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1.
Methods Mol Biol ; 2072: 85-99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31541440

RESUMO

cis-regulatory DNA elements (CREs) are noncoding but functional DNA sequences. The binding of regulatory proteins into CRE regions leads to chromatin high sensitive to DNase I digestion, which are termed as DNase I hypersensitive sites (DHSs). These DHSs can be efficiently detected through DNase I digestion followed by high-throughput DNA sequencing (DNase-seq). Thus, DNase-seq has become a powerful technique for DHSs mapping at whole-genome level in both plants and animals. Here we describe a DNase-seq procedure modified and developed for crop plants. These plants usually contain large amounts of repetitive sequences and complex organic constituents. With the main improvement in nuclei isolation, this method has been successfully used in mapping DHSs in cotton and sugarcane.

2.
Chemosphere ; 238: 124640, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31524609

RESUMO

Triclosan (TCS) is a kind of chronic toxicity to aquatic organisms. Due to its highly effective antimicrobial, TCS has been widely applied in personal-care products, which naturally poses a potential risk to the ecological system and human health since its release into water-ecological environment. Therefore, it urgently demands a selective, easily separated, recyclable, and low-cost adsorbent to remove the residues of TCS from aquatic environments. In this study, a novel magnetic molecularly imprinted nano-polymers (TMIPs) were prepared for selective adsorption and convenient collection of TCS in aquatic samples, based on a core-shell technique using TCS as template molecule and SiO2-coated Fe3O4 nanoparticles as the support substrate. The functional groups, particle size, morphology and magnetic property of TMIPs were characterized by Fourier-transform infrared spectroscopy, scanning electron microscope, transmission electron microscopy and vibrating sample magnetometer, respectively. The obtained TMIPs possessed excellent adsorption capacity (Qe = 53.12 mg g-1), speedy adsorption equilibrium time (2 min) and high selectivity (k' = 6.321) for TCS. Moreover, the pH-tolerance and stability tests manifested that the adsorption capacity of TMIPs for TCS was acid-resistance and could retain 94.2% of the maximum Qe after 5 times removal-regeneration cycles. The feature of magnetically susceptibility can simplify the procedures of sample handling in TCS determination, because the TMIPs of TCS are easy to be recycled from aquatic samples. As an application demonstration, the toxicity test in microalgae confirmed that a tiny amount of TMIPs could significantly eliminate the toxic effect of TCS on Chlamydomonas reinhardtii via the efficient binding with TCS.

3.
Chemosphere ; 239: 124712, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31499310

RESUMO

Selenium can regulate arsenic toxicity by strengthening antioxidant potential, but the antagonism between selenite or selenate nutrient and the translocation of arsenic species from paddy soil to different rice organs are poorly understood. In this study, a pot experiment was designed to investigate the effect of selenite or selenate on arsenite or arsenate toxicity to two indica rice cultivars (namely Ming Hui 63 and Lu You Ming Zhan), and the uptake and transportation of arsenic species from paddy soil to different rice organs. The results showed that selenite or selenate could significantly decrease the arsenate concentration in pore water of soils, and thus inhibited arsenate uptake by rice roots. However, the existence of selenite or selenate didn't decrease arsenate concentration in rhizosphere pore water of two indica rice cultivars. There existed good antagonistic effect between selenite or selenate and the uptake of arsenite and arsenate in rice plant in the case of low arsenic paddy soil. However, this antagonism depended on rice cultivars, arsenic species and arsenic level in soil. There existed both synergistic and inhibiting effects between the addition of selenite or selenate and the uptake of trimethylarsinoxide and dimethylarsinic acid by two indica rice cultivars, but the mechanism was unclear. Both selenite and selenate are all effective to decrease the translocation of inorganic arsenic from the roots to their above-ground rice organs in arsenite/arsenate-spiked paddy soil, but selenate had stronger inhibiting effect on their transfer factors than selenite.

