Structural snapshots of the reaction coordinate for O-GlcNAc transferase

Visualization of the reaction coordinate undertaken by glycosyltransferases has remained elusive, but is critical for understanding this important class of enzyme. Using substrates and substrate mimics, we describe structural snapshots of all species along the kinetic pathway for human O-GlcNAc transferase, an intracellular enzyme that catalyzes installation of a dynamic post-translational modification. The structures reveal key features of the mechanism and show that substrate participation is important during catalysis

Effects of egg and vitamin A supplementation on hemoglobin, retinol status and physical growth levels of primary and middle school students in

Lack of protein and vitamin A influences the growth of student in impoverished mountain areas. The aim of the study was to assess the effects of egg and vitamin A supplementation on hemoglobin, serum retinol and anthropometric indices of 10-18 years old students of a low socioeconomic status. A total number of 288 students from four boarding schools were randomly selected by using cluster sampling method in Chongqing, and they were assigned into supplement group and control group non-randomly. Students in supplement group received a single 200,000 international units vitamin A and 1 egg/day (including weekends) for 6 months. The control group did not receive any supplementation. We measured hemoglobin, serum retinol and height and weight at baseline and after supplementation. The supplementation increased the mean hemoglobin concentration by 7.13 g/L compared with 1.38 g/L in control group (p<0.001), the mean serum retinol concentration by 0.31 μmol/L compared with 0.09 μmol/L in the control group (p=0.005), the mean height-for-age z score by 0.05 compared with 0.03 in the control group (p=0.319), the mean weight-for-age z score by 0.05 compared with -0.12 in the control group (p<0.001). Our results revealed that egg and vitamin A supplementation is an effective, convenient, and practical method to improve the levels of hemoglobin, serum retinol and prevent the deterioration of growth in terms of weight for primary and middle school students from outlying poverty-stricken areas. Our intervention did not have a beneficial effect on linear growth

A Neural Network Based Approach to Inverse Kinematics Problem for General Six-Axis Robots

Inverse kinematics problems (IKP) are ubiquitous in robotics for improved robot control in widespread applications. However, the high non-linearity, complexity, and equation coupling of a general six-axis robotic manipulator pose substantial challenges in solving the IKP precisely and efficiently. To address this issue, we propose a novel approach based on neural network (NN) with numerical error minimization in this paper. Within our framework, the complexity of IKP is first simplified by a strategy called joint space segmentation, with respective training data generated by forward kinematics. Afterwards, a set of multilayer perception networks (MLP) are established to learn from the foregoing data in order to fit the goal function piecewise. To reduce the computational cost of the inference process, a set of classification models is trained to determine the appropriate forgoing MLPs for predictions given a specific input. After the initial solution is sought, being improved with a prediction error minimized, the refined solution is finally achieved. The proposed methodology is validated via simulations on Xarm6—a general 6 degrees of freedom manipulator. Results further verify the feasibility of NN for IKP in general cases, even with a high-precision requirement. The proposed algorithm has showcased enhanced efficiency and accuracy compared to NN-based approaches reported in the literature

The Emerging Roles of Protein Interactions with O-GlcNAc Cycling Enzymes in Cancer

The dynamic O-GlcNAc modification of intracellular proteins is an important nutrient sensor for integrating metabolic signals into vast networks of highly coordinated cellular activities. Dysregulation of the sole enzymes responsible for O-GlcNAc cycling, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), and the associated cellular O-GlcNAc profile is a common feature across nearly every cancer type. Many studies have investigated the effects of aberrant OGT/OGA expression on global O-GlcNAcylation activity in cancer cells. However, recent studies have begun to elucidate the roles of protein–protein interactions (PPIs), potentially through regions outside of the immediate catalytic site of OGT/OGA, that regulate greater protein networks to facilitate substrate-specific modification, protein translocalization, and the assembly of larger biomolecular complexes. Perturbation of OGT/OGA PPI networks makes profound changes in the cell and may directly contribute to cancer malignancies. Herein, we highlight recent studies on the structural features of OGT and OGA, as well as the emerging roles and molecular mechanisms of their aberrant PPIs in rewiring cancer networks. By integrating complementary approaches, the research in this area will aid in the identification of key protein contacts and functional modules derived from OGT/OGA that drive oncogenesis and will illuminate new directions for anti-cancer drug development

