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To break the narrow diversity bottleneck of the wheat D genome, a set of Aegilops tauschii-wheat introgression (A-WI) lines was developed by crossing Ae. tauschii accession T015 with common wheat elite cultivar Zhoumai 18 (Zhou18). A high-density genetic map was constructed based on Single Nucleotide Polymorphism (SNP) markers and 15 yield-related traits were evaluated in 11 environments for detecting quantitative trait loci (QTL). A total of 27 environmentally stable QTL were identified in at least five environments, 20 of which were derived from Ae. tauschii T015, explaining up to 24.27% of the phenotypic variations. The major QTL for kernel length (KL), QKl-2D.5, was delimited to a physical interval of approximately 2.6 Mb harboring 52 candidate genes. Three Kompetitive Allele Specific PCR (KASP) markers were successfully developed based on nonsynonymous nucleotide mutations of candidate gene AetT093_2Dv1G100900.1 and showed that A-WI lines with the T015 haplotype had significantly longer KL than the Zhou18 haplotype across all 11 environments. Four primary valuable A-WIs with good trait performance and carrying yield-related QTL were selected for breeding improvement. The results will facilitate the efficient transfer of beneficial genes from Ae. tauschii into wheat cultivars to improve wheat yield and other traits. [ABSTRACT FROM AUTHOR]

Introduction: Identification of stable major quantitative trait loci (QTLs) for yieldrelated traits is important for yield potential improvement in wheat breeding. Methods: In the present study, we genotyped a recombinant inbred line (RIL) population using the Wheat 660K SNP array and constructed a high-density genetic map. The genetic map showed high collinearity with the wheat genome assembly. Fourteen yield-related traits were evaluated in six environments for QTL analysis. Results and Discussion: A total of 12 environmentally stable QTLs were identified in at least three environments, explaining up to 34.7% of the phenotypic variation. Of these, QTkw-1B.2 for thousand kernel weight (TKW), QPh-2D.1 (QSl-2D.2/QScn-2D.1) for plant height (PH), spike length (SL) and spikelet compactness (SCN), QPh-4B.1 for PH, and QTss-7A.3 for total spikelet number per spike (TSS) were detected in at least five environments. A set of Kompetitive Allele Specific PCR (KASP) markers were converted based on the above QTLs and used to genotype a diversity panel comprising of 190 wheat accessions across four growing seasons. QPh-2D.1 (QSl-2D.2/QScn-2D.1), QPh-4B.1 and QTss-7A.3 were successfully validated. Compared with previous studies, QTkw-1B.2 and QPh-4B.1 should be novel QTLs. These results provided a solid foundation for further positional cloning and marker-assisted selection of the targeted QTLs in wheat breeding programs. [ABSTRACT FROM AUTHOR]

