Enhancement of Refractive Index Sensitivity Using Small Footprint S-Shaped Double-Spiral Resonators for Biosensing.

We demonstrate an S-shaped double-spiral microresonator (DSR) for detecting small volumes of analytes, such as liquids or gases, penetrating a microfluidic channel. Optical-ring resonators have been applied as label-free and high-sensitivity biosensors by using an evanescent field for sensing the refractive index of analytes. Enlarging the ring resonator size is a solution for amplifying the interactions between the evanescent field and biomolecules to obtain a higher refractive index sensitivity of the attached analytes. However, it requires a large platform of a hundred square millimeters, and 99% of the cavity area would not involve evanescent field sensing. In this report, we demonstrate the novel design of a Si-based S-shaped double-spiral resonator on a silicon-on-insulator substrate for which the cavity size was 41.6 µm × 88.4 µm. The proposed resonator footprint was reduced by 680 times compared to a microring resonator with the same cavity area. The fabricated resonator exposed more sensitive optical characteristics for refractive index biosensing thanks to the enhanced contact interface by a long cavity length of DSR structures. High quality factors of 1.8 × 104 were demonstrated for 1.2 mm length DSR structures, which were more than two times higher than the quality factors of microring resonators. A bulk sensitivity of 1410 nm/RIU was calculated for detecting 1 µL IPA solutions inside a 200 µm wide microchannel by using the DSR cavity, which had more than a 10-fold higher sensitivity than the sensitivity of the microring resonators. A DSR device was also used for the detection of 100 ppm acetone gas inside a closed bottle.

Intestinal Absorption of Alogliptin Is Mediated by a Fruit-Juice-Sensitive Transporter.

Alogliptin (ALG), an inhibitor of dipeptidylpeptidase-4, is used in the management of type 2 diabetes mellitus, and has a high absorption rate (>60-71%), despite its low lipophilicity (logP=-1.4). Here, we aimed to clarify the mechanism of its intestinal absorption. ALG uptake into Caco-2 cells was time-, temperature-, and concentration-dependent, but was not saturated at concentrations up to 10 mmol/L. The uptake was significantly inhibited by the organic anion transporting polypeptide (OATP) substrate fexofenadine and by the OATP inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), but was not inhibited by organic cation transporter (OCT)/organic cation/carnitine transporter (OCTN) or peptide transporter 1 (PEPT1) substrates. Grapefruit, orange, and apple juices and their constituents, which are known to strongly inhibit intestinal OATPs, significantly inhibited ALG uptake into Caco-2 cells. The pH dependence was bell-shaped, indicating the involvement of a pH-sensitive transporter. However, ALG uptake by HEK293 cells overexpressing OATP2B1, a key intestinal OATP transporter of amphiphilic drugs, was not different from that of mock cells. In a rat in vivo study, apple juice reduced systemic exposure to orally administered ALG without changing the terminal half-life. These observations suggest that intestinal absorption of ALG is carrier-mediated, and involves a fruit-juice-sensitive transporter other than OATP2B1.

Seasonal Fluctuation of Endotoxin and Protein Concentrations in Outdoor Air in Sasebo, Japan.

To determine the levels of endotoxin, which is a major component of outer membrane of Gram-negative bacteria, and protein in the atmosphere in Sasebo, Japan, we measured these biological materials in fine (aerodynamic diameter ≤2.5 µm) and coarse (≥2.5 µm) particles collected for 81 weeks (September 2014 to May 2016). The monthly concentrations (i.e., the mean value of weekly concentrations for each month) of endotoxin were higher in coarse particles than in fine particles. Fluctuations in monthly endotoxin concentrations were large in both fine (0.0005-0.0208 EU/m3) and coarse (0.0032-0.1164 EU/m3) particles. Furthermore, the endotoxin concentrations in coarse particles were highest in October 2014 and 2015 as well as September 2014 (0.0407-0.1164 EU/m3). However, the monthly protein concentrations were higher in fine particles than in coarse particles. Compared to the endotoxin concentrations, the fluctuations in the monthly protein concentrations were smaller in both coarse and fine particles. To our knowledge, this study is the first to report long-term atmospheric concentrations of endotoxin and protein in Japan. Since the endotoxin concentrations in coarse particles were positively associated with the concentrations of Na+ and Cl-, it suggests the involvement of Gram-negative bacteria from seawater to the endotoxin levels in the atmosphere. For fine particles, the protein concentrations were positively associated with the concentrations of particles, NO3- and SO42-. These results suggest that combustion of organic materials, such as biomass burning, may be a contributor to atmospheric protein during this study period.

Comparison of Air Pollution in Metropolises in China (Beijing) and Japan (Osaka and Nagoya) on the Basis of the Levels of Contaminants and Mutagenicity.

