Background Diabetes mellitus (DM) increases the risk of adverse maternal and neonatal outcomes, and optimization of glycemic control during pregnancy can help mitigate risks associated with diabetes. However, studies seldom focus precisely on maternal blood glucose level prior to pregnancy. We aimed to evaluate the associations between preconception blood fasting plasma glucose (FPG) level and subsequent pregnancy outcomes. Methods and findings We conducted a population-based retrospective cohort study among 6,447,339 women aged 20-49 years old who participated in National Free Pre-Pregnancy Checkups Project and completed pregnancy outcomes follow-up between 2010 and 2016 in China. During the preconception health examination, serum FPG concentration was measured, and selfreported history of DM was collected. Women were classified into three groups (normal FPG group: FPG < 5.6 mmol/L and no self-reported history of DM; impaired fasting glucose [IFG]: FPG 5.6-6.9 mmol/L and no self-reported history of DM; and DM: FPG � 7.0 mmol/L or self-reported history of DM). The primary outcomes were adverse pregnancy outcomes, including spontaneous abortion, preterm birth (PTB), macrosomia, small for gestational age infant (SGA), birth defect, and perinatal infant death. Logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval (CI) after adjusting for confounding

Background: Source plasma (SP) is the primary starting material for 87% of plasma-derived medicinal products globally. Plasmavigilance is a program designed to collect, analyze, and monitor donor adverse events (AEs) across the SP collection industry. Donor retention depends on donors having a safe and satisfactory experience. This study analyzes AE rates and SP donor characteristics that may be predictors of an AE. Study Design and Methods: Donation data for 1.1 million donors making 12,183,182 SP donations over a 4-month period were analyzed. This represented approximately 72% of the donations collected by the U.S. plasma industry. The Standard for Recording Donor Adverse Events was used for AE definitions and classifications.Results: The overall AE rate was 15.85/10 4 donations. The two AEs with the highest rates were Hypotensive and Phlebotomy events (8.32 and 5.91/10 4 donations, respectively). Females had higher overall AE rates than males (25.76 vs. 9.85/10 4 donations), and first-time donors had higher overall AE rates than repeat donors (136.66 vs. 12.37/10 4 donations). Weight, body mass index, age, and pre-donation estimated blood volume also were predictors of AE.Discussion: SP donors have low AE rates with 90% being events classified as Hypotensive or Phlebotomy. Special attention and mitigation strategies should be directed to donors who are young, lightweight (between 100 and 124 pounds), female, or first-time donors to further reduce the incidence of AE, continue to ensure the donor has a safe experience, and facilitate donor retention.

BackgroundMicroRNAs (miRNAs) are a class of small non-coding RNAs that play important roles in biotic and abiotic stresses by regulating their target genes. For common wheat, spring frost damage frequently occurs, especially when low temperature coincides with plants at early floral organ differentiation, which may result in significant yield loss. Up to date, the role of miRNAs in wheat response to frost stress is not well understood.ResultsWe report here the sequencing of small RNA transcriptomes from the young spikes that were treated with cold stress and the comparative analysis with those of the control. A total of 192 conserved miRNAs from 105 families and nine novel miRNAs were identified. Among them, 34 conserved and five novel miRNAs were differentially expressed between the cold-stressed samples and the controls. The expression patterns of 18 miRNAs were further validated by quantitative real time polymerase chain reaction (qRT-PCR). Moreover, nearly half of the miRNAs were cross inducible by biotic and abiotic stresses when compared with previously published work. Target genes were predicted and validated by degradome sequencing. Gene Ontology (GO) enrichment analysis showed that the target genes of differentially expressed miRNAs were enriched for response to the stimulus, regulation of transcription, and ion transport functions. Since many targets of differentially expressed miRNAs were transcription factors that are associated with floral development such as ARF, SPB (Squamosa Promoter Binding like protein), MADS-box (MCM1, AG, DEFA and SRF), MYB, SPX (SYG1, Pho81 and XPR1), TCP (TEOSINTE BRANCHED, Cycloidea and PCF), and PPR (PentatricoPeptide Repeat) genes, cold-altered miRNA expression may cause abnormal reproductive organ development.ConclusionAnalysis of small RNA transcriptomes and their target genes provide new insight into miRNA regulation in developing wheat inflorescences under cold stress. MiRNAs provide another layer of gene regulation in cold stress response that can be genetically manipulated to reduce yield loss in wheat.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3556-2) contains supplementary material, which is available to authorized users.

BackgroundRecently, the CRISPR/Cas9 system has been widely used to precisely edit plant genomes. Due to the difficulty in Agrobacterium-mediated genetic transformation of wheat, the reported applications in CRISPR/Cas9 system were all based on the biolistic transformation.ResultsIn the present study, we efficiently applied targeted mutagenesis in common wheat (Triticum aestivum L.) protoplasts and transgenic T0 plants using the CRISPR/Cas9 system delivered via Agrobacterium tumefaciens. Seven target sites in three genes (Pinb, waxy and DA1) were selected to construct individual expression vectors. The activities of the sgRNAs were evaluated by transforming the constructed vectors into wheat protoplasts. Mutations in the targets were detected by Illumina sequencing. Genome editing, including insertions or deletions at the target sites, was found in the wheat protoplast cells. The highest mutation efficiency was 6.8% in the DA1 gene. The CRISPR/Cas9 binary vector targeting the DA1 gene was then transformed into common wheat plants by Agrobacterium tumefaciens-mediated transformation, resulting in efficient target gene editing in the T0 generation. Thirteen mutant lines were generated, and the mutation efficiency was 54.17%. Mutations were found in the A and B genomes of the transgenic plants but not in the D genome. In addition, off-target mutations were not detected in regions that were highly homologous to the sgRNA sequences.ConclusionsOur results showed that our Agrobacterium-mediated CRISPR/Cas9 system can be used for targeted mutations and facilitated wheat genetic improvement.Electronic supplementary materialThe online version of this article (10.1186/s12870-018-1496-x) contains supplementary material, which is available to authorized users.

