Use of tree-based machine learning methods to screen affinitive peptides based on docking data.

Screening peptides with good affinity is an important step in peptide-drug discovery. Recent advancement in computer and data science have made machine learning a useful tool in accurately affinitive-peptide screening. In current study, four different tree-based algorithms, including Classification and regression trees (CART), C5.0 decision tree (C50), Bagged CART (BAG) and Random Forest (RF), were employed to explore the relationship between experimental peptide affinities and virtual docking data, and the performance of each model was also compared in parallel. All four algorithms showed better performances on dataset pre-scaled, -centered and -PCA than other pre-processed dataset. After model re-built and hyperparameter optimization, the optimal C50 model (C50O) showed the best performances in terms of Accuracy, Kappa, Sensitivity, Specificity, F1, MCC and AUC when validated on test data and an unknown PEDV datasets evaluation (Accuracy=80.4 %). BAG and RFO (the optimal RF), as two best models during training process, did not performed as expecting during in testing and unknown dataset validations. Furthermore, the high correlation of the predictions of RFO and BAG to C50O implied the high stability and robustness of their prediction. Whereas although the good performance on unknown dataset, the poor performance in test data validation and correlation analysis indicated CARTO could not be used for future data prediction. To accurately evaluate the peptide affinity, the current study firstly gave a tree-model competition on affinitive peptide prediction by using virtual docking data, which would expand the application of machine learning algorithms in studying PepPIs and benefit the development of peptide therapeutics.

Improving the Corrosion Resistance of Aluminum Alloy by Creating a Superhydrophobic Surface Structure through a Two-Step Process of Etching Followed by Polymer Modification.

A multifunctional aviation aluminum alloy with good superhydrophobicity and corrosion resistance was prepared by a two-step process of etching followed by polymer modification. Meanwhile, micro- and nanostructures formed on the processed sample. Compared with bare sample, the static liquid contact angle on the as-prepared sample was increased by 100.8°. Further polarization tests showed that the corrosion potential of such a sample increased, and the corrosion current density decreased obviously, thus suggesting that the corrosion resistance of the modified sample was significantly improved. The same conclusion was confirmed by subsequent impedance testing. The work is of great economic value and practical significance to enhance the corrosion resistance of aviation actuator materials and also lays a foundation for future hydrophobic application research in aeronautical engineering.

Cross-sectional analysis of gonadal hormone expression and relevant factors in female centenarians in Hainan, China. / ä¸­å›½æµ·å—ç™¾å²å¥³æ€§è€äººæ€§è ºæ¿€ç´ è¡¨è¾¾ç‰¹å¾åŠå ³è”å› ç´ çš„æ¨ªæ–­é¢åˆ†æž.

OBJECTIVES: Gonadal hormone is essential for the health of postmenopausal women, however, few studies have focused on the epidemiological distribution of gonadal hormones in postmenopausal women in very late postmenopausal women. This study aims to investigate and analyze the differences of serum gonadal hormone content and its influential factors among female centenarians in Hainan, China. METHODS: The questionnaire and physical examination data of 741 female centenarians and 401 elderly females in Hainan Province were collected, and venous blood samples were taken to detect the indexes of lipid metabolism, bone metabolism, and gonadal hormone. The differences of gonadal hormones and relavant factors in female centenarians were analyzed and compared. RESULTS: The serum levels of estradiol and progesterone of female centenarians were significantly higher than those of the elderly females (both P<0.001). The serum levels of estradiol and testosterone of ethnic minority centenarians were higher than those in Han nationality (P<0.001), and the serum estradiol and testosterone concentrations were relatively higher when the daily activities were more than 10 min (both P<0.05). Serum estradiol concentration was negatively correlated with apolipoprotein A-I, high density lipoprotein, triglyceride and bone formation markers such as calcium, inorganic phosphorus and vitamin D3, and was positively correlated with the special sequence of ß-collagen (markers of bone resorption) (all P<0.01). CONCLUSIONS: For the extremely late postmenopausal women (such as centenarians), there may be characteristic expressions of gonadal hormones, especially estradiol. There is an unprotective correlation of serum estradiol with lipid metabolism index and bone metabolism index in female centenarians, so it is necessary to evaluate the estrogen content and the use of estrogen therapy in postmenopausal women.

Vesicular stomatitis virus glycoprotein suppresses nuclear factor kappa-B- and mitogen-activated protein kinase-mediated pro-inflammatory responses dependent on sialic acids.

