Objective To investigate the characteristics of intestinal microbiota in neonates on the first and third day after birth.Methods A total of 50 healthy singleton neonates who were born between June 15,2016 and August 3,2016 in Shanghai First Maternity and Infant Hospital were enrolled.Their stool samples were collected on the first and third day after birth and the samples were labeled according to the time of collection (D1 and D3 groups,n=50 each).Illumina NexSeq high-throughput sequencing platform was used to sequence the variable region 4 and 5 of all bacterial 16S rRNA genes in the samples.The composition of intestinal microbial communities was determined and the differences between the two groups were compared by Metastats analysis.Results (1) A total of 100 stool samples were sequenced and the retrieved sequences were from 25 bacterial phyla,119 families,227 genera and 159 species.(2) Major phyla in the two groups were the same,namely,Proteobacteria,Frimicutes,Bacteroidetes and Actinobacteria.The relative abundances of Frimicutes (0.27 ± 0.03 vs 0.41 ± 0.05) and Bacteroidetes (0.07 ± 0.01 vs 0.09 ± 0.03) increased over time,while that of Actinobacteria (0.10±0.01 vs 0.01 ±0.00) decreased on day 3.No significant difference in the relative abundance of Proteobacteria (0.51 ±0.03 vs 0.49± 0.05) was observed between D1 and D3 groups.There were significant difference in relative abundances of Frimicutes and Actinobacteria between the two groups (both q=-0.01,both P＜0.05).(3) Among the top ten most abundant families,Enterobacteriaceae,Staphylococcaceae,Enterococcaceae,Streptococcaceae and Lachnospiraceae were detected in both of the two groups.The relative abundances of Enterobacteriaceae (0.25 ± 0.02 vs 0.46 ± 0.06),Staphylococcaceae (0.07 ± 0.02 vs 0.12 ± 0.03),Enterococcaceae (0.04±0.02 vs 0.10±0.04),Streptococcaceae (0.03 ±0.02 vs 0.06±0.01) increased over time,while that of Lachnospiraceae (0.03 ± 0.01 vs 0.02 ± 0.02) decreased on day 3.Only the relative abundance of Enterobacteriaceae had statistical difference between the two groups (q=0.00,P＜0.05).(4) Among the top ten most abundant genera,Staphylococcus,Enterococcus,Streptococcus,Bacteroides and Pseudomonas were detected in both groups.The relative abundances of aerobic and facultative anaerobic bacteria which belonged to genera of Stenotrophomonas,Propionibacterium,Acinetobacter,Bacillus,Sphingomonas and so on decreased on day 3 as compared with those on day 1 (0.00±0.00 vs 0.07±0.02,0.00±0.00 vs 0.06±0.01,0.00±0.00 vs 0.03±0.01,0.00±0.00 vs 0.02±0.01,0.00±0.00 vs 0.02±0.00,all q=0.00,all P＜0.05).However,the relative abundances of anaerobic bacteria which belonged to Bacteroides,Veillonella,Parabacteroides and so on increased on day 3 (0.01 ±0.00 vs 0.08±0.03,0.00±0.00 vs 0.03±0.02,0.00±0.00 vs 0.01 ±0.00,q=0.01,0.01 and 0.00,all P＜0.05).(5) The most abundant species in intestinal microbiota was escherichia coli in both groups.Three less abundant species including lactobacillus gasseri,lactobacillus animalis and bifidobacterium bifidum were detected in both groups.(6) Regardless of the mode of delivery,Staphylococcus,was the highest predominant genera in meconium samples,followed by stenotrophomonas.Stool samples collected on the third day after birth were divided into four groups based on deliver modes and feeding patterns.Neonates who were born abdominally with exclusive breastfed thereafter were different from those of the other three groups in predominant intestinal bacteria,but the difference was not statistically significant.Bifidobacterium and Subdoligranulum were only detected in the vaginally born neonates.Conclusions Meconium is not sterile.Although the intestinal microbiota on the first day of life is different from that on the third day of life,the dominant bacteria are common.During the first three days of life,the relative abundances of aerobic and facultative anaerobic bacteria decreased significantly over time,while the relative abundance of anaerobic bacteria increased.

Lymphoid-specific tyrosine phosphatase (LYP) is a phosphatase that is encoded by protein tyrosine phosphatase non-receptor type 22 and is mainly distributed in lymphoid. In psychological condition, LYP inhibits T-cell receptor (TCR) signaling in association with C-terminal kinase (CSK). While in pathological condition, mutant LYP dissociates with CSK, which augments the inhibition of TCR signaling and leads to autoimmune diseases. Consequently, LYP is now considered as a new target of type I diabetes, rheumatic arthritis and Graves disease and some other autoimmune disorders. This review mainly focuses on the development of LYP inhibitors in their structures and activities.

Benzoxaborole is a series of compounds with five member ring and boron atom. Since the approval of crisaborole and tavaborole by FDA, benzoxaborole gained lots of research interests and become widely used in current drug discovery. Specially, benzoxaborole derivatives were found to exhibit anti-bacterial, anti-fungal, anti-protozoal, anti-tumor and anti-inflammatory activities. Here, we will review the properties of benzoxaborole, structure activity relationships as well as the recent progress in the biological activity of benzoxaborole derivatives.

