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Introduction: The Prunella vulgaris L. (PVL) and Taraxacum mongolicum Hand.-Mazz. (TH) herb pair, which is commonly used in traditional Chinese medicine (TCM), has been applied for the treatment of breast cancer. Although its efficacy is validated, the synergistic anti-breast cancer compound combinations within this herb pair and their underlying mechanisms of action remain unclear. Methods: This study aimed to identify and validate synergistic anti-breast cancer compound combinations within the PVL-TH pair using large-scale biomedical data, artificial intelligence and experimental methods. The first step was to investigate the anti-breast cancer effects of various PVL and TH extracts using in vitro cellular assays to identify the most effective superior extracts. These superior extracts were subjected to liquid chromatography-mass spectrometry (LC-MS) analysis to identify their constituent compounds. A deep learning-based prediction model, DeepMDS, was applied to predict synergistic anti-breast cancer multi-compound combinations. These predicted combinations were experimentally validated for their anti-breast cancer effects at actual content ratios found in the extracts. Preliminary bioinformatics analyses were conducted to explore the mechanisms of action of these superior combinations. We also compared the anti-breast cancer effects of superior extracts from different geographical origins and analyzed the contents of compounds to assess their representation of the anti-tumor effect of the corresponding TCM. Results: The results revealed that LC-MS analysis identified 27 and 21 compounds in the superior extracts (50% ethanol extracts) of PVL and TH, respectively. Based on these compounds, DeepMDS model predicted synergistic anti-breast cancer compound combinations such as F973 (caffeic acid, rosmarinic acid, p-coumaric acid, and esculetin), T271 (chlorogenic acid, cichoric acid, and caffeic acid), and T1685 (chlorogenic acid, rosmarinic acid, and scopoletin) from single PVL, single TH and PVL-TH herb pair, respectively. These combinations, at their actual concentrations in extracts, demonstrated superior anti-breast cancer activity compared to the corresponding extracts. The bioinformatics analysis revealed that these compounds could regulate tumor-related pathways synergistically, inhibiting tumor cell growth, inducing cell apoptosis, and blocking cell cycle progression. Furthermore, the concentration ratio and total content of compounds in F973 and T271 were closely associated with their anti-breast cancer effects in extracts from various geographical origins. The compound combination T1685 could represent the synergistic anti-breast cancer effects of the PVL-TH pair. Discussion: This study provides insights into exploring the representative synergistic anti-breast cancer compound combinations within the complex TCM. [ABSTRACT FROM AUTHOR]

Background: The optimal definition and risk stratification approach to identify high-risk patients with prediabetes and stable coronary heart disease has not been well studied to date. The objective of the current study is to compare the prognostic value of different definitions of prediabetes, and to explore the role of "very-high-risk" (VHR) criteria according to the 2018 American Heart Association/American College of Cardiology cholesterol guideline in the risk stratification of patients with prediabetes and stable coronary heart disease., Methods and Results: This prospective large-cohort study enrolled a total of 7930 patients with stable coronary heart disease. Prediabetes was defined according to various guidelines and further classified on the basis of the VHR criteria according to the 2018 American Heart Association/American College of Cardiology guideline. The primary end point was major adverse cardiovascular events (MACEs), which was defined as the composite end point of cardiac death, nonfatal acute myocardial infarction, and stroke. During a median of 3 years' follow-up, a total of 256 MACEs occurred. Prediabetes defined according to the World Health Organization/International Expert Committee criteria was associated with significant increased MACE risk compared with normoglycemia (adjusted hazard ratio [HR], 1.484 [95% CI, 1.139-1.935]; P =0.0035). The VHR group was associated with increased MACE risk compared with the non-VHR group (adjusted HR, 1.783 [95% CI, 1.344-2.366], P <0.0001). The VHR criteria played an important role in risk stratification, and prediabetes combined with VHR criteria was associated with higher MACE risk regardless of the prediabetes definition., Conclusions: Our findings suggested the potential use of the World Health Organization/International Expert Committee definition and VHR criteria in risk stratification of patients with prediabetes and stable coronary heart disease.

Glycosphingolipids (GSL) are natural ligands of NKT cells. Several laboratories have reported the in vitro activity of isoglobotriosylceramide (iGb3) in stimulating NKT cells. However, the knockout mice of iGb3 synthase showed no deficiency in development and function of NKT cells. There is a lack of knowledge on the genetics of redundant natural glycosphingolipid ligands. We have identified additional glycosphingolipid with stimulatory activity to NKT cells, including fucosyl lactosylceramide (H antigen). Here we describe the procedures to generate mice with deficiencies in Fut1, Fut2, and Sec1 genes to deplete H antigen through BAC engineering for the generation of ES cell-targeting construct, as well as the mice with deficiency of both blood group H-GSL ligand and isoglobotriosylceramide., (© 2021. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

A simple and practical extraction method of supramolecular solvents (SUPRAS) was developed for separation and enrichment of trace amounts of palladium (Pd) and silver (Ag) in water samples prior to flame atomic absorption spectrometry (FAAS) analysis. The SUPRAS selected was made up of an aqueous solution containing tetrahydrofuran and nonanoic acid. Pd and Ag reacted with diethyldithiocarbamate to form hydrophobic chelates, which were extracted into the vesicles of SUPRAS. Different parameters such as the concentration of chelating agent, sample pH, supramolecular solvent and the effect of foreign ions were studied. Under the optimal conditions, the linear ranges of Pd and Ag were from 10 to 1,000 μg/L. The relative recoveries of Pd and Ag in tap and river water samples at the spiking level of 10 ug/mL ranged from 90.8 to 116%. The relative standard deviations were 3.6-4.0% (n = 9), the limits of detection were 2.8 and 1.9 μg/L and the enrichment factors were 36 and 18 for Pd and Ag, respectively. The quantification limits were 3.2 and 2.4 μg/L. The method was successfully applied to the determination of Pd and Ag in water samples.