Vesicular stomatitis (VS), characterized by vesicular lesions, produces significant economic losses in livestock industry. Infection by its causative agent, VS virus (VSV), has been previously shown to be mediated by the glycoprotein (G) during attachment, endocytosis and membrane fusion. In the current study, we revealed a novel role of VSV G protein in negative regulation of host cell pro-inflammatory responses. We determined that VSV G protein inhibited lipopolysaccharide (LPS)-induced pro-inflammatory responses as naïve VSV virions in murine peritoneal macrophage-like cell line RAW 264.7. Furthermore, we identified that VSV G protein suppressed nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK)-mediated pro-inflammatory pathways in a dose-dependent manner. Moreover, we demonstrated that α2-3-linked sialic acids on VSV G protein were involved in antagonizing NF-κB- and MAPK-mediated pro-inflammatory responses. All these results expand the knowledge of VSV pathogenesis and strengthen the importance of VSV G protein in host innate immunity, which support implications for the development of VSV-based vaccination and oncolysis.

[Research on risk factors of depression symptoms in 1 327 patients with obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To investigate the comorbidity rate of depression symptoms in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) in Henan province and to ascertain the risk factors. METHODS: One thousand three hundred and twenty-seven patients with OSAHS determined by overnight polysomnogram (PSG) were enrolled in this study. After screening the Symptom Checklist 90 (SCL-90) and Self-rating Depression Scale (SDS), the patients were divided into two groups: OSAHS (control group, n = 698) and OSAHS+depression (n = 629). The correlation was explored between the depression symptoms in patients with OSAHS and the sociodemographic variables and health status including smoking, drinking, marital status, apnea hyponea index (AHI), anoxicity, Family Burden Scale of Disease (FBS), Family APGAR Index (APGAR), Perceived Social Support Scale (PSSS) and so on. Furthermore, In-depth analyses were carried out between the depression symptoms in patients with OSAHS and the social and family factor items (FBS, APGAR and PSSS). RESULTS: The comorbidity rate of depression symptoms in patients with OSAHS in Henan province was 47.4%, and was correlated with the gender, marital status, FBS, APGAR, AHI, PSSS and anoxicity. Logistic regression analysis indicated that single marital status, APGAR, AHI, PSSS, hypoxemia and heart disease were all independent risk factors for depression in OSAHS patients. The total of the FBS score and three of its subfactors scores (family daily activities, family relationships and mental health of family members) were higher, and the total of the APGAR score and two of its subfactors scores (adaptabilith and affection) were lower in OSAHS with depression compared with the control group (P < 0.05). Besides, the total score for the PSSS AND Scores for its two subfactors (family support and social support) were all lower in OSAHS patients with depression than those of the control group (P < 0.05). CONCLUSION: In patients with OSAHS, depression symptoms are common and are associated with marital status, AHI, anoxicity, concomitant diseases (hypertension, heart disease), concerns and supports from the family and society.

Development of an immunochromatographic strip for rapid detection of antibodies against classical swine fever virus.

The genes encoding the Erns and E2 antigen epitopes of classical swine fever virus (CSFV) were expressed as a chimeric protein in Escherichia coli BL21 by pET expression system. The antigenicity of the expressed protein CnC2 was identified by indirect enzyme-linked immunoabsorbant assay (ELISA) and immunoblot with anti-CSFV antibodies. Based on the CnC2 protein, an immunochromatographic strip was developed to evaluate the antibody titer of serum samples from swine vaccinated with CSFV vaccine rapidly. The chimeric protein used as a detector was labeled with colloidal gold. Staphylococcal protein A (SPA) and anti-CnC2 monoclonal antibodies (mAbs) were blotted onto the nitrocellulose membrane as the test and control lines, respectively. The strip assay could be performed within 5min, which did not require any special equipment or skills. Through testing sera against various strains of CSFV, the sensitivity of the strip was determined to be 97.0% (65/67) and the specificity was 100% (98/98). The strip results were consistent with those of the existing commercial ELISA kit, and their correlation coefficient was 0.935. In conclusion, the immunochromatographic strip was an acceptable method for surveying CSFV-antibody titers in pigs.

Identification of host cell binding peptide from an overlapping peptide library for inhibition of classical swine fever virus infection.

