Clinical Significance of Tumor Infiltrating Lymphocytes in Association with Hormone Receptor Expression Patterns in Epithelial Ovarian Cancer

Hormone receptor expression patterns often correlate with infiltration of specific lymphocytes in tumors. Specifically, the presence of specific tumor-infiltrating lymphocytes (TILs) with particular hormone receptor expression is reportedly associated with breast cancer, however, this has not been revealed in epithelial ovarian cancer (EOC). Therefore, we investigated the association between hormone receptor expression and TILs in EOC. Here we found that ERα, AR, and GR expression increased in EOC, while PR was significantly reduced and ERβ expression showed a reduced trend compared to normal epithelium. Cluster analysis indicated poor disease-free survival (DFS) in AR+/GR+/PR+ subgroup (triple dominant group); while the Cox proportional-hazards model highlighted the triple dominant group as an independent prognostic factor for DFS. In addition, significant upregulation of FoxP3+ TILs, PD-1, and PD-L1 was observed in the triple dominant group compared to other groups. NanoString analyses further suggested that tumor necrosis factor (TNF) and/or NF-κB signaling pathways were activated with significant upregulation of RELA, MAP3K5, TNFAIP3, BCL2L1, RIPK1, TRAF2, PARP1, and AKT1 in the triple dominant EOC group. The triple dominant subgroup correlates with poor prognosis in EOC. Moreover, the TNF and/or NF-κB signaling pathways may be responsible for hormone-mediated inhibition of the immune microenvironment.     

Current Perspectives on the Physiological Activities of Fermented Soybean-Derived Cheonggukjang

Cheonggukjang (CGJ, fermented soybean paste), a traditional Korean fermented dish, has recently emerged as a functional food that improves blood circulation and intestinal regulation. Considering that excessive consumption of refined salt is associated with increased incidence of gastric cancer, high blood pressure, and stroke in Koreans, consuming CGJ may be desirable, as it can be made without salt, unlike other pastes. Soybeans in CGJ are fermented by Bacillus strains (B. subtilis or B. licheniformis), Lactobacillus spp., Leuconostoc spp., and Enterococcus faecium, which weaken the activity of putrefactive bacteria in the intestines, act as antibacterial agents against pathogens, and facilitate the excretion of harmful substances. Studies on CGJ have either focused on improving product quality or evaluating the bioactive substances contained in CGJ. The fermentation process of CGJ results in the production of enzymes and various physiologically active substances that are not found in raw soybeans, including dietary fiber, phospholipids, isoflavones (e.g., genistein and daidzein), phenolic acids, saponins, trypsin inhibitors, and phytic acids. These components prevent atherosclerosis, oxidative stress-mediated heart disease and inflammation, obesity, diabetes, senile dementia, cancer (e.g., breast and lung), and osteoporosis. They have also been shown to have thrombolytic, blood pressure-lowering, lipid-lowering, antimutagenic, immunostimulatory, anti-allergic, antibacterial, anti-atopic dermatitis, anti-androgenetic alopecia, and anti-asthmatic activities, as well as skin improvement properties. In this review, we examined the physiological activities of CGJ and confirmed its potential as a functional food.     

Computational-Driven Epitope Verification and Affinity Maturation of TLR4-Targeting Antibodies

Toll-like receptor (TLR) signaling plays a critical role in the induction and progression of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematous, experimental autoimmune encephalitis, type 1 diabetes mellitus and neurodegenerative diseases. Deciphering antigen recognition by antibodies provides insights and defines the mechanism of action into the progression of immune responses. Multiple strategies, including phage display and hybridoma technologies, have been used to enhance the affinity of antibodies for their respective epitopes. Here, we investigate the TLR4 antibody-binding epitope by computational-driven approach. We demonstrate that three important residues, i.e., Y328, N329, and K349 of TLR4 antibody binding epitope identified upon in silico mutagenesis, affect not only the interaction and binding affinity of antibody but also influence the structural integrity of TLR4. Furthermore, we predict a novel epitope at the TLR4-MD2 interface which can be targeted and explored for therapeutic antibodies and small molecules. This technique provides an in-depth insight into antibody–antigen interactions at the resolution and will be beneficial for the development of new monoclonal antibodies. Computational techniques, if coupled with experimental methods, will shorten the duration of rational design and development of antibody therapeutics.     

Micron-Scale Soft Actuators Fabricated from Multi-Shell Polystyrene Particle-Gold Nanoparticle Nanohybrids

Actuators made of soft matter are needed for a variety of fields ranging from biomedical devices to soft robotics to microelectromechanical systems. While there are a variety of excellent methods of soft actuation known, the field is still an area of intense research activity as new niches and needs emerge with new technology development. Here, a soft actuation system is described, based on a core-multi-shell particle, which moves via photothermal expansion. The system consists of a novel polystyrene-based thermally expandable microsphere, with a secondary shell of a silicate-silane graft copolymer, to which gold nanoparticles are covalently linked. The gold nanoparticles act as photothermal nano-transducers, converting light energy into the thermal energy necessary for microsphere expansion, which in turn results in material movement. Actuation is shown in isolated particles in thermal and photothermal regimes using metal ceramic heaters or 520 nm laser illumination, respectively. Macroscale actuation is demonstrated by making a composite material of particles suspended in the transparent elastomer polydimethylsiloxane. The sample demonstrates an inchworm-like movement by starting from an arched geometry. Overall, this work describes a new particle-based actuation method for soft materials, and demonstrates its utility in driving the movement of a composite elastomer.     

