Biodegradable Polymeric Nanoparticles Containing an Immune Checkpoint Inhibitor (aPDL1) to Locally Induce Immune Responses in the Central Nervous System

Immunotherapy is an efficient approach to clinical oncology. However, the immune privilege of the central nervous system (CNS) limits the application of immunotherapeutic strategies for brain cancers, especially glioblastoma (GBM). Tumor resistance to immune checkpoint inhibitors is a further challenge in immunotherapies. To overcome the immunological tolerance of brain tumors, a novel multifunctional nanoparticle (NP) for highly efficient synergetic immunotherapy is reported. The NP contains an anti-PDL1 antibody (aPDL1), upconverting NPs, and the photosensitizer 5-ALA; the surface of the NP is conjugated with the B1R kinin ligand to facilitate transport across the blood-tumor-barrier. Upon irradiation with a 980 nm laser, 5-ALA is transformed into protoporphyrin IX, generating reactive oxygen species. Photodynamic therapy (PDT) further promotes intratumoral infiltration of cytotoxic T lymphocytes and sensitizes tumors to PDL1 blockade therapy. It is demonstrated that combining PDT and aPDL1 can effectively suppress GBM growth in mouse models. The proposed NPs provide a novel and effective strategy for boosting anti-GBM photoimmunotherapy.     

High-Pressure Reverse Osmosis for Industrial Water Recycling: Permeate-Sided Pressure Drop as Performance-Limiting Factor

In the chemical industry large amounts of saline wastewater occur. Its disposal into rivers is a considerable burden to the ecosystem. To strive for a circular economy and enable a viable raw material recycling, energy-efficient concentration processes are requisite. High-pressure reverse osmosis meets this criterion, but its industrial application demands suitable membrane elements that withstand the exceptional operation conditions and provide sufficient performance. Hence, new requirements regarding the design of spiral-wound elements arise. To identify those, specific performance-limiting effects need a better understanding.     

珠江口盆地珠一坳陷古近系高自然伽马砂岩形成机制及油气地质意义

运用放射性元素寻找油气是一种非常规油气勘探手段。近年来,在珠江口盆地珠一坳陷富烃凹陷周边古近系钻遇高自然伽马(GR)砂岩,其GR值(100~300 API)甚至大于同区泥岩的GR值(100~200 API)。为了弄清该特殊现象背后的地质意义,对珠江口盆地珠一坳陷古近系高自然伽马砂岩开展了铀(U)、钍(Th)、钾(K)等3种元素含量与GR值的相关趋势线分析,从井震特征、岩性特征及矿物成分特征等入手分析了砂岩GR值增高的主要原因及成因机制,探讨了放射性元素聚集的条件、运移通道、驱动力以及油气意义。结果表明:西江、惠州地区由U含量增高导致砂岩GR值偏高,恩平、番禺地区由K,Th含量增高导致砂岩GR值偏高;砂岩GR值增高有两大成因机制,一是地下流体带来的放射性元素离子U4+在氧化-还原面处富集后导致地层GR值偏高,这种特殊现象说明在具有连通基底大断裂旁的圈闭中,U4+的富集指示了曾经油气的存在,证实了研究区油气运移通道的有效性,对于油气藏的预测有着非常重要的指导性意义,二是地表流体带来的含放射性元素的矿物大量沉积后导致地层GR值偏高,含放射性元素矿物性质不稳定,可指示近源供给的存在,对于判断物源及沉积环境有着非常重要的意义。该研究成果为预测研究区油气成藏有利区带提供了依据。     

车门铰链系统与车门下沉刚度的相关性

针对某型车门下沉问题,通过台架试验获得车门、铰链和车身等各单因素下沉量和车门绞链系统整体下沉量,对单因素下沉量与系统整体下沉刚度进行线性拟合分析,得到车门铰链系统各单因素与系统下沉刚度的相关度排序.对前、后车门分别选取相关度较高的单因素进行优化,最终改进方案的仿真和试验结果证明该方案可有效地提升车门下沉刚度.采用定量分析法可快速找出影响下沉刚度的敏感因素,并能够快速生成优化方案,为新车型设计提供参考.     

Stress field and damage evolution in C/SiC woven composites: Image-based finite element analysis and in situ X-ray computed tomography tests

The construction and examination of meso-structural finite element models of a Chemical-Vapor-Infiltrated (CVI) C/SiC composite is carried out based on X-ray microtomography digital images (IB-FEM). The accurate meso-structural features of the C/SiC composites, which are consisted of carbon fiber tows and CVI-SiC matrix, in particular the cavity defects, are reconstructed. With the IB-FEM, the damage evolution and fracture behaviors of the C/SiC composite are investigated. At the same time, an in situ tensile test is applied to the C/SiC composite under a CT real-time quantitative imaging system, aiming to investigate the damage and failure features of the material as well as to verify the IB-FEM. The IB-FEM results indicate that material damage initially occur at the defects, followed by propagating toward the fiber-tow/SiC-matrix interfaces, ultimately, combined into macro-cracks, which is in good agreement with the in situ CT experiment results.     

