Human papillomavirus (HPV) integration is a key genetic event in cervical carcinogenesis. By conducting whole-genome sequencing and high-throughput viral integration detection, we identified 3,667 HPV integration breakpoints in 26 cervical intraepithelial neoplasias, 104 cervical carcinomas and five cell lines. Beyond recalculating frequencies for the previously reported frequent integration sites POU5F1B (9.7%), FHIT (8.7%), KLF12 (7.8%), KLF5 (6.8%), LRP1B (5.8%) and LEPREL1 (4.9%), we discovered new hot spots HMGA2 (7.8%), DLG2 (4.9%) and SEMA3D (4.9%). Protein expression from FHIT and LRP1B was downregulated when HPV integrated in their introns. Protein expression from MYC and HMGA2 was elevated when HPV integrated into flanking regions. Moreover, microhomologous sequence between the human and HPV genomes was significantly enriched near integration breakpoints, indicating that fusion between viral and human DNA may have occurred by microhomology-mediated DNA repair pathways. Our data provide insights into HPV integration-driven cervical carcinogenesis.

We have developed pLink, software for data analysis of cross-linked proteins coupled with mass-spectrometry analysis. pLink reliably estimates false discovery rate in cross-link identification and is compatible with multiple homo- or hetero-bifunctional cross-linkers. We validated the program with proteins of known structures, and we further tested it on protein complexes, crude immunoprecipitates and whole-cell lysates. We show that it is a robust tool for protein-structure and protein-protein-interaction studies.

Background China faces a major increase in cardiovascular disease, yet there is limited population-based data on risk factors, particularly in children. Methods and Results Fasting blood samples, anthropometry and blood pressure were collected on 9,244 children and adults aged ≥7 years in late 2009 as part of the national China Health and Nutrition Survey. Prevalent overweight, elevated blood pressure, and cardiometabolic risk factors: glucose, HbA1c, triglycerides (TG), total cholesterol (TC), high and low density lipoprotein cholesterol (HDL-C and LDL-C), and C-reactive protein (CRP) are presented. Results 11% of Chinese children and 30% of Chinese adults are overweight. Rates of diabetes, dyslipidemia, hypertension, and inflammation are high and increased with age and were associated with urbanization. Approximately 42% of children have at least one of the following: pre-diabetes or diabetes, hypertension, high TC, LDL-C, TG, and CRP and low HDL-C, as do 70% males and 60% females aged 18–40 years and >86% of males and females ≥40 years. Conclusions HbA1c findings suggest that as many as 29.4 million Chinese children and 415.8 million Chinese adults may be prediabetic or diabetic. The high prevalence in less urban areas and across all income levels suggests that cardiometabolic risk is pervasive across rural and urban China.

Enzymes are protein molecules functioning as specialized catalysts for chemical reactions. They have contributed greatly to the traditional and modern chemical industry by improving existing processes. In this article, we first give a survey of representative industrial applications of enzymes, focusing on the technical applications, feed industry, food processing and cosmetic products. The recent important developments and applications of enzymes in industry are reviewed. Then large efforts are dedicated to the worldwide enzyme market from the demand and production perspectives. Special attention is laid on the Chinese enzyme market. Although enzyme applications are being developed in full swing, breakthroughs are needed to overcome their weaknesses in maintaining activities during the catalytic processes. Strategies of metagomic analysis, cell surface display technology and cell-free system might give valuable solutions in novel enzyme exploiting and enzyme engineering.

BackgroundHemoglobin (Hb) measurement is a standard test among pregnant women during the first perinatal visit that is used to evaluate physical status and anemia. However, studies focusing on Hb levels and pregnancy outcomes are scarce. This study aimed to determine whether Hb levels in early pregnancy were associated with the risk of gestational diabetes mellitus (GDM), pre-eclampsia (PE) and preterm birth.MethodsA hospital-based retrospective study was conducted among 21,577 singleton, non-smoking pregnancies between June 2013 and January 2015. The demographic data and medical information of each participant were collected individually through questionnaires and patient medical records. Odds ratios were generated using a multivariate logistic regression analysis to evaluate the relative risk of GDM, PE and preterm birth continuously and across different hemoglobin ranges in the overall population and in women from different pre-pregnancy body mass index (BMI) categories, respectively. The level of statistical significance was set at 0.05.Results(1) For women who were underweight, normal-weight, overweight and obese, early pregnancy Hb levels were 127.8 ± 10.1 g/L, 129.6 ± 9.7 g/L, 132.2 ± 9.5 g/L and 133.4 ± 9.4 g/L, respectively. (2) Women with GDM and PE had significantly increased Hb levels during early pregnancy compared with controls, whereas women with preterm birth processed significantly decreased Hb levels. (3) After adjusting for confounders, the risks for GDM and PE increased with high maternal Hb (OR: 1.27 for Hb 130–149; OR: 2.06 for Hb ≥ 150 g/L), and the risk for preterm birth decreased with high maternal Hb (OR: 1.30 for Hb 130–149; OR: 2.38 for Hb ≥ 150 g/L) and increased with low maternal Hb (OR: 1.41 for Hb <  110 g/L). Among women whose BMI was < 24 kg/m2, high GDM (OR: 1.27 for Hb 130–149; OR: 1.84 for Hb ≥ 150 g/L) and low preterm rates (OR: 0.77 for Hb 130–149; OR: 0.23 for Hb ≥ 150 g/L) were observed with high Hb, whereas in women whose BMI was ≥24 kg/m2, only high GDM rates were observed with Hb > 150 g/L (OR: 2.33).ConclusionThese findings suggest that Hb levels during early pregnancy play a role in predicting the risk of GDM, PE and preterm birth.

Ovarian cancer is the leading cause of death from gynaecological malignancies worldwide. Here we perform a three-stage genome-wide association study (GWAS) in Han Chinese women to identify risk genetic variants for epithelial ovarian cancer (EOC). We scan 900,015 single-nucleotide polymorphisms (SNPs) in 1,057 EOC cases and 1,191 controls in stage I, and replicate 41 SNPs (P meta o10 À 4 ) in 960 EOC cases and 1,799 controls (stage II), and an additional 492 EOC cases and 1,004 controls (stage III). Finally, we identify two EOC susceptibility loci at 9q22.33 (rs1413299 in COL15A1, P meta ¼ 1.88 Â 10 À 8 ) and 10p11.21 (rs1192691 near ANKRD30A, P meta ¼ 2.62 Â 10 À 8 ), and two consistently replicated loci at 12q14.2 (rs11175194 in SRGAP1, P meta ¼ 1.14 Â 10 À 7 ) and 9q34.2 (rs633862 near ABO and SURF6, P meta ¼ 8.57 Â 10 À 7 ) (Po0.05 in all three stages). These results may advance our understanding of genetic susceptibility to EOC.

This study showed that in central south Chinese postmenopausal women, serum sclerostin is lower in women with osteoporosis than without. Serum sclerostin is positively correlated with fat mass and BMD for the whole body, lumbar spine and hip.

These results indicate that Asp supplementation is associated with inhibition of TLR4 and NODs/NF-κB and p38 signaling pathways and concomitant improvement of intestinal integrity under an inflammatory condition.