The three-dimensional (3D) structure prediction of proteins is an important task in bioinformatics. Finding energy functions that can better represent residue-residue and residue-solvent interactions is a crucial way to improve the prediction accuracy. The widely used contact energy functions mostly only consider the contact frequency between different types of residues; however, we find that the contact frequency also relates to the residue hydrophobic environment. Accordingly, we present an improved contact energy function to integrate the two factors, which can reflect the influence of hydrophobic interaction on the stabilization of protein 3D structure more effectively. Furthermore, a fold recognition (threading) approach based on this energy function is developed. The testing results obtained with 20randomly selected proteins demonstrate that, compared with common contact energy functions, the proposed energy function can improve the accuracy of the fold template prediction from 20% to 50%, and can also improve the accuracy of the sequence-template alignment from 35% to 65%.

BACKGROUNDIncreased blood pressure and elevated total cholesterol (TC) level are the two most important modifiable risk factors of cardiovascular disease (CVD) in the world. Hypertension and hypercholesterolemia co-exist more often than would be expected and whether there is a synergistic impact on fatal CVD between elevated TC and hypertension need to be further examined in Chinese population.

METHODSWe conducted a cohort study which recruited 5092 Chinese male steelworkers aged 18 - 74 years in 1974 - 1980 and followed up for an average of 20.84 years. Totally 302 fatal CVD events were documented by the year of 2001. Cox proportional hazards regression models were undertaken to adjust for baseline variables with fatal CVD events as the outcome variable. Additive interaction model was used to evaluate the interaction between elevated TC and hypertension.

RESULTSHypercholesterolemia and hypertension were significantly associated with an increased hazard ratio (HR) of fatal CVD (1.67 (95%CI 1.18 - 2.38) and 2.91 (95%CI 2.23 - 3.80) respectively. Compared to participants with normotension and TC < 240 mg/dl, the HRs were 1.11 (95%CI 0.56 - 2.21), 2.74 (95%CI 2.07 - 3.64) for hypercholesterolemia and hypertension respectively, and 5.51 (95%CI 3.58 - 8.46) for participants with both risk factors. There was an additive interaction with a 2.65 (95%CI 0.45 - 4.85) relative excess risk (RERI) between hypercholesterolemia and hypertension on CVD.

CONCLUSIONWe found that the risk of fatal CVD was significantly associated with an additive interaction due to hypercholesterolemia and hypertension besides a conventional main effect derived from either of them, which highlights that the prevention and treatment of both risk factors might improve the individual risk profile thus reduce the CVD mortality.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; Cardiovascular Diseases ; blood ; etiology ; mortality ; Cholesterol ; blood ; Humans ; Hypercholesterolemia ; blood ; complications ; Hypertension ; blood ; complications ; Male ; Middle Aged ; Steel ; Young Adult

Objective To analyze epidemiological characters of an outbreak of rotavirus diarrhea in Daxing county, Guangxi province. Methods Rotavirus-positive specimens were identified by ELBA kit. G/P typing assays were confirmed with multiplex seminested RT-PCR. Full-length VP7 genes of 4 positive specimens were amplified and analyzed. Results 30 cases of Rotavirus-positive were identified from 64 specimens. The attack rate was 46.9% , and G/P typing was G1P[8]. A change of VP7 amino acid residue is at positions 68.Conclusion G1P[8] rotavirus is the etiologic agents of this diarrhea outbreak. In addition, adults were included in this outbreak.

