Reinforcement Learning Based Minimum State-flipped Control for the Reachability of Boolean Control Networks

To realize reachability as well as reduce control costs of Boolean Control Networks (BCNs) with state-flipped control, a reinforcement learning based method is proposed to obtain flip kernels and the optimal policy with minimal flipping actions to realize reachability. The method proposed is model-free and of low computational complexity. In particular, Q-learning (QL), fast QL, and small memory QL are proposed to find flip kernels. Fast QL and small memory QL are two novel algorithms. Specifically, fast QL, namely, QL combined with transfer-learning and special initial states, is of higher efficiency, and small memory QL is applicable to large-scale systems. Meanwhile, we present a novel reward setting, under which the optimal policy with minimal flipping actions to realize reachability is the one of the highest returns. Then, to obtain the optimal policy, we propose QL, and fast small memory QL for large-scale systems. Specifically, on the basis of the small memory QL mentioned before, the fast small memory QL uses a changeable reward setting to speed up the learning efficiency while ensuring the optimality of the policy. For parameter settings, we give some system properties for reference. Finally, two examples, which are a small-scale system and a large-scale one, are considered to verify the proposed method

Nox2 dependent redox-regulation of microglial response to amyloid-β stimulation and microgliosis in aging

Microglia express constitutively a Nox2 enzyme that is involved in neuroinflammation by the generation of reactive oxygen species (ROS). Amyloid β (Aβ) plays a crucial role in Alzheimer’s disease. However, the mechanism of Aβ-induced microglial dysfunction and redox-regulation of microgliosis in aging remains unclear. In this study, we examined Nox2-derived ROS in mediating microglial response to Aβ peptide 1–42 (Aβ42) stimulation in vitro, in aging-associated microgliosis in vivo and in post-mortem human samples. Compared to controls, Aβ42 markedly induced BV2 cell ROS production, Nox2 expression, p47phox and ERK1/2 phosphorylation, cell proliferation and IL-1β secretion. All these changes could be inhibited to the control levels in the presence of Nox2 inhibitor or superoxide scavenger. Compared to young (3–4 months) controls, midbrain tissues from wild-type aging mice (20– 22 months) had significantly higher levels of Nox2-derived ROS production, Aβ deposition, microgliosis and IL-1β production. However, these aging-related changes were reduced or absent in Nox2 knockout aging mice. Clinical significance of aging-associated Nox2 activation, microgliosis and IL-1β production was investigated using post-mortem midbrain tissues of humans at young (25–38 years) and old age (61–85 years). In conclusion, Nox2-dependent redox-signalling is crucial in microglial response to Aβ42 stimulation and in aging-associated microgliosis and brain inflammation

In vivo and in silico characterization of apocynin in reducing organ oxidative stress: a pharmacokinetic and pharmacodynamic study

Apocynin has been widely used in vivo as a Nox2-contaninig NADPH oxidase inhibitor. However, its time-dependent tissue distribution and inhibition on organ reactive oxygen species (ROS) production remained unclear. In this study, we examined apocynin pharmacokinetics and pharmacodynamics (PKPD) after iv injection (bolus, 5 mg/kg) of mice (CD1, 12-week). Apocynin was detected using a HPLC coupled to a linear ion-trap tandem mass spectrometer. Apocynin peak concentrations were detected in plasma at 1 min (5494±400 ng/mL) (t1/2=0.05 h, clearance=7.76 L/h/kg), in urine at 15 min (14942±5977 ng/mL), in liver at 5 min (2853±35 ng/g), in heart at 5 min (3161±309 ng/g) and in brain at 1 min (4603±208 ng/g) after iv injection. These were accompanied with reduction of ROS production in the liver, heart and brain homogenates. Diapocynin was not detected in these samples. Therapeutic effect of apocynin was examined using a mouse model (C57BL/6J) of high-fat diet (HFD, 16 weeks)-induced obesity and accelerated aging. Apocynin (5 mM) was supplied in drinking water during the HFD period and was detected at the end of treatment in the brain (5369±1612 ng/g), liver (4818±1340 ng/g) and heart (1795±1487 ng/g) along with significant reductions of ROS production in these organs. In conclusion, apocynin PKPD is characterized by a short half-life, rapid clearance, good distribution and inhibition of ROS production in major organs. Diapocynin is not a metabolite of apocynin in vivo. Apocynin crosses easily the blood-brain barrier and reduces brain oxidative stress associated with metabolic disorders and aging

p47phox-dependent oxidant signalling through ASK1, MKK3/6 and MAPKs in Angiotensin II-induced cardiac hypertrophy and apoptosis

