Molecular Basis Underlying Hepatobiliary and Renal Excretion of Phenolic Acids of Salvia miltiorrhiza Roots (Danshen).

Phenolic acids are cardiovascular constituents (originating from the Chinese medicinal herb Salvia miltiorrhiza root/Danshen) of DanHong and many other Danshen-containing injections. Our earlier pharmacokinetic investigation of DanHong suggested that hepatic and/or renal uptake of the Danshen compounds was the crucial steps in their systemic elimination. This investigation was designed to survey the molecular basis underlying hepatobiliary and renal excretion of the Danshen compounds, i.e., protocatechuic acid, tanshinol, rosmarinic acid, salvianolic acid D, salvianolic acid A, lithospermic acid, and salvianolic acid B. A large battery of human hepatic and renal transporters were screened for transporting the Danshen compounds and then characterized for the uptake kinetics and also compared with associated rat transporters. The samples were analyzed by liquid chromatography/mass spectrometry. Because the Danshen phenolic acids are of poor or fairly good membrane permeability, their elimination via the liver or kidneys necessitates transporter-mediated hepatic or renal uptake from blood. Several human transporters were found to mediate hepatic and/or renal uptake of the Danshen compounds in a compound-molecular-mass-related manner. Lithospermic acid and salvianolic acid B (both >500 Da) underwent systemic elimination, initiated by organic anion-transporting polypeptide (OATP)1B1/OATP1B3-mediated hepatic uptake. Rosmarinic acid and salvianolic acids D (350-450 Da) underwent systemic elimination, initiated by OATP1B1/OATP1B3/organic anion transporter (OAT)2-mediated hepatic uptake and by OAT1/OAT2-mediated renal uptake. Protocatechuic acid and tanshinol (both <200 Da) underwent systemic elimination, initiated by OAT1/OAT2-mediated renal uptake and OAT2-mediated hepatic uptake. A similar scenario was observed with the rat orthologs. The investigation findings advance our understanding of the disposition of the Danshen phenolic acids and could facilitate pharmacokinetic research on other Danshen-containing injections.

Effect of Sn Content on the Microstructure and Properties of Wire and Arc Additive Manufactured Al-Cu Alloy Deposits.

Al-Cu-Sn alloy deposits with different Sn contents were prepared by the wire and arc additive manufacturing process. The microstructure and mechanical properties of the deposits were examined by metallography, scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy, and tensile tests. The results indicated that the addition of Sn significantly refined the microstructure of the deposits in their as-deposited state, and the grains were transformed from dendrites to equiaxed crystals with a uniform grain size of ∼30 µm. For the deposits with Sn ≥0.15%, the continuous and elongated θ phase on the grain boundary became block-shaped, and the size of the precipitated phase increased. After T6 heat treatment, the θ phase completely dissolved in the substrate in the deposits with Sn ≤0.1%, whereas the θ-phase solid dissolution was incomplete in the deposits with Sn ≥0.15%; the higher the Sn content, the greater the amount of θ phase remaining. After the T6 treatment, the deposits with an Sn content of 0.25% exhibited cracks distributed along the grain boundaries. The addition of Sn significantly increased the density of the θ' phase, which was diffused and uniform in size; with an increase in the Sn content, the distribution density of the θ' phase in the deposits first increased and then decreased as the peak-aging condition was reached. The addition of Sn could effectively improve the mechanical properties of the deposits, which first increased and then decreased with an increase in the Sn content. The mechanical properties of the deposits were optimal at an Sn content of 0.1%, with a tensile strength of 493 MPa, yield strength of 434 MPa, and elongation of 9.5%.

Impact of maternal thyroid autoantibodies positivity on the risk of early term birth: Ma'anshan Birth Cohort Study.

PURPOSE: We aim to investigate associations of maternal serum anti-thyroperoxidase autoantibody (TPOAb) with duration of gestation. We aim to investigate whether maternal TPOAb positivity is associated with the risk of premature or early term birth. METHODS: This was a prospective birth cohort study performed in an iodine sufficient area of China. Serum samples were collected from 2931 women at both the first and second trimesters of pregnancy. Thyrotropin (TSH), free thyroxine (FT4), and TPOAb levels were measured. Data on gestational age at birth was obtained from delivery records. RESULTS: The prevalence of early term birth was 23.8%, while the prevalence of premature birth was 4.2%. The prevalence of TPOAb positivity was 12.1% in the first trimester and was 7.2% in the second trimester. Gestational age at birth was inversely associated with lgTPOAb both in the first trimester (ß, -0.283, 95% CI -0.408, -0.158; P < 0.001) and in the second trimester (ß, -0.174, 95% CI -0.319, -0.030; P = 0.018), after adjustment for potential confounding factors. There was a positive association of TPOAb positivity with the risk of early term birth both in the first (OR = 1.691, 95% CI 1.302, 2.197) and second trimesters (OR = 1.644, 95% CI 1.193, 2.264), after adjustment for potential confounding factors. TPOAb positivity in the second trimester was associated with a 1.863-fold higher risk of premature birth (OR = 1.863, 95% CI 1.009, 3.441), after adjustment for potential confounding factors. CONCLUSIONS: Our results show that TPOAb is associated with shorter duration of gestation and with higher risk of premature and early term birth.

