Table_1_A Structure-Based B-cell Epitope Prediction Model Through Combing Local and Global Features.pdf

B-cell epitopes (BCEs) are a set of specific sites on the surface of an antigen that binds to an antibody produced by B-cell. The recognition of BCEs is a major challenge for drug design and vaccines development. Compared with experimental methods, computational approaches have strong potential for BCEs prediction at much lower cost. Moreover, most of the currently methods focus on using local information around target residue without taking the global information of the whole antigen sequence into consideration. We propose a novel deep leaning method through combing local features and global features for BCEs prediction. In our model, two parallel modules are built to extract local and global features from the antigen separately. For local features, we use Graph Convolutional Networks (GCNs) to capture information of spatial neighbors of a target residue. For global features, Attention-Based Bidirectional Long Short-Term Memory (Att-BLSTM) networks are applied to extract information from the whole antigen sequence. Then the local and global features are combined to predict BCEs. The experiments show that the proposed method achieves superior performance over the state-of-the-art BCEs prediction methods on benchmark datasets. Also, we compare the performance differences between data with or without global features. The experimental results show that global features play an important role in BCEs prediction. Our detailed case study on the BCEs prediction for SARS-Cov-2 receptor binding domain confirms that our method is effective for predicting and clustering true BCEs.</p

Virtual Screening with a Structure-Based Pharmacophore Model to Identify Small-Molecule Inhibitors of CARM1

CARM1 (coactivator-associated arginine methyltransferase 1), also known as PRMT4 (protein arginine N-methyltransferase 4), belongs to the protein arginine methyltransferase (PRMT) family, which has emerged as a potential anticancer drug target. To discover new CARM1 inhibitors, we performed virtual screening against the substrate-binding site in CARM1. Structure-based pharmacophore models, which were generated according to three druggable subpockets embedding critical residues for ligand binding, were applied for virtual screening. The importance of the solvent-exposed substrate-binding cavity was highlighted due to significant hydrophobicity. Aided by molecular docking, 15 compounds structurally distinct from known CARM1 inhibitors were selected to evaluate their inhibitory effects on CARM1 methyltransferase activity, which resulted in seven compounds exhibiting micromolar inhibition, with selectivity over other members in the PRMT protein family. Moreover, three of them exhibited potent antiproliferation activities in breast cancer cells. Particularly, compound NO.2 exhibited potent activity both in vitro and in cultured cells, which will serve as a leading hit for developing CARM1 inhibitors with improved efficacy. The virtual screening strategy in this study will be applicable for the discovery of substrate-competitive inhibitors targeting other members in the PRMT protein family

MOESM2 of Ginsenoside Rb1 can ameliorate the key inflammatory cytokines TNF-α and IL-6 in a cancer cachexia mouse model

Additional file 2. Certificate of Analysis

MOESM1 of Ginsenoside Rb1 can ameliorate the key inflammatory cytokines TNF-α and IL-6 in a cancer cachexia mouse model

Additional file 1. Quality control of water extract of ginseng (WEG)

Copper-Mediated C–H Amination of Imidazopyridines with <i>N</i>‑Fluorobenzenesulfonimide

A copper-mediated direct C3 amination of imidazopyridines has been disclosed under additive-free conditions in short reaction times. This methodology utilizes commercially available N-fluorobenzenesulfonimide (NFSI) as the amino source, which exhibits broad substrate scope and good functional group tolerance. The obtained C3-aminated imidazopyridines can undergo further desulfonylation transformations. Control experiments suggest that this reaction probably proceeds via a free-radical mechanism. Moreover, NFSI also shows potential application in C–H fluorination of imidazopyridines

Faecal microbiota transplantation is better than probiotics for tissue regeneration of type 2 diabetes mellitus injuries in mice

