regulatory pathways demonstrates significant potential as a novel immunotherapy approach.     

发挥设备专业化优势探索项目建设设备综合管理标准化工作

设备综合管理工作始终贯穿在项目建设整个过程中.从项目立项审查、基础设计审查、设备订货前的技术把关,到工程施工环节的专业技术检查,再到项目中交、联动试车、投料试车,处处可见设备综合管理的内容.本文梳理出设备综合管理的主要节点内容、现状和存在的问题,针对镇海基地项目群的建设,就如何发挥设备专业化的优势、如何对设备综合管理工作进行创新、如何优化工作流程进行了探索.旨在通过设备综合管理工作的统筹和协调,将专业化优势形成合力,更高质量、更高效率地为项目建设服务.     

Biomimetic Lamellar Chitosan Scaffold for Soft Gingival Tissue Regeneration

Mucogingival surgery has become a common procedure for soft gingival tissue reparation in dental clinical practice, which mainly relies on autograft or commercial collagen membranes (CM). However, the autograft faces grand challenges in source availability and long-term post-surgery pain management, and the CM is restricted by its poor mechanical properties in an aqueous environment. Here, it is reported that a bio-inspired lamellar chitosan scaffold (LCS) with long range ordered porous structure, manufactured through a bidirectional freezing method, can serve as a promising gingival tissue engineering material. The LCS not only exhibits excellent mechanical properties in the hydrated state but also accelerates vessel formation and soft tissue regeneration in vivo. Most interestingly, the LCS is found to be capable of inducing macrophage differentiation to M2 macrophages, which is thought to play an important role in tissue regeneration. These advantages combined with its easy and low-cost preparation process make the LCS a promising candidate for dental clinical applications.     

Spinel CoFe2O4 /carbon nanotube composites as efficient bifunctional electrocatalysts for oxygen reduction and oxygen evolution reaction

In the development of fuel cells, it is the key to large-scale commercialization of fuel cells to rationally design and synthesize efficient and non-noble metals-based bifunctional electrocatalysts for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). In this paper, spinel CoFe₂O₄/carbon nanotube composites (CoFe₂O₄/CNTs/FA) were synthesized by solvothermal and calcination method. XRD, TEM, XPS and BET characterizations indicate that the addition of complexing agent fumaric acid can improve the crystal growth kinetics and morphology of CoFe₂O₄/CNTs nanohybirds. The as-synthesized CoFe₂O₄/CNTs/FA pyrolyzed at 500 °C have an outstanding bifunctional catalytic activity for ORR and OER with the potential of 1.62V (vs. RHE) at a current density of 10 mA/cm² and half-wave potential E_1/2 = 0.808V (vs. RHE) in alkaline electrolyte, respectively. It is obviously better than unloaded CoFe₂O₄ nanoparticles and commercial CNTs. CoFe₂O₄/CNTs/FA also exhibit better methanol tolerance ability and durability than commercial Pt/C and RuO₂ catalyst. This investigation broadens an idea of simple compounding of spinel with carbon-based materials to improve electrochemical properties.     

Achieving thermally stable and anti-hydrolytic Sr2Si5N8:Eu2+ phosphor via a nanoscale carbon deposition strategy

Chemical stability of phosphors is critical to the efficiency and lifetime of the white light-emitting diodes. Therefore, many strategies have been adopted to improve the stability of phosphors. However, it is still lack of report on the improvement of thermal stability and hydrolysis resistance of phosphors by a single layer coating. Due to the high transmittance and high chemical inertness of graphene, it was coated on the surface of Sr₂Si₅N₈:Eu²⁺ phosphor by chemical vapor deposition, aiming to improve its thermal stability and hydrolysis resistance. The chemical composition and microstructure of the coating were characterized and analyzed. A nanoscale carbon layer was attached on the surface of Sr₂Si₅N₈:Eu²⁺ phosphor particles in an amorphous state. In coated Sr₂Si₅N₈:Eu²⁺ phosphor, the oxidation degree of Eu²⁺ to Eu³⁺ was significantly suppressed. At the same time, the surface of Sr₂Si₅N₈:Eu²⁺ particle turned from hydrophilic to hydrophobic after carbon coating, and consequently the hydrolysis resistance of Sr₂Si₅N₈:Eu²⁺ phosphor was greatly improved. After tests at 85 °C and 85% humidity for 200 h, the carbon coated Sr₂Si₅N₈:Eu²⁺ phosphor still maintained about 95% of its initial luminous intensity as compared with 35% of the uncoated. By observing the in-situ microstructure evolution of coated phosphor in air-water vapor environment, remained presence of the carbon layer even at 500 °C explained the excellent chemical stability of carbon coated Sr₂Si₅N₈:Eu²⁺ phosphor in complex environment. These results indicate that a nanoscale carbon layer can be used to provide superior thermal stability and hydrolysis resistance of (oxy) nitrides phosphors.     

CO2 sensing properties and mechanism of PrFeO3 and NdFeO3 thick film sensor

The CO_2 sensing of PrFeO_3 and NdFeO_3 sensors were investigated. Experimental results show that the resistances for PrFeO_3 and NdFeO_3 in CO_2 gas are larger than those in air and the responses for PrFeO_3and NdFeO_3 sensors increase with an increase in room-temperature relative humidity. When exposed to1000 ppm CO_2, the response of PrFeO_3 thick film based on nano-powders annealed at 700℃can reach8.44 at 160℃for the background of wet air with 58%of room-temperature relative humidity (RH),which is much larger than the corresponding value (3.03) in wet air with 25%RH. The sensing response S of NdFeO_3 thick-film sensor based on nano-powders annealed at 600℃to 3000 ppm CO_2 at the operating temperature 200℃can reach 2.36 for the background of wet air with 72%RH, which is larger than the corresponding value (1.83) in the air with 25%RH. Compared with other CO_2 sensing materials, the PrFeO_3 sensor has larger response at lower operating temperature for CO_2 gas and may be used as a new CO_2 sensing material.