Two questions in diophantine approximation

The first question is about a possible variation on Dirichlet's approximation theorem for linear forms x+y+z, wherex,y are restricted topositive integers. The second question, which turns out to be related to the first, is about approximation to elements in a power series fieldk((t ^–1)) by solutions of first order linear differential equationsx+y+z=0, wherex,y,z are polynomials int. Dedicated to Prof. Dr. E. Hlawka on the occasion of his 60th birthday     

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.     

Anti-Inflammatory Effects of Spiramycin in LPS-Activated RAW 264.7 Macrophages

Drug repurposing is a simple concept with a long history, and is a paradigm shift that can significantly reduce the costs and accelerate the process of bringing a new small-molecule drug into clinical practice. We attempted to uncover a new application of spiramycin, an old medication that was classically prescribed for toxoplasmosis and various other soft-tissue infections; specifically, we initiated a study on the anti-inflammatory capacity of spiramycin. For this purpose, we used murine macrophage RAW 264.7 as a model for this experiment and investigated the anti-inflammatory effects of spiramycin by inhibiting the production of pro-inflammatory mediators and cytokines. In the present study, we demonstrated that spiramycin significantly decreased nitric oxide (NO), interleukin (IL)-1β, and IL-6 levels in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Spiramycin also inhibited the expression of NO synthase (iNOS), potentially explaining the spiramycin-induced decrease in NO production. In addition, spiramycin inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs); extracellular signal-regulated kinase (ERK) and c-Jun N terminal kinase (JNK) as well as the inactivation and subsequent nuclear translocation of nuclear factor κB (NF-κB). This indicated that spiramycin attenuates macrophages’ secretion of IL-6, IL-1β, and NO, inducing iNOS expression via the inhibition of the NF-κB and MAPK signaling pathways. Finally, we tested the potential application of spiramycin as a topical material by human skin primary irritation tests. It was performed on the normal skin (upper back) of 31 volunteers to determine whether 100 μM and μM of spiramycin had irritation or sensitization potential. In these assays, spiramycin did not induce any adverse reactions. In conclusion, our results demonstrate that spiramycin can effectively attenuate the activation of macrophages, suggesting that spiramycin could be a potential candidate for drug repositioning as a topical anti-inflammatory agent.     

Switchable photocatalysis for the chemodivergent benzylation of 4-cyanopyridines

We report a photocatalytic strategy for the chemodivergent radical benzylation of 4-cyanopyridines. The chemistry uses a single photoredox catalyst to generate benzyl radicals upon N–F bond activation of 2-alkyl N-fluorobenzamides. The judicious choice of different photocatalyst quenchers allowed us to select at will between mechanistically divergent processes. The two reaction manifolds, an ipso-substitution path proceeding via radical coupling and a Minisci-type addition, enabled selective access to regioisomeric C4 or C2 benzylated pyridines, respectively. Mechanistic investigations shed light on the origin of the chemoselectivity switch.

We report a photocatalytic strategy for the chemodivergent radical benzylation of 4-cyanopyridines. The chemistry uses a single photoredox catalyst to generate benzyl radicals upon N–F bond activation of 2-alkyl N-fluorobenzamides.     

利用对系统误差修正的逆测法测量电表的内阻

本文在伏安法测电阻实验的基础上,将系统误差修正方法进行逆运用,介绍一种测量电表内阻的方法。     

Dynamic Deformation of Frozen Soil at a High Strain Rate:Experiments and Damage-Coupled Constitutive Model

The dynamic compressive deformation of frozen soil was investigated by conduct-ing the split-Hopkinson pressure bar (SHPB) experiments at three temperatures and...     