Western diet and unhealthy lifestyle have contributed to the continued growth of type 2 diabetes mellitus (T2DM). T2DM is associated with dysbacteriosis, and studies have found that altering the gut microbiota has a positive effect on treatment. In addition to hyperglycaemia, T2DM often causes damage to multiple organs. However, there are few studies on organ damage from faecal microbiota transplantation (FMT). T2DM mice were divided into four groups and were given phosphate buffered saline (PBS) (T2DM group), FMT (FMT group), Lactobacillus (LAB group), and Bifidobacterium (BIO group) by gavage for six weeks, respectively. Mice on a normal diet (control group) were gavaged with PBS for six weeks. After gavage treatment, FMT, LAB, and BIO groups were similar in lowering glucose, endotoxemia was slightly reduced, and the colonic mucus layer and liver lobules developed towards normal tissue. Surprisingly, we found that the FMT group had unique effects on islet cell regeneration, increased functional β cells, and insulin sensitivity. Lactobacillus has the best glucose-lowering effect, but FMT has obvious advantages in β-cell regeneration, which provides new treatment ideas for tissue damage caused by T2DM.</p

Copper-Mediated C–H Amination of Imidazopyridines with <i>N</i>‑Fluorobenzenesulfonimide

A copper-mediated direct C3 amination of imidazopyridines has been disclosed under additive-free conditions in short reaction times. This methodology utilizes commercially available N-fluorobenzenesulfonimide (NFSI) as the amino source, which exhibits broad substrate scope and good functional group tolerance. The obtained C3-aminated imidazopyridines can undergo further desulfonylation transformations. Control experiments suggest that this reaction probably proceeds via a free-radical mechanism. Moreover, NFSI also shows potential application in C–H fluorination of imidazopyridines

Data_Sheet_1_Improved Prediction of Aqueous Solubility of Novel Compounds by Going Deeper With Deep Learning.ZIP

Aqueous solubility is an important physicochemical property of compounds in anti-cancer drug discovery. Artificial intelligence solubility prediction tools have scored impressive performances by employing regression, machine learning, and deep learning methods. The reported performances vary significantly partly because of the different datasets used. Solubility prediction on novel compounds needs to be improved, which may be achieved by going deeper with deep learning. We constructed deeper-net models of ~20-layer modified ResNet convolutional neural network architecture, which were trained and tested with 9,943 compounds encoded by molecular fingerprints. Retrospectively tested by 62 recently-published novel compounds, one deeper-net model outperformed four established tools, shallow-net models, and four human experts. Deeper-net models also outperformed others in predicting the solubility values of a series of novel compounds newly-synthesized for anti-cancer drug discovery. Solubility prediction may be improved by going deeper with deep learning. Our deeper-net models are accessible at http://www.npbdb.net/solubility/index.jsp.</p

Copper-Catalyzed Double Thiolation To Access Sulfur-Bridged Imidazopyridines with Isothiocyanate

A copper­(I)-catalyzed sulfur-bridged dimerization of imidazopyridines has been developed using isothiocyanate as the sulfur source. This method enables a switchable synthesis of bis­(imidazo­[1,2-a]­pyridin-3-yl)­sulfanes or bis­(2-(imidazo­[1,2-a]­pyridin-2-yl)­phenyl)­sulfanes in the presence of 4-dimethylaminopyridine (DMAP) or K2CO3 when different imidazopyridines were employed. Under optimized conditions, a variety of sulfur-bridged imidazopyridines were obtained in good yields. Moreover, thiourea was proved to be the key intermediate under catalytic system A

Copper-Catalyzed Double Thiolation To Access Sulfur-Bridged Imidazopyridines with Isothiocyanate

A copper­(I)-catalyzed sulfur-bridged dimerization of imidazopyridines has been developed using isothiocyanate as the sulfur source. This method enables a switchable synthesis of bis­(imidazo­[1,2-a]­pyridin-3-yl)­sulfanes or bis­(2-(imidazo­[1,2-a]­pyridin-2-yl)­phenyl)­sulfanes in the presence of 4-dimethylaminopyridine (DMAP) or K2CO3 when different imidazopyridines were employed. Under optimized conditions, a variety of sulfur-bridged imidazopyridines were obtained in good yields. Moreover, thiourea was proved to be the key intermediate under catalytic system A