Altered glucose metabolism has been implicated in the pathogenesis of Alzheimer’s disease (AD). Aerobic glycolysis from astrocytes is a critical metabolic pathway for brain energy metabolism. Disturbances of circadian rhythm have been associated with AD. While the role of circadian locomotor output cycles kaput (CLOCK) and brain muscle ARNT-like1 (BMAL1), the major components in the regulation of circadian rhythm, has been identified in the brain, the mechanism by which CLOCK and BMAL1 regulates the dysfunction of astrocytes in AD remains unclear. Here, we show that the protein levels of CLOCK and BMAL1 are significantly elevated in impaired astrocytes of cerebral cortex from patients with AD. We demonstrate that the over-expression of CLOCK and BMAL1 significantly suppresses aerobic glycolysis and lactate production by the reduction in hexokinase 1 (HK1) and lactate dehydrogenase A (LDHA) protein levels in human astrocytes. Moreover, the elevation of CLOCK and BMAL1 induces functional impairment by the suppression of glial fibrillary acidic protein (GFAP)-positive filaments in human astrocytes. Furthermore, the elevation of CLOCK and BMAL1 promotes cytotoxicity by the activation of caspase-3-dependent apoptosis in human astrocytes. These results suggest that the elevation of CLOCK and BMAL1 contributes to the impairment of astrocytes by inhibition of aerobic glycolysis in AD.

Since the onset of the COVID-19 pandemic, there has been a growing demand for effective and safe disinfectants. A novel use of chlorine dioxide (ClO₂) gas, which can satisfy such demand, has been reported. However, its efficacy and safety remain unclear. For the safe use of this gas, the stable release of specific concentrations is a must. A new type of ClO₂ generator called Dr.CLO^TM has recently been introduced. This study aimed to investigate: (1) the effects of Dr.CLO^TM on inhibiting adenoviral amplification on human bronchial epithelial (HBE) cells; and (2) the acute inhalation safety of using Dr.CLO^TM in animal models. After infecting HBE cells with a recombinant adenovirus, the inhibitory power of Dr.CLO^TM on the virus was expressed as IFU/mL in comparison with the control group. The safety of ClO₂ gas was indirectly predicted using mice by measuring single-dose inhalation toxicity in specially designed chambers. Dr.CLO^TM was found to evaporate in a very constant concentration range at 0–0.011 ppm/m³ for 42 days. In addition, 36–100% of adenoviral amplification was suppressed by Dr.CLO^TM, depending on the conditions. The LC₅₀ of ClO₂ gas to mice was approximately 68 ppm for males and 141 ppm for females. Histopathological evaluation showed that the lungs of female mice were more resistant to the toxicity from higher ClO₂ gas concentrations than those of male mice. Taken together, these results indicate that Dr.CLO^TM can be used to provide a safe indoor environment due to its technology that maintains the stable concentration and release of ClO₂ gas, which could suppress viral amplification and may prevent viral infections.