Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.

Risk prediction of neonatal hyperbilirubinemia / 中国新生儿科杂志

Objective:To study the predictive value of hour-specific total serum bilirubin(TSB) nomogram combined with clinical risk factors in the risk of hyperbilirubinemia.Method:Perinatal clinical data of newborns born in Shanghai Pudong New Area Health Care Hospital for Women and Children, Shanghai Pudong New Area People's Hospital and Shanghai Pudong Hospital from August 2017 to July 2018 were collected in this prospective study. Transcutaneous bilirubin (TcB) was monitored before discharge from hospital. Enrolled neonates were followed up for 28 days. The patients were assigned to neonatal hyperbilirubinemia group (NHB) and non-hyperbilirubinemia group (Non-HB) according to the occurrence of hyperbilirubinemia. The predictive value of models for the risk of hyperbilirubinemia was evaluated by receiver operating characteristic (ROC) curves and Logistic regression analysis.Result:A total of 8 664 newborns were included in this study, with 1 196 cases of hyperbilirubinemia, with an incidence of 13.8%. Logistic regression analysis showed that maternal blood type O, premature rupture of membranes, male gender, gestational age 35~37 weeks, subcutaneous ecchymosis/cranial edema, and breastfeeding were independent risk factors for NHB ( P<0.05). The area under receiver operative characteristic curve (ROC) of predischarge bilirubin risk zone only was 0.874(95% CI 0.861~0.885, P<0.05)and for all independent risk factors was 0.664 (95% CI 0.647~0.680, P<0.05). The area under ROC curve was 0.891 (95% CI 0.880~0.902, P<0.05) by combining predischarge bilirubin risk zone with clinical risk factors. Conclusion:Predischarge bilirubin risk zone combined with clinical risk factors can reasonably predict neonatal hyperbilirubinemia well.