Synergistic Flame Retardant Effects of Carbon Nanotube-Based Multilayer Nanocoatings

In an effort to develop highly functionalized flame retardant materials, hybrid nanocoatings are prepared by alternately depositing a positively charged polyaniline (PANi) and negatively charged montmorillonite (MMT) using the layer-by-layer (LbL) assembly technique. Carbon nanotubes (CNTs) are employed in polymer nanocomposites as effective reinforcement, where nanotubes are stabilized in MMT aqueous solution. The 3D structure and high density of CNTs deposited in the PANi/CNTs-MMT multilayers produce thicker and heavier coatings in comparison to the LbL assemblies without CNTs. Vertical and horizontal flame testing show that the incorporation of CNTs improves fire resistance. Additionally, cone calorimetry reveals that stacking two nanomaterials (MMT and CNTs) in a single coating shows a significant reduction in peak heat release rate (up to 51%), total smoke release (up to 47%), and total heat release (up to 37%) for the polyurethane foam. The enhancement of flame retardancy is attributed to a synergistic effect; MMT serves as a physical barrier that retards the diffusion of heat and gas. The addition of CNTs strengthens the thermal stability and high char yield. These results, coupled with the simplicity with which the LbL deposition is applied, present a viable alternative to halogen-free flame retardant nanocoatings to natural and synthetic fibers.     

PAN/FPU Composite Nanofiber Membrane with Superhydrophobic and Superoleophobic Surface as a Filter Element for High-Efficiency Protective Masks

Recently, because of the outbreak of COVID-19, the demand for various types of filter elements in protective materials has increased globally. Furthermore, new requirements for the filtration performance of PM2.5 liquid (oil) particles have been put forward. In this work, Superhydrophobic and superoleophobic composite nanofibers with excellent filtration capacity for oil and salt particles are developed through the modification of polyacrylonitrile (PAN) by fluoro-polyurethane (FPU) doping. The results show that the PAN/FPU composite nanofibers doped with 9 wt% FPU has a uniform fiber morphology with a diameter of 240 ± 30 nm. Compared to the pure PAN nanofibers, the water-based contact angle of PAN/FPU increases from 90 ± 5° to 151 ± 5°, and the oil-based contact angle increases from 58 ± 2° to 152 ± 3°. Importantly, at a high flow rate of 95 L min⁻¹, the filtration efficiency of the PAN/FPU nanofiber membrane for 0.3 µm oil particles increases from 92 ± 1% to 99.2 ± 0.1%. After cyclic loading, the filtration efficiency of 0.3 µm oil particles remains above 98%. Meanwhile, the filtration efficiency for 0.3 µm salt particles remains at 98.23 ± 0.1%. The PAN/FPU nanofiber membrane developed in this work is effective in applications and has good market prospects as a protective filtration material.     

Effect of SiC nanowhisker addition on microstructure and mechanical properties of regenerated cemented carbides by low-pressure sintering

The hardness and toughness of regenerated cemented carbides, in general, are contradictory. Therefore, it is critical to explore regenerated cemented carbides with both high hardness and high toughness. In this study, regenerated WC-8-wt% Co cemented carbide with SiC nanowhisker were prepared by low-pressure sintering. The influence of SiCw contents on the microstructure and mechanical properties of regenerated WC-8-wt% Co cemented carbide was investigated. The results indicated that the hardness, density, flexural strength, and fracture toughness of regenerated cemented carbide first increased and then decreased with the addition of SiCw. The Vickers hardness, density, flexural strength, and fracture toughness could reach 1575 HV, 14.6 g/cm³, 2204 MPa, 16.85 MPa·m^1/2, respectively, with SiCw content 0.5 wt%, which were increased by 14.4%, 0.7%, 12.2%, and 17.3%, respectively, when compared with the regenerated cemented carbide without SiCw. The lowest friction coefficient and the best wear resistance could be also reached when 0.5-wt% SiCw was added. The fracture mechanism of the regenerated cemented carbide contained both transgranular and intergranular fracture through the microscopic observation of fracture surface via scanning electron microscope.     

GM模型的几何性质及统计检验

以空间向量几何理论为基础，详细地分析了Ｇａｕｓｓ－Ｍａｒｋｏｖ线性模型的几何性质；在实现了模型图形化描述的基础上，利用各解向量的几何及统计性质构造出了不同情形下的统计检验方法和相应的检验统计量，为全面、深入地研究和灵活运用该模型提出了一种简洁直观的数学方法     

Implementation of pole placement adaptive controller for force control of non-minimum phase end milling operations

The design and implementation of a pole placement adaptive controller are discussed for force control of the end milling process. The end milling process considered is a non-minimum phase system whose computational delay exceeds one half of the control interval. The internal model principle is included in the controller design to ensure a zero steady-state tracking error. Experimental results show that the pole placement adaptive controller is effective for force control of the non-minimum phase end milling operation and the closed-loop control system is stable over a wide range of cutting conditions.     

工艺因素对82B钢280 mm x325 mm铸坯凝固过程的影响

为模拟不同工艺条件下的连铸坯的凝固过程,采用有限元法模拟了82B钢连铸的凝固过程,获得280 mm×325 mm连铸坯的温度场。结果表明,随拉速从0.60 m/min增加到0.76 m/min,凝固时f_s=1处与f_s=0处皆后移,但中心凝固时间反而增加了9.8%。随过热度由15℃增加到50℃时,凝固末端f_s=1处同样后移,约后移1.1 m。根据模拟结果改进连铸工艺,当拉速从0.60 m/min增加到0.76m/min,增加轻压下工艺可改善低倍质量。