The p47phox is a key regulatory subunit of Nox2-containing NADPH oxidase (Nox2) that by generating reactive oxygen species (ROS) plays an important role in Angiotensin II (AngII)-induced cardiac hypertrophy and heart failure. However, the signalling pathways of p47phox in the heart remains unclear. In this study, we used wild-type (WT) and p47phox knockout (KO) mice (C57BL/6, male, 7-month-old, n = 9) to investigate p47phox-dependent oxidant-signalling in AngII infusion (0.8 mg/kg/day, 14 days)-induced cardiac hypertrophy and cardiomyocyte apoptosis. AngII infusion resulted in remarkable high blood pressure and cardiac hypertrophy in WT mice. However, these AngII-induced pathological changes were significantly reduced in p47phox KO mice. In WT hearts, AngII infusion increased significantly the levels of superoxide production, the expressions of Nox subunits, the expression of PKCα and C-Src and the activation of ASK1 (apoptosis signal-regulating kinase 1), MKK3/6, ERK1/2, p38 MAPK and JNK signalling pathways together with an elevated expression of apoptotic markers, i.e., γH2AX and p53 in the cardiomyocytes. However, in the absence of p47phox, although PKCα expression was increased in the hearts after AngII infusion, there was no significant activation of ASK1, MKK3/6 and MAPKs signalling pathways and no increase in apoptosis biomarker expression in cardiomyocytes. In conclusion, p47phox-dependent redox-signalling through ASK1, MKK3/6 and MAPKs plays a crucial role in AngII-induced cardiac hypertrophy and cardiomyocyte apoptosis

Inhibition of endothelial Nox2 activation by LMH001 protects mice from angiotensin II-induced vascular oxidative stress, hypertension and aortic aneurysm

Endothelial oxidative stress and inflammation attributable to the activation of a Nox2-NADPH oxidase are key features of many cardiovascular diseases. Here, we report a novel small chemical compound (LMH001, MW=290.079), by blocking phosphorylated p47phox interaction with p22phox, inhibited effectively angiotensin II (AngII)-induced endothelial Nox2 activation and superoxide production at a small dose (IC50=0.25µM) without effect on peripheral leucocyte oxidative response to pathogens. The therapeutic potential of LMH001 was tested using a mouse model (C57BL/6J, 7-month-old) of AngII infusion (0.8mg/kg/d, 14 days)-induced vascular oxidative stress, hypertension and aortic aneurysm. Age-matched littermates of p47phox knockout mice were used as controls of Nox2 inhibition. LMH001 (2.5mg/kg/d, ip. once) showed no effect on control mice, but inhibited completely AngII infusion-induced excess ROS production in vital organs, hypertension, aortic walls inflammation and reduced incidences of aortic aneurysm. LMH001 effects on reducing vascular oxidative stress was due to its inhibition of Nox2 activation and was abrogated by knockout of p47phox. LMH001 has the potential to be developed as a novel drug candidate to treat oxidative stress-related cardiovascular diseases

Research on Teaching Reform of “Software Development and Practice”

Software development practice course unlike any experimental courses of high-level programming languages and software engineering, as an independent, practical, comprehensive software development practices and research training courses, training students’ capabilities of software development, and other courses teaching content simultaneously, whose purpose is to enable students to understand the basic idea of software technology, to master methods, techniques and tools for software development, to master software development skills, to develop creative engineering design capability and ability to work together, to improve the ability of the comprehensive analysis and problem solving. In this paper, a new reform program in the teaching process has been put forward based on the software development and practice of curriculum reform

Dietary Supplementation with Sea Buckthorn Berry Puree Alters Plasma Metabolomic Profile and Gut Microbiota Composition in Hypercholesterolemia Population

