Detailed resume of RNA m6A demethylases

N6-Methyladenosine (m6A) is the most abundant internal modification in eukaryotic mRNA, playing critical role in various bioprocesses. Like other epigenetic modifications, m6A modification can be catalyzed by the methyltransferase complex and erased dynamically to maintain cells homeostasis. Up to now, only two m6A demethylases have been reported, fat mass and obesity-associated protein (FTO) and alkylation protein AlkB homolog 5 (ALKBH5), involving in a wide range of mRNA biological progress, including mRNA shearing, export, metabolism and stability. Furthermore, they participate in many significantly biological signaling pathway, and contribute to the progress and development of cancer along with other diseases. In this review, we focus on the studies about structure, inhibitors development and biological function of FTO and ALKBH5.

Effect of microbial community structure of activated sludge in an Anaerobic-anoxic-oxic process with Actinic reaction enzyme system start-up / 生物工程学报

In order to explore the microbial communities and functions of activated sludge in an Anaerobic-anoxic-oxic (A²/O) process under the start-up of Actinic reaction enzyme system (ARES) system and to understand the impact of the ARES system in domestic sewage treatment process, the activated sludge microbial community structure in the A²/O process system before and after ARES system start-up was analyzed by Illumina-HiSeq 2000 high-throughput sequencing platform. By combining with the main parameters related to the effect of sewage treatment, we analyzed the environmental functions of the microbial communities. The microbial community structure of activated sludge was significantly different before and after the ARES system start-up. There were 9 main bacterial phyla in the system (average relative abundance ≥1%), accounting for 96%-98% of the total bacteria sequenced. After the ARES system was started, the relative abundance of Betaproteobacteria and Chlorobi increased by 3.45%-3.85% and 0.45%-2.61%, respectively. In the anaerobic unit, the relative abundance of Bacteroidetes increased by 12.97%, while the Actinobacteria and Firmicutes decreased by 9.60% and 1.45%, respectively. At the genus level of bacteria, the relative abundance of Denitratisoma increased by 0.80%-3.27%, while the Haliangium and Arcobacter decreased by 3.36%-4.52% and 1.48%-3.45%, respectively. The relative abundance of bacteria was significantly different before and after the ARES system start-up. There were 7 abundant fungi phyla (average relative abundance ≥1%) in the system. After the ARES system was started, the relative abundance of Rozellomycota decreased by 42.71%-46.77%. In the anaerobic unit, the relative abundance of Ascomycota decreased by 13.39%, while the relative abundance of Glomeromycota increased by 13.86%. At the genus level of fungi. The relative abundance of Entomophthoraceae sp. and Glomcromycota sp. increased by 31.35%-36.50% and 6.27%-13.84%, respectively, while the Rozellomycota sp. and Xylochrysis lucida decreased by 42.71%-46.77% and 3.67%-5.54%, respectively. Our results showed that the application of ARES system caused the response of the microbial community to environmental changes, especially for the fungi communities, in the meanwhile, improved the effluent quality, especially the removal rate of total nitrogen.

Tobacco point-of-purchase marketing in primary and middle school neighbourhoods in Tianjin / 中国学校卫生

Objective@#To understand the distribution of tobacco point-of-purchase(pop) activies 100 meters around the primary and middle school and the situation of selling cigarettes to students of Tianjin. To provide evidence for creating a smoke-free and healthy school environment.@*Methods@#With the method of simple random sampling, 195 schools were selected to investigate the tobacco retailers within 100 meters around the school, and the nearest tobacco retailers was observed.@*Results@#Totally 36.9 percent of the schools found tobacco retailers within 100 meters. There were 127 tobacco retailers, and no tobacco advertisements were found. The percentage of tobacco retailers within 100 meters of vocational schools, primary schools and middle schools was 33.3%, 34.1% and 40.4%, respectively. Among the 72 tobacco retailers observed, the proportion of tobacco retailers within 20, 21-50, and 51-100 meters from the school were 9.7%, 36.1% and 54.2%, respectively. The majority of tobacco retailers were grocery stores/convenience stores (55.6%), followed by alcohol and tobacco stores (34.7%). The proportion of tobacco selling points failing to set up the signs of "smoking harmful to health" and "not selling cigarettes to minors" were 81.9% and 86.1% respectively.@*Conclusion@#It’s concerning that the layout of tobacco retailers and the posting of signs, and the tobacco products for to minors in Tianjin. It is necessary to strengthen the surrounding environment renovation and publicity and law enforcement.

