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Our previous study together with other investigations have reported that neonatal hypoxia or ischemia induces long-term cognitive impairment, at least in part through brain inflammation and hypomyelination. However, the detailed mechanisms are not fully understood. Here, we used a rodent model of neonatal hypoxia by subjecting postnatal day 0 (P0) rat pups to systemic hypoxia (3.5 h). We found that neonatal hypoxia increased the glutamate content and initiated inflammatory responses at 4 h and 1 day after hypoxia, caused hypomyelination in the corpus callosum, and impaired hippocampus-dependent learning and memory when assessed 30-60 days after hypoxia. Interestingly, much of the hypoxia-induced brain damage was ameliorated by treatment with the ATP analogue 2',3'-0-(2,4,6-trinitrophenyl)-adenosine 5'-triphosphate (TNP-ATP; blocks all ionotropic P2X1-7 receptors), whereas treatment with pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; inhibits P2X1-3 and P2X5-7 receptors) was less neuroprotective. Our data indicated that activation of ionotropic ATP receptors might be partially, if not fully, involved in glutamate deregulation, neuroinflammation, hypomyelination, and cognitive dysfunction after neonatal hypoxia.

To address the effect of metro train blockage on the critical ventilation velocity in a long tunnel, a series of scenarios were conducted numerically through this study, including different fire sizes (5-10 MW), metro train lengths (80-120 m), and blockage ratios (φ, 0.50, and 0.57). It is known from the numerical results that the metro train length shows a limited effect on the critical ventilation velocity, which is because the longitudinal ventilation has become stable before reaching the fire source to prevent smoke back-layering, and increasing the metro train length only increases the distance of stabilizing the longitudinal ventilation. The blockage ratio shows an obvious influence on the critical ventilation velocity, which is because the presence of the metro train can obviously reduce the flow cross-sectional area of the tunnel. An empirical model is developed as well, while it is known that the critical ventilation velocity increases with the one-third power of dimensionless heat release rate and (1-φ). The research outcomes of this study provide a technical guide for the design of the metro tunnel and the relevant emergency management of fire rescue under fire conditions. K E Y W O R D S blockage ratio, critical velocity, FDS, metro train, subway tunnel 1 | INTRODUCTION An increasing number of metro systems have been designed and constructed recently to release the urgent issues of accelerated urbanization and growing population in metropolises. The companied fire risk is always an important and hot research topic from both the academia and industries. Consequence and impact of the relevant fire accidents are very high, which can be proved by the large number of fire casualties and very bad influence in the past few decades, such as the Daegu metro fire in South Korea, the Viamala tunnel fire in Switzerland, and the Burnley tunnel fire in Austria. [1][2][3][4] To benefit with the fire safety of those metro systems, smoke movement is an inevitable aspect during the design as it is the most fatal factor of a tunnel fire. 5-7 Therefore, how to control the smoke movement effectively to provide a safe zone for the occupants and firefighters during the evacuation and rescuing processes, respectively, becomes an important question that needs to be answered urgently.It is indicated that the metro train fails to reach the next station and stops between the two stations in about 50% of fires. 8,9 When a fire occurs in the metro tunnel, the relevant ventilation facilities in the adjacent stations will be started, where longitudinal ventilation is triggered, which not only can prevent the smoke from spreading to the upstream and also offer a safe zone without smoke for both occupants and firefighters. If the designed longitudinal ventilation velocity is smaller than the critical value, the smoke released from the fire can break through the barrier raised by the longitudinal ventilation and then threaten the people upstream.Many studies have been undertaken in identifying the appropriate longitudinal ventilation v...

While extensive studies report that neonatal hypoxia-ischemia (HI) induces long-term cognitive impairment via inflammatory responses in the brain, little is known about the role of early peripheral inflammation response in HI injury. Here we used a neonatal hypoxia rodent model by subjecting postnatal day 0 (P0d) rat pups to systemic hypoxia (3.5 h), a condition that is commonly seen in clinic neonates, Then, an initial dose of minocycline (45 mg/kg) was injected intraperitoneally (i.p.) 2 h after the hypoxia exposure ended, followed by half dosage (22.5 mg/kg) minocycline treatment for next 6 consecutive days daily. Saline was injected as vehicle control. To examine how early peripheral inflammation responded to hypoxia and whether this peripheral inflammation response was associated to cognitive deficits. We found that neonatal hypoxia significantly increased leukocytes not only in blood, but also increased the monocytes in central nervous system (CNS), indicated by presence of C-C chemokine receptor type 2 (CCR2+)/CD11b+CD45+ positive cells and CCR2 protein expression level. The early onset of peripheral inflammation response was followed by a late onset of brain inflammation that was demonstrated by level of cytokine IL-1β and ionized calcium binding adapter molecule 1(Iba-1; activated microglial cell marker). Interrupted blood-brain barrier (BBB), hypomyelination and learning and memory deficits were seen after hypoxia. Interestingly, the cognitive function was highly correlated with hypoxia-induced leukocyte response. Notably, administration of minocycline even after the onset of hypoxia significantly suppressed leukocyte-mediated inflammation as well as brain inflammation, demonstrating neuroprotection in systemic hypoxia-induced brain damage. Our data provided new insights that systemic hypoxia induces cognitive dysfunction, which involves the leukocyte-mediated peripheral inflammation response.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is the major risk factor leading to hepatocellular carcinoma (HCC). haploinsufficiency in mice causes NAFLD by disrupting Ca homeostasis, indicating that CISD2 is a molecular target for the treatment of NAFLD and the prevention of HCC.