PPI-Miner: A Structure and Sequence Motif Co-Driven Protein-Protein Interaction Mining and Modeling Computational Method.

Protein-protein interactions (PPIs) play important roles in biological processes of life, and predicting PPIs becomes a critical scientific issue of concern. Most PPIs occur through small domains or motifs (fragments), which are challenging and laborious to map by standard biochemical approaches because they generally require the cloning of several truncation mutants. Here, we present a computational method, named as PPI-Miner, to fish potential protein interacting partners utilizing protein motifs as queries. In brief, this work first developed a motif-matching algorithm designed to identify the proteins that contain sequential or structural similar motifs with the given query motif. Being aligned to the query motif, the binding mode of the discovered motif and its receptor protein will be initially determined to be used to build PPI complexes accordingly. Eventually, a PPI complex structure could be built and optimized with a designed automatic protocol. Besides discovering PPIs, PPI-Miner can also be applied to other areas, i.e., the rational design of molecular glues and protein vaccines. In this work, PPI-Miner was employed to mine the potential cereblon (CRBN) substrates from human proteome. As a result, 1,739 candidates were predicted, and 16 of them have been experimentally validated in previous studies. The source code of PPI-Miner can be obtained from the GitHub repository (https://github.com/Wang-Lin-boop/PPI-Miner), the webserver is freely available for users (https://bailab.siais.shanghaitech.edu.cn/services/ppi-miner), and the database of predicted CRBN substrates is accessible at https://bailab.siais.shanghaitech.edu.cn/services/crbn-subslib.

Family history of esophageal cancer modifies the association of serum lipids and malignant esophageal lesions: a nested case-control study from the "Endoscopic Screening for Esophageal Cancer in China" trial.

BACKGROUND: The association of lipids and cancer has varied greatly among different cancer types, lipid components and study populations. This study is aimed to investigate the association of serum lipids and the risk of malignant lesions in esophageal squamous epithelium. METHODS: In the "Endoscopic Screening for Esophageal Cancer in China" (ESECC) trial, serum samples were collected and tested for total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol at the time of subject enrollment. Cases were defined as malignant esophageal lesions identified by baseline endoscopic examination or by follow-up to May 31, 2018. Controls were randomly selected using incidence density sampling in the same cohort. Conditional logistic models were applied to identify the association of serum lipids and the risk of malignant esophageal lesions. Effect modification was evaluated by testing interaction terms of the factor under assessment and these serum lipid indicators. RESULTS: No consistent association between serum lipid levels and esophageal malignant lesions were found in a pooled analysis of 211 cases and 2101 controls. For individuals with a family history of esophageal cancer (EC), high TC, and LDL-C were associated with a significantly increased risk of having malignant lesions (odds ratio [OR]High vs. Low TC = 2.22, 95% confidence interval [CI]: 1.14-4.35; ORHigh vs. Low LDL-C = 1.93, 95% CI: 1.01-3.65). However, a negative association was observed in participants without an EC family history (ORHigh vs. Low TC = 0.69, 95% CI: 0.48-0.98, Pinteraction = 0.002; ORHigh vs. Low LDL-C = 0.50, 95% CI: 0.34-0.76, Pinteraction < 0.001). CONCLUSIONS: In this study, we found that the association of serum lipids and malignant esophageal lesions might be modified by EC family history. The stratified analysis would be crucial for population-based studies investigating the association of serum lipids and cancer. The mechanism by which a family history of EC modifies this association warrants further investigation.

Efficient and Highly Stereoselective Syntheses of (+)-proto-Quercitol and (-)-gala-Quercitol Starting from the Naturally Abundant (-)-Shikimic Acid.

Efficient and highly stereoselective syntheses of (+)-proto-quercitol and (-)-gala-quercitol starting from the naturally abundant (-)-shikimic acid were described in this article. (-)-Shikimic acid was first converted to the key intermediate by eight steps in 53% yield. It was then converted to (+)-proto-quercitol by three steps in 78% yield and was also converted to (-)-gala-quercitol by five steps in 63% yield. In summary, (+)-proto-quercitol and (-)-gala-quercitol were synthesized from (-)-shikimic acid by 11 and 13 steps in 41 and 33% overall yields, respectively.

Novel stereoselective syntheses of N-octyl-ß-valienamine (NOV) and N-octyl-4-epi-ß-valienamine (NOEV) from (-)-shikimic acid.

N-Octyl-ß-valienamine (NOV) 1 and N-octyl-4-epi-ß-valienamine (NOEV) 2 are potent chemical chaperone drug candidates for the therapy of lysosomal storage disorders. Novel stereoselective syntheses of NOV 1 and NOEV 2 starting from naturally abundant (-)-shikimic acid are described in this article. The common key intermediate compound 5 was first synthesized from readily available (-)-shikimic acid via 9 steps in 50% yield. Compound 5 was then converted to NOV 1via 5 steps in 61% yield, and it was also converted to NOEV 2via 8 steps in 38% yield. In summary, NOV 1 was synthesized via 14 steps in 31% overall yield; and NOEV 2 was synthesized via 17 steps in 19% overall yield.

Copper-Catalyzed Benign and Efficient Oxidation of Tetrahydroisoquinolines and Dihydroisoquinolines Using Air as a Clean Oxidant.

A green chemical method for mild oxidation of 1,2,3,4-tetrahydroisoquinolines (THIQs) and 3,4-dihydroisoquinolines (DHIQs) has been developed using air (O2) as a clean oxidant. DHIQs and THIQs could be efficiently oxidized to isoquinolines in dimethyl sulfoxide at 25 °C under an open air atmosphere with CuBr2 (20 mol %) as the catalyst; different bases [NaOEt and/or 1,8-diazabicyclo[5,4,0]undec-7-ene] were used for the reaction according to the patterns of substituents (R1, R2).

[Prevalence and risk factors for hepatitis B in Hua County, Henan Province].

OBJECTIVE: To determine the epidemiological characteristics and associated risk factors of hepatitis B surface antigens (HBsAg) prevalence in rural areas of Hua County, Henan Province, and to provide scientific evidence for Hepatitis B prevention and control in local areas. METHODS: On the basis of an ongoing esophageal cancer cohort study in rural Anyang, a total of 5 104 subjects aged 25-65 years were clustered and selected from 5 targeted villages for this study in rural areas of Hua County, Henan Province. HBsAg was detected in their blood samples and a questionnaire was completed by all the subjects in a manner of one-on-one interview. All statistical analyses were conducted using SPSS for Windows version 13.0. RESULTS: Of the 5 104 studied subjects (overall participation rate: 92.05%), 5.17% were positive for HBsAg. The detection rate was significantly higher in males than in females (6.54% vs. 3.87%, P<0.001) and the highest detection rates were observed in the 25-29 and 55-59 years groups in both males and females. Multiple Logistic analyses showed unmarried status (OR=1.80, 95% CI: 1.00-3.25) and high frequency of sexual intercourse (Ptrend=0.049) were associated with higher the risk for hepatitis B virus (HBV) infection. CONCLUSION: The prevalence of HBsAg in rural Hua County, Henan Province, was slightly lower than the national average of the same time period. More attention should be attached to high risk groups of HBV infection in this population, i.e. males aged 25-29 years and 55-59 years and sexually active population. Immunization and health education projects against hepatitis B should be carried out in this population to further reduce the overall prevalence of hepatitis B.