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.     

轿顶子电站引水隧洞富水破碎围岩洞段超前帷幕注浆堵水施工技术研究

超前帷幕注浆堵水是富水围岩地下洞室工程止水加固的重要手段.文章以轿顶子水电站发电引水隧洞富水破碎围岩洞段为例,详细介绍了超前帷幕注浆堵水施工的总体思路和具体流程.施工结果显示,该施工方案的堵水加固效果良好,对相关类似工程具有一定的借鉴意义.     

Engineering Silver-Enriched Copper Core-Shell Electrocatalysts to Enhance the Production of Ethylene and C2+ Chemicals from Carbon Dioxide at Low Cell Potentials

Copper catalysts are widely studied for the electroreduction of carbon dioxide (CO₂) to value-added hydrocarbon products. Controlling the surface composition of copper nanomaterials may provide the electronic and structural properties necessary for carbon-carbon coupling, thus increasing the Faradaic efficiency (FE) towards ethylene and other multi-carbon (C₂₊) products. Synthesis and catalytic study of silver-coated copper nanoparticles (Cu@Ag NPs) for the reduction of CO₂ are presented. Bimetallic CuAg NPs are typically difficult to produce due to the bulk immiscibility between these two metals. Slow injection of the silver precursor, concentrations of organic capping agents, and gas environment proved critical to control the size and metal distribution of the Cu@Ag NPs. The optimized Cu@Ag electrocatalyst exhibited a very low onset cell potential of −2.25 V for ethylene formation, reaching a FE towards C₂₊ products (FE_C2+) of 43% at −2.50 V, which is 1.0 V lower than a reference Cu catalyst to reach a similar FE_C2+. The high ethylene formation at low potentials is attributed to enhanced C C coupling on the Ag enriched shell of the Cu@Ag electrocatalysts. This study offers a new catalyst design towards increasing the efficiency for the electroreduction of CO₂ to value-added chemicals.     

Optical properties of gadolinia-doped cubic yttria stabilized zirconia single crystals

Cubic zirconia single crystals stabilized with yttria and doped with Gd₂O₃ (0.10–5.00 mol%) were prepared by the optical floating zone method, and characterized by a combination of X-ray diffraction (XRD), and Raman, electron paramagnetic resonance (EPR), ultraviolet–visible (UV–Vis), photoluminescence excitation (PLE) and photoluminescence (PL) spectroscopic techniques. XRD and Raman spectroscopy showed that the crystal samples were all in the cubic phase, whereas the ceramic sample consisted of a mixture of monoclinic and cubic phases. The absorption spectrum showed four peaks at 245, 273, 308, and 314 nm in the ultraviolet region, and the optical band gap differed between samples with ≤3.00 mol% and those with >3.00 mol% Gd₂O₃. The emission spectrum showed a weak peak at 308 nm and a strong peak at 314 nm, which are attributed to the ⁶P_5/2 → ⁸S_7/2 and ⁶P_7/2 → ⁸S_7/2 transitions of Gd³⁺, respectively. The intensities of the peaks in the excitation and emission spectra increased with Gd³⁺ concentration, reached a maximum at 2.00 mol%, then decreased with higher concentrations. This quenching is considered to be the result of the electric dipole-dipole interactions, and this interpretation is supported by the Gd³⁺ EPR spectra, which showed progressive broadening with increasing Gd³⁺ concentration throughout the concentration range investigated.     

极间距对车用MAO层组织结构及耐蚀性的影响

在硅酸盐电解液体系中用不同极间距制备汽车用镁合金表面微弧氧化(MAO)层.对比不同极间距(40、120、200、280、360 mm)的涂层微观结构,设计电化学试验,分析极间距对涂层耐蚀性的影响.结果表明:将极间距增至200 mm,涂层表面平整,微孔较小,且均匀分布,缺陷数量低,致密度更高.MAO层由内部致密层与外部疏松层构成,致密层和基体结合层厚度较小.以不同极间距制备的涂层元素与物相成分基本一致.增大极间距后,涂层厚度降低,正面涂层厚度比反面大,在距离达到200 mm前,正反面涂层厚度相近.当距离达到200 mm时,腐蚀电流密度最小,涂层耐蚀性最优,涂层耐蚀能力可通过设定极间距调节.     

