Incorporation of a hinge domain improves the expansion of chimeric antigen receptor T cells

© 2017 The Author(s). Background: Multiple iterations of chimeric antigen receptors (CARs) have been developed, mainly focusing on intracellular signaling modules. However, the effect of non-signaling extracellular modules on the expansion and therapeutic efficacy of CARs remains largely undefined. Methods: We generated two versions of CAR vectors, with or without a hinge domain, targeting CD19, mesothelin, PSCA, MUC1, and HER2, respectively. Then, we systematically compared the effect of the hinge domains on the growth kinetics, cytokine production, and cytotoxicity of CAR T cells in vitro and in vivo. Results: During in vitro culture period, the percentages and absolute numbers of T cells expressing the CARs containing a hinge domain continuously increased, mainly through the promotion of CD4+ CAR T cell expansion, regardless of the single-chain variable fragment (scFv). In vitro migration assay showed that the hinges enhanced CAR T cells migratory capacity. The T cells expressing anti-CD19 CARs with or without a hinge had similar antitumor capacities in vivo, whereas the T cells expressing anti-mesothelin CARs containing a hinge domain showed enhanced antitumor activities. Conclusions: Hence, our results demonstrate that a hinge contributes to CAR T cell expansion and is capable of increasing the antitumor efficacy of some specific CAR T cells. Our results suggest potential novel strategies in CAR vector design.Link_to_subscribed_fulltex

Magnetism and microstructure of compositionally modulated disordered Fe/Ta films

Results are presented on compositionally modulated disordered magnetic films of the form (XÅFe/YÅTa), as a function of the modulation wavelength λ≡X+Y. Magnetization, ac susceptibility, torque magnetometry, x-ray diffraction, and Mössbauer measurements are used to probe magnetic transitions and microstructure. For X and Y values less than about 12 Å the structure is amorphous within the layers and compositionally modulated in the direction perpendicular to the film. Films with ultrathin individual layers (1–3 atomic diameters) exhibit perpendicular anisotropy while the thicker ones have in-plane magnetization. Spin-glass and ferromagnetic transitions are observed and are associated with specific regions of the multilayered films. Journal of Applied Physics is copyrighted by The American Institute of Physics

Plate-Focusing Based on a Meta-Molecule of Dendritic Structure in the Visible Frequency

To study the potential application of metasurfaces in lens technology, we propose a dendritic meta-molecule surface (also referred to as a dendritic metasurface) and realize the focusing effect in the visible spectrum through simulations and experiments. Using asymmetric dendritic structures, this metasurface can achieve distinct broadband anomalous reflection and refraction. When the metasurface is rotated by 180° around the z axis, anomalous reflection and refraction in vertically incident optical waves are in opposite directions. Considering this feature, a metasurface is designed to achieve a prominent plate-focusing effect. Samples with a transmission peak of green light at 555 nm, yellow light at 580 nm, and red light at 650 nm were prepared using bottom-up electrochemical deposition, and the focus intensity of approximately 10% and focal length of almost 600 µm were experimentally demonstrated

Analysis on bacterial community structure of new and old fermented pit mud of Shedian Liquor

AbstractThe richness and diversity of bacterial community in the fermented pit mud from the new and old distilleries of Shedian Liquor were analysed via the Illumina Miseq PE300 high-throughput sequencing technology, so as to further understand the differences of bacterial community structure in fermented pit muds with different pit ages. The results show that the bacterial community is mainly distributed into five dominant phyla (> 1.0%): Firmicutes, Synergistes, Bacteroidetes, Proteobacteria and Verrucomicrobia. There are 13 dominant genera (> 1.0%), of which Lactobacillus is dominant in both samples with a higher content in the new pit (61.12%) and lower in the old pit (1.15%). Caproiciproducens accounting for 43.53% and Syntrophomonas accounting for 6.20%, norank_f__Family_XIV (17.68%), Aminobacterium (17.68%), Sedimentibacter (1.89%), Caldicoprobacter (1.52%) and Sporanaerobacter (1.29%) are the dominant bacteria in the old pit mud. Bacillus accounting for 6.02%, Bacteroides (6.27%), Akkermansia (1.51%), Hydrogenispora (2.15%) and norank_f__Bacteroidales_S24-7_group (1.15%) are the dominant bacteria in the new pit mud. The results showed that there is a great difference in the bacterial community structure of in the new and old pit mud. In addition, compared with the bacterial community composition in the pit mud of Luzhou flavour Baijiu in Sichuan, it was found that the microorganisms that formed caproic acid and butyric acid were different

Novel mulberry silkworm cocoon-derived carbon dots and their anti-inflammatory properties

AbstractMulberry silkworm cocoon (MSC) carbonisata has been used for the treatment of inflammatory diseases for hundreds of years; however, after years of research efforts, little information is available on its anti-inflammatory components and underlying mechanism. We developed novel carbon dots (CDs) derived from MSC carbonisata (MSC-CDs), for the first time, with an average diameter of 2.26–9.35 nm and a quantum yield (QY) of 6.32%. The MSC-CDs were prepared using a modified pyrolysis method, and no further modification and external surface passivation agent was required. With abundant surface groups, MSC-CDs showed distinct solubility and bioactivity. In this study, we innovatively used three classical experimental models of inflammation to evaluate the anti-inflammatory bioactivity of MSC-CDs. The results indicated that MSC-CDs exhibited marked anti-inflammatory bioactivity which was likely mediated by inhibition of the expression of interleukin-6 and tumour necrosis factor-α. These results suggest that MSC-CDs possess a remarkable anti-inflammatory property, which provides evidence to support further investigation of the considerable potential and effective material basis of this traditional Chinese medicine

Cd-MOF and Its Ln³⁺-Post Modification Products: Regulation of Luminescence Properties and Improved Detection of Uric Acid, Quinine, and Quinidine

One 3D Cd-MOF, namely, {[(HDMA)2][Cd3(L)2]·5H2O·2DMF}n (LCU-124, LCU indicates Liaocheng University), was synthesized from an ether-containing ligand 1,3-bis(3,5-dicarboxylphenoxy)benzene (H4L). Its Ln3+-postmodified samples, Eu3+@LCU-124 and Tb3+@LCU-124, were obtained through cation exchange of dimethylamine cation (HDMA) with Eu3+ and Tb3+. The successful entry of rare earth into LCU-124 by cation exchange modification was verified by IR, XRD, XPS, EDS mapping, and luminescence spectra. The proportion of Eu3+/Tb3+ was adjusted during the modification process, leading to fluorescent materials with different emissions. Luminescence measurements indicated that these complexes exhibited interesting multiresponsive sensing activities toward biomarkers urine acid (UA), quinine (QN), and quinidine (QND). First, LCU-124 has a pronounced quenching effect toward UA with the detection limit of 31.01 μM. After modification, the visualization of the detection was improved significantly and the detection limit of Eu3+@LCU-124 was reduced to 0.868 μM. Second, when QN and QND were present in the suspensions of Eu3+@LCU-124 and Tb3+@LCU-124, strong blue light emission peaks occurred, while the characteristic emission of Eu3+/Tb3+ decreased, forming ratiometric fluorescent sensors with the detection limit in the range of 0.199–9.49 μM. The fluorescent probes have high selectivity, excellent sensitivity recycling, and fast response time (less than 1 min). Besides, a simple logic gate circuit and a range of luminescent mixed matrix membranes were designed to provide simple and fast detection of above biomarkers. Our work indicated that modification of Eu3+/Tb3+ could improve the detection ability significantly