Development of the triazole-fused pyrimidine derivatives as highly potent and reversible inhibitors of histone lysine specific demethylase 1 (LSD1/KDM1A)

Histone lysine specific demethylase 1 (LSD1) has been recognized as an important modulator in post-translational process in epigenetics. Dysregulation of LSD1 has been implicated in the development of various cancers. Herein, we report the discovery of the hit compound (IC = 3.93 μmol/L) and further medicinal chemistry efforts, leading to the generation of compound (IC = 49 nmol/L, and = 16 nmol/L), which inhibited LSD1 reversibly and competitively with H3K4me2, and was selective to LSD1 over MAO-A/B. Docking studies were performed to rationalize the potency of compound . Compound also showed strong antiproliferative activity against four leukemia cell lines (OCL-AML3, K562, THP-1 and U937) as well as the lymphoma cell line Raji with the IC values of 1.79, 1.30, 0.45, 1.22 and 1.40 μmol/L, respectively. In THP-1 cell line, significantly inhibited colony formation and caused remarkable morphological changes. Compound induced expression of CD86 and CD11b in THP-1 cells, confirming its cellular activity and ability of inducing differentiation. The findings further indicate that targeting LSD1 is a promising strategy for AML treatment, the triazole-fused pyrimidine derivatives are new scaffolds for the development of LSD1/KDM1A inhibitors.

Effect of shuxuening injection in the adjuvant treatment of cerebral infarction and its clinical nursing / 中国生化药物杂志

Objective To evaluate the clinical efficacy of shuxuening injection in the adjuvant treatment of cerebral infarction (CI) and its clinical nursing. Methods A total of 114 patients with CI were randomly divided into two groups: The control group (n=57) were received conventional treatment and nursing, the observation group (n=57) were received shuxuening injection on the basis of control group. The efficacy and incidence of complications were compared between the two groups, the NIHSS and MMSE scores were evaluated before and after treatment. Results The total effective rate in the observation group was significantly higher than that in the control group (96.49％ vs 82.46％)( P<0.05), while the complication rate in the observation group was significantly lower than that in the control group(7.02％ vs 21.05％)( P<0.05). After treatment, the NIHSS score in the observation group was significantly lower than that in the control group, while the MMSE score was significantly higher than that in the control group(P<0.05). Conclusion Shuxuening injection is effective in the treatment of CI, which can reduce the complications, promote the rehabilitation of neurological function and protect the cognitive function, proper nursing intervention can promote the rehabilitation.

Correlation between polymorphism of monocyte chemoatt-ractant protein-1 gene A-2518G single nucleotide and acute coronary syndrome / 中华急诊医学杂志

Objective To investigate the possible correlation between the monocyte chemoattractant protein-1 ( MCP-1 ) gene A-2518G single nucleotide polymorphism (SNPs) in the promoter region and acute coronary syndrome (ACS) in Chinese Han ethnic population of Sunan region,Methods This study was conducted with a case-control design in 484 ACS patients including 290 acute myocardial infarction (AMI)patients and 194 patients with unstable angina pectoris (UAP) and 346 control subjects ruled out coronary disease by coronary angiography (control group),including 166 patients with coronary atherosclerosis and 180 subjects without coronary stenosis.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for the detection of the A-2518G polymorphism in MCP-1 gene,and then thefrequency of genetype was statistically analyzed.Results There were AA,AG and GG genotypes of MCP-1 gene A-2518G polymorphism in the ACS group and control group.The two groups could be considered as a genetic equilibrium representative by Hardy-Weinberg equilibrium ( P ＞ 0.05 ).Compared with the control group,the frequencies of AA genotype ( 15.32％ vs.16.12％ ),AG genotype (53.47％ vs.51.86％ ),GG genotype (31.21％ vs.32.02％ ) and G allele genotype (57.95％ vs.57.95％ ) in ACS group were not significantly different ( P was 0.083,0.673,0.821 and 1.00,respectively).Multivariate logistic regression analysis indicated that there was no significant correlation between MCP-1 gene A-2518G polymorphism and ACS regardless of differences in gender,age,smoking,diabetes,TG and LDL-C ( P ＞0.05 ).There was no significant difference in gender and age of ACS onset between two groups ( P ＞ 0.05).There were no significant differences in the frequencies of AA,AG and GG genotypes and G allele genotype among AMI group,UAP group and normal coronary group ( P ＞ 0.05).Conclusions The data shows that MCP-1 gene A-2518G polymorphism is not associated with the risk of ACS in the Chinese Han ethnic population living in Sunan region.