Homogeneous,Low-volume,Efficient, and Sensitive Quantitation of Circulating Exosomal PD-L1 for Cancer Diagnosis and Immunotherapy Response Prediction

Immunotherapy has revolutionized cancer treatment, but its efficacy is severely hindered by the lack of effective predictors. Herein, we developed a homogeneous, low-volume, efficient, and sensitive exosomal programmed death-ligand 1 (PD-L1, a type of transmembrane protein) quantitation method for cancer diagnosis and immunotherapy response prediction (HOLMES-Exo_PD-L1). The method combines a newly evolved aptamer that efficiently binds to PD-L1 with less hindrance by antigen glycosylation than antibody, and homogeneous thermophoresis with a rapid binding kinetic. As a result, HOLMES-Exo_PD-L1 is higher in sensitivity, more rapid in reaction time, and easier to operate than existing enzyme-linked immunosorbent assay (ELISA)-based methods. As a consequence of an outstanding improvement of sensitivity, the level of circulating exosomal PD-L1 detected by HOLMES-Exo_PD-L1 can effectively distinguish cancer patients from healthy volunteers, and for the first time was found to correlate positively with the metastasis of adenocarcinoma. Overall, HOLMES-Exo_PD-L1 brings a fresh approach to exosomal PD-L1 quantitation, offering unprecedented potential for early cancer diagnosis and immunotherapy response prediction.     

Redox Dyshomeostasis Strategy for Hypoxic Tumor Therapy Based on DNAzyme-Loaded Electrophilic ZIFs

Redox homeostasis is one of the main reasons for reactive oxygen species (ROS) tolerance in hypoxic tumors, limiting ROS-mediated tumor therapy. Proposed herein is a redox dyshomeostasis (RDH) strategy based on a nanoplatform, FeCysPW@ZIF-82@CAT Dz, to disrupt redox homeostasis, and its application to improve ROS-mediated hypoxic tumor therapy. Once endocytosed by tumor cells, the catalase DNAzyme (CAT Dz) loaded zeolitic imidazole framework-82 (ZIF-82@CAT Dz) shell can be degraded into Zn²⁺ as cofactors for CAT Dz mediated CAT silencing and electrophilic ligands for glutathione (GSH) depletion under hypoxia, both of which lead to intracellular RDH and H₂O₂ accumulation. These “disordered” cells show reduced resistance to ROS and are effectively killed by ferrous cysteine-phosphotungstate (FeCysPW) induced chemodynamic therapy (CDT). In vitro and in vivo data demonstrate that the pH/hypoxia/H₂O₂ triple stimuli responsive nanocomposite can efficiently kill hypoxic tumors. Overall, the RDH strategy provides a new way of thinking about ROS-mediated treatment of hypoxic tumors.     

固相萃取-离子色谱法测定血液中草甘膦及其代谢物氨甲基膦酸

草甘膦是目前世界上使用量最大的除草剂之一,被广泛应用于控制农田或非耕作用地中一年生或多年生杂草的生长[1]。草甘膦是一种生物蛋白质合成抑制剂,其通过抑制5-烯醇丙酮莽草酸-3-磷酸盐合成酶(EPSPs)的活性,使植物体内蛋白质合成受阻,致使植物死亡[2]。草甘膦原药在美国毒性分级中被评定为Ⅲ,被认为是相对较安全的农药,但经商品化改造的草甘膦的毒性是前者的数倍[3],会造成人体上皮细胞膜的损伤[4]、细胞中的血浆损伤和线粒体功能受损[5],甚至有致癌的风险。     

高比能锂硫电池正极材料

锂硫电池被认为是最有发展潜力的新型多电子反应的二次电池体系之一.单质硫与锂反应的理论比容量为1675 mA h g?1,质量比能量达2600 W h kg?1,远远高于现行的传统锂离子二次电池材料.同时硫又具有来源丰富、环境友好等优点.然而,仍然有许多问题制约了锂硫电池的发展与广泛应用.本文综述了近年来锂硫电池正极材料的研究进展.     

Molecular Rotors in Porous Organic Frameworks

Porous organic frameworks perform a variety of functions, owing to their extremely large surface areas, but the dynamics of the structural elements have never been explored. Our discovery of ultra‐fast molecular rotors (10⁶ Hz at 225 K) in their architectures allows us to look at them from a new perspective. The constructive elements are robust struts and rapid rotors, resulting in a dynamic material whose motion can be frozen or released at will. The rotational motion can be actively regulated in response to guests. As the temperature is increased, the rotors spin ever faster, approaching free‐rotational diffusion at 550 K. The unusual combination of remarkable nanoporosity with fast dynamics is intriguing for engineering oscillating dipoles and producing responsive materials with switchable ferroelectricity, and for applications spanning from sensors to actuators, which capture and release chemicals on command.     

