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Background: Data-independent acquisition (DIA) is one of the most powerful and reproducible proteomic technologies for large-scale digital qualitative and quantitative research. The aim of this study was to use proteomic methodologies for the identification of biomarkers that are over or underexpressed in women with intrahepatic cholestasis of pregnancy (ICP) compared with controls and discover a potential biomarker panel for ICP detection. Methods: The participants included 11 ICP patients and 11 healthy pregnant women as controls. The clinical characteristic data and the laboratory biochemical data were collected at the time of recruitment. Then, a data-independent acquisition (DIA)-based proteomics approach was used to identify differentially expressed proteins (DEPs) in serum exosomes between ICP patients and controls. Finally, bioinformatics analysis was used to identify the relevant processes in which these DEPs were involved. Results: The proteomics results showed that there were 162 DEPs in serum exosomes between pregnant women with ICP and healthy pregnant women, of which 106 were upregulated and 56 were downregulated in ICP. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the identified proteins were functionally related to specific cell processes including apoptosis, lipid metabolism, immune response and cell proliferation, and metabolic disorders, suggesting that these may be primary causative factors in ICP pathogenesis. Meanwhile, complement and coagulation cascades may be closely related to the development of ICP. Receiver operating characteristic curve (ROC) analysis showed that the area under the curve values of Elongation factor 1-alpha 1, Beta-2-glycoprotein I, Zinc finger protein 238, CP protein and Ficolin-3 were all approximately 0.9, indicating the promising diagnostic value of these proteins. Conclusions: This preliminary work provides a better understanding of the proteomic alterations in the serum exosomes of pregnant women with ICP. [ABSTRACT FROM AUTHOR]

Multistage planetary gear transmission has a large speed ratio, compact structure and large load capacity in engineering practice. However, its vibration affects the performance and reliability of the transmission, especially under a stochastic load condition with different dynamic characteristics. In this context, the dynamic behavior of a four-stage planetary gear transmission system is investigated using the lumped-parameter model. First, the translation-torsion dynamics model of the multistage planetary gear transmission system is established. Then, the natural frequency and the effect of meshing stiffness and component mass on the natural frequency are investigated. Further, the dynamics equation of the planetary gear transmission system is solved by the Runge–Kutta method, and the damped dynamic response with an equivalent load and the dynamic responses with stochastic loads are analyzed. Notably, the displacement amplitude increases with the increment of the stochastic load. In addition, the frequency domain response under 50%, 75%, 100% and 120% of the equivalent torque are studied. Lastly, a test rig is built for a yaw drive in a wind turbine with the four-stage planetary gear transmission system, and the vibration of the ring gear of the second stage and output shaft are tested with 50%, 75%, 100% and 120% of equivalent load. The experiment results verify the correctness of the theoretical dynamic model of the multistage planetary gear transmission system. [ABSTRACT FROM AUTHOR]

Growing studies have demonstrated that circRNAs (circular RNAs) act potential roles in tumor metastasis and progression. However, the expression and function of circ_0006404 in hepatocellular carcinoma (HCC) remain to be investigated. The expression of circ_0006404 and miR-624 was detected by qRT-PCR. CCK-8 assay, flow cytometry, and wound healing were performed to determine cell proliferation, cycle, and migration. The target of circ_0006404 was studied by bioinformatics and luciferase activity analysis. Our data indicated that circ_0006404 was overexpressed in HCC specimens and cells and ectopic expression of circ_0006404 increased HCC cell growth, cycle, and migration. Moreover, we showed that miR-624 was downregulated in HCC specimens and cells and miR-624 expression was negatively correlated with circ_0006404 expression in HCC specimens. Circ_0006404 sponged miR-624 in HCC cell, and the overexpression of circ_0006404 suppressed miR-624 expression in HCC cell. Furthermore, circ_0006404 induced HCC cell growth, cycle, and migration via regulating miR-624. These results elucidated that circ_0006404 facilitated HCC progression and might act as one new biomarker for this carcinoma. [ABSTRACT FROM AUTHOR]

