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.     

Study on Runoff Control Effect of Different Drainage Schemes in Sponge Airport

Water Resources Management - The low impact development (LID) concept aims to control storm runoff and pollution through decentralized, small-scale source control to bring the development area as...     

乌兰矿采矿现状及技术应对方案

本文分析了乌兰矿投产前期采矿现状及存在的主要问题,针对该矿所处蒙古国经济落后、投资风险大的现实状况,为避免生产中断、规避投资风险,早日回收前期投资考虑,采取了双斜坡道开拓、全尾胶结充填、高端壁空场嗣后充填采矿、多中段组合式连续开采等系列技术应对方案。大大降低了一次性投资规模及投资风险,前期投资得以快速回笼的同时,矿山产能也充分释放,确保了矿山的持续稳定,取得了较好的经济和社会效益。为海外地下近地表矿体开采矿山规避投资风险提供了很好的技术方案借鉴。     

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.     

A Highly Sensitive,Reversible, and Bidirectional Humidity Actuator by Calcium Carbonate Ionic Oligomers Incorporated Poly(Vinylidene Fluoride)

Sensitivity and multi-directional motivation are major two factors for developing optimized humidity-response materials, which are promising for sensing, energy production, etc. Organic functional groups are commonly used as the water sensitive units through hydrogen bond interactions with water molecules in actuators. The multi-coordination ability of inorganic ions implies that the inorganic ionic compounds are potentially superior water sensitive units. However, the particle forms of inorganic ionic compounds produced by classical nucleation limit the number of exposed ions to interact with water. Recent progress on the inorganic ionic oligomers has broken through the limitation of classical nucleation, and realized the molecular-scaled incorporation of inorganic ionic compounds into an organic matrix. Here, the incorporation of hydrophilic calcium carbonate ionic oligomers into hydrophobic poly(vinylidene fluoride) (PVDF) is demonstrated. The ultra-small calcium carbonate oligomers within a PVDF film endow it with an ultra-sensitive, reversible, and bidirectional response. The motivation ability is superior to other bidirectional humidity-actuators at present, which realizes self-motivation on an ice surface, converting the chemical potential energy of the humidity gradient from ice to kinetic energy.     

基于FLAC3D的破碎围岩巷道支护效果分析

为了解破碎围岩分别采用锚杆支护、锚喷支护以及锚喷+锚索耦合三种支护方式下的支护效果,进而为破碎围岩巷道选择合理的支护方式提供参考。通过借助FLAC^3D软件建立数值模型,分析不同支护条件下的破碎围岩巷道位移量、应力分布以及塑性区的时空演化特征。结果表明,采用锚喷+锚索耦合支护时,可以较好的控制巷道围岩的位移量、减小应力集中效应、缩小塑性区的影响范围。     

Performance analysis of bit error rate of data link system under pulse LFM interference in time-varying rayleigh channel

Wireless Networks - In such mobile platforms as ships and aircraft, the detection and reconnaissance devices are near to the communication facilities. When working at the same time, they will...     

Revealing cracking and breakage behaviours of gibbsite particles

Mitigating gibbsite particle cracking and breakage during industrial alumina production can increase the quality of smelter grade alumina product by reducing the ultrafine particle content. Therefore, it is essential to investigate the particle cracking during static calcination and the breakage of calcined gibbsite particles under external force. In this work, we investigated the impact of the calcination ramping rate and the crystallite size on gibbsite particle cracking during static calcination. A slow ramping rate and a large pristine crystallite size tend to increase particle cracking. Apart from the study of particle cracking behaviour, we also investigated the breakage of calcined gibbsite particle under external force. Cracks on the particle surface can initiate breakage within the crystallite and along the grain boundary under external force. The breakage within crystallite occurs as the cleavage of the crystallite, while the breakage along the grain boundary leads to the shedding of a whole crystallite. We further explored the factors influencing the strength of calcined gibbsite particles. With increasing calcination temperature, the strength of particle increases when gibbsite converts to boehmite, and then decreases when boehmite converts into amorphous alumina. Particles containing smaller crystallites and calcined with fast ramping rates exhibit higher resistance to breakage.     

Nacre-Inspired,Liquid Metal-Based Ultrasensitive Electronic Skin by Spatially Regulated Cracking Strategy

The realization of liquid metal-based wearable systems will be a milestone toward high-performance, integrated electronic skin. However, despite the revolutionary progress achieved in many other components of electronic skin, liquid metal-based flexible sensors still suffer from poor sensitivity due to the insufficient resistance change of liquid metal to deformation. Herein, a nacre-inspired architecture composed of a biphasic pattern (liquid metal with Cr/Cu underlayer) as “bricks” and strain-sensitive Ag film as “mortar” is developed, which breaks the long-standing sensitivity bottleneck of liquid metal-based electronic skin. With 2 orders of magnitude of sensitivity amplification while maintaining wide (>85%) working range, for the first time, liquid metal-based strain sensors rival the state-of-art counterparts. This liquid metal composite features spatially regulated cracking behavior. On the one hand, hard Cr cells locally modulate the strain distribution, which avoids premature cut-through cracks and prolongs the defect propagation in the adjacent Ag film. On the other hand, the separated liquid metal cells prevent unfavorable continuous liquid-metal paths and create crack-free regions during strain. Demonstrated in diverse scenarios, the proposed design concept may spark more applications of ultrasensitive liquid metal-based electronic skins, and reveals a pathway for sensor development via crack engineering.     

4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene,a Major Active Metabolite of Bisphenol A,Triggers Pancreatic β-Cell Death via a JNK/AMPKα Activation-Regulated Endoplasmic Reticulum Stress-Mediated Apoptotic Pathway

4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), a major active metabolite of bisphenol A (BPA), is generated in the mammalian liver. Some studies have suggested that MBP exerts greater toxicity than BPA. However, the mechanism underlying MBP-induced pancreatic β-cell cytotoxicity remains largely unclear. This study demonstrated the cytotoxicity of MBP in pancreatic β-cells and elucidated the cellular mechanism involved in MBP-induced β-cell death. Our results showed that MBP exposure significantly reduced cell viability, caused insulin secretion dysfunction, and induced apoptotic events including increased caspase-3 activity and the expression of active forms of caspase-3/-7/-9 and PARP protein. In addition, MBP triggered endoplasmic reticulum (ER) stress, as indicated by the upregulation of GRP 78, CHOP, and cleaved caspase-12 proteins. Pretreatment with 4-phenylbutyric acid (4-PBA; a pharmacological inhibitor of ER stress) markedly reversed MBP-induced ER stress and apoptosis-related signals. Furthermore, exposure to MBP significantly induced the protein phosphorylation of JNK and AMP-activated protein kinase (AMPK)α. Pretreatment of β-cells with pharmacological inhibitors for JNK (SP600125) and AMPK (compound C), respectively, effectively abrogated the MBP-induced apoptosis-related signals. Both JNK and AMPK inhibitors also suppressed the MBP-induced activation of JNK and AMPKα and of each other. In conclusion, these findings suggest that MBP exposure exerts cytotoxicity on β-cells via the interdependent activation of JNK and AMPKα, which regulates the downstream apoptotic signaling pathway.