The envelope proteins of classical swine fever virus (CSFV) mediate the binding of CSFV to cell surface molecules and allow CSFV subsequent to enter host cells. However, the proteins binding to host cells and their binding sequences are uncertain. The results showed that the protein E1, E2, and Erns were displayed on the surfaces of T7 phages. The E2 and Erns phage clones showed high binding affinity to host cells, in which the E2 phage clone interacted more specifically with host cells than with other cells, while the Erns phage clone interacted with all tested cells. A 30-mer phage displaying peptide library was constructed and screened against immobilized host cells, in which each peptide was overlapped 10aa to another peptide and spanned all amino acid sequences of Erns and E2. Fifty-eight clones with specific binding to host cells were isolated. Amino acid sequence analyses for two phage clones (P2 and P6) demonstrated the strongest binding positions were at 101-130 (S2) in Erns, and 141-170 (S6) in E2, respectively. The synthetic peptides (S2 and S6) could inhibit the binding of phage clones (P2 and P6) and CSFV to cell. About 86.74 and 74.24% inhibition rates of CSFV infection were achieved at 55 µM of the synthetic peptides S2 and S6. The results also indicated that the S2 (LAEGPPVKECAVTCRYDKDADINVVTQARN) and S6 (AVSPTTLRTEVVKTFRRDKPFPHRMDCVTT) from CSFV were host cell binding peptides, and both of them had potential for research of CSFV entering host cells.

The nonstructural protein 1 papain-like cysteine protease was necessary for porcine reproductive and respiratory syndrome virus nonstructural protein 1 to inhibit interferon-ß induction.

Porcine reproductive and respiratory syndrome virus nonstructural protein 1 (nsp1) could be auto-cleaved into nsp1α and nsp1ß, both of which had the papain-like cysteine protease activities. Previous studies have shown that porcine reproductive and respiratory syndrome virus nsp1 was an interferon (IFN) antagonist. However, the mechanism by which nsp1 inhibited IFN-ß production was unclear. Here, we used site-directed mutagenesis that inactivated the papain-like cysteine protease activities of nsp1 to explore whether the papain-like cysteine protease activities were required for nsp1 to disrupt IFN-ß production. The results showed that mutations that inactivated papain-like cysteine protease activity of nsp1α made nsp1 lose its IFN antagonism activity, whereas mutations that inactivated papain-like cysteine protease activity of nsp1ß did not influence the IFN antagonism activity of nsp1. In conclusion, our present work indicated that the papain-like cysteine protease activity of nsp1α was necessary for nsp1 to inhibit IFN-ß induction.

Surface IgM on DT40 cells may be a component of the putative receptor complex responsible for the binding of infectious bursal disease virus.

To investigate the host-pathogen interactions between infectious bursal disease virus (IBDV) and target B-lymphocytic cells, a cDNA T7 phage display library from the chicken bursa of Fabricius was constructed and screened for virus binding. Surface immunoglobulin M (sIgM) was isolated as a putative candidate binding site and its interactions with IBDV were further investigated using a chicken bursal lymphoma-derived cell line DT40. The results showed that the λ light chain of sIgM specifically interacted with IBDV in a virulence-independent manner in vitro, and most of the binding of IBDV to DT40 cells was inhibited by sIgM-specific monoclonal antibodies. Further, the infectivity of IBDV in vitro was reduced by sIgM-specific monoclonal antibodies. Our data provided evidence that sIgM may participate as one of the putative membrane binding sites responsible for IBDV infection.

Identification of neutralizing epitopes on the VP2 protein of infectious bursal disease virus by phage-displayed heptapeptide library screening and synthetic peptide mapping.

Infectious bursal disease virus (IBDV) is the causative agent of infectious bursal disease, which is one of the most important and widespread infectious diseases in commercial chickens. Conformational epitopes have been reported in the highly variable region of the VP2 protein of IBDV. In the present study, a random heptapeptide library was screened by using monoclonal antibodies (mAbs), YNW17 and YNW29, directed to the VP2 of IBDV and two peptide motifs, D-X-P-R and A-R-G, were identified. The motifs are present on the N and C terminal sequences of the highly variable region of VP2. Synthetic overlapping peptides covering the motifs on VP2 were analyzed by Dot- ELISA with the mAbs and two epitopes 197CDSSDRPRVYTIT209 and 329ARGSLAVTI337 identified. The above epitopes were also recognized by chicken anti-IBDV sera and shown to inhibit the binding of their mAbs to recombinant VP2. Both mAbs and sera from mice immunized with the conjugated epitope-peptides were able to neutralize serotype I IBDV. These results indicated that the epitopes are two neutralizing linear B-cell epitopes and would be useful for the development of peptide-based IBD vaccines.