Chinese eye exercises and myopia development in school age children: a nested case-control study

Chinese eye exercises have been implemented in China as an intervention for controlling children’s myopia for over 50 years. This nested case-control study investigated Chinese eye exercises and their association with myopia development in junior middle school children. Outcome measures were the onset and progression of myopia over a two-year period. Cases were defined as 1. Myopia onset (cycloplegic spherical equivalent ≤ −0.5 diopter in non-myopic children). 2. Myopia progression (myopia shift of ≥1.0 diopter in those who were myopic at baseline). Two independent investigators assessed the quality of Chinese eye exercises performance at the end of the follow-up period. Of 260 children at baseline (mean age was 12.7 ± 0.5 years), 201 were eligible for this study. There was no association between eye exercises and the risk of myopia-onset (OR = 0.73, 95%CI: 0.24–2.21), nor myopia progression (OR = 0.79, 95%CI: 0.41–1.53). The group who performed high quality exercises had a slightly lower myopia progression of 0.15 D than the children who did not perform the exercise over a period of 2 years. However, the limited sample size, low dosage and performance quality of Chinese eye exercises in children did not result in statistical significance and require further studies

MMP Mediated Degradation of Type VI Collagen Is Highly Associated with Liver Fibrosis - Identification and Validation of a Novel Biochemical Marker Assay

Background and Aims: During fibrogenesis, in which excessive remodeling of the extracellular matrix occurs, both the quantity of type VI collagen and levels of matrix metalloproteinases, including MMP-2 and MMP-9, increase significantly. Proteolytic degradation of type VI collagen into small fragments, so-called neo-epitopes, may be specific biochemical marker of liver fibrosis. The aim of this study was to develop an ELISA detecting a fragment of type VI collagen generated by MMP-2 and MMP-9, and evaluate this assay in two preclinical models of liver fibrosis. Methods: Mass spectrometric analysis of cleaved type VI collagen revealed a large number of protease-generated neo-epitopes. A fragment unique to type VI collagen generated by MMP-2 and MMP-9 was selected for ELISA development. The CO6-MMP assay was evaluated in two rat models of liver fibrosis: bile duct ligation (BDL) and carbon tetrachloride (CCl4)-treated rats. Results: Intra-and inter-assay variation was 4.1% and 10.1% respectively. CO6-MMP levels were significantly elevated in CCl4-treated rats compared to vehicle-treated rats at weeks 12 (mean 30.9 ng/mL vs. 12.8 ng/mL, p = 0.002); week 16 (mean 34.0 ng/mL vs. 13.7 ng/mL, p = 0.0018); and week 20 (mean 35.3 ng/mL vs. 13.3 ng/mL, p = 0.0033) with a tight correlation between hepatic collagen content and serum levels of CO6-MMP (R-2 = 0.58,

Analysis of the transcriptome of Panax notoginseng root uncovers putative triterpene saponin-biosynthetic genes and genetic markers

<p>Abstract</p> <p>Background</p> <p><it>Panax notoginseng </it>(Burk) F.H. Chen is important medicinal plant of the <it>Araliacease </it>family. Triterpene saponins are the bioactive constituents in <it>P. notoginseng</it>. However, available genomic information regarding this plant is limited. Moreover, details of triterpene saponin biosynthesis in the <it>Panax </it>species are largely unknown.</p> <p>Results</p> <p>Using the 454 pyrosequencing technology, a one-quarter GS FLX titanium run resulted in 188,185 reads with an average length of 410 bases for <it>P. notoginseng </it>root. These reads were processed and assembled by 454 GS <it>De Novo </it>Assembler software into 30,852 unique sequences. A total of 70.2% of unique sequences were annotated by Basic Local Alignment Search Tool (BLAST) similarity searches against public sequence databases. The Kyoto Encyclopedia of Genes and Genomes (KEGG) assignment discovered 41 unique sequences representing 11 genes involved in triterpene saponin backbone biosynthesis in the 454-EST dataset. In particular, the transcript encoding dammarenediol synthase (DS), which is the first committed enzyme in the biosynthetic pathway of major triterpene saponins, is highly expressed in the root of four-year-old <it>P. notoginseng</it>. It is worth emphasizing that the candidate cytochrome P450 (Pn02132 and Pn00158) and UDP-glycosyltransferase (Pn00082) gene most likely to be involved in hydroxylation or glycosylation of aglycones for triterpene saponin biosynthesis were discovered from 174 cytochrome P450s and 242 glycosyltransferases by phylogenetic analysis, respectively. Putative transcription factors were detected in 906 unique sequences, including Myb, homeobox, WRKY, basic helix-loop-helix (bHLH), and other family proteins. Additionally, a total of 2,772 simple sequence repeat (SSR) were identified from 2,361 unique sequences, of which, di-nucleotide motifs were the most abundant motif.</p> <p>Conclusion</p> <p>This study is the first to present a large-scale EST dataset for <it>P. notoginseng </it>root acquired by next-generation sequencing (NGS) technology. The candidate genes involved in triterpene saponin biosynthesis, including the putative CYP450s and UGTs, were obtained in this study. Additionally, the identification of SSRs provided plenty of genetic makers for molecular breeding and genetics applications in this species. These data will provide information on gene discovery, transcriptional regulation and marker-assisted selection for <it>P. notoginseng</it>. The dataset establishes an important foundation for the study with the purpose of ensuring adequate drug resources for this species.</p

