Multistability of State-Dependent Switched Fractional-Order Hopfield Neural Networks With Mexican-Hat Activation Function and Its Application in Associative Memories.

The multistability and its application in associative memories are investigated in this article for state-dependent switched fractional-order Hopfield neural networks (FOHNNs) with Mexican-hat activation function (AF). Based on the Brouwer's fixed point theorem, the contraction mapping principle and the theory of fractional-order differential equations, some sufficient conditions are established to ensure the existence, exact existence and local stability of multiple equilibrium points (EPs) in the sense of Filippov, in which the positively invariant sets are also estimated. In particular, the analysis concerning the existence and stability of EPs is quite different from those in the literature because the considered system involves both fractional-order derivative and state-dependent switching. It should be pointed out that, compared with the results in the literature, the total number of EPs and stable EPs increases from 5l1 3l2 and 3l1 2l2 to 7l1 5l2 and 4l1 3l2 , respectively, where 0 ≤ l1 + l2 ≤ n with n being the system dimension. Besides, a new method is designed to realize associative memories for grayscale and color images by introducing a deviation vector, which, in comparison with the existing works, not only improves the utilization efficiency of EPs, but also reduces the system dimension and computational burden. Finally, the effectiveness of the theoretical results is illustrated by four numerical simulations.

Hydrogen inhalation therapy regulates lactic acid metabolism following subarachnoid hemorrhage through the HIF-1α pathway.

The neuroprotective effects of hydrogen have been demonstrated, but the mechanism is still poorly understood. In a clinical trial of inhaled hydrogen in patients with subarachnoid hemorrhage (SAH), we found that hydrogen reduced the accumulation of lactic acid in the nervous system. There are no studies demonstrating the regulatory effect of hydrogen on lactate and in this study we hope to further clarify the mechanism by which hydrogen regulates lactate metabolism. In cell experiments, PCR and Western Blot showed that HIF-1α was the target related to lactic acid metabolism that changed the most before and after hydrogen intervention. HIF-1α levels were suppressed by hydrogen intervention treatment. Activation of HIF-1α inhibited the lactic acid-lowering effect of hydrogen. We have also demonstrated the lactic acid-lowering effect of hydrogen in animal studies. Our work clarifies that hydrogen can regulate lactate metabolism via the HIF-1αpathway, providing new insights into the neuroprotective mechanisms of hydrogen.

Coexistence and local stability of multiple equilibrium points for fractional-order state-dependent switched competitive neural networks with time-varying delays.

This paper investigates the coexistence and local stability of multiple equilibrium points for a class of competitive neural networks with sigmoidal activation functions and time-varying delays, in which fractional-order derivative and state-dependent switching are involved at the same time. Some novel criteria are established to ensure that such n-neuron neural networks can have [Formula: see text] total equilibrium points and [Formula: see text] locally stable equilibrium points with m1+m2=n, based on the fixed-point theorem, the definition of equilibrium point in the sense of Filippov, the theory of fractional-order differential equation and Lyapunov function method. The investigation implies that the competitive neural networks with switching can possess greater storage capacity than the ones without switching. Moreover, the obtained results include the multistability results of both fractional-order switched Hopfield neural networks and integer-order switched Hopfield neural networks as special cases, thus generalizing and improving some existing works. Finally, four numerical examples are presented to substantiate the effectiveness of the theoretical analysis.

Reliability of using generic flow conditions to quantify aneurysmal haemodynamics: A comparison against simulations incorporating boundary conditions measured in vivo.