Public concern regarding the transport of air pollutants from mainland East Asia to the leeward area by the prevailing westerlies in spring and winter monsoon has been growing in recent years. We collected total suspended particle (TSP) in Beijing, a metropolis of China located windward of Japan, in spring (late February 2011-May 2011) and in winter (November 2012-early February 2013), then analyzed metals, ions, and organic compounds and mutagenicity, and compared the pollution levels with samples collected at two Japanese metropolises (Osaka and Nagoya) during the same periods. The medians of concentration of TSP and other factors in Beijing were much larger than those in the Japanese metropolises. Especially, the concentrations of polycyclic aromatic hydrocarbons (PAHs) were remarkably high in Beijing in winter, and the median of total PAHs concentration in Beijing was 62-63 times larger than that in the Japanese sites. The mutagenicity of TSP from Beijing toward Salmonella typhimurium YG1024, with and without a mammalian metabolic system (S9 mix), was 13-25 times higher than that from the Japanese sites in winter. These results suggest that air pollution levels in Beijing are very high compared with those at the two Japanese metropolises we evaluated. The diagnostic ratios of PAHs and nitrated polycyclic aromatic hydrocarbons (NPAHs) suggest that the major sources of PAHs and NPAHs in Beijing are different from those at the two Japanese sites in winter, and that the major source in Beijing is coal/biomass combustion.

Seasonal Fluctuations in Air Pollution in Dazaifu, Japan, and Effect of Long-Range Transport from Mainland East Asia.

To clarify the seasonal fluctuations in air pollution and the effect of long-range transport, we collected airborne particles (n=118) at Dazaifu in Fukuoka, Japan, from June 2012 to May 2013 and measured Pb and SO4(2-), which are indicators of the long-range transport of anthropogenic air pollutants, as well as their mutagenicity, and other factors. The levels of airborne particles, Pb, and SO4(2-) were very high on March 4, 8, 9, and 19, and May 13, 21, and 22, 2013. The backward trajectories indicated that air masses had arrived from the Gobi Desert and northern China on those days. The mutagenicity of airborne particles was examined using the Ames test on Salmonella typhimurium YG1024. Highly mutagenic airborne particles were mostly collected in winter, and most of them showed high activity both with and without S9 mix. High levels of polycyclic aromatic hydrocarbons (PAHs) were found in many samples that showed high mutagenicity. For the samples collected on January 30, February 21, and March 4, the levels of Pb, SO4(2-), PAHs, and mutagenicity were high, and the backward trajectories indicated that air masses present on those days had passed through northern or central China. The Japan Meteorological Agency registered Asian dust events at Fukuoka on March 8, 9, and 19, 2013. The results of the present study suggest that high levels of anthropogenic air pollutants were transported with Asian dust. Similarly, long-range transport of air pollutants including mutagens occurred on days when Asian dust events were not registered.

Long-range transport of mutagens and other air pollutants from mainland East Asia to western Japan.

INTRODUCTION: Asian dust events, transport of dust particles from arid and semi-arid areas in China and Mongolia to the east by prevailing westerlies, are often observed in Japan in spring. In recent decades, consumption of fossil fuels has markedly increased in mainland East Asia with rapid economic growth, and severe air pollution has occurred. A part of air pollutants including mutagens, such as polycyclic aromatic hydrocarbons (PAHs), generated in mainland East Asia are thought to be transported to Japan by the prevailing westerlies, like Asian dust, and winter monsoon. The objective of this study was to clarify the long-range transport of mutagens and other air pollutants in East Asia. Thus, we collected total suspended particles (TSP) at a rural town in western Japan, namely, Yurihama in Tottori Prefecture, for 1 year (June 2012-May 2013), and investigated their chemical constituents and mutagenicity. RESULTS: Many TSP collected from January to March showed high mutagenicity toward Salmonella typhimurium YG1024 with and without S9 mix, and high levels of lead (Pb) and sulfate ions (SO4 (2-)), which are indicators of transboundary air pollutions from mainland East Asia, were detected in those TSP. A large amount of iron, which is an indicator of sand, was found in highly mutagenic TSP collected in March, but not in TSP collected in January and February. High levels of PAHs were detected in highly mutagenic TSP collected from January to March. The ratios of the concentration of fluoranthene to those of fluoranthene and pyrene suggested that the main source of PAHs in TSP collected in winter and spring was coal and biomass combustion. Backward trajectories of air masses on days when high levels of mutagenicity were found indicated that these air masses had traveled from eastern or northern China to Yurihama. CONCLUSIONS: These results suggest that high levels of mutagens were transported from mainland East Asia to western Japan, and this transportation accompanied Asian dust in March, but not in January and February.