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ABSTRACTThere is limited evidence to support the association between tuberculosis (TB) and the occurrence of Takayasu arteritis (TAK). To investigate the incidence of active TB (ATB) in TAK and explore the impact of anti-rheumatic therapy on the occurrence of ATB or reactivation of Latent TB infection (LTBI) and their effect on interferon-γ release assay (IGRA) results, we conducted a prospective study based on the Chinese Registry for Systemic Vasculitis cohort. The standard incidence ratio (SIR) was calculated and stratified by age. Kaplan–Meier analysis was used to determine the effect of variables on ATB or LTBI reactivation in patients with TAK. Data from 825 patients with TAK in the registry were analysed. During a median follow-up of 5 years, 5 patients developed ATB with a crude incidence of 154 (95%CI:57–381) person-years/100,000. The SIR was 5.59 (95%CI:1.81–13.04). Glucocorticoids and conventional disease-modifying anti-rheumatic drugs (cDMARDs) did not increase the risk of ATB or LTBI reactivation (P > 0.05). However, the use of tumour necrosis factor inhibitor (TNFi) increased the risk of ATB in patients with LTBI (P

Burdock (Arctium lappa L.), which belongs to the Compositae family, possesses significant medicinal and nutritional value. Burdock root is abundant in proteins and essential amino acids. In this study, proteins from burdock roots were extracted by alkali extraction and acid sedimentation, and the optimal conditions for protein extraction from burdock roots and protein characteristics were explored. The optimal conditions for protein extraction with a yield rate of 9.03% were 40°C extraction temperature, pH 8.0, a solid–liquid ratio of 1:25 (g/mL), and extraction time of 65 minutes. Single-factor and orthogonal tests on the extraction rate of burdock proteins under different conditions found that the extraction rate of protein from burdock roots were influenced by pH, extraction temperature, solid–liquid ratio, and extraction time, in this order. The solubility and gelation properties of burdock protein were similar to those of soybean protein; however, burdock protein demonstrated 1.2 times the oil absorption capacity and half the water retention capacity of soybean protein. Analysis of the amino acid contents of burdock protein revealed that burdock root contains significant essential and non-essential amino acids, with valine content being the highest.

Abstract Background In view of the fact that radiomics features have been reported as predictors of immunotherapy to various cancers, this study aimed to develop a prediction model to determine the response to anti‐programmed death‐1 (anti‐PD‐1) therapy in esophageal squamous cell carcinoma (ESCC) patients from contrast‐enhanced CT (CECT) radiomics features. Methods Radiomic analysis of images was performed retrospectively for image samples before and after anti‐PD‐1 treatment, and efficacy analysis was performed for the results of two different time node evaluations. A total of 68 image samples were included in this study. Quantitative radiomic features were extracted from the images, and the least absolute shrinkage and selection operator method was applied to select radiomic features. After obtaining selected features, three classification models were used to establish a radiomics model to predict the ESCC status and efficacy of therapy. A cross‐validation strategy utilizing three folds was employed to train and test the model. Performance evaluation of the model was done using the area under the curve (AUC) of receiver operating characteristic, sensitivity, specificity, and precision metric. Results Wavelet and area of gray level change (log‐sigma) were the most significant radiomic features for predicting therapy efficacy. Fifteen radiomic features from the whole tumor and peritumoral regions were selected and comprised of the fusion radiomics score. A radiomics classification was developed with AUC of 0.82 and 0.884 in the before and after‐therapy cohorts, respectively. Conclusions The combined model incorporating radiomic features and clinical CECT predictors helps to predict the response to anti‐PD‐1therapy in patients with ESCC.

