Search

Objective To develop a high performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS） method for the determination of the content of 4-fluoromethamphetamine （4-FMA） in rat plasma, and to provide a methodological basis for the study of the toxicokinetics of 4-FMA in rats. Methods Rat plasma samples were added into internal standard methamphetamine （MA）. Its proteins were precipitated with methanol and then separated with Poroshell 120 EC-C18 chromatographic column. A 0.1% formic acid aqueous solution and a 0.1% formic acid acetonitrile solution were used as the mobile phase at the flow rate of 0.4 mL/min. Electrospray ionization source was used for detection in the multiple reaction monitoring （MRM） mode. Results The linear relationship was good when the mass concentration of 4-FMA in plasma samples was in the range of 5-1 000 ng/mL （r>0.999）. The limit of detection （LOD） was 3 ng/mL and the limit of quantification （LOQ） was 5 ng/mL. The accuracy was expressed as relative error （RE）, and in the range of ±5%, the intra-day precision and inter-day precision （relative standard deviation, RSD） less than 9%, and the extraction recovery rate was more than 90%. The analysis and detection of plasma samples were completed within 2.5 min. Conclusion This study developed a HPLC-MS/MS method for the determination of 4-FMA in rat plasma samples. This method is accurate, rapid, simple and sensitive and can be applied to the study of toxicokinetics of 4-FMA.

Polycyclic aromatic hydrocarbons (PAHs) are known environmental pollutants. Studies are very limited regarding the impacts of paternal PAHs exposure on birth outcomes as well as the underpinning mechanisms in human. In this study, 302 reproductive-aged males (22–46 years old) were enrolled and demographic informatics data were obtained by questionnaires. The levels of urinary hydroxylated PAHs (OH-PAHs) were assessed by ultra-high performance liquid chromatography-tandem mass spectrometry; and methylation levels of the imprinting genes H19, Meg3, and Peg3 of sperm DNA were evaluated via bisulfite pyrosequencing. The analysis of the correlation between OH-PAHs levels and methylation levels of imprinting genes showed that OH-PAHs are correlated with some CpG sites in H19, Peg3, and Meg3. To further investigate an association of urinary OH-PAHs with birth outcomes, follow-up study of wives of these subjects has been performed for 1–3 years. As the result, a total of 157 babies were born. The birth outcomes parameters including birth weight (BW), length (BL), and ponderal index (PI) were recorded. The further analysis of generalized estimating equation indicated a negative correlation between urinary total OH-PAHs levels and newborn BW (β = −0.081, p = 0.020); but this association has not been found for BL and PI. Furthermore, a logistic regression analysis was employed for examining associations of the methylation of imprinting genes with birth outcomes parameters, which indicated a negative correlation between BW and H19, namely, each unit percent (%) elevation in methylation of H19 (but not Peg3 and Meg3) was significantly associated with a 0.135 g reduction of BW (β = −0.135; 95% CI 0.781–0.978). Putting together, these results show that paternal non-occupational environmental exposure to PAHs is associated with newborn BW. And imprinting gene H19 methylation may be involved in the underlying mechanisms. This study in human population adds a support for previous animal study and implies that environmental impact on the offspring through paternal pathway.

Mercury (Hg) is a well-recognized environmental pollutant known by its toxicity of development and neurotoxicity, which results in adverse health outcomes. However, the mechanisms underlying the teratogenic effects of Hg are not well understood. Imprinting genes are emerging regulators for fetal development subjecting to environmental pollutants impacts. In this study, we examined the association between preconceptional Hg exposure and the alteration of DNA methylation of imprinting genes H19, Meg3, and Peg3 in human sperm DNA.A total of 616 men, aged from 22 to 59, were recruited from Reproductive Medicine Clinic of Maternal and Child Care Service Center and the Urologic Surgery Clinic of Shanxi Academy of Medical Sciences during April 2015 and March 2016. Demographic information was collected through questionnaires. Urine was collected and urinary Hg concentrations were measured using a fully-automatic double-channel hydride generation atomic fluorescence spectrometer. Methylation of imprinting genes H19, Meg3 and Peg3 of sperm DNA from 242 participants were examined by bisulfite pyrosequencing. Spearman's rank and multivariate regression analysis were used for correlation analysis between sperm DNA methylation status of imprinting genes and urinary Hg levels.The median concentration of Hg for 616 participants was 9.14μg/l (IQR: 5.56-12.52 μg/l; ranging 0.16-71.35μg/l). A total of 42.7% of the participants are beyond normal level for non-occupational exposure according to the criterion of Hg poisoning (≥10 μg/L). Spearman's rank analysis indicated a negative correlation between urinary Hg concentrations and average DNA methylation levels of imprinted genes H19 (rs = -0.346, p

