MiR-135a-5p suppresses breast cancer cell proliferation, migration, and invasion by regulating BAG3

Background: MicroRNAs (miRNAs) are involved in the progression of diverse human cancers. This work aimed to delve into how microRNA-135a-5p (miR-135a-5p) affects the biological behaviors of Breast Cancer (BC) cells. Methods: Gene Expression Omnibus (GEO) datasets were used to analyze the expression differences of miR-135a-5p in cancer tissues of BC patients. Quantitative real-time PCR and western blot were conducted to detect miR-135a-5p and Bcl-2 Associated Athanogene (BAG3) expression levels in BC tissues and cells, respectively. The proliferation, migration, invasion, and cell cycle of BC cells were detected by cell counting kit-8 assay, BrdU assay, wound healing assay, transwell assay, and flow cytometry. The targeted relationship between miR-135a-5p and BAG3 mRNA 3′UTR predicted by bioinformatics was further testified by a dual-luciferase reporter gene assay. Pearson's correlation analysis was adopted to analyze the correlation between miR-135a-5p expression and BAG3 expression. The downstream pathways of BAG3 were analyzed by the LinkedOmics database. Results: MiR-135a-5p was significantly down-regulated and BAG3 expression was significantly raised in BC tissues. MiR-135a-5p overexpression repressed the viability, migration and invasion of BC cells, and blocked cell cycle progression in G0/G1 phase while inhibiting miR-135a-5p worked oppositely. BAG3 was verified as a target of miR-135a-5p. Overexpression of BAG3 reversed the impacts of miR-135a-5p on the malignant biological behaviors of BC cells. The high expression of BAG3 was associated with the activation of the cell cycle, mTOR and TGF-β signaling pathways. Conclusion: MiR-135a-5p regulates BAG3 to repress the growth, migration, invasion, and cell cycle progression of BC cells

G-protein-coupled estrogen receptor agonist G-1 inhibits the proliferation of breast cancer cells through induction of apoptosis and cycle arrest

Purpose: To determine the effect of G-1, a G-protein-linked estrogen receptor (GPER) agonist on apoptosis, cell cycle, and proliferative potential of mammary tumor cells, and the associated mechanisms of action. Methods: Three groups of human breast cancer cell line MDA-MB-231 were used: control group, estradiol (E2) group and G-1 group. Control group was not treated. The effects of treatment (10 M G1) on cell proliferation were determined and compared amongst the groups. Cell cycle distribution and apoptosis were determined while expression levels of proteins related to pi3k/AKT/MAPK were assessed by western blotting. Results: Apoptosis was significantly reduced in E2 group relative to control, but was enhanced in G-1 group, when compared to the other 2 groups (p < 0.05). There were marked down-regulations in protein levels of cylinb1, p21, caspase 6, p53, p-ERK in E2 group, relative to the corresponding expression levels in the control group. Conclusion: GPER agonist G-1 suppresses the proliferation of mammary tumor cells and induces apoptotic changes and cycle blockage in the cells via inhibition of pi3k/AKT pathway and activation of MAPKs pathway. Thus, GPER is a potential target in breast tumor treatment, and G-1 is a potential new anti-tumor drug

Oscillatory Stability and Eigenvalue Sensitivity Analysis of A DFIG Wind Turbine System

2010-2011 > Academic research: refereed > Publication in refereed journa

The allogeneic umbilical cord mesenchymal stem cells regulate the function of T helper 17 cells from patients with rheumatoid arthritis in an in vitro co-culture system