Abstract Developing a multifunctional nanoplatform to achieve efficient theranostics of tumors through multi‐pronged strategies remains to be challenging. Here, the design of the intelligent redox‐responsive generation 3 (G3) poly(amidoamine) dendrimer nanogels (NGs) loaded with gold nanoparticles (Au NPs) and chemotherapeutic drug toyocamycin (Au/Toy@G3 NGs) for ultrasound‐enhanced cancer theranostics is showcased. The constructed hybrid NGs with a size of 193 nm possess good colloidal stability under physiological conditions, and can be dissociated to release Au NPs and Toy in the reductive glutathione‐rich tumor microenvironment (TME). The released Toy can promote the apoptosis of cancer cells through endoplasmic reticulum stress amplification and cause immunogenic cell death to maturate dendritic cells. The loaded Au NPs can induce the conversion of tumor‐associated macrophages from M2‐type to antitumor M1‐type to remodulate the immunosuppressive TME. Combined with antibody‐mediated immune checkpoint blockade, effective chemoimmunotherapy of a pancreatic tumor mouse model can be realized, and the chemoimmunotherapy effect can be further ultrasound enhanced due to the sonoporation‐improved tumor permeability of NGs. The developed Au/Toy@G3 NGs also enable Au‐mediated computed tomography imaging of tumors. The constructed responsive dendrimeric NGs tackle tumors through a multi‐pronged chemoimmunotherapy strategy targeting both cancer cells and immune cells, which hold a promising potential for clinical translations.

[Introduction] Under the wave-current combinations during the service period of offshore wind turbine, local scour inevitably occurs around pile foundation, which threatens the overall stability and safety of offshore wind turbine. [Method] In this paper, the normal physical model test at a scale of 1∶30 was carried out for the wind power foundation with a diameter of 8.0 m to study the scour depth, sand cover, solidified soil protection range, and protection effect. [Result] The results show that due to the good hydrodynamic conditions considered in this test, the maximum scour depth is 0.133 cm. In this case, the 1 cm-thick sand cover with a splicing size of 1.0 m×1.0 m can meet the stability requirements. When solidified soil is adopted for protection, the protection range shall not be less than 5 times the pile diameter, and block stones shall be laid at the edge of solidified soil to avoid scouring at the lower part of solidified soil. [Conclusion] The test results can provide reference for scouring test and engineering design of similar projects.

Abstract Background Nonalcoholic fatty liver disease (NAFLD) as the leading chronic liver disease worldwide causes hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The aim of this study was to find potential aberrantly methylated and differentially expressed genes in NAFLD of HCC patients with cirrhosis. Methods DNA methylation data, mRNA expression data, and the corresponding clinical information of HCC were downloaded from the Cancer Genome Atlas (TCGA, tissue sample) database. HCC patients with cirrhosis were divided into two groups according to the presence of NAFLD. The differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were obtained. Results By overlapping 79 up-regulated genes and 1020 hypomethylated genes, we obtained 5 hypomethylated-highly expressed genes (Hypo­HGs). By overlapping 365 down-regulated genes and 481 hypermethylated genes, we identified 13 hypermethylated-lowly expressed genes (Hyper-LGs). Survival analysis of these 18 MDEGs indicated that the expression of DGKK and HOXD9 was significantly correlated with the overall survival time of NAFLD patients. Conclusions We identified several candidate genes whose expressions were regulated by DNA methylation of NAFLD of HCC with cirrhosis, which may provide a new field in understanding the clinical pathological mechanism of NAFLD of HCC with cirrhosis.

Abstract Background Hepatocellular carcinoma (HCC) is often caused by chronic liver infection or inflammation. Searching for potential immunotherapy targets will aid the early diagnosis and treatment of HCC. Methods Firstly, detailed HCC data were downloaded from The Cancer Genome Atlas database. GDCRNATools was used for the comprehensive analysis of RNA sequencing data. Subsequently, the CIBERSORT package was used to estimate infiltration scores of 22 types of immune cells in complex samples. Furthermore, hub genes were identified via weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis. In addition, multiple databases were used to validate the expression of hub gene in the tumor tissue. Finally, prognostic, diagnostic and immunohistochemical analysis of key hub genes was performed. Results In the present study, 9 hub genes were identified using WGCNA and PPI network analysis. Furthermore, the expression levels of 9 genes were positively correlated with the infiltration levels of CD8-positive T (CD8+ T) cells. In multiple dataset validations, the expression levels of CCL5, CXCR6, CD3E, and LCK were decreased in cancer tissues. In addition, survival analysis revealed that patients with LCK low expression had a poor survival prognosis (P

