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Overexpression of legumain is closely associated with tumor proliferation, invasion, and metastasis. Because of its intrinsic properties, such as high sensitivity and resolution, positron emission tomography (PET) has become an effective imaging technique for early diagnosis, treatment response prediction, and monitoring. Herein, two legumain-targeting radiofluorinated smart probes ( 18 F-2 and 18 F-3) as well as a control probe ( 18 F-1) were specifically designed for PET imaging of legumain activity in tumors. 18 F-1, 18 F-2, and 18 F-3 were obtained with high radiochemical yield (RCY > 60%) and radiochemical purity (RCP > 99%) using a convenient "one-step" 18F-labeling method. The probes 18 F-2 and 18 F-3 exhibited high response to legumain activity and reductive environment and revealed comparable uptake in HCT116 cells (4.22% ± 0.14% and 4.64% ± 0.32% for 18 F-2 and 18 F-3, respectively; 8.46% ± 0.33% and 9.05% ± 0.24% for co-treatment of 18 F-2 + 2 and 18 F-3 + 3 at 1 h), while the control probe 18 F-1 showed no response. PET imaging of tumor-bearing mice showed that the co-injection strategy ( 18 F-2 + 2 and 18 F-3 + 3) resulted in higher tumor uptake (3.57% ± 0.37% and 3.72% ± 0.19% ID/g at 10 min, respectively) than the single injection strategy (2.59% ± 0.19% and 2.60% ± 0.46% ID/g for 18 F-2 and 18 F-3, respectively). In addition, introduction of the trimeric histidine-glutamate (HEHEHE) tag to 18 F-3 reduced the liver uptake by almost two-fold without any noticeable effect on the tumor uptake. All the results indicate that 18 F-3 holds great potential applications in clinics for sensitive and specific PET imaging of legumain activity in tumors.Most studies of ultrasensitive diagnosis of biomolecules from liquid specimens are limited by problems during sample preparation steps, including enrichment and isolation of biomolecules. Here we report a novel platform combining bis(sulfosuccinimidyl)suberate (BS3) and helix-shaped microchannels (BSH) to change the sample preparation paradigm. This BSH system is composed of BS3 for pathogen enrichment and nucleic acid isolation by electrostatic and covalent interaction, and helix-shaped microchannels to minimize sample loss and remove bubbles in large liquid specimens without pH change. The system detected Mycobacterium tuberculosis following enrichment and isolation of 10 mL of liquefied sputum from 11 patients with tuberculosis. Moreover, the system identified KRAS mutations following cell-free DNA isolation of blood plasma from 10 patients with colorectal cancer. This system allows ultrasensitive diagnosis in various disease applications with large volumes of liquid samples.Stimulated emission depletion (STED) nanoscopy provides subdiffraction resolution while preserving the benefits of fluorescence confocal microscopy in live-cell imaging. However, there are several challenges for multicolor STED nanoscopy, including sophisticated microscopy architectures, fast photobleaching, and cross talk of fluorescent probes. Here, we introduce two types of nanoscale fluorescent semiconducting polymer dots (Pdots) with different emission wavelengths CNPPV (poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-(1-cyanovinylene-1,4-phenylene)]) Pdots and PDFDP (poly[9,9-dihexyl-2,7-bis(1-cyanovinylene)fluorene-alt-co-2,5-bis (N,N'-diphenylamino)-1,4-phenylene]) Pdots, for dual-color STED bioimaging and cellular tracking. Besides bright fluorescence, strong photostability, and easy bioconjugation, these Pdots have large Stokes shifts, which make it possible to share both excitation and depletion beams, thus requiring only a single pair of laser beams for the dual-color STED imaging. Long-term tracking of cellular organelles by the Pdots has been achieved in living cells, and the dynamic interaction of endosomes derived from clathrin-mediated and caveolae-mediated endocytic pathways has been monitored for the first time to propose their interaction models. These results demonstrate the promise of Pdots as excellent probes for live-cell multicolor STED nanoscopy.OATP2B1, a member of the solute carrier (SLC) transporter family, is an important mechanism of substrate drug uptake in the intestine and liver and therefore a determinant of clinical pharmacokinetics and site of drug-drug interactions. Other SLC transporters have emerged as pharmacology targets. Studies of SLC transporter uptake to-date relied on radioisotope- or fluorescence-labeled reagents or low-throughput quantification of unlabeled compounds in cell lysate. In this study, we developed a cell-based MALDI MS workflow for investigation of OATP2B1 cellular uptake by optimizing the substrate, matrix, matrix-analyte ratio, and matrix application and normalization method. This workflow was automated and applied to characterize substrate transport kinetics and to test 294 top-marketed drugs for OATP2B1 inhibition and quantify inhibitory potencies necessary for extrapolation of clinical drug-drug interaction potential. Intra-assay reproducibility of this MALDI MS method was high (CV less then 10%), and results agreed well (83% overlap) with previously published radioisotope assay data. Our results indicate that fast and robust MALDI MS cellular assays could emerge as a high-throughput label-free alternative for direct assessment of drug transporter function in DDIs and toxicities as well as enable drug discovery for transporters as pharmacology targets.In this work, a novel study for acid mine drainage remediation and reutilization by means of a forward osmosis technology is addressed. The proposed process is a potential alternative path, which allows to recover high-quality water and to concentrate metals for its possible reutilization as synthetic minerals. https://www.selleckchem.com/products/fluoxetine.html This novel process will help in the mining industry evolving toward more sustainable processes and favors circular economy policies. Four inorganic salts (NaCl, KCl, CaCl2, and MgCl2) were evaluated as draw solutions from 1 to 5 M concentrations, in terms of water flux, water recovery, and metal rejection, using a thin-film composite (TFC) membrane. Water flux obtained was in the range of 14-53 L/(m2 h). The highest water flux was found for MgCl2, whereas the lowest correspond to KCl. The metal rejection obtained was greater than 99%. After a discussion and comparison of the results, MgCl2 was chosen for evaluating long-term assay performance. Scanning electron microscope images of the thin-film composite membrane after long-term assays were taken.
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