Quinolinone inhibits proliferation of gastric cancer cells and induces their apoptosis via down-regulation of the expression of pro-oncogene c-Myc

Purpose: To determine the anti-proliferative potential of quinolinone against gastric cancer cells, and the underlying mechanism of action.Methods: Quinolinone-mediated proliferative changes were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, while its effect on apoptosis was determined by flow cytometry. Transwell and wound healing assays were used for the determination of the effect of quinolinone on cell invasion and migration. The effect of quinolinone on protein expression levels were assayed with western blotting.Results: Quinolinone caused reduction in gastric cancer cell viability, but it had no effect on normal (GES-1) cells. Treatment with 8 μM quinolinone reduced the viability of SNU-5 and SGC-7901 cells to 32 and 27 %, respectively. Moreover, 8 μM quinolinone induced 67.90 and 71.54 % apoptosis in SNU-5 and SGC-7901 cells, respectively. Quinolinone significantly increased the population of cells in G1 phase, and suppressed migration potential (p < 0.05). Furthermore, in quinolinone-treated cells, the expression levels of p-PI3K, c-Myc and p-AKT were much lower than those in untreated cells (p < 0.05). Quinolinone also downregulated the expressions of MMP-2 and MMP-9, while it upregulated p21 expression in SNU-5 and SGC-7901 cells.Conclusion: Quinolinone suppresses the growth of SNU-5 and SGC-7901 gastric cancer cells via cell cycle arrest, induction of apoptosis and downregulation of the expressions of c-Myc and metalloproteinases. Thus, quinolinone may be developed as a potential drug candidate for the treatment of gastric cancer. Keywords: Gastric cancer, Apoptosis, Metalloproteinases, Phosphorylatio

Changes in Quality Characteristics of Snakehead Surimi during Fermentation

In this study, the effects of Pediococcus pentosaceus inoculation on the quality characteristics of snakehead surimi during fermentation were analyzed in comparison with natural fermentation. The quality of fermented surimi was evaluated in terms of pH, total acid, total volatile basic nitrogen (TVB-N), fatty acids, color difference, texture, amino acids and sensory scores. The results showed that pH declined and total acid content gradually increased during fermentation. After fermentation for 48 h, total acid content in the inoculated fermentation group increased by 52.29% when compared with that in the natural fermentation group. Compared with the natural fermentation group, the increase in TVB-N content was significantly inhibited in the inoculated fermentation group. The content of saturated fatty acids increased during natural fermentation, but decreased during inoculated fermentation. The content of monounsaturated fatty acids was lower while the content of polyunsaturated fatty acids was higher in the inoculated fermentation group than in the natural fermentation group at the end of fermentation. The inoculated fermentation group showed an increase in L* value and the absolute values of hardness and adhesiveness, and increased the contents of total essential amino acids and umami amino acids in surimi samples and the essential amino acid index from 73.9 to 74.8. After fermentation for 48 h, the scores for odor, color and overall acceptability in the inoculated fermentation group were higher than those in the natural fermentation group, which were significantly correlated with quality characteristics. Therefore, the quality of snakehead surimi can be better improved by fermentation with P. pentosaceus

CFAD: A Chinese Dataset for Fake Audio Detection

Fake audio detection is a growing concern and some relevant datasets have been designed for research. However, there is no standard public Chinese dataset under complex conditions.In this paper, we aim to fill in the gap and design a Chinese fake audio detection dataset (CFAD) for studying more generalized detection methods. Twelve mainstream speech-generation techniques are used to generate fake audio. To simulate the real-life scenarios, three noise datasets are selected for noise adding at five different signal-to-noise ratios, and six codecs are considered for audio transcoding (format conversion). CFAD dataset can be used not only for fake audio detection but also for detecting the algorithms of fake utterances for audio forensics. Baseline results are presented with analysis. The results that show fake audio detection methods with generalization remain challenging. The CFAD dataset is publicly available at: https://zenodo.org/record/8122764.Comment: FAD renamed as CFA

Spatio-Temporal Patterns and Impacts of Sediment Variations in Downstream of the Three Gorges Dam on the Yangtze River, China

Spanning the Yangtze River of China, the Three Gorges Dam (TGD) has received considerable concern worldwide with its potential impacts on the downstream side of the dam. This work investigated the spatio-temporal variations of suspended sediment concentration (SSC) at the downstream section of Yichang-to-Chenglingji from 2002 to 2015. A random forest model was developed to estimate SSC using MODIS ground reflectance products, and the spatio-temporal distributions of SSC were retrieved with this model to investigate the characteristics of water-silt variation. Our results revealed that, relatively, SSC before 2003 was evenly distributed in the downstream Yangtze River, while this spatial distribution pattern changed ce 2003 when the dam started storing water. Temporally, the SSC demonstrated a W-shaped curve of seasonal variation as one peak occurred in September and two troughs in March and November, and showed a significantly decreasing trend after three-stage impoundment. After official operation of the TGD in 2009, the SSC was reduced by over 40% than before 2003. Spatially, the most significant changes occurred in the upper Jingjiang section, where the SSC dropped by 45%. During all stages of impoundment, the water impoundment to 135 m in 2003 had the most significant impact on suspended sediment. The decreased SSC has led to emerging risks of bank failure, aggravated erosion of water front and aggressive down-cutting erosion along the downstream of the dam, as well as other ecological and environmental issues that require urgent attention by the government

Direct Conversion of Mouse Astrocytes Into Neural Progenitor Cells and Specific Lineages of Neurons

