Sulphur metabolism in colon cancer tissues: a case report and literature review.

Sulphur-containing compounds have been linked to colorectal cancer by factors such as the presence of methyl mercaptan in intestinal gas and long-term dietary intake associated with sulphur-metabolizing microbiota. Therefore, this current case report hypothesized that active sulphur metabolism in colorectal cancer results in the formation of sulphur compounds in the intestine and, thus, examined sulphur metabolites possibly associated with sulphur respiration in colon cancer tissues. The patient was a 73-year-old female that underwent laparoscopic right hemicolectomy for ascending colon cancer. During the surgery, colon cancer tissues and normal intestinal mucosa samples were collected. After optimizing the sample concentrations for homogenization (pre-treatment), the samples were stabilized using a hydroxyphenyl-containing derivative and the relevant metabolites were quantified using liquid chromatography with tandem mass spectrometry. The results showed that cysteine persulfide and cysteine trisulfide levels were higher in colon cancer tissues than in normal mucosal tissues. Thus, sulphur metabolism, possibly sulphur respiration, is enhanced in colon cancer tissues.

A Fluorine-free Slippery Surface with Hot Water Repellency and Improved Stability against Boiling.

Inspired by natural living things such as lotus leaves and pitcher plants, researchers have developed many excellent antifouling coatings. In particular, hot-water-repellent surfaces have received much attention in recent years because of their wide range of applications. However, coatings with stability against boiling in hot water have not been achieved yet. Long-chain perfluorinated materials, which are often used for liquid-repellent coatings owing to their low surface energy, hinder the potential application of antifouling coatings in food containers. Herein, we design a fluorine-free slippery surface that immobilizes a biocompatible lubricant layer on a phenyl-group-modified smooth solid surface through OH-π interactions. The smooth base layer was fabricated by modification of phenyltriethoxysilane through a sol-gel method. The π-electrons of the phenyl groups interact with the carboxyl group of the oleic acid used as a lubricant, which facilitates immobilization on the base layer. Water droplets slid off the surface in the temperature range from 20 to 80 °C at very low sliding angles (<2°). Furthermore, we increased the π-electron density in the base layer to strengthen the OH-π interactions, which improved long-term boiling stability under hot water. We believe that this surface will be applied in fields in which the practical use of antifouling coatings is desirable, such as food containers, drink cans, and glassware.

Metabolomics of postprandial plasma alterations: a comprehensive Japanese study.

While endogenous metabolites in plasma can be used as clinical biomarkers, intra-day variations should be carefully considered. The postprandial effect is a large contributing factor and is dependent on regional features (e.g. meals, ethnicity). Thus, for clinical application, regional-specific postprandial baseline data are required. In this study, 10 healthy Japanese volunteers of different ages and genders ate the same meal, and blood samples were taken 30 min before and 1 h after the meal challenge. Plasma metabolomics was conducted and metabolites that significantly changed with the meal challenge were extracted. Principal component analysis of the data from 1101 metabolites showed a postprandial shift with a common direction despite marked individual variation. Pathway enrichment analysis demonstrated known postprandial effects, including the energy utilization shift from lipolysis to glycolysis and the elevation of bile acids for lipid absorption. Other postprandial metabolic changes were observed, including decreases in orexigenic signals and increases of food-derived components. The postprandial alteration accumulated in this study will be used for the understanding of Japanese clinical metabolomics for health promotion in Japan.

Discovery of Novel Selective Acetyl-CoA Carboxylase (ACC) 1 Inhibitors.

We initiated our structure-activity relationship (SAR) studies for selective ACC1 inhibitors from 1a as a lead compound. SAR studies of bicyclic scaffolds revealed many potent and selective ACC1 inhibitors represented by 1f; however most of them had physicochemical issues, particularly low aqueous solubility and potent CYP inhibition. To address these two issues and improve the druglikeness of this chemical series, we converted the bicyclic scaffold into a monocyclic framework. Ultimately, this lead us to discover a novel monocyclic derivative 1q as a selective ACC1 inhibitor, which showed highly potent and selective ACC1 inhibition as well as acceptable solubility and CYP inhibition profiles. Since compound 1q displayed favorable bioavailability in mouse cassette dosing testing, we conducted in vivo PD studies of this compound. Oral administration of 1q significantly reduced the concentration of malonyl-CoA in HCT-116 xenograft tumors at doses of more than 30 mg/kg. Accordingly, our novel series of selective ACC1 inhibitors represents a set of useful orally available research tools, as well as potential therapeutic agents for cancer and fatty acid related diseases.

