BackgroundIn structure-based drug design, binding affinity prediction remains as a challenging goal for current scoring functions. Development of target-biased scoring functions provides a new possibility for tackling this problem, but this approach is also associated with certain technical difficulties. We previously reported the Knowledge-Guided Scoring (KGS) method as an alternative approach (BMC Bioinformatics, 2010, 11, 193–208). The key idea is to compute the binding affinity of a given protein-ligand complex based on the known binding data of an appropriate reference complex, so the error in binding affinity prediction can be reduced effectively.ResultsIn this study, we have developed an upgraded version, i.e. KGS2, by employing 3D protein-ligand interaction fingerprints in reference selection. KGS2 was evaluated in combination with four scoring functions (X-Score, ChemPLP, ASP, and GoldScore) on five drug targets (HIV-1 protease, carbonic anhydrase 2, beta-secretase 1, beta-trypsin, and checkpoint kinase 1). In the in situ scoring test, considerable improvements were observed in most cases after application of KGS2. Besides, the performance of KGS2 was always better than KGS in all cases. In the more challenging molecular docking test, application of KGS2 also led to improved structure-activity relationship in some cases.ConclusionsKGS2 can be applied as a convenient “add-on” to current scoring functions without the need to re-engineer them, and its application is not limited to certain target proteins as customized scoring functions. As an interpolation method, its accuracy in principle can be improved further with the increasing knowledge of protein-ligand complex structures and binding affinity data. We expect that KGS2 will become a practical tool for enhancing the performance of current scoring functions in binding affinity prediction. The KGS2 software is available upon contacting the authors.

BackgroundAccording to renal M type phospholipase A2 receptor (PLA2R) immunohistochemistry, idiopathic membranous nephropathy (IMN) could be categorized into PLA2R-associated and non-PLA2R-associated IMN. We conducted a retrospective, multicenter cohort study with 91 patients to compare the effect of immunosuppressive therapy between PLA2R-associated and non-PLA2R-associated IMN patients.MethodsA total of 91 biopsy-proven IMN patients from Huashan hospital and People’s Hospital of Wuxi in past 5 years were collected into this study. IMN with positive PLA2R immunohistochemistry in kidney biopsies were designated as PLA2R-associated IMN. Seventy-eight of the 91 IMN patients was PLA2R-associated IMN and 13 were non-PLA2R-associated IMN. Forty-five patients were treated with prednisone plus cyclophosphamide (CTX), and 46 with prednisone plus calcineurin inhibitors (CNIs). The follow-up duration was 15 months.ResultsThe total remission rate (76.9% versus 44.9%, p = 0.032) and complete remission rate (30.8% versus 2.6%, p = 0.003) were both significantly higher in the non-PLA2R-associated group than in the PLA2R-associated group at the 3rd month visit point, and at the 6th month time point, the complete remission rate was still significantly higher in the non-PLA2R-associated group (46.2% versus 11.5%,p = 0.007). But similar remission rates were found after the 9th month. Relapses were observed in 8 patients in PLA2R-associated group and none in non-PLA2R-associated group, although there was no significant difference between these two groups.ConclusionCompared with the PLA2R-associated IMN, the non-PLA2R-associated IMN responded quicker to the immunosuppressive therapy.

BackgroundHere, we aimed to investigate the effects of ensiled mulberry leaves (EML) and sun-dried mulberry fruit pomace (SMFP) on fecal bacterial communities in Simmental crossbred finishing steers. To this end, the steers were reared on a standard TMR diet, standard diet containing EML, and standard diet containing SMFP. The protein and energy levels of all the diets were similar. Illumina MiSeq sequencing of the V4 region of the 16S rRNA gene and quantitative real-time PCR were used to analyze and detect the fecal bacterial community.ResultsMost of the sequences were assigned to Firmicutes (56.67%) and Bacteroidetes (35.90%), followed by Proteobacteria (1.87%), Verrucomicrobia (1.80%) and Tenericutes (1.37%). The predominant genera were 5-7 N15 (5.91%), CF231 (2.49%), Oscillospira (2.33%), Paludibacter (1.23%) and Akkermansia (1.11%). No significant differences were observed in the numbers of Firmicutes (p = 0.28), Bacteroidetes (p = 0.63), Proteobacteria (p = 0.46), Verrucomicrobia (p = 0.17), and Tenericutes (p = 0.75) populations between the treatment groups. At the genus level, genera classified with high abundance (more than 0.1%) belonged primarily to Bacteroidetes and Firmicutes. Furthermore, no differences were observed at the genus level: 5-7 N15, CF231, Oscillospira, Paludibacter, and Akkermansia (p > 0.05 in all cases), except that rc4–4 was lower in the CON and SMFP groups than in the EML group (p = 0.02). There were no significant differences in the richness estimate and diversity indices between the groups (p > 0.16), and the different diets did not significantly influence most selected fecal bacterial species (p > 0.06), except for Ruminococcus albus, which was higher in the EML group (p < 0.01) and Streptococcus bovis, which was lower in the CON group (p < 0.01) relative to the other groups.ConclusionsIn conclusion, diets supplemented with EML and SMFP have little influence on the fecal bacterial community composition in finishing steers.

