[Medicinal laws and application examples of traditional Chinese medicine prescriptions for multiple aorto-arteritis].

To collect the literature on traditional Chinese medicine treatment for multiple aorto-arteritis from China National Knowledge Infrastructure(CNKI), establish prescriptions database after screening and normalizing the prescriptions reported in these literature, and analyze their medicinal rules by using traditional Chinese medicine inheritance support system. A total of 126 prescriptions for multiple aorto-arteritis were screened, containing 212 kinds of Chinese herbs. 26 core herb combinations were obtained by analysis of the commonly used herbs and their use frequencies. The treatment for multiple aorto-arteritis was manly of tonifying qi to nourish blood, promoting blood circulation to remove blood stasis, warming yang to dredge collaterals, and four new prescriptions were obtained. On this basis, two clinical cases were taken as the examples by analyzing the medicinal rules and the features of multiple aorto-arteritis. The first case showed that the herb combination of this study conformed to the basic core drug application mode and the core pathogenesis of multiple aorto-arteritis. The second case reflected the characteristics of the new prescriptions' herb combinations based on entropy hierarchical clustering. The practical analysis of the two clinical cases further indicated the reliability of the results. This study has certain guiding significance and reference value on new medicine research and development as well as clinical traditional Chinese medicine treatment for multiple aorto-arteritis.

Single-Cell Transcriptome Analysis Identified Core Genes and Transcription Factors in Mesenchymal Cell Differentiation during Liver Cirrhosis.

BACKGROUND: Mesenchymal cells, including hepatic stellate cells (HSCs), fibroblasts (FBs), myofibroblasts (MFBs), and vascular smooth muscle cells (VSMCs), are the main cells that affect liver fibrosis and play crucial roles in maintaining tissue homeostasis. The dynamic evolution of mesenchymal cells is very important but remains to be explored for researching the reversible mechanism of hepatic fibrosis and its evolution mechanism of hepatic fibrosis to cirrhosis. METHODS: Here, we analysed the transcriptomes of more than 50,000 human single cells from three cirrhotic and three healthy liver tissue samples and the mouse hepatic mesenchymal cells of two healthy and two fibrotic livers to reconstruct the evolutionary trajectory of hepatic mesenchymal cells from a healthy to a cirrhotic state, and a subsequent integrative analysis of bulk RNA sequencing (RNA-seq) data of HSCs from quiescent to active (using transforming growth factor ß1 (TGF-ß1) to stimulate LX-2) to inactive states. RESULTS: We identified core genes and transcription factors (TFs) involved in mesenchymal cell differentiation. In healthy human and mouse livers, the expression of NR1H4 and members of the ZEB families (ZEB1 and ZEB2) changed significantly with the differentiation of FB into HSC and VSMC. In cirrhotic human livers, VSMCs transformed into HSCs with downregulation of MYH11, ACTA2, and JUNB and upregulation of PDGFRB, RGS5, IGFBP5, CD36, A2M, SOX5, and MEF2C. Following HSCs differentiation into MFBs with the upregulation of COL1A1, TIMP1, and NR1H4, a small number of MFBs reverted to inactivated HSCs (iHSCs). The differentiation trajectory of mouse hepatic mesenchymal cells was similar to that in humans; however, the evolution trajectory and proportion of cell subpopulations that reverted from MFBs to iHSCs suggest that the mouse model may not accurately reflect disease progression and outcome in humans. CONCLUSIONS: Our analysis elucidates primary genes and TFs involved in mesenchymal cell differentiation during liver fibrosis using scRNA-seq data, and demonstrated the core genes and TFs in process of HSC activation to MFB and MFB reversal to iHSC using bulk RNA-seq data of human fibrosis induced by TGF-ß1. Furthermore, our findings suggest promising targets for the treatment of liver fibrosis and provide valuable insights into the molecular mechanisms underlying its onset and progression.

2-Substituted N-aryl piperazines as novel triple reuptake inhibitors for the treatment of depression.