PurposeTo assess predictive value of clinical and pathological characteristics for metastatic radioactive iodine-refractory differentiated thyroid carcinoma (RAIR-DTC) in early stage retrospectively.MethodsWe studied 199 metastatic DTC patients who were divided into two groups (TgAb negative and TgAb positive). The stimulated Tg (Sti-Tg) at the first and second radioiodine therapy (RIT) were defined as Sti-Tg1 and Sti-Tg2, the suppressed Tg (Sup-Tg) were designated as Sup-Tg1 and Sup-Tg2, while the TgAb were defined as TgAb1 and TgAb2, respectively. Univariate analysis and Logistic regression were used to investigate the effects of 13 observed factors to predict RAIR-DTC.ResultsIn TgAb negative group, ROC curve analysis showed that cut-off values of age, Sti-Tg2/Sti-Tg1 and Sup-Tg2/Sup-Tg1 to predict RAIR-DTC were 40 years old, 57.0% and 81.0%, respectively. Age, extrathyroid invasion, Sti-Tg2/Sti-Tg1, Sup-Tg2/Sup-Tg1 and BRAF gene mutation were proved to be independent factors predicting RAIR-DTC. In TgAb-positive group, ROC curve analysis showed that cut-off values of age, TgAb1 and TgAb2/TgAb1 to predict RAIR-DTC were 55 years old, 297 IU/ml (14.8 times higher than the upper limit) and 53.6%, respectively.ConclusionsFor TgAb-negative DTC, age over 40, extraglandular invasion, mutated BRAF gene, Sti-Tg decreased less than 43%, and Sup-Tg decreased less than 19% after the first two courses of RIT were independent predictors for RAIR-DTC. For TgAb-positive DTC, age over 55, extraglandular invasion, mutated BRAF gene, distant metastasis before RIT, TgAb level 14.8 times higher than the upper limit, TgAb dropped less than 46.4% after two courses of RIT were influencing factors.

Boll weight (BW) is a key determinant of yield component traits in cotton, and understanding the genetic mechanism of BW could contribute to the progress of cotton fiber yield. Although many yield-related quantitative trait loci (QTLs) responsible for BW have been determined, knowledge of the genes controlling cotton yield remains limited. Here, association mapping based on 25,169 single-nucleotide polymorphisms (SNPs) and 2,315 insertions/deletions (InDels) was conducted to identify high-quality QTLs responsible for BW in a global collection of 290 diverse accessions, and BW was measured in nine different environments. A total of 19 significant markers were detected, and 225 candidate genes within a 400 kb region (± 200 kb surrounding each locus) were predicted. Of them, two major QTLs with highly phenotypic variation explanation on chromosomes A08 and D13 were identified among multiple environments. Furthermore, we found that two novel candidate genes (Ghir_A08G009110 and Ghir_D13G023010) were associated with BW and that Ghir_D13G023010 was involved in artificial selection during cotton breeding by population genetic analysis. The transcription level analyses showed that these two genes were significantly differentially expressed between high-BW accession and low-BW accession during the ovule development stage. Thus, these results reveal valuable information for clarifying the genetic basics of the control of BW, which are useful for increasing yield by molecular marker-assisted selection (MAS) breeding in cotton.

Abstract Leaf angle is an important agronomic trait affecting photosynthesis efficiency and crop yield. Although the mechanisms involved in the leaf angle control are intensively studied in monocots, factors contribute to the leaf angle in dicots are largely unknown. In this article, we explored the physiological roles of an Arabidopsis glucosyltransferase, UGT74D1, which have been proved to be indole-3-acetic acid (IAA) glucosyltransferase in vitro. We found that UGT74D1 possessed the enzymatic activity toward IAA glucosylation in vivo and its expression was induced by auxins. The ectopically expressed UGT74D1 obviously reduced the leaf angle with an altered IAA level, auxin distribution and cell size in leaf tissues. The expression of several key genes involved in the leaf shaping and leaf positioning, including PHYTOCHROME KINASE SUBSTRATE (PKS) genes and TEOSINTE BRANCHED1, CYCLOIDEA, and PCF (TCP) genes, were dramatically changed by ectopic expression of UGT74D1. In addition, clear transcription changes of YUCCA genes and other auxin related genes can be observed in overexpression lines. Taken together, our data indicate that glucosyltransferase UGT74D1 could affect leaf positioning through modulating auxin homeostasis and regulating transcription of PKS and TCP genes, suggesting a potential new role of UGT74D1 in regulation of leaf angle in dicot Arabidopsis.

