A Distribution Evolutionary Algorithm for Graph Coloring

Graph Coloring Problem (GCP) is a classic combinatorial optimization problem that has a wide application in theoretical research and engineering. To address complicated GCPs efficiently, a distribution evolutionary algorithm based on population of probability models (DEA-PPM) is proposed. Based on a novel representation of probability model, DEA-PPM employs a Gaussian orthogonal search strategy to explore the probability space, by which global exploration can be realized using a small population. With assistance of local exploitation on a small solution population, DEA-PPM strikes a good balance between exploration and exploitation. Numerical results demonstrate that DEA-PPM performs well on selected complicated GCPs, which contributes to its competitiveness to the state-of-the-art metaheuristics

Applications of Catalytic Hairpin Assembly Reaction in Biosensing.

Nucleic acids are considered as perfect programmable materials for cascade signal amplification and not merely as genetic information carriers. Among them, catalytic hairpin assembly (CHA), an enzyme-free, high-efficiency, and isothermal amplification method, is a typical example. A typical CHA reaction is initiated by single-stranded analytes, and substrate hairpins are successively opened, resulting in thermodynamically stable duplexes. CHA circuits, which were first proposed in 2008, present dozens of systems today. Through in-depth research on mechanisms, the CHA circuits have been continuously enriched with diverse reaction systems and improved analytical performance. After a short time, the CHA reaction can realize exponential amplification under isothermal conditions. Under certain conditions, the CHA reaction can even achieve 600 000-fold signal amplification. Owing to its promising versatility, CHA is able to be applied for analysis of various markers in vitro and in living cells. Also, CHA is integrated with nanomaterials and other molecular biotechnologies to produce diverse readouts. Herein, the varied CHA mechanisms, hairpin designs, and reaction conditions are introduced in detail. Additionally, biosensors based on CHA are presented. Finally, challenges and the outlook of CHA development are considered

Methylation of CYP1A1 and VKORC1 promoter associated with stable dosage of warfarin in Chinese patients

Objective To investigate the association between DNA methylation and the stable warfarin dose through genome-wide DNA methylation analysis and pyrosequencing assay. Method This study included 161 patients and genome-wide DNA methylation analysis was used to screen potential warfarin dose-associated CpGs through Illumina Infinium HumanMethylation 450 K BeadChip; then, the pyrosequencing assay was used to further validate the association between the stable warfarin dose and alterations in the methylation of the screened CpGs. GenomeStudio Software and R were used to analyze the differentially methylated CpGs. Results The methylation levels of CpGs surrounding the xenobiotic response element (XRE) within the CYP1A1 promoter, differed significantly between the different dose groups (P  0, P < 0.05) with an increase in the stable dose of warfarin. At the VKORC1 promoter, two CpGs methylation levels were significantly different between the differential dose groups (P < 0.05), and one CpG (Chr16: 31106793) presented a significant negative correlation (r <  0, P <  0.05) among different dose (low, medium, and high) groups. Conclusion This is a novel report of the methylation levels of six CpGs surrounding the XRE within the CYP1A1 promoter and one differential CpG at the VKORC1 promoter associated with stable warfarin dosage; these methylation levels might be applied as molecular signatures for warfarin

Latitudinal Variation in the Pattern of Temperature-Dependent Sex Determination in the Japanese Gecko, <i>Gekko japonicus</i>

Identifying latitudinal variation in the pattern of temperature-dependent sex determination (TSD) may provide insight into the evolution of sex determining system in vertebrates, but such studies remain limited. Here, we quantified TSD patterns of three geographically separated populations of the Japanese gecko (Gekko japonicus) along the latitudinal cline of China. We incubated gecko eggs from the three populations at constant temperatures of 24, 26, 28, 30, and 32 °C to quantify the TSD pattern. Our study demonstrated that G. japonicus exhibited a FMF pattern of TSD, with the low and high incubation temperatures yielding significantly female-biased hatchlings, and the medium temperatures producing male-biased hatchlings. More interestingly, we found latitudinal variations in the TSD pattern in terms of pivotal temperatures (Tpivs), transitional range of temperatures (TRT), and the sex ratios at the medium temperatures. The Tpivs for the low-latitude population were lower than those for the two high-latitude populations. The low-latitude population has a narrower FM TRT, but a wider MF TRT. The sex ratio is almost 50:50 for the low-latitude population when eggs were incubated from 26 to 30 °C. Conversely, the sex ratio is male-biased for the two high-latitude populations at 28 or 30 °C. Therefore, G. japonicus may provide an interesting system to explore the evolution of TSD in reptiles given the diversity of TSD patterns among populations

A novel AllGlo probe-quantitative PCR method for detecting single nucleotide polymorphism in CYP2C19 to evaluate the antiplatelet activity of clopidogrel

