Andrographolide Inhibits Biofilm and Virulence in Listeria monocytogenes as a Quorum-Sensing Inhibitor

Listeria monocytogenes is a major foodborne pathogen that can cause listeriosis in humans and animals. Andrographolide is known as a natural antibiotic and exhibits good antibacterial activity. We aimed to investigate the effect of andrographolide on two quorum-sensing (QS) systems, LuxS/AI-2 and Agr/AIP of L. monocytogenes, as well as QS-controlled phenotypes in this study. Our results showed that neither luxS expression nor AI-2 production was affected by andrographolide. Nevertheless, andrographolide significantly reduced the expression levels of the agr genes and the activity of the agr promoter P₂. Results from the crystal violet staining method, confocal laser scanning microscopy (CLSM), and field emission scanning electron microscopy (FE-SEM) demonstrated that andrographolide remarkably inhibited the biofilm-forming ability of L. monocytogenes 10403S. The preformed biofilms were eradicated when exposed to andrographolide, and reduced surviving cells were also observed in treated biofilms. L. monocytogenes treated with andrographolide exhibited decreased ability to secrete LLO and adhere to and invade Caco-2 cells. Therefore, andrographolide is a potential QS inhibitor by targeting the Agr QS system to reduce biofilm formation and virulence of L. monocytogenes.     

PTC: Full and Drift Particle Orbit Tracing Code for α Particles in Tokamak Plasmas

Fusion born α particle confinement is one of the most important issues in burning plasmas,such as ITER and CFETR.However,it is extremely complex due to the nonequilibrium characteristics,and multiple temporal and spatial scales coupling with background plasma.A numerical code using particle orbit tracing method(PTC)has been developed to study energetic particle confinement in tokamak plasmas.Both full orbit and drift orbit solvers are implemented to analyze the Larmor radius effects on α particle confinement.The elastic collisions between alpha particles and thermal plasma are calculated by a Monte Carlo method.A triangle mesh in poloidal section is generated for electromagnetic fields expression.Benchmark between PTC and ORBIT has been accomplished for verification.For CFETR burning plasmas,PTC code is used for α particle source and slowing down process calculation in 2D equilibrium.In future work,3D field like toroidal field ripples,Alfven and magnetohydrodynamics instabilities perturbation inducing α particle transport will be analyzed.     

Rutin Inhibits Ox-LDL-Mediated Macrophage Inflammation and Foam Cell Formation by Inducing Autophagy and Modulating PI3K/ATK Signaling

Atherosclerosis (AS) is one of the leading causes of death among the elderly, and is primarily caused by foam cell generation and macrophage inflammation. Rutin is an anti-inflammatory, anti-oxidant, anti-allergic, and antiviral flavonoid molecule, known to have anti-atherosclerotic and autophagy-inducing properties, but its biological mechanism remains poorly understood. In this study, we uncovered that rutin could suppress the generation of inflammatory factors and reactive oxygen species (ROS) in ox-LDL-induced M2 macrophages and enhance their polarization. Moreover, rutin could decrease foam cell production, as shown by oil red O staining. In addition, rutin could increase the number of autophagosomes and the LC3II/I ratio, while lowering p62 expression. Furthermore, rutin could significantly inhibit the PI3K/ATK signaling pathway. In summary, rutin inhibits ox-LDL-mediated macrophage inflammation and foam cell formation by inducing autophagy and modulating PI3K/ATK signaling, showing potential in treating atherosclerosis.     

The Pharmacokinetics in Mice and Cell Uptake of Thymus Immunosuppressive Pentapeptide Using LC-MS/MS Analysis

Thymus immunosuppressive pentapeptide (TIPP) is a novel anti-inflammatory peptide with high efficacy and low toxicity. This study aims to establish a selective LC-MS/MS method for analyzing the analyte TIPP in biological samples, laying the foundation for further PK and PD studies of TIPP. Protein precipitation was conducted in acetonitrile supplemented with 2% formic acid and 25 mg/mL dithiothreitol as a stabilizer, which was followed by backwashing the organic phase using dichloromethane. The chromatographic separation of TIPP was achieved on a C18 column with a gradient elution method. During positive electrospray ionization, TIPP was analyzed via multiple-reaction monitoring. The linear relationships between the concentration of TIPP and peak area in murine plasma cell lysates, supernatants, and the final cell rinse PBS were established within the ranges of 20–5000 ng/mL, 1–200 ng/mL, 10–200 μg/mL, and 0.1–20 ng/mL, respectively (r² > 0.99). Validated according to U.S. FDA guidelines, the proposed method was proved to be acceptable. Such a method had been successfully applied to investigate the pharmacokinetics of TIPP in mice via subcutaneous injection. The plasma half-life in mice was 5.987 ± 1.824 min, suggesting that TIPP is swiftly eliminated in vivo. The amount of TIPP uptake by RBL-2H3 cells was determined using this method, which was also visually verified by confocal. Furthermore, the effective intracellular concentration of TIPP was deduced by comparing the intracellular concentration of TIPP and degrees of inflammation, enlightening further investigation on the intracellular target and mechanism of TIPP.     

