Application of the Artificial Intelligence Algorithm Model for Screening of Inborn Errors of Metabolism.

Inborn errors of metabolism (IEMs) are strongly related to abnormal growth and development in newborns and can even result in death. In total, 94,648 newborns were enrolled for expanded newborn screening using tandem mass spectrometry (MS/MS) from 2016 to 2020 at the Neonatal Disease Screening Center of the Maternal and Child Health Hospital in Shaoyang City, China. A total of 23 confirmed cases were detected in our study with an incidence rate of 1:4,115. A total of 10 types of IEM were identified, and the most common IEMs were phenylalanine hydroxylase deficiency (PAHD; 1:15,775) and primary carnitine deficiency (PCD; 1:18,930). Mutations in phenylalanine hydroxylase (PAH) and SLC22A5 were the leading causes of IEMs. To evaluate the application effect of artificial intelligence (AI) in newborn screening, we used AI to retrospectively analyze the screening results and found that the false-positive rate could be decreased by more than 24.9% after using AI. Meanwhile, a missed case with neonatal intrahepatic cholestasis citrin deficiency (NICCD) was found, the infant had a normal citrulline level (31 µmol/L; cutoff value of 6-32 µmol/L), indicating that citrulline may not be the best biomarker of intrahepatic cholestasis citrin deficiency. Our results indicated that the use of AI in newborn screening could improve efficiency significantly. Hence, we propose a novel strategy that combines expanded neonatal IEM screening with AI to reduce the occurrence of false positives and false negatives.

Chinese newborn screening for the incidence of G6PD deficiency and variant of G6PD gene from 2013 to 2017.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common X-linked enzymopathies caused by G6PD gene variant. We aimed to provide the characteristics of G6PD deficiency and G6PD gene variant distribution in a large Chinese newborn screening population. We investigated the prevalence of G6PD in China from 2013 to 2017. Then, we examined G6PD activity and G6PD gene in representative Chinese birth cohort to explore the distribution of G6PD gene variant in 2016. We then performed multicolor melting curve analysis to classify G6PD gene variants in 10,357 neonates with activity-confirmed G6PD deficiency, and DNA Sanger sequencing for G6PD coding exons if hot site variants were not found. The screened population, organizations, and provinces of G6PD deficiency were increased from 2013 to 2017 in China. The top five frequency of G6PD gene variants were c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, and c.871G>A and varied in different provinces, with regional and ethnic features, and four pathogenic variant sites (c.152C>T, c.290A>T, c.697G>C, and c.1285A>G) were first reported. G6PD deficiency mainly occurs in South China, and the frequency of G6PD gene variant varies in different regions and ethnicities.

Territrem and butyrolactone derivatives from a marine-derived fungus Aspergillus terreus.

Seventeen lactones including eight territrem derivatives (1-8) and nine butyrolactone derivatives (9-17) were isolated from a marine-derived fungus Aspergillus terreus SCSGAF0162 under solid-state fermentation of rice. Compounds 1-3 and 9-10 were new, and their structures were elucidated by spectroscopic analysis. The acetylcholinesterase inhibitory activity and antiviral activity of compounds 1-17 were evaluated. Among them, compounds 1 and 2 showed strong inhibitory activity against acetylcholinesterase with IC50 values of 4.2 ± 0.6, 4.5 ± 0.6 nM, respectively. This is the first time it has been reported that 3, 6, 10, 12 had evident antiviral activity towards HSV-1 with IC50 values of 16.4 ± 0.6, 6.34 ± 0.4, 21.8 ± 0.8 and 28.9 ± 0.8 µg·mL-1, respectively. Antifouling bioassay tests showed that compounds 1, 11, 12, 15 had potent antifouling activity with EC50 values of 12.9 ± 0.5, 22.1 ± 0.8, 7.4 ± 0.6, 16.1 ± 0.6 µg·mL-1 toward barnacle Balanus amphitrite larvae, respectively.