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Cumulative fluoride exposure has adverse influences on children's intelligence quotient (IQ). In addition, catechol-O-methyltransferase (COMT) gene Val158Met polymorphism (rs4680) is associated with cognitive performance. This study aimed to evaluate the associations of COMT polymorphism and alterations of protein profiles with children's intelligence in endemic fluorosis area. We recruited 180 schoolchildren (10-12 years old) from high fluoride exposure (1.40 mg/l) and control areas (0.63 mg/l) in Tianjin City, China. The children's IQ, fluoride contents in drinking water (W-F), serum (S-F), and urine (U-F); serum thyroid hormone levels, COMT Val158Met polymorphism, and plasma proteomic profiling were determined. Significant high levels of W-F, S-F, U-F, along with poor IQ scores were observed in the high fluoride exposure group compared with those in control (all P < 0.05). S-F and U-F were inversely related with IQ (r(s) = -0.47, P < 0.01; r(s) = -0.45, P = 0.002). Importantly, higher fluoride exposure was associated with steeper cognitive decline among children with the reference allele Val compared with those homozygous or heterozygous for the variant allele Met (95% CI, -16.80 to 2.55; P interaction < 0.01). Additionally, 5 up-regulated protein spots related to cell immunity and metabolism were detected in children with high fluoride exposure compared with the control. In conclusion, fluoride exposure was adversely associated with children's intelligence, whereas the COMT polymorphism may increase the susceptibility to the deficits in IQ due to fluoride exposure. Moreover, the proteomic analysis can provide certain basis for identifying the early biological markers of fluorosis among children.

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Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants and are ubiquitous in the environment and human tissues. Recent evidence has demonstrated that PBDE-induced neurotoxicity is associated with neuronal apoptosis via interfering with the calcium ion (Ca) homeostasis; however, the underlying mechanisms remain elusive. Thus, we sought to investigate the role of Ca homeostasis in PBDE-47-induced neuronal apoptosis. Here, we showed that PBDE-47 significantly decreased neuronal number while increased neuronal apoptosis in vitro and in vivo, as manifested by an increased percentage of Annexin V-positive staining cells and caspase-3 activation in human neuroblastoma SH-SY5Y cells and hippocampal neurons of rats. Further study identified that PBDE-47 elicited ΔΨ collapse following an early and sustained [Ca] overload, as well as stimulated cytochrome c release from mitochondria into the cytosol in SH-SY5Y cells and rat hippocampal tissue. Interestingly, the extracellular Ca chelator ethylene glycol-bis (2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA) blocked PBDE-47-induced [Ca] elevation, ΔΨ collapse, cytochrome c release, and caspase-3 activation in SH-SY5Y cells, whereas the intracellular Ca chelator 1,2-bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM) had no influences on them, indicating that the [Ca] overload originates primarily from extracellular Ca component rather than from intracellular calcium storage and that the increase in [Ca] is a major contributor to ΔΨ collapse and subsequent neuronal apoptosis. Overall, these findings suggest that PBDE-47 affects Ca homeostasis as a crucial event in activation of neuronal death associated with mitochondria and provide novel insight into the mechanism of action underlying PBDE neurotoxicity.

Background As a low pathogenic influenza virus, avian influenza virus subtype H9N2 (H9N2 AIV) often induces high morbidity in association with secondary bacterial infections in chickens or mammals. To explore this phenomenon, the relationship between intestinal microflora changes and bacterial translocations was studied post H9N2 AIV challenge and post AIV infection plus Ageratum-liquid treatment. Methods Illumina sequencing, histological examination and Neongreen-tagged bacteria were used in this study to research the microbiota composition, intestinal barrier, and bacterial translocation in six weeks of BALB/c mice. Results H9N2 AIV infection caused intestinal dysbacteriosis and mucosal barrier damages. Notably, the villus length was significantly reduced ( p < 0.01) at 12 dpi and the crypt depth was significantly increased ( p < 0.01) at 5 dpi and 12 dpi with infection, resulting in the mucosal regular villus-length/crypt-depth (V/C) was significantly reduced ( p < 0.01) at 5 dpi and 12 dpi. Moreover, degeneration and dissolution of the mucosal epithelial cells, loose of the connective tissue and partial glandular atrophy were found in infection group, indicating that intestinal barrier function was weakened. Eventually, intestinal microbiota ( Staphylococcus , E. coli , etc.) overrun the intestinal barrier and migrated to liver and lung tissues of the mice at 5 and 12 dpi. Furthermore, the bacteria transferred in mesentery tissue sites from intestine at 36 h through tracking the Neongreen-tagged bacteria. Then the Neongreen-tagged bacteria were isolated from liver at 48 h post intragastrical administration. Simultaneously, Ageratum-liquid could inhibit the intestinal microbiota disorder post H9N2 AIV challenge via the respiratory tract. In addition, this study also illustrated that Ageratum-liquid could effectively prevent intestinal bacterial translocation post H9N2 AIV infection in mice. Conclusion In this study, we report the discovery that H9N2 AIV infection could damage the ileal mucosal barrier and induce the disturbance of the intestinal flora in BALB/c mice resulting in translocation of intestinal bacteria. In addition, this study indicated that Ageratum-liquid can effectively prevent bacterial translocation following H9N2 infection. These findings are of important theoretical and practical significance in prevention and control of H9N2 AIV infection. Electronic supplementary material The online version of this article (10.1186/s12985-019-1131-y) contains supplementary material, which is available to authorized users.

In order to study the restoring-force characteristics of precast concrete ring-lap beam-column joints, three precast concrete ring-lap beam-column joint specimens and one cast-in-place concrete beam-column joint specimen were designed and fabricated, and low-circumferential repeated loading tests were conducted. The results show that the bearing capacity of the ring-lap beam-column joint is higher than that of the cast-in-place beam-column joint, and with the increase in the lap length, the bearing capacity, ductility, and energy dissipation capacity of the ring-lap beam-column joint increase significantly, and the local damage is also mitigated. Based on the test results and the existing restoring-force model theory, a trifold restoring-force model is proposed for precast concrete ring-lap beam-column joints considering the effect of lap length. The proposed restoring-force model is consistent with the hysteresis curve of the assembled column, which indicates that the proposed restoring-force model can better reflect the influence of the lap length on the hysteresis characteristics, and can provide a reference for the structural elastic–plastic analysis and engineering application of the precast concrete ring-lap beam-column joint. The proposed restoring-force model can better reflect the influence of lap length on the hysteretic properties, which can provide a reference for the structural elastoplastic analysis and engineering application of this precast concrete ring-lap beam-column joint.

In this article, we mainly analyze and develop three different SOR-type iterative methods with parameter based on the preconditioned for the linear system. We present some comparison theorems on preconditioned iterative methods, and the results show that the rate of convergence of these new splitting preconditioned Successive Overrelaxation (SOR) iterative methods with parameter is faster than that of the general preconditioned iterative methods and the classical SOR iterative methods. Finally, numerical results completely agree with theoretical results.