Thyroid autoantibodies in pregnancy are associated with hypertensive disorders of pregnancy: Ma'anshan Birth Cohort Study.

OBJECTIVE: Hypertensive disorders of pregnancy (HDP) have been associated with adverse health outcomes for both mothers and children. Previous studies examining associations of maternal thyroid autoantibodies with HDP indicate conflicting results. The objective of this study was to examine associations of maternal thyroid autoantibody positivity in the first and the second trimesters with the risk of HDP. DESIGN, PARTICIPANTS AND MEASUREMENTS: In the Ma'anshan Birth Cohort study, a population-based prospective study in China, a total of 3474 pregnant women were enrolled between May 2013 and September 2014. Thyroid autoantibodies, including antithyroperoxidase autoantibody (TPOAb) and antithyroglobulin autoantibody (TgAb), as well as thyroid function tests, were measured in both the first and the second trimesters in 2893 pregnant women. Multivariate logistic regression analyses were conducted to calculate the odds ratio (OR) and 95% confidence interval (CI) for the associations between thyroid autoantibodies and HDP. RESULTS: Multivariate logistic regression analyses showed that TPOAb positivity in the first trimester was associated with a 1.80 (95% CI = 1.17-2.78) increased odds of HDP after adjustment for confounders, which was mainly due to an increased risk of gestational hypertension (OR = 1.93, 95% CI = 1.17-3.18). In addition, TgAb positivity in the first trimester was associated with a higher risk of HDP (OR = 1.78, 95% CI = 1.16-2.73) after adjustment for confounders, which was mainly due to an increased risk of gestational hypertension (OR = 1.89, 95% CI = 1.15-3.11). These associations were also seen among euthyroid women. Women with positive TPOAb in the second trimester seemed to have a higher risk of gestational hypertension (OR = 1.87, 95% CI = 1.02-3.43) after adjustment for confounders. However, among euthyroid women, TPOAb positivity in the second trimester was not associated with HDP. The TgAb status in the second trimester was not associated with HDP. CONCLUSIONS: Our results show that TPOAb positivity and TgAb positivity in the first trimester are associated with an increased risk of HDP. These data demonstrate that these associations are even seen among euthyroid women.

Season-dependent concentrations of urinary phthalate metabolites among Chinese pregnant women: Repeated measures analysis.

In utero exposure to phthalates may have adverse effects on pregnant women and their offsprings. Therefore, the exposure level of these substances among individuals, particularly among sensitive population, is of concern. The objective of the present study is to characterize urinary concentrations of phthalate metabolites at multiple time points during pregnancy in Chinese women. A total of 3455 pregnant women were included from Ma'anshan Birth Cohort in China. Spot urine samples in the morning (8:00-10:00) and questionnaires were obtained at three separate visits (approximately in 10, 26, and 34 gestational weeks). Seven phthalate metabolites from urine samples were analyzed, including monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), mono benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). Geometric means of concentrations were ranged from 0.05 to 41.0ng/mL for all the metabolites mentioned above. No individual exposure level was above the 95th percentiles for all the seven phthalates. On the three separate visits, 0.5%, 0.9% and 1.2% of the participants had coexposure to above the 75th percentiles for all metabolites. Taken these visits together, a total of 29 urine samples had concentrations above the 95th percentiles, while 3.0%-5.6% of urine levels were above 75th percentiles for at least one specific phthalate metabolite. We observed moderate intraclass correlation coefficients (ICCs) ranging from 0.44 to 0.56 for MBzP, MEHP and MEP, and lower ICCs, from 0.28 to 0.32, for MMP, MBP, MEOHP and MEHHP. Sampling season was associated with concentrations of all phthalate metabolites, showing heavier exposure was more likely to occur during summer. In summary, phthalate exposure is prevalent in Chinese pregnant women. However, throughout pregnancy coexposure to multiple phthalates at the upper percentile of exposure is infrequent. Mild to moderate temporal stability indicates that a single measurement in spot urine collected in the morning (8:00-10:00) seems not enough to describe throughout pregnancy phthalate exposure. Urinary levels vary by sampling seasons, which should be taken into consideration in future analyses.

Emotion regulation, emotional eating and the energy-rich dietary pattern. A population-based study in Chinese adolescents.