Background: Cytokeratin is associated with the recurrence and metastasis of some cancers and tends to increase the malignancy of the disease. It is getting more and more attention in cancer research. Abnormal expression of cytokeratin 19 (CK19) has been reported as an important prognostic factor in cancers. CK19 is a marker of bile duct cells, liver progenitor cells (HPCs), and early hepatoblasts, and its expression is associated with poor prognosis in patients diagnosed with hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the predictive value of CK19 for tumor recurrence after radical resection in patients with hepatitis B virus (HBV) positive HCC. Methods: This study was a retrospective study conducted in two institutions. A total of 674 patients with HBV positive HCC who underwent radical HCC resection from January 2010 to May 2020 were included in this study. Chi-square test or Fisher's exact test was used to compare the classification variables and continuous variables were compared by t-test or Wilcoxon rank sum test. Cox regression model was used for univariate and multi-variable survival analyses. Based on the results of the multi-variable analyses of Cox regression, the nomogram of 2-year recurrence-free survival (RFS) was plotted. The model was validated internally in the Hangzhou cohort (training set) and then externally in the Lanzhou cohort (test set) and the effectiveness of the model was tested. Results: For all 674 patients, 223 cases (33.1%) were positive and 451 cases (66.9%) were negative for CK19. The 2-year RFS rate was higher in patients with CK19 negative than in patients with CK19 positive. In the training set, correlation analysis showed that CK19 expression was correlated with preoperative potassium (P value(P) = 0.030), satellite nodules (P < 0.001) and microvascular invasion (P = 0.020). In the test set, CK19 expression was correlated with postoperative platelet (P = 0.038), satellite nodules (P = 0.003), microvascular invasion (P = 0.011), and maximum tumor size (P = 0.039). Univariate Cox regression correlation analyses showed that CK19 expression was correlated with preoperative potassium (P value(P) = 0.030), satellite nodules (P < 0.001), and microvascular invasion (P = 0.020). Training and test sets showed that postoperative platelet (> 300/L), CK19, satellite nodules in the training set, microvascular invasion, maximum tumor size, and tumor boundary were adverse factors for predicting RFS. Multi-variable analyses showed that in the training set, postoperative platelet > 300/L (hazard ratios (HR) = 2.753, 95% confidence interval (95%CI):1.234–6.142, P = 0.013), CK19 (HR = 1.410, 95%CI:1.006–1.976, P = 0.046), satellite nodule (HR = 1.476, 95%CI:1.026–2.120, P = 0.036), microvascular invasion (HR = 2.927, 95%CI:2.006–4.146, P < 0.001), incomplete tumor capsule (HR = 1.539, 95%CI:1.012–2.341, P = 0.044) were independent prognostic indicator of poor RFS. In the test set, postoperative platelet > 300/L (HR = 2.816, 95%CI:1.043–7.603, P = 0.041), CK19 (HR = 1.586, 95%CI:1.016–2.475, P = 0.042), satellite nodule (HR = 1.706, 95%CI:1.067–2.728, P = 0.026), microvascular invasion (HR = 1.611, 95%CI:1.034–2.510, P = 0.035), and tumor without capsule (HR = 1.870, 95%CI:1.120–3.120, P = 0.017) were independent prognostic indicators of poor RFS. The C-index for the nomogram was 0.698 (95%CI: 0.654–0.742) and the C-index for the test set was 0.670 (95%CI: 0.616–0.724). Both internal and external verification showed good results in identification and calibration. Conclusion: CK19 plays a key role in tumor malignancy through overexpression and the expression of CK19 is an independent adverse factor affecting recurrence; therefore, CK19 can be used as a potential biomarker to predict adverse prognosis after surgery and adjuvant therapy in HCC patients. [ABSTRACT FROM AUTHOR]

Background: Folic acid (FA) is an antioxidant that can reduce reactive oxygen species generation and can blunt cardiac dysfunction during ischemia. We hypothesized that FA supplementation prevents cardiac fibrosis and cardiac dysfunction induced by obesity. Methods: Six-week-old C57BL6/J mice were fed a high-fat diet (HFD), normal diet (ND), or an HFD supplemented with folic acid (FAD) for 14 weeks. Cardiac function was measured using a transthoracic echocardiographic exam. Phenotypic analysis included measurements of body and heart weight, blood glucose and tissue homocysteine (Hcy) content, and heart oxidative stress status. Results: HFD consumption elevated fasting blood glucose levels and caused obesity and heart enlargement. FA supplementation in HFD-fed mice resulted in reduced fasting blood glucose, heart weight, and heart tissue Hcy content. We also observed a significant cardiac systolic dysfunction when mice were subjected to HFD feeding as indicated by a reduction in the left ventricular ejection fraction and fractional shortening. However, FAD treatment improved cardiac function. FA supplementation protected against cardiac fibrosis induced by HFD. In addition, HFD increased malondialdehyde concentration of the heart tissue and reduced the levels of antioxidant enzyme, glutathione, and catalase. HFD consumption induced myocardial oxidant stress with amelioration by FA treatment. Conclusion: FA supplementation significantly lowers blood glucose levels and heart tissue Hcy content and reverses cardiac dysfunction induced by HFD in mice. These functional improvements of the heart may be mediated by the alleviation of oxidative stress and myocardial fibrosis. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are implicated in the pathogenesis of obesity. The aim of the present study was to characterize the miRNA profile associated with early childhood obesity in peripheral blood mononuclear cells (PBMCs). A total of 12 children (6 obese and 6 lean controls) aged 36 months old to 48 months old were recruited. The miRNA expression profile from PBMCs was detected using the multiplexed NanoString nCounter system. Bioinformatics was employed to detect target genes and miRNA‑regulated biological function. A total of 9 differentially expressed miRNAs were identified in obese children compared with lean children (P<0.05). Among the 9 miRNAs, miR‑199a‑3p/miR‑199b‑3p and miR‑4454 presented at least a 1.5‑fold change in expression. A total of 643 potential target genes were regulated by the three miRNAs, and 291 of the potential genes were involved in a protein interaction network. Gene ontology annotation indicated that 291 potential genes were enriched in 14 biological process annotations and 2 molecular function annotations. miRNA dysregulation may be involved in early childhood obesity. [ABSTRACT FROM AUTHOR]

