Modification in the side chain of solomonsterol A: discovery of cholestan disulfate as a potent pregnane-X-receptor agonist

Seven synthetic analogues of the PXR (pregnane-X-receptor) potent natural agonist solomonsterol A were prepared by total synthesis. Their activity toward PXR was assessed by transactivation and RT-PCR assays. The study discloses cholestan disulfate (8) as a new, simplified agonist of PXR. By in vitro studies on hepatic cells we have demonstrated that this compound is a potent PXR agonist and functional characterization in human macrophages and hepatic stellate cells provided evidence that cholestan disulfate (8) has the ability to modulate the immune response triggered by bacterial endotoxin as well as to counter-activate hepatic stellate cell activation induced by thrombin. Because inhibition of immune-driven circuits might have relevance in the treatment of inflammation and liver fibrosis, the present data support the development of cholestan disulfate (8) in preclinical models of inflammatory diseases.     

Chaos in the square billiard with a modified reflection law

The purpose of this paper is to study the dynamics of a square billiard with a non-standard reflection law such that the angle of reflection of the particle is a linear contraction of the angle of incidence. We present numerical and analytical arguments that the nonwandering set of this billiard decomposes into three invariant sets, a parabolic attractor, a chaotic attractor, and a set consisting of several horseshoes. This scenario implies the positivity of the topological entropy of the billiard, a property that is in sharp contrast with the integrability of the square billiard with the standard reflection law.     

Efficient synthesis of N-methoxyindoles via alkylative cycloaddition of nitrosoarenes with alkynes

[reaction: see text] N-Methoxyindoles are produced in moderate to excellent yields from the reaction between nitrosoarenes and alkynes in the presence of K2CO3/(CH3)2SO4. Terminal alkynes with conjugating substituents afford 3-substituted N-methoxyindoles exclusively. The analogous reactions with methyl propiolate provide a one-step preparation of phytoalexin analogues from Wasabi.     

Surface‐initiated atom transfer radical polymerization grafting of poly(2,2,2‐trifluoroethyl methacrylate) from flat silicon wafer surfaces

Poly(2,2,2‐trifluoroethyl methacrylate) (PTFEMA), a partially fluorinated polymer, was directly grafted from silicon wafer surfaces by a surface‐initiated atom‐transfer radical polymerization (ATRP). The polymer layer thickness increased linearly with monomer conversion and molecular weight of free polymers in solution. The thickness was mainly determined by the experimental conditions such as activator/deactivator ratio, monomer/catalyst ratio, and monomer concentration. PTFEMA layers of more than 100‐nm thick were obtained. The grafted PTFEMA chains were “living” and allowed the extension of a second block of PMMA. X‐ray photoelectron spectroscopy study showed that the chemical compositions at the surfaces agreed well with their theoretical values. A novel surface‐attachable difunctional initiator was also synthesized and applied to the grafting of PTFEMA. The grafting density was doubled using this difunctional initiator, from 0.48 to 0.86 chains/nm². © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 1252–1262, 2006     

Ternary Sn‐Ti‐O Electrocatalyst Boosts the Stability and Energy Efficiency of CO2 Reduction

Simultaneously improving energy efficiency (EE) and material stability in electrochemical CO₂ conversion remains an unsolved challenge. Among a series of ternary Sn‐Ti‐O electrocatalysts, 3D ordered mesoporous (3DOM) Sn_0.3Ti_0.7O₂ achieves a trade‐off between active‐site exposure and structural stability, demonstrating up to 71.5 % half‐cell EE over 200 hours, and a 94.5 % Faradaic efficiency for CO at an overpotential as low as 430 mV. DFT and X‐ray absorption fine structure analyses reveal an electron density reconfiguration in the Sn‐Ti‐O system. A downshift of the orbital band center of Sn and a charge depletion of Ti collectively facilitate the dissociative adsorption of the desired intermediate COOH* for CO formation. It is also beneficial in maintaining a local alkaline environment to suppress H₂ and formate formation, and in stabilizing oxygen atoms to prolong durability. These findings provide a new strategy in materials design for efficient CO₂ conversion and beyond.     

Residues of 165 pesticides in citrus fruits using LC-MS/MS: a study of the pesticides distribution from the peel to the pulp

Abstract

A sensitive LC–ESI-MS/MS method was developed for the determination of 165 pesticides in 50 citrus fruit samples collected in Sicily. Moreover, an evaluation of pesticides levels in the citrus layers (peel, albedo, and pulp) was carried out. The method presented acceptable trueness, precision, and linearity with LOQ of 5?μg/kg. The results obtained showed a high frequency of fungicides class pesticides in all the citrus samples examined (>95%) with the highest concentrations in the peel (4468?µg/Kg). A significant difference of concentrations was found between the layers of the citrus fruits analysed (p?<?0.05). In particular, the peel and albedo present higher pesticides significantly higher than the pulp. Our findings confirming the widespread use of these substances in citrus cultivation and suggesting the importance of pesticides analysis in all the citrus fruit layers separately, considering the different interactions between the physicochemical characteristics of the matrices and the pesticides.     

Automatic transwell assay by an EIS cell chip to monitor cell migration

Here an EIS (electrochemical impedance spectroscopy) biochip to detect cell migration is demonstrated. This biochip has been inspired by a traditional transwell assay/modified Boyden chamber and consists of two compartments separated by a porous membrane. This structure (PDMS-based) is aligned to EIS sensors. Cells are seeded in the upper chamber through microfluidic channels. During migration cells go through the pores of the membrane and get in touch with the electrodes that detect migrated cells. The performance of our cell-chip was tested by investigating the migratory ability of hepatocellular carcinoma (HCC) cells as a function of microenvironment. For this purpose we challenged HCC cells to migrate on different extra-cellular matrix (ECM) components including laminin 1, collagen IV and laminin 5. The results reveal that our cell chip provides reliable results that consistently overlap with those obtained with traditional standardized Boyden chambers. Thus, we demonstrate a new, easy tool to study cell migration and to perform automatic assays. This approach is easier and faster than traditional transwell assays and can be suitable for high-throughput studies in drug discovery applications.