Identifying potential Q-markers for quality evaluation of Zhenyuan capsule by integrating chemical analysis, network pharmacology, molecular docking, and molecular dynamics simulations.

Quality markers (Q-markers) are of great significance for quality evaluation of herbal medicines. Zhenyuan Capsule (ZYC) is a kind of Chinese patent medicine used to treat cardiovascular diseases. However, reliable and effective Q-markers for ZYC are still lacking. Herein, a UHPLC-Q/Orbitrap-MS/MS was performed to characterise the preliminary chemical profile of ZYC. A total of 86 components were characterised among which 20 constituents were unambiguously identified by reference compounds. Based on network pharmacology, seven major ginsenosides with great importance in the network were identified as Q-markers among which ginsenoside Re with the highest betweenness was screened to inhibit the development of coronary heart disease (CHD) by binding with vascular endothelial growth factor A (VEGFA). Docking and molecular dynamics simulation studies suggested that ginsenoside Re stably bound to VEGFA. Quantitative determination and chemical fingerprinting analysis were performed using HPLC-DAD. The results showed that ginsenosides screened might function as potential Q-markers for ZYC.

Polyamine pathways interconnect with GABA metabolic processes to mediate the low-temperature response in plants.

Low temperatures are among the most commonly encountered environmental conditions that adversely affect plant growth and development, leading to substantial reductions in crop productivity. Plants have accordingly evolved coordinated mechanisms that confer low-temperature adaptation and resistance. The plant metabolic network, including polyamines (PAs) and γ-aminobutyric acid (GABA) is reprogrammed to ensure that essential metabolic homeostasis is maintained in response to cold stress conditions. Additionally, GABA might serve as a central molecule in the defense system during low-temperature tolerance in plants. However, our understanding of how these metabolites function in conferring cold tolerance is still far from complete. Here, we summarized how PAs and GABA function in conferring cold tolerance, and describe the crucial role of GABA in the mitigation of ROS during cold stress in plants.

Soulieoside U, a new cycloartane triterpene glycoside from Actaea vaginata.

One new cycloartane triterpene bisdesmoside, soulieoside U, was isolated from the rhizomes of Actaea vaginata. Its structure was elucidated by extensive analysis of the NMR and MS data. Soulieoside U was evaluated for cytotoxic activities against three human cancer cell lines.

A clinical prediction model for predicting the risk of liver metastasis from renal cell carcinoma based on machine learning.

Background: Renal cell carcinoma (RCC) is a highly metastatic urological cancer. RCC with liver metastasis (LM) carries a dismal prognosis. The objective of this study is to develop a machine learning (ML) model that predicts the risk of RCC with LM, which is used to assist clinical treatment. Methods: The retrospective study data of 42,547 patients with RCC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. ML includes algorithmic methods and is a fast-rising field that has been widely used in the biomedical field. Logistic regression (LR), Gradient Boosting Machine (GBM), Extreme Gradient Boosting (XGB), random forest (RF), decision tree (DT), and naive Bayesian model [Naive Bayes Classifier (NBC)] were applied to develop prediction models to predict the risk of RCC with LM. The six models were 10-fold cross-validated, and the best-performing model was selected based on the area under the curve (AUC) value. A web online calculator was constructed based on the best ML model. Results: Bone metastasis, lung metastasis, grade, T stage, N stage, and tumor size were independent risk factors for the development of RCC with LM by multivariate regression analysis. In addition, the correlation of the relative proportions of the six clinical variables was shown by a heat map. In the prediction models of RCC with LM, the mean AUC of the XGB model among the six ML algorithms was 0.947. Based on the XGB model, the web calculator (https://share.streamlit.io/liuwencai4/renal_liver/main/renal_liver.py) was developed to evaluate the risk of RCC with LM. Conclusions: This XGB model has the best predictive effect on RCC with LM. The web calculator constructed based on the XGB model has great potential for clinicians to make clinical decisions and improve the prognosis of RCC patients with LM.

A new cycloartane triterpene bisdesmoside from the rhizomes of Actaea vaginata.

A new cycloartane triterpene bisdesmoside, soulieoside T (1), and one known compound, oleanolic acid (2), were isolated from the ethanolic extract of the rhizomes of Actaea vaginata. Their structures were elucidated by spectroscopic methods and by comparison with data reported in the literature. Compound 1 was evaluated for cytotoxic activities against three human cancer cell lines.

Case Report: Abomasum Impaction in Beef Cattle Due to High Intake of Distillers' Grain and Treatment Options in Southwest China.

In Southern China, distillers' grain is the main feed ingredient for small beef cattle farms. High intake of distillers' grain may lead to abomasum impaction, a disorder caused by the accumulation of solid content within the organ. For treatment, there are non-surgical and surgical options. In this study, we aimed to describe the clinical presentation, diagnosis, and treatment of beef cattle with abomasum impaction due to high intake of distillers' grain. Forty-nine Simmental beef cattle from 13 farms in Chongqing, China, were diagnosed with abomasum impaction. Animals were male, aged ≤2 years, and weighed between 200 and 350 kg. In this retrospective study, information on distillers' grain intake and clinical data were collected for 49 beef cattle diagnosed with abomasum impaction. The animals were treated between 2011 and 2019 with either non-surgical therapy or surgery. Animals diagnosed with mild abomasum impaction (n = 14) fully recovered after non-surgical treatment. Among moderate cases (n = 19), 12 cattle recovered after non-surgical treatment (63%), while the remaining seven did not respond well and underwent surgery. Three of those animals were subsequently cured (3/7). Among the severe cases (n = 16), four cattle were cured after non-surgical treatment (25%) (4/16). Of the remaining 12 cattle, six were slaughtered, and six died after surgery. Non-surgical treatment is efficient for mild abomasum impaction caused by a high intake of distillers' grain and may be considered for both moderate and severe cases. However, the treatment success rate for more severe cases decreases as the disease severity worsens.

Discovery and synthesis of novel beesioside I derivatives with potent anti-HIV activity.

In this study, 12 known cycloartane triterpenoids (1-12) with four different skeletons isolated from the roots of Souliea vaginata were screened for the first time for in vitro anti-HIV activity using AZT as a standard. Among the compounds, beesioside I (1) showed the highest potency against HIV-1NL4-3 with an EC50 value of 2.32 µM (CC50 > 40 µM). Preliminary structure-activity relationship (SAR) studies on 1 indicated that simple modification of its aglycone (13) could significantly influence the antiviral activity. Particularly, the introduction of an acyl group at the C-3 position of 13 led to significant improvement in both anti-HIV potency and selectivity index. Among all synthetically modified derivatives, compound 13g was the most potent compound with an EC50 value of 0.025 µM and TI value greater than 800, comparable to those of 3-O-(3',3'-dimethylsuccinyl)-betulinic acid (DSB, bevirimat). Other analogues exhibited strong to weak inhibition of HIV-1 replication in MT-4 cells. The length, carboxylic terminus, and C-3' dimethyl substitution of the C-3 side chain substantially affected the anti-HIV activity. Finally, compound 13g was an effective agent against HIV with high potential for further investigation.