用于检测细胞内谷胱甘肽的比率型荧光探针

设计合成了1种用于检测生物巯基的比率型荧光探针(4),并考察了其对谷胱甘肽的识别作用.在4-羟乙基哌嗪乙磺酸(HEPES)缓冲液中,探针4可与谷胱甘肽快速反应,溶液颜色由淡黄色变为粉红色,从而实现"裸眼"检测,且在608 nm处的荧光信号增强.在1.6×10-5~2×10-4mol/L范围内,探针4能够定量检测谷胱甘肽,检出限为8.9×10-7mol/L.此外,探针4还可用于MCF-7细胞中谷胱甘肽的成像.     

Optical coherence tomography based imaging of dental demineralisation and cavity restoration in 840 nm and 1310 nm wavelength regions

In this paper, a study of in-house built optical coherence tomography (OCT) system with a wavelength of 840 nm for imaging of dental caries, progress in demineralisation and cavity restoration is presented. The caries when imaged with the 840 nm OCT system showed minute demineralisation in the order of 5 μm. The OCT system was also proposed to study the growth of lesion and this was demonstrated by artificially inducing caries with a demineralisation solution of pH 4.8. The progress of carious lesion to a depth of about 50–60 μm after 60 hours of demineralisation was clearly observed with the 840 nm OCT system. The tooth samples were subjected to accelerated demineralisation condition at pH of approximately 2.3 to study the adverse effects and the onset of cavity formation was clearly observed. The restoration of cavity was also studied by employing different restorative materials (filled and unfilled). In the case of restoration without filler material (unfilled), the restoration boundaries were clearly observed. Overall, results were comparable with that of the widely used 1310 nm OCT system. In the case of restoration with filler material, the 1310 nm OCT imaging displayed better imaging capacity due to lower scattering than 840 nm imaging.     

Structurally Defined αMHC‐II Nanobody–Drug Conjugates: A Therapeutic and Imaging System for B‐Cell Lymphoma

Antibody–drug conjugates (ADCs) of defined structure hold great promise for cancer therapies, but further advances are constrained by the complex structures of full‐sized antibodies. Camelid‐derived single‐domain antibody fragments (VHHs or nanobodies) offer a possible solution to this challenge by providing expedited target screening and validation through switching between imaging and therapeutic activities. We used a nanobody (VHH7) specific for murine MHC‐II and rendered “sortase‐ready” for the introduction of oligoglycine‐modified cytotoxic payloads or NIR fluorophores. The VHH7 conjugates outcompeted commercial monoclonal antibodies (mAbs) for internalization and exhibited high specificity and cytotoxicity against A20 murine B‐cell lymphoma. Non‐invasive NIR imaging with a VHH7–fluorophore conjugate showed rapid tumor targeting on both localized and metastatic lymphoma models. Subsequent treatment with the nanobody–drug conjugate efficiently controlled tumor growth and metastasis without obvious systemic toxicity.     

Dual‐Targeting Nanovesicles for In Situ Intracellular Imaging of and Discrimination between Wild‐type and Mutant p53

p53 is a tumor‐suppressor protein related to the cell cycle and programmed cell apoptosis. Herein, dual‐targeting nanovesicles are designed for in situ imaging of intracellular wild‐type p53 (WTp53) and mutant p53 (MUp53). Nanovesicle‐encapsulated plasmonic gold nanoparticles (AuNPs) were functionalized with consensus DNA duplexes, and a fluorescein isothiocyanate (FITC)‐marked anti‐MUp53 antibody was conjugated to the nanovesicle surface. After entering the cytoplasm, the released AuNPs aggregated through recognition of WTp53 and the double‐stranded DNA. The color changes of AuNPs were observed using dark‐field microscopy, which showed the intracellular WTp53 distribution. The MUp53 location was detected though the immunological recognition between FITC‐labeled anti‐MUp53 and MUp53. Thus, a one‐step incubation method for the in situ imaging of intracellular WTp53 and MUp53 was obtained; this was used to monitor the p53 level under a drug treatment.     

Firefly Luciferase Mutants Allow Substrate‐Selective Bioluminescence Imaging in the Mouse Brain

Bioluminescence imaging is a powerful approach for visualizing specific events occurring inside live mice. Animals can be made to glow in response to the expression of a gene, the activity of an enzyme, or the growth of a tumor. But bioluminescence requires the interaction of a luciferase enzyme with a small‐molecule luciferin, and its scope has been limited by the mere handful of natural combinations. Herein, we show that mutants of firefly luciferase can discriminate between natural and synthetic substrates in the brains of live mice. When using adeno‐associated viral (AAV) vectors to express luciferases in the brain, we found that mutant luciferases that are inactive or weakly active with d ‐luciferin can light up brightly when treated with the aminoluciferins CycLuc1 and CycLuc2 or their respective FAAH‐sensitive luciferin amides. Further development of selective luciferases promises to expand the power of bioluminescence and allow multiple events to be imaged in the same live animal.     

A Single Excitation‐Duplexed Imaging Strategy for Profiling Cell Surface Protein‐Specific Glycoforms

This work develops a site‐specific duplexed luminescence resonance energy transfer system on cell surface for simultaneous imaging of two kinds of monosaccharides on a specific protein by single near‐infrared excitation. The single excitation‐duplexed imaging system utilizes aptamer modified upconversion luminescent nanoparticles as an energy donor to target the protein, and two fluorescent dye acceptors to tag two kinds of cell surface monosaccharides by a dual metabolic labeling technique. Upon excitation at 980 nm, only the dyes linked to protein‐specific glycans can be lit up by the donor by two parallel energy transfer processes, for in situ duplexed imaging of glycoforms on specific protein. Using MUC1 as the model, this strategy can visualize distinct glycoforms of MUC1 on various cell types and quantitatively track terminal monosaccharide pattern. This approach provides a versatile platform for profiling protein‐specific glycoforms, thus contributing to the study of the regulation mechanisms of protein functions by glycosylation.     

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介绍了EAST装置上的384道(极向24道径向16道)的外差混频式电子回旋辐射成像诊断系统及其在EAST及其复杂的电磁环境中的运行情况。在低杂波电流驱动期间,高灵敏度的电子回旋辐射成像系统受到严重干扰以至于无法提供正确的实验数据。通过优化系统各模块的接地、外加多层铜网屏蔽等措施,使得ECEI系统屏蔽效能与改善之前相比提高了40dB,基本保障了EAST装置上电子回旋辐射成像诊断的正常工作。