We previously reported a schizophrenia-associated polymorphic CT di-nucleotide repeat (DNR) at the 5′-untranslated repeat (UTR) of DPYSL2, which responds to mammalian target of Rapamycin (mTOR) signaling with allelic differences in reporter assays. Now using microarray analysis, we show that the DNR alleles interact differentially with specific proteins, including the mTOR-related protein HuD/ELAVL4. We confirm the differential binding to HuD and other known mTOR effectors by electrophoretic mobility shift assays. We edit HEK293 cells by CRISPR/Cas9 to carry the schizophrenia risk variant (13DNR) and observe a significant reduction of the corresponding CRMP2 isoform. These edited cells confirm the response to mTOR inhibitors and show a twofold shortening of the cellular projections. Transcriptome analysis of these modified cells by RNA-seq shows changes in 12.7% of expressed transcripts at a false discovery rate of 0.05. These transcripts are enriched in immunity-related genes, overlap significantly with those modified by the schizophrenia-associated gene, ZNF804A, and have a reverse expression signature from that seen with antipsychotic drugs. Our results support the functional importance of the DPYSL2 DNR and a role for mTOR signaling in schizophrenia.

Background: Recent studies indicate farnesoid X receptor (FXR) plays an important role in regulating lipid metabolism in kidney disease. The purpose of the present study is to investigate the effect of chenodeoxycholic acid (CDCA), a FXR agonist, on fibrosis, inflammation and oxidative stress in kidney in rats fed on high fructose. Methods: Twenty-four healthy male Wistar rats were randomly divided into three groups (n=8): normal control group, high fructose group and chenodeoxycholic acid group. Rats were sacrificed by the end of 16 weeks after feeding. Blood urea nitrogen, serum creatinine, fast glucose, lipid concentration were observed, spot urine samples were obtained to measure the albumin and creatinine levels. Triglyceride of renal cortices was detected. The mRNA level and protein contents of the fibrosis-inducing growth factor transforming growth factor β1 (TGF-β1) and plasminogen activator inhibitor (PAI-I), inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), oxidative stress index NADPH oxidase 2 (Nox2) and p22phox in kidney were examined. The pathological changes of kidney were examined by PAS staining and immunohistochemical staining. Electron microscope sections were made to measure glomerular basement membrane (GBM) width. Results: Renal injuries including mesangial expansion, GBM thickness and podocyte foot process effacement were found in fructose-fed Wistar rats, FXR agonist CDCA modulates renal lipid metabolism, decreases proteinuria and improves renal fibrosis, inflammation and oxidation stress. High-fructose-feeding may cause lipid nephrotoxicity through down-regulated farnesoid X receptor and increases expression of profibrotic growth factors, proinflammatory cytokines, and oxidative stress in Wistar rats. Conclusion: FXR activation by chenodeoxycholic acid can prevent the injury in kidney induced by high fructose feeding.

Background Gestational diabetes mellitus (GDM) is a common cause of maternal morbidity, and can lead to the development of diabetes later in life. Pre-pregnancy body weight is associated with the change in body mass index (BMI) between a first and second pregnancy. Compared with long-term change in BMI between pregnancies, the most accessible follow-up point to investigate BMI change is 6 weeks after the initial pregnancy. The present study aimed to assess the association between weight retention at 6 weeks postpartum and the risk of GDM in a subsequent pregnancy. Methods We recruited 6429 singleton pregnancies into this retrospective cohort study. For each pregnancy, we calculated weight retention at 6 weeks postpartum after the first pregnancy, the interpregnancy BMI change between pregnancies, and the gestational weight gain in the second pregnancy. Risk was represented by the odds ratio (OR) and 95% confidence intervals (CIs). We then determined the relationship between postpartum weight retention at 6 weeks after the initial pregnancy, and the interpregnancy change in BMI between pregnancies. Analyses were stratified by BMI during the first pregnancy. Results Compared to women with a stable BMI (− 1 to 1), interpregnancy BMI gains were associated with an increased risk of GDM in the second pregnancy. Risk increased significantly for women with a BMI below and above 25 during the first pregnancy, although the increase was greater in the women with a BMI < 25. The risk of GDM in the second pregnancy was higher in women with inadequate weight gain during the second gestation. The weight retention at 6 weeks postpartum, where there was a gain of > 3 BMI units was significantly more related to weight gain more than when there was 1 BMI unit gain between pregnancies ( P < 0.05) and associated with an increased incidence of GDM in the second pregnancy (OR = 2.95, 95% CI: 1.95 ~ 4.45). Women who showed a change in BMI that was > 3 units at 6 weeks postpartum after the first pregnancy showed an increased risk for BMI subsequently (OR = 1.42, 95% CI: 1.08~1.87). Conclusions Women who gained more than 3 BMI units at 6 weeks postpartum were associated with an increased risk of BMI in a subsequent pregnancy. Six weeks postpartum provides a new early window of opportunity to identify risk factors for a subsequent pregnancy and allows us to implement primary prevention strategies.

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