Fast Metabolic Glycan Labeling for Click-Labeling and Imaging of Sialoglycans in Living Acute Brain Slices from Mice and Human Patients.

Living acute brain slices provide a practical platform for imaging sialylation in human brain pathology. However, the limited lifespan of acute brain slices has impeded the use of metabolic glycan labeling (MGL), which requires long-term incubation of clickable unnatural sugars such as N-azidoacetylmannosamine (ManNAz) to metabolically incorporate azides into sialoglycans. Here, we report a fast variant of MGL (fMGL), in which ManNAz-6-phosphate enables efficient azidosugar incorporation within 12 h by bypassing the bottleneck step in the sialic acid biosynthesis pathway, followed by click-labeling with fluorophores and imaging of sialoglycans in acute brain slices from mice and human patients. In the clinical samples of ganglioglioma, fMGL-based imaging reveals specific upregulation of sialylation in astrocyte-like but not neuron-like tumor cells. In addition, fMGL is integrated with click-expansion microscopy for high-resolution imaging of sialoglycans in brain slices. The fMGL strategy should find broad applications in the tissue imaging of glycans and surgical pathology.

Covalent versus Noncovalent Binding of Ruthenium η6 -p-Cymene Complexes to Zinc-Finger Protein NCp7.

Ruthenium-arene complexes are a unique class of organometallic compounds that have been shown to have prominent therapeutic potencies. Here, we have investigated the interactions of Ru-cymene complexes with a zinc-finger protein NCp7, aiming to understand the effects of various ligands on the reaction. Five different binding modes were observed on selected Ru-complexes. Ru-cymene complex can bind to proteins through either noncovalent binding alone or through a combination of covalent and noncovalent binding modes. Moreover, the noncovalent interaction can promote the coordination of RuII to NCp7, resulting synergistic effects of the different ligands. The binding of Ru(Cym) complexes leads to dysfunction of NCp7 through zinc-ejection and structural perturbation. These results indicate that the reactivity of Ru-complexes can be modulated by ligands through different approaches, which could be closely correlated to their different therapeutic effects.

Blood lead level and its association with body mass index and obesity in China - Results from SPECT-China study.

UNLABELLED: We aimed to report environmental and blood lead level (BLL) in China, and investigate the relationship of BLL with body mass index (BMI) and obesity. 5558 subjects were enrolled from 16 sites in China. BLL was measured by atomic absorption spectrometry. Obesity was defined as BMI ≥ 30 kg/m(2). Median (interquartile range) of BLL was 44.00 µg/L (29.00-62.16) for men and 37.79 µg/L (25.13-54.35) for women, about twice higher than in U.S. POPULATION: Subjects in rural and high-economic-status areas had significantly greater BLL (P < 0.001). However, in these areas, the lead levels in drinking water, river water and rice were comparable to or significantly lower than those in urban and low-economic-status areas. After adjustment for age, urbanization, economic status and metabolic factors, BLL was independently associated with BMI in women (P for trend < 0.001), but not in men. In fully adjusted model, increased quartiles of BLL were associated with significantly increased odds ratios of obesity (P for trend < 0.01) in women. In conclusion, BLLs in Chinese adults were much higher than in developed countries. There was a sex-specific association between BLL and BMI. Elevated BLL does not appear to be associated with lead levels in drinking water or rice, suggesting some other exposure source.