Synergistic enhancement of iron oxide nanoparticle and gadolinium for dual-contrast MRI

National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH); National Science Foundation of China (NSFC) [81201086]Purpose: The use of MR contrast agents allows accurate diagnosis by exerting an influence on the longitudinal (T-1) or transverse (T-2) relaxation time of the surrounding tissue. In this study, we combined the use of iron oxide (IO) particles and nonspecific extracellular gadolinium chelate (Gd) in order to further improve the sensitivity and specificity of lesion detection. Procedures: With a 7-Tesla scanner, pre-contrasted, IO-enhanced and dual contrast agent enhanced MRIs were performed in phantom, normal animals, and animal models of lymph node tumor metastases and orthotopic brain tumor. For the dual-contrast (DC) MRI, we focused on the evaluation of T-2 weighted DC MRI with IO administered first, then followed by the injection of a bolus of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). Results: Based on the C/N ratios and MRI relaxometry, the synergistic effect of coordinated administration of Gd-DTPA and IO was observed and confirmed in phantom, normal liver and tumor models. At 30 min after administration of Feridex, Gd-DTPA further decreased T-2 relaxation in liver immediately after the injection. Additional administration of Gd-DTPA also immediately increased the signal contrast between tumor and brain parenchyma and maximized the C/N ratio to -4.12 +/- 0.71. Dual contrast MRI also enhanced the delineation of tumor borders and small lesions. Conclusions: DC-MRI will be helpful to improve diagnostic accuracy and decrease the threshold size for lesion detection. (C) 2012 Elsevier Inc. All rights reserved

Versatile RNA Interference Nanoplatform for Systemic Delivery of RNAs

Development of nontoxic, tumor-targetable, and potent in vivo RNA delivery systems remains an arduous challenge for clinical application of RNAi therapeutics. Herein, we report a versatile RNAi nanoplatform based on tumor-targeted and pH-responsive nanoformulas (NFs). The NF was engineered by combination of an artificial RNA receptor, Zn(II)-DPA, with a tumor-targetable and drug-loadable hyaluronic acid nanoparticle, which was further modified with a calcium phosphate (CaP) coating by in situ mineralization. The NF can encapsulate small-molecule drugs within its hydrophobic inner core and strongly secure various RNA molecules (siRNAs, miRNAs, and oligonucleotides) by utilizing Zn(II)-DPA and a robust CaP coating. We substantiated the versatility of the RNAi nanoplatform by demonstrating effective delivery of siRNA and miRNA for gene silencing or miRNA replacement into different human types of cancer cells in vitro and into tumor-bearing mice in vivo by intravenous administration. The therapeutic potential of NFs coloaded with an anticancer drug doxorubicin (Dox) and multidrug resistance 1 gene target siRNA (siMDR) was also demonstrated in this study. NFs loaded with Dox and siMDR could successfully sensitize drug-resistant OVCAR8/ADR cells to Dox and suppress OVCAR8/ADR tumor cell proliferation in vitro and tumor growth in vivo. This gene/drug delivery system appears to be a highly effective nonviral method to deliver chemo- and RNAi therapeutics into host cells.National Institute for Biomedical Imaging and Bioengineering (U.S.)National Institutes of Health (U.S.)AXA Research Fund (Postdoctoral Fellowship)National Research Foundation of Korea (Postdoctoral Fellowship 2013R1A6A3A03)National Research Foundation of Korea (Grant 2009-0080734

Synthesis of Aqueous CdTe/CdS/ZnS Core/shell/shell Quantum Dots by a Chemical Aerosol Flow Method