Research investigating the influence of emotion regulation (ER) strategies on emotional eating and diet among Chinese adolescents is scarce. The aim of this study was to test associations between two ER strategies (suppression/cognitive reappraisal), emotional eating, and an energy-rich dietary pattern. A total of 4316 adolescents from 10 high schools were surveyed. Dietary patterns were derived using factor analysis. Bivariate correlations were analyzed to examine associations between ER strategies, emotional eating behavior and an energy-rich dietary pattern, by gender. The mediating effect of emotional eating in the relationship between ER and energy-rich food consumption by gender was estimated using structural equation modeling. A higher level of suppression, but no lack of cognitive reappraisal, was associated with emotional eating in boys and girls. A higher level of suppression and lack of cognitive reappraisal were associated with a greater intake of energy-rich foods in girls only. Emotional eating mediated the relationship between a higher level of suppression and a greater intake of energy-rich food in girls. This study revealed significant associations between two ER strategies and an energy-rich dietary pattern in girls, and provided evidence that higher levels of suppression may put girls at risk for emotional eating, potentially affecting the energy-rich dietary pattern.

[Calibration Procedure of Laser Confocal Micro-Raman Spectrometer].

As a common spectral characterization technique, Raman spectroscopy is widely used and has a specified calibration procedure. Based on laser confocal micro-Raman spectrometer, in this paper, we briefly introduced the principle, configuration and main components of Raman spectrometer. In addition, the calibration procedures were also presented, with an emphasis on the calibration of spectrometer (spectrograph) and that of excitation laser wavelength. On the basis of conventional calibration method, a novel and more accurate method was proposed to obtain the actual excitation wavelength, that is, calibration at the point of Raman shift Δν=0. Using this novel calibration method of excitation wavelength, Raman frequency shift values of sulfur were measured, and compared with the standard values from American Society Testing and Materials (ASTM). As a result, the measured values after calibration were consistent with those ASTM values, which indicated that the calibration method is accurate. Thus, a more reasonable calibration procedure of the laser confocal micro-Raman spectrometer was provided.

RET and PHOX2B genetic polymorphisms and Hirschsprung's disease susceptibility: a meta-analysis.

BACKGROUND: Many publications have evaluated the correlation between RET, PHOX2B polymorphisms and Hirschsprung's disease with conflicting results. We performed this meta-analysis to clarify the association of RET, PHOX2B polymorphisms with HSCR. METHODS: We searched Pubmed, Elsevier Science Direct, China National Knowledge Infrastructure database, Chinese Biomedical database, Google scholar. The combined odds ratio (OR) with 95% CI was calculated to estimate the strength of the association. Heterogeneity and publication bias were also assessed. RESULTS: In total, 16 studies concerning RET and 4 studies concerning PHOX2B were included in the meta-analysis. The effects of five polymorphisms of RET (rs1800858, rs1800860, rs1800861, rs10900297, rs2435357) and one polymorphism (rs28647582) of PHOX2B were evaluated. We found a significant correlation between RET polymorphisms and HSCR. For rs1800858, the overall ORs (95% CI) of the A versus G, AA versus GG, AA/AG versus GG and AA versus GG/AG were 3.81 (2.28-6.35); 8.36 (3.45-20.25); 3.59 (1.83-7.02); and 6.60 (3.66-11.89). For rs1800861, the comparison of subjects in the G versus T, GG versus TT, GG/TG versus TT and GG versus TT/TG were 2.85(1.81-4.47); 5.38(2.68-10.80); 3.07(2.17-4.34) and 4.14(1.84-9.30) respectively. For rs10900297, the comparison results showed statistically significant. (OR(C versus A) = 5.05,95%CI = 4.16-6.13; OR(CC versus AA) = 9.73, 95%CI = 5.94-15.94; OR(CC/AC versus AA) = 5.31, 95%CI = 3.27-6.82; OR(CC versus AC/AA) = 7.06,95%CI = 5.60-8.91.) But, for rs1800860, the GG/GA versus AA did not reach statistical association (OR = 3.77, 95% CI = 0.94-15.07) and the G versus A, GG versus AA, GG versus GA/AA were 2.23 (1.60-3.11);4.56 (1.14-18.27); 2.38 (1.66-3.43) respectively. For rs2435357, the T versus C, TT versus CC, TT/TC versus CC and TT versus CC/TC were 4.53 (3.27-6.27); 11.44 (5.67-23.10); 4.04 (2.92-5.57), and 9.01(5.25-15.46).The single polymorphism of PHOX2B gene wasn't related to the risk for HSCR. CONCLUSIONS: This meta-analysis shows a significant association between RET polymorphisms and HSCR.

Electronic characteristics of Au-mercaptohexadecanoic acid-Au junction in a capillary.

The electrical property of a self-assembled monolayer (SAM) of mercaptohexadecanoic acid (HS-C15H30-COOH) has been investigated with a tunneling junction confined in a capillary. This capillary method can shun the interference of vacuum gap. The contact area can be determined according to the diameter of capillary. The nonlinear current-voltage curve and dl/dV curve are measured in the potential range of +/-0.8 V. The slight asymmetry of I-V curve and dl/dV curve is attributed to the different coupling between the metal and the end-groups of molecule. This method will supply a simple way to measure the property of single molecules and monolayers.