4.
Carbohydr Polym ; 228: 115372, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31635745

RESUMO

This study aimed at providing a novel approach for improving the physicochemical stability and solubility of algal oil nanocapsules through formation of electrostatic interactions and prebiotic carbohydrates systems composed of: octenyl-succinic anhydride (OSA) starch, OSA/inulin (IN), OSA/maltodextrin (MD), OSA/chitosan (CS), OSA/MD/IN, and OSA/CS/IN. IN, a functional prebiotic modifier, was found to significantly (p < 0.05) decrease emulsion viscosity and particle size, with OSA/CS/IN particles having significantly (p < 0.05) improved water solubility (4.96%) and wettability (749 s) compared to OSA/CS particles. Interestingly, OSA/CS/IN particles had the highest oxidative stability (three times that of bulk oil) and encapsulation efficiency (98.57%). OSA/CS/IN particles were also more hygroscopic than pure OSA particles. Furthermore, scanning electron microscopy (SEM) revealed OSA/CS/IN particles had less wrinkled, smoother surfaces, providing lower air permeability and better protection. Therefore, OSA/CS/IN, as a prebiotic encapsulation system, may lead to the value addition of algal oil.

5.
Gene ; : 144169, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31669642

RESUMO

BACKGROUND (OBJECTIVE): In the development of tumor therapy, the role of long non-coding RNA actin filagenin 1 antisense RNA 1 (1ncRNA AFAP1-AS1) is quite significant, but the actual role of AFAP1-AS1 in the treatment of prostate cancer has not been determined. In view of this, the author took AFAP1-AS1 as the research object to design an experimental study, and conducted an in-depth exploration of the pathogenesis of prostate cancer. METHODS: RT-qPCR was used to detect the expression of AFAP1-AS1 and miR-512-3p in prostate cancer tissues and cell lines. Perforation, flow cytometry and CCK-8 were used to detect the effects of cell proliferation, migration and invasion of mir-512-3p and a AFAP1-AS1. And the luciferase reporter gene was used to detect the downstream target gene of AFAP1-AS1, and the expression of CDK4, CDK6 and CCND1 protein was detected by Western blot. RESULTS: AFAP1-AS1 is highly expressed in prostate cancer tissues and cell lines. The expression level of AFAP1-AS1 is correlated with histological grade and distant metastasis. The overall level of patients with high expression of AFAP1-AS1 is low, and their survival rate is relatively low. Silencing AFAP1-AS1 can significantly increase the proliferation and migration of prostate cancer cells. AFAP1-AS1 silencing induces cell cycle arrest at G0/G1 phase. The downstream target of AFAP1-AS1 was mir-512-3p. The role of AFAP1-AS1 in the progression of prostate cancer cells was mediated by mir-512-3p. CONCLUSION: AFAP1-AS1 regulates miR-512-3p, so as to realize the regulation effect on the proliferation, invasion and migration of prostate cancer cells, and thereby promote the occurrence and development of prostate cancer, so as to provide the corresponding program for the treatment of prostate cancer. Abberivation: ADPC, androgen-dependent prostate cancer; CRPC, castrated prostate cancer; RNA1 AFAP1-Asl, Actin fiber-associated protein 1-anti-RNA1; miRNAs, MicroRNAs.

6.
Glob Chang Biol ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31670435

RESUMO

With accumulation of carbon cycle observations and model developments over the past decades, exploring interannual variations (IAV) of terrestrial carbon cycle offers the opportunity to better understand climate-carbon cycle relationships. However, despite growing research interest, uncertainties remain on some fundamental issues, such as the contributions of different regions, constituent fluxes and climatic factors to carbon cycle IAV. Here, we overviewed the literature on carbon cycle IAV about current understanding of these issues. Observations and models of the carbon cycle unanimously show the dominance of tropical land ecosystems to the signal of global carbon cycle IAV, where tropical semi-arid ecosystems contribute as much as the combination of all other tropical ecosystems. Vegetation photosynthesis contributes more than ecosystem respiration to IAV of the global net land carbon flux, but large uncertainties remain on the contribution of fires and other disturbance fluxes. Climatic variations are the major driver to the IAV of net land carbon flux. Although debate remains on whether the dominant driver is temperature or moisture variability, their interaction, i.e. the dependence of carbon cycle sensitivity to temperature on moisture conditions, is emerging as key regulators of the carbon cycle IAV. On time-scales from the interannual to the centennial, global carbon cycle variability will be increasingly contributed by northern land ecosystems and oceans. Therefore, both improving Earth system models (ESMs) with the progressive understanding on the fast processes manifested at interannual time-scale and expanding carbon cycle observations at broader spatial and longer temporal scales are critical to better prediction on evolution of the carbon-climate system.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31773234

