Three metabotropic glutamate receptor subtype 5 (mGluR5) PET tracers have been labeled with either carbon-11 or fluorine-18 and their in vitro and in vivo behavior in rhesus monkey has been characterized. Each of these tracers share the common features of high affinity for mGluR5 (0.08-0.23 nM vs. rat mGluR5) and moderate lipophilicity (log P 2.8-3.4). Compound 1b was synthesized using a Suzuki or Stille coupling reaction with [11C]MeI. Compounds 2b and 3b were synthesized by a SNAr reaction using a 3-chlorobenzonitrile precursor. Autoradiographic studies in rhesus monkey brain slices using 2b and 3b showed specific binding in cortex, caudate, putamen, amygdala, hippocampus, most thalamic nuclei, and lower binding in the cerebellum. PET imaging studies in monkey showed that all three tracers readily enter the brain and provide an mGluR5-specific signal in all gray matter regions, including the cerebellum. The specific signal observed in the cerebellum was confirmed by the autoradiographic studies and saturation binding experiments that showed tracer binding in the cerebellum of rhesus monkeys. In vitro metabolism studies using the unlabeled compounds showed that 1a, 2a, and 3a are metabolized slower by human liver microsomes than by monkey liver microsomes. In vivo metabolism studies showed 3b to be long-lived in rhesus plasma with only one other more polar metabolite observed.

Oil-in-water nanoemulsions stabilized by food-grade biopolymer emulsifiers (modified starches) were fabricated using high-pressure homogenization in an effort to improve the stability and bioaccessibility of β-carotene. Physicochemical and biological properties of β-carotene nanoemulsions were investigated considering the particle size, β-carotene retention, and in vitro digestion. During 30 days of storage at different conditions, the mean diameters of the emulsion systems were increased by 30-85%. The retention of β-carotene in nanoemulsions was significantly higher compared to that of the β-carotene dispersed in bulk oil. After in vitro digestion, the bioaccessibility of β-carotene was increased from 3.1% to 35.6% through nanoencapsulation. The results also indicated that modified starch with high dispersed molecular density led to a higher retention but lower bioaccessibility of β-carotene in nanoemulsions. This could be due to the thick and dense interfacial layer around the oil droplets. This result provides useful information for developing protection and delivery systems for carotenoids.

BackgroundThe Oxford classification of IgA nephropathy (IgAN) provides a useful tool for prediction of renal prognosis. However, the application of this classification in children with IgAN needs validation in different patient populations.MethodsA total of 218 children with IgAN from 7 renal centers in China were enrolled. The inclusion criteria was similar to the original Oxford study.ResultsThere were 98 patients (45%) with mesangial proliferation (M1), 51 patients (23%) with endocapillary proliferation (E1), 136 patients (62%) with segmental sclerosis/adhesion lesion (S1), 13 patients (6%) with moderate tubulointerstitial fibrosis (T1 26-50% of cortex scarred), and only 2 patients (1%) with severe tubulointerstitial fibrosis (T2, >50% of cortex scarred). During a median follow-up duration of 56 months, 24 children (12.4%) developed ESRD or 50% decline in renal function. In univariate COX analysis, we found that tubular atrophy/interstitial fibrosis (HR 4.3, 95%CI 1.8-10.5, P < 0.001) and segmental glomerulosclerosis (HR 9.2 1.2-68.6, P = 0.03) were significant predictors of renal outcome. However, mesangial hypercellularity, endocapillary proliferation, crescents, and necrosis were not associated with renal prognosis. In the multivariate COX regression model, none of these pathologic lesions were shown to be independent risk factors of unfavorable renal outcome except for tubular atrophy/interstitial fibrosis (HR 2.9, 95%CI 1.0-7.9 P = 0.04).ConclusionsWe confirmed tubular atrophy/interstitial fibrosis was the only feature independently associated with renal outcomes in Chinese children with IgAN.

A series of deep eutectic solvents (DESs), consisting of protic ionic liquids (PILs) and amines, feature effective catalytic activity for the fixation of CO 2 to cyclic carbonates at ambient temperature and pressure without any solvents and additives. Good yields of cyclic carbonates are achieved (up to 99%), and no obvious deactivation in catalytic activity is found after five cycles. Mechanistic research reveals that CO 2 and epoxides are activated simultaneously through the synergistic catalysis of PILs and amines.

The aim of the present study was to investigate the effects of oil-in-water (O/W) nanoemulsions combined with six different natural antioxidants on the stability of citral. Acidic emulsions (lecithin-stabilized palm kernel lipid in pH 3 buffer) containing 1000 ppm citral and 1000 ppm antioxidants (black tea extract, ascorbic acid, naringenin, tangeretin, β-carotene, and tanshinone) were stored at 25 and 50 °C, respectively. The emulsions with and without antioxidants were analyzed by solid phase microextraction gas chromatography (SPME-GC) to monitor the degradation process of citral and the formation of different off-flavor compounds, such as α,p-dimethylstyrene and p-methylacetophenone. The results suggested that encapsulation of citral in emulsions and the addition of the appropriate antioxidants (β-carotene, tanshinone, and black tea extract) could greatly enhance citral's chemical stability during storage.