Based on the specific folic acid-folate receptor (FA-FR) interaction, macromolecular FR can bind with FA-linked DNA-small molecule chimeras, which can prevent enzymolysis by exonuclease III (Exo III), enabling a novel fluorescence biosensor for FR to be developed using quinaldine red as a G-quadruplex-binding probe.

Although clinical trials for the enterovirus type 71 (EV71) inactivated vaccine have been progressing, the potential mechanism of EV71 infection and its associated pathogenesis are not well-characterized in terms of comprehensive analysis of the induced immune response, which is generally recognized as an important indicator of the safety of vaccines. To investigate the Th1/Th2 response following viral challenge in neonatal rhesus monkeys immunized with different doses of EV71 inactivated vaccines, the variety of different Th1 and Th2 cytokines in the organs or tissues of the monkeys were identified. The results suggest that depending on the viral challenge, the Th1/Th2 reaction induced by different doses of EV71 inactivated vaccine varies. More specifically, there is an enhanced immune response in 80EU- and 1280EU-immunized monkeys, whereas 320EU immunization induces a mild response. Although there is no direct impact on the variation in immune protection induced by the vaccine, the Th1 reaction functions in T-cell cytotoxicity, which will aid further investigation of the pathogenic characteristics of small pathological changes in the central nerves system (CNS) likely induced by the Th1 response.

Inflammation may activate stem cells via prostaglandin E2 (PGE2) production mediated by cyclooxygenase-2 (COX-2) expression. We performed an immunohistochemical analysis of the expression of stemness markers (Oct3/4 and CD44v6) and COX-2 in urinary bladder tissues obtained from cystitis and cancer patients with and without Schistosoma haematobium infections. Immunoreactivity to Oct3/4 was significantly higher in S. haematobium-associated cystitis and cancer tissues than in normal tissues. CD44v6 expression was significantly higher in bladder cancer without S. haematobium than in normal tissues. COX-2 was located in the cytoplasmic membrane, cytoplasm, and nucleus of the cancer cells. Interestingly, the nuclear localization of COX-2, which was reported to function as a transcription factor, was significantly associated with the upregulation of Oct3/4 and CD44v6 in bladder cancer tissues with and without S. haematobium infection, respectively. COX-2 activation may be involved in inflammation-mediated stem cell proliferation/differentiation in urinary bladder carcinogenesis.

It has been suggested that the temporo-parietal junction (TPJ) is involved in inferring immediate goals and intentions from behaviors, whereas the medial prefrontal cortex (mPFC) integrates social information, such as traits, at a more abstract level. To explore the differential role of the TPJ and mPFC, participants read several verbal descriptions about an agent. Embedded in a factorial design, in one-half of the trials (behavior condition), the agent was engaged in a simple goal-directed behavior, whereas in the other half this description was absent. In another half of the trials (trait condition), the participants had to answer a question about a trait of the agent, whereas in the other half the question was about the agent's physical appearance. The results revealed that the dorsal mPFC was recruited when participants inferred the agent's trait, irrespective of a behavioral description. In contrast, the TPJ, posterior superior temporal sulcus (pSTS), anterior intraparietal sulcus, and premotor cortex were activated when goal-directed behavioral information was presented, irrespective of a trait question. These findings confirm that in a social context, the TPJ (and pSTS) is activated for understanding goal-directed behaviors, whereas the mPFC is involved in processing traits.

Arsenic exposure can result in damages of the neurological system. The present study aimed at whether cell proliferation and neurogenesis in the adult mouse hippocampus were affected after arsenic exposure and whether they could recover after exposure cessation. Mice were randomly placed into 3 groups. The first group received distilled water alone for 4 months (control group); the second group received 4.0mg/L As(2)O(3) through drinking water for 4 months (arsenic group); the third group received 4.0mg/L As(2)O(3) for 2 months and then changed to distilled water for another 2 months (recovery group). Serum and cerebrum arsenic concentrations of the arsenic group were significantly elevated, and then decreased to normal after the change of arsenic to water in the diet. After a four-month administration, the hippocampal number of proliferative cells and the percentage of new mature neurons decreased in the arsenic group as compared with the control group, however, increased significantly in the recovery group when compared with the arsenic group, and restored to the control level. There were no significant differences for apoptosis in different groups. Obvious histopathological ameliorations were observed in the hippocampus of the recovery group. The inhibition of hippocampus cell proliferation and neurogenesis by arsenic is reversible after the arsenic administration was terminated.