Liquid-Infused Smooth Surface for Improved Condensation Heat Transfer.

Control of vapor condensation properties is a promising approach to manage a crucial part of energy infrastructure conditions. Heat transfer by vapor condensation on superhydrophobic coatings has garnered attention, because dropwise condensation on superhydrophobic surfaces with rough structures leads to favorable heat-transfer performance. However, pinned condensed water droplets within the rough structure and a high thermodynamic energy barrier for nucleation of superhydrophobic surfaces limit their heat-transfer increase. Recently, slippery liquid-infused surfaces (SLIPS) have been investigated, because of their high water sliding ability and surface smoothness originating from the liquid layer. However, even on SLIPS, condensed water droplets are eventually pinned to degrade their heat-transfer properties after extended use, because the rough base layer is exposed as infused liquid is lost. Herein, we report a liquid-infused smooth surface named "SPLASH" (surface with π electron interaction liquid adsorption, smoothness, and hydrophobicity) to overcome the problems derived from the rough structures in previous approaches to obtain stable, high heat-transfer performance. The SPLASH displayed a maximum condensation heat-transfer coefficient that was 175% higher than that of an uncoated substrate. The SPLASH also showed higher heat-transfer performance and more stable dropwise condensation than superhydrophobic surfaces and SLIPS from the viewpoints of condensed water droplet mobility and the thermodynamic energy barrier for nucleation. The effects of liquid-infused surface roughness and liquid viscosity on condensation heat transfer were investigated to compare heat-transfer performance. This research will aid industrial applications using vapor condensation.

Bioinspired Hand-Operated Smart-Wetting Systems Using Smooth Liquid Coatings.

Manually controllable "hand-operated" smart systems have been developed in many fields, including smart wetting materials, electronic devices, molecular machines, and drug delivery systems. Because complex morphological or chemical control are generally required, versatile strategies for constructing the system are technologically important. Inspired by the natural phenomenon of raindrops rarely bouncing and usually spreading on a puddle, we introduce a droplet-impact-triggering smart-wetting system using "non-smart" smooth liquid coating materials. Changing the droplet impact energy by changing the volume or casting height causes the droplet to completely bounce or spread on the liquid surface, regardless of the miscibility between the two liquids, owing to the stability of air layer. As the bouncing of a droplet on a liquid interface is not usually observed during wetting, we first analyze how the droplet bounces, then prove that the wettability is triggered by the droplet's impact energy, and finally introduce some applications using this system.

Slippery Liquid-Immobilized Coating Films Using in Situ Oxidation-Reduction Reactions of Metal Ions in Polyelectrolyte Films.

We fabricated slippery liquid-immobilized coating (SLIC) films by reacting a slippery liquid (polymethylhydrosiloxane) near the surface of a polyelectrolyte film containing silver ions prepared by the layer-by-layer method. The obtained films maintained their slipperiness after chemical and physical treatments, in contrast to slippery liquid-infused porous surfaces. The high chemical and physical stabilities of the films were attributable to gelation and immobilization of the lubricant owing to an oxidation-reduction reaction with subsequent dehydration condensation of Si-OH on the outer surface of the polyelectrolyte film and the bonding of Si-H with NH2 groups within the polyelectrolyte film, respectively. Moreover, the SLIC films exhibited a high degree of slipperiness with respect to low-surface-tension liquids. To the best of our knowledge, this technique of lubricant immobilization using silver ions has not been reported previously. The films should be suitable for use in various applications where contamination must be prevented under extreme conditions, such as those requiring high physical durability and organic solvent use.

Droplet Motion Control on Dynamically Hydrophobic Patterned Surfaces as Multifunctional Liquid Manipulators.

In this letter, we introduce a novel liquid manipulation strategy to design dynamically hydrophobic and statically hydrophobic/hydrophilic patterned surfaces using an "omniphobicity"-based technique. The surfaces guide the sliding direction of a droplet in the presence of a statically hydrophilic area where the droplet does not stick on the transport path significantly enhancing the fluidic system transport efficiency. The concept of dynamically hydrophobic and statically hydrophobic/hydrophilic patterned surfaces in conjunction with omniphobic patterning techniques having surface multifunctionality, we believe, has potential not only for fluidic applications but also for future material engineering development.