Current commercial H9 avian influenza viruses (AIVs) vaccines cannot provide satisfactory antibody titers and protective immunity against AIVs in duck. Toll like receptors (TLR) ligand as AIVs adjuvants can activate dendritic cells to improve immune responses in multiple animals, while the studies were absent in duck. Therefore, we investigated TLR ligands pam2CSK4, poly (I:C) and/or imiquimod enhance immune responses to inactivated H9N2 avian influenza antigen (H9N2 IAIV) in peripheral blood monocyte-derived dendritic cells (MoDCs) and duck. In vitro, we observed that transcription factor NF-κB, Th1/Th2 type cytokines (IFN-γ, IL-2 and IL-6) and the ability of catching H9N2 IAIV antigen were significantly up-regulated when H9N2 IAIV along with TLR ligands (pam2CSK4, poly (I:C) and imiquimod, alone or combination) in duck MoDCs. Also, the best enhancement effects were showed in combination of pam2CSK4, poly (I:C) and imiquimod group, whereas IFN-α showed no significant enhancement in all experimental groups. In vivo, the results demonstrated that the percentages of CD4+/ CD8+ T lymphocytes, the levels of Th1/Th2 type cytokines and H9N2 HI titers were significant enhanced in combination of pam2CSK4, poly (I:C) and imiquimod group. However, pam2CSK4 alone or combining with imiquimod showed no enhancement or additive effects on Th1 cytokines (IFN-γ and IL-2), Th2 cytokines (IL-6) and HI titers in Muscovy duck, respectively. Taken together, our results concluded that not all TLR ligands showed enhancement of immune responses to H9N2 IAIV in duck. The combination of poly (I:C), imiquimod and pam2CSK4 that can be an effectively adjuvant candidate for H9N2 AIVs inactivated vaccine in duck, which provide novel insights in explore waterfowl vaccine.

BackgroundThere are no definite recommendations on the optimal time of initiating radioactive iodine (RAI) therapy for differentiated thyroid cancer (DTC) patients in current relevant guidelines. This study aimed to investigate the relationship between the timing of initiating radioiodine adjuvant therapy (RAT) and the clinical outcomes based on dynamic follow-ups and assessments in intermediate- to high-risk DTC patients.MethodsA total of 206 patients with intermediate- to high-risk DTC receiving RAT of 150 mCi were retrospectively reviewed. According to the time interval (TI: between thyroidectomy and initial RAT), the patients were divided into 2 groups: Group 1: TI < 3 months (n=148), and Group 2: TI ≥ 3 months (n=58). The RAT therapy response was evaluated as excellent response (ER), indeterminate response (IDR), biochemical incomplete response (BIR), structural incomplete response (SIR). The univariate and multivariate analyses were conducted to screen out factors associated with incomplete response (IR= BIR+SIR). Finally, the prognostic nomogram was used to explain IR rates as a valuable tool in clinical practice.ResultsResponse to initial RAT was significantly different between 2 groups during dynamic follow-ups (all P

BackgroundSerum thyroglobulin (Tg) serves as a sensitive and easily available tumor marker for patients with metastatic differentiated thyroid carcinoma (m-DTC). The aim of the present study was to evaluate the predictive value of suppressed Tg changes (Δsup-Tg) and/or stimulated Tg changes (Δsti-Tg) to evaluate the efficacy of radioiodine therapy (RT).MethodsWe studied 117 patients with m-DTC who received RT. Δsup-Tg and Δsti-Tg were compared after the first RT in different therapeutic response groups and a receiver-operating characteristic (ROC) curve was used to determine the cut-off values to predict non-remission. Univariate and multivariate analyses were used to investigate the effects of 17 observed factors on the efficacy of RT.ResultsA total of 218 RT events in 117 patients with m-DTC were analyzed. After the last RT, the remission rate was 70.94% (83/117), and the proportion of remission events accounted for 74.77% (163/218). ROC curve analysis showed that the cut-off values for Δsup-Tg and Δsti-Tg after the first RT to predict the non-remission of RT were 21.54% and 27.63%, respectively. Age, the size of the metastasis, the maximum count of target metastatic lesions and the average count of contralateral non-target tissue on tomographic imaging (Tmax/NTmean) of the first RT, and Δsup-Tg after the first RT were identified as independent factors associated with RT efficacy.ConclusionsTg response was valuable to predict RT efficacy for patients with m-DTC. Age, the size of the metastasis, Tmax/NTmean, and Δsup-Tg after the first RT were verified as independent predictive factors of RT efficacy.