The ovine HIAT1 gene: mRNA expression, InDel mutations, and growth trait associations

BackgroundThe hippocampal abundant transcript 1 (HIAT1) gene, also known as major facilitator superfamily domain-containing 14A (MFSD14A), encodes for a transmembrane transporter protein and has been previously shown to be associated with milk production in buffalo and sheep breeds, as well as growth traits in chicken and goats. However, tissue level distribution of the ovine HIAT1 gene, as well as its effect on body morphometric traits in sheep, has yet to be studied.MethodsThe HIAT1 mRNA expression profile of Lanzhou fat-tailed (LFT) sheep was determined by quantitative real-time PCR (qPCR). A total of 1498 sheep of three indigenous Chinese sheep breeds were PCR-genotyped for polymorphisms of HIAT1 gene. Student's t-test was used to observe the association between the genotype and sheep morphometric traits.ResultsHIAT1 was widely expressed in all examined tissues, and was particularly abundant in the testis of male LFT sheep. Additionally, a 9-bp insertion mutation (rs1089950828) located within the 5'-upstream region of HIAT1 was investigated in Luxi black-headed (LXBH) sheep and Guiqian semi-fine wool (GSFW) sheep. The wildtype allele frequency 'D' was found to be more prevalent than that of the mutant allele ‘I'. Furthermore, low genetic diversity was confirmed in all sampled sheep populations. Subsequent association analyses indicated an association between the 9-bp InDel mutation of interest and the morphometric traits of LXBH and GSFW sheep. Furthermore, yearling ewes with a heterozygous genotype (ID) demonstrated smaller body sizes, while yearling rams and adult ewes with the heterozygous genotype were found to have overall better growth performance.ConclusionThese findings imply that functional InDel polymorphism (rs1089950828) has the potential to be utilized for marker-assisted selection (MAS) of growth traits in domestic Chinese sheep populations

Global distribution and evolutionary transitions of angiosperm sexual systems

Angiosperm sexual systems are fundamental to the evolution and distribution of plant diversity, yet spatiotemporal patterns in angiosperm sexual systems and their drivers remain poorly known. Using data on sexual systems and distributions of 68453 angiosperm species, we present the first global maps of sexual system frequencies and evaluate sexual system evolution during the Cenozoic. Frequencies of dioecy and monoecy increase with latitude, while hermaphrodites are more frequent in warm and arid regions. Transitions to dioecy from other states were higher than to hermaphroditism, but transitions away from dioecy increased since the Cenozoic, suggesting that dioecy is not an evolutionary end point. Transitions between hermaphroditism and dioecy increased, while transitions to monoecy decreased with paleo-temperature when paleo-temperature >0℃. Our study demonstrates the biogeography of angiosperm sexual systems from a macroecological perspective, and enhances our understanding of plant diversity patterns and their response to climate change.acceptedVersio

MiR-574-5p Activates Human TLR8 to Promote Autoimmune Signaling and Lupus

Endosomal single-stranded RNA-sensing Toll-like receptor-7/8 (TLR7/8) plays a pivotal role in inflammation and immune responses and autoimmune diseases. However, the mechanisms underlying the initiation of the TLR7/8-mediated autoimmune signaling remain to be fully elucidated. Here, we demonstrate that miR-574-5p is aberrantly upregulated in tissues of lupus prone mice and in the plasma of lupus patients, with its expression levels correlating with the disease activity. miR-574-5p binds to and activates human hTLR8 or its murine ortholog mTlr7 to elicit a series of MyD88-dependent immune and inflammatory responses. These responses include the overproduction of cytokines and interferons, the activation of STAT1 signaling and B lymphocytes, and the production of autoantigens. In a transgenic mouse model, the induction of miR-574-5p overexpression is associated with increased secretion of antinuclear and anti-dsDNA antibodies, increased IgG and C3 deposit in the kidney, elevated expression of inflammatory genes in the spleen. In lupus-prone mice, lentivirus-mediated silencing of miR-574-5p significantly ameliorates major symptoms associated with lupus and lupus nephritis. Collectively, these results suggest that the miR-574-5p-hTLR8/mTlr7 signaling is an important axis of immune and inflammatory responses, contributing significantly to the development of lupus and lupus nephritis

Maternal, neonatal, pregnancy outcome characteristics of pregnant women with high plasma cell-free DNA concentration in non-invasive prenatal screening: a retrospective analysis