The Stoichiometry of TCNQ-Based Organic Charge-Transfer Cocrystals

Organic charge-transfer cocrystals (CTCs) have attracted significant research attention due to their wide range of potential applications in organic optoelectronic devices, organic magnetic devices, organic energy devices, pharmaceutical industry, etc. The physical properties of organic charge transfer cocrystals can be tuned not only by changing the donor and acceptor molecules, but also by varying the stoichiometry between the donor and the acceptor. However, the importance of the stoichiometry on tuning the properties of CTCs has still been underestimated. In this review, single-crystal growth methods of organic CTCs with different stoichiometries are first introduced, and their physical properties, including the degree of charge transfer, electrical conductivity, and field-effect mobility, are then discussed. Finally, a perspective of this research direction is provided to give the readers a general understanding of the concept

The stoichiometry of TCNQ-based organic charge-transfer cocrystals

Organic charge-transfer cocrystals (CTCs) have attracted significant research attention due to their wide range of potential applications in organic optoelectronic devices, organic magnetic devices, organic energy devices, pharmaceutical industry, etc. The physical properties of organic charge transfer cocrystals can be tuned not only by changing the donor and acceptor molecules, but also by varying the stoichiometry between the donor and the acceptor. However, the importance of the stoichiometry on tuning the properties of CTCs has still been underestimated. In this review, single-crystal growth methods of organic CTCs with different stoichiometries are first introduced, and their physical properties, including the degree of charge transfer, electrical conductivity, and field-effect mobility, are then discussed. Finally, a perspective of this research direction is provided to give the readers a general understanding of the concept.National Research Foundation (NRF)Published versionThis research was funded by the National Natural Science Foundation of China (No. 51803168) and the APC was funded by Nowthwest University. P.H. also acknowledges financial support from the Youth Innovation Team of Shaanxi Universities. H.Z. acknowledges financial support from the National Natural Science Foundation of China (11704311), Natural Science Foundation of Shaanxi Provincial Department of Education (17JK0772) and Natural Science Foundation of Shaanxi Province (2018JQ1069). H.J. acknowledges the grants from the National Research Foundation, Prime Minister’s Office, Singapore under its Campus of Research Excellence and Technological Enterprise (CREATE) programme

Analysis of the Fungal Community in Ziziphi Spinosae Semen through High-Throughput Sequencing

Ziziphi Spinosae Semen (ZSS) has been widely used in traditional Chinese medicine system for decades. Under proper humidity and temperature, ZSS is easily contaminated by fungi and mycotoxins during harvest, storage, and transport, thereby posing a considerable threat to consumer health. In this study, we first used the Illumina MiSeq PE250 platform and targeted the internal transcribed spacer 2 sequences to investigate the presence of fungi in moldy and normal ZSS samples collected from five producing areas in China. Results showed that all 14 samples tested were contaminated by fungi. Ascomycota was the dominant fungus at the phylum level, accounting for 64.36⁻99.74% of the fungal reads. At the genus level, Aspergillus, Candida, and Wallemia were the most predominant genera, with the relative abundances of 13.52⁻87.87%, 0.42⁻64.56%, and 0.06⁻34.31%, respectively. Meanwhile, 70 fungal taxa were identified at the species level. Among these taxa, three potential mycotoxin-producing fungi, namely, Aspergillus flavus, A. fumigatus, and Penicillium citrinum that account for 0.30⁻36.29%, 0.04⁻7.37%, and 0.01⁻0.80% of the fungal reads, respectively, were detected in all ZSS samples. Moreover, significant differences in fungal communities were observed in the moldy and normal ZSS samples. In conclusion, our results indicated that amplicon sequencing is feasible for the detection and analysis of the fungal community in the ZSS samples. This study used a new approach to survey the fungal contamination in herbal materials. This new approach can provide early warning for mycotoxin contamination in herbal materials, thereby ensuring drug efficacy and safety