Validation of the children international IgA nephropathy prediction tool based on data in Southwest China

BackgroundImmunoglobulin A nephropathy (IgAN) is one of the most common kidney diseases leading to renal injury. Of pediatric cases, 25%–30% progress into end-stage kidney disease (ESKD) in 20–25 years. Therefore, predicting and intervening in IgAN at an early stage is crucial. The purpose of this study was to validate the availability of an international predictive tool for childhood IgAN in a cohort of children with IgAN treated at a regional medical centre.MethodsAn external validation cohort of children with IgAN from medical centers in Southwest China was formed to validate the predictive performance of the two full models with and without race differences by comparing four measures: area under the curve (AUC), the regression coefficient of linear prediction (PI), survival analysis curves for different risk groups, and R2D.ResultsA total of 210 Chinese children, including 129 males, with an overall mean age of 9.43 ± 2.71 years, were incorporated from this regional medical center. In total, 11.43% (24/210) of patients achieved an outcome with a GFR decrease of more than 30% or reached ESKD. The AUC of the full model with race was 0.685 (95% CI: 0.570–0.800) and the AUC of the full model without race was 0.640 (95% CI: 0.517–0.764). The PI of the full model with race and without race was 0.816 (SE = 0.006, P < 0.001) and 0.751 (SE = 0.005, P < 0.001), respectively. The results of the survival curve analysis suggested the two models could not well distinguish between the low-risk and high-risk groups (P = 0.359 and P = 0.452), respectively, no matter the race difference. The evaluation of model fit for the full model with race was 66.5% and without race was 56.2%.ConclusionsThe international IgAN prediction tool has risk factors chosen based on adult data, and the validation cohort did not fully align with the derivation cohort in terms of demographic characteristics, clinical baseline levels, and pathological presentation, so the tool may not be highly applicable to children. We need to build IgAN prediction models that are more applicable to Chinese children based on their particular data

Defining Global Gene Expression Changes of the Hypothalamic-Pituitary-Gonadal Axis in Female sGnRH-Antisense Transgenic Common Carp (Cyprinus carpio)

BACKGROUND: The hypothalamic-pituitary-gonadal (HPG) axis is critical in the development and regulation of reproduction in fish. The inhibition of neuropeptide gonadotropin-releasing hormone (GnRH) expression may diminish or severely hamper gonadal development due to it being the key regulator of the axis, and then provide a model for the comprehensive study of the expression patterns of genes with respect to the fish reproductive system. METHODOLOGY/PRINCIPAL FINDINGS: In a previous study we injected 342 fertilized eggs from the common carp (Cyprinus carpio) with a gene construct that expressed antisense sGnRH. Four years later, we found a total of 38 transgenic fish with abnormal or missing gonads. From this group we selected the 12 sterile females with abnormal ovaries in which we combined suppression subtractive hybridization (SSH) and cDNA microarray analysis to define changes in gene expression of the HPG axis in the present study. As a result, nine, 28, and 212 genes were separately identified as being differentially expressed in hypothalamus, pituitary, and ovary, of which 87 genes were novel. The number of down- and up-regulated genes was five and four (hypothalamus), 16 and 12 (pituitary), 119 and 93 (ovary), respectively. Functional analyses showed that these genes involved in several biological processes, such as biosynthesis, organogenesis, metabolism pathways, immune systems, transport links, and apoptosis. Within these categories, significant genes for neuropeptides, gonadotropins, metabolic, oogenesis and inflammatory factors were identified. CONCLUSIONS/SIGNIFICANCE: This study indicated the progressive scaling-up effect of hypothalamic sGnRH antisense on the pituitary and ovary receptors of female carp and provided comprehensive data with respect to global changes in gene expression throughout the HPG signaling pathway, contributing towards improving our understanding of the molecular mechanisms and regulative pathways in the reproductive system of teleost fish

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Structural Characterization and Antioxidant Activity of Milled Wood Lignin from Xylose Residue and Corncob

