Nanovaccine-Mediated Cell Selective Delivery of Neoantigens Potentiating Adoptive Dendritic Cell Transfer for Personalized Immunization

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.     

Phase and microstructure evolution of Sc2O3–CeO2 –ZrO2ceramics in Na2SO4 + V2O5 molten salts

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.     

主存高效的公交网络路径规划索引

在公交时间表下给定起始和目标站点,路径规划查询返回一组到达时间早和换乘次数少的帕雷托最优路径.现有的索引方法需要大量运行时内存.本文提出主存空间高效的索引方法(a-)PAINT.(a-)PAINT对每个站点v预计算一组标签,使得对于从站点s到站点d的查询可以通过匹配s和d相关的标签高效地生成查询结果的一条路径.PAINT对任意查询返回最优路径.a-PAINT只需要很小的预处理开销,但可能返回多一趟换乘的次优路径.用真实的公交时间表与模拟查询测试,PAINT具有合理的预处理开销.a-PAINT需要更少量的预处理开销,在大规模公交网络下准确率达90％.     

Research on Crop Irrigation Schedules Under Deficit Irrigation—A Meta-analysis

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...     

Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

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.     

Effect of MoS2/PTFE coatings on performance of Si3N4/TiC ceramics in dry sliding against WC/Co

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.     

A blind dual color images watermarking based on quaternion singular value decomposition

Multimedia Tools and Applications - With the rapid development of the Internet, the color digital image copyright protection is facing severe challenges. Simultaneously, the color digital images...     

Fire safe,sustainable loose furnishing

The aim of this exploratory study has been to investigate the fire properties and environmental aspects of different upholstery material combinations, mainly for domestic applications. An analysis of the sustainability and circularity of selected textiles, along with lifecycle assessment, is used to qualitatively evaluate materials from an environmental perspective. The cone calorimeter was the primary tool used to screen 20 different material combinations from a fire performance perspective. It was found that textile covers of conventional fibres such as wool, cotton and polyester, can be improved by blending them with fire resistant speciality fibres. A new three‐dimensional web structure has been examined as an alternative padding material, showing preliminary promising fire properties with regard to ignition time, heat release rates and smoke production.     

Novel TiC-based composites with enhanced mechanical properties

Novel TiC-based composites were synthesized by reactive hot-pressing at 1800 °C for 1 h with ZrB₂ addition as a sintering aid for the first time. The effects of ZrB₂ contents on the phase composition, microstructure evolution, and mechanical properties were reported. Based on the reaction and solid solution coupling effects between ZrB₂ and TiC, the product ZrC may be partially or completely dissolved into the TiC matrix, and then phase separation within the miscibility gap is observed to form lamellar nanostructured ZrC-rich (Zr, Ti)C. The TiC-10 mol.% ZrB₂ (starting batch composition) exhibits good comprehensive mechanical properties of hardness 27.7 ± 1.3 GPa, flexural strength 659 ± 48 MPa, and fracture toughness of 6.5 ± 0.6 MPa m^1/2, respectively, which reach or exceed most TiC-based composites using ceramics as sintering aids in the previous reports.