This work described a continuous method to synthesize CdTe/CdS/ZnS core/shell/shell quantum dots. In an integrated system by flawlessly combining the chemical aerosol flow system working at high temperature (200–300°C) to generate CdTe/CdS intermediate products and an additional heat-up setup at relatively low temperature to overcoat the ZnS shells, the CdTe/CdS/ZnS multishell structures were realized. The as-synthesized CdTe/CdS/ZnS core/shell/shell quantum dots are characterized by photoluminescence spectra, X-ray diffraction (XRD), energy-dispersive X-ray spectra (EDS), transmission electron microscopy (TEM), and high-resolution transmission electron microscopy (HRTEM). Fluorescence and XRD results confirm that the obtained quantum dots have a core/shell/shell structure. It shows the highest quantum yield above 45% when compared to the rhodamine 6G. The core/shell/shell QDs were more stable via the oxidation experiment by H2O2

Differentiation of Reactive and Tumor Metastatic Lymph Nodes with Diffusion-weighted and SPIO-Enhanced MRI

National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH); National Science Foundation of China (NSFC) [81028009]Determination of lymphatic metastasis is of great importance for both treatment planning and patient prognosis. We aim to distinguish tumor metastatic lymph nodes (TLNs) and reactive lymph nodes (RLNs) with diffusion-weighted and superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI). Ipsilateral popliteal lymph node metastasis or lymphadenitis model was established by hock injection of either luciferase-expressing 4T1 murine breast cancer cells or complete Freund's adjuvant in male BALB/c mice. At different time points after inoculation, bioluminescence imaging and T-2-weighted, diffusion-weighted, and SPIO-enhanced MRI were performed. Imaging findings were confirmed by histopathological staining. Size enlargement was observed in both TLNs and RLNs. At day 28, TLNs showed strong bioluminescence signal and bigger size than RLNs (p < 0.01). At early stages up to day 21, both TLNs and RLNs appeared homogeneous on diffusion-weighted imaging. At day 28, TLNs showed heterogeneous apparent diffusion coefficient (ADC) map with significantly higher average ADC value of 0.41 +/- 0.03 x 10(-3)mm(2)/s than that of RLNs (0.34 +/- 0.02 x 10(-3)mm(2)/s; p < 0.05). On SPIO-enhanced MRI, both TLNs and RLNs showed distinct T-2 signal reduction at day 21 after inoculation. At day 28, TLNs demonstrated partial uptake of the iron oxide particles, which was confirmed by Prussian blue staining. Both diffusion-weighted and SPIO-enhanced MRI can distinguish tumor metastatic lymph nodes from reactive lymph nodes. However, neither method is able to detect tumor metastasis to the draining lymph nodes at early stages

Effects of Different Irrigation Methods on Growth, Fruit Quality and Yield of Apple Trees

Water-saving irrigation is an important way to realize the sustainable development of the apple industry. In order to screen the best irrigation pattern for apple, taking 9-year-old ‘Yanfu 10’ Fuji / Malus robusta apple as the material, the effects of different irrigation methods (drip irrigation, sprinkling irrigation, and flood irrigation) on the growth, fruit quality, and yield of apple trees were studied. The results showed that compared with the flood irrigation, drip irrigation and sprinkling irrigation significantly increased the spring shoot length by 14.8% and 9.1%, respectively, and decreased the autumn shoot length by 11.7% and 8.8%, respectively. Drip irrigation and sprinkling irrigation significantly increased the leaf area, chlorophyll content, and leaf weight, the leaf area increased by 3.0% and 1.9%, respectively, the chlorophyll content increased by 13.9% and 11.5%, respectively, and the leaf weight increased by 5.8% and 5.1%, respectively. Drip irrigation and sprinkling irrigation could slightly increase the single fruit weight and fruit shape index, significantly increase the coloring index and smoothness index. The single fruit weight increased by 3.2% and 1.9%, the coloring index increased by 6.1% and 4.1%, the smoothness index increased by 4.7% and 2.8%, and the proportion of red fruit increased by 4.2% and 2.2%, respectively. The content of soluble solids in drip irrigation and sprinkling irrigation was significantly higher than that in flood irrigation, which was 13.0% and 2.6% higher than CK, respectively. The fruit hardness in drip irrigation and sprinkling irrigation was 7.9% and 2.2% higher than CK, respectively, and that in drip irrigation increased significantly. The yield in drip irrigation and sprinkling irrigation was 12.1% and 8.2% higher than CK, respectively. In conclusion, drip irrigation and sprinkling irrigation could promote the growth of apple trees, improve the fruit quality, and increase the yield of apple trees, and the effect of drip irrigation is better than sprinkling irrigation