Tunable Surface‐Enhanced Raman Scattering from High‐Density Gold Semishell Arrays with Controllable Dimensions

A convenient reproducible technique is reported for the fabrication of large‐area gold semishell arrays by mechanically pressing porous anodic alumina (PAA) stamps into gold/polymer bilayer structures that serve as robust and cost‐efficient surface‐enhanced Raman‐scattering (SERS) substrates. The surface structure can be tuned further to optimize the enhancement factor according to optional PAA fabrication parameters and imprinting pressures. Finite‐difference time‐domain calculations indicate that the structure may possess excellent SERS characteristics due to the high density and abundance of hot spots.     

Synthesis,Crystal Structure and Photoluminescence of a Three-coordinate Ag(Ⅰ) Complex

A three-coordinate Ag(I) complex, [Ag(Mepzpy)(PAr3)]BF4·H2O(1, Mepzpy = 3-methyl-1-(2-pyridyl)pyrazole, PAr3 = tri(o-tolyl)phosphine), was synthesized from the reaction of Ag(CH3CN)4BF4, PAr3 and Mepzpy in CH3 CN at room temperature. The compound was characterized by UV-vis, NMR and X-ray single-crystal structure analysis. It crystallizes in triclinic space group P1 with a = 10.2251(5), b = 10.6014(5), c = 15.7012(5) , α = 92.963(3), β = 92.641(3), γ = 114.647(4)o, V = 1540.6(1) 3, Z = 2, Mr = 676.24, Dc = 1.458 g/cm3, F(000) = 688, μ = 6.187 mm-1, GOOF = 1.038, the final R = 0.0530 and w R = 0.1493 for 6371 observed reflections with I 2σ(I). Compound 1 is ionic. It is composed of a BF4- anion and a [Ag(Mepzpy)(PAr3)]+ cation. The Ag(I) ion adopts a distorted trigonal pyramidal coordination geometry defined by two nitrogen atoms and a phosphorous atom. The complex emits blue luminescence with maximum peaks at 470 nm in solid state at room temperature.     

A novel voltammetric sensor for ascorbic acid based on molecularly imprinted poly(o-phenylenediamine-co-o-aminophenol)

A molecularly imprinted copolymer, poly(o-phenylenediamine-co-o-aminophenol) (PoPDoAP), was prepared as a new ascorbic acid (AA) sensor. The copolymer was synthesized by incorporation of AA as template molecules during the electrochemical copolymerization of o-phenylenediamine and o-aminophenol, and complementary sites were formed after the copolymer was electrochemically reduced in ammonium aqueous solution. The molecularly imprinted copolymer sensor exhibited a high sensitivity and selectivity toward AA. Differential pulse voltammograms (DPVs) showed a linear concentration range of AA from 0.1 to 10 mM, and the detection limit was calculated to be 36.4 μM. Compared to conventional polyaniline-based AA sensors, the analytical performance of the imprinted copolymer sensor was improved due to the broadened usable pH range of PoPDoAP (from pH 1.0 to pH 8.0). The sensor also exhibited a good reproducibility and stability. And it has been successfully applied in the determination of AA in real samples, including vitamin C tablet and orange juices, with satisfactory results.     

Simultaneous determination of the repertoire of classical neurotransmitters released from embryonal carcinoma stem cells using online microdialysis coupled with hydrophilic interaction chromatography–tandem mass spectrometry

Dynamic, continuous, and simultaneous multi-analysis of transmitters is important for the delineation of the complex interactions between the neuronal and intercellular communications. But the analysis of the whole repertoire of classical transmitters of diverse structure is challenging due to their different physico-chemical properties and to their high polarity feature which leads to poor retention in traditional reversed-phase columns during LC–MS analysis. Here, an online microdialysis coupled with hydrophilic interaction chromatography–tandem mass spectrometry (online MD-HILIC–MS/MS) detection method was developed for the simultaneous measurement of the repertoire of classical transmitters (acetylcholine, serotonin, dopamine, norepinephrine, glutamate, GABA, and glycine). Stable isotope labeled internal standards and authentic matrix have been applied to guarantee reliable results. The method was successfully employed to reveal the characteristics of transmitter release from embryonal carcinoma stem cells. The method features simple procedure (no sample preparation), high recovery (≥73%), high accuracy (89.36% ≤ RE ≤ 116.89%), good reproducibility (2.18% ≤ RSD ≤ 14.56%), and sensitive limits of detection (2 pg for acetylcholine, serotonin, and glutamate, 10 pg for dopamine, norepinephrine, GABA, and glycine). It can be flexibly applied to determine the contents of the classical transmitters in other biological matrix samples with minor changes.     

医用生物材料的低温保存研究

生物材料的低温保存一般都要经历降温过程、低温储存过程及复温过程,其中降温过程中对生物细胞的影响最大.每一种生物细胞都有自己合适的降温速率,如能满足其这种降温速率,细胞所受到的低温损伤最小,则生物细胞的复活率最高.文中介绍程序控制变速降温装置的主要结构及几种典型生物体的降温过程.最后,对器官的低温保存进行分析讨论.