Sea buckthorn berries have been reported to have beneficial effects on plasma lipid profile and cardiovascular health. This study aimed to investigate the impact of intervention with sea buckthorn berry puree on plasma metabolomics profile and gut microbiota in hypercholesterolemic subjects. A total of 56 subjects with hypercholesterolemia consumed 90 g of sea buckthorn berry puree daily for 90 days, and plasma metabolomic profile was studied at 0 (baseline), 45, and 90 days of intervention by using proton nuclear magnetic resonance spectroscopy (H-1 NMR). Gut microbiota composition was analyzed at the baseline and after 90 days of supplementation by using high-throughput sequencing. The plasma metabolic profile was significantly altered after 45 days of intervention as compared to the baseline (day 0). A clear trend of returning to the baseline metabolomic profile was observed in plasma when the intervention extended from 45 days to 90 days. Despite this, the levels of several key plasma metabolites such as glucose, lactate, and creatine were lowered at day 90 compared to the baseline levels, suggesting an improved energy metabolism in those patients. In addition, intervention with sea buckthorn puree enriched butyrate-producing bacteria and other gut microbes linked to lipid metabolisms such as Prevotella and Faecalibacterium while depleting Parasutterella associated with increased risks of cardiovascular disease. These findings indicate that sea buckthorn berries have potential in modulating energy metabolism and the gut microbiota composition in hypercholesterolemic patients

Developing the theoretical model of Chinese physical education teachers’ health communication competence: based on grounded theory

BackgroundPhysical education teachers’ health communication competence is a key factor in health promotion. Although health communication is a multidisciplinary field, medical practitioners are the primary focus of health communication research, whereas physical education teachers are marginalized. Therefore, this study proposes a theoretical model of health communication competence for physical education teachers.MethodsThis qualitative research utilized interviews as the primary data collection method. Purposeful sampling was employed to select participants, including university teachers, primary and secondary school teachers, and health education professionals from diverse regions of China. A total of 31 participants were interviewed through two focus groups (N = 15) and individual semi-structured interviews (N = 16). Grounded theory was used to analyze and code the collected interview materials.ResultsThe health communication competence of physical education teachers consisted of three main categories, 10 subcategories, 30 concepts, and 240 statement labels. The three main categories were as follows: (i) foundations of health communication knowledge and skills (this category encompassed three subcategories, namely sport and health knowledge reserve, health beliefs, and health behaviors); (ii) health communication perception competence (this category included two subcategories, namely health risk and crisis perception competence and communication audience perception competence); and (iii) practical competence of health communication (this category consisted of five subcategories, namely language expression competence, organizational and design competence, utilization of new media tools competence, communication content selection and processing competence, and professional skills).ConclusionThe theoretical model of health communication competence in this study provides a foundation for the involvement of physical education teachers in health communication work. It can serve as a reference for the development of both pre-service health education courses and in-service training systems for physical education teachers. Future research can expand the sample size and geographic coverage to further validate the applicability of the findings. Additionally, investigating the factors influencing the formation of the identified competencies is recommended

Two-Dimensional Platinum Telluride with Ordered Te Vacancy Superlattice for Efficient and Robust Hydrogen Evolution

Defect engineering to activate the basal planes of transition metal dichalcogenides (TMDs) is critical for the development of TMD-based electrocatalysts as the chemical inertness of basal planes restrict their potential applications in hydrogen evolution reaction (HER). Here, we report the synthesis and evaluation of few-layer (7x7)-PtTe2-x with an ordered, well-defined and high-density Te vacancy superlattice. Compared with pristine PtTe2, (2x2)-PtTe2-x and Pt(111), (7x7)-PtTe2-x exhibits superior HER activities in both acidic and alkaline electrolytes due to its rich structures of undercoordinated Pt sites. Furthermore, the (7x7)-PtTe2-x sample features outstanding catalytic stability even compared to the state-of-the-art Pt/C catalyst. Theoretical calculations reveal that the interactions between various undercoordinated Pt sites due to proximity effect can provide superior undercoordinated Pt sites for hydrogen adsorption and water dissociation. This work will enrich the understanding of the relationship between defect structures and electrocatalytic activities and provide a promising route to develop efficient Pt-based TMD electrocatalysts