Piezoelectric properties and microstructure of ceramicrete-based piezoelectric composites

Inorganic piezoelectric ceramic composite is the potential sensing element for long-term structural health monitoring due to its excellent durability and compatibility. In this study, a Ceramicrete-based piezoelectric composite is proposed preliminarily, in which the magnesium potassium phosphate cement is used as the matrix and the lead zirconate titanate particle is utilized as the functional phase. Piezoelectric properties test and microstructure analysis are performed to evaluate the testing samples. Results show that the piezoelectric performance of the composite increase with the increase of piezoelectric ceramic particle size. The value of the piezoelectric strain factor (d₃₃) can reach 83.8 pC/N, while the corresponding piezoelectric voltage factor (g₃₃) is 50.1 × 10^-3 V•m/N at the 50th day after polarization. Microstructure analysis illustrates that the interfacial transition zone (ITZ) between the matrix and the particles is dense. Moreover, the influence of aging on the composite is attributed to the continuous hydration after polarization. It indicates that the composites have a higher piezoelectric performance, which can be regarded as a promising sensing element material.     

Evidence of fluid evolution of Baoshan Cu−Pb−Zn polymetallic deposit: Constraints from in-situ sulfur isotope and trace element compositions of pyrite

In-situ LA-ICP-MS and S isotopes of pyrite from the Baoshan Cu polymetallic deposit were conducted to investigate the ore-forming process and the enrichment mechanism of elements. Three generations of pyrite (Py I, Py II, and Py III) in the skarn-type ores and pyrite in the carbonate-hosted sulfide ores from central, western, and northern (C_Py, W_Py, and N_Py) mining districts are selected for comparison. Compared with Py I and Py III, the contents of most elements in Py II are apparently higher. The As and Se contents are high within a wide range and are decoupled in the growth band of the C_Py. The highest As, Se, and Pb contents were found in W_Py and N_Py. These results indicate the drastic changes in the temperature and fluid mixing during the mineralization. The occurrence of fluctuation and change in temperature and f(O₂) was triggered by intermittent pulses of magmatic-hydrothermal fluids, mixing with meteoric water, and water−rock interactions. The sulfur isotopes of all species of pyrite indicated the magmatic source. The change in the f(O₂) conditions caused slight differences in the sulfur isotope compositions. Consequently, a metallogenic model was proposed to explain the ore-forming processes.     

Mangiferin Inhibits Apoptosis in Doxorubicin-Induced Vascular Endothelial Cells via the Nrf2 Signaling Pathway

Doxorubicin increases endothelial permeability, hence increasing cardiomyocytes’ exposure to doxorubicin (DOX) and exposing myocytes to more immediate damage. Reactive oxygen species are major effector molecules of doxorubicin’s activity. Mangiferin (MGN) is a xanthone derivative that consists of C-glucosylxanthone with additional antioxidant properties. This particular study assessed the effects of MGN on DOX-induced cytotoxicity in human umbilical vein endothelial cells’ (HUVECs’) signaling networks. Mechanistically, MGN dramatically elevated Nrf2 expression at both the messenger RNA and protein levels through the upregulation of the PI3K/AKT pathway, leading to an increase in Nrf2-downstream genes. Cell apoptosis was assessed with a caspase-3 activity assay, transferase-mediated dUTP-fluorescein nick end labeling (TUNEL) staining was performed to assess DNA fragmentation, and protein expression was determined by Western blot analysis. DOX markedly increased the generation of reactive oxygen species, PARP, caspase-3, and TUNEL-positive cell numbers, but reduced the expression of Bcl-2 and antioxidants’ intracellular concentrations. These were effectively antagonized with MGN (20 μM), which led to HUVECs being protected against DOX-induced apoptosis, partly through the PI3K/AKT-mediated NRF2/HO-1 signaling pathway, which could theoretically protect the vessels from severe DOX toxicity.     

FE-SEA方法在平台支持船噪声预报中的应用

平台支持船由于作业需要通常配备有动力定位系统,其在侧推工况下舱室噪声超标较为严重。针对这个问题采用计算流体力学(CFD)方法,得到侧推螺旋桨作用在导管上的脉动压力,并将时域计算结果转换成噪声计算的激励条件。采用有限元(FE)与统计能量分析(SEA)混合方法建立船体中频段FE-SEA耦合模型并建立船体高频段SEA模型,对某65 m AHTS船侧推工况下全频段(63 Hz~8000 Hz)舱室噪声进行预报,分析该船噪声分布规律及主要影响因素。并建立起全船的SEA模型,在中频段对比SEA与FE-SEA两种方法得到的舱室声压级频谱曲线,验证了使用混合模型的必要性。