RESUMO

PURPOSE: To develop and validate an integrated model for discriminating tumor recurrence from radiation necrosis in glioma patients. METHODS: Data from 160 pathologically confirmed glioma patients were analyzed. The diagnostic model was developed in a primary cohort (n = 112). Textural features were extracted from postoperative 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET), 11C-methionine (11C-MET) PET, and magnetic resonance images. The least absolute shrinkage and selection operator regression model was used for feature selection and radiomics signature building. Multivariable logistic regression analysis was used to develop a model for predicting tumor recurrence. The radiomics signature, quantitative PET parameters, and clinical risk factors were incorporated in the model. The clinical value of the model was then assessed in an independent validation cohort using the remaining 48 glioma patients. RESULTS: The integrated model consisting of 15 selected features was significantly associated with postoperative tumor recurrence (p < 0.001 for both primary and validation cohorts). Predictors contained in the individualized diagnosis model included the radiomics signature, the mean of tumor-background ratio (TBR) of 18F-FDG, maximum of TBR of 11C-MET PET, and patient age. The integrated model demonstrated good discrimination, with an area under the curve (AUC) of 0.988, with a 95% confidence interval (CI) of 0.975-1.000. Application in the validation cohort showed good differentiation (AUC of 0.914 and 95% CI of 0.881-0.945). Decision curve analysis showed that the integrated diagnosis model was clinically useful. CONCLUSIONS: Our developed model could be used to assist the postoperative individualized diagnosis of tumor recurrence in patients with gliomas.

8.
New Phytol ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31774178

RESUMO

Brachypodium distachyon is a weedy grass species that is firmly established as a model for the comparative and functional genomics of temperate cereals and grasses. Its simple, nuclear genome of five chromosomes contrasts it with other relatives of the genus with different, and usually higher basic chromosome numbers and ploidy levels. This variation in karyotypic structure affords the possibility of reconstructing evolutionary pathways which have shaped the genome structure of extant species. This Tansley insight documents how key refinements in molecular cytogenetic approaches from simple fluorescence in situ hybridisation to comparative chromosome barcoding have enabled genome structure studies, and have yielded valuable information about the drivers of karyotypic reorganisation and evolution in the model grass genus Brachypodium.

9.
Chemosphere ; 243: 125398, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31770698

RESUMO

Different ionomic profiles of plants are associated with different external stresses to which they are exposed. Investigation of ionomic variation is necessary for understanding the migration and detoxification of toxic elements in plants. In the current study, rice plants were treated with arsenite, arsenate, monomethylarsonic acid and dimethylarsinic acid in hydroponics. The ionomic responses of the rice plants to different arsenic (As) species stresses were measured and analyzed. The multielement approach is more sensitive at detecting significant variations from external environmental stresses than the consideration of several individual elements. The pairs of significant correlations between elements varied based on the rice tissues and As species used in treatment, resulting in specific correlation networks. However, some pairs of correlations existed regardless of As species treatment used in this study. Positive correlations between P and Fe were observed in rice roots treated with any of the As species, implying that P and Fe share similar biological processes. The heatmap from hierarchical cluster analysis (HCA) agreed with the principal component analysis (PCA) results in ionomic differentiation between roots and shoots. Furthermore, ionomic differences between rice plants treated with different As species were identified through PCA. This study revealed that the ionomic profiles in rice plants are sufficient to detect responses to environmental perturbations. Association studies between ionomics and genomics are necessary to further understand the potential mechanisms that promote uptake or exclusion of elements in plants.

10.
J Med Chem ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747282

RESUMO

Although intensively expressed within intestine, the precise roles of intestinal dipeptidyl peptidase IV (DPPIV) in numerous pathologies remain incompletely understood. Here, we firstly reported a non-systemic intestine-targeted (NSIT) DPPIV inhibitor with ß-homophenylalanine scaffold, compound 7, which selectively inhibited the intestinal rather than plasmatic DPPIV at an oral dosage as high as 30 mg/kg. We expect compound 7 could serve as a qualified tissues-selective tool to determine the undetected physiological or pathological roles of intestinal DPPIV.

