Neoantigen vaccines and adoptive dendritic cell (DC) transfer are major clinical approaches to initiate personalized immunity in cancer patients. However, the immunization efficacy is largely limited by the in vivo trajectory including neoantigens’ access to resident DCs and DCs’ access to lymph nodes (LNs). Herein, an innovative strategy is proposed to improve personalized immunization through neoantigen-loaded nanovaccines synergized with adoptive DC transfer. It is found that it enables selective delivery of neoantigens to resident DCs and macrophages by coating cancer cell membranes onto neoantigen-loaded nanoparticles. In addition, the nanovaccines promote the secretion of chemokine C-C motif ligand 2 (CCL2), CCL3, and C-X-C motif ligand 10 from macrophages, thus potentiating the access of transferred DCs to LNs. This immunization strategy enables coordinated delivery of identified neoantigens and autologous tumor lysate-derived undefined antigens, leading to initiation of antitumor T cell immunity in a personalized manner. It significantly inhibits tumor growth in prophylactic and established mouse tumor models. The findings provide a new vision for potentiating adoptive cell transfer by nanovaccines, which may open the door to a transformative possibility for improving personalized immunization. 相似文献
In this study, the destabilization resistance of Sc2O3 and CeO2 co-stabilized ZrO2 (SCZ) ceramics was tested in Na2SO4 + V2O5 molten salts at 750°C–1100 °C. The phase structure and microstructure evolution of the samples during the hot corrosion testing were analyzed with X-ray diffraction (XRD), Raman spectra, scanning electron microscopy (SEM), energy dispersive X-ray spectrum (EDS), and X-ray photoelectron spectroscopy (XPS). Results showed that the destabilization of SCZ ceramics at 750 °C was the result of the chemical reaction with V2O5 to produce m-ZrO2 and CeVO4, and little ScVO4 was detected in the Sc2O3-rich SCZ ceramics. The primary corrosion products at 900 °C and 1100 °C were CeO2 and m-ZrO2 due to the mineralization effect. The Sc2O3-rich SCZ ceramics exhibited excellent degradation resistance and phase stability owing to the enhanced bond strength and the decreased size misfit between Zr4+ and Sc3+. The destabilization mechanism of SCZ ceramic under hot corrosion was also discussed. 相似文献
This work presents the dielectric properties of YNbO4 (YNO)–TiO2 composites in the microwave range. X-ray diffraction analysis demonstrates that the addition of TiO2 to YNO results in the formation of a Y(Nb0.5Ti0.5)2O6 phase. In the microwave range, the values of permittivity and dielectric loss did not present major changes with the increment of TiO2. Moreover, the addition of TiO2 results in an improvement in the thermal stability of YNO, with YNO63 demonstrating a resonant frequency of ?8.96 ppm.°C?1. We utilised numerical simulations to evaluate the behaviour of these materials as dielectric resonator antennae and it is found that they exhibit a reflection coefficient below ?10 dB at the resonant frequency, with a realised gain of 4.94 – 5.76 dBi, a bandwidth of 665–1050 MHz and a radiation efficiency above 84%. Our results indicate that YNO–TiO2 composites are interesting candidates for microwave operating devices. 相似文献
Water Resources Management - Increasing water consumption in agriculture due to global climate change has posed considerable challenges to food security, thus improving the efficiency of water... 相似文献
At present, the development and implementation of digital transformation are the keys to promoting high-quality industry development. The new digital fabrication method of robotic 3D printing is a research area being studied by many to tackle the issue of the declining productivity of traditional construction methods. Although many studies have been done, most of the current 3D printing projects are facing limitations in terms of scale. In order to bridge the gap, this article proposed a mass customization 3D printing framework system for large-scale projects. This article discusses how mass customization is made possible through the joint operation of the FUROBOT software and 3D printing hardware. By taking the east gate of Nanjing Happy Valley Plaza as a case study, the article demonstrates and studies the feasibility of the large-scale mass customization 3D printing framework system. 相似文献
Radiochemistry - Ferrugination, sericitization, desulfitization, chloritization, and kaolinitization of hydrothermal origin are the main wall rock alterations occurring within the NNW shear zones... 相似文献
Modern metrics for evaluating agreement coefficients between the experimental results and expert opinion are compared, and the possibility of using these metrics in experimental research in automatic text processing by machine learning methods is assessed. The choice of Cohen’s kappa coefficient as a measure of expert opinion agreement in the NLP and Text Mining problems is justified. An example of using Cohen’s kappa coefficient for evaluating the level of agreement between the opinion of an expert and the results of ML classification and the measure of agreement of expert opinions in the alignment of sentences of the Kazakh-Russian parallel corpus is given. Based on this analysis, it is proved that Cohen’s kappa coefficient is one of the best statistical methods for determining the level of agreement in experimental studies due to its ease of use, computing simplicity, and high accuracy of the results.
Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes. Since ER stress in cancers usually persists and is essentially not induced by genetic manipulations, we used low doses of ER stress inducers at levels that allowed cell adaptation to occur in order to investigate the effect of stress response on chemoresistance. We found that prolonged tolerable ER stress promotes mesenchymal–epithelial transition, slows cell-cycle progression, and delays the S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased in stress-adapted cells, implying their acquisition of cisplatin resistance. Molecularly, we found that proliferating cell nuclear antigen (PCNA) ubiquitination and the expression of polymerase η, the main polymerase responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated in ER stress-adaptive cells, and their enhanced cisplatin resistance was abrogated by the knockout of polymerase η. We also found that a fraction of p53 in stress-adapted cells was translocated to the nucleus, and that these cells exhibited a significant decline in the level of cisplatin-DNA damage. Consistently, we showed that the nuclear p53 coincided with strong positivity of glucose-related protein 78 (GRP78) on immunostaining of clinical biopsies, and the cisplatin-based chemotherapy was less effective for patients with high levels of ER stress. Taken together, this study uncovers that adaptation to ER stress enhances DNA repair and damage tolerance, with which stressed cells gain resistance to chemotherapeutics. 相似文献
Bioactive glasses and glass-ceramics (GCs) effectively regenerate bone tissue, however most GCs show improved mechanical properties. In this work, we developed and tested a rarely studied bioactive glass composition (24.4K2O-26.9CaO-46.1SiO2-2.6P2O5 mol%, identified as 45S5-K) with different particle sizes and heating rates to obtain a sintered GC that combines good fracture strength, low elastic modulus, and bioactivity. We analyzed the influence of the sintering processing conditions in the elastic modulus, Vickers microhardness, density, and crystal phase formation in the GC. The best GC shows improved properties compared with its parent glass. This glass achieves a good densification degree with a two-step viscous flow sintering approach and the resulting GC shows as high bioactivity as that of the standard 45S5 Bioglass®. Furthermore, the GC elastic modulus (56 GPa) is relatively low, minimizing stress shielding. Therefore, we unveiled the glass sintering behavior with concurrent crystallization of this complex bioactive glass composition and developed a potential GC for bone regeneration. 相似文献
To enhance the tribological performance of Si3N4/TiC ceramics, MoS2/PTFE composite coatings were deposited on the ceramic substrate through spraying method. The micrographs and basic properties of the MoS2/PTFE coated samples were investigated. Dry sliding friction experiments against WC/Co ball were performed with the coated ceramics and traditional ones. These results showed that the composite coatings could significantly reduce the friction coefficient of ceramics, and protect the substrate from adhesion wear. The primary tribological mechanisms of the coated ceramics were abrasive wear, coating spalling and delamination, and the tribological property was transited from slight wear to serious wear with the increase of load because of the lower surface hardness and shear strength. The possible mechanisms for the effects of MoS2/PTFE composite coatings on the friction performance of ceramics were discussed. 相似文献