The Euclidean distance is usually used in heuristic planning of Dyna_Q-learning based on reinforcement learning tasks of goal position. But it is not suitable for these tasks whose state space is not continuous in Euclidean space such as path planning of disaster rescue robot in underground coal mine. For the problem, the paper introduced the Laplacian Eigenmap whose computational complexity is lower in manifold learning, then proposed an improved Dyna_Q-learning algorithm based on manifold distance metric. The proposed algorithm is simulated in grid world that is similar to underground environment. The simulation results verified validity of the algorithm.

Recently, an increasing number of human and animal studies have reported that exposure to benzo(a)pyrene (BaP) induces neurological abnormalities and is also associated with adverse effects, such as tumor formation, immunosuppression, teratogenicity, and hormonal disorders. However, the exact mechanisms underlying BaP-induced impairment of neurological function remain unclear. The aim of this study was to examine the regulating mechanisms underlying the impact of chronic BaP exposure on neurobehavioral performance.C57BL mice received either BaP in different doses (1.0, 2.5, 6.25 mg/kg) or olive oil twice a week for 90 days. Memory and emotional behaviors were evaluated using Y-maze and open-field tests, respectively. Furthermore, levels of mRNA expression were measured by using qPCR, and DNA methylation of NMDA receptor 2B subunit (NR2B) was examined using bisulfate pyrosequencing in the prefrontal cortex and hippocampus.Compared to controls, mice that received BaP (2.5, 6.25 mg/kg) showed deficits in short-term memory and an anxiety-like behavior. These behavioral alterations were associated with a down-regulation of the NR2B gene and a concomitant increase in the level of DNA methylation in the NR2B promoter in the two brain regions.Chronic BaP exposure induces an increase in DNA methylation in the NR2B gene promoter and down-regulates NR2B expression, which may contribute to its neurotoxic effects on behavioral performance. The results suggest that NR2B vulnerability represents a target for environmental toxicants in the brain.

The mechanism of the impact of social capital of scientific and technological intermediary on knowledge transfer is not yet clear. This research tries to build a theoretical framework of the social capital of scientific and technological intermediary for the knowledge transfer performance, and also selects the incubators of the Science and Technology Park of Nanjing University as a typical case of the scientific and technological intermediary, analyzes the differences between the social capital of scientific and technological intermediary and the social capital of the government, colleges and universities, enterprises and different subjects of knowledge innovation through open research, and discusses the effect and mechanism of knowledge transfer, so as to clarify the nature of social capital of scientific and technological intermediary, and give play to positive effect in the knowledge transfer and innovation, and provide scientific basis and reference experience.

The effect of La on Al/NaBH4 hydrolysis was elaborated in the present paper. Hydrogen generation amount increases but hydrogen generation rate decreases with La content increasing. There is an optimized composition that Al-15 wt% La-5 wt% NiCl2/NaBH4 mixture (Al-15 wt% La-5 wt% NiCl2/NaBH4 weight ratio, 1 : 3) has 126 mL g−1 min−1 maximum hydrogen generation rate and 1764 mL g−1 hydrogen generation amount within 60 min. The efficiency is 88%. Combined with NiCl2, La has great effect on NaBH4 hydrolysis but has little effect on Al hydrolysis. Increasing La content is helpful to decrease the particle size of Al-La-NiCl2 in the milling process, which induces that the hydrolysis byproduct Ni2B is highly distributed into Al(OH)3 and the catalytic reactivity of Ni2B/Al(OH)3 is increased therefore. But hydrolysis byproduct La(OH)3 deposits on Al surface and leads to some side effect. The Al-La-NiCl2/NaBH4 mixture has good stability in low temperature and its hydrolytic performance can be improved with increasing global temperature. Therefore, the mixture has good safety and can be applied as on board hydrogen generation material.