ObjectiveCell-free DNA (cfDNA) is a useful biomarker in various clinical contexts. Herein, we aimed to identify maternal characteristics and pregnancy outcomes associated with a failed NIPS test due to high cfDNA concentrations.MethodsA retrospective study of cases with high plasma cfDNA concentration in pregnant women in which NIPS test was performed (from 174,318 cases). We reported the detection of 126 cases (118 with complete clinical information) in which the high amount of cfDNA did not allow the performance of NIPS and study the possible causes of this result.Results622 (0.35%) of 174,318 pregnant women had failed the NIPS test, including 126 (20.3%) cases with high plasma cfDNA concentrations. The failed NIPS due to high plasma cfDNA concentrations was associated with maternal diseases and treatment with low-molecular-weight heparin (LMWH). Further follow-up of the 118 pregnant women in the case group revealed that the pregnancy outcomes included 31 premature deliveries, 21 abortions. The cfDNA concentrations of pregnant women with preterm deliveries were 1.15 (0.89, 1.84), which differed significantly from those who had full-term deliveries.ConclusionsAmong pregnant women with high cfDNA concentrations, systemic autoimmune diseases, pregnancy complications and LMWH were associated with increased incidence of failed NIPS test. High maternal cfDNA concentrations may not be associated with chromosomal abnormalities in the fetus. However, they should be alerted to the possibility of preterm births and stillbirths. Further clinical studies on pregnant women with high cfDNA concentrations are required

Alterations in brain structure and function associated with pediatric growth hormone deficiency: A multi-modal magnetic resonance imaging study

IntroductionPediatric growth hormone deficiency (GHD) is a disease resulting from impaired growth hormone/insulin-like growth factor-1 (IGF-1) axis but the effects of GHD on children’s cognitive function, brain structure and brain function were not yet fully illustrated.MethodsFull Wechsler Intelligence Scales for Children, structural imaging, diffusion tensor imaging, and resting-state functional magnetic resonance imaging were assessed in 11 children with GHD and 10 matched healthy controls.Results(1) The GHD group showed moderate cognitive impairment, and a positive correlation existed between IGF-1 levels and cognitive indices. (2) Mean diffusivity was significantly increased in both corticospinal tracts in GHD group. (3) There were significant positive correlations between IGF-1 levels and volume metrics of left thalamus, left pallidum and right putamen but a negative correlation between IGF-1 levels and cortical thickness of the occipital lobe. And IGF-1 levels negatively correlated with fractional anisotropy in the superior longitudinal fasciculus and right corticospinal tract. (4) Regional homogeneity (ReHo) in the left hippocampus/parahippocampal gyrus was negatively correlated with IGF-1 levels; the amplitude of low-frequency fluctuation (ALFF) and ReHo in the paracentral lobe, postcentral gyrus and precentral gyrus were also negatively correlated with IGF-1 levels, in which region ALFF fully mediates the effect of IGF-1 on working memory index.ConclusionMultiple subcortical, cortical structures, and regional neural activities might be influenced by serum IGF-1 levels. Thereinto, ALFF in the paracentral lobe, postcentral gyrus and precentral gyrus fully mediates the effect of IGF-1 on the working memory index

Extensive pyrosequencing reveals frequent intra-genomic variations of internal transcribed spacer regions of nuclear ribosomal DNA

BACKGROUND: Internal transcribed spacer of nuclear ribosomal DNA (nrDNA) is already one of the most popular phylogenetic and DNA barcoding markers. However, the existence of its multiple copies has complicated such usage and a detailed characterization of intra-genomic variations is critical to address such concerns. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used sequence-tagged pyrosequencing and genome-wide analyses to characterize intra-genomic variations of internal transcribed spacer 2 (ITS2)regions from 178 plant species. We discovered that mutation of ITS2 is frequent, with a mean of 35 variants per species. And on average, three of the most abundant variants make up 91% of all ITS2 copies. Moreover, we found different congeneric species share identical variants in 13 genera. Interestingly, different species across different genera also share identical variants. In particular, one minor variant of ITS2 in Eleutherococcus giraldii was found identical to the ITS2 major variant of Panax ginseng, both from Araliaceae family. In addition, DNA barcoding gap analysis showed that the intra-genomic distances were markedly smaller than those of the intra-specific or inter-specific variants. When each of 5543 variants were examined for its species discrimination efficiency, a 97% success rate was obtained at the species level. CONCLUSIONS: Identification of identical ITS2 variants across intra-generic or inter-generic species revealed complex species evolutionary history, possibly, horizontal gene transfer and ancestral hybridization. Although intra-genomic multiple variants are frequently found within each genome, the usage of the major variants alone is sufficient for phylogeny construction and species determination in most cases. Furthermore, the inclusion of minor variants further improves the resolution of species identification.Jingyuan Song, Linchun Shi, Dezhu Li, Yongzhen Sun, Yunyun Niu, Zhiduan Chen, Hongmei Luo, Xiaohui Pang, Zhiying Sun, Chang Liu, Aiping Lv, Youping Deng, Zachary Larson-Rabin, Mike Wilkinson and Shilin Che