Colorimetric signaling of Hg ions by a nitrobenzoxadiazole-appended cyclen-triester

A novel Hg²⁺-selective colorimetric sensor based on a cyclen–nitrobenzoxadiazole (NBD) conjugate was investigated. A cyclen derivative with three ester ligands was used as the binding site and the NBD moiety acted as the reporting chromogenic subunit. Interaction of 1 with Hg²⁺ ions resulted in a pronounced color change from pink to yellow, and fluorescence signaling was also possible. Selective colorimetric signaling of Hg²⁺ ions by NBD-functionalized cyclen with a detection limit of 1.5 × 10⁻⁶ M in aqueous environments was successfully achieved.     

Inhibition of phospholipase D2 induces autophagy in colorectal cancer cells

Autophagy is a conserved lysosomal self-digestion process used for the breakdown of long-lived proteins and damaged organelles, and it is associated with a number of pathological processes, including cancer. Phospholipase D (PLD) isozymes are dysregulated in various cancers. Recently, we reported that PLD1 is a new regulator of autophagy and is a potential target for cancer therapy. Here, we investigated whether PLD2 is involved in the regulation of autophagy. A PLD2-specific inhibitor and siRNA directed against PLD2 were used to treat HT29 and HCT116 colorectal cancer cells, and both inhibition and genetic knockdown of PLD2 in these cells significantly induced autophagy, as demonstrated by the visualization of light chain 3 (LC3) puncta and autophagic vacuoles as well as by determining the LC3-II protein level. Furthermore, PLD2 inhibition promoted autophagic flux via the canonical Atg5-, Atg7- and AMPK-Ulk1-mediated pathways. Taken together, these results suggest that PLD2 might have a role in autophagy and that its inhibition might provide a new therapeutic basis for targeting autophagy.     

Understanding the congener-specific toxicity in polychlorinated dibenzo-p-dioxins: chlorination pattern and molecular quadrupole moment.

It is well known that the biological activities and toxicities of planar polychlorinated aromatic compounds are extremely sensitive to chlorination pattern. Although their toxic responses have been correlated with the relative affinity for the receptor, the origin of this congener specificity is not well understood. We present a general interpretation of the congener-specific activity in polychlorinated dibenzo-p-dioxins, which concludes that molecular electrostatics is the principal factor determining the structure-activity relationship in this highly controversial environmental pollutant even though this electrostatic interaction represents only a part of the total interaction energy. Through calculations of the molecular charge distribution in the complete set of 76 dioxin congeners, we show that all active congeners share a unique charge distribution pattern, which is quantitatively described in terms of the molecular quadrupole moment (QM). The QM of dioxins changes sensitively and systematically with chlorination pattern. The three-dimensional electrostatic interactions at the receptor-binding site, which are optimized at a specific QM pattern represented by that of 2,3,7,8-tetrachlorodibenzo-p-dioxin, could explain the congener specificity in the binding affinity and toxicity. Although the polarizability also changes systematically with chlorination, it can only account for the effect of the degree of chlorination, not the congener specificity.     

Regional Absolute Quantification of the Neurochemical Profile of the Canine Brain: Investigation by Proton Nuclear Magnetic Resonance Spectroscopy and Tissue Extraction

The purpose of this study was to characterize the neurochemical profiles of various parts of the canine brain using proton nuclear magnetic resonance spectroscopy, tissue extraction, and external simulated phantom concentration quantification. The occipital, frontal, and temporal lobes, thalami, cerebellar cortices, and spinal cords of five pure bred adult beagles were collected, and heavy water solutions for the nuclear magnetic resonance sample were prepared using the methanol–chloroform–water extraction method. The metabolite concentrations in canine brain tissues were measured and compared with those found in human and rat brain tissues. In addition, the cross peaks of Lac, Glu/Gln, and mIns were identified using two-dimensional correlation spectroscopy in the canine frontal cortex. The present study demonstrated the absolute quantification of canine neuronal parts using in vitro high-resolution magnetic resonance spectroscopy, with tissue extraction used to accurately measure metabolite concentrations, thus providing valuable metabolic information regarding the various canine neuronal regions.     

Precise determination of lithium isotopes in seawater using MC-ICP-MS

Li (lithium) isotope analysis using MC-ICP-MS is a very powerful tracer measurement method. This is widely used for identification of Li isotopes in many fields of study. This useful method, however, has an effect on the natural Li isotope background. This is impacted by the instrument matrix. In this study, we show that the MC-ICP-MS condition is characterized by both a low baseline background and a high-sensitivity distance at Ar plasma condition. In addition, the Li isotope ratio was measured by the use of experimental conditions that were superior to both the general plasma condition and those used in other studies. The samples were subjected to both acid leaching and a cation exchange resin (Bio-Rad AG 50 W-X8 200–400 mesh) modified for seawater samples. The isotope variations were corrected using the bracket method, the measured Li isotope ratio of sample, and the mean ratios of the L-SVEC standard (NIST L-SVEC Li₂CO₃) measured before and after the sample run. The isotope variation was presented as the deviation (per mil) of the measured ratio from that of the recommended value.