The NMDA receptor represents a particularly important site of ethanol action in the CNS. We recently reported that NMDA receptor 2B (NR2B) gene expression was persistently up-regulated following chronic intermittent ethanol (CIE) treatment. Increasing evidence that epigenetic mechanisms are involved in dynamic and long-lasting regulation of gene expression in multiple neuroadaptive processes prompted us to investigate the role of DNA methylation in mediating CIE-induced up-regulation of NR2B gene transcription. To dissect the changes of DNA methylation in the NR2B gene, we have screened a large number of CpG sites within its 5'-regulatory area following CIE treatment.Primary cortical cultured neurons were subjected to ethanol treatment in a CIE paradigm. Bisulfite conversion followed by pyrosequencing was used for quantitative measurement and analysis of CpG methylation status within the 5'-regulatory area of the NR2B gene; chromatin immunoprecipitation (ChIP) assay was used to examine DNA levels associated with methylation and transcription factor binding. Electrophoretic mobility shift assay (EMSA) and in vitro DNA methylation assays were performed to determine the direct impact of DNA methylation on the interaction between DNA and transcription factor and promoter activity.Analysis of individual CpG methylation sites within the NR2B 5'regulatory area revealed three regions with clusters of site-specific CpG demethylation following CIE treatment and withdrawal. This was confirmed by ChIP showing similar decreases of methylated DNA in the same regions. The CIE-induced demethylation is characterized by being located near certain transcription factor binding sequences, AP-1 and CRE, and occurred during treatment as well as after ethanol withdrawal. Furthermore, the increase in vitro of methylated DNA decreased transcription factor binding activity and promoter activity. An additional ChIP assay indicated that the CIE-induced DNA demethylation is accompanied by increased occupation by transcription factors.These results suggest an important role of DNA demethylation in mediating CIE-induced NR2B gene up-regulation, thus implicating a novel molecular site of alcohol action.

A new triple fixed-point theorem is applied to investigate the existence of at least triple positive solutions of fourth-order four-point boundary value problems for p-Laplacian dynamic equations on a time scale. The interesting point is that we choose an inversion technique employed by Avery and Peterson in 1998.

Abstract Background MTHFR 677C>T polymorphism is a genetic alteration in an enzyme involved in folate metabolism, but its effect on host susceptibility to cervical cancer is still uncertain. The aim of this study was to investigate the association between MTHFR 677C>T polymorphism and cervical cancer by performing a meta-analysis. Methods Pubmed, Embase, Web of Science, and the Chinese Biomedical Database (CBM) databases were searched for case–control studies investigating the association between MTHFR 677C>T polymorphism and cervical cancer. Odds ratios (OR) and 95% confidence intervals (95%CI) were used to assess this possible association. Results 11 studies with a total of 1898 cervical cancer cases and 2678 controls were included. Meta-analyses of a total 11 studies showed no association between MTHFR 677C>T polymorphism and cervical cancer using all five genetic models (All P values > 0.05). However, subgroup analyses showed the odds of the homozygous TT genotype were much less in cervical cancer cases than in controls in Europeans, which implied an association between the homozygous TT genotype and cervical cancer in Europeans (For TT versus CC, fixed-effects OR = 0.65, 95%CI 0.45-0.93, P = 0.020, I2 = 0.0%). The odds for the homozygous TT genotype were greater in cervical cancer cases than in controls in East Asians, which also implied an association between the homozygous TT genotype and cervical cancer in East Asians (For TT versus CC, random-effects OR = 1.66, 95%CI 1.05-2.62, P = 0.029, I2 = 52.6%; For TT versus CT/CC, random-effects OR = 1.55, 95%CI 1.09-2.22, P = 0.016, I2 = 42.4%). Both subgroup analyses and meta-regression analyses suggested ethnicity was the major source of heterogeneity. Publication bias was not evident. Conclusions This meta-analysis supports an association between MTHFR 677C>T polymorphism and cervical cancer, and the effect of this association may be race specific. Further studies with large sample sizes and careful design are needed to identify this association more comprehensively.

A new triple fixed-point theorem is applied to investigate the existence of at least triple positive solutions of fourth-order four-point boundary value problems for -Laplacian dynamic equations on a time scale. The interesting point is that we choose an inversion technique employed by Avery and Peterson in 1998.