BACKGROUND AND OBJECTIVES: Initiation, growth, and rupture of intracranial aneurysms are believed to be closely related to their local haemodynamic environment. While haemodynamics can be characterised by use of computational fluid dynamics (CFD), its reliability depends heavily upon accurate assumption of the boundary conditions. Herein, we compared the simulated aneurysmal haemodynamics obtained by use of generic boundary conditions against those obtained under flow conditions measured in vivo. METHODS: We prospectively recruited 19 patients with intracranial aneurysms requiring 3-dimensional rotational angiography, during which blood pressure at the internal carotid artery was probed by catheter and flowrate measured by a dedicated software tool. Using these flow conditions measured in vivo, we quantified the aneurysmal haemodynamics for each patient by CFD, and then compared the results with those derived from a generic condition reported in the literature, in terms of the time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and percentage of the intra-aneurysmal flow (PIAF). In addition, the effects on aneurysmal haemodynamics of different outflow strategies (splitting method vs. Murray's Law) and simulation schemes (transient vs. steady-state) relative to each flow condition were also assessed. RESULTS: Differences in the simulated TAWSS (-6.08 ± 10.64 Pa, p = 0.001), OSI (0.06 ± 0.13, p = 0.001), and PIAF (-0.05 ± 0.20, p = 0.012) between the patient-specific and generic boundary conditions were found to be statistically significant, in contrast to that in the RRT (49 ± 307 Pa-1, p = 0.062). Outflow strategies did not yield statistically significant differences in any of the investigated parameters (all p > 0.05); rather, the resulting parameters were found to be in good correlations (all r > 0.71, p < 0.001). Difference between the aneurysmal TAWSS and the WSS derived from cycle-averaged flowrate condition was found to be minor (0.66 ± 1.36 Pa, p = 0.000), so was that between PIAFs obtained respectively from the transient and steady-state simulations (0.02 ± 0.05, p = 0.000). CONCLUSIONS: Incorporating into simulation the patient-specific boundary conditions is critical for CFD to characterise aneurysmal haemodynamics, while outflow strategies may not introduce significant uncertainties. Steady-state simulation incorporating the cycle-averaged flow condition may produce unbiased WSS and PIAF compared to the transient analysis.

LINC00467 facilitates the proliferation, migration and invasion of glioma via promoting the expression of inositol hexakisphosphate kinase 2 by binding to miR-339-3p.

Our previous studies indicate that long noncoding RNA (lncRNA) LINC00467 can act as an oncogene to participate in the malignant progression of glioma, but the underlying molecular mechanism remains to be studied further. This study aimed to explore the biological role of the LINC00467/miR-339-3p/ inositol hexakisphosphate kinase 2 (IP6K2) regulatory axis in glioma. The Cancer Genome Atlas (TCGA), Oncomine databases and reverse transcription­quantitative PCR (RT­qPCR) were used to analyze IP6K2 expression in glioma. RT-PCR, EdU and transwell assays were conducted to observe the effect of IP6K2 on glioma cell proliferation, migration and invasion. Using bioinformatics analysis, RT-PCR, and dual luciferase reporter gene assay, the potential role of the LINC00467/miR-339-3p/IP6K2 regulatory axis in glioma was verified. The results showed that IP6K2 was up-regulated in glioma tissues and cell lines. Moreover, the expression level of IP6K2 was correlated with the clinical features of glioma patients. In vitro and in vivo experiments indicated that IP6K2 overexpression could promote the proliferation, migration, and invasion of glioma cells. Further bioinformatics analysis and in vitro assays revealed that LINC00467 could promote IP6K2 expression by binding to miR-339-3p and promote the malignant progression of glioma. Overall, LINC00467 could upregulate IP6K2 by binding to miR-339-3p and promote the proliferation, migration, and invasion of glioma cells. The LINC00467/miR-339-3p/IP6K2 regulatory axis might be a potential therapeutic target for glioma.

Event-triggered adaptive neural networks control for fractional-order nonstrict-feedback nonlinear systems with unmodeled dynamics and input saturation.

The event-triggered adaptive neural networks control is investigated in this paper for a class of fractional-order systems (FOSs) with unmodeled dynamics and input saturation. Firstly, in order to obtain an auxiliary signal and then avoid the state variables of unmodeled dynamics directly appearing in the designed controller, the notion of exponential input-to-state practical stability (ISpS) and some related lemmas for integer-order systems are extended to the ones for FOSs. Then, based on the traditional event-triggered mechanism, we propose a novel adaptive event-triggered mechanism (AETM) in this paper, in which the threshold parameters can be adjusted dynamically according to the tracking performance. Besides, different from the previous works where the derivative of hyperbolic tangent function tanh(⋅) needs to have positive lower bound, a new type of auxiliary signal is introduced in this paper to handle the effect of input saturation and thus this limitation is released. Finally, two numerical examples and some comparisons are provided to illustrate our proposed controllers.

SP1-induced lncRNA ZFPM2 antisense RNA 1 (ZFPM2-AS1) aggravates glioma progression via the miR-515-5p/Superoxide dismutase 2 (SOD2) axis.

