NFBTA: A Potent Cytotoxic Agent against Glioblastoma
MOLECULES
Authors: Turkez, Hasan; da Nobrega, Flavio Rogerio; Ozdemir, Ozlem; Maia Bezerra Filho, Carlos da Silva; de Almeida, Reinaldo Nobrega; Tejera, Eduardo; Perez-Castillo, Yunierkis; de Sousa, Damiao Pergentino
Abstract
Piplartine (PPL), also known as piperlongumine, is a biologically active alkaloid extracted from the Piper genus which has been found to have highly effective anticancer activity against several tumor cell lines. This study investigates in detail the antitumoral potential of a PPL analogue; (E)-N-(4-fluorobenzyl)-3-(3,4,5-trimethoxyphenyl) acrylamide (NFBTA). The anticancer potential of NFBTA on the glioblastoma multiforme (GBM) cell line (U87MG) was determined by 3-(4,5-dimethyl-2-thia-zolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT), and lactate dehydrogenase (LDH) release analysis, and the selectivity index (SI) was calculated. To detect cell apoptosis, fluorescent staining via flow cytometry and Hoechst 33258 staining were performed. Oxidative alterations were assessed via colorimetric measurement methods. Alterations in expressions of key genes related to carcinogenesis were determined. Additionally, in terms of NFBTA cytotoxic, oxidative, and genotoxic damage potential, the biosafety of this novel agent was evaluated in cultured human whole blood cells. Cell viability analyses revealed that NFBTA exhibited strong cytotoxic activity in cultured U87MG cells, with high selectivity and inhibitory activity in apoptotic processes, as well as potential for altering the principal molecular genetic responses in U87MG cell growth. Molecular docking studies strongly suggested a plausible anti-proliferative mechanism for NBFTA. The results of the experimental in vitro human glioblastoma model and computational approach revealed promising cytotoxic activity for NFBTA, helping to orient further studies evaluating its antitumor profile for safe and effective therapeutic applications.
Neural Network Language Model Compression With Product Quantization and Soft Binarization
IEEE-ACM TRANSACTIONS ON AUDIO SPEECH AND LANGUAGE PROCESSING
Authors: Yu, Kai; Ma, Rao; Shi, Kaiyu; Liu, Qi
Abstract
Large memory consumption of the neural network language models (NN LMs) prohibits their use in many resource-constrained scenarios. Hence, effective NN LM compression approaches that are independent of NN structures are of great interest. However, previous approaches usually achieve a high compression ratio at the cost of obvious performance loss. In this paper, two recently proposed quantization approaches, product quantization (PQ) and soft binarization are effectively combined to address the issue. PQ decomposes word embedding matrices into a Cartesian product of low dimensional subspaces and quantizes each subspace separately. Soft binarization uses a small number of float scalars and the knowledge distillation technique to recover the performance loss during the binarization. Experiments show that the proposed approaches can achieve a high compression ratio, from 70 to over 100, while still maintaining comparable performance to the uncompressed NN LM on both PPL and word error rate criteria.