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Protein O-GlcNAcylation is involved in regulating gene expression and maintaining cellular homeostasis. Here, the authors develop a chemical reporter-based strategy for the proteomic profiling and genome-wide mapping of genotoxic stress-induced O-GlcNAcylated chromatin-associated proteins.

The human gut microbiome is a reservoir for antibiotic resistance gene (ARG). Therefore, characterizing resistome distribution and potential disease markers can help manage antibiotics at the clinical level. While much population-level research has highlighted the strong effect of donor geographic origin on ARG prevalence in the human gut, little is known regarding the effects of other properties, such as age, sex, and disease. Here we employed 2,037 fecal metagenomes from 12 countries. By quantifying the known resistance genes for 24 types of antibiotics in each community, we showed that tetracycline, aminoglycoside, beta-lactam, macrolide-lincosamide-streptogramin (MLS), and vancomycin resistance genes were the dominant ARG types in the human gut. We then compared the ARG profiles of 1427 healthy individuals from the 2,037 samples and observed significant differences across countries. This was consistent with expectations that regional antibiotic usage and exposure in medical and food production contexts affect distribution. Although no specific uniform pattern of ARG was observed, a significant increase in resistance potential among multiple disease groups implied that the disease condition may be another source of ARG variance. In particular, the co-occurrence pattern of some enriched bacterial species and ARGs that were obtained in type 2 diabetes (T2D) and liver cirrhosis patients implied that some disease-associated species may be potential hosts of enriched ARGs, which could be potential biomarkers for the prediction and intervention of such diseases. Overall, our study identifies factors associated with the human gut resistome, including substantial effects of region and heterogeneous effects of disease status, and highlights the value of ARG analysis in disease research and clinical applications.

Abstract Background An increasing number of studies reported that exogenous miRNAs (xenomiRs) can be detected in animal bodies, however, some others reported negative results. Some attributed this divergence to the selective absorption of plant-derived xenomiRs by animals. Results Here, we analyzed 166 plant-derived xenomiRs reported in our previous study and 942 non-xenomiRs extracted from miRNA expression profiles of four species of commonly consumed plants. Employing statistics analysis and cluster analysis, our study revealed the potential sequence specificity of plant-derived xenomiRs. Furthermore, a random forest model and a one-dimensional convolutional neural network model were trained using miRNA sequence features and raw miRNA sequences respectively and then employed to predict unlabeled plant miRNAs in miRBase. A total of 241 possible plant-derived xenomiRs were predicted by both models. Finally, the potential functions of these possible plant-derived xenomiRs along with our previously reported ones in human body were analyzed. Conclusions Our study, for the first time, presents the systematic plant-derived xenomiR sequences analysis and provides evidence for selective absorption of plant miRNA by human body, which could facilitate the future investigation about the mechanisms underlying the transference of plant-derived xenomiR.

In this study, daphnetin 1 was chosen as the lead compound, and C-3 or C-4-substituted daphnetins were designed and synthesized to explore the potential relationship between the antioxidant activities and the chemical structures of daphnetin derivatives. The antioxidant activities of the generated compounds were evaluated utilizing the free radical scavenging effect on 2,2′-diphenyl-1-picrylhydrazyl, 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulfonate) cation, and the ferric reducing power assays, and were then compared with those of the standard antioxidant Trolox. The results showed that the catechol group was the key pharmacophore for the antioxidant activity of the daphnetins. The introduction of an electron-withdrawing hydrophilic group at the C-4 position of daphnetin enhanced the antioxidative capacity, but this trend was not observed for C-3 substitution. In addition, introduction of a a hydrophobic phenyl group exerted negative effects on the antioxidant activity in both the C-3 and C-4 substitutions. Among all of the derivatives tested, the most powerful antioxidant was 4-carboxymethyl daphnetin (compound 9), for which the strongest antioxidant activity was observed in all of the assays. In addition, compound 9 also displayed strong pharmaceutical properties in the form of metabolic stability. To summarize, compound 9 holds great potential to be developed as an antioxidant agent with excellent antioxidant activity and proper pharmacokinetic behavior.

Berberine is a traditional medicine that has multiple medicinal and agricultural applications. However, little is known about whether berberine can be a bioactive molecule toward carbohydrate-active enzymes, which play numerous vital roles in the life process. In this study, berberine and its analogs were discovered to be competitive inhibitors of glycoside hydrolase family 20 β-N-acetyl-D-hexosaminidase (GH20 Hex) and GH18 chitinase from both humans and the insect pest Ostrinia furnacalis. Berberine and its analog SYSU-1 inhibit insect GH20 Hex from O. furnacalis (Of Hex1), with Ki values of 12 and 8.5μM, respectively. Co-crystallization of berberine and its analog SYSU-1 in complex with Of Hex1 revealed that the positively charged conjugate plane of berberine forms л-л stacking interactions with Trp490, which are vital to its inhibitory activity. Moreover, the 1,3-dioxole group of berberine binds an unexplored pocket formed by Trp322, Trp483, and Val484, which also contributes to its inhibitory activity. Berberine was also found to be an inhibitor of human GH20 Hex (HsHexB), human GH18 chitinase (HsCht and acidic mammalian chitinase), and insect GH18 chitinase (Of ChtI). Besides GH18 and GH20 enzymes, berberine was shown to weakly inhibit human GH84 O-Glc NAcase (HsOGA) and Saccharomyces cerevisiae GH63 α-glucosidase I (ScGluI). By analyzing the published crystal structures, berberine was revealed to bind with its targets in an identical mechanism, namely via л-л stacking and electrostatic interactions with the aromatic and acidic residues in the binding pockets. This paper reports new molecular targets of berberine and may provide a berberine-based scaffold for developing multitarget drugs. [ABSTRACT FROM AUTHOR]