Sequencing-based genome-wide association studies (GWAS) have facilitated the identification of causal associations between genetic variants and traits in diverse species. However, it is cost-prohibitive for the majority of research groups to sequence a large number of samples. Here, we carried out genotype imputation to increase the density of single nucleotide polymorphisms in a large-scale Swine F2 population using a reference panel including 117 individuals, followed by a series of GWAS analyses. The imputation accuracies reached 0.89 and 0.86 for allelic concordance and correlation, respectively. A quantitative trait nucleotide (QTN) affecting the chest vertebrate was detected directly, while the investigation of another QTN affecting the residual glucose failed due to the presence of similar haplotypes carrying wild-type and mutant allelesin the reference panel used in this study. A high imputation accuracy was confirmed by Sanger sequencing technology for the most significant loci. Two candidate genes, CPNE5 and MYH3, affecting meat-related traits were proposed. Collectively, we illustrated four scenarios in imputation-based GWAS that may be encountered by researchers, and our results will provide an extensive reference for future genotype imputation-based GWAS analyses in the future. [ABSTRACT FROM AUTHOR]

Neuroblastoma (NB), as a metastatic form of solid tumor, has a high fatality rate found in early childhood. The two anaplastic lymphoma kinase (ALK) neoepitopes nonamer and decamer used in cancer immunotherapy against NB cancer can selectively bind to the human leukocyte antigen (HLA-B*15:01) groove with high affinities, whereas the native self-peptide is unable to interact with the HLA-B*15:01. Here, we performed molecular dynamics (MD) simulations and subsequent molecular mechanics-generalized born surface area (MM-GBSA) binding free energy calculations to explore the selective binding mechanisms of nonamer and decamer to the HLA-B*15:01 against the self-peptide. MD simulations revealed the significant conformational dynamics of the self-peptide in the HLA-B*15:01 groove against the nonamer and decamer. Binding free energy calculations showed that the binding affinities of HLA-B*15:01-neoepitope complexes were followed in the order decamer > nonamer > self-peptide. Detailed analysis of HLA-B*15:01-neoepitope structural complexes showed that compared to the nonamer, the self-peptide tended to move outward to the solvent, whereas the decamer moved deep to the HLA-B*15:01 groove. These different dynamic observations of the ALK neoepitopes can explain the distinct binding affinities of self-peptide, nonamer, and decamer to the HLA-B*15:01. The results may be useful for the design of more selective ALK neoepitopes. [ABSTRACT FROM AUTHOR]

Meat quality traits have economically significant impacts on the pig industry, and can be improved using molecular approaches in pig breeding. Since 1994 when the first genome-wide scan for quantitative trait loci (QTLs) in pig was reported, over the past two decades, numerous QTLs have been identified for meat quality traits by family based linkage analyses. However, little is known about the genetic variants for meat quality traits in Chinese purebred or outbred populations. To unveil it, we performed a genome-wide association study for 10 meat quality traits in Chinese purebred Laiwu pigs. In total, 75 significant SNPs ( P < 1.01 × 10) and 33 suggestive SNPs ( P < 2.03 × 10) were identified. On SSC12, a region between 56.22 and 61.49 Mb harbored a cluster of SNPs that were associated with meat color parameters (L*, lightness; a*, redness; b*, yellowness) and moisture content of longissimus muscle (LM) and semimembranosus muscle at the genome-wide significance level. A region on SSC4 also has pleiotropic effects on moisture content and drip loss of LM. In addition, this study revealed at least five novel QTLs and several candidate genes including 4-linked MYH genes ( MYH1, MYH2, MYH3, and MYH13), MAL2, LPAR1, and PRKAG3 at four significant loci. Except for the SSC12 QTL, other QTLs are likely tissue-specific. These results provide new insights into the genetic basis of meat quality traits in Chinese Laiwu pigs and some significant SNPs reported here could be incorporated into the selection programs involving this breed. [ABSTRACT FROM AUTHOR]

Starting from dehydrobaietic acid with the analogous structure of carnosic acid, the intermediate methyl 12-bromo-13-nitro-7-oxo dehydrodeisopropylabietate was synthesized through methylation, bromination, carbonylation, and nitration. Subsequently, the coupling of methyl 12-bromo-13-nitro-7-oxo dehydrodeisopropylabietate with aliphatic or aromatic primary amine by Ullmann condensation reaction produced a series of methyl 12-imino-13-nitro-7-oxo dehydrodeisopropylabietate derivatives. In order to probe their antioxidant effects through metal ion chelation mechanism, the metal ion binding abilities on Cu and Fe of these compounds were studied using fluorescence quenching method. The results indicated that each compound showed obvious chelation activity with the binding constants ( K) of the 10 L mol order of magnitude, which implied its potential pharmacology application as antioxidant by the inhibition of Feton reaction through chelation with Cu and Fe. [ABSTRACT FROM AUTHOR]