Integral Operators Between Fock Spaces∗

In this paper, the authors study the integral operator Sφf(z) = Z C φ(z, w)f(w)dλα(w) induced by a kernel function φ(z, ·) ∈ F ∞α between Fock spaces. For 1 ≤ p ≤ ∞, they prove that Sφ : F 1 α → F p α is bounded if and only if sup a∈C kSφkakp,α < ∞, (?) where ka is the normalized reproducing kernel of F 2 α; and, Sφ : F 1 α → F p α is compact if and only if lim |a|→∞ kSφkakp,α = 0. When 1 < q ≤ ∞, it is also proved that the condition (?) is not sufficient for boundedness of Sφ : F q α → F p α . In the particular case φ(z, w) = eαzw?(z ? w) with ? ∈ F 2 α, for 1 ≤ q < p < ∞, they show that Sφ : F p α → F q α is bounded if and only if ? = 0; for 1 < p ≤ q < ∞, they give sufficient conditions for the boundedness or compactness of the operator Sφ : F p α → F q α.     

Insights into the Allosteric Effect of SENP1 Q597A Mutation on the Hydrolytic Reaction of SUMO1 via an Integrated Computational Study

Small ubiquitin-related modifier (SUMO)-specific protease 1 (SENP1) is a cysteine protease that catalyzes the cleavage of the C-terminus of SUMO1 for the processing of SUMO precursors and deSUMOylation of target proteins. SENP1 is considered to be a promising target for the treatment of hepatocellular carcinoma (HCC) and prostate cancer. SENP1 Gln597 is located at the unstructured loop connecting the helices α4 to α5. The Q597A mutation of SENP1 allosterically disrupts the hydrolytic reaction of SUMO1 through an unknown mechanism. Here, extensive multiple replicates of microsecond molecular dynamics (MD) simulations, coupled with principal component analysis, dynamic cross-correlation analysis, community network analysis, and binding free energy calculations, were performed to elucidate the detailed mechanism. Our MD simulations showed that the Q597A mutation induced marked dynamic conformational changes in SENP1, especially in the unstructured loop connecting the helices α4 to α5 which the mutation site occupies. Moreover, the Q597A mutation caused conformational changes to catalytic Cys603 and His533 at the active site, which might impair the catalytic activity of SENP1 in processing SUMO1. Moreover, binding free energy calculations revealed that the Q597A mutation had a minor effect on the binding affinity of SUMO1 to SENP1. Together, these results may broaden our understanding of the allosteric modulation of the SENP1−SUMO1 complex.     

复数星图与单路的多染色拉姆齐数

对给定的简单图$H_1,H_2,\ldots,H_c$, 我们将使完全图$K_n$的任意边分解$\{G_i\}^c_{i=1}$都存在至少一个$G_i$有子图同构于$H_i$的最小正整数$n$称为多染色拉姆齐数 $R(H_1,H_2,\ldots,$ $H_c)$. 对正整数$m,n_1,n_2,\ldots,n_c$, 令$\Sigma=\sum_{i=1}^{c}(n_i-1)$. 在文献中,我们已经获得了$R(K_{1,n_1},\ldots,K_{1,n_c},P_m)$ 的一些界和精确值.Wang推测若$\Sigma\not\equiv 0\pmod{m-1}$且$\Sigma+1\ge (m-3)^2$, 则有$R(K_{1,n_1},\ldots, K_{1,n_c}, P_m)=\Sigma+m-1.$ 本文中, 我们给出了一个新的下界并给出$R(K_{1,n_1},\ldots,K_{1,n_c},P_m)$在$m\leq\Sigma$, $\Sigma\equiv k\pmod{m-1}$且$2\leq k \leq m-2$情况下的部分精确值. 这些结果部分证实了Wang的猜想.     

Asymmetric synthesis of chromanone lactones via vinylogous conjugate addition of butenolide to 2-ester chromones

Chiral chromanone lactones are a class of natural products with important biological activity. We report a direct diastereo- and enantioselective vinylogous conjugate addition of butenolide to 2-ester substituted chromones. The transformation proceeded well in the presence of as low as 1 mol% of a chiral N,N′-dioxide/Sc^III complex, 3 Å MS and a catalytic amount of hexafluoroisopropanol (HFIP). The scope of Michael acceptors includes a variety of substituted chromones at different positions, and the desired chromanone lactones upon reduction are afforded in good yield and diastereoselectivity, and excellent enantioselectivity (up to 99% ee). The strategy could be used in the concise synthesis of blennolide C and gonytolide A, C and G.

We report a direct, diastero- and enantioselective vinylogous 1,4-addition of butanolide to 2-ester chromones. A chiral Sc^III complex enabled the reaction to proceed smoothly to give a variety of chraomanone lactones.     

ZnO纳米钉的制备和光学性质研究

通过化学气相沉积(CVD)方法在Si(100)衬底上制备出新型的ZnO纳米钉结构.X射线衍射(XRD)结果表明纳米钉是六角纤锌矿结构.纳米钉顶部对角线在450～750 nm之间,纳米钉长度为几个微米.研究了不同气氛下退火样品的可见发光性质,认为绿光发射来自于导带电子和反位氧中空穴的辐射复合.