Abstract Anaplastic thyroid cancer (ATC) comprises approximately 2% of all thyroid cancers, and its median survival rate remains poor because of its resistance to conventional therapy. Vascular endothelial growth factor receptor (VEGFR)-targeted therapeutics-loaded mesoporous silica nanoparticles represent a major advance for angiogenesis imaging and inhibition in lethal cancers. In the present study, we aimed to assess whether 131I-labeled anti-VEGFR2 targeted mesoporous silica nanoparticles would have antitumor efficacy in an ATC tumor-bearing nude mouse model. Using in vitro and in vivo studies, we investigated the increased targeting ability and retention time in the anti-VEGFR2 targeted group using confocal microscopy and a γ counter. The tumor tissue radioactivity of the anti-VEGFR2 targeted group at 24 and 72 h after intratumoral injection was significantly higher than that of the non-targeted groups (all P

The significant progress in cancer treatment, including chemotherapy, immunotherapy, radiotherapy, and combination therapies, has led to higher long-term survival rates in cancer patients, while the cardiotoxicity caused by cancer treatment has become increasingly prominent. Cardiovascular magnetic resonance (CMR) is a non-invasive comprehensive imaging modality that provides not only anatomical information, but also tissue characteristics and cardiometabolic and energetic assessment, leading to its increased use in the early identification of cardiotoxicity, and is of major importance in improving the survival rate of cancer patients. This review focused on CMR techniques, including myocardial strain analysis, T1 mapping, T2 mapping, and extracellular volume fraction (ECV) calculation in the detection of early myocardial injury induced by cancer therapies. We summarized the existing studies and ongoing clinical trials using CMR for the assessment of subclinical ventricular dysfunction and myocardial changes at the tissue level. The main focus was to explore the potential of clinical and preclinical CMR techniques for continuous non-invasive monitoring of myocardial toxicity associated with cancer therapy.

Structure elucidations of giant fullerenes composed of 100 or more carbon atoms are severely hampered by their extremely low yield, poor solubility and huge numbers of possible cage isomers. High-temperature exohedral chlorination followed by X-ray single crystal diffraction studies of the chloro derivatives offers a practical solution for structure elucidations of giant fullerenes. Various isomers of giant fullerenes have been determined by this method, specially, non-classical giant fullerenes containing heptagons generated by the skeletal transformations of carbon cages. Alternatively, giant fullerenes can be also stabilized by encapsulating metal atoms or clusters through intramolecular electron transfer from the encapsulated species to the outer fullerene cage. In this review, we present a comprehensive overview on synthesis, separation and structural elucidation of giant fullerenes. The isomer structures, chlorination patterns of a series of giant fullerenes C2n (2n = 100-108) and heptagon-containing non-classical fullerenes derived from giant fullerenes are summarized. On the other hand, giant endohedral fullerenes bearing different endohedral species are also discussed. At the end, we propose an outlook on the future development of giant fullerenes.

Protein- and starch-related quality traits, which are quantitatively inherited and significantly influenced by the environment, are critical determinants of the end-use quality of wheat. We constructed a high-density genetic map containing 10,739 loci (5,399 unique loci) using a set of 184 recombinant inbred lines (RILs) derived from a cross of 'Tainong 18 × Linmai 6' (TL-RILs). In this study, a quantitative trait loci (QTLs) analysis was used to examine the genetic control of grain protein content, sedimentation value, farinograph parameters, falling number and the performance of the starch pasting properties using TL-RILs grown in a field for three years. A total of 106 QTLs for 13 quality traits were detected, distributed on the 21 chromosomes. Of these, 38 and 68 QTLs for protein- and starch-related traits, respectively, were detected in three environments and their average values (AV). Twenty-six relatively high-frequency QTLs (RHF-QTLs) that were detected in more than two environments. Twelve stable QTL clusters containing at least one RHF-QTL were detected and classified into three types: detected only for protein-related traits (type I), detected only for starch-related traits (type II), and detected for both protein- and starch-related traits (type III). A total of 339 markers flanked with 11 QTL clusters (all except C6), were found to be highly homologous with 282 high confidence (HC) and 57 low confidence (LC) candidate genes based on IWGSC RefSeq v 1.0. These stable QTLs and RHF-QTLs, especially those grouped into clusters, are credible and should be given priority for QTL fine-mapping and identification of candidate genes with which to explain the molecular mechanisms of quality development and inform marker-assisted breeding in the future.

