Agilent Technologies (Japan)

AimInulin, a soluble dietary fiber, is a source of energy for the host while the metabolites, such as short-chain fatty acids (SCFAs), produced in the gut through bacterial fermentation exerts the anti-obesity effect. In this study, we aimed to apply a metabolomics approach and clarify the role of this soluble dietary fiber on glucose and lipid metabolism under the calorie-matched condition.Materials and methodsEight-week-old male C57BL/6J mice were fed a high-fat/high-sucrose based diet containing maltodextrin or inulin for 12 weeks through calorie-matched pair feeding. We evaluated glucose tolerance, and energy expenditure using indirect calorimetry, comprehensive metabolites in the content of jejunum, feces, and portal vein serum using gas chromatography-mass spectrometry, and histological changes in the adipose tissue.ResultsThe inulin group exhibited reduced visceral adipose tissue and smaller size of visceral adipocyte. It also exhibited improved glucose tolerance and an increase in energy expenditure. Reflecting the results of fermentation, the metabolomics analysis revealed an increase in the succinic acid and SCFA contents in both feces and portal vein serum in the inulin group.ConclusionsInulin altered the gut metabolites and reduced visceral adipose tissue, thereby resulting in improved glucose tolerance.

BackgroundDiabetes mellitus increases the excretion of urinary glucose from the renal glomeruli due to elevated blood glucose levels. In the renal tubules, SGLT2 is expressed and reabsorbs the excreted urinary glucose. In the pathogenesis of diabetes mellitus, glucose reabsorption by SGLT2 is increased, and SGLT2 inhibitors improve hyperglycaemia by inhibiting this reabsorption. When urinary glucose excretion is enhanced, glucose supply to skeletal muscle may be insufficient and muscle protein catabolism may be accelerated. On the other hand, SGLT2 inhibitors not only ameliorate hyperglycaemia but also improve fatty acid metabolism in muscle, which may prevent muscle atrophy.MethodsEight‐week‐old male db/m mice or db/db mice were fed a standard diet with or without the SGLT2i luseogliflozin (0.01% w/w in chow) for 8 weeks. Mice were sacrificed at 16 weeks of age, and skeletal muscle and serum lipidomes, as well as skeletal muscle transcriptome, were analysed.ResultsAdministration of SGLT2i led to not only decreased visceral fat accumulation (P = 0.004) but also increased soleus muscle weight (P = 0.010) and grip strength (P = 0.0001). The levels of saturated fatty acids, especially palmitic acid, decreased in both muscles (P = 0.017) and sera (P = 0.041) upon administration of SGLT2i, while the content of monosaturated fatty acids, especially oleic acid, increased in both muscle (P < 0.0001) and sera (P = 0.009). Finally, the accumulation of transcripts associated with fatty acid metabolism, such as Scd1, Fasn, and Elovl6, and of muscle atrophy‐associated transcripts, such as Foxo1, Mstn, Trim63, and Fbxo32, decreased following SGLT2i administration.ConclusionsIntramuscular fatty acid metabolism and gene expression were influenced by the extracellular lipidome, which was modified by SGLT2i. Hence, secondary effects, other than the hypoglycaemic effects of SGLT2i, might lead to the alleviation of sarcopenia.

ObjectivesThe purpose of this study was to develop a simple and accurate gas chromatography‐mass spectrometry (GC‐MS) method for simultaneous determination of four urinary metabolites from four organic solvents, that is, hippuric acid (HA) from toluene, methylhippuric acid (MHA) from xylene, and mandelic acid (MA) and phenylglyoxylic acid (PGA) from styrene or ethylbenzene for biological monitoring.MethodsThe four metabolites were directly methyl‐esterified with 2,2‐dimethoxypropane and analyzed using GC‐MS. The proposed method was validated according to the US Food and Drug Administration guidance. The accuracy of the proposed method was confirmed by analyzing a ClinChek®—Control for occupational medicine (RECIPE Chemicals +Instruments GmbH).ResultsCalibration curves showed linearity in the concentration range of 10‐1000 mg/L for each metabolite, with correlation coefficients >0.999. For each metabolite, the limits of detection and quantification were 3 mg/L and 10 mg/L, respectively. The recovery was 93%‐117%, intraday accuracy, expressed as the deviation from the nominal value, was 92.7%‐103.0%, and intraday precision, expressed as the relative standard deviation (RSD), was 1.3%‐4.7%. Interday accuracy and precision were 93.4%‐104.0% and 1.2%‐9.5%, respectively. The analytical values of ClinChek obtained using the proposed method were sufficiently accurate.ConclusionsThe proposed method is a simple and accurate which is suitable for routine analyses that could be used for biological monitoring of occupational exposure to four organic solvents.

Tools that provide absolute quantification of biomolecules, particularly of proteins and their post-translational modifications, without needing suitable specific standards, are urgently demanded nowadays. To this end, we have significantly improved the recently introduced strategy based on CH4 addition to the plasma for absolute quantification of biomolecules using HPLC-ICP-MS. Addition of CO2 has been optimized and finally selected as a safer, more efficient quantitative strategy that is able to provide constant (<6% error) signal response factor for the six elements assayed (S, P, As, Se, Br, I) under compromised conditions. In the particular case of absolute protein quantification, accuracy and precision attainable for S-based absolute determination of intact proteins using internal and external S-generic standards were compared. Potential for real sample analysis was demonstrated by the high-sensitivity analysis of toxins present in snake venoms. Finally, multielemental speciation capabilities of the approach have been also demonstrated through P and S simultaneous analysis in phosphoproteomics. Simultaneous accurate determination of both absolute protein amount and corresponding phosphorylation degree for intact β-casein, and even impurity traces of κ and α-s1 isoforms present, has been successfully achieved using a simple mixture of inorganic P and S standards. The lowest detection limits (<1 fmol protein) ever published for S- and P-based intact protein quantification with ICP-MS are reported.