Xylose residue (XR), after diluted acid treatment of corncob, consists of cellulose and lignin. However, structural changes of XR lignin have not been investigated comprehensively, and this has seriously hindered the efficient utilization of lignin. In this study, corncob milled wood lignin (CC MWL), and xylose residue milled wood lignin (XR MWL) were isolated according to the modified milled wood lignin (MWL) method. The structural features of two lignin fractions were thoroughly investigated via fourier transform infrared spectroscopy (FTIR), gel permeation chromatography (GPC), thermogravimetric analysis (TGA) and two dimensional nuclear magnetic resonance (2D NMR) spectroscopy techniques. XR MWL with higher yield and lower bound carbohydrate contents presented more phenolic OH contents than CC MWL due to partial cleavage of β-O-4. Furthermore, the molecular weights of XR MWL were increased, possibly because of condensation of the lignin during the xylose production. A study on antioxidant activity showed that XR lignin had better radical scavenging ability than that of 2,6-Di-tert-butyl-4-methyl-phenol (BHT) and CC MWL. The results suggested that the lignin in xylose residue, showing great antioxidant properties, has potential applications in food additives

Mettl3 Mutation Disrupts Gamete Maturation and Reduces Fertility in Zebrafish

N-6-methyladenosine (m(6)A), catalyzed by Mettl3 methyltransferase, is a highly conserved epigenetic modification in eukaryotic messenger RNA (mRNA). Previous studies have implicated m(6)A modification in multiple biological processes, but the in vivo function of m(6)A has been difficult to study, because mettl3 mutants are embryonic lethal in both mammals and plants. In this study, we have used transcription activator-like effector nucleases and generated viable zygotic mettl3 mutant, Zmettl3(m/m), in zebrafish. We find that the oocytes in Zmettl3(m/m) adult females are stalled in early development and the ratio of full-grown stage (FG) follicles is significantly lower than that of wild type. Human chorionic gonadotropin-induced ovarian germinal vesicle breakdown in vitro and the numbers of eggs ovulated in vivo are both decreased as well, while the defects of oocyte maturation can be rescued by sex hormone in vitro and in vivo. In Zmettl3(m/m) adult males, we find defects in sperm maturation and sperm motility is significantly reduced. Further study shows that 11-ketotestosterone (11-KT) and 17-estradiol (E2) levels are significantly decreased in Zmettl3(m/m), and defective gamete maturation is accompanied by decreased overall m(6)A modification levels and disrupted expression of genes critical for sex hormone synthesis and gonadotropin signaling in Zmettl3(m/m). Thus, our study provides the first in vivo evidence that loss of Mettl3 leads to failed gamete maturation and significantly reduced fertility in zebrafish. Mettl3 and m(6)A modifications are essential for optimal reproduction in vertebrates.</p

Transcriptomic analysis reveals the molecular basis of photoperiod-regulated sex differentiation in tropical pumpkins (Cucurbita moschata Duch.)

Abstract Background Photoperiod, or the length of the day, has a significant impact on the flowering and sex differentiation of photoperiod-sensitive crops. The “miben” pumpkin (the main type of Cucurbita moschata Duch.) is well-known for its high yield and strong disease resistance. However, its cultivation has been limited due to its sensitivity to photoperiod. This sensitivity imposes challenges on its widespread cultivation and may result in suboptimal yields in regions with specific daylength conditions. As a consequence, efforts are being made to explore potential strategies or breeding techniques to enhance its adaptability to a broader range of photoperiods, thus unlocking its full cultivation potential and further promoting its valuable traits in agriculture. Results This study aimed to identify photoperiod-insensitive germplasm exhibiting no difference in sex differentiation under different day-length conditions. The investigation involved a phenotypic analysis of photoperiod-sensitive (PPS) and photoperiod-insensitive (PPIS) pumpkin materials exposed to different day lengths, including long days (LDs) and short days (SDs). The results revealed that female flower differentiation was significantly inhibited in PPS_LD, while no differences were observed in the other three groups (PPS_SD, PPIS_LD, and PPIS_SD). Transcriptome analysis was carried out for these four groups to explore the main-effect genes of sex differentiation responsive to photoperiod. The main-effect gene subclusters were identified based on the principal component and hierarchical cluster analyses. Further, functional annotations and enrichment analysis revealed significant upregulation of photoreceptors (CmCRY1, F-box/kelch-repeat protein), circadian rhythm-related genes (CmGI, CmPRR9, etc.), and CONSTANS (CO) in PPS_LD. Conversely, a significant downregulation was observed in most Nuclear Factor Y (NF-Y) transcription factors. Regarding the gibberellic acid (GA) signal transduction pathway, positive regulators of GA signaling (CmSCL3, CmSCL13, and so forth) displayed higher expression levels, while the negative regulators of GA signaling, CmGAI, exhibited lower expression levels in PPS_LD. Notably, this effect was not observed in the synthetic pathway genes. Furthermore, genes associated with ethylene synthesis and signal transduction (CmACO3, CmACO1, CmERF118, CmERF118-like1,2, CmWIN1-like, and CmRAP2-7-like) showed significant downregulation. Conclusions This study offered a crucial theoretical and genetic basis for understanding how photoperiod influences the mechanism of female flower differentiation in pumpkins