Background/Aims: Chronic inflammation is associated with increased risk of cardiovascular death in patients with end-stage renal disease (ESRD). Although elevated neutrophil-to-lymphocyte ratio (NLR), a novel inflammatory marker, has been shown to predict cardiovascular disease and all-cause mortality in the general population, limited evidence is available for its role in ESRD. Methods: We enrolled 86 patients undergoing peritoneal dialysis (PD) for a 36-month follow-up to investigate the association between the NLR and arterial stiffness markers, namely, carotid-femoral pulse wave velocity (cfPWV) and carotid augmentation index (AIx), and mortality in PD patients. The primary endpoints were cardiovascular mortality and all-cause mortality. Kaplan–Meier curves were used to show the cumulative incidence of cardiovascular mortality and all-cause mortality. Results: High NLR was found to be a predictor of increased cfPWV (β = 1.150; P < 0.001) and AIx (β = 3.945; P < 0.001) in patients on PD. Patients with higher NLR had lower survival during follow-up. Kaplan–Meier curves showed that the cumulative incidences of both cardiovascular mortality and all-cause mortality were significantly higher in patients with NLR ≥ 4.5 (both P < 0.01). Conclusion: Our results suggest that high NLR is independently associated with arterial stiffness and predicts cardiovascular and all-cause mortality in PD patients.

RAD52 motif containing 1 (RDM1) encodes the RAD52 protein involved in DNA double-strand break repair and recombination events. However, the importance of RDM1 in papillary thyroid carcinoma (PTC) is largely unknown. In the present study, we examined the role of RDM1 in thyroid cancer. The RDM1 expression in PTC patients was examined using immunohistochemistry. The expression levels of RDM1 mRNA in thyroid cancer cells were measured by quantitative real-time PCR (qRT-PCR). Lentivirus-mediated small interfering RNAs (siRNAs) were used to knock down the RDM1 expression in the K1 and TPC1 cells. Then, changes in the RDM1 target gene expression were determined by qRT-PCR and Western blot. Cell proliferation was examined by a high content screening assay. Cell cycle distribution and apoptosis were detected by flow cytometric analysis and MTT analysis. We showed that the RDM1 expression was higher in PTC tissue compared to pericarcinous tissue. RDM1 mRNA was found to be expressed by qRT-PCR. Using a lentivirus-based RNA interference (RNAi) approach, the RDM1 expression was significantly inhibited. The inhibition of RDM1 expression by RNAi significantly impaired cell proliferation, increased apoptosis and arrested cells in the G2/M phase. These data showed that RDM1 was highly expressed in PTC tissue and thyroid cancer cell lines. Moreover, RDM1 may play an important role in cell proliferation, cell cycle distribution and apoptosis of human PTC cells.

Abstract Rapid iodine-131(131I) turnover in the thyroid gland is an important feature of Graves’ disease (GD) and also a strong predictor of radioiodine therapy failure. The aim of this study was to explore the predictors of rapid 131I turnover. The clinical data on 2543 patients were retrospectively reviewed. Patients were divided into 2 groups depending on present or absent with rapid 131I turnover defined as a 4-hour to 24-hour 131I uptake ratio of ≥1. Overall, 590 cases (23.2%) had a rapid 131I turnover. In the univariate analysis, gender, age, FT3/FT4 concentration, disease duration, with or without antithyroid drugs (ATD), time of ATD, thyroid weight and thyroid textures displayed significant differences. Cutoff values of age, FT3 and thyroid weight to predict rapid 131I turnover were 38 years, 35 pmol/l and 56 g by receiver operating characteristic curves. Binary logistic regression analysis further revealed higher probability of rapid 131I turnover in patients with thyroid weight ≥56 g (odds ratio [OR]:3.7, 95% confidence interval [CI]: 3.032–4.559), age