Glioma is a common life-threatening tumor with high malignancy and high invasiveness. LncRNA ZFPM2 antisense RNA 1 (ZFPM2-AS1) was confirmed to be implicated in numerous tumors, while its biological function and mechanism have not been thoroughly understood in glioma. The gene expression was measured by RT-qPCR. Cell proliferation, cell cycle, and cell apoptosis of glioma cells were validated by CCK-8, colony formation, flow cytometry and TUNEL assays. The effect of ZFPM2-AS1 on tumor growth was verified by in vivo assay. The exploration on ZFPM2-AS1-mediated mechanism was carried out via ChIP, luciferase reporter, and RIP assays. In the present study, ZFPM2-AS1 was demonstrated as a highly-expressed lncRNA in glioma tissues and cells. ZFPM2-AS1 silencing suppressed cell proliferation and cell cycle, but facilitated cell apoptosis. In addition, the inhibitive effect of silenced ZFPM2-AS1 was also observed in tumor growth. Furthermore, we found that SP1 interacted with ZFPM2-AS1 promoter to transcriptionally activate ZFPM2-AS1 expression. Moreover, ZFPM2-AS1 was identified as a competing endogenous RNA (ceRNA) for miR-515-5p to target SOD2. Rescue assays verified that SOD2 overexpression partially abolished the suppressive impact of ZFPM2-AS1 silencing on glioma cell growth. In conclusion, this study corroborated the regulatory mechanism of SP1/ZFPM2-AS1/miR-515-5p/SOD2 axis in glioma, indicating that targeting ZFPM2-AS1 might be an effective way to treat glioma.

Nonlinear adaptive control of COVID-19 with media campaigns and treatment.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the infection of severe acute respiratory syndrome coronavirus 2, which is spreading all over the world and causing huge human and economic losses. For these reasons, we study the adaptive control problem of COVID-19 in consideration of media campaigns and treatment in this paper. Firstly, a novel compartment model is constructed by analysing the spread mechanism of COVID-19 and a nonlinear adaptive control problem is established. Then, using the estimation of parameters updated by adaptive laws, the controllers are designed to achieve the control goals. Finally, numerical examples are presented to illustrate the control capability to the outbreak of COVID-19.

MicroRNA-524 inhibits the progress of glioma via the direct targeting of NCF2.

In recent years, a large amount of research has reported that microRNA (miRNA) dysregulation is closely related to glioma progression. miR-524, a member of the miRNA family, has been confirmed to be involved in many human diseases, including glioma. However, the role and molecular mechanism of miR-524 in glioma have not been clarified. In our study, we showed that miR-524 expression was significantly decreased in glioma and was associated with glioma recurrence. Next, we performed a series of assays and confirmed that the upregulation of miR-524 suppressed glucose uptake, proliferation, migration and invasion in glioma cell lines. Then, through bioinformatics software and a dual luciferase assay, we demonstrated that NCF2 was a target gene of miR-524. In addition, we found that NCF2 reintroduction restored the inhibitor effect of miR-524 on glioma progression. These results elucidate the mechanism of miR-524 in glioma development and provide a potential therapeutic strategy for glioma patients.

Association between ABCB1 genetic polymorphism and the effect on epilepsy following phenytoin treatment.

The aim of the study was to analyze the effect of ABCB1 genetic polymorphisms on the efficacy of phenytoin (PHT) treatment in epilepsy patients. In total, 200 epilepsy patients who were administered PHT were divided into the responsive and pharmaco-resistance groups depending on the clinical data of PHT treatment in epilepsy patients. The serum concentration of PHT was detected by high-performance liquid chromatography (HPLC). ABCB1 polymorphisms were analyzed by the polymerase chain reaction restriction-fragment length polymorphism method. The C1236T, C3435T and G2677T/A haplotypes were reconstructed for the ABCB1 gene using SHEsis programs. One-way analysis of variance was used for data analysis. In ABCB1 C1236T, the rate of the CC genotype in pharmaco-resistance (17.5%) was higher than that of the responsive group (2.1%), while the rate of the TT genotype in pharmaco-resistance (41.6%) was lower than that of the responsive group (55.4%) (P<0.05). In ABCB1 G2677T/A, the rate of the GG genotype in pharmaco-resistance (29.6%) was higher than that of the responsive group (9.7%), while the rate of the TT genotype in pharmaco-resistance (4.6%) was lower than that of the responsive group (30.4%) (P<0.05). The rate of the TTC haploid in pharmaco-resistance (24.1%) was higher than that of the responsive group (8.8%) (P<0.05). The PHT serum concentration had no statistical significance in the patients with different genotypes. In conclusion, there was no association between ABCB1 genetic polymorphism and PHT serum concentration, although the polymorphisms affected the efficacy of PHT treatment in patients with epilepsy.