Multiple unknown high-order cluster ions were observed as the results of ion-molecule reactions between strontium ions and fluoromethane molecules in the reaction-cell of an inductively coupled plasma tandem quadrupole mass spectrometer (ICP-QMS/QMS). In order to elucidate the structures of these unknown cluster ions, isotope-enriched fluoromethane (CD3F) was used as the reaction-cell gas compared to natural fluoromethane (CH3F). As results, SrF(CH3F)0-4+ and SrF(H2O)(CH3F)0-3+ cluster ions were experimentally confirmed in the present work, while SrF(H2O)(CH3F)0-3+ cluster ions in the reaction-cell of ICP-QMS/QMS were observed and confirmed for the first time in the world.

40Ar+ related product ions in an octopole reaction cell (ORC) were observed with an inductively coupled plasma tandem quadrupole mass spectrometer (ICP-QMS/QMS). In order to simplify the ion composition of the plasma, the carrier gas was directly connected to the torch injector, i.e. without introduction of the sample solution. The m/z of the first QMS was set to 40 permitting the passage of 40Ar+. Isotope enriched oxygen gas (18O2) was used as the reaction gas in order to separate the spectra of O3+ and Ar2O2+. The intensities of the ions produced in the ORC were measured by the second QMS. As the products of the reactions among 40Ar+ ions and 18O2 molecules in the ORC, the following ions were observed: 18O+, 18O2+, 18O3+, 18O4+, 40Ar18O+, 40Ar18O2+, 40Ar218O2+, and 40Ar18O22+. At a reaction gas flow rate of 0.3 mL min−1, the ionic species with the highest signal intensity was 18O2+, followed by 40Ar+ and 18O+. The maximum signal intensities of different product ions were obtained at different flow rates of the reaction gas. A lower flow rate of the reaction gas benefited the production of 40Ar18O+ and 18O3+, while a higher flow rate of the reaction gas benefited the production of 40Ar18O2+ and 40Ar218O2+. The maximum transfer efficiency from 40Ar+ to the resulting ionic species was 91%, 2.0%, and 0.12% for 18O2+, 18O+, and 40Ar18O+, respectively. The maximum transfer efficiency to the other investigated ionic species was less than 0.023%. By using 18O2 as the reaction gas, the mechanisms of 40Ar+ resulted ionic species interfering with the measurement of 32S16O+ were confirmed. The results showed that the contributions of 16O3+ and 40Ar2O2+ were almost equivalent to each other.

水道水中の臭素酸イオン (BrO3-) を既存の告示法よりも高精度かつ迅速・簡便に分析するために, LC/MS/MSによる測定方法を検討し, 臭素酸イオンを高感度に検出でき, さらに水道水中に含まれる他の陰イオンを良好に分離可能な測定条件を確立した。さらに, 本研究で確立した測定条件が全国の水道水に適用できるかどうかを検証するために, 水道事業体等の23機関において水道水に臭素酸イオンを基準値 (0.01 mg L-1) およびその1/10 (0.001 mg L-1) となるように添加した試料を調製し, 各機関で最適化した様々な測定条件で試験を行った。その結果, いずれの機関においても厚生労働省が示している「水道水質検査方法の妥当性評価ガイドライン」の真度, 併行精度および室内精度の目標を満たしたことから, 本分析法は水道水中の臭素酸イオンを基準値の1/10 (0.001 mg L-1) まで高精度に分析可能であると評価した。

As process technologies continually advance, process variation has greatly increased and has gradually become one of the most critical factors for IC manufacturing. Furthermore, these increasingly complex processes continue to make greater use of stressors for mobility enhancement, thus requiring large volumes of data for extensive characterization of layout-dependent effects (LDE) for validation of both SPICE models and design for manufacturing. Transistor threshold voltage (Vt) is a commonly used parameter both for characterization during process development and for monitoring of volume manufacturing. To adequately quantify local process variation or LDE, Vt must be measured for a sufficiently large number of device-under-tests (DUTs) to obtain a statistically representative sample population. The number of Vt measurements required to obtain such a statistically significant result, however, requires extremely long testing time, especially for array-based test structure designs including thousands of DUTs. In this paper, we present a very fast threshold voltage measurement methodology using an operational amplifier-based source-measure unit test configuration, which greatly improves testing efficiency and accuracy, and is not sensitive to process variation. The proposed test methodology can improve Vt testing time by a factor of 5-10 relative to the commonly used binary-search algorithm, and by a factor of ~2 relative to an optimized interpolation algorithm, and achieves better accuracy (standard deviation of Vt = 0.15 mV, versus typical accuracy of ~ 0.5 mV for the two algorithms mentioned). Furthermore, the layout and configuration of conventional test structures need not be modified to adapt the proposed methodology. The measured results from the most advanced process technology nodes demonstrate the testing efficiency and accuracy of the proposed test structure in characterizing the large number of DUTs required for quantifying process variation or LDEs.

[Background] Inorganic arsenic (iAs) is methylated to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in the human body, however, large amounts of DMA have been observed in the urine of...