Tumor differentiation is an important process in the development of cancer. It is valuable to identify key differentiation related genes in the prognosis and therapy of pancreatic adenocarcinoma.The mRNA expression data were downloaded from the Cancer Genome Atlas database. Then, differentially expressed tumor differentiation related genes were identified. Additionally, Gene Ontology functional categories and Kyoto Encyclopedia of Genes and Genomes biochemical pathway was used to explore the function. In addition, receiver operating characteristic and survival analysis were carried out to assess the diagnosis and prognosis value. Finally, the electronic validation of selected tumor differentiation related genes was performed.A total of 932 genes were identified. Among which, 8 genes including JUB, ERLIN1, HMGA2, FAM110B, EGFR, MCM2, TCTA and SSTR1 were differentially expressed in all different tumor differentiation grades. Functional analysis revealed those genes between highly differentiated and other differentiation were remarkably enriched in pancreatic adenocarcinoma and cell cycle pathway. Finally, ERLIN1, HMGA2, FAM110B, EGFR, MCM2, BCL2L1, E2F1 and RAC1 were associated with the survival time of pancreatic adenocarcinoma patient. Among these genes, JUB, ERLIN1, FAM110B, MCM2 and BCL2L1 also had a diagnosis value for pancreatic adenocarcinoma. Additionally, the expression trend of JUB, HMGA2 and MCM2 was increased along with the tumor differentiation grades. And the expression trend of FAM110B was decreased along with the tumor differentiation grades. The electronic validation result was consistent with the bioinformatics analysis.12 tumor differentiation related genes including JUB, ERLIN1, HMGA2, FAM110B, EGFR, MCM2, TCTA, SSTR1, BCL2L1, E2F1, RAC1 and STAT1 played crucial roles in the differentiation of pancreatic adenocarcinoma.

Production of mutants with altered phenotypes is a powerful approach for determining the biological functions of genes in an organism. In this study, a high-grain-weight mutant line M8008 was identified from a library of mutants of the common wheat cultivar YN15 treated with ethylmethane sulfonate (EMS). F2 and F2:3 generations produced from crosses of M8008 × YN15 (MY) and M8008 × SJZ54 (MS) were used for genetic analysis. There were significant differences between M8008 and YN15 in plant height (PH), spike length (SL), fertile spikelet number per spike (FSS), grain width (GW), grain length (GL), GL/GW ratio (GLW), and thousand-grain weight (TGW). Most simple correlation coefficients were significant for the investigated traits, suggesting that the correlative mutations occurred in M8008. Approximately 21% of simple sequence repeat (SSR) markers showed polymorphisms between M8008 and YN15, indicating that EMS can induce a large number of mutated loci. Twelve quantitative trait loci (QTLs) forming QTL clusters (one in MY and two in MS) were detected. The QTL clusters coinciding with (MY population) or near (MS population) the marker wmc41 were associated mainly with grain-size traits, among which the M8008 locus led to decreases in GW, factor form density (FFD), and TGW and to increases in GLW. The cluster in the wmc25–barc168 interval in the MS population was associated with yield traits, for which the M8008 locus led to decreased PH, spike number per plant (SN), and SL.

We aimed to measure prevalence of sleep disturbance in patients with differentiated thyroid cancer (DTC) by calculating Pittsburgh Sleep Quality Index (PSQI), and compare these data with patients with benign thyroid nodules or normal participants.Three groups of patients participated in this cross-sectional study. In the first group, 162 patients with DTC received total thyroidectomy, and then 131I therapy. The second group consisted of 84 patients with benign thyroid nodules, who received partial thyroidectomy. The third group was 78 normal healthy control cases. PSQI was used to assess the sleep quality. Inter-group differences were analyzed by Kruskal-Wallis test or independent samples T test. χ2 test was also used to check prevalence differences of poor sleep quality among the groups. Differences of PSQI score and poor sleep quality prevalence before and after 131I therapy in the same group of DTC participants were analyzed by paired T test and Mcnemar's test.Higher PSQI score (7.59 ± 4.21) and higher rate of poor sleep quality (54.32%) were shown in DTC patients than in any other group. After 131I therapy, PSQI score and prevalence of poor sleep quality in DTC patients increased significantly to 8.78 ± 4.72 and 70.99%. Then DTC patients were divided into two subgroups based on their metastatic status. DTC patients with metastasis (87/162 cases, 53.70%) had significantly higher PSQI score (10.87 ± 5.18) and higher prevalence of poor sleep quality (79.31%).DTC patients suffer from sleep disturbance, 131I therapy and awareness of metastatic status could worsen sleep problem. Psychological fear of cancer, nuclear medicine therapy and metastasis could be one major underlying reason. Longitude and interventional studies are necessary for further investigations.