Lineage Tracing and Molecular Real-Time Imaging of Cancer Stem Cells

The cancer stem cells (CSC) are the roots of cancer. The CSC hypothesis may provide a model to explain the tumor cell heterogeneity. Understand the biological mechanism of CSC will help the early detection and cure of cancer. The discovery of the dynamic changes in CSC will be possible by the using of bio-engineering techniques-lineage tracing. However, it is difficult to obtain real-time, continuous, and dynamic live-imaging information using the traditional approaches that take snapshots of time points from different animals. The goal of molecular imaging is to monitor the in situ, continuous molecular changes of cells in vivo. Therefore, the most advanced bioengineering lineage tracing approach, while using a variety of molecular detection methods, will maximize the presentation of CSC. In this review, we first introduce the method of lineage tracing, and then introduce the various components of molecular images to dynamic detect the CSC. Finally, we analyze the current situation and look forward the future of CSC detection

Increase in Cd Tolerance through Seed-Borne Endophytic Fungus Epichlo&euml; gansuensis Affected Root Exudates and Rhizosphere Bacterial Community of Achnatherum inebrians

Soil cadmium (Cd) pollution is a serious environmental problem imperiling food safety and human health. The endophyte Epichlo&euml; gansuensis can improve the tolerance of Achnatherum inebrians to Cd stress. However, it is still unknown whether and how the endophyte helps host plants build up a specific bacterial community when challenged by CdCl2. In this study, the responses of the structure and function of bacterial community and root exudates of E+ (E. gansuensis infected) and E&minus; (E. gansuensis uninfected) plants to Cd stress were investigated. Analysis of bacterial community structure indicated that the rhizosphere bacterial community predominated over the root endosphere bacterial community in enhancing the resistance of CdCl2 in a host mediated by E. gansuensis. E+ plant strengthened the interspecific cooperation of rhizosphere bacterial species. Moreover, the analysis of root exudates demonstrated E. gansuensis and increased the contents of organic acids and amino acids under Cd stress, and most root exudates were significantly correlated with rhizosphere bacteria. These results suggested that E. gansuensis employed a specific strategy to recruit distinct rhizosphere bacterial species and relevant functions by affecting root exudates to improve the tolerance of the host to Cd stress. This study provides a firm foundation for the potential application of symbionts in improving phytostabilization efficiency

Real-time monitoring of caspase cascade activation in living cells

We introduce a simple, versatile and robust one-step technique that enables real-time imaging of multiple intracellular caspase activities in living cells without the need for complicated synthetic protocols. Conventional fluorogenic probes or recently reported activatable probes have been designed to target various proteases but are limited to extracellular molecules. Only a few have been applied to image intracellular proteases in living cells because most of these probes have limited cell-permeability. Our platform does not need complicated synthetic processes; instead it involves a straightforward peptide synthesis and a simple mixing step with a commercial transfection agent. The transfection agent efficiently delivered the highly quenched fluorogenic probes, comprised of distinctive pairs of dyes and quenchers, to the initiator caspase-8 and the effector caspase-3 in MDA-MB-435 cells, allowing dual-imaging of the activities of both caspases during the apoptotic process induced by TNF-related apoptosis induced ligand (TRAIL). With the combination of multiple fluorogenic probes, this simple platform can be applied to multiplexed imaging of selected intracellular proteases to study apoptotic processes in pathologies or for cell-based high throughput screening systems for drug discovery

Étude des événements précipitants intenses en Méditerranée (approche par la modélisation climatique régionale)

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