Synthesis, antibacterial activity evaluation and molecular docking studies of coumarin modified thiouracil derivatives as SecA inhibitor

A series of thiouracil derivatives containing coumarin were designed and synthesized with SecA inhibitor 1 as the lead. The in vitro antibacterial activities of the newly synthesized compounds were evaluated, and the results revealed that some of the new compounds (such as 14k and 14q) had strong inhibitory effect against the tested bacteria. The inhibitory activities of 14k, 14 l, 14r, 14p and 14q against SecA were tested, and the IC50 of 14K was 17.6 μg/mL which was significantly lower than that of lead compound 1. The molecular docking of the compounds 14k, 14 l, 14r, 14p and 14q with SecA were investigated and these compounds can successfully bind to SecA in the two selected pocket. Compound 14k had strong SecA inhibitory activity and antibacterial activity, which was worthy of further study.</p

DataSheet_1_Genetic polymorphism in HTR2A rs6313 is associated with internet addiction disorder.docx

IntroductionInternet addiction disorder (IAD) has grown into public health concern of global proportions. Previous studies have indicated that individuals with IAD may exhibit altered levels of serotonin and dopamine, which are known to play crucial roles in depression, anxiety, impulsivity, and addiction. Therefore, polymorphisms in the receptors that mediate the effects of serotonin and dopamine and affect their functional states as well as their activities are suspect. In this study, we aimed to investigate the association between IAD and rs6313 (T102C) polymorphism in the serotonin 2A receptor (5-HT2A) gene, (HTR2A).MethodsTwenty patients with IAD and twenty healthy controls (HCs) were included in this study. Young’s Internet Addiction Test (IAT), Self-Rating Anxiety Scale, Self-Rating Depression Scale, Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Barratt Impulse Scale, Pittsburgh Sleep Quality Index (PSQI), and Social Support Rating Scale (SSRS) were used to assess the severity of internet addiction, mental status, impulsive traits, sleep quality, and social support. Genotyping was performed to identify rs6313 polymorphisms in the HTR2A gene of all participants.ResultsThe frequencies of the C and T alleles of HTR2A T102C were 28% and 72% in the IAD group and 53% and 47% in the HCs group, respectively, indicating that the differences between these two groups were significant. No significant difference was observed in the distribution of the CC, CT, and TT genotypes of HTR2A gene T102C between the IAD and the HCs groups. Additionally, there was no difference in the distribution of the frequencies of the HTR2A gene T102C CC and CT+TT genotypes between the two groups. However, the distribution between the TT and CC+CT genotypes showed an apparent statistical difference in the HTR2A gene T102C between the two groups. Correlation analysis indicated that the IAT score was positively correlated with the Y-BOCS and BIS scores for the CC+CT genotype in patients with IAD. Moreover, the IAT score was positively correlated with the PSQI score in patients with IAD carrying the TT genotype.ConclusionThe present study demonstrates that rs6313 in HTR2A is associated with IAD, and that the T allele of rs6313 in HTR2A may be a risk factor for IAD.</p

Data_Sheet_1_Transcriptomic and metabolomic analysis reveals the influence of carbohydrates on lignin degradation mediated by Bacillus amyloliquefaciens.zip

IntroductionLigninolytic bacteria can secrete extracellular enzymes to depolymerize lignin into small-molecular aromatics that are subsequently metabolized and funneled into the TCA cycle. Carbohydrates, which are the preferred carbon sources of bacteria, influence the metabolism of lignin-derived aromatics through bacteria.MethodsIn this study, untargeted metabolomics and transcriptomics analyses were performed to investigate the effect of carbohydrates on lignin degradation mediated by Bacillus amyloliquefaciens MN-13, a strain with lignin-degrading activity that was isolated in our previous work.ResultsThe results demonstrated that the cell growth of the MN-13 strain and lignin removal were promoted when carbohydrates such as glucose and sodium carboxymethyl cellulose were added to an alkaline lignin-minimal salt medium (AL-MSM) culture. Metabolomics analysis showed that lignin depolymerization took place outside the cells, and the addition of glucose regulated the uptake and metabolism of lignin-derived monomers and activated the downstream metabolism process in cells. In the transcriptomics analysis, 299 DEGs were screened after 24 h of inoculation in AL-MSM with free glucose and 2 g/L glucose, respectively, accounting for 8.3% of the total amount of annotated genes. These DEGs were primarily assigned to 30 subcategories, including flagellar assembly, the PTS system, RNA degradation, glycolysis/gluconeogenesis, the TCA cycle, pyruvate metabolism, and tryptophan metabolism. These subcategories were closely associated with the cell structure, generation of cellular energy, and precursors for biosynthetic pathways, based on a − log 10 (P adjust) value in the KEGG pathway analysis.ConclusionIn summary, the addition of glucose increased lignin degradation mediated by the MN-13 strain through regulating glycolysis, TCA cycle, and central carbon metabolism.</p

Total Synthesis of Polysubstituted γ‑Butyrolactone Lignans (−)-Hinokinin, (−)-Bicubebin B, and (−)-Isodeoxypodophyllotoxin via Oxime Carbonate Formation

The diverse structures and profound biological activities of lignan natural products have enticed significant effort in the exploration of new methodologies for their total synthesis. We have prepared γ-butyrolactone oximes from readily available δ-nitro alcohols via Boc2O mediated cyclization. The mild conditions are compatible with a wide range of functional groups, and this methodology has been applied to the total synthesis of five lignan natural products