Development of a Glassy Carbon Electrode Modified with Graphene/Au Nanoparticles for Determination of Acetaminophen in Pharmaceutical Preparation

Russian Journal of Electrochemistry - A graphene/Au nanoparticles composite modified glassy carbon electrode (GR/AuNPs/GCE) was developed. Electrochemical behavior of acetaminophen (ACOP) at this...     

Screening and identification of Caulis Sinomenii bioactive ingredients with dual‐target NF‐κB inhibition and β2‐AR agonizing activities

Caulis Sinomenii (CS) is a valuable traditional medicine in China. Its extract can act as an anti‐inflammatory agent and a vascular smooth muscle relaxant. However, the underlying mechanisms remain unknown. In this study, we developed a simple dual‐target method based on ultra‐performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry combined with a dual‐target bioactive screening assay for anti‐inflammatory and antispasmodic activities to characterize the chemical structure of various bioactive compounds of CS rapidly. Seven potential NF‐κB inhibitors were identified, including laudanosoline‐1‐O‐xylopyranose, 6‐O‐methyl‐laudanosoline‐1‐O‐glucopyranoside, menisperine, sinomenine, laurifoline, magnoflorine and norsinoacutin. Furthermore, IL‐6 and IL‐8 assays confirmed the anti‐inflammatory effects of these potential NF‐κB inhibitors, in which laudanosoline‐1‐O‐d ‐xylopyranose and menisperine were revealed as novel NF‐κB inhibitors. Among the seven identified alkaloids, three potential β₂‐adrenergic receptor agonists, including sinomenine, magnoflorine and laurifoline, were characterized using a luciferase reporter system to measure for the activity of β₂‐adrenergic receptor agonists. Finally, sinomenine, magnoflorine and laurifoline were identified not only as potential NF‐κB inhibitors but also as potential β₂‐adrenegic receptor agonists, which is the first time this has been reported. Molecular dynamic simulation and docking results suggest that the three dual‐bioactive constituents could not only inhibit Pseudomonas aeruginosa PAK strain‐induced inflammatory responses via a negative regulation of the Braf protein that participates in MAPK signaling pathway but also activate the β₂‐adrenegic receptor. These results suggest that CS extract has dual signaling activities with potential clinical application as a novel drug for asthma.     

Heat transfer simulation in cavity of twin screw compressor under coupling of clearance leakage-heat by utilizing fuzzy beamlet finite element model

Journal of Thermal Analysis and Calorimetry - In order to optimize structure of twin screw compressor, and improve the working efficiency of twin screw refrigeration compressor, the heat transfer...     

3-O-Sulfation of Heparan Sulfate Enhances Tau Interaction and Cellular Uptake

Prion-like transcellular spreading of tau in Alzheimer's Disease (AD) is mediated by tau binding to cell surface heparan sulfate (HS). However, the structural determinants for tau–HS interaction are not well understood. Microarray and SPR assays of structurally defined HS oligosaccharides show that a rare 3-O-sulfation (3-O-S) of HS significantly enhances tau binding. In Hs3st1^−/− (HS 3-O-sulfotransferase-1 knockout) cells, reduced 3-O-S levels of HS diminished both cell surface binding and internalization of tau. In a cell culture, the addition of a 3-O-S HS 12-mer reduced both tau cell surface binding and cellular uptake. NMR titrations mapped 3-O-S binding sites to the microtubule binding repeat 2 (R2) and proline-rich region 2 (PRR2) of tau. Tau is only the seventh protein currently known to recognize HS 3-O-sulfation. Our work demonstrates that this rare 3-O-sulfation enhances tau–HS binding and likely the transcellular spread of tau, providing a novel target for disease-modifying treatment of AD and other tauopathies.     

Stabilization in three-dimensional chemotaxis-growth model with indirect attractant production

This paper deals with the chemotaxis-growth system: $u_t=\mathrm{\Delta }u?\mathrm{?}?(u\mathrm{?}v)+\mu u(1?u)$, $v_t=\mathrm{\Delta }v?v+w$, $\tau w_t+\delta w=u$ in a smooth bounded domain $\mathrm{\Omega }?{\mathbb{R}}^3$ with zero-flux boundary conditions, where μ, δ, and τ are given positive parameters. It is shown that the solution $(u,v,w)$ exponentially stabilizes to the constant stationary solution $(1,\frac{1}{\delta },\frac{1}{\delta })$ in the norm of $L^{\infty }(\mathrm{\Omega })$ as $t\to \infty$ provided that $\mu >0$ and any given nonnegative and suitably smooth initial data $(u_0,v_0,w_0)$ fulfills $u_0?0$, which extends the condition $\mu >\frac{1}{8{\delta }^2}$ in [8].     

Optimal strategy of vaccination and treatment in an SIRS model with Markovian switching

Medical treatment and vaccination decisions are often sequential and uncertain. Markov decision process is an appropriate means to model and handle such stochastic dynamic decisions. This paper studies the near‐optimality of a stochastic SIRS epidemic model that incorporates vaccination and saturated treatment with regime switching. The stochastic model takes white noises and color noise into account. We first prove some priori estimates of the susceptible, infected, and recovered populations. Moreover, we establish some sufficient and necessary conditions of the near‐optimality by Pontryagin stochastic maximum principle. Our results show that the two kinds of environmental noises have great impacts on the infectious diseases. Finally, we illustrate our conclusions through numerical simulations.     

Screening potential antagonists of epidermal growth factor receptor from Marsdenia tenacissima via cell membrane chromatography model assisted by HPLC–ESI–IT–TOF–MS

Marsdenia tenacissima, or Tongguanteng in Chinese, is a traditional Chinese herb and has a broad application in clinical practice for its pharmacological effects of treating asthma, pneumonia, tonsillitis, pharyngitis tumors, etc. However, few studies have reported the screening of the active components of this medicine for tumor therapy. In this work, a two‐dimensional analytical system was developed to screen antagonists of epidermal growth factor receptor (EGFR) from M. tenacissima. A fraction was retained on the EGFR cell membrane chromatography (CMC) column, separated and identified as tenacissoside G (TG), tenacissoside H (TH) and tenacissoside I (TI) by two‐dimensional HPLC–IT–TOF–MS. Molecular docking and 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) assay were carried out to assess the activity of TS (including TG, TH and TI). Molecular docking results showed that the binding mode of TS on EGFR is similar to that of gefitinib. The MTT assay demonstrated that gefitinib and TS (especially TI) could inhibit the growth of EGFR highly expressed cell lines in a dose‐dependent manner in the range of 5–50 μmol/L. In conclusion, the two‐dimensional EGFR/CMC–HPLC–IT–TOF–MS system could be a useful approach in drug discovery from traditional Chinese medicines for searching for potential antitumor candidates.