Microglia mediate the early-life programming of adult glucose control.

Mammalian glucose homeostasis is, in part, nutritionally programmed during early neonatal life, a critical window for the formation of synapses between hypothalamic glucoregulatory centers. Although microglia are known to prune synapses throughout the brain, their specific role in refining hypothalamic glucoregulatory circuits remains unknown. Here, we show that microglia in the mediobasal hypothalamus (MBH) of mice actively engage in synaptic pruning during early life. Microglial phagocytic activity is induced following birth, regresses upon weaning from maternal milk, and is exacerbated by feeding dams a high-fat diet while lactating. In particular, we show that microglia refine perineuronal nets (PNNs) within the neonatal MBH. Indeed, transiently depleting microglia before weaning (P6-16), but not afterward (P21-31), remarkably increased PNN abundance in the MBH. Furthermore, mice lacking microglia only from P6-16 had glucose intolerance due to impaired glucose-responsive pancreatic insulin secretion in adulthood, a phenotype not seen if microglial depletion occurred after weaning. Viral retrograde tracing revealed that this impairment is linked to a reduction in the number of neurons in specific hypothalamic glucoregulatory centers that synaptically connect to the pancreatic ß-cell compartment. These findings show that microglia facilitate synaptic plasticity in the MBH during early life through a process that includes PNN refinement, to establish hypothalamic circuits that regulate adult glucose homeostasis.

[The association between aflatoxin exposure and primary hepatocellular carcinoma risks: a case-control study in Chongqing].

Objective: To investigate the association between aflatoxin exposure and primary hepatocellular carcinoma (PHC) development. Methods: From December 2013 to May 2016, we selected 214 patients newly diagnosed with PHC as cases, and 214 patients as controls from three hospitals in Chongqing. Cases were confirmed with PHC diagnosis standard. And cases caused by clear reasons such as drug-induced liver injury, alcoholic liver damage, fatty liver and gallstones etiology, were excluded. Controls were included with no cancer and no digestive system disease, and recruited simultaneously with cases. Cases and controls were frequency-matched (1∶1) by same gender and age (±3 years). Peripheral blood and random urine samples were collected and analyzed for serum HBsAg status by biochemistry analyzer, and serum AFB(1)-ALB adduct and urinary AFB(1)-N(7)-GUA adduct by ELISA. Basic information, living habits and history of disease for patients were obtained by questionnaires. We used wilcoxon rank sum test to compare the median of serum AFB(1)-ALB adduct and urinary AFB(1)-N(7)-GUA adduct in cases and controls. Logistic regression analyses were performed to assess risk factors for PHC, and synergism index (S) of aflatoxin with other factors was estimated by the method of Andersson. Results: There was no significant difference in age between PHC cases (50.74±9.67) years and controls (51.15±9.90) years. Logistic regression showed that the odds ratio of HBV infection for PHC development was 46.3 (95% CI: 23.3-88.0). There was a significant difference in median concentrations of serum AFB(1)-ALB adduct (cases vs controls: 146.23 vs 74.42 ng/g albumin, P<0.001), but no difference in median concentrations of urinary AFB(1)-N(7)-GUA adduct was observed (cases vs controls: 0.17 vs 0.14 ng/mg creatinine, P<0.210). The odd ratios for PHC risk after adjustment were 1.9 (95%CI: 1.1-3.4) for AFB(1)-ALB adduct, and 2.1 (95%CI: 1.0-4.2) for AFB(1)-N(7)-GUA adduct. Moreover, we observed a positive interaction of aflatoxin exposure with HBV, alcohol drinking, and diabetes. The S was 4.7 (95%CI: 2.8-7.9), 3.5 (95%CI: 1.0-12.0), and 12.4 (95%CI: 1.8-84.2), respectively for serum AFB(1)-ALB adduct with each of the three factors mentioned, and was 1.9 (95%CI:1.1-3.1), 2.0 (95%CI: 1.1-3.6), and 2.0 (95%CI: 1.1-3.6), respectively for urinary AFB(1)-N(7)-GUA adduct with each of the three factors mentioned. Conclusion: HBV was still the main risk factor, and AFB(1) exposure was also an independent risk factor for PHC in Chongqing. There was a positive interaction of aflatoxin with HBV, alcohol drinking, and diabetes.

Delivery of AIB1 siRNA by Ca2+/PEI/heparin composite nanoparticles effectively inhibits the growth of human breast cancer.

Here, a novel carrier fabricated by the interaction of negatively charged heparin and positively charged PEI and Ca2+ was investigated to deliver AIB1 siRNA into breast cancer cells both in vitro and in vivo. Ca2+/PEI/heparin nanoparticles were prepared by simply mixing heparin, PEI and CaCl2 aqueous solution. Heparin in the Ca2+/PEI/heparin nanoparticles (40.9% heparin, w/w) decreased the cytotoxicity of PEI. According to the MTT assay, Ca2+/PEI/heparin NPs are superior to commercial Lipofectamine 2000 considering the safety. The Ca2+/PEI/heparin NPs are able to deliver siAIB1 into breast cancer cells as effectively as Lipofectamine 2000 both in vitro and in vivo. The in vivo experiment also indicated that the NF-κB/BCL-2 signal pathway might be the downstream signal pathway of AIB1 in regulating breast cancer proliferation and progression.

Tris(2-cyanoethyl)amine.

In the title compound, N(CH(2)CH(2)CN)(3), (I), the three cyanoethyl groups adopt a conformation with the CN groups oriented in the same direction, suggesting the compound may behave as a potential tripodal ligand.

Hexakis(antipyrine-O)terbium(III) triperchlorate.

In the title compound, hexakis(1,2-dihydro-1,5-dimethyl-2-phenyl-3H-pyrazol-3-one-O)terbium(III) triperchlorate, [Tb(C(11)H(12)N(2)O)(6)](ClO(4))(3), the Tb atom lies on a site of $\overline 3$ crystallographic symmetry and the unique Tb-O distance is 2.278 (2) A. One of the perchlorate anions has threefold crystallographic symmetry, while the other is disordered about a $\overline 3$ site.