Fabrication of highly ordered TiO2 nanotube arrays using an organic electrolyte

Anodization of titanium in a fluorinated dimethyl sulfoxide (DMSO) and ethanol mixture electrolyte is investigated. The prepared anodic film has a highly ordered nanotube-array surface architecture. Using a 20 V anodization potential (vs Pt) nanotube arrays having an inner diameter of 60 nm and 40 nm wall thickness are formed. The overall length of the nanotube arrays is controlled by the duration of the anodization, with nanotubes appearing only after approximately 48 h; a 72 h anodization results in a nanotube array approximately 2.3 mum in length. The photoelectrochemical response of the nanotube-array photoelectrodes is studied using a 1 M KOH solution under both UV and visible (AM 1.5) illumination. Enhanced photocurrent density is observed for samples obtained in the organic electrolyte, with an UV photoconversion efficiency of 10.7%.     

The Role of Methoxy Group in the Nazarov Cyclization of 1,5-bis-(2-Methoxyphenyl)-1,4-Pentadien-3-one in the Gas Phase and Condensed Phase

ESI-protonated 1,5-bis-(2-methoxyphenyl)-1,4-pentadien-3-one (1) undergoes a gas-phase Nazarov cyclization and dissociates via expulsions of ketene and anisole. The dissociations of the [M + D]⁺ ions are accompanied by limited HD scrambling that supports the proposed cyclization. Solution cyclization of 1 was effected to yield the cyclic ketone, 2,3-bis-(2-methoxyphenyl)-cyclopent-2-ene-1-one, (2) on a time scale that is significantly shorter than the time for cyclization of dibenzalacetone. The dissociation characteristics of the ESI-generated [M + H]⁺ ion of the synthetic cyclic ketone closely resemble those of 1, suggesting that gas-phase and solution cyclization products are the same. Additional mechanistic studies by density functional theory (DFT) methods of the gas-phase reaction reveals that the initial cyclization is followed by two sequential 1,2-aryl migrations that account for the observed structure of the cyclic product in the gas phase and solution. Furthermore, the DFT calculations show that the methoxy group serves as a catalyst for the proton migrations necessary for both cyclization and fragmentation after aryl migration. An isomer formed by moving the 2-methoxy to the 4-position requires relatively higher collision energy for the elimination of anisole, as is consistent with DFT calculations. Replacement of the 2-methoxy group with an OH shows that the cyclization followed by aryl migration and elimination of phenol occurs from the [M + H]⁺ ion at low energy similar to that for 1.

Piceatannol Protects Brain Endothelial Cell Line (bEnd.3) against Lipopolysaccharide-Induced Inflammation and Oxidative Stress

Dysfunction of the blood–brain barrier (BBB) is involved in the pathogenesis of many cerebral diseases. Oxidative stress and inflammation are contributing factors for BBB injury. Piceatannol, a natural ingredient found in various plants, such as grapes, white tea, and passion fruit, plays an important role in antioxidant and anti-inflammatory responses. In this study, we examined the protective effects of piceatannol on lipopolysaccharide (LPS) insult in mouse brain endothelial cell line (bEnd.3) cells and the underlying mechanisms. The results showed that piceatannol mitigated the upregulated expression of adhesion molecules (ICAM-1 and VCAM-1) and iNOS in LPS-treated bEnd.3 cells. Moreover, piceatannol prevented the generation of reactive oxygen species in bEnd.3 cells stimulated with LPS. Mechanism investigations suggested that piceatannol inhibited NF-κB and MAPK activation. Taken together, these observations suggest that piceatannol reduces inflammation and oxidative stress through inactivating the NF-κB and MAPK signaling pathways on cerebral endothelial cells in vitro.     

Natural Dietary Compound Xanthohumol Regulates the Gut Microbiota and Its Metabolic Profile in a Mouse Model of Alzheimer’s Disease

Discovering new and effective drugs for the treatment of Alzheimer’s disease (AD) is a major clinical challenge. This study focuses on chemical modulation of the gut microbiome in an established murine AD model. We used the 16S rDNA sequencing technique to investigate the effect of xanthohumol (Xn) on the diversity of intestinal microflora in 2-month- and 6-month-old APP/PS1 mice, respectively. APP/PS1 and wild-type mice were treated by gavage with corn oil with or without Xn every other day for 90 days. Prior to and following treatment, animals were tested for spatial learning, cognitive and memory function. We found Xn reduced cognitive dysfunction in APP/PS1 mice and significantly regulated the composition and abundance of gut microbiota both in prevention experiments (with younger mice) and therapeutic experiments (with older mice). Differential microflora Gammaproteobacteria were significantly enriched in APP/PS1 mice treated with Xn. Nodosilineaceae and Rikenellaceae may be the specific microflora modulated by Xn. The penicillin and cephalosporin biosynthesis pathway and the atrazine degradation pathway may be the principal modulation pathways. Taken together, oral treatment with Xn may have a neuroprotective role by regulating the composition of intestinal microflora, a result that contributes to the scientific basis for a novel prophylactic and therapeutic approach to AD.     

Inhomogeneous magnetism in single crystalline Sr(3)CuIrO(6+delta): implications to phase-separation concepts

The single crystalline form of an insulator, Sr(3)CuIrO(6+delta), is shown to exhibit unexpectedly more than one magnetic transition (at 5 and 19 K) with spin-glass-like magnetic susceptibility behavior. On the basis of this finding, viz., inhomogeneous magnetism in a chemically homogeneous material, we propose that the idea of "phase separation" described for manganites is more widespread in different ways. The observed experimental features enable us to make a comparison with the predictions of a recent toy model on magnetic phase separation in an insulating environment.     

Towards a new age of virtual ADME/TOX and multidimensional drug discovery

With the continual pressure to ensure follow-up molecules to billion dollar blockbuster drugs, there is a hurdle in profitability and growth for pharmaceutical companies in the next decades. With each success and failure we increasingly appreciate that a key to the success of synthesized molecules through the research and development process is the possession of drug-like properties. These properties include an adequate bioactivity as well as adequate solubility, an ability to cross critical membranes (intestinal and sometimes blood-brain barrier), reasonable metabolic stability and of course safety in humans. Dependent on the therapeutic area being investigated it might also be desirable to avoid certain enzymes or transporters to circumvent potential drug-drug interactions. It may also be important to limit the induction of these same proteins that can result in further toxicities. We have clearly moved the assessment of in vitro absorption, distribution, metabolism, excretion and toxicity (ADME/TOX) parameters much earlier in the discovery organization than a decade ago with the inclusion of higher throughput systems. We are also now faced with huge amounts of ADME/TOX data for each molecule that need interpretation and also provide a valuable resource for generating predictive computational models for future drug discovery. The present review aims to show what tools exist today for visualizing and modeling ADME/TOX data, what tools need to be developed, and how both the present and future tools are valuable for virtual filtering using ADME/TOX and bioactivity properties in parallel as a viable addition to present practices.     

Micromachined array tip for multifocus fiber-based optical coherence tomography

High-resolution optical coherence tomography demands a large detector bandwidth and a high numerical aperture for real-time imaging, which is difficult to achieve over a large imaging depth. To resolve these conflicting requirements we propose a novel multifocus fiber-based optical coherence tomography system with a micromachined array tip. We demonstrate the fabrication of a prototype four-channel tip that maintains a 9-14-microm spot diameter with more than 500 microm of imaging depth. Images of a resolution target and a human tooth were obtained with this tip by use of a four-channel cascaded Michelson fiber-optic interferometer, scanned simultaneously at 8 kHz with geometric power distribution across the four channels.