Growth hormone transgene effects on growth performance are inconsistent among offspring derived from different homozygous transgenic common carp (Cyprinus carpio L.)

Higher productivity of cultivated fish is required to sustain the supply of fisheries products in the light of increasing demand. We established different lines of homozygous growth hormone (GH) transgenic common carp and analyzed their biological characteristics. Comparing transgenic and control larvae derived from the same control fish mother, we found there was no significant difference in fertilization and hatch rates, but that hatch timing was advanced and average total length was significantly longer in transgenic carp. Early growth performance and other biological characteristics were compared among homozygous, hemizygous and control fish. Both the #TG2 and #TG3 lines exhibited greater average body weight, specific growth rate (SGR), feed conversion efficiency (FCE) and protein retention efficiency (PRE), as well as lower feeding rate (FR) and lipid and energy content than control fish. The energy retention efficiency (ERE) was significantly lower in the #TG3 line, while no difference was observed between the #TG2 line and control fish. These results indicate that the GH transgene initiated effects on growth enhancement in the early developmental stages and played an important role in improving protein synthesis and lipolysis. Conversely, homozygous transgenic fish No. 14960 grew faster than the control fish, but the culture traits of its hemizygous offspring (#TG1 line) were comparatively reduced, including lower SGR, FCE, PRE and ERE levels, and higher FR and lipid contents. Our results suggest that even if fast-growing GH-transgenic homozygous parental fish are generated, we still need to practice classical selective breeding in order to produce transgenic fish with improved traits that can meet aquaculture demand. (C) 2012 Elsevier B. V. All rights reserved.Higher productivity of cultivated fish is required to sustain the supply of fisheries products in the light of increasing demand. We established different lines of homozygous growth hormone (GH) transgenic common carp and analyzed their biological characteristics. Comparing transgenic and control larvae derived from the same control fish mother, we found there was no significant difference in fertilization and hatch rates, but that hatch timing was advanced and average total length was significantly longer in transgenic carp. Early growth performance and other biological characteristics were compared among homozygous, hemizygous and control fish. Both the #TG2 and #TG3 lines exhibited greater average body weight, specific growth rate (SGR), feed conversion efficiency (FCE) and protein retention efficiency (PRE), as well as lower feeding rate (FR) and lipid and energy content than control fish. The energy retention efficiency (ERE) was significantly lower in the #TG3 line, while no difference was observed between the #TG2 line and control fish. These results indicate that the GH transgene initiated effects on growth enhancement in the early developmental stages and played an important role in improving protein synthesis and lipolysis. Conversely, homozygous transgenic fish No. 14960 grew faster than the control fish, but the culture traits of its hemizygous offspring (#TG1 line) were comparatively reduced, including lower SGR, FCE, PRE and ERE levels, and higher FR and lipid contents. Our results suggest that even if fast-growing GH-transgenic homozygous parental fish are generated, we still need to practice classical selective breeding in order to produce transgenic fish with improved traits that can meet aquaculture demand. (C) 2012 Elsevier B. V. All rights reserved