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Wheat stripe rust is one of the most destructive diseases to affect wheat. Although the major resistant wheat varieties have made a great contribution to global food security, yield losses from stripe rust still occur in large wheat growing areas when climatic conditions are unstable. Despite this threat, resistance levels and yield losses of these elite wheat cultivars under wheat stripe rust infection have not been well studied. Based on this investigation of natural infection conditions over 2 years, analysis of the area-under-the-disease-progress-curves differentiated the susceptible cultivars Mianmai 367 (MM367; 788.59), Jinmai 47 (JM47; 1,087.71), and Avocet Susceptible (AvS; 1,314.59) from resistant cultivars Xikemai 18 (XKM18; 177.50) and Xiaoyan 6 (XY6; 545.67). Stripe rust resulted in a 2-year mean yield loss of 32% for all tested varieties. The susceptible varieties JM47, AvS, and MM367 lost 64, 55, and 21% of grain yield, respectively. On the contrary, rust-resistant cultivars XKM18 and XY6 lost only 11 and 28%, respectively. In addition, stripe rust resulted in reduced kernel hardness, flour yield, and flour whiteness. Dough and gluten properties were also affected. Overall, results revealed that the grain yield and quality loss values of the resistant wheat cultivars were less than in the susceptible cultivars. Disease-resistant cultivars such as XKM18 should be promoted and recommended for application. It may also be suggested that growing a susceptible variety such as MM367 could be feasible in combination with fungicide application under high disease pressure. [ABSTRACT FROM AUTHOR]

Chronic hypothyroidism is associated with an increased risk for cardiovascular disease attributed, in part, to increased serum cholesterol and atherosclerosis. Decreased hepatic activity of cholesterol 7a-hydroxylase (CYP7A1) is thought to contribute to hypercholesterolemia in hypothyroidism. The endoplasmic reticulum (ER) has been shown to be a central organelle, and it is the location of CYP7A1 in hepatocyte. The aim of the present study was to determine whether the expression of CYP7A1 mRNA and protein could be decreased and whether ER could undergo morphological changes in a rodent model of chronic hypothyroidism induced by methimazole (MMI). Male Wistar rats were treated with MMI (0.04% wt/vol) or regular water for 14 weeks. Hepatic CYP7A1 mRNA was analyzed on quantitative real-time polymerase chain reaction (PCR). Hepatic CYP7A1 protein expression was assessed on western blot. In conjunction with these molecular biological assessments the morphology of ER was evaluated on transmission electron microscopy (TEM). Serum total cholesterol increased significantly compared to controls and was associated with decreased CYP7A1 mRNA and protein, and TEM indicated remarkable dilation of ER in hepatocytes in the chronic hypothyroid rats. These findings suggest that a relationship between the decreased expression of hepatic CYP7A1 mRNA and protein and dilated ER could exist, which may contribute to hypercholesterolemia in chronic hypothyroidism. [ABSTRACT FROM AUTHOR]

Due to the complicated metabolic and regulatory networks of L-serine biosynthesis and degradation, microbial cell factories for L-serine production using non-model microorganisms have not been reported. In this study, a combination of synthetic biology and process optimization were applied in an ethanologenic bacterium Zymomonas mobilis for L-serine production. By blocking the degradation pathway while introducing an exporter EceamA from E. coli, L-serine titer in recombinant Z. mobilis was increased from 15.30 mg/L to 62.67 mg/L. It was further increased to 260.33 mg/L after enhancing the L-serine biosynthesis pathway. Then, 536.70 mg/L L-serine was achieved by removing feedback inhibition with a SerA mutant, and an elevated titer of 687.67 mg/L was further obtained through increasing serB copies while enhancing the precursors. Finally, 855.66 mg/L L-serine can be accumulated with the supplementation of the glutamate precursor. This work thus not only constructed an L-serine producer to help understand the bottlenecks limiting L-serine production in Z. mobilis for further improvement, but also provides guidance on engineering non-model microbes to produce biochemicals with complicated pathways such as amino acids or terpenoids. [ABSTRACT FROM AUTHOR]

In flowering plants, the inflorescence meristem (IM) provides founder cells to form successive floral meristems, which are precursors of fruits and seeds. The activity and developmental progression of IM are thus critical for yield production in seed crops. In some cereals, such as rice (Oryza sativa) and maize (Zea mays), the size of undifferentiated IM, which is located at the inflorescence apex, is positively associated with yield traits such as spikelet number. However, the relationship between IM size and yieldrelated spike traits remains unknown in the Triticeae tribe. Here we report that IM size has a negative correlation with yield traits in barley (Hordeum vulgare). Three FASCIATED EAR (FEA) orthologs, HvFEA2, HvFEA3, and HvFEA4, regulate IM size and spike morphogenesis and ultimately affect yield traits. Three HvFEAs genes are highly expressed in developing spikes, and all three loss-of-function mutants exhibit enlarged IM size, shortened spikes, and reduced spikelet number, which may lead to reduced grain yield. Natural variations identified in HvFEAs indicate selection events during barley domestication. We further reveal that HvFEA4, as a transcription factor, potentially targets multiple pathways during reproductive development, including transcriptional control, phytohormone signaling, and redox status. The roles of barley FEA genes in limiting IM size and promoting spikelet formation suggest the potential of increasing yield by manipulating IM activity. [ABSTRACT FROM AUTHOR]