At present, most of released wheat cultivars or breeding lines in China are susceptible to powdery mildew (Pm) (caused by Blumeria graminis f. sp. tritici, Bgt), so there is an urgent need to rapidly transfer effective and broad-spectrum Pm resistance genes into elite cultivars/lines. Near-isogenic lines (NILs) with short target gene region are very important in molecular breeding and map-based cloning and can be developed by combining marker-assisted selection and conventional phenotypic identification. However, no Pm gene NILs were reported by using this method in the previous studies. A new broad-spectrum dominant resistance gene Pm2b, derived from the Chinese wheat breeding line KM2939, conferred high resistance to Pm at both the seedling and adult stages. In this study, with the aid of forward and background selection (FS and BS) using molecular markers, the Pm2b gene was introgressed into three elite susceptible commercial cultivars Shimai 15, Shixin 828, and Kenong 199 through the back-crossing procedure. With the appropriate backcrossing generations, selected population sizes and marker number for BS, the homozygous resistant BC3F2:3 NILs of Pm2b gene in the three genetic backgrounds with the highest recipient genome composition of about 99%, confirmed by simple sequence repeat markers and 660K single nucleotide polymorphic array, were developed and evaluated for the powdery mildew resistance and agronomic traits. The different resistance and similar or improved agronomic performance between Pm2b NILs and their corresponding recurrent parents indicated their potential value in the marker-assisted breeding of the Pm2b gene. Moreover, the development of four flanked diagnostic markers (CFD81, BWM25, BWM20, and BWM21) of the Pm2 gene can effectively assist the forward selection and accelerate the transfer and use of this resistance gene. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are important post-transcriptional regulators during adipocyte adipogenesis. MiR-206-3p, a tissue-specific miRNA, is absent in white adipocytes. In this study, we examined the roles of mmu-miR-206-3p in the adipogenic differentiation of 3T3-L1 preadipocytes. The miR-206-3p expression has shown an apparent decreasing trend after induction, and sustained low expression throughout the differentiation of 3T3-L1 cells. miR-206-3p blocked the adipogenic differentiation of 3T3-L1 cells by attenuating c-Met expression; the inhibition effect of miR-206 to the adipogenic differentiation can be counteracted by restoring c-Met expression. In addition, miR-206-3p decreased the phosphorylation of Akt, which is the downstream effector of c-Met in the PI3K/Akt signaling pathway. These data indicate that miR-206-3p inhibits adipocyte adipogenesis through silencing c-Met and subsequently inactivating the PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Background: To describe the characteristics of patients with syphilitic uveitis in northern China.Methods: A case series of 21 patients (33 eyes) diagnosed with syphilitic uveitis from 2011 to 2016 at a tertiary center in northern China was retrospectively analyzed.Results: Twenty-one patients (33 eyes) were diagnosed as syphilitic uveitis. Posterior segment involvement was found in 32 eyes (97.0%). Vitreous haze, neuroretinitis, and posterior placoid chorioretinitis were mainly found in patients with a relatively short duration of the disease, while diffuse chorioretinitis, pseudoretinitis pigmentosa, cystoid macular edema, and epiretinal membrane were found in patients with relatively long duration of ocular involvement. A low best-corrected visual acuity (P = 0.022) and a delay of syphilis treatment (P < 0.001) were associated with a significantly worse visual outcome.Conclusions: Syphilitic uveitis should be included in the differential diagnosis of any form of posterior ocular inflammation. The pattern of ocular involvement may change with the disease progression. [ABSTRACT FROM AUTHOR]

Background/Aims: Obesity is a major contributor to the growing prevalence of metabolic and cardiovascular diseases. This study was designed to investigate the effect of folic acid (FA) on obese mice by detecting the genome-wide expression profile of lncRNAs and mRNAs in the heart. Methods: Heart samples were collected from mice fed with standard diet (SD), high- fat diet (HFD) and high-fat diet with FA intake (HFDF). LncRNAs and mRNAs between HFD and HFDF group were analyzed by lncRNA microarray. Nine lncRNAs and mRNAs were validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Bioinformatics prediction was used to investigate the potential function of these differentially expressed lncRNAs. Co-expresson analysis was used to determine the transcriptional regulatory relationship of differentially expressed lncRNAs and mRNAs between two groups. Results: The expression of 58,952 lncRNAs and 20,145 mRNAs in HFD and HFDF groups was profiled by using microarrays. Gene Ontology and pathway analyses indicated that the biological functions of differentially expressed mRNAs were related to inflammation, energy metabolism, and cell differentiation. Co-expression networks composed of lncRNAs and mRNAs were also constructed to investigate the potential regulatory roles of differentially expressed lncRNAs on mRNAs. LncRNAs, namely, NONMMUT033847, NONMMUT070811, and NONMMUT015327, were validated through qRT-PCR, and these lncRNAs may be important factors regulating inflammation, energy metabolism, and cell differentiation. The expression levels of Dnajbl, Egr2, Hba-a1, Illß, Cxcl2, and Tnfsf9 were significantly different between HFD and HFDF. Conclusions: Results suggested that FA may improve the cardiovascular function of obesity and contribute to those lncRNAs associated with inflammation and cell differentiation. In a nutshell, the present study identified a panel of lncRNAs and mRNAs that may be potential biomarkers or drug targets relevant to the high-fat diet related obesity. [ABSTRACT FROM AUTHOR]