Labeling and Characterization of Phenol-Containing Glycopeptides Using Chemoselective Probes with Isotope Tags

Secondary metabolites are structurally diverse natural products (NPs) and have been widely used for medical applications. Developing new tools to enrich NPs can be a promising solution to isolate novel NPs from the native and complex samples. Here, we developed native and deuterated chemoselective labeling probes to target phenol-containing glycopeptides by the ene-type labeling used in proteomic research. The clickable azido-linker was included for further biotin functionalization to facilitate the enrichment of labeled substrates. Afterward, our chemoselective method, in conjunction with LC-MS and MSn analysis, was demonstrated in bacterial cultures. A vancomycin-related phenol-containing glycopeptide was labeled and characterized by our labeling strategy, showing its potential in glycopeptide discovery in complex environments.     

Neuroprotective and Anti-Inflammatory Effects of Evernic Acid in an MPTP-Induced Parkinson’s Disease Model

Oxidative stress, mitochondrial dysfunction, and neuroinflammation are strongly associated with the pathogenesis of Parkinson’s disease (PD), which suggests that anti-oxidative and anti-inflammatory compounds might provide an alternative treatment for PD. Here, we evaluated the neuroprotective effects of evernic aid (EA), which was screened from a lichen library provided by the Korean Lichen Research Institute at Sunchon National University. EA is a secondary metabolite generated by lichens, including Ramalina, Evernia, and Hypogymnia, and several studies have described its anticancer, antifungal, and antimicrobial effects. However, the neuroprotective effects of EA have not been studied. We found that EA protected primary cultured neurons against 1-methyl-4-phenylpyridium (MPP⁺)-induced cell death, mitochondrial dysfunction, and oxidative stress, and effectively reduced MPP⁺-induced astroglial activation by inhibiting the NF-κB pathway. In vivo, EA ameliorated MPTP-induced motor dysfunction, dopaminergic neuronal loss, and neuroinflammation in the nigrostriatal pathway in C57BL/6 mice. Taken together, our findings demonstrate that EA has neuroprotective and anti-inflammatory effects in PD models and suggest that EA is a potential therapeutic candidate for PD.     

Dynamic Oscillation via Negative Differential Resistance in Type III Junction Organic/Two-Dimensional and Oxide/Two-Dimensional Transition Metal Dichalcogenide Diodes

Among many of 2D semiconductor-based devices, type III PN junction diodes are given special attentions due to their unique function, negative differential resistance (NDR). However, it has been found uneasy to achieve well-matched type III PN junctions from 2D–2D van der Waals heterojunctions. Here, the authors present other alternatives of type III heterojunctions, using 2D p-MoTe₂/organic n-type dipyrazino[2,3-f:2′,3′-h]quinoxaline-2,3,6,7,10,11-hexacarbonitrile (HAT-CN) and 2D p-WSe₂/n-MoO_x systems. Those junction diodes appear to well-demonstrate static and dynamic NDR behavior via resonant tunneling and electron–hole recombination. Extended to an inverter circuit, p-MoTe₂/n-HAT-CN diode enables multilevel inverter characteristics as monolithically integrated with p-MoTe₂ channel field effect transistor. The same NDR diode shows dynamic LC oscillation behavior under a constant DC voltage, connected to an external inductor. From p-WSe₂/n-MoO_x oxide diode, similar NDR behavior to those of p-MoTe₂/n-HAT-CN is again observed along with LC oscillations. The authors attribute these visible oscillation results to high peak-to-valley current ratios of their organic or oxide/2D heterojunction diodes.     

砖混房屋抗震性能加固的子结构布局优化分析

文章针对江苏省典型砖混结构提出了3种低干预子结构加固方案,利用PKPM和ABAQUS软件考察了附加子结构布置刚度、布置楼层、布置位置和布置方向等因素对加固结构抗震性能的影响,基于分析结果提出了附加子结构布局设计建议.     

Surface energies in high-entropy carbides with variable carbon stoichiometry

The carbon vacancy in high-entropy carbides (HECs) has a significant impact on their physical and chemical properties, yet relevant studies have still been relatively few. In this study, we investigate the surface energies of HECs with variable carbon vacancies through first-principles calculations. The results show that the surface energy of the (1 0 0) surface of the stoichiometric HECs is significantly lower than that of (1 1 1) surface. With the decrease in carbon stoichiometry, the surface energies of both (1 0 0) and (1 1 1) surfaces increase gradually, which is mainly due to the weakening of covalent bonding and the decrease of metal Hirshfeld-I (HI) charges. However, the surface energy of (1 0 0) surface increases more quickly than that of (1 1 1) surface and will exceed that of (1 1 1) surface when the carbon stoichiometry decreases to a certain extent, which is primarily attributed to the greater decrease rate of metal HI charges of (1 0 0) surface.