Based on the improved isospin-dependent Boltzmann-Langevin model which incorporates the dynamical fluctuations, we study the π production in central heavy ion collisions at different incident energies from 250 to 1200 A MeV. It is found that the π multiplicity is sensitive to the nuclear equation of state. At π subthreshold energy, the fluctuations have a larger effect on the π multiplicity. The π − /π + ratios as a probe of nuclear symmetry energy are calculated with different stiffness of symmetry energy. The results favor a supersoft symmetry energy of the potential term in comparison with the FOPI data, which supports the one obtained by the usual Boltzmann-Uehling-Uhlenbeck model.During the last few years, the study of nuclear symmetry energy E sym (ρ) has been a highly interesting subject. The constraining of E sym (ρ) is important for not only understanding of heavy-ion reactions [1] but also many issues in astrophysics [1,2].Unfortunately, the form of E sym (ρ) is very controversial, especially at supra-saturation density. At sub-saturation density, constraints on the E sym (ρ) were obtained by analyzing the isospin diffusion data [3]. At supra-saturation density, the main difference of the E sym (ρ) forms predicted by some microscopical or phenomenological many-body approaches is the trend of the E sym (ρ) with the density. One is the E sym (ρ) increases continuously with the increasing density, and the other is the E sym (ρ) increases

Previous studies have shown that metformin not only is a hypoglycemic agent but also has neuroprotective effects. However, the mechanism of action of metformin in ischemic stroke is unclear. Oxidative stress is an important factor in the pathogenesis of cerebral ischemia-reperfusion injury. It has been reported that metformin is associated with stroke risk in the clinical population. This study is aimed at investigating the effect and mechanism of metformin in an experimental model of oxidative stress induced by ischemia/reperfusion (I/R) in vivo and oxygen glucose deprivation/reperfusion (OGD/R) in vitro. Metformin (100, 200, and 300 mg/kg) was administered intraperitoneally immediately after induction of cerebral ischemia. The indicators of oxidative stress selected were antioxidant enzyme activities of catalase, malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and glutathione peroxidation enzyme (GSHPx). First, we demonstrated that metformin can significantly alleviate acute and chronic cerebral I/R injury and it has a strong regulatory effect on stroke-induced oxidative stress. It can reduce the elevated activities of MDA and NO and increase the levels of GSHPx and SOD in the cerebrum of mice and N2a cells exposed to I/R. Furthermore, real-time PCR and western blot were used to detect the expression of long noncoding RNA H19 (lncRNA-H19), microRNA-148a-3p (miR-148a-3p), and Rho-associated protein kinase 2 (Rock2). The direct interaction of lncRNA-H19, miR-148a-3p, and Rock2 was tested using a dual luciferase reporter assay. lncRNA-H19 altered OGD/R-induced oxidative stress by modulating miR-148a-3p to increase Rock2 expression. The expression of lncRNA-H19 and Rock2 could be downregulated with metformin in vivo and in vitro. In conclusion, our study confirmed that metformin exerts neuroprotective effects by regulating ischemic stroke-induced oxidative stress injury via the lncRNA-H19/miR-148a-3p/Rock2 axis. These results provide new evidence that metformin may represent a potential treatment for stroke-related brain injury.

No abstract