Tumor-Localized Administration of α-GalCer to Recruit Invariant Natural Killer T Cells and Enhance Their Antitumor Activity against Solid Tumors

Invariant natural killer T (iNKT) cells have the capacity to mount potent anti-tumor reactivity and have therefore become a focus in the development of cell-based immunotherapy. iNKT cells attack tumor cells using multiple mechanisms with a high efficacy; however, their clinical application has been limited because of their low numbers in cancer patients and difficulties in infiltrating solid tumors. In this study, we aimed to overcome these critical limitations by using α-GalCer, a synthetic glycolipid ligand specifically activating iNKT cells, to recruit iNKT to solid tumors. By adoptively transferring human iNKT cells into tumor-bearing humanized NSG mice and administering a single dose of tumor-localized α-GalCer, we demonstrated the rapid recruitment of human iNKT cells into solid tumors in as little as one day and a significantly enhanced tumor killing ability. Using firefly luciferase-labeled iNKT cells, we monitored the tissue biodistribution and pharmacokinetics/pharmacodynamics (PK/PD) of human iNKT cells in tumor-bearing NSG mice. Collectively, these preclinical studies demonstrate the promise of an αGC-driven iNKT cell-based immunotherapy to target solid tumors with higher efficacy and precision.     

基于嵌入式系统的检测平台硬件设计

电台的备件检测是备件保养的一个难题,本文提出了一种以ARM和UC/OS-Ⅱ为开发平台,以MiniGUI为图形界面的备件检测平台的设计方案.首先分析了备件检测的重要性,然后重点设计了备件检测平台的总体框架,描述了其各组成模块及其实现的功能,最后通过硬件和软件设计实现了备件检测平台.     

TP347H与T91异种钢焊接性能分析

随着电站设备中金属部件使用钢材种类的逐渐增多,不可避免地会遇到异种钢焊接的问题.为此,通过对马氏体耐热钢(T91)和奥氏体钢(TP347H)的性能分析,详细阐述了T91 TP347H焊接存在的问题,探讨了T91与TP347H异种钢接头的焊接方法、焊接材料及焊接工艺要点.     

电机转速和转子位置数字测量方法的研究

电机转速和转子位置的测量在电机交直流调速控制系统中占有重要的位置,为提高测量的精度和避免噪声影响,多采用数字式测量方法.基于常规的M/T法,提出了电机转速和转子位置测量的综合M/T法,该方法是利用测量电路对光电编码器信号进行预处理,以确定采样信号脉冲与码盘信号脉冲之间的相对位置,并将这个相对位置表示为含有小数的码盘脉冲个数,由此不仅可以测量出电机在采样时刻的转速,同时还可以测量出该时刻电机的转子位置.与常规的M/T法相比,该方法提高了测量的精度,扩展了M/T法的应用范围.     

Function of Graphene Oxide as the “Nanoquencher” for Hg2+ Detection Using an Exonuclease I-Assisted Biosensor

Graphene oxide is well known for its excellent fluorescence quenching ability. In this study, positively charged graphene oxide (pGO25000) was developed as a fluorescence quencher that is water-soluble and synthesized by grafting polyetherimide onto graphene oxide nanosheets by a carbodiimide reaction. Compared to graphene oxide, the fluorescence quenching ability of pGO25000 is significantly improved by the increase in the affinity between pGO25000 and the DNA strand, which is introduced by the additional electrostatic interaction. The FAM-labeled single-stranded DNA probe can be almost completely quenched at concentrations of pGO25000 as low as 0.1 μg/mL. A simple and novel FAM-labeled single-stranded DNA sensor was designed for Hg²⁺ detection to take advantage of exonuclease I-triggered single-stranded DNA hydrolysis, and pGO25000 acted as a fluorescence quencher. The FAM-labeled single-stranded DNA probe is present as a hairpin structure by the formation of T–Hg²⁺–T when Hg²⁺ is present, and no fluorescence is observed. It is digested by exonuclease I without Hg²⁺, and fluorescence is recovered. The fluorescence intensity of the proposed biosensor was positively correlated with the Hg²⁺ concentration in the range of 0–250 nM (R² = 0.9955), with a seasonable limit of detection (3σ) cal. 3.93 nM. It was successfully applied to real samples of pond water for Hg²⁺ detection, obtaining a recovery rate from 99.6% to 101.1%.     