BACKGROUND It has been extensively developed in recent years that cell-permeable small molecules, such as polyamide, can be programmed to disrupt transcription factor-DNA interfaces and can silence aberrant gene expression. For example, cyclic pyrrole-imidazole polyamide that competes with glucocorticoid receptor (GR) for binding to glucocorticoid response elements could be expected to affect the DNA dependent binding by interfering with the protein-DNA interface. However, how such small molecules affect the transcription factor-DNA interfaces and gene regulatory pathways through DNA structure distortion is not fully understood so far. METHODOLOGY/PRINCIPAL FINDINGS In the present work, we have constructed some models, especially the ternary model of polyamides+DNA+GR DNA-binding domain (GRDBD) dimer, and carried out molecular dynamics simulations and free energy calculations for them to address how polyamide molecules disrupt the GRDBD and DNA interface when polyamide and protein bind at the same sites on opposite grooves of DNA. CONCLUSIONS/SIGNIFICANCE We found that the cyclic polyamide binding in minor groove of DNA can induce a large structural perturbation of DNA, i.e. a >4 Å widening of the DNA minor groove and a compression of the major groove by more than 4 Å as compared with the DNA molecule in the GRDBD dimer+DNA complex. Further investigations for the ternary system of polyamides+DNA+GRDBD dimer and the binary system of allosteric DNA+GRDBD dimer revealed that the compression of DNA major groove surface causes GRDBD to move away from the DNA major groove with the initial average distance of ∼4 Å to the final average distance of ∼10 Å during 40 ns simulation course. Therefore, this study straightforward explores how small molecule targeting specific sites in the DNA minor groove disrupts the transcription factor-DNA interface in DNA major groove, and consequently modulates gene expression.

A large body of research has explored the links between women's decision making and their uptake of maternal health services, but the evidence so far is inconclusive. This study uses the Pakistan Social and Living Standards Measurement Survey to examine the influence of household decision making on women's uptake of maternal health services. We find that women's decision-making power has a significant positive correlation with maternal health services uptake and that influential males' decision-making power has the opposite effect, after controlling for socio-economic indicators and supply-side conditions. Our findings suggest that empowering women and increasing their ability to make decisions may increase their uptake of maternal health services. They also suggest that policies directed toward improving women's utilization of maternal health services in Pakistan must target men as well as women.

Backward extrusion was used to improve the properties of Mg-based biomaterials. The microstructures, mechanical performance and corrosion properties of as-cast and backward extruded Mg-xZn (x=0.5, 1, 1.5, 2, wt.%) alloys were investigated. The secondary dendrite arm spacing of as-cast Mg-xZn alloys and the grain size of backward extruded Mg-xZn alloys were decreased with the increment of Zn content. Meanwhile, both strength and elongation were improved by backward extruded treatment. With increasing Zn addition, the corrosion properties of both as-cast and backward extruded Mg-xZn alloys were decreased. However, the corrosion performance of backward extruded sample was improved obviously compared to the corresponding as-cast one. More importantly, the degradation rate of the backward extruded alloy was stable, which was mainly associated with the fine second precipitates and the homogeneous microstructure. It was demonstrated that backward extrusion was an effective approach to manufacture high performance Mg-based biomaterials.

Barrett's esophagus (BE), an inflammatory disease, is a risk factor for Barrett's esophageal adenocarcinoma (BEA). Treatment of BE patients with proton pump inhibitors (PPIs) is expected to reduce the risk of BEA. We performed an immunohistochemical study to examine the formation of nitrative and oxidative DNA lesions, 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxygaunosine (8-oxodG), in normal esophageal, BE with pre- and post-treatment by PPIs and BEA tissues. We also observed the expression of an oxidant-generating enzyme (iNOS) and its transcription factor NF-κB, an antioxidant enzyme (Mn-SOD), its transcription factor (Nrf2) and an Nrf2 inhibitor (Keap1). The immunoreactivity of DNA lesions was significantly higher in the order of BEA>BE>normal tissues. iNOS expression was significantly higher in the order of BEA>BE>normal tissues, while Mn-SOD expression was significantly lower in the order of BEA<BE<normal tissues. Interestingly, Mn-SOD expression and the nuclear localization of Nrf2 were significantly increased, and the formation of DNA lesions was significantly decreased in BE tissues after PPIs treatment for 3-6months. Keap1 and iNOS expression was not significantly changed by the PPIs treatment in BE tissues. These results indicate that 8-nitroguanine and 8-oxodG play a role in BE-derived BEA. Additionally, PPIs treatment may trigger the activation and nuclear translocation of Nrf2 resulting in the expression of antioxidant genes, leading to DNA damage suppression. These DNA lesions can be useful biomarkers to predict both the risk of BEA and the efficacy of PPIs treatment to prevent BEA in BE patients.

This is a retrospective, observational study to determine how often repeated consecutive miscarriages occur consistently in the same gestational period, including 1589 miscarriages among 543 women with recurrent miscarriage. In women who had two miscarriages only, 49.17% of both miscarriages occurred in the same gestational period, which was significantly higher than the expected probability of 34.54%(P<0.01). The proportions of all miscarriages occurring in the same gestational period in women with three, four and five or more miscarriages were 28.72%, 19.44% and 18.60%, compared with the expected probabilities of 14.36%(P<0.01), 6.57%(P<0.05) and <3.15%(P<0.05). The proportions of miscarriages occurring consistently in the same gestational period are higher than the theoretical probabilities calculated for the whole population. To determine how often repeated consecutive miscarriages occur consistently in the same gestational period, we did a retrospective, observational study including 1589 miscarriages among 543 women with recurrent miscarriage. It was found that in women who had two miscarriages only, 49.17% of both miscarriages occurred in the same gestational period, which was significantly higher than the expected probability of 34.54%. The proportions of all miscarriages occurring in the same gestational period in women with three, four or five or more miscarriages were 28.72%, 19.44% and 18.60%, compared with the expected probabilities of 14.36%, 6.57% and <3.15%. So we draw the conclusion that the proportions of the miscarriages occurring consistently in the same gestational period are higher than the theoretical probabilities calculated for the whole population.