A quantized iterative learning control (QILC) for continuous-time multi-agent systems with finite-leveled sigma- delta (ΣA) quantization and random packet losses is first proposed in this paper. To ...realize the digital communication between signals and utilize limited communication bandwidth effectively, we introduce the ΣA quantizer with limited communication data rate (quantization bits) into the control field and for the design of the QILC in this paper. In addition, the packet losses are also first considered into the QILC, which makes the controller more close to the practical engineering applications. Since the nonlinearity and randomness introduced by the quantization and packet losses, a decreasing learning gain is utilized with the help of the non-smooth analysis and mathematical expectation for the analysis of convergence. Accurate tracking in the sense of expectation can be obtained based on randomly small number of quantization bits, even merely one bit of quantization information. Numerical simulations are given to show the effectiveness of the proposed protocol.
Metformin is a commonly used drug for the treatment of diabetes. Accumulating evidence suggests that it exerts anti-tumor effects in many cancers, including multiple myeloma (MM); however, the ...underlying molecular mechanisms have not been clearly elucidated.
The anti-myeloma effects of metformin were evaluated using human MM cell lines (RPMI8226 and U266) in vitro and in vivo NOD-SCID murine xenograft MM model. Cell viability was assessed with CCK8 and cell proliferation was measured by EdU incorporation assay. Cell cycle distribution and apoptosis were examined by flow cytometry. Transmission electron microscopy was used to visualized autophagosomes. Activation of AMPK and inhibition of mTORC1/C2 pathways was assessed by Western blot analysis. RPMI8226 cells and U266 cell lines with AMPK knockdown were generated by transfection with small interfering RNA targeting the AMPK-α1 and α2 subunits using Lipofectamine 2000 reagent.
Metformin effectively inhibited the proliferation of MM cell lines, an effect that was associated with the induction of autophagy and G0/G1 cell cycle arrest, but not apoptosis. Metformin activated AMPK and repressed both mTORC1 and mTORC2 signaling pathways in myeloma cells as well as downstream molecular signaling pathways, such as p-4EBP1 and p-AKT. AMPK activation resulted in direct phosphorylation and activation of tuberous sclerosis complex 2 (TSC2), leading to inhibition of the mammalian target of rapamycin (mTOR). In addition, metformin inhibited myeloma cell growth in an AMPK-dependent manner. The xenograft mouse model further confirmed that metformin inhibited tumor growth by upregulation of AMPK and downregulation of mTOR.
Metformin inhibits the proliferation of myeloma cells by inducing autophagy and cell-cycle arrest. Our results suggest that the molecular mechanism involves dual repression of mTORC1 and mTORC2 pathways via AMPK activation. Our study provides a theoretical basis for the development of novel strategies for the treatment of MM using metformin as an already approved and safe drug.
Tea polyphenols (TPs) are the general compounds of natural polyhydroxyphenols extracted in tea. Although a large number of studies have shown that TPs have obvious neuroprotective and neuro repair ...effects, they are limited due to the low bioavailability in vivo. However, TPs can act indirectly on the central nervous system by affecting the “microflora–gut–brain axis”, in which the microbiota and its composition represent a factor that determines brain health. Bidirectional communication between the intestinal microflora and the brain (microbe–gut–brain axis) occurs through a variety of pathways, including the vagus nerve, immune system, neuroendocrine pathways, and bacteria-derived metabolites. This axis has been shown to influence neurotransmission and behavior, which is usually associated with neuropsychiatric disorders. In this review, we discuss that TPs and their metabolites may provide benefits by restoring the imbalance of intestinal microbiota and that TPs are metabolized by intestinal flora, to provide a new idea for TPs to play a neuroprotective role by regulating intestinal flora.
Low R/FR irradiation can promote dodder haustorium formation on the host plant; however, the mechanisms underlying the process are still unknown. In this study, we compared the transcriptomic data ...during the formation of haustorium of Cuscuta chinensis on host plant Arabidopsisthaliana under low (R/FR = 0.1) versus high (R/FR = 0.2) R/FR irradiation at 12 h, 24 h and 72 h time points. The results show that low R/FR radiation significantly promoted the entanglement and haustorium formation. Transcriptome analysis showed that during the early stage of haustorium formation, low R/FR radiation significantly up-regulated ARR-A related genes and down-regulated peroxidase related genes compared with high R/FR radiation. Meanwhile, during the middle stage of haustorium formation, low R/FR treatment significantly increased the expression of genes related to pectinesterase (PE), polygalacturonase (PG) and pectin lyase (Pel) production, while, during the late stage of haustorium formation, peroxidase (Prx)-related genes were differentially expressed under different R/FR treatments. Overall, our findings show that a low R/FR ratio promotes the parasitism of C. chinensis through plant hormone signal transduction and cell wall degradation pathways. This study provides a basis for the control of parasitic plants.
A growing body of evidence has demonstrated the vital roles of circular RNAs (circRNAs) in cancer progression and drug resistance. We intended to explore the roles and mechanisms of circ_ZFR in the ...paclitaxel (PTX) resistance and progression of non-small cell lung cancer (NSCLC).
Two NSCLC cell lines A549 and H460 were used in this study. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was conducted to measure the levels of circ_ZFR, ZFR, miR-195-5p and karyopherin subunit alpha 4 (KPNA4) mRNA. RNase R assay was used to analyze the characteristic of circ_ZFR. MTT assay was carried out to assess PTX resistance and cell proliferation. Flow cytometry analysis was utilized to analyze cell cycle and apoptosis. Transwell assay was used to examine cell migration and invasion. Western blot assay was conducted to measure the protein levels of Ki67, Twist1, E-cadherin and KPNA4. Dual-luciferase reporter assay was adopted to verify the combination between miR-195-5p and circ_ZFR or KPNA4. Murine xenograft model assay was used to investigate the effect of circ_ZFR on PTX resistance of NSCLC in vivo.
Circ_ZFR level was enhanced in PTX-resistant NSCLC tissues and cells. Knockdown of circ_ZFR suppressed PTX resistance, cell cycle process, proliferation, migration and invasion and induced apoptosis in PTX-resistant NSCLC cells. For mechanism analysis, circ_ZFR knockdown markedly downregulated the expression of KPNA4 by sponging miR-195-5p, thereby promoting PTX sensitivity and suppressing cell progression in PTX-resistant NSCLC cells. In addition, circ_ZFR silencing enhanced PTX sensitivity of NSCLC in vivo.
Circ_ZFR knockdown played a positive role in overcoming PTX resistance of NSCLC via regulating miR-195-5p/KPNA4 axis, which might provide a possible circRNA-targeted therapy for NSCLC.
This paper studies the consensus of mixed-order unknown periodic time-vary parameterized nonlinear multi-agent systems over heterogeneous network topology. The follower is represented by a ...first-order or second-order periodic parameterized dynamic system, and the leader is presented through a second-order dynamic system. For unknown leader dynamics and bounded input disturbances, a differential adaptive parameter learning law is designed. For unknown periodic time-varying parameters, a repetitive learning law is designed based on the design method of repeated learning. Based on Lyapunov-like stability theory and repetitive learning control method, a new repetitive learning controller is designed and a sufficient condition of consensus for the MAS is also given in this paper. Unlike some existing results, this study is a fully distributed result. Finally, a simulation example is given to verify the effectiveness of this study.
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