Identification of New Non-BBB Permeable Tryptophan Hydroxylase Inhibitors for Treating Obesity and Fatty Liver Disease

Serotonin (5-hydroxytryptophan) is a hormone that regulates emotions in the central nervous system. However, serotonin in the peripheral system is associated with obesity and fatty liver disease. Because serotonin cannot cross the blood-brain barrier (BBB), we focused on identifying new tryptophan hydroxylase type I (TPH1) inhibitors that act only in peripheral tissues for treating obesity and fatty liver disease without affecting the central nervous system. Structural optimization inspired by para-chlorophenylalanine (pCPA) resulted in the identification of a series of oxyphenylalanine and heterocyclic phenylalanine derivatives as TPH1 inhibitors. Among these compounds, compound 18i with an IC₅₀ value of 37 nM was the most active in vitro. Additionally, compound 18i showed good liver microsomal stability and did not significantly inhibit CYP and Herg. Furthermore, this TPH1 inhibitor was able to actively interact with the peripheral system without penetrating the BBB. Compound 18i and its prodrug reduced body weight gain in mammals and decreased in vivo fat accumulation.     

Reaction dynamics studied via femtosecond X-ray liquidography at X-ray free-electron lasers

X-ray free-electron lasers (XFELs) provide femtosecond X-ray pulses suitable for pump–probe time-resolved studies with a femtosecond time resolution. Since the advent of the first XFEL in 2009, recent years have witnessed a great number of applications with various pump–probe techniques at XFELs. Among these, time-resolved X-ray liquidography (TRXL) is a powerful method for visualizing structural dynamics in the liquid solution phase. Here, we classify various chemical and biological molecular systems studied via femtosecond TRXL (fs-TRXL) at XFELs, depending on the focus of the studied process, into (i) bond cleavage and formation, (ii) charge distribution and electron transfer, (iii) orientational dynamics, (iv) solvation dynamics, (v) coherent nuclear wavepacket dynamics, and (vi) protein structural dynamics, and provide a brief review on each category. We also lay out a plausible roadmap for future fs-TRXL studies for areas that have not been explored yet.

Femtosecond X-ray liquidography using X-ray free-electron lasers (XFELs) visualizes various aspects of reaction dynamics.     

Packed-Fiber Solid Phase-Extraction Coupled with HPLC-MS/MS for Rapid Determination of Lipid Oxidative Damage Biomarker 8-Iso-Prostaglandin F2α in Urine

The 8-iso-prostaglandin F_2α (8-iso-PGF_2α) biomarker is used as the gold standard for tracing lipid oxidative stress in vivo. The analysis of urinary 8-iso-PGF_2α is challenging when dealing with trace amounts of 8-iso-PGF_2α and the complexity of urine matrixes. A packed-fiber solid-phase extraction (PFSPE)–coupled with HPLC-MS/MS–method, based on polystyrene (PS)-electrospun nanofibers, was developed for the specific determination of 8-iso-PGF_2α in urine and compared with other newly developed LC-MS/MS methods. The method, which simultaneously processed 12 samples within 5 min on a self-made semi-automatic array solid-phase extraction processor, was the first to introduce PS-electrospun nanofibers as an adsorbent for the extraction of 8-iso-PGF_2α and was successfully applied to real urine samples. After optimizing the PFSPE conditions, good linearity in the range of 0.05–5 ng/mL with R² > 0.9996 and a satisfactory limit of detection of 0.015 ng/mL were obtained, with good intraday and interday precision (RSD < 10%) and recoveries of 95.3–103.8%. This feasible method is expected to be used for the batch quantitative analysis of urinary 8-iso-PGF_2α.     

Oscillation of coercivity between positive and negative in MnxGe1-x：H ferromagnetic semiconductor films

Amorphous MnxGe1-x :H ferromagnetic semiconductor films prepared in mixed Ar with 20% H2 by magnetron cosputtering show global ferromagnetism with positive coercivity at low temperatures. With increasing temperature, the coercivity of MnxGe1-x :H films first changes from positive to negative, and then back to positive again, which was not found in the corresponding MnxGe1-x and other ferromagnetic semiconductors before. For Mn0.4Ge0.6 :H film, the inverted Hall loop is also observed at 30 K, which is consistent with the negative coercivity. The negative coercivity is explained by the antiferromagnetic exchange coupling between the H-rich ferromagnetic regions separated by the H-poor non-ferromagnetic spacers. Hydrogenation is a useful method to tune the magnetic properties of MnxGe1-x films for the application in spintronics.