Multimodel habitats constructed by perfusion and/or diffusion MRI predict isocitrate dehydrogenase mutation status and prognosis in high-grade gliomas.

AIM: To determine whether tumour vascular and cellular heterogeneity of high-grade glioma (HGG) is predictive of isocitrate dehydrogenase (IDH) mutation status and overall survival (OS) by using tumour habitat-based analysis constructed by perfusion and/or diffusion magnetic resonance imaging (MRI). MATERIALS AND METHODS: Seventy-eight HGG patients that met the 2021 World Health Organization WHO Classification of Tumors of the Central Nervous System, 5th edition (WHO CNS5), were enrolled to predict IDH mutation status, of which 32 grade 4 patients with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter were enrolled for prognostic analysis. The deep-learning-based model nnU-Net and K-means clustering algorithm were applied to construct the Traditional Habitat, Vascular Habitat (VH), Cellular Density Habitat (DH), and their Combined Habitat (CH). Quantitative parameters were extracted and compared between IDH-mutant and IDH-wild-type patients, respectively, and the prediction potential was evaluated by receiver operating characteristic (ROC) curve analysis. OS was analysed using Kaplan-Meier survival analysis and the log-rank test. RESULTS: Compared with IDH-mutants, median relative cerebral blood volume (rCBVmedian) values in the whole enhancing tumour (WET), VH1, VH3, CH1-4 habitats were significantly increased in IDH-wild-type HGGs (all p<0.05). Additionally, the accuracy of rCBVmedian values in CH1 outperformed other habitats in identifying IDH mutation status (p<0.001) at a cut-off value of 4.83 with AUC of 0.815. Kaplan-Meier survival analysis highlighted significant differences in OS between the populations dichotomised by the median of rCBVmedian in WET, VH1, CH1-3 habitats (all p<0.05). CONCLUSIONS: The habitat imaging technique may improve the accuracy of predicting IDH mutation status and prognosis, and even provide a new direction for subsequent personalised precision treatment.

Systematic analysis of copy-number variations associated with early pregnancy loss.

OBJECTIVES: Embryonic numerical and structural chromosomal abnormalities are the most common cause of early pregnancy loss. However, the role of submicroscopic copy-number variations (CNVs) in early pregnancy loss is unclear, and little is known about the critical regions and candidate genes for miscarriage, because of the large size of structural chromosomal abnormalities. The aim of this study was to identify potential miscarriage-associated submicroscopic CNVs and critical regions of large CNVs as well as candidate genes for miscarriage. METHODS: Over a 5-year period, 5180 fresh miscarriage specimens were investigated using quantitative fluorescent polymerase chain reaction/CNV sequencing or chromosomal microarray analysis. Statistically significant submicroscopic CNVs were identified by comparing the frequency of recurrent submicroscopic CNVs between cases and a published control cohort. Furthermore, genes within critical regions of miscarriage-associated CNVs were prioritized by integrating the Residual Variation Intolerance Score and the human gene expression dataset for identification of potential miscarriage candidate genes. RESULTS: Results without significant maternal-cell contamination were obtained in 5003 of the 5180 (96.6%) cases. Clinically significant chromosomal abnormalities were identified in 59.1% (2955/5003) of these cases. Three recurrent submicroscopic CNVs (microdeletions in 22q11.21, 2q37.3 and 9p24.3p24.2) were significantly more frequent in miscarriage cases, and were considered to be associated with miscarriage. Moreover, 44 critical regions of large CNVs were observed, including 14 deletions and 30 duplications. There were 309 genes identified as potential miscarriage candidate genes through gene-prioritization analysis. CONCLUSIONS: We identified potential miscarriage candidate CNVs and genes. These data demonstrate the importance of CNVs in the etiology of miscarriage and highlight the importance of ongoing analysis of CNVs in the study of miscarriage. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Identification of Magnolia wufengensis (Magnoliaceae) cultivars using phenotypic traits, SSR and SRAP markers: insights into breeding and conservation.