Abstract CYP2C19 gene has multiple single nucleotide polymorphism (SNP), which is the major determinant for clopidogrel treatment responses. Therefore, CYP2C19 SNP detection is essential for predicting clopidogrel efficacy. Currently, there is still no quick and effective method for routine detection of common CYP2C19 SNPs in clinical laboratories, which is critically needed prior to clopidogrel treatment. AllGlo™ based quantitative PCR was used to develop a novel genotyping method for CYP2C19 SNP detection, termed CyPAllGlo. The performance of CyPAllGlo was compared with that of the commonly used fluorescence in situ hybridization (FISH) method, and the data was verified by DNA sequencing. CyPallGlo was used to identify CYP2C19 polymorphisms in 363 patients with coronary heart disease. The univariate analysis was used to access the antiplatelet efficacy of clopidogrel in patients. The associations between CYP2C19 polymorphisms and clopidogrel efficacy were analyzed. Using CyPAllGlo to detect CYP2C19*2 and CYP2C19*3 alleles was highly specific and fast. The detection limit was approximately 0.07 µg/µl and 0.7 µg/µl for CYP2C19*2 and CYP2C19*3, respectively. The consistency between FISH and CyPAllGlo were 98.07% for CYP2C19*2 and 99.17% for CYP2C19*3. DNA sequencing showed that the accuracy of CyPAllGlo was 100%. The analysis time for the whole CyPAllGlo procedure was approximately 60 min. Univariate analysis showed that the anticoagulation efficacy of clopidogrel was related to patient age, CYP2C19 genotype, metabolic phenotype, and LDL level. The logistic regression analysis showed that the genotype of CYP2C19 and metabolic phenotype was the two risk factors for clopidogrel antiplatelet ineffectiveness. This novel CyPAllGlo is a rapid and accurate method for detection of CYP2C19 SNP. The specificity and consistency of CyPAllGlo are comparable with that of widely used DNA sequencing. These findings provide valuable rapid method for predicting clopidogrel efficacy, which can be quickly translated to improve personalized precision medicine for coronary heart disease treatment

Synthesis, structural andin vitrostudies of well-dispersed monomethoxy-poly(ethylene glycol)–honokiol conjugate micelles

Honokiol, an active principle extracted from Magnolia officinalis, has great potential as a cancer treatment. However, its poor water solubility greatly hampers its delivery to the tumor sites at an effective concentration. In this study, an amphiphilic polymer–drug conjugate was successfully prepared by condensation of low molecular weight monomethoxy-poly(ethylene glycol) (MPEG)-2000 with honokiol (HK) through an ester linkage to increase the hydrophilicity of honokiol. The MPEG–honokiol (MPEG–HK) conjugate prepared formed nano-sized micelles, with a mean particle size of less than 20 nm (MPEG–HK, 360 µg ml−1) in water, which could be well dispersed in water. The nanoparticles obtained were characterized by particle size distribution, morphology and zeta potential. The stability and hydrolysis profile of the polymeric pro-drug in phosphate-buffered saline (PBS) and plasma were also studied and the results showed that only 20% of the conjugated honokiol was released in 2.0 h in beagle dog plasma, while in PBS the time required to reach 20% of honokiol release was >200 h. Meanwhile, the inhibitory activity of the honokiol conjugate was found to be retained in vitro against LL/2 cell lines with an IC50 value of 10.7 µg ml−1. These results suggest that the polymer–drug conjugate provides a potential new approach to hydrophobic drugs, such as honokiol, in formulation design

Plasma miRNA profiles associated with stable warfarin dosage in Chinese patients

Background We used bioinformatic analysis and quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays to investigate the association between plasma microRNAs (miRNAs) and stable warfarin dosage in a Chinese Han population. Methods Bioinformatics analysis was used to screen out potential warfarin dose-associated miRNAs. Three plasma miRNAs were validated in 99 samples by RT-qPCR. Kruskal–Wallis test and multivariate logistic regression were used to compare differences in plasma miRNAs expression levels between three warfarin dosage groups. Results There were significant between-group differences among the three dose groups for hsa-miR-133b expression (p = 0.005), but we observed an “n-shaped” dose-dependent curve rather than a linear relationship. Expression levels of hsa-miR-24-3p (p = 0.475) and hsa-miR-1276 (p = 0.558) were not significantly different in the multivariate logistic regression. Conclusion miRNAs have received extensive attention as ideal biomarkers and possible therapeutic targets for various diseases. However, they are not yet widely used in precision medicine. Our results indicate that hsa-miR-133b may be a possible reference factor for the warfarin dosage algorithm. These findings emphasize the importance of a comprehensive evaluation of complex relationships in warfarin dose prediction models and provide new avenues for future pharmacogenomics studies