The antidepressant mechanism of Sini Powder was investigated by metabonomics based on UHPLC-Q-TOF-MS, and the roles of processing and compatibility in the antidepression of Sini Powder were discussed in the present study. The chronic unpredictable mild stress(CUMS) model of depression was induced in the model group, the Bupleuri Radix group, the Paeoniae Radix Alba group, the herb-pair group(Bupleuri Radix-Paeoniae Radix Alba), the Sini Powder group, and the vinegar-processed Sini Powder group(Bupleuri Radix and Paeoniae Radix Alba were vinegar-processed). After the establishment of the model, the rats in each group were continuously administered with corresponding drugs(ig) at a dose of 9.6 g·kg~(-1) for eight days [the rats in the model group and the normal group(without model induction) received the same volume of normal saline at the same time]. Following the last administration, the differential metabolites were identified to analyze metabolic pathways based on the rat plasma samples collected from each group. A total of sixteen potential biomarkers were identified. The metabolites with significant changes were involved in many biological metabolic pathways, such as amino acid metabolism, pentose phosphate pathway, glycerol phospholipid metabolism, sphingolipid metabolism, and purine metabolism. After drug intervention, some biomarkers returned to normal levels. Further comparisons of processing and compatibility revealed that the vinegar-processed Sini Powder group had the most total metabolic pathways where differential metabolites were returned to normal. Compared with the individual herbs, the herb-pair significantly improved the recovery of differential metabolites in the pentose phosphate and purine metabolic pathways. Compared with the Sini Powder, the vinegar-processed Sini Powder facilitated the recovery of differential metabolites in the arginine biosynthesis, and pyrimidine and pentose phosphate metabolic pathways. As indicated by the results, Sini Powder may interfere with depression by regulating lipid and nucleotide metabolisms. The processing and compatibility of Chinese herbal medicines can potentiate the intervention on depression by regulating nucleotide, energy, and amino acid metabolisms to a certain extent.
Animals ; Antidepressive Agents ; Drugs, Chinese Herbal ; Metabolomics ; Paeonia ; Powders ; Rats

BACKGROUND: Irritable bowel syndrome (IBS) is reported associated with the alteration of gut microbial composition termed as dysbiosis. However, the pathogenic mechanism of IBS remains unclear, while the studies of Chinese individuals are scarce. This study aimed to understand the concept of dysbiosis among patients with Chinese diarrhea-predominant IBS (IBS-D), as a degree of variance between the gut microbiomes of IBS-D population and that of a healthy population. METHODS: The patients with IBS-D were recruited (assessed according to the Rome III criteria, by IBS symptom severity score) from the Outpatient Department of Gastroenterology of Peking University Third Hospital, and volunteers as healthy controls (HCs) were enrolled, during 2013. The 16S rRNA sequences were extracted from fecal samples. Ribosomal database project resources, basic local alignment search tool, and SparCC software were used to obtain the phylotype composition of samples and the internal interactions of the microbial community. Herein, the non-parametric test, Wilcoxon rank-sum test was carried out to find the statistical significance between HC and IBS-D groups. All the P values were adjusted to q values to decrease the error rate. RESULTS: The study characterized the gut microbiomes of Chinese patients with IBS-D, and demonstrated that the dysbiosis could be characterized as directed alteration of the microbiome composition leading to greater disparity between relative abundance of two phyla, Bacteroidetes (Z = 4.77, q = 1.59 × 10) and Firmicutes (Z = -3.87, q = 5.83 × 10). Moreover, it indicated that the IBS symptom features were associated with the dysbiosis of whole gut microbiome, instead of one or several certain genera even they were dominating. Two genera, Bacteroides and Lachnospiracea incertae sedis, were identified as the core genera, meanwhile, the non-core genera contribute to a larger pan-microbiome of the gut microbiome. Furthermore, the dysbiosis in patients with IBS-D was associated with a reduction of network complexity of the interacted microbial community (HC vs. IBS-D: 639 vs. 154). The disordered metabolic functions of patients with IBS-D were identified as the potential influence of gut microbiome on the host (significant difference with q < 0.01 between HC and IBS-D). CONCLUSIONS This study supported the view of the potential influence of gut microbiome on the symptom of Chinese patients with IBS-D, and further characterized dysbiosis in Chinese patients with IBS-D, thus provided more pathological evidences for IBS-D with the further understanding of dysbiosis.
Diarrhea ; microbiology ; Dysbiosis ; microbiology ; Feces ; microbiology ; Gastrointestinal Microbiome ; genetics ; Humans ; Irritable Bowel Syndrome ; microbiology ; Models, Theoretical ; RNA, Ribosomal, 16S ; genetics