BackgroundEchovirus 14 (E-14) causes various clinical recognized syndromes, mostly with gastrointestinal syndrome and paralysis. The current study summarized the Shandong E-14 strains isolated from a 26-year acute flaccid paralysis (AFP) surveillance, and elucidated the characterization of phylogenetic and phylogeographic relationships of E-14 worldwide.ResultsAs a predominant serotype circulating in AFP surveillance, phylogenetic analysis showed that E-14 exhibited both time and geographic subdivision worldwide. In order to know the evolutionary history and spatial temporal dynamics of E-14, evolutionary phylogeography was reconstructed using BEAST and SPREAD software based on the VP1 sequences. The time of the most recent common ancestor of E-14 was estimated around 85 years and evolved with 9.17 × 10−3 substitutions/site/year. Phylogeographic analysis suggested that two regional transmissions of E-14 were mainly detected, with one located between Europe and Africa countries and the other was in the Asia-Pacific region.ConclusionsOur study investigates the molecular evolution and phylogeographic of E-14, and brings new insight to the dispersal of E-14 worldwide. Regional transmission was mainly detected and Australia may be responsible for the spread of E-14 in recent years.

BackgroundMyocardial 18F-deoxyglucose (18F-FDG) uptake has been observed to be enhanced in patients with coronary artery disease (CAD) under fasting conditions. However, whether the increased 18F-FDG is induced by myocardial ischemia and how to discriminate ischemic from physiological 18F-FDG uptake have rarely been investigated.MethodsUnder fasting conditions, 18F-FDG PET imaging was performed in 52 patients with suspected CAD. Two 18F-FDG imaging sessions were conducted within two hours after a single administration of 18F-FDG (dual-time-point imaging), and with an intervention of an exercise test after the first imaging. Abnormal 18F-FDG uptake was determined by the classification of the 18F-FDG distribution pattern, and the changes of the 18F-FDG distribution between the two PET imaging sessions were analyzed. 99mTc-sestamibi was injected at peak exercise and myocardial perfusion imaging (MPI) was conducted after 18F-FDG imaging. Coronary angiography was considered the reference for diagnosing CAD.ResultsOverall, 54.8% (17/31) of CAD patients and 36.2% (21/58) of stenotic coronaries showed exercise-induced abnormal uptake of 18F-FDG. Based on the classification of the 18F-FDG distribution pattern, the sensitivity and specificity of exercise 18F-FDG imaging to diagnose CAD was 80.6% and 95.2% by patient analysis, 56.9% and 98.0% by vascular analysis, respectively. Compared with MPI, 18F-FDG imaging had a tendency to have higher sensitivity (80.6% vs 64.5%, P = 0.06) on the patient level.ConclusionMyocardial ischemia can induce 18F-FDG uptake. With the classification of the 18F-FDG distribution pattern, dual-time-point 18F-FDG imaging under fasting conditions is efficient in diagnosing CAD.

BackgroundThis study assessed the prevalence and severity of early childhood caries (ECC) and identified socioeconomic and behavioral correlates of the disease in preschool children living in Xinjiang.MethodsFor this cross-sectional survey, 1727 children aged 3–5 years in Xinjiang were randomly recruited using a three-stage cluster sampling procedure. The “dmft” index according to the WHO 1997 criteria was used to assess ECC and severe ECC (S-ECC). A questionnaire was completed by caregivers. Variables included sociodemographic characteristics, dietary and oral hygiene behaviors, and access to dental services. The statistical associations of variables with ECC, S-ECC, and dmft were evaluated by univariate and multiple logistic regression analyses.ResultsThe prevalence of ECC was 78.2% and that of S-ECC was 41.2%; mean dmft scores were 5.61 ± 3.56 and 8.17 ± 2.94, respectively. The prevalence of ECC was significantly higher in children from Ining (OR 2.747; 95% CI 2.033–3.713), those whose caregivers had caries (OR 1.78; 95% CI 1.245–2.547), those with a dental visit in the past (OR 2.023; 95% CI 1.429–2.865), and those whose parents had received instructions on oral health care (OR 2.171; 95% CI 1.44–3.272), and increased significantly at age 4 years (OR 2.09; 95% CI 1.506–2.901) and 5 years (OR 2.666; 95% CI 1.855–3.833) and in children who starting tooth brushing at a young age (OR 1.363; 95% CI 1.171–1.587), and decreased significantly in children with a more educated mother (OR 0.817; 95% CI 0.688–1), those from high-income families (OR 0.667; 95% CI 0.582–0.765), those with low consumption of sweets (OR 0.66; 95% CI 0.57–0.763), and those who seldom ate before sleep (OR 0.557; 95% CI 0.437–0.712).ConclusionsECC and S-ECC remain a serious problem among preschool children in Xinjiang. Caries rates were associated with sociodemographic and behavioral factors, which could be modified by public health strategies, including protection of primary dentition, extension of insurance to cover oral preventive services, improvement of the oral health care system, and public health education.