As a member of class I histone deacetylase (HDACs), HDAC8 is an important anticancer drug target. Based on our previously developed pharmacophore model for the HDAC8 inhibitor, we designed and synthesized 13 quinoline acid derivatives as new HDAC8 inhibitors. Among them, the compound SDFZ-E2 and SDFZ-E3 exhibited good HDAC8 inhibitory activities and isoform selectivity. In cell experiments, the target compounds SDFZ-E2 and SDFZ-E3 showed better antiproliferation activities than the known HDAC8 selective inhibitor PCI-34051. In addition, the proposed binding mode of SDFZ-E2 was investigated using molecular docking and molecular dynamics simulation. This work is a new attempt to develop HDAC8 selective inhibitor using quinoline as the scaffold, and the active compounds could serve as lead compounds for further structural optimization.

Aim Human TMPRSS2 is a transmembrane serine protease.In this paper, the structure and func¬tion of the protein were systematically analyzed by bioinformatics, the codon was optimized and the pro- karvotie expression vector was constructed to explore the molecular mechanism of SARS-CoV-2 infecting host cells.Methods The recombinant expression vector pET-22b-TMPRSS2 was generated by molecular clo¬ning technology.The homology, functional sites, sub¬cellular localization, three-dimensional structure and evolutionary characteristics of TMPRSS2 protein were systematically analyzed by using analytical tools such as Protparam, NetPhos3.1, Blast, Clustal X2 and MEGA7.0.Results The prokarvotic expression plas- mid was constructed correctly; TMPRSS2 belongs to medium molecular weight protein, which is composed of 492 amino acid residues.The theoretical isoelectric point is 8.12, the molecular extinction coefficient is 118 145 L • mol~1 • cm"1 , and the half-life is 30 h; TMPRSS2 has 15 potential glycosylation sites and 49 possible phosphorylation sites.It is a transmembrane hydrophilie protein without signal sequenee.In addi¬tion, the protein has 13 potential B-cell epitopes and 7 T-eell epitopes.Seeondarv structure analysis showed that random coil accounted for the highest proportion of TMPRSS2 protein ( 0.453 3) , followed by extended strand (0.252 0).Sequence comparison and evolu¬tionary analysis showed that the highest sequence con¬sistency and closest genetic relationship with human TMPRSS2 was Pan troglodytes, followed by gorilla.Conclusions Human-derived TMPRSS2 protein is ev- olutionarilv conserved and functionally important.Hie results of this study can help to reveal the structure and mechanism of action of TMPRSS2 protein, provide ide¬as for the diagnosis and treatment of COYID-19, and accelerate the research and development process of new drugs targeting TMPRSS2 protein.

Objective: To understand the prevalence of HIV, hepatitis C virus (HCV) and syphilis and related factors among cross-border couples in Mangshi county, Dehong autonomous prefecture, Yunnan province. Methods: From May, 2017 to April, 2019, 2 500 couples with 5 000 cross-border marriages were selected by using cluster sampling method. The demographic characteristics, AIDS-related health services, HIV, HCV, syphilis infection and other information were collected through questionnaires and laboratory tests. The influencing factors of HIV, HCV and syphilis infection were analyzed by multivariate logistic regression model. Results: A total of 2 500 couples with cross-border marriage were investigated, among which 2 438 (97.5%) couples were Chinese men with Myanmar women. The average age of 5 000 participants was (34.16±9.00) years. Most of them were minority groups (59.9%), farmers (98.5%), education years ≤6 years (81.4%), marriage years>3 years (80.0%), and from mountainous areas (61.7%). The HIV prevalence of Chinese and Myanmar populations was 1.7% (43/2 500) and 2.0% (49/2 500), respectively. The HCV infection rates were 2.0% (49/2 500) and 1.3% (32/2 500), respectively and the infection rates of syphilis were 0.4% (10/2 500) and 0.2% (4/2 500), respectively. There were no statistically significant differences in the prevalence of three diseases among Chinese and Myanmar populations (P>0.05). The multivariate analysis showed that compared with those aged ≤ 30 years, having lower AIDS awareness, never receiving HIV testing, without HCV and syphilis infection, HIV prevalence was higher among those aged>30 years (OR=3.21, 95%CI: 1.80-5.73), having higher AIDS awareness (OR=17.41, 95%CI: 4.27-70.91), receiving HIV testing (OR=4.93, 95%CI: 2.72-8.92), with HCV infection (OR=5.64, 95%CI: 2.72-11.70) and syphilis infection (OR=8.37, 95%CI: 1.63-43.08). Compared with those aged ≤ 30 years, having marriage years ≤ 3 years, and with HIV negatives, HCV infection rate was higher among those age>30 years (OR=3.02, 95%CI: 1.69-5.38), having marriage years>3 years (OR=2.24, 95%CI: 1.34-3.74), and with HIV positives (OR=6.69, 95%CI: 3.29-13.59). Compared with those having HIV negatives, the syphilis infection rate was relatively higher among participants with HIV positives (OR=9.07, 95%CI: 2.00-41.10). Conclusion: The prevalence of HIV, HCV, and syphilis among cross-border couples in Mangshi county, Dehong autonomous prefecture of Yunnan province is relatively high. Age, AIDS awareness, HIV testing history, and the length of marriage are associated with the HIV, HCV, and syphilis infection.
Acquired Immunodeficiency Syndrome ; China/epidemiology* ; Female ; HIV Infections/epidemiology* ; Hepacivirus ; Hepatitis C/epidemiology* ; Humans ; Male ; Prevalence ; Risk Factors ; Syphilis/epidemiology*