To predict the subcellular location of ascorbate peroxidase 1 (APX1) protein in Arabidopsis thaliana, a plasmid expressing APX1-enhance green fluorescent protein (EGFP) fusion protein was constructed, transformed into Agrobacterium tunwfaciens GV3101, and transiently expressed in tobacco leaves. The localization of APX1 protein in the ceHs was determined by detecting the distribution of the fusion protein in tobacco epidermal cells. The results showed APX1 protein was mainly distributed in the cytoplasm of the plant. [ABSTRACT FROM AUTHOR]

Increasing evidence has demonstrated that changes in plasma nuclear matrix proteins are specific markers of cancer. Furthermore, proteomic analysis has revealed that calponin-h2 is upregulated in human breast cancer tissue, but is absent in healthy and benign controls. However, the roles of levels of plasma calponin-h2 in the diagnosis of breast cancer and its association with clinicopathological parameters remain to be elucidated. In the present study, the plasma levels of calponin-h2 in patients with breast cancer, benign breast disease and in healthy controls were examined using an enzyme-linked immunosorbent assay. The expression levels of calponin-h2 in invasive breast cancer and normal breast tissues were measured using immunohistochemistry. Statistical analyses examined the association between the levels of plasma calponin-h2 and clinicopathological parameters. The results demonstrated that the plasma level of calponin-h2 in breast cancer was significantly higher than those in the healthy control and benign breast disease groups (P<0.05). The combination of calponin-h2, carcinoembryonic antigen, carbohydrate antigen 15-3 improved the diagnosis of breast cancer. The plasma levels of calponin-h2 PR- breast cancers was significantly higher, compared with PR+ breast cancers (P=0.033), and the plasma levels of calponin-h2 in patients with breast cancer aged >50 years was significantly higher than in patients ≤50 years of age (P=0.001). No association was found between the level of plasma calponin-h2 and other clinicopathological parameters of breast cancer. Taken together, these results indicated that calponin-h2 may be a useful marker of breast cancer. [ABSTRACT FROM AUTHOR]

Interleukin-6 (IL-6) is an important cytokine participating in multiple biologic activities in immune regulation and inflammation. IL-6 has been associated with cardiovascular remodeling. However, the mechanism of IL-6 in hypertensive cardiac fibrosis is still unclear. Angiotensin II (Ang II) infusion in mice increased IL-6 expression in the heart. IL-6 knockout (IL- 6-/-) reduced Ang II-induced cardiac fibrosis: 1) Masson trichrome staining showed that Ang II infusion significantly increased fibrotic areas of the wild-type mouse heart, which was greatly suppressed in IL-6-/- mice and 2) immunohistochemistry staining showed decreased expression of a-smooth muscle actin (a-SMA), transforming growth factor α1 (TGF-α1) and collagen I in IL-6-/- mouse heart. The baseline mRNA expression of IL-6 in cardiac fibroblasts was low and was absent in cardiomyocytes or macrophages; however, co-culture of cardiac fibroblasts with macrophages significantly increased IL-6 production and expression of a-SMA and collagen I in fibroblasts. Moreover, TGF-α1 expression and phosphorylation of TGF-α downstream signal Smad3 was stimulated by co-culture of macrophages with cardiac fibroblasts, while IL-6 neutralizing antibody decreased TGF-α1 expression and Smad3 phosphorylation in co-culture of macrophage and fibroblast. Taken together, our results indicate that macrophages stimulate cardiac fibroblasts to produce IL-6, which leads to TGF-α1 production and Smad3 phosphorylation in cardiac fibroblasts and thus stimulates cardiac fibrosis. [ABSTRACT FROM AUTHOR]