Pharmacokinetics and pharmacodynamics of a novel Acetylcholinesterase Inhibitor, DMNG-3

DMNG-3 (3β-Methyl-[2-(4-nitrophenoxy)ethyl]-amino]con-5-enine), is a new and the potentially most potent acetylcholinesterase inhibitor recently obtained from conessine by N-demethylation and nucleophilic substitution reaction. In the present study, a step‑down passive avoidance test was used to investigate whether DMNG-3 could modulate impairment of learning and memory induced by scopolamine, and a high performance liquid chromatography (HPLC) method for the determination of DMNG-3 in biological samples was applied to study its pharmacokinetics and tissues distribution. Separation was achieved on C18 column using a mobile phase consisting methanol‑water (70:30, v/v) at a flow rate of 1.0 ml/min. The intra- and inter-day precisions were good and the RSD was all lower than 1.30%. The mean absolute recovery of DMNG-3 in plasma ranged from 88.55 to 96.45%. Our results showed oral administration of DMNG-3 (10, 25, 50 mg/kg/day) can significantly improve the latency and number of errors and had a positive effect of improvement of learning and memory in mice in passive avoidance tests. The elimination half-life (T1/2) was 14.07±1.29, 15.87±1.03 h, and the total clearance (CL) values were 0.70±0.11, 0.78±0.13 L/h/kg, respectively. The pharmacokinetic studies showed that DMNG-3 has a slowly clearance and large distribution volume in experimental animals, and its disposition is linear over the range of doses tested. The liver, small intestine, stomach, and large intestine were the major distribution tissues of DMNG-3 in mice. It was found that DMNG-3 could be detected in brain, suggesting that DMNG-3 can cross the blood-brain barrier. The present study shows that DMNG-3 can be possible developed as a new drug for the treatment of Alzheimer's disease in the future

Assessing the concentration and potential health risk of heavy metals in China's main deciduous fruits

AbstractTo assess levels of contamination and human health risk, we analyzed the concentrations of the heavy metals lead (Pb), cadmium (Cd), chromium (Cr), and nickel (Ni) in China's main deciduous fruits — apple, pear, peach, grape, and jujube. The concentration order of the heavy metals was Ni>Cr>Pb>Cd. In 97.5% of the samples, heavy metal concentrations were within the maximum permissible limits. Among the fruits studied, the heavy metal concentrations in jujube and peach proved to be the highest, and those in grape proved to be the lowest. Only 2.2% of the samples were polluted by Ni, only 0.4% of the samples were polluted by Pb, and no samples were polluted by Cd or Cr. Compared with the other fruits, the combined heavy metal pollution was significantly higher (P<0.05) in peach and significantly lower (P<0.05) in grape. For the combined heavy metal pollution, 96.9% of the samples were at safe level, 2.32% at warning level, 0.65% at light level, and 0.13% at moderate level. In the fruits studied, the contribution of heavy metals to the daily intake rates (DIR) followed the order of Ni>Cr>Pb>Cd. The highest DIR came from apple, while the lowest DIR came from grape. For each of the heavy metals, the total DIR from five studied fruits corresponded to no more than 1.1% of the tolerable daily intake, indicating that no significant adverse health effects are expected from the heavy metals and the fruits studied. The target hazard quotients and the total target hazard quotients demonstrated that none of the analyzed heavy metals may pose risk to consumers through the fruits studied. The highest risk was posed by apple, followed in decreasing order by peach and pear, jujube, and grape. We suggest that the main deciduous fruits (apple, pear, peach, grape, and jujube) of China's main producing areas are safe to eat

Using a new fish indicator-based index with scoring and evaluation criteria to assess the ecological status in a disturbed subtropical river of China

Rivers are constantly disturbed by anthropogenic stressors. Developing robust biotic indicators to assess river environments across large spatial scales is important. In the subtropical Liuxi River of China, 34 native fish indicators, including 4 genera and 30 species, were selected from 108 fish species by linear discriminant analysis. These indicators were grouped into 19 ecological items and assigned evaluation scores according to the roles they played in the food web (e.g., keystoneness and trophic level) and their positive feedback on the environment (e.g., requirements for feeding, spawning/nursing, and migrating). Three formulae for calculating the index of fish indicators (IFI) were developed based on the scoring of each indicator and weighted by relative abundance (individual number, i.e., IFIN) and relative biomass (wet weight, i.e., IFIB). Spearman correlation analysis showed that IFIB, which had positive (P&lt; 0.05) correlations with elevation (m), dissolved oxygen (mg/L), flow velocity (cm/s), Shannon-Wiener diversity, benthic index of biotic integrity, exhibited a more powerful explanation of biodiversity and environmental factors than IFIN and unweighted IFI. Therefore, IFIB was most suitable for constructing a scoring system to evaluate ecological status (e.g., water and habitat quality). These results suggested that fish indicator-based scoring and evaluation system was effectively in not only assessing the site- or region-specific ecological status bot also reflecting the fluvial biodiversity and food web integrity. Further application and promotion of this indicator-based evaluation method may improve field investigation efficiency and contribute greatly to the conservation and management of river ecosystems

Cell transcriptomic atlas of the non-human primate Macaca fascicularis.

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.We thank W. Liu and L. Xu from the Huazhen Laboratory Animal Breeding Centre for helping in the collection of monkey tissues, D. Zhu and H. Li from the Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) for technical help, G. Guo and H. Sun from Zhejiang University for providing HCL and MCA gene expression data matrices, G. Dong and C. Liu from BGI Research, and X. Zhang, P. Li and C. Qi from the Guangzhou Institutes of Biomedicine and Health for experimental advice or providing reagents. This work was supported by the Shenzhen Basic Research Project for Excellent Young Scholars (RCYX20200714114644191), Shenzhen Key Laboratory of Single-Cell Omics (ZDSYS20190902093613831), Shenzhen Bay Laboratory (SZBL2019062801012) and Guangdong Provincial Key Laboratory of Genome Read and Write (2017B030301011). In addition, L.L. was supported by the National Natural Science Foundation of China (31900466), Y. Hou was supported by the Natural Science Foundation of Guangdong Province (2018A030313379) and M.A.E. was supported by a Changbai Mountain Scholar award (419020201252), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16030502), a Chinese Academy of Sciences–Japan Society for the Promotion of Science joint research project (GJHZ2093), the National Natural Science Foundation of China (92068106, U20A2015) and the Guangdong Basic and Applied Basic Research Foundation (2021B1515120075). M.L. was supported by the National Key Research and Development Program of China (2021YFC2600200).S