BACKGROUND: Previous in vivo studies have shown that mesenchymal stem cell (MSC) transplantation significantly improves the condition of a number of autoimmune diseases including autoimmune cerebrospinal meningitis, multiple sclerosis, glomerulonephritis and systemic lupus erythematosus. METHODS: To investigate the immunoregulatory effect of stem cell transplantation, human umbilical cord MSCs were co-cultured with peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis (RA). Orphan nuclear receptor gamma (ROR-γ) mRNA and protein expression was detected with real-time PCR and Western blotting. Interleukin (IL)-17, IL-6 and tumor necrosis factor (TNF-α) in the cell culture supernatant were measured using a flow cytometric bead capture method. RESULTS: After 72 hours of co-culture, the mRNA and protein expression levels of ROR-γ in co-cultured PBMCs were decreased compared with that in PBMC of RA patients cultured alone (p < 0.05). Moreover, the decrement was positively related to the disease activity of RA (p < 0.05). Decreased secretion of IL-17, TNF-α and IL-6 were also found in co-culture supernatants of PBMCs from patients with severe and moderate disease activity, but not in supernatant from PBMCs cultured alone. The decreased cytokine expression levels were positively correlated to the concentrations of MSCs. In contrast, PBMCs from healthy controls or patients with mild RA did not show significant differences in ROR-γ expression or cytokine secretion following co-culture with MSCs as compared with those cultured alone. CONCLUSIONS: In vitro co-culture with MSCs down-regulated the inflammatory response of PBMCs from RA patients with severe disease activity, but had no significant effect on PBMCs from healthy controls or patients with mild disease activity, suggesting that the immunoregulatory role of MSCs may associate with the occurrence of inflammatory mediators

Synthetic Datasets for Autonomous Driving: A Survey

Autonomous driving techniques have been flourishing in recent years while thirsting for huge amounts of high-quality data. However, it is difficult for real-world datasets to keep up with the pace of changing requirements due to their expensive and time-consuming experimental and labeling costs. Therefore, more and more researchers are turning to synthetic datasets to easily generate rich and changeable data as an effective complement to the real world and to improve the performance of algorithms. In this paper, we summarize the evolution of synthetic dataset generation methods and review the work to date in synthetic datasets related to single and multi-task categories for to autonomous driving study. We also discuss the role that synthetic dataset plays the evaluation, gap test, and positive effect in autonomous driving related algorithm testing, especially on trustworthiness and safety aspects. Finally, we discuss general trends and possible development directions. To the best of our knowledge, this is the first survey focusing on the application of synthetic datasets in autonomous driving. This survey also raises awareness of the problems of real-world deployment of autonomous driving technology and provides researchers with a possible solution.Comment: 19 pages, 5 figure

Advances in the Antifungal Effects of Plant Essential Oils

Foods, agricultural by-products and medicinal plants are often contaminated by pathogenic fungi and mycotoxins. Pathogenic fungi not only lead to food deterioration, but also harm people’s health. The commonly used methods for detoxification include physical, chemical and biological methods. A large number of studies have shown that natural plant essential oils inhibit the growth of pathogenic fungi and the accumulation of mycotoxins and have good biodegradability, making them a promising environmental-friendly alternative to traditional synthetic fungicides. In this review, the classification and harm of common pathogenic fungi and mycotoxins, as well as the antifungal components and mechanisms of plant essential oils are introduced, and recent progress on plant essential oils in the control of pathogenic fungi and mycotoxins is summarized. This review provides a theoretical basis for the development and application of plant essential oils

Seasonal variations in carbon, nitrogen and phosphorus concentrations and C:N:P stoichiometry in different organs of a Larix principis-rupprechtii Mayr. plantation in the Qinling Mountains, China

Understanding how concentrations of elements and their stoichiometry change with plant growth and age is critical for predicting plant community responses to environmental change. Weusedlong-term field experiments to explore how the leaf, stem and root carbon (C), nitrogen (N) and phosphorous (P) concentrations and their stoichiometry changed with growth and stand age in a L.principis-rupprechtii Mayr. plantation from 2012–2015 in the Qinling Mountains, China. Our results showed that the C, N and P concentrations and stoichiometric ratios in different tissues of larch stands were affected by stand age, organ type andsampling month and displayed multiple correlations with increased stand age in different growing seasons. Generally, leaf C and N concentrations were greatest in the fast-growing season, but leaf P concentrations were greatest in the early growing season. However, no clear seasonal tendencies in the stem and root C, N and P concentrations were observed with growth. In contrast to N and P, few differences were found in organ-specific C concentrations. Leaf N:P was greatest in the fast-growing season, while C:N and C:P were greatest in the late-growing season. No clear variations were observed in stem and root C:N, C:P andN:Pthroughout the entire growing season, but leaf N:P was less than 14, suggesting that the growth of larch stands was limited by N in our study region. Compared to global plant element concentrations and stoichiometry, the leaves of larch stands had higher C, P, C:NandC:PbutlowerNandN:P,andtherootshadgreater PandC:NbutlowerN,C:Pand N:P. Our study provides baseline information for describing the changes in nutritional elements with plant growth, which will facilitates plantation forest management and restoration, and makes avaluable contribution to the global data pool on leaf nutrition and stoichiometry

