Concepts and Application of DNA Origami and DNA Self-Assembly: A Systematic Review.

With the arrival of the post-Moore Era, the development of traditional silicon-based computers has reached the limit, and it is urgent to develop new computing technology to meet the needs of science and life. DNA computing has become an essential branch and research hotspot of new computer technology because of its powerful parallel computing capability and excellent data storage capability. Due to good biocompatibility and programmability properties, DNA molecules have been widely used to construct novel self-assembled structures. In this review, DNA origami is briefly introduced firstly. Then, the applications of DNA self-assembly in material physics, biogenetics, medicine, and other fields are described in detail, which will aid the development of DNA computational model in the future.

Classification and Design of HIV-1 Integrase Inhibitors Based on Machine Learning.

A key enzyme in human immunodeficiency virus type 1 (HIV-1) life cycle, integrase (IN) aids the integration of viral DNA into the host DNA, which has become an ideal target for the development of anti-HIV drugs. A total of 1785 potential HIV-1 IN inhibitors were collected from the databases of ChEMBL, Binding Database, DrugBank, and PubMed, as well as from 40 references. The database was divided into the training set and test set by random sampling. By exploring the correlation between molecular descriptors and inhibitory activity, it is found that the classification and specific activity data of inhibitors can be more accurately predicted by the combination of molecular descriptors and molecular fingerprints. The calculation of molecular fingerprint descriptor provides the additional substructure information to improve the prediction ability. Based on the training set, two machine learning methods, the recursive partition (RP) and naive Bayes (NB) models, were used to build the classifiers of HIV-1 IN inhibitors. Through the test set verification, the RP technique accurately predicted 82.5% inhibitors and 86.3% noninhibitors. The NB model predicted 88.3% inhibitors and 87.2% noninhibitors with correlation coefficient of 85.2%. The results show that the prediction performance of NB model is slightly better than that of RP, and the key molecular segments are also obtained. Additionally, CoMFA and CoMSIA models with good activity prediction ability both were constructed by exploring the structure-activity relationship, which is helpful for the design and optimization of HIV-1 IN inhibitors.

Screening and Identification of Differentially Expressed and Adipose Growth-Related Protein-Coding Genes During the Deposition of Perirenal Adipose Tissue in Rabbits.

BACKGROUND: Rabbit is a good model for genetic and medical studies in other livestock species. The rabbit shows low adipose tissue deposition, and the phenomena indicates that there is some specificity of adipose deposition during the rabbit growth. However, little is known about genes that regulate the growth of adipose tissue in rabbits. MATERIALS AND METHODS: Deep RNA-seq and comprehensive bioinformatics analyses were used to characterize the genes of rabbit visceral adipose tissue (VAT) at 35, 85 and 120 days after birth. Differentially expressed genes (DEGs) were identified at the three growth stages by DESeq. To explore the function of the candidate genes, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Six DEGs were randomly selected, and their expression profiles were validated by q-PCR. RESULTS: A total of 20,303 known transcripts and 99,199 new transcripts from 8 RNA sequencing libraries were identified, and 34 differentially expressed genes (DEGs) were screened. GO enrichment and KEGG pathway analyses revealed that the DEGs were mainly involved in lipid metabolism regulation including acylglycerol metabolic process and mobilization, and decomposition of lipids to generate ATP in adipocytes and fatty acid metabolism, included LOC100342322 and LOC100342572. In addition, 133 protein-coding genes that play a role in adipose growth and development were screened, including acyl-CoA synthetase long-chain family member 5 (ACSL5) and fatty acid-binding protein 2 (FABP2). The validation results of six DEGs by q-PCR showed similar trends with the results of RNA-seq. CONCLUSION: In summary, this study provides the first report of the coding genes profiles of rabbit adipose tissue during different growth stages. These data allow for the identification of candidate genes for subsequent studies on rabbit genetics and regulation of adipose cells, and provide an animal model for studying obesity in humans.

BP[dG]-induced distortions to DNA polymerase and DNA duplex: A detailed mechanism of BP adducts blocking replication.

