Substituting Nε-thioacetyl-lysine for Nε-acetyl-lysine in Peptide Substrates as a General Approach to Inhibiting Human NAD+-dependent Protein Deacetylases

Inhibitors of human NAD+-dependent protein deacetylases possess great value for deciphering the biology of these enzymes and as potential therapeutics for metabolic and age-related diseases and cancer. In the current study, we have experimentally demonstrated that, the potent inhibition we obtained previously for one of these enzymes (i.e. sirtuin type 1 (SIRT1)) by simply replacing Nε-thioacetyl-lysine for Nε-acetyl-lysine in its peptide substrate, represented a general and efficient strategy to develop potent and selective inhibitors of human NAD+-dependent protein deacetylase enzymes. Indeed, by using this simple inhibition strategy, potent (low-micromolar) and selective (≤40-fold) SIRT2 and SIRT3 inhibitors, which were either comparable or superior to currently existing inhibitors, have also been quickly identified in the current study. These inhibitors could be used as chemical biological tools or as lead compounds for further focused structure-activity optimization

Sensitive HPV Genotyping Based on the Flow-Through Hybridization and Gene Chip

Persistent infection of high-risk human papillomavirus (HPV) has been recognized as the direct cause of cervical carcinoma. Therefore, detection and genotyping of HPV are important to cervical-cancer screening. In this study, we have evaluated the efficacy of flow-through hybridization and gene chip (HybriMax) on HPV genotyping through comparison of the results with Hybrid Capture II (HC-II) and in situ hybridization (ISH). 591 women were classified into 6 groups according to their histological diagnoses. The overall accordance rate on 13 types of HPV genotypes between HybriMax and HC-II were 92.5% and 100% in the cancer group. The overall accordance was excellent with the Kappa index (KI) of 0.814. The value of KI in each group was 0.750 (normal cytological diagnosis), 0.781 (chronic cervicitis), 0.80 (condyloma acuminatum), 0.755 (cervical intraepithelial neoplasia (CIN) I), 0.723 (CIN II), and 0.547 (CIN III) (0.75>KI>0.4, good; KI≥0.75, excellent). The 10 most common HPV subtype detected by HybriMax were 16, 52/58, 18, 33, 31, 81, 53, 68, and 66 in patients, and 16, 68, 18, 52, 58, 11, 53, 31/39, and 33 in normal controls. In conclusion, HybriMax is an efficient method for HPV genotyping and more suitable for clinical use

CQNV: A combination of coarsely quantized bitstream and neural vocoder for low rate speech coding

Recently, speech codecs based on neural networks have proven to perform better than traditional methods. However, redundancy in traditional parameter quantization is visible within the codec architecture of combining the traditional codec with the neural vocoder. In this paper, we propose a novel framework named CQNV, which combines the coarsely quantized parameters of a traditional parametric codec to reduce the bitrate with a neural vocoder to improve the quality of the decoded speech. Furthermore, we introduce a parameters processing module into the neural vocoder to enhance the application of the bitstream of traditional speech coding parameters to the neural vocoder, further improving the reconstructed speech's quality. In the experiments, both subjective and objective evaluations demonstrate the effectiveness of the proposed CQNV framework. Specifically, our proposed method can achieve higher quality reconstructed speech at 1.1 kbps than Lyra and Encodec at 3 kbps.Comment: Accepted by INTERSPEECH 202