Purpose: A preliminary analysis on the risk factors of liver dysfunction was made after the investigation of hepatitis B prevalence and chemotherapy-related hepatic dysfunction occurrence for patients with lung cancer. Patients and methods: Consecutively diagnosed 950 lung cancer patients treated in Huashan Hospital, Fudan University from 1999 to 2009 were enrolled in the study. We investigated hepatitis B (HB) prevalence and analyzed chemotherapy-related hepatic dysfunction occurrence and its influencing factors. Liver dysfunction was considered when alanine transaminase, aspartate aminotransferase, and serum bilirubin levels exceeded at least 1.25-fold of normal levels, and HB statuses were categorized into diagnosed HB, previous HB infection, HB immunity, and no HB infection. Results: Among the 950 lung cancer patients, 632 accepted the HB serum marker tests: 8.4 % (53/632) were HB surface antigen positive, and 37.2 % (235/632) were HB core antibody positive. A number of 281 patients received liver function follow-up examinations after they underwent a total of 774 chemotherapy courses, and 34 liver dysfunctions were detected. A logistic regression analysis showed that younger age at diagnosis (≤60 years; P = 0.029) and abnormal liver function before chemotherapy ( P = 0.000) were the risk factors for liver dysfunctions after chemotherapy, but HB status had no influence. Conclusions: The screening rates for serum HB marker and HB prevalence in patients with lung cancer were high in mainland China. Lung cancer patients with abnormal liver function before chemotherapy and in younger ages had higher risks for liver dysfunctions after chemotherapies, whereas HB status before the first chemotherapy is not an independent impact factor for post-treatment liver dysfunctions. [ABSTRACT FROM AUTHOR]

Abstract: Cheap and reusable task-specific ionic liquids that bear an alkanesulfonic acid group in an acyclic trialkylammonium cation were found to be effective catalysts for synthesizing 3,4-dihydropyrimidine-2-(1H)-ones via the one-pot three-component Biginelli reaction. The satisfactory results were obtained with good yields, short reaction time and simplicity in the experimental procedure. The catalysts could be recycled and reused six times without noticeably decrease in the catalytic activity. [Copyright &y& Elsevier]

Androgen insensitivity syndrome (AIS; OMIM 300068) is the most frequent cause of 46, XY disorders of sex development (DSD). However, the correlation between genotype and phenotype has not been determined. We conducted a systematic analysis of the clinical characteristics, hormone levels, ultrasonography data and histopathology of a 46, XY Chinese patient with AIS. The family was followed up for nearly 8 years. We applied whole-exome sequencing (WES) for genetic analysis of the pedigree and performed bioinformatic analysis of the identified variants. Human embryonic kidney 293T/17 (HEK293T/17) cells were transiently transfected with wild-type or mutant AR and MAP3K1 plasmid. Cell lysates were used to analyze androgen receptor (AR) production. A novel hemizygous AR variant (c.2070C>A, p. His690Glu) and a rare heterozygous MAP3K1 variant (c.778C>T, p. Arg260Cys) were identified by WES in the proband and her mother. Bioinformatic analysis predicted these two variants to be pathogenic. Multiple amino acid sequence alignments showed that p. His690 and p. Arg260 are conserved among various species. His690Glu is a mutation that decreased the AR production, whereas the Arg260Cys mutation increased the AR production. The novel compound variants of the AR and MAP3K1 genes also increased the production of AR protein. Thus, the phenotype of the patient may be caused by defects in both the AR and MAP3K1 signaling pathways. Compound variants of the AR and MAP3K1 genes resulted in a specific phenotype in this patient with AIS. WES might reveal genetic variants that explain the heterogeneity of AIS. [ABSTRACT FROM AUTHOR]

