Although erythropoietin treatment has demonstrated remarkable neuroprotection in infants, the window of opportunity and optimal dosage is still controversial. Therapeutic hypothermia within 6 h of hypoxia–ischemia (HI) onset has been clinically shown to be a promising therapeutic intervention, but it only reduces the risk of death and disability by about 11%, meaning that up to 40% of the treated infants still develop neurological deficits. HIE is a global problem with an estimated incidence ranging from 1 to live births in developed countries to live births in underdeveloped countries. It is a major cause of mortality in neonates and can result in profound and devastating lifelong mental and physical disabilities, including cerebral palsy, seizures, and cognitive impairments in both term and preterm neonates. Hypoxic–ischemic encephalopathy (HIE) is a severe central nervous system injury caused by oxygen deprivation and limited blood flow in the neonatal brain. Altogether, these findings corroborate earlier studies and further demonstrate that AIF is involved in oxidative stress, which contributes to the sex-specific differences observed in neonatal HI brain injury. We also found that AIF stimulated carbohydrate metabolism in young males. Under physiological conditions (without HI), the doublecortin-positive area in the dentate gyrus of females was 1.15 times larger than in males, indicating that AIF upregulation effectively promoted neurogenesis in females in the long term. As compared to females, male mice exhibited more severe brain injury, correlating with reduced antioxidant capacities, more pronounced protein carbonylation and nitration, and increased neuronal cell death. We found that the male sex significantly aggravated AIF-driven brain damage, as indicated by the injury volume in the gray matter (2.25 times greater in males) and by the lost volume of subcortical white matter (1.71 greater in males) after HI. Based on previous findings that AIF overexpression aggravates neonatal HI brain injury, we further investigated potential sex differences in the severity and molecular mechanisms underlying the injury using mice that overexpress AIF from homozygous transgenes. The changes in the quality of the phenols, phenolic components, and antioxidant activity were elucidated during the development of the main plum cultivars in Sichuan, particularly the changes that provided a theoretical basis for the development of bioactive substances in local plum cultivars.There are sex differences in the severity, mechanisms, and outcomes of neonatal hypoxia–ischemia (HI) brain injury, and apoptosis-inducing factor (AIF) may play a critical role in this discrepancy. HCT1 may be an important regulator involved in the accumulation of chlorogenic acid in plums. CHS, PA元, and HCT1 may be the regulatory genes related to the accumulation of phenolic substances in the pericarp and pulp of ‘Qiangcuili’ and ‘Cuihongli’. In the two cultivars, the total phenols, phenolic components, and antioxidant capacity were higher in the peel than in the pulp. The antioxidant capacity was positively correlated with the TPC, TFC, and TFAC. The changes in the DPPH and FRAP scavenging activities decreased with fruit ripening. The main phenolic components were neochlorogenic acid, chlorogenic acid, ferulic acid, benzoic acid, rutin, and proanthocyanidin B1. The phenolic contents (total phenol content (TPC), total flavonoid content (TFC), and total flavanol content (TFAC)) trended gradually downward as the fruits of the two cultivars matured, while the total anthocyanin content gradually increased in ‘Cuihongli’. The results showed that, during development of the two plums, the total soluble solid and soluble sugar contents were highest at the mature stage. In this study, the main Sichuan cultivars ‘Qiangcuili’ and ‘Cuihongli’ were used to study the changes in the appearance, internal quality, phenolic compounds, and antioxidant activities during fruit development and the expression of phenolic-compound-related structural genes. Abstract : Plums are widely consumed, contain high levels of phenolic compounds, and have strong antioxidant activity.
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