11.
Oncologist ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31748336

RESUMO

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-mutant lung cancer remains an orphan of specific targeted therapy. The variable responses to anti-HER2 therapies in these patients prompt us to examine impact of HER2 variants and co-mutations on responses to anti-HER2 treatments in lung cancer. PATIENTS AND METHODS: Patients with stage IV/recurrent HER2-mutant lung cancers identified through next-generation sequencings were recruited from seven hospitals. The study comprised a cohort A to establish the patterns of HER2 variants and co-mutations in lung cancer and a cohort B to assess associations between HER2 variants, co-mutations, and clinical outcomes. RESULTS: The study included 118 patients (cohort A, n = 86; cohort B, n = 32). Thirty-one HER2 variants and 35 co-mutations were detected. Predominant variants were A775_G776insYVMA (49/118, 42%), G778_P780dup (11/118, 9%), and G776delinsVC (9/118, 8%). TP53 was the most common co-mutation (61/118, 52%). In cohort B, objective response rates with afatinib were 0% (0/14, 95% confidence interval [CI], 0%-26.8%), 40% (4/10, 14.7%-72.6%), and 13% (1/8, 0.7%-53.3%) in group 1 (A775_G776insYVMA, n = 14), group 2 (G778_P780dup, G776delinsVC, n = 10), and group 3 (missense mutation, n = 8), respectively (p = .018). Median progression-free survival in group 1 (1.2 months; 95% CI, 0-2.4) was shorter than those in group 2 (7.6 months, 4.9-10.4; hazard ratio [HR], 0.009; 95% CI, 0.001-0.079; p < .001) and group 3 (3.6 months, 2.6-4.5; HR, 0.184; 95% CI, 0.062-0.552; p = .003). TP53 co-mutations (6.317; 95% CI, 2.180-18.302; p = .001) and PI3K/AKT/mTOR pathway activations (19.422; 95% CI, 4.098-92.039; p < .001) conferred additional resistance to afatinib. CONCLUSION: G778_P780dup and G776delinsVC derived the greatest benefits from afatinib among HER2 variants. Co-mutation patterns were additional response modifiers. Refining patient population based on patterns of HER2 variants and co-mutations may help improve the efficacy of anti-HER2 treatment in lung cancer. IMPLICATIONS FOR PRACTICE: Human epidermal growth factor receptor 2 (HER2)-mutant lung cancers are a group of heterogenous diseases with up to 31 different variants and 35 concomitant genomic aberrations. Different HER2 variants exhibit divergent sensitivities to anti-HER2 treatments. Certain variants, G778_P780dup and G776delinsVC, derive sustained clinical benefits from afatinib, whereas the predominant variant, A775_G776insYVMA, is resistant to most anti-HER2 treatments. TP53 is the most common co-mutation in HER2-mutant lung cancers. Co-mutations in TP53 and the PI3K/AKT/mTOR pathway confer additional resistance to anti-HER2 treatments in lung cancer. The present data suggest that different HER2 mutations in lung cancer, like its sibling epidermal growth factor receptor, should be analyzed independently in future studies.

12.
Nat Commun ; 10(1): 5231, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31745074

RESUMO

The grand challenge in the development of atomically dispersed metallic catalysts is their low metal-atom loading density, uncontrollable localization and ambiguous interactions with supports, posing difficulty in maximizing their catalytic performance. Here, we achieve an interface catalyst consisting of atomic cobalt array covalently bound to distorted 1T MoS2 nanosheets (SA Co-D 1T MoS2). The phase of MoS2 transforming from 2H to D-1T, induced by strain from lattice mismatch and formation of Co-S covalent bond between Co and MoS2 during the assembly, is found to be essential to form the highly active single-atom array catalyst. SA Co-D 1T MoS2 achieves Pt-like activity toward HER and high long-term stability. Active-site blocking experiment together with density functional theory (DFT) calculations reveal that the superior catalytic behaviour is associated with an ensemble effect via the synergy of Co adatom and S of the D-1T MoS2 support by tuning hydrogen binding mode at the interface.

13.
Small ; : e1902828, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31755221

RESUMO

Modern nanotechnologies bring humanity to a new age, and advanced methods for preparing functional nanocrystals are cornerstones. A considerable variety of nanomaterials has been created over the past decades, but few were prepared on the macro scale, even fewer making it to the stage of industrial production. The gap between academic research and engineering production is expected to be filled by flow chemistry technology, which relies on microreactors. Microreaction devices and technologies for synthesizing different kinds of nanocrystals are discussed from an engineering point of view. The advantages of microreactors, the important features of flow chemistry systems, and methods to apply them in the syntheses of salt, oxide, metal, alloy, and quantum dot nanomaterials are summarized. To further exhibit the scaling-up of nanocrystal synthesis, recent reports on using microreactors with gram per hour and larger production rates are highlighted. Finally, an industrial example for preparing 10 tons of CaCO3 nanoparticles per day is introduced, which shows the great potential for flow chemistry processes to transfer lab research to industry.

14.
Gastrointest Endosc ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31738926

RESUMO

BACKGROUND AND AIMS: The studies comparing the diagnostic efficacy of liquid-based cytology (LBC) and smear cytology (SC) of pancreatic tissue sampling obtained via endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are still insufficient. Results were controversial. We compared the diagnostic efficiency of LBC and SC of EUS-FNA of pancreatic lesions in one of the largest tertiary hospitals in China. METHODS: A retrospective database search (Jan 2015 to Jan 2019) was performed for patients who underwent EUS-FNA with both LBC and SC. Demographic, cytological and endosonographic data were collected from 819 patients. 514 cases met the inclusion criteria. Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) were compared. Rapid on-site evaluation (ROSE) was not available in all cases. RESULTS: Three hundred eighty-five cases (74.90%) confirmed with malignancy, 40 cases (7.78%) confirmed benign neoplasm. Adequate tissue sampling rates showed no significant difference between the 2 groups. The sensitivity, accuracy, and NPV of LBC were higher than those of SC with statistical significance (71.4% versus 55.1%, 76.1% versus 61.6%, 40.6% versus 27.7%, respectively).The sensitivity, accuracy and NPV of combined SC and LBC were higher than those of LBC alone with statistical significance (83.9% versus 71.4%, 86.5% versus 76.1%, 56.8% versus 40.6%, respectively). Multivariate analysis revealed that pancreatic neck/body/tail lesions(P=0.003), solid lesions(P<0.001), needle size of 22-gauge (P<0.001), and number of needle passage>3(P=0.041) were associated with higher diagnostic sensitivity in all participants using LBC, whereas number of needle passage>3(P=0.017)was associated with higher diagnostic sensitivity using SC. CONCLUSIONS: LBC was more accurate and sensitive than SC in EUS-FNA of pancreatic lesion with higher NPV, when ROSE is unavailable. Pancreatic neck/body/tail lesions, solid lesions, 22-gauge needle and more than 3 passes are associated with higher sensitivity when using LBC. Doing more than 3 passes is associated with higher sensitivity when using SC.

15.
Int J Biol Macromol ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31739016

RESUMO

Pullulan, a biological macromolecule, has many applications. However, it is completely unknown how and where it is synthesized. In this study, it was found that the multidomain AmAgs2 (α-glucan synthase 2) encoded by an AmAGS2 gene in Aureobasidium melanogenum P16 contained the amylase domain (Amy_D), the glycogen synthetase domain (Gys_D) and the transmembrane regions in which the exopolysaccharide transporter domain (EPST_D) was embedded. Removal of the AmAGS2 gene in A. melanogenum P16 rendered the disruptants not to synthesize any pullulan and complementation of the AmAGS2 gene in the disruptants restored pullulan synthesis. Overexpression of the gene in Aureobasidium melanogenum CBS105.22, a non-pullulan producer, resulted in the transformants producing pullulan. Therefore, the AmAGS2 gene was the key gene responsible for pullulan biosynthesis in A. melanogenum P16. It was speculated that the short α-1,4-glucosyl chains (pullulan primers) were elongated by the Gys_D of the AmAgs2 to form long α-1,4-glucosyl chains (precursors of pullulan). All the precursors were transported to outside plasma membrane by the EPST_D in the transmembrane regions of the AmAgs2. Then, the Amy_D of the AmAgs2 was responsible for both hydrolysis of the endo-α-1,4-linkages in the precursors to release maltotriose and transfer of the maltotriose to Lph-glucose to form α-1,6 glucosidic bonds between maltotrioses in pullulan molecule. This is the first time to report that the AmAgs2 can play the key role in pullulan biosynthesis.

17.
Clin Exp Med ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31745677

RESUMO

To investigate the expression levels of fibroblast activation protein (FAP) in human osteosarcoma tissues and its possible correlations with clinical pathological characteristics of patients with osteosarcoma, and to explore the potential effects of FAP on progression and development of osteosarcoma. Immunohistochemistry (IHC) assay was initially performed to detect the expression levels of FAP in 66 tumor tissues and adjacent non-tumor tissues. Patients were sequentially divided into two groups based on different expression levels of FAP. The correlations between the expression levels of FAP and the clinical pathological characteristics were investigated, and the role of FAP in proliferation, migration, and invasion of osteosarcoma cells was assessed via colony formation, MTT, wound healing, and transwell assays, respectively. The possible effects of FAP on tumor growth and metastasis were evaluated in vivo. We further attempted to reveal the underlying mechanism of FAP involved in tumor growth through bioinformatics and IHC assays. High expression levels of FAP were noted in human osteosarcoma tissues. It also was unveiled that FAP was significantly associated with the tumor size (P = 0.005*) and clinical stage (P = 0.017*). Our data further confirmed that knockdown of FAP remarkably blocked proliferation, migration, and invasion of osteosarcoma cells in vitro, and suppressed tumor growth and metastasis in mice via AKT signaling pathway. The possible role of FAP in progression and development of osteosarcoma could be figured out. Our data may be helpful to develop a novel therapeutic target for the treatment of osteosarcoma.

18.
J Org Chem ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31746602

RESUMO

The first palladium-catalyzed Hiyama cross-coupling of arylsilanes with benzyltrimethyl-ammonium salts is reported. The reaction proceeds smoothly to facilitate C(sp2)-C(sp3) bond formation via cleavage of the C-N bond, and provides a useful approach to various diarylmethanes with a broad substrate scope and excellent functional group tolerance in good to excellent yields.

19.
Nucleic Acids Res ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31680137

RESUMO

ANISEED (https://www.aniseed.cnrs.fr) is the main model organism database for the worldwide community of scientists working on tunicates, the vertebrate sister-group. Information provided for each species includes functionally-annotated gene and transcript models with orthology relationships within tunicates, and with echinoderms, cephalochordates and vertebrates. Beyond genes the system describes other genetic elements, including repeated elements and cis-regulatory modules. Gene expression profiles for several thousand genes are formalized in both wild-type and experimentally-manipulated conditions, using formal anatomical ontologies. These data can be explored through three complementary types of browsers, each offering a different view-point. A developmental browser summarizes the information in a gene- or territory-centric manner. Advanced genomic browsers integrate the genetic features surrounding genes or gene sets within a species. A Genomicus synteny browser explores the conservation of local gene order across deuterostome. This new release covers an extended taxonomic range of 14 species, including for the first time a non-ascidian species, the appendicularian Oikopleura dioica. Functional annotations, provided for each species, were enhanced through a combination of manual curation of gene models and the development of an improved orthology detection pipeline. Finally, gene expression profiles and anatomical territories can be explored in 4D online through the newly developed Morphonet morphogenetic browser.

20.
J Exp Clin Cancer Res ; 38(1): 438, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666108

RESUMO

BACKGROUND: Glutathione S-transferase zeta 1 (GSTZ1) is the penultimate enzyme in phenylalanine/tyrosine catabolism. GSTZ1 is dysregulated in cancers; however, its role in tumorigenesis and progression of hepatocellular carcinoma (HCC) is largely unknown. We aimed to assess the role of GSTZ1 in HCC and to reveal the underlying mechanisms, which may contribute to finding a potential therapeutic strategy against HCC. METHODS: We first analyzed GSTZ1 expression levels in paired human HCC and adjacent normal tissue specimens and the prognostic effect of GSTZ1 on HCC patients. Thereafter, we evaluated the role of GSTZ1 in aerobic glycolysis in HCC cells on the basis of the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Furthermore, we assessed the effect of GSTZ1 on HCC proliferation, glutathione (GSH) concentration, levels of reactive oxygen species (ROS), and nuclear factor erythroid 2-related factor 2 (NRF2) signaling via gain- and loss- of GSTZ1 function in vitro. Moreover, we investigated the effect of GSTZ1 on diethylnitrosamine (DEN) and carbon tetrachloride (CCl4) induced hepatocarcinogenesis in a mouse model of HCC. RESULTS: GSTZ1 was downregulated in HCC, thus indicating a poor prognosis. GSTZ1 deficiency significantly promoted hepatoma cell proliferation and aerobic glycolysis in HCC cells. Moreover, loss of GSTZ1 function depleted GSH, increased ROS levels, and enhanced lipid peroxidation, thus activating the NRF2-mediated antioxidant pathway. Furthermore, Gstz1 knockout in mice promoted DEN/CCl4-induced hepatocarcinogenesis via activation of the NRF2 signaling pathway. Furthermore, the antioxidant agent N-acetylcysteine and NRF2 inhibitor brusatol effectively suppressed the growth of Gstz1-knockout HepG2 cells and HCC progression in Gstz1-/- mice. CONCLUSIONS: GSTZ1 serves as a tumor suppressor in HCC. GSH depletion caused by GSTZ1 deficiency elevates oxidative stress, thus constitutively activating the NRF2 antioxidant response pathway and accelerating HCC progression. Targeting the NRF2 signaling pathway may be a promising therapeutic approach for this subset of HCC.

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