Generalized Approach towards Secretion-Based Protein Production via Neutralization of Secretion-Preventing Cationic Substrate Residues

Many heterologous proteins can be secreted by bacterial ATP-binding cassette (ABC) transporters, provided that they are fused with the C-terminal signal sequence, but some proteins are not secretable even though they carry the right signal sequence. The invention of a method to secrete these non-secretable proteins would be valuable both for understanding the secretory physiology of ABC transporters and for industrial applications. Herein, we postulate that cationic “supercharged” regions within the target substrate protein block the secretion by ABC transporters. We also suggest that the secretion of such substrate proteins can be rescued by neutralizing those cationic supercharged regions via structure-preserving point mutageneses. Surface-protruding, non-structural cationic amino acids within the cationic supercharged regions were replaced by anionic or neutral hydrophilic amino acids, reducing the cationic charge density. The examples of rescued secretions we provide include the spike protein of SARS-CoV-2, glutathione-S-transferase, streptavidin, lipase, tyrosinase, cutinase, growth factors, etc. In summary, our study provides a method to predict the secretability and a tool to rescue the secretion by correcting the secretion-blocking regions, making a significant step in understanding the physiological properties of ABC transporter-dependent protein secretion and laying the foundation for the development of a secretion-based protein-producing platform.     

基于岩心核磁共振实验数据确定阳离子交换容量

以HSK方程为基础,提出了一种利用岩心核磁共振实验数据计算阳离子交换容量Qv的方法.该方法与湿式化学阳离子交换容量分析法相比存在一定的误差.12块岩样数据显示,相对误差范围12％～95％,平均相对误差为55％.分别从溶液矿化度、核磁共振总孔隙度以及黏土束缚水T2截止值等参数出发,开展了核磁共振确定阳离子交换容量影响因素分析研究.黏土束缚水T2截止值是影响核磁共振计算阳离子交换容量的关键参数,黏土束缚水T2截止值是可变的,而不是传统意义上的3 ms.基于岩心核磁共振准确求取阳离子交换容量的前提是准确求取黏土束缚水T2截止值.     

基于ARM＋Linux2．6内核的控制系统驱动设计

在Linux 2.6内核下驱动的设计相对以往版本Linux内核有了很多改进,而ARM9被广泛用于控制领域.结合项目背景,介绍在Linux 2.6.21.7内核下基于AT91RM9200硬件平台的某仪器控制系统驱动设计,重点介绍I/O口和中断驱动设计方法,引入阻塞型I/O.通过在交叉开发环境编译调试进行验证,该设计已应用到仪器中.     

Mutated KIT Tyrosine Kinase as a Novel Molecular Target in Acute Myeloid Leukemia

KIT is a type-III receptor tyrosine kinase that contributes to cell signaling in various cells. Since KIT is activated by overexpression or mutation and plays an important role in the development of some cancers, such as gastrointestinal stromal tumors and mast cell disease, molecular therapies targeting KIT mutations are being developed. In acute myeloid leukemia (AML), genome profiling via next-generation sequencing has shown that several genes that are mutated in patients with AML impact patients’ prognosis. Moreover, it was suggested that precision-medicine-based treatment using genomic data will improve treatment outcomes for AML patients. This paper presents (1) previous studies regarding the role of KIT mutations in AML, (2) the data in AML with KIT mutations from the HM-SCREEN-Japan-01 study, a genome profiling study for patients newly diagnosed with AML who are unsuitable for the standard first-line treatment (unfit) or have relapsed/refractory AML, and (3) new therapies targeting KIT mutations, such as tyrosine kinase inhibitors and heat shock protein 90 inhibitors. In this era when genome profiling via next-generation sequencing is becoming more common, KIT mutations are attractive novel molecular targets in AML.     

Macrophage Migration Inhibitory Factor (MIF) as a Stress Molecule in Renal Inflammation

Renal inflammation is an initial pathological process during progressive renal injury regardless of the initial cause. Macrophage migration inhibitory factor (MIF) is a truly proinflammatory stress mediator that is highly expressed in a variety of both inflammatory cells and intrinsic kidney cells. MIF is released from the diseased kidney immediately upon stimulation to trigger renal inflammation by activating macrophages and T cells, and promoting the production of proinflammatory cytokines, chemokines, and stress molecules via signaling pathways involving the CD74/CD44 and chemokine receptors CXCR2, CXCR4, and CXCR7 signaling. In addition, MIF can function as a stress molecule to counter-regulate the immunosuppressive effect of glucocorticoid in renal inflammation. Given the critical position of MIF in the upstream inflammatory cascade, this review focuses on the regulatory role and molecular mechanisms of MIF in kidney diseases. The therapeutic potential of targeting MIF signaling to treat kidney diseases is also discussed.