A combination of phenotypic characterization and molecular markers may provide reliable information on new plant varieties and elucidate the conservation status of rare species. Five newly developed Magnolia wufengensis cultivars, an endangered plant species endemic to Hubei Province, China, possess more distinctive phenotypes than common Magnolia cultivars. With reference to a wild species population of M. wufengensis and a population of Magnolia denudata, morphological traits of flower organs, simple sequence repeat (SSR), and sequence-related amplified polymorphism (SRAP) markers were used. In the morphological study, six traits of floral organs were investigated and their relationships were analyzed between cultivars. In the genetic study, 9 SSR primer pairs and 10 SRAP primer combinations were screened. The five cultivars maintained a high level of genetic diversity. Genetic diversity of each M. wufengensis cultivar was much lower than that of the wild population, but was slightly higher than that of the M. denudata population. Analysis of molecular variance (AMOVA) revealed that genetic variation among populations was 20% (SRAP) and 30% (SSR), which showed a high degree of genetic differentiation among populations of the five cultivars. The dendrograms illustrated a clear separation between M. wufengensis populations and outer species, and identified two major groups among cultivars. Correlation analysis indicated a good fit between the two marker systems, but a relatively low fit between morphological and genetic traits (SRAP: r = 0.60, SSR: r = 0.52). These findings provide reliable references for the application of these molecular markers in the breeding and conservation of M. wufengensis.

[Production of transgenic lamb integrated with modified human anti-trypsin gene].

This experiment is to produce the human mAAT(modified anti-trypsin) which cures the emphysema specifically through mammalian galactophore of transgenic goat. 56 goats were selected as donor for superovulation by FSF + LH microinjection in this experiment. The pronucleic embryos were injected with human mAAT gene after fertilization in vivo, and transferred to the donors or receptors directly. The superovulation was better in March and May than in December with the number of ovulation of 19.50, 21.70 and 16.06, and number of fertilized embryos of 4.31, 6.48 and 3.57 per-animal respectively. The pregnant rates were 18.18% and 25% respectively after transferred to donors and receptors with natural estrus. The donors also can be used as the embryo receptor with no remarkable decrease of pregnant rate. 29 lamb were labored. 4 positive transgenic lamb were checked by PCR, PCR-Southern and Southern analysis. The integrated efficiency of foreign DNA was 13.79% with microinjection of high copy number of foreign DNA fragment.

Depletion of pre-mRNA splicing factor Cdc5L inhibits mitotic progression and triggers mitotic catastrophe.

Disturbing mitotic progression via targeted anti-mitotic therapy is an attractive strategy for cancer treatment. Therefore, the exploration and elucidation of molecular targets and pathways in mitosis are critical for the development of anti-mitotic drugs. Here, we show that cell division cycle 5-like (Cdc5L), a pre-mRNA splicing factor, is a regulator of mitotic progression. Depletion of Cdc5L causes dramatic mitotic arrest, chromosome misalignments and sustained activation of spindle assembly checkpoint, eventually leading to mitotic catastrophe. Moreover, these defects result from severe impairment of kinetochore-microtubule attachment and serious DNA damage. Genome-wide gene expression analysis reveals that Cdc5L modulates the expression of a set of genes involved in the mitosis and the DNA damage response. We further found that the pre-mRNA splicing efficiency of these genes were impaired when Cdc5L was knocked down. Interestingly, Cdc5L is highly expressed in cervical tumors and osteosarcoma. Finally, we demonstrate that downregulation of Cdc5L decreases the cell viability of related tumor cells. These results suggest that Cdc5L is a key regulator of mitotic progression and highlight the potential of Cdc5L as a target for cancer therapy.

Image synthesizing for all-weather outdoor scenes.

Lighting simulation and image synthesis for outdoor scenes are difficult because of the geometric complexity and the presence of lighting interaction and atmospheric extinction in the outdoor environment. An efficient method of image synthesis by use of a linear combination of basic images is presented. With respect to linearity of the illumination function, the coefficients of basic images of various Sun positions and sky situations can be calculated. Furthermore, the relationship among visibility distance, image contrast, and resolution is addressed so that the desired images can be generated under all weather conditions. It is shown that a uniform formula is available and feasible for fixed scene and camera geometry.