Objective To explore the relationship between urinary activin A and neonatal hypoxic-ischemic encephalopathy(HIE).Methods 50 full-term neonatal with HIE were selected as the observation group,48 normal full-term neonatal in the same period were selected as the normal control group randomly.Within 7 days after birth,the observation group was divided into the group of 30 patients with mild HIE and the group of 20 patients with moderate and severe HIE,according to diagnostic criteria and clinical grading of neonatal HIE.The levels of urinary activin A in two groups after birth at different time(2,12,24,48,72h)was determined by using ELISA method.Results The levels of urinary activin A in moderate and severe HIE group was significantly higher than than in the normal control group(P＜0.01)and mild HIE group(P＜0.01);The levels of urinary activin A in the normal control group and mild HIE group showed no significant differences(P＞0.05).Urinary activin A level＞70 ng/L for the critical value to determine the occurrence of moderate and severe HIE,the sensitivity and specificity of 2 h urinary activin A levels were separately 86％ and 99％;The sensitivity and specificity of 12～72 h urinary activin A levels were separately 100％ and 98％.Conclusion The correlation between the level of urinary activin A and the severity of HIE was positive,the level of urinary activin A had a high degree of sensitivity and specificity for determine the incidence of moderate and severe HIE,it provided an important basis for diagnosis of moderate and severe HIE.

Mitophagy is an essential intracellular process that eliminates dysfunctional mitochondria and maintains cellular homeostasis. Mitophagy is regulated by the post-translational modification of mitophagy receptors. Fun14 domain-containing protein 1 (FUNDC1) was reported to be a new receptor for hypoxia-induced mitophagy in mammalian cells and interact with microtubule-associated protein light chain 3 beta (LC3B) through its LC3 interaction region (LIR). Moreover, the phosphorylation modification of FUNDC1 affects its binding affinity for LC3B and regulates selective mitophagy. However, the structural basis of this regulation mechanism remains unclear. Here, we present the crystal structure of LC3B in complex with a FUNDC1 LIR peptide phosphorylated at Ser17 (pS), demonstrating the key residues of LC3B for the specific recognition of the phosphorylated or dephosphorylated FUNDC1. Intriguingly, the side chain of LC3B Lys49 shifts remarkably and forms a hydrogen bond and electrostatic interaction with the phosphate group of FUNDC1 pS. Alternatively, phosphorylated Tyr18 (pY) and Ser13 (pS) in FUNDC1 significantly obstruct their interaction with the hydrophobic pocket and Arg10 of LC3B, respectively. Structural observations are further validated by mutation and isothermal titration calorimetry (ITC) assays. Therefore, our structural and biochemical results reveal a working model for the specific recognition of FUNDC1 by LC3B and imply that the reversible phosphorylation modification of mitophagy receptors may be a switch for selective mitophagy.
Crystallography, X-Ray ; Membrane Proteins ; chemistry ; metabolism ; Microtubule-Associated Proteins ; chemistry ; metabolism ; Mitochondrial Degradation ; Mitochondrial Proteins ; chemistry ; metabolism ; Peptides ; chemistry ; metabolism ; Phosphorylation ; Protein Structure, Quaternary