OBJECTIVE:The goal of the study is to examine the impact on the malignant biological behaviors of non-small cell lung cancer (NSCLC) of a novel coumarin derivative, ethyl 2,2-difluoro-2-(2-oxo-2H-chromen-3-yl) acetate (C2F). It also aims to define its underlying mechanism.METHODS:NSCLC cell lines and xenograft nude mice model were conducted to explore the anti-NSCLC effects of C2F in vitro and in vivo. Then, network pharmacology analysis and molecular docking were applied to estimate the possible targets of C2F in NSCLC. Finally, the underlying mechanism of C2F against NSCLC cellular proliferation and tumor development was confirmed using inhibitors or activators of the PI3K/AKT signaling pathway.RESULTS:Our results showed that C2F was able to inhibit proliferation, migration, and invasion of NSCLC cell lines, induce cell cycle arrest and apoptosis in vitro, and prevent tumor growth in vivo. In addition, the estimated glomerular filtration rate and its downstream pathway (PI3K/AKT/mTOR) were found to be critical for the anti-NSCLC activity of C2F.CONCLUSIONS:C2F inhibits malignant biological behaviors of NSCLC by suppressing EGFR/PI3K/AKT/mTOR signaling pathway.

In this article, two undescribed amides (1-2) with an unusual (2-formyl-5-hydroxymethyl)pyrroyl-butylamine moiety were obtained from the Physochlainae Radix. Comprehensive spectroscopic studies, including NMR and HR-ESI-MS, coupling with spectroscopic data comparisons were used to determine structures. Anti-inflammatory assay results showed that new amides possessed significant inhibitory activities of the NO production of LPS-induced RAW 264.7 cells, with IC50 values of 17.52±1.68 μM and 20.37±2.42 μM, respectively.

Introduction: Circular RNA (circRNAs) are a type of non-coding RNA (ncRNAs) with a wealth of functions. Recently, circRNAs have been identified as important regulators of diabetic kidney disease (DKD), owing to their stability and enrichment in exosomes. However, the role of circRNAs in exosomes of tubular epithelial cells in DKD development has not been fully elucidated. Methods: In our study, microarray technology was used to analyze circRNA expression in cell supernatant exosomes isolated from HK-2 cells with or without high glucose (HG) treatment. The small interfering RNAs (siRNA) and plasmid overexpression were used to validate functions of differentially expressed circRNAs. Results: We found that exosome concentration was higher in HG-stimulated HK-2 cells than in controls. A total of 235 circRNAs were significantly increased and 458 circRNAs were significantly decreased in the exosomes of the HG group. In parallel with the microarray data, the qPCR results showed that the expression of circ_0009885, circ_0043753, and circ_0011760 increased, and the expression of circ_0032872, circ_0004716, and circ_0009445 decreased in the HG group. Rescue experiments showed that the effects of high glucose on regulation of CCL2, IL6, fibronetin, n cadherin, e cadherin and epcam expression can be reversed by inhibiting or overexpressing these circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses indicated that circRNA parental genes are associated with glucose metabolism, lipid metabolism, and inflammatory processes, which are important in DKD development. Further analysis of circRNA/miRNA interactions indicated that 152 differentially expressed circRNAs with fold change (FC) >= 1.5 could be paired with 43 differentially expressed miRNAs, which are associated with diabetes or DKD. Discussion: Our results indicate that exosomal circRNAs may be promising diagnostic and therapeutic biomarkers, and may play a critical role in the progression of DKD.

Alzheimer's disease (AD) is one of the major worldwide causes of dementia that is characterized by irreversible decline in learning, memory loss, and behavioral impairments. Mitophagy is selective autophagy through the clearance of aberrant mitochondria, specifically for degradation to maintain energy generation and neuronal and synaptic function in the brain. Accumulating evidence shows that defective mitophagy is believed to be as one of the early and prominent features in AD pathogenesis and has drawn attention in the recent few years. APOE ε4 allele is the greatest genetic determinant for AD and is widely reported to mediate detrimental effects on mitochondria function and mitophagic process. Given the continuity of the physiological process, this review takes the mitochondrial dynamic and mitophagic core events into consideration, which highlights the current knowledge about the molecular alterations from an APOE-genotype perspective, synthesizes ApoE4-associated regulations, and the cross-talk between these signaling, along with the focuses on general autophagic process and several pivotal processes of mitophagy, including mitochondrial dynamic (DRP1, MFN-1), mitophagic induction (PINK1, Parkin). These may shed new light on the link between ApoE4 and AD and provide novel insights for promising mitophagy-targeted therapeutic strategies for AD.

