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Abstract Base editors are powerful tools for making precise single-nucleotide changes in the genome. However, they can lead to unintended insertions and deletions at the target sites, which is a significant limitation for clinical applications. In this study, we aimed to eliminate unwanted indels at the target sites caused by various evolved base editors. Accordingly, we applied dead Cas9 instead of nickase Cas9 in the base editors to induce accurate substitutions without indels. Additionally, we tested the use of chromatin-modulating peptides in the base editors to improve nucleotide conversion efficiency. We found that using both dead Cas9 and chromatin-modulating peptides in base editing improved the nucleotide substitution efficiency without unintended indel mutations at the desired target sites in human cell lines and mouse primary myoblasts. Furthermore, the proposed scheme had fewer off-target effects than conventional base editors at the DNA level. These results indicate that the suggested approach is promising for the development of more accurate and safer base editing techniques for use in clinical applications.

Abstract Prime editors, novel genome-editing tools consisting of a CRISPR-Cas9 nickase and an engineered reverse transcriptase, can induce targeted mutagenesis. Nevertheless, much effort is required to optimize and improve the efficiency of prime-editing. Herein, we introduce two strategies to improve the editing efficiency using proximal dead sgRNA and chromatin-modulating peptides. We used enhanced prime-editing to generate Igf2 mutant mice with editing frequencies of up to 47% and observed germline transmission, no off-target effects, and a dwarf phenotype. This improved prime-editing method can be efficiently applied to cell research and to generate mouse models.

Smoking is an extremely important health problem in modern society. This study focuses on a method for preventing smoking in non-smoking areas, such as public places, as well as the development of an artificial neural network based smoking motion recognition system for more accurately recognizing smokers in such areas. In particular, we attempted to increase the rate of recognition of smoking behaviors using an OpenPose based algorithm and the accuracy of such recognition by additionally applying a hardware device for recognizing cigarette smoke. In addition, a preprocessing method for inputting a dataset into the proposed system is proposed. To improve the recognition performance, four types of dataset models were created, and the most suitable dataset model was selected experimentally. Based on this dataset model, test data were created and input into the proposed neural network based smoking behavior recognition system. In addition, the nearest neighbor interpolation method was selected experimentally as an image interpolation approach and applied to the image preprocessing. When applying experimental data based on learned data, the developed system showed a recognition rate of 70-75%, and the smoking recognition accuracy was increased through the addition of the hardware device. [ABSTRACT FROM AUTHOR]

Objectives The purpose of this study was to examine the changes in metabolic parameters and Positive and Negative Syndrome Scale (PANSS) scores of patients previously treated with atypical antipsychotic drugs other than paliperidone, after 8 weeks of treatment with paliperidone. Methods Changes in body weight, body mass index, leptin, lipid levels, fasting glucose, and PANSS scores of patients who switched from other atypical antipsychotic drugs to paliperidone were measured after 8 weeks of treatment with paliperidone. We compared these results with those of patients who had not been treated with antipsychotic drugs for at least 2 weeks prior to treatment with paliperidone (antipsychotic drug-free patients). Results The antipsychotic drug-free group (n = 9) did not show significant changes in metabolic parameters, but showed a significant improvement in total and subscale scores of PANSS. In the group that switched from other atypical antipsychotic drugs to paliperidone (n = 13), body weight, body mass index and fasting glucose level significantly increased, while total and subscale scores of PANSS significantly improved. Conclusions Paliperidone treatment will benefit patients with schizophrenia who have been antipsychotic drug-free or who have had difficulty with other atypical antipsychotic drugs, with regard to their psychopathological state. However, if patients have been treated with other atypical antipsychotic drugs before switching to paliperidone, they could gain body weight or their fasting glucose level could increase over a short period because of a change in receptor number and sensitivity caused by the previously prescribed antipsychotic drugs, and hence, paliperidone should be prescribed with caution for these patients. [ABSTRACT FROM AUTHOR]