Combination of Clostridium butyricum and Corn Bran Optimized Intestinal Microbial Fermentation Using a Weaned Pig Model

Experimental manipulation of the intestinal microbiota influences health of the host and is a common application for synbiotics. Here Clostridium butyricum (C. butyricum, C.B) combined with corn bran (C.B + Bran) was taken as the synbiotics application in a waned pig model to investigate its regulation of intestinal health over 28 days postweaning. Growth performance, fecal short chain fatty acids (SCFAs) and bacterial community were evaluated at day 14 and day 28 of the trial. Although the C.B + Bran treatment has no significant effects on growth performance (P &gt; 0.05), it optimized the composition of intestinal bacteria, mainly represented by increased acetate-producing bacteria and decreased pathogens. Microbial fermentation in the intestine showed a shift from low acetate and isovalerate production on day 14 to enhanced acetate production on day 28 in the C.B + Bran treatment. Thus, C.B and corn bran promoted intestinal microbial fermentation and optimized the microbial community for pigs at an early age. These findings provide perspectives on the advantages of synbiotics as a new approach for effective utilization of corn barn

AaABF3, an Abscisic Acid–Responsive Transcription Factor, Positively Regulates Artemisinin Biosynthesis in Artemisia annua

Artemisinin is well known for its irreplaceable curative effect on the devastating parasitic disease, Malaria. This sesquiterpenoid is specifically produced in Chinese traditional herbal plant Artemisia annua. Earlier studies have shown that phytohormone abscisic acid (ABA) plays an important role in increasing the artemisinin content, but how ABA regulates artemisinin biosynthesis is still poorly understood. In this study, we identified that AaABF3 encoded an ABRE (ABA-responsive elements) binding factor. qRT-PCR analysis showed that AaABF3 was induced by ABA and expressed much higher in trichomes where artemisinin is synthesized and accumulated. To further investigate the mechanism of AaABF3 regulating the artemisinin biosynthesis, we carried out dual-luciferase analysis, yeast one-hybrid assay and electrophoretic mobility shift assay. The results revealed that AaABF3 could directly bind to the promoter of ALDH1 gene, which is a key gene in artemisinin biosynthesis, and activate the expression of ALDH1. Functional analysis revealed that overexpression of AaABF3 in A. annua enhanced the production of artemisinin, while RNA interference of AaABF3 resulted in decreased artemisinin content. Taken together, our results demonstrated that AaABF3 played an important role in ABA-regulated artemisinin biosynthesis through direct regulation of artemisinin biosynthesis gene, ALDH1

Discovery of novel SOS1 inhibitors using machine learning

Overactivation of the rat sarcoma virus (RAS) signaling is responsible for 30% of all human malignancies. Son of sevenless 1 (SOS1), a crucial node in the RAS signaling pathway, could modulate RAS activation, offering a promising therapeutic strategy for RAS-driven cancers. Applying machine learning (ML)-based virtual screening (VS) on small-molecule databases, we selected a random forest (RF) regressor for its robustness and performance. Screening was performed with the L-series and EGFR-related datasets, and was extended to the Chinese National Compound Library (CNCL) with more than 1.4 million compounds. In addition to a series of documented SOS1-related molecules, we uncovered nine compounds that have an unexplored chemical framework and displayed inhibitory activity, with the most potent achieving more than 50% inhibition rate in the KRAS G12C/SOS1 PPI assay and an IC50 value in the proximity of 20 μg mL−1. Compared with the manner that known inhibitory agents bind to the target, hit compounds represented by CL01545365 occupy a unique pocket in molecular docking. An in silico drug-likeness assessment suggested that the compound has moderately favorable drug-like properties and pharmacokinetic characteristics. Altogether, our findings strongly support that, characterized by the distinctive binding modes, the recognition of novel skeletons from the carboxylic acid series could be candidates for developing promising SOS1 inhibitors