AbstractCircular ribonucleic acids (circRNAs) are single-stranded RNAs with covalently closed-loop structures that lack terminal 5′ caps and 3′ poly-(A) tails. Recent evidence confirmed that some circRNAs can be translated into proteins. More importantly, there is a growing body of evidence that dysregulation of circRNAs is closely associated with the development of human diseases, especially malignant tumors. CircZNF609 is a novel circular RNA with an open reading frame and an internal ribosomal entry site that can interact with microRNAs and mRNAs and be translated into proteins. Studies have shown that circZNF609 is abnormally expressed in various human diseases, especially malignant tumors such as hepatocellular carcinoma, nasopharyngeal carcinoma, colorectal cancer and glioma, which lead to the occurrence and development of diseases. This article attempts to provide a comprehensive overview of the structural properties of circZNF609 discovered so far and focuses on the pathogenesis of circZNF609 in human diseases and its potential clinical application value. Finally, we elaborate on the directions of future investigations of this molecule.

Purpose Enhancer RNAs (eRNAs) are non-coding RNAs, which are characterized as transcripts without protein coding functions. Increasing evidence indicates that eRNAs play important roles in gene regulation and cancer progression. Furthermore, various roles of eRNAs in sex hormone-induced signaling pathways are emerging, indicating the important roles of eRNAs in the development of sex hormone-dependent cancers. The aim of this study is to summarize the current knowledge about eRNAs in several typical sex hormone-dependent cancers, mainly involving their roles in sex hormones mediated pathways and cancer progression. Methods We reviewed all the published articles concerning eRNAs in sex hormone-dependent cancers, and summarized the roles of eRNAs in these cancers. Results In cancer development, elevated expression of some eRNAs could promote the progression of cancer cells. In gene regulation, eRNAs not only regulate gene activation but also participate in gene repression. Additionally, in androgen receptor signaling, eRNAs were found to play a role at cis and trans loci, and both sense and antisense strands of eRNAs are both important. Conclusion Abnormal overexpression of eRNAs is mostly oncogenic, leading to cancer progression, and both strands of eRNAs play multiple and complex roles at cis and trans loci in sex hormones mediated pathways, which are tightly associated with sex hormone-dependent tumorigenesis.

The communication between neurons constitutes the basis of all neural activities, and synaptic vesicle exocytosis is the fundamental biological event that mediates most communication between neurons in the central nervous system. The SNARE complex is the core component of the protein machinery that facilitates the fusion of synaptic vesicles with presynaptic terminals and thereby the release of neurotransmitters. In synapses, each release event is dependent on the assembly of the SNARE complex. In recent years, basic research on the SNARE complex has provided a clearer understanding of the mechanism underlying the formation of the SNARE complex and its role in vesicle formation. Emerging evidence indicates that abnormal expression or dysfunction of the SNARE complex in synapse physiology might contribute to abnormal neurotransmission and ultimately to synaptic dysfunction. Clinical research using postmortem tissues suggests that SNARE complex dysfunction is correlated with various neurological diseases, and some basic research has also confirmed the important role of the SNARE complex in the pathology of these diseases. Genetic and pharmacogenetic studies suggest that the SNARE complex and individual proteins might represent important molecular targets in neurological disease. In this review, we summarize the recent progress toward understanding the SNARE complex in regulating membrane fusion events and provide an update of the recent discoveries from clinical and basic research on the SNARE complex in neurodegenerative, neuropsychiatric, and neurodevelopmental diseases.

目的 构建一种基于深度学习的革兰染色图像自动分类模型EKNet,实现对泌尿系统感染常见的大肠埃希菌(Eco)和肺炎克雷伯菌(Kpn)的快速诊断.方法 将预处理后的细菌图像输入残差网络模型,计算交叉熵损失,通过反向传播算法进行参数优化,获得预训练模型EKNet.共采集368例Eco和292例Kpn显微图像,其中272例Eco和214例Kpn进行训练,40例Eco和30例Kpn进行验证,余下104例图像进行测试.以ResNet50模型和AlexNet模型作为对照,评估EKNet模型的实用性.结果 EKNet模型测试一个样本的平均用时是0.165 s,优于ResNet50模型的0.38 s和AlexNet模型的0.66 s;图像识别准确率达98.8％,优于ResNet50模型的96.4％和AlexNet模型的78.6％.EKNet模型对104例临床测试的显微图像输出结果与尿培养的结果完全吻合,正确率为100％.结论 成功构建Eco和Kpn的图像诊断模型EKNet,为临床泌尿系统感染的快速诊断提供参考.