Background: Cell replacement therapy has been envisioned as a promising treatment for neurodegenerative diseases. Due to the ethical concerns of ESCs-derived neural progenitor cells (NPCs) and tumorigenic potential of iPSCs, reprogramming of somatic cells directly into multipotent NPCs has emerged as a preferred approach for cell transplantation. Methods: Mouse astrocytes were reprogrammed into NPCs by the overexpression of transcription factors (TFs) Foxg1, Sox2, and Brn2. The generation of subtypes of neurons was directed by the force expression of cell-type specific TFs Lhx8 or Foxa2/Lmx1a. Results: Astrocyte-derived induced NPCs (AiNPCs) share high similarities, including the expression of NPC-specific genes, DNA methylation patterns, the ability to proliferate and differentiate, with the wild type NPCs. The AiNPCs are committed to the forebrain identity and predominantly differentiated into glutamatergic and GABAergic neuronal subtypes. Interestingly, additional overexpression of TFs Lhx8 and Foxa2/Lmx1a in AiNPCs promoted cholinergic and dopaminergic neuronal differentiation, respectively. Conclusions: Our studies suggest that astrocytes can be converted into AiNPCs and lineage-committed AiNPCs can acquire differentiation potential of other lineages through forced expression of specific TFs. Understanding the impact of the TF sets on the reprogramming and differentiation into specific lineages of neurons will provide valuable strategies for astrocyte-based cell therapy in neurodegenerative diseases

The Synthesis and Initial Evaluation of MerTK Targeted PET Agents

MerTK (Mer tyrosine kinase), a receptor tyrosine kinase, is ectopically or aberrantly expressed in numerous human hematologic and solid malignancies. Although a variety of MerTK targeting therapies are being developed to enhance outcomes for patients with various cancers, the sensitivity of tumors to MerTK suppression may not be uniform due to the heterogeneity of solid tumors and different tumor stages. In this report, we develop a series of radiolabeled agents as potential MerTK PET (positron emission tomography) agents. In our initial in vivo evaluation, [18F]-MerTK-6 showed prominent uptake rate (4.79 ± 0.24%ID/g) in B16F10 tumor-bearing mice. The tumor to muscle ratio reached 1.86 and 3.09 at 0.5 and 2 h post-injection, respectively. In summary, [18F]-MerTK-6 is a promising PET agent for MerTK imaging and is worth further evaluation in future studies

Detecting influenza and emerging avian influenza virus by influenza and pneumonia surveillance systems in a large city in China, 2005 to 2016.

BACKGROUND(#br)Detecting avian influenza virus has become an important public health strategy for controlling the emerging infectious disease.(#br)METHODS(#br)The HIS (hospital information system) modified influenza surveillance system (ISS) and a newly built pneumonia surveillance system (PSS) were used to monitor the influenza viruses in Changsha City, China. The ISS was used to monitor outpatients in two sentinel hospitals and to detect mild influenza and avian influenza cases, and PSS was used to monitor inpatients in 49 hospitals and to detect severe and death influenza cases.(#br)RESULTS(#br)From 2005 to 2016, there were 3,551,917 outpatients monitored by the ISS system, among whom 126,076 were influenza-like illness (ILI) cases, with the ILI proportion (ILI%) of 3.55%. After the HIS was used, the reported incident cases of ILI and ILI% were increased significantly. From March, 2009 to September, 2016, there were 5,491,560 inpatient cases monitored by the PSS system, among which 362,743 were pneumonia cases, with a proportion of 6.61%. Among pneumonia cases, about 10.55% (38,260/362,743) of cases were severe or death cases. The pneumonia incidence increased each year in the city. Among 15 avian influenza cases reported from January, 2005 to September, 2016, there were 26.7% (4/15) mild cases detected by the HIS-modified ISS system, while 60.0% (9/15) were severe or death cases detected by the PSS system. Two H5N1 severe cases were missed by the ISS system in January, 2009 when the PSS system was not available.(#br)CONCLUSIONS(#br)The HIS was able to improve the efficiency of the ISS for monitoring ILI and emerging avian influenza virus. However, the efficiency of the system needs to be verified in a wider area for a longer time span in China

Top 100 cited classical articles in sentinel lymph nodes biopsy for breast cancer

BackgroundThe sentinel lymph node biopsy (SLNB) takes on a critical significance in breast cancer surgery since it is the gold standard for assessing axillary lymph node (ALN) metastasis and determining whether to perform axillary lymph node dissection (ALND). A bibliometric analysis is beneficial to visualize characteristics and hotspots in the field of sentinel lymph nodes (SLNs), and it is conducive to summarizing the important themes in the field to provide more insights into SLNs and facilitate the management of SLNs.Materials and methodsSearch terms relating to SLNs were aggregated and searched in the Web of Science core collection database to identify the top 100 most cited articles. Bibliometric tools were employed to identify and analyze publications for annual article volume, authors, countries, institutions, keywords, as well as hotspot topics.ResultsThe period was from 1998 to 2018. The total number of citations ranged from 160 to 1925. LANCET ONCOLOGY and JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION were the top two journals in which the above articles were published. Giuliano, AE was the author with the highest number of articles in this field with 15. EUROPEAN INST ONCOL is the institution with the highest number of publications, with 35 articles. Hotspots include the following 4 topics, false-negative SLNs after neoadjuvant chemotherapy; prediction of metastatic SLNs; quality of life and postoperative complications; and lymphography of SLNs.ConclusionThis study applies bibliometric tools to analyze the most influential literature, the top 100 cited articles in the field of SLNB, to provide researchers and physicians with research priorities and hotspots