Robust exponential stability of discrete-time uncertain impulsive stochastic neural networks with delayed impulses.

This paper is devoted to the study of the robust exponential stability (RES) of discrete-time uncertain impulsive stochastic neural networks (DTUISNNs) with delayed impulses. Using Lyapunov function methods and Razumikhin techniques, a number of sufficient conditions for mean square (RES-ms) robust exponential stability are derived. The obtained results show that the hybrid dynamic is RES-ms with regard to lower boundary of impulse interval if the discrete-time stochastic neural networks (DTSNNs) is RES-ms and that the impulsive effects are instable. Conversely, if DTSNNs is not RES-ms, impulsive effects can induce unstable neural networks (NNs) to stabilize again concerning an upper bound of the impulsive interval. The results obtained in this study have a broader scope of application than some previously existing findings. Two numerical examples were presented to verify the availability and advantages of the results.

Imatinib prevents elastase-induced abdominal aortic aneurysm progression by regulating macrophage-derived MMP9.

Abdominal aortic aneurysm (AAA) is characterized with progressive weakening and considerable dilation of the aortic wall. Despite the high risk of mortality in the elderly population, there are still no clinical pharmacological therapies to alleviate AAA progression. Macrophage-derived MMP9 acts as a key factor in extracellular matrix degradation and is crucial for aortic aneurysm development and aortic rupture. Here, we demonstrated that the transcription level of MMP9 was suppressed with a concentration-dependent manner in macrophages after Imatinib treatment, which was accompanied by the down-regulation of MMP9 protein expression and reduced MMP9 secretion in vitro. Imatinib administration (50 mg/kg/d, i.g.) was carried out one week after the establishment of elastase-induced AAA in rats, stabilizing aneurysm progression and improving survival rate via decreasing the aortic diameter and preventing elastin degradation. Expression and activity of MMP9 in the artery tissues were significantly suppressed after Imatinib treatment via in situ assessment like immunohistochemistry and zymography, although macrophage infiltration was not affected. Furthermore, we found that Imatinib inhibited MMP9 transcription through reduction of STAT3 phosphorylation and translocation from nucleus to cytoplasm. These observations indicated that Imatinib prevents aneurysm progression by inhibiting STAT3-mediated MMP9 expression and activation, suggesting a new application of Imatinib on AAA clinical therapy.

PARP1 Suppresses the Transcription of PD-L1 by Poly(ADP-Ribosyl)ating STAT3.

Studies have pointed to a role of PARP1 in regulating gene expression through poly(ADP-ribosyl)ating, sequence-specific, DNA-binding transcription factors. However, few examples exist that link this role of PARP1 to the immunogenicity of cancer cells. Here, we report that PARP1 poly(ADP-ribosyl)ates STAT3 and subsequently promotes STAT3 dephosphorylation, resulting in reduced transcriptional activity of STAT3 and expression of PD-L1. In this study, we showed that PARP1 silencing or pharmacologic inhibition enhanced the transcription of PD-L1 in cancer cells, which was accompanied by the upregulation of PD-L1 protein expression, both in the cytoplasm and on the cell surface. This induction of PD-L1 was attenuated in the absence of the transcription factor STAT3. Cell-based studies indicated that PARP1 interacted directly with STAT3 and caused STAT3 poly(ADP-ribosyl)ation. STAT3's activation of PD-L1 transcription was abolished by the overexpression of wild-type PARP1 but not mutant PARP1, which lacks catalytic activity. PARP1 downregulation or catalytic inhibition enhanced the phosphorylation of STAT3, which was reversed by the ectopic expression of wild-type PARP1 but not by mutated PARP1. An inverse correlation between PARP1 and PD-L1 was also observed in clinical ovarian cancer samples. Overall, our study revealed PARP1-mediated poly(ADP-ribosyl)ation of STAT3 as a key step in inhibiting the transcription of PD-L1, and this mechanism exists in a variety of cancer cells.

Imatinib prevents lung cancer metastasis by inhibiting M2-like polarization of macrophages.

Although M2-like tumor-associated macrophages (TAMs) have been considered as a vital therapeutic target in cancer therapy due to their role in promoting tumor progression and metastasis, very few compounds have been identified to inhibit M2-like polarization of TAMs. Here, we showed that Imatinib significantly prevented macrophage M2-like polarization induced by IL-13 or IL-4 in vitro, as illustrated by reduced expression of cell surface marker CD206 and M2-like genes, including Arg1, Mgl2, Mrc1, CDH1, and CCL2. Further, the migration of lung cancer cells promoted by the conditioned medium from M2-like macrophages could be restrained by Imatinib. Mechanistically, Imatinib inhibited STAT6 phosphorylation and nuclear translocation, resulting in the macrophage M2-like polarization arrest. Furthermore, Imatinib reduced the number of metastasis of Lewis lung cancer without affecting tumor growth. Both in tumor and lung tissues, the percentage of M2-like macrophages decreased after the administration of Imatinib for one week. Taken together, these data suggest that Imatinib is able to inhibit macrophage M2-like polarization, which plays a vital role in Imatinib suppressed metastasis of Lewis lung cancer.

Bergamotane Sesquiterpenes with Alpha-Glucosidase Inhibitory Activity from the Plant Pathogenic Fungus Penicillium expansum.

Two new bergamotane sesquiterpene lactones, named expansolides C and D (1 and 2), together with two known compounds expansolides A and B (3 and 4), were isolated from the plant pathogenic fungus Penicillium expansum ACCC37275. The structures of the new compounds were established by detailed analyses of the spectroscopic data, especially 1D-, 2D-NMR, and HR-ESI-MS. In an in vitro bioassay, the epimeric mixture of expansolides C and D (1 and 2) (in a ratio of 2:1 at the temprature of the bioassay) exhibited more potent α-glucosidase inhibitory activity (IC50 =0.50 ± 0.02 mm) as compared with the positive control acarbose (IC50 = 1.90 ± 0.05 mm). To the best of our knowledge, it was the first report on the α-glucosidase inhibitory activity of bergamotane sesquiterpenes.

Network-Based Robust H2/H∞ Control for Linear Systems With Two-Channel Random Packet Dropouts and Time Delays.

This paper focuses on the robust output feedback H2/H∞ control issue for a class of discrete-time networked control systems with uncertain parameters and external disturbance. Sensor-to-controller and controller-to-actuator packet dropouts and time delays are considered simultaneously. According to the stochastic characteristic of the packet dropouts and time delays, a model based on a Markov jump system framework is proposed to randomly compensate for the adverse effect of the two-channel packet dropouts and time delays. To analyze the robust stability of the resulting closed-loop system, a Lyapunov function is proposed, based on which sufficient conditions for the existence of the H2/H∞ controller are derived in terms of linear matrix inequalities, ensuring robust stochastic stability as well as the prescribed H2 and H∞ performance. Finally, an angular positioning system is exploited to demonstrate the effectiveness and applicability of the proposed design strategy.