The tuberous root of radish is an important vegetable, but insufficient transcriptomic and genomic data are currently available to understand the molecular mechanisms underlying tuberous root formation and development. High-throughput transcriptomic sequencing is essential to generate a large transcript sequence data set for gene discovery and molecular marker development. In this study, a total of 107.3 million clean reads were generated using Illumina paired-end sequencing technology. De novo assembly generated 61,554 unigenes with an average length of 820 bp. Based on a sequence similarity search with known proteins or nucleotides, 85.51 % (52,634), 90.18 % (55,507) and 54 % (33,242) consensus sequences showed homology with sequences in the Nr, Nt and Swiss-Prot databases, respectively. Of these annotated unigenes, 21,109 and 17,343 unigenes were assigned to gene ontology categories and clusters of orthologous groups, respectively. A total of 27,809 unigenes were assigned to 123 pathways in the Kyoto Encyclopedia of Genes and Genomes database. Analysis of transcript differences between libraries from the early and late seedling developmental stages demonstrated that starch and sucrose metabolism and phenylpropanoid biosynthesis may be the dominant metabolic events during tuberous root formation and plant hormones probably play critical roles in regulation of this developmental process. In total, 14,641 potential EST-SSRs were identified among the unigenes, and 12,733 primer pairs for 2,511 SSR were obtained. Summarily, this study gave us a clue to understand the radish tuberous root formation and development, and also provided us with a valuable sequence resource for novel gene discovery and marker-assisted selective breeding in radish. Key message: De novo assembled and characterized the radish tuberous root transcriptome; explored the mechanism of radish tuberous root formation; development of EST-SSR markers in radish. [ABSTRACT FROM AUTHOR]

Esculetin was isolated from Cortex fraxini and identified by UV, IR, H NMR, C NMR . Its antioxidant properties were investigated employing various in vitro assays, such as 2,2′-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, hydroxyl radical scavenging assay in a new resonance scattering (RS) method, reducing power and total antioxidant assay. Esculetin showed excellent antioxidant properties superior to synthetic antioxidant butylated hydroxytoluene (BHT). Subsequently, inhibition effect of esculetin on human colon carcinoma (HT-29) cells proliferation was measured by thymidine incorporation assay. HT-29 cell number was decreasing with increasing concentration of esculetin at the lower concentrations of 0.25, 0.5, 1.0, and 2.0 mg/ml, compared to the positive control and HT-29 cells were stimulated in response to treatment with esculetin which decreases in a dose-dependent manner. However, at the higher concentrations of 4.0, 8.0, 12.0 and 16.0 mg/ml, growth of HT-29 cells were inhibited in a concentration-dependent fashion. [ABSTRACT FROM AUTHOR]

High-throughput small RNA sequencing and degradome analysis were used in this study to thoroughly investigate the role of miRNA-mediated regulatory network in tuberous root development of radish. Samples from the early seedling stage (RE) and the cortex splitting stage (RL) were used for the construction of six small RNA libraries and one degradome library. A total of 518 known and 976 novel miRNAs were identified, of which, 338 known and 18 novel miRNAs were expressed in all six libraries, respectively. A total of 52 known and 57 novel miRNAs were identified to be significantly differentially expressed between RE and RL, and 195 mRNAs were verified to be the targets of 194 miRNAs by degradome sequencing. According to the degradome analysis, 11 differentially expressed miRNAs had miRNA-mRNA targets, and 13 targets were identified for these 11 miRNAs. Of the 13 miRNA-mRNA targets, 4 genes (RSG11079.t1, RSG11844.t1, RSG16775.t1, and RSG42419.t1) were involved in hormone-mediated signaling pathway, 2 gens (RSG11079.t1 and RSG16775.t1) were related to post-embryonic root development, and 1 gene (RSG23799.t1) was involved in anatomical structure morphogenesis, according to the GO function analysis for biological process. Target Genes participated in these processes are important candidates for further studies. This study provides valuable information for a better understanding of the molecular mechanisms involved in radish tuberous root formation and development. [ABSTRACT FROM AUTHOR]