Controllable Broadband Optical Transparency and Wettability Switching of Temperature-Activated Solid/Liquid-Infused Nanofibrous Membranes.

Inspired by biointerfaces, such as the surfaces of lotus leaves and pitcher plants, researchers have developed innovative strategies for controlling surface wettability and transparency. In particular, great success has been achieved in obtaining low adhesion and high transmittance via the introduction of a liquid layer to form liquid-infused surfaces. Furthermore, smart surfaces that can change their surface properties according to external stimuli have recently attracted substantial interest. As some of the best-performing smart surface materials, slippery liquid-infused porous surfaces (SLIPSs), which are super-repellent, demonstrate the successful achievement of switchable adhesion and tunable transparency that can be controlled by a graded mechanical stimulus. However, despite considerable efforts, producing temperature-responsive, super-repellent surfaces at ambient temperature and pressure remains difficult because of the use of nonreactive lubricant oil as a building block in previously investigated repellent surfaces. Therefore, the present study focused on developing multifunctional materials that dynamically adapt to temperature changes. Here, we demonstrate temperature-activated solidifiable/liquid paraffin-infused porous surfaces (TA-SLIPSs) whose transparency and control of water droplet movement at room temperature can be simultaneously controlled. The solidification of the paraffin changes the surface morphology and the size of the light-transmission inhibitor in the lubricant layer; as a result, the control over the droplet movement and the light transmittance at different temperatures is dependent on the solidifiable/liquid paraffin mixing ratio. Further study of such temperature-responsive, multifunctional systems would be valuable for antifouling applications and the development of surfaces with tunable optical transparency for innovative medical applications, intelligent windows, and other devices.

Porous Transition of Polyelectrolyte Film through Reaction-Induced Phase Separation Caused by Interaction with Specific Metal Ions.

We describe a novel method for the simple and eco-friendly fabrication of porous polyelectrolyte films. A polyelectrolyte with many amine groups undergoes structural transformation from a dense to a porous structure upon immersion in a specific metal ion solution. The porous transition was the result of a reaction-induced phase separation, which was caused by the formation of new bonds between the polyelectrolyte and metal ions. This method enables control of the pore size of the porous structure in the nanoscale (54 nm) to microscale (1.63 µm) range through variation of the concentration or type of metal ions in the solution. To the best of our knowledge, this is the first report illustrating wide-range control of the pore size of a porous polyelectrolyte structure achieved by metal ions. These porous polyelectrolyte films with adjustable pore size and metastable metal ions can be employed in applications such as adsorption and catalysis.

Identification of a G protein-coupled receptor specifically responsive to beta-alanine.

We isolated a cDNA encoding an orphan G protein-coupled receptor, TGR7, which has been recently reported to correspond to MrgD. To search for ligands for TGR7, we screened a series of small molecule compounds by detecting the Ca2+ influx in Chinese hamster ovary cells expressing TGR7. Through this screening, we found that beta-alanine at micromolar doses specifically evoked Ca2+ influx in cells expressing human, rat, or mouse TGR7. A structural analogue, gamma-aminobutyric acid, weakly stimulated cells expressing human or rat TGR7, but another analogue, glycine, did not. In addition, beta-alanine decreased forskolin-stimulated cAMP production in cells expressing TGR7, suggesting that TGR7 couples with G proteins Gq and Gi. In guanosine 5'-O-3-thiotriphosphate binding assays conducted using a membrane fraction of cells expressing TGR7, beta-alanine specifically increased the binding of guanosine 5'-O-3-thiotriphosphate. When a fusion protein composed of TGR7 and green fluorescent protein was expressed in cells, it localized at the plasma membrane but internalized into the cytoplasm after treatment with beta-alanine. In addition, we found that beta-[3H]alanine more efficiently bound to TGR7-expressing cells than to control cells. From these results, we concluded that TGR7 functioned as a specific membrane receptor for beta-alanine. Quantitative PCR analysis revealed that TGR7 mRNA was predominantly expressed in the dorsal root ganglia in rats. By in situ hybridization and immunostaining, we confirmed that TGR7 mRNA was co-expressed in the small diameter neurons with P2X3 and VR1, both in rat and monkey dorsal root ganglia. Our results suggest that TGR7 participates in the modulation of neuropathic pain.