Recently a class of compounds known as triple reuptake inhibitors has emerged as a new strategy for the treatment of depression. These compounds work by simultaneously inhibiting the synaptic reuptake of serotonin, norepinephrine and dopamine. In this Letter we describe the optimization of a novel series of 2-substituted N-aryl piperazine based triple reuptake inhibitors.

Design, synthesis, and biological evaluation of new monoamine reuptake inhibitors with potential therapeutic utility in depression and pain.

Two new series of monoamine triple reuptake inhibitors (TRIs) have been discovered through scaffold homologation of our recently reported series of 3,3-disubstituted pyrrolidine TRIs. The regioisomeric 2- and 3-ketopyrrolidines demonstrated high levels of potency against all three monoamine transporters as well as good human in vitro stability, low drug-drug interaction potential and a decreased propensity for hERG channel binding. Representative compounds from these series displayed good in vivo pharmacokinetics and high monoamine receptor occupancies which are indicators of good brain penetration.

Retraction Note to: Effects of dietary glycerol monolaurate on productive performance, egg quality, serum biochemical indices, and intestinal morphology of laying hens.

Retraction Note to: J Zhejiang Univ-Sci B (Biomed & Biotechnol) 2019 20(11):877-890. https://doi.org/10.1631/jzus.B1800530. The authors have retracted this article (Zhao et al., 2019) due to significant overlap with a previously published Chinese language article (Liu et al., 2017), including overlap in Table 1, Table 2, Table 3, Table 6, Fig. 4, and part of the results (Sections 3.1, 3.2, 3.5, and 3.7). All authors agree with this retraction.

Novel, achiral aminoheterocycles as selective monoamine reuptake inhibitors.

A variety of novel aminoheterocycle scaffolds as selective monoamine reuptake inhibitors have been prepared and one of these scaffolds is achiral. The main elements responsible for hERG channel, CYP2D6 and CYP3A4 inhibition were identified.

Effects of dietary glycerol monolaurate on productive performance, egg quality, serum biochemical indices, and intestinal morphology of laying hens.

Glycerol monolaurate (GML) has been widely used as an effective antibacterial emulsifier in the food industry. A total of 360 44-week-old Hy-Line brown laying hens were randomly distributed into four groups each with six replicates of 15 birds, and fed with corn-soybean-meal-based diets supplemented with 0, 0.15, 0.30, and 0.45 g/kg GML, respectively. Our results showed that 0.15, 0.30, and 0.45 g/kg GML treatments significantly decreased feed conversion ratios (FCRs) by 2.65%, 7.08%, and 3.54%, respectively, and significantly increased the laying rates and average egg weights. For egg quality, GML drastically increased albumen height and Haugh units, and enhanced yolk color. Notably, GML increased the concentrations of polyunsaturated and monounsaturated fatty acids and reduced the concentration of total saturated fatty acids in the yolk. The albumen composition was also significantly modified, with an increase of 1.02% in total protein content, and increased contents of His (4.55%) and Glu (2.02%) under the 0.30 g/kg GML treatment. Additionally, GML treatments had positive effects on the lipid metabolism of laying hens, including lowering the serum triglyceride and total cholesterol levels and reducing fat deposition in abdominal adipose tissue. Intestinal morphology was also improved by GML treatment, with increased villus length and villus height to crypt depth ratio. Our data demonstrated that GML supplementation of laying hens could have beneficial effects on both their productivity and physiological properties, which indicates the potential application of GML as a functional feed additive and gives us a new insight into this traditional food additive.

Novel 3,3-disubstituted pyrrolidines as selective triple serotonin/norepinephrine/dopamine reuptake inhibitors.

A series of 3,3-disubstituted pyrrolidine monoamine triple reuptake inhibitors were discovered. Analogues with low nanomolar potency, good human in vitro microsomal stability and in vitro permeability, and low drug-drug interaction potential are described. One example showed in vivo anti-depressant-like effects in the mouse tail suspension assay with a minimum effective dose of 30 mg/kg i.p.