PML fuses with retinoic acid receptor ␣ (RAR␣) in the t(15;17) translocation that causes acute promyelocytic leukemia (APL). In addition to localizing diffusely throughout the nucleoplasm, PML mainly resides in discrete nuclear structures known as PML oncogenic domains (PODs), which are disrupted in APL and spinocellular ataxia cells. We isolated the Fas-binding protein Daxx as a PML-interacting protein in a yeast two-hybrid screen. Biochemical and immunofluorescence analyses reveal that Daxx is a nuclear protein that interacts and colocalizes with PML in the PODs. Reporter gene assay shows that Daxx drastically represses basal transcription, likely by recruiting histone deacetylases. PML, but not its oncogenic fusion PML-RAR␣, inhibits the repressor function of Daxx. In addition, SUMO-1 modification of PML is required for sequestration of Daxx to the PODs and for efficient inhibition of Daxx-mediated transcriptional repression. Consistently, Daxx is found at condensed chromatin in cells that lack PML. These data suggest that Daxx is a novel nuclear protein bearing transcriptional repressor activity that may be regulated by interaction with PML.

Here we describe a simple method to estimate the inner-sphere hydration state of the Mn(II) ion in coordination complexes and metalloproteins. The linewidth of bulk H217O is measured in the presence and absence of Mn(II) as a function of temperature, and transverse 17O relaxivities are calculated. It is demonstrated that the maximum 17O relaxivity is directly proportional to the number of inner-sphere water ligands (q). Using a combination of literature data and experimental data for twelve Mn(II) complexes, we show that this method provides accurate estimates of q with an uncertainty of ±0.2 water molecules. The method can be implemented on commercial NMR spectrometers working at fields of 7T and higher. The hydration number can be obtained for micromolar Mn(II) concentrations. We show that the technique can be extended to metalloproteins or complex:protein interactions. For example, Mn(II) binds to the multi-metal binding site A on human serum albumin with two inner-sphere water ligands that undergo rapid exchange (1.06 × 108 s−1 at 37 °C). The possibility of extending this technique to other metal ions such as Gd(III) is discussed.

Photodynamic therapy (PDT) is an auspicious strategy for cancer therapy by yielding reactive oxygen species (ROS) under light irradiation. Here, we have developed near-infrared (NIR) triggered polymer encapsulated upconversion nanoparticles (UCNPs) based on aggregation-induced emission (AIE) characteristics and mitochondria target ability for PDT. The coated AIE polymer as a photosensitizer can be photoactivated by the up-converted energy of UCNPs upon 980 nm laser irradiation, which could generate ROS efficiently in mitochondria and induce cell apoptosis. Moreover, a "sheddable" poly(ethylene glycol) (PEG) layer was easily conjugated at the surface of NPs. The pH-responsive PEG layer shields the surface positive charges and shows stronger protein-resistance ability. In the acidic tumor environment, PEGylated NPs lose the PEG layer and show the mitochondria-targeting ability by responding to tumor acidity. A cytotoxicity study indicated that these NPs have good biocompatibility in the dark but exert severe cytotoxicity to cancer cells, with only 10% cell viability, upon being irradiated with an NIR laser. The AIE nanoparticles are a good candidate for effective mitochondria targeting photosensitizer for PDT.

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AIE nanoparticles show mitochondrial targeting, harvest FR/NIR emission and exert severe ROS cytotoxicity under ultralow-power-intensity (10 mW cm−2) light irradiation.

A novel method of starch modification was developed to obtain thermoplastic starch plastics with improved comprehensive properties. Corn starch was oxidized under mild conditions using sodium periodate to prepare dialdehyde starch, which had an acceptable average molecular weight. The dialdehyde starch with 35.2% carbonyl content was reacted with different alcohols (methanol, ethanol, and glycol) to prepare a series of novel starch derivatives, whose structures were characterized by 1H‐NMR and FT‐IR. The thermogravimetric analysis showed that these starch derivatives had an improved thermal stability compared with dialdehyde starch. Thermoplastic starch and its derivatives were prepared when water and glycerol were added as plasticizers. The modified thermoplastic starch and its derivatives had better mechanical properties than other modified starches, and lower humidity absorption than conventional thermoplastic starches. The highest tensile strength and elongation at break reached 17.5 MPa and 149%, respectively, and the highest humidity absorption was about 37%.

Liver-specific contrast agents (CAs) can improve the Magnetic resonance imaging (MRI) detection of focal and diffuse liver lesions by increasing the lesion-to-liver contrast. A novel Mn­(II) complex, Mn-BnO-TyrEDTA, with a lipophilic group-modified ethylenediaminetetraacetic acid (EDTA) structure as a ligand to regulate its behavior in vivo, is superior to Gd-EOB-DTPA in terms of a liver-specific MRI contrast agent. An MRI study on mice demonstrated that Mn-BnO-TyrEDTA can be rapidly taken up by hepatocytes with a combination of hepatobiliary and renal clearance pathways. Bromosulfophthalein (BSP) inhibition imaging, biodistribution, and cellular uptake studies confirmed that the mechanism of hepatic targeting of Mn-BnO-TyrEDTA is the hepatic uptake of the amphiphilic anion contrast agent mediated by organic anion transporting polypeptides (OATPs) expressed by functional hepatocytes.

A Mn(II) chelating dendrimer was prepared as a contrast agent for MRI applications. The dendrimer comprises six tyrosine-derived [Mn(EDTA)(H2O)]2− moieties coupled to a cyclotriphosphazene core. Variable temperature 17O NMR revealed a single water co-ligand per Mn(II) that undergoes fast water exchange (kex = (3.0±0.1) × 108 s−1 at 37 °C). The 37 °C per Mn(II) relaxivity ranged from 8.2 to 3.8 mM−1s−1 from 0.47 to 11.7T, and is 6-fold higher on a per molecule basis. From this field dependence a rotational correlation time was estimated as 0.45±0.02 ns. The imaging and pharmacokinetic properties of the dendrimer were compared to clinically used [Gd(DTPA)(H2O)]2− in mice at 4.7T. On first pass, the higher per ion relaxivity of the dendrimer resulted in 2-fold greater blood signal than for [Gd(DTPA)(H2O)]2−. Blood clearance was fast and elimination occurred through both the renal and hepatobiliary routes. This Mn(II) containing dendrimer represents potential alternative to Gd-based contrast agents, especially in patients with chronic kidney disease where the use of current Gd-based agents may be contraindicated.