Biodegradable Nanoglobular Magnetic Resonance Imaging Contrast Agent Constructed with Host–Guest Self-Assembly for Tumor-Targeted Imaging

Gadolinium-based macromolecular magnetic resonance imaging (MRI) contrast agents (CAs) have attracted increasing interest in tumor diagnosis. However, their practical application is potentially limited because the long-term retention of gadolinium ion in vivo will induce toxicity. Here, a nanoglobular MRI contrast agent (CA) PAMAM-PG-<i>g</i>-s-s-DOTA­(Gd) + FA was designed and synthesized on the basis of the facile host–guest interaction between β-cyclodextrin and adamantane, which initiated the self-assembly of poly­(glycerol) (PG) separately conjugated with gadolinium chelates by disulfide bonds and folic acid (FA) molecule onto the surface of poly­(amidoamine) (PAMAM) dendrimer, finally realizing the biodegradability and targeting specificity. The nanoglobular CA has a higher longitudinal relaxivity (<i>r</i>₁) than commercial gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA), showing a value of 8.39 mM^–1 s^–1 at 0.5 T, and presents favorable biocompatibility on the observations of cytotoxicity and tissue toxicity. Furthermore, MRI on cells and tumor-bearing mice both demonstrate the obvious targeting specificity, on the basis of which the effective contrast enhancement at tumor location was obtained. In addition, this CA exhibits the ability of cleavage to form free small-molecule gadolinium chelates and can realize minimal gadolinium retention in main organs and tissues after tumor detection. These results suggest that the biodegradable nanoglobular PAMAM-PG-<i>g</i>-s-s-DOTA­(Gd) + FA can be a safe and efficient MRI CA for tumor diagnosis

VAMP724 and VAMP726 are involved in autophagosome formation in <i>Arabidopsis thaliana</i>

Macroautophagy/autophagy, an evolutionarily conserved degradative process essential for cell homeostasis and development in eukaryotes, involves autophagosome formation and fusion with a lysosome/vacuole. The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins play important roles in regulating autophagy in mammals and yeast, but relatively little is known about SNARE function in plant autophagy. Here we identified and characterized two Arabidopsis SNAREs, AT4G15780/VAMP724 and AT1G04760/VAMP726, involved in plant autophagy. Phenotypic analysis showed that mutants of VAMP724 and VAMP726 are sensitive to nutrient-starved conditions. Live-cell imaging on mutants of VAMP724 and VAMP726 expressing YFP-ATG8e showed the formation of abnormal autophagic structures outside the vacuoles and compromised autophagic flux. Further immunogold transmission electron microscopy and electron tomography (ET) analysis demonstrated a direct connection between the tubular autophagic structures and the endoplasmic reticulum (ER) in vamp724-1 vamp726-1 double mutants. Further transient co-expression, co-immunoprecipitation and double immunogold TEM analysis showed that ATG9 (autophagy related 9) interacts and colocalizes with VAMP724 and VAMP726 in ATG9-positive vesicles during autophagosome formation. Taken together, VAMP724 and VAMP726 regulate autophagosome formation likely working together with ATG9 in Arabidopsis.</p

Supplementary document for A flexible and accurate total variation and cascaded denoisers-based image reconstruction algorithm for hyperspectrally compressed ultrafast photography - 6744828.pdf

Supplemental Documen

Single- and multiple-variable conditional logistic regression analyses for identifying risk factors for scrub typhus.

<p>Single- and multiple-variable conditional logistic regression analyses for identifying risk factors for scrub typhus.</p

Phylogenetic analysis based on the <i>O</i>. <i>tsutsugamushi</i> 56-kDa TSA gene.

<p>All the sequences of <i>O</i>. <i>tsutsugamushi</i> in this study marked with black triangles, were compared with other reference sequences available in GenBank. The MEGA 4.0 software was used for the phylogenetic analysis. The stability of the nodes was assessed using neighbor-joining cluster analysis with 1,000 bootstrap replications, and only bootstrap values.70% are shown at the nodes.</p

Demographic characteristics of the scrub typhus cases and controls that were enrolled in the study.

<p>Demographic characteristics of the scrub typhus cases and controls that were enrolled in the study.</p

Clinical and laboratory findings for scrub typhus cases of Jinjiang City.

<p>Clinical and laboratory findings for scrub typhus cases of Jinjiang City.</p

PCR and ELISA results of 187 cases.

<p>PCR and ELISA results of 187 cases.</p