As one of the most widespread environmental pollutants, benzo[α]pyrene is metabolized to diol epoxides and then covalently breaks the initial DNA base pairs, which has been closely related to the occurrence and development of many human cancers. High fidelity DNA polymerases play an extremely important role in maintaining the reliability or fidelity of nucleic acid replication, which is generally blocked by BP adducts. To reveal the blocking mechanism of BP, two comparative molecular dynamics simulations were performed for the thermophilic Bacillus stearothermophilus DNA polymerase I large fragment (BF) complexes with normal and BP-bound DNA duplexes. The results of global conformational changes and molecular interactions show that the association of BP leads to the rearrangement of intramolecular hydrogen bonds, impairing the molecular recognition between the polymerase and the DNA duplex. It is also found that the conformation of DNA duplex is distorted, accompanied by an increase in molecular overall rigidity. In terms of possible blocking mechanisms, the BP moiety perfectly integrates itself into the base-paired environment in a special vertical conformation and occupies the space required for the incoming nucleotide. This work provides useful dynamics and structural information for understanding the toxic effect of BP on DNA replication at atomic level.

Reactions of polyphenols in pomegranate peel with nitrite under simulated stomach conditions.

Punicalagin and ellagic acid are the major polyphenols present in pomegranate peels. The contents of α-punicalagin, ß-punicalagin, and ellagic acid in the pomegranate peels were approximately 75, 72, and 20 µM, respectively. The reactions of polyphenols in pomegranate peels with sodium nitrite under simulated stomach conditions were studied. The reactions decreased the polyphenolic contents of the pomegranate peels and accompanied the formation of nitroso compounds. The oxidation rates followed the order ellagic acid ＜α-punicalagin ≈ ß-punicalagin. The results suggested that the reactions can occur in the stomach after a meal, while the pH changes from 2 to 4.5.

Enhancement of the thermostability of halohydrin dehalogenase from Agrobacterium radiobacter AD1 by constructing a combinatorial smart library.

Halohydrin dehalogenase from Agrobacterium radiobacter AD1 (HheC) is a key enzyme in preparing ß-substituted alcohols and optically pure epoxides. However, the weak thermostability of HheC greatly limits its industrial application and needs to be improved. In this study, a combinatorial smart library was constructed and screened for enhancing the thermostability of HheC. Mutation sites Lys203 and Lys204 located at the protein surface were selected and simultaneously randomized with charged amino acids (Arg, Asp, Glu, Lys), resulting in a combinatorial smart library. After screening a total of only 48 clones, three positive variants CSL1 (Lys203Arg), CSL2 (Lys204Arg) and CSL3 (Lys203Arg/Lys204Arg) were obtained. Compared to the wild type HheC, variant CSL2 exhibited an increase in thermal stability with a nearly 6.9-fold improvement of half-life (τ1/2, 55°C) at 55 °C without compromising catalytic activity. In addition, the double mutant CSL3 displayed approximately 3.4-fold higher τ1/2, 55°C value and 1.8-fold higher kcat value toward 1,3-dicholoro-2-propanol (1,3-DCP) than that of the wild-type HheC. Homology modeling analysis highlights that the newly gained hydrogen bonds and optimizing charge-charge interactions at the protein surface might contribute to the overall conformational stabilization, leading to improving the thermostability of HheC.

[Research progress on alkaloids constituents from Zanthoxylum and their pharmacological activities].

There are 250 species of Zanthoxylum (Rutaceae) in the world. This genus distributed in tropical and subtropical regions. Alkaloids are the major and representative ingredients in these plants including quinolines, isoquinolines, and amide alkaloids, with such biological activities as anti-tumor, anti-inflammatory, analgesic, anti-virus, anti-platelet aggregation, anti-bacteria and anti- oxidant. These species have been used for a long time to treat toothache, urinary and venereal diseases, lumbago and rheumatism. This review summarizes the chemical constituents and pharmacological activities from the Z. sppplants, in an effort to the systematic research and application of the alkaloids of this genus.