Background: Brain metastases (BM) from non-small cell lung cancer (NSCLC) are the most frequent intracranial tumors. To identify patients who might benefit from intracranial surgery, we compared the six existing prognostic indexes(PIs) and built a nomogram to predict the survival for NSCLC with BM before they intended to receive total intracranial resection in China.Methods: First, clinical data of NSCLC presenting with BM were retrospectively reviewed. All of the patients had received total intracranial resection and were randomly distributed to developing cohort and validation cohort by 2:1. Second, we stratified the cohort using a recursive partitioning analysis(RPA), a score index for radiosurgery (SIR), a basic score for BM (BS-BM), a Golden Grading System (GGS), a disease-specific graded prognostic assessment (DS-GPA) and by NSCLC-RADES. The predictive power of the six PIs was assessed using the Kaplan-Meier method and the log-rank test. Third, univariate and multivariate analysis were explored, and the nomogram predicting survival of BMs from NSCLC was constructed using R 3.2.3 software. The concordance index (C-index) was calculated to evaluate the discriminatory power of the nomogram in the developing cohort and validation cohort.Results: BS-BM could better predict survival of patients before intracranial surgery compared with other PIs. In the final multivariate analysis, KPS at diagnosis of BM, metachronous or synchronous BM and the histology of lung cancer appeared to be the independent prognostic predictors for survival. The C-index in the developing cohort and validation cohort were 0.75 and 0.71 respectively, which was better than the C-index of the other six PIs.Conclusions: The new nomogram is a promising tool in further choosing the candidates for intracranial surgery among NSCLC with BM and in helping physicians tailor suitable treatment options before operation in clinical practice. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSCs), one of the major orchestrators of the immunosuppressive network, are associated with immune suppression and considered a prime target for cancer immunotherapy. At present, various strategies have been explored to deplete and/or inactivate MDSCs in vivo. In this study, we investigated the effect of arsenic trioxide (ATO) on MDSCs derived from tumor-bearing mice. This study examined the in vitro and in vivo effects of ATO administration on MDSCs from C57/j mice bearing either the B16 or H22 tumor. The MDSCs were then characterized for phenotype, gene expression and function. Administration with ATO in vitro significantly induced MDSC differentiation, inhibited their proliferation and triggered apoptosis. Treatment with ATO in these murine tumor models significantly inhibited tumor growth and splenomegaly, decreased the percentages of MDSCs in the spleen, promoted their differentiation, reduced tumor necrosis factor-a and interleukin-10 levels and weakened the immune inhibition activity of MDSCs on T cells. In addition, we observed the underlying mechanism involved in the regulation of MDSCs by ATO, which included a panel of cytokines and signaling pathways. The findings showed the immunoregulatory effects of ATO by inducing apoptosis, promoting differentiation and inhibiting the function of MDSCs, suggesting that ATO has potential clinical benefit as it selectively attenuates MDSC-induced immunosuppression. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous myeloid cells that can suppress antitumor immunity. MDSCs are divided into granulocytic (G-MDSCs) and monocytic subsets. In the present study, the microRNA profiles of the G-MDSCs were determined and the differential expression of microRNAs between G-MDSCs from tumor-bearing mice and tumor-free mice was examined. The number of G-MDSCs in spleens of Lewis lung carcinoma (LLC)-bearing mice was ~6-fold higher than in spleens of normal mice (13.54±1.74% vs. 2.14±1.44%; P<0.01) and G-MDSCs account for about 72.9% of all MDSCs. The microRNA (miRNA) profiles of the G-MDSCs from spleen of LLC-bearing mice were obtained using a microRNA microarray and compared with their counterparts from spleens of tumor-free mice. A total of 43 miRNAs with >1.3-fold increased or decreased change were differentially expressed between the experimental and control group mice. The levels of nine of these differentially expressed miRNAs, miRNA-468 (miR-486), miR-192, miR-128, miR-125a, miR-149, miR-27a, miR-125b, miR-350 and miR-328, were also analyzed by RT-qPCR to validate the microarray data. The concordance rate between the results tested by the two methods was 88.9%. Bioinformatics analyses revealed that these miRNAs may act on various target genes, including Adar, Pik3r1, Rybp and Rabgap1, to regulate the survival, differentiation and the function of tumor-induced granulocytic MDSCs. The results revealed microRNAs and potential targets that may be vital for regulating survival, differentiation and function of G-MDSCs induced by LLC. Further investigation should be performed to clarify the roles of these microRNAs in regulating LLC-induced granulocytic MDSCs and the target genes that mediate their functions. [ABSTRACT FROM AUTHOR]

Abstract: A cheap and recyclable task-specific ionic liquid N, N, N-trimethyl-N-propanesulfic acid ammonium hydrogen sulfate [TMPSA]·HSO4 was used as the catalyst for the synthesis of quinoxaline derivatives. The reaction could be accomplished in water as well as organic solvent, and the satisfactory results were obtained under the mild conditions. The products could be separated from the catalyst simply by filtration and the catalyst could be recycled and reused for several times without noticeably decreasing the catalytic activity. [Copyright &y& Elsevier]