Caffeine-induced nuclear translocation of FoxO1 triggers Bim-mediated apoptosis in human glioblastoma cells.

Caffeine is one of the most commonly ingested neuroactive compounds and exhibits anticancer effects through induction of apoptosis and suppression of cell proliferation. However, the mechanisms underlying these effects are currently unknown. In this study, we investigated the mechanisms of caffeine-induced apoptosis in U251 cells (human glioma cell line). We analyzed the inhibitory effects of caffeine on cell proliferation by performing WST-8 and colony formation assays; in addition, cell survival was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and flow cytometric analysis. Western blotting was used to investigate the role played by FoxO1 in the proapoptotic effects of caffeine on glioma cells. Results showed that caffeine inhibited proliferation and survival of human glioma cells, induced apoptosis, and increased the expression of FoxO1 and its proapoptotic target Bim. In addition, we found that FoxO1 enhanced the transcription of its proapoptotic target Bim. In summary, our data indicates that FoxO1-Bim mediates caffeine-induced regression of glioma growth by activating cell apoptosis, thereby providing new mechanistic insight into the possible use of caffeine in treating human cancer.

Curcumin enhances the radiosensitivity of U87 cells by inducing DUSP-2 up-regulation.

OBJECTIVE: Glioblastoma multiforme (GBM), an aggressive primary brain tumor, is radioresistant and recurs despite aggressive surgery, chemotherapy, and radiotherapy. Curcumin as a potential radiosensitizer has received extensive attention in cancer treatment. To explore an effectiveness of this radiosensitizer for GBM treatment, we evaluated the radiosensitizing effect of curcumin and investigated its potential molecular mechanisms in the human glioma cell line U87. METHODS: The cytotoxic effects of curcumin on U87 cells were evaluated using the Cell Counting Kit-8 assay, and the radiosensitivity of U87 cells treated with curcumin was accessed by colony information assay. The effects of curcumin on cell proliferation and cell cycle regulation were determined using the 5-ethynyl-2-deoxyuridine incorporation assay and flow cytometry, respectively. Western blotting was applied to determine the effects of curcumin on protein expression of dual-specificity phosphatase-2 (DUSP-2), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) as well as phosphorylated ERK and JNK. RESULTS: Curcumin significantly inhibited the proliferation of U87 cells in a dose-and time-dependent manner. Curcumin treatment at the concentrations of 5 µM and 10 M could significantly reduce the clonogenic activity and enhance the radiosensitivity of U87 cells with sensitive enhancement ratios (SERs) of 1.71 and 4.65, respectively. Curcumin resulted in G2/M cell cycle arrest in U87 cells, which were radiosensitive. Pre-treatment of U87-MG cells with 5 µM curcumin enhanced radiation-induced cell proliferation inhibition and apoptosis. Furthermore, we observed that curcumin increased DUSP-2 protein expression and decreased the phosphorylation of ERK and JNK. CONCLUSION: Our results suggest that low-dose curcumin may enhance the radiosensitivity of human glioma U87 cells in vitro by inducing G2/M cell cycle arrest through up-regulation of DUSP-2 expression and inhibition of ERK and JNK phosphorylation.

AntagomiR-27a targets FOXO3a in glioblastoma and suppresses U87 cell growth in vitro and in vivo.

OBJECTIVE: To study the effect of the antagomiR-27a inhibitor on glioblastoma cells. METHODS: The miR- 27a expression level in specimens of human glioblastoma and normal human brain tissues excised during decompression for traumatic brain injury was assessed using qRT-PCR; The predicted target gene of miR-27a was screened out through bioinformatics databases, and the predicted gene was verified using genetic report assays; the effect of antagomiR-27a on the invasion and proliferation of glioma cells was analyzed using MTT assays and 5-ethynyl-2'-deoxyuridine (EdU) labeling. A xenograft glioblastoma model in BALB-c nude mice was established to detect the effect of antagomiR-27a on tumour growth. RESULTS: qRT-PCR results showed that miR-27a significantly increased in specimens from glioblastoma comparing with normal human brain tissues. Th miR-27a inhibitor significantly suppressed invasion and proliferation of glioblastoma cells. FOXO3a was verified as a new target of miR-27a by Western blotting and reporter analyzes. Tumor growth in vivo was suppressed by administration of the miR-27a inhibitor. CONCLUSION: MiR-27a may be up-regulated in human glioblastoma, and antagomiR-27a could inhibit the proliferation and invasion ability of glioblastoma cells.