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1.
Anticancer Drugs ; 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31913196

RESUMO

Gastric cancer (GC) is lethal and there is an urgent need for improved understanding of this disease. Recent studies have reported that microRNAs (miRNAs) play increasingly important roles in the regulation of GC. In this study, we explored the target genes and effects of miR-7641 in GC. Our data showed that high miR-7641 expression was associated with low expression of ARID1A in GC tissue. miR-7641 expression promoted GC cell proliferation and colony formation. Luciferase reporter assay results confirmed that ARID1A was a target gene of miR-7641. Furthermore, downregulation of ARID1A expression caused a significant increase in GC cell proliferation. In vivo depletion of miR-7641 reduced tumor volume and weight and increased ARID1A and Ki67 expression as well as a decreased terminal-deoxynucleotidyl transferase-mediated nick end labeling in mouse tumor tissues. Conversely, ARID1A silencing reversed the suppressive effects of miR-7641 inhibitors on GC cells. Overall, these findings indicate that miR-7641 is a promising novel prognostic biomarker of GC and may represent a novel target for clinical management of GC.

2.
Abdom Radiol (NY) ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932878

RESUMO

OBJECTIVES: To accurately identify the relationship between a portal radiomics score (rad-score) and pathologic superior mesenteric vein (SMV) resection margin and to evaluate the diagnostic performance in patients with pancreatic head cancer. MATERIALS AND METHODS: A total of 181 patients with postoperatively and pathologically confirmed pancreatic head cancer who underwent multislice computed tomography within one month of resection between January 2016 and December 2018 were retrospectively investigated. For each patient, 1029 radiomics features of the portal phase were extracted, which were reduced using the least absolute shrinkage and selection operator (LASSO) logistic regression algorithm. Multivariate logistic regression models were used to analyze the association between the portal rad-score and SMV resection margin. RESULTS: Patients with negative (R0) and positive (R1) margins accounted for 70.17% (127) and 29.83% (54) of the cohort, respectively. The rad-score was significantly associated with the SMV resection margin status (p < 0.05). Multivariate analyses confirmed a significant and independent association between the portal rad-score and SMV resection margin (OR 4.62; 95% CI 2.19-9.76; p < 0.0001). The portal rad-score had high accuracy (area under the curve = 0.750). The best cut point based on maximizing the sum of sensitivity and specificity was - 0.741 (sensitivity = 64.8%; specificity = 74.0%; accuracy = 71.3%). Decision curve analysis indicated the clinical usefulness of radiomics score. CONCLUSIONS: The portal rad-score is significantly associated with the pathologic SMV resection margin, and it can accurately and noninvasively predict the SMV resection margin in patients with pancreatic cancer.

3.
Cancer Imaging ; 19(1): 83, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801587

RESUMO

BACKGROUND: To investigate and compare the diagnostic performance in T staging for patients with esophagogastric junction cancer using high-resolution magnetic resonance imaging (HR MRI), as compared with conventional MRI at 3 Tesla. METHODS: A total of 118 patients with pathologically confirmed esophagogastric junction cancer were included and underwent multiparameter HR MRI (Cohort 1, 62 patients) or conventional MRI (Cohort 2, 56 patients). T2-weighted, T1-weighted, diffusion-weighted and contrast-enhanced T1-weighted images of each patient were evaluated by two radiologists who determined the preoperative T staging by consensus. Using pathologic staging as the gold standard, the consistency between HR MRI and pathology and between conventional MRI and pathology in T staging was calculated and compared. The overall accuracy, overstatement and understatement of HR MRI and conventional MRI in T staging of patients with esophagogastric junction cancer were computed and compared. Moreover, the diagnostic performance of HR MRI and conventional MRI in T staging (≤ T1 and ≥ T4) of patients with esophagogastric junction cancer were evaluated. RESULTS: There were no significant differences in age (p = 0.465) and sex (p = 0.175) between Cohorts 1 and 2. Excellent agreement was observed in the T staging of patients with esophagogastric junction cancer between pathology and HR MRI (kappa = 0.813), while moderate agreement was observed between pathology and conventional MRI (kappa = 0.486). Significant differences were observed in overall accuracy (88.7% vs 64.3%, p = 0.002) and understatement (1.6% vs 26.8%, p < 0.001) but not for overstatement (9.7% vs 8.9%, p = 0.889) in T staging between HR MRI and conventional MRI techniques. For differentiating the T stages of ≤ T1 from ≥ T2 and the T stages of ≤ T3 from ≥ T4, no significant differences were observed between the imaging techniques. CONCLUSIONS: HR MRI has good diagnostic performance and may serve as an alternative technique in the T staging of patients with esophagogastric junction cancer in clinical practice.

4.
J Immunother Cancer ; 7(1): 327, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779710

RESUMO

BACKGROUND: Programmed death-1 (PD-1) immune checkpoint blockade has achieved clinical successes in cancer therapy. However, the response rate of anti-PD-1 agents remains low. Additionally, a subpopulation of patients developed hyperprogressive disease upon PD-1 blockade therapy. Combination therapy with targeted agents may improve immunotherapy. Recent studies show that p53 activation in the myeloid linage suppresses alternative (M2) macrophage polarization, and attenuates tumor development and invasion, leading to the hypothesis that p53 activation may augment antitumor immunity elicited by anti-PD-1 therapy. METHOD: Using APG-115 that is a MDM2 antagonist in clinical development as a pharmacological p53 activator, we investigated the role of p53 in immune modulation and combination therapy with PD-1 blockade. RESULTS: In vitro treatment of bone marrow-derived macrophages with APG-115 resulted in activation of p53 and p21, and a decrease in immunosuppressive M2 macrophage population through downregulation of c-Myc and c-Maf. Increased proinflammatory M1 macrophage polarization was observed in the spleen from mice treated with APG-115. Additionally, APG-115 has co-stimulatory activity in T cells and increases PD-L1 expression in tumor cells. In vivo, APG-115 plus anti-PD-1 combination therapy resulted in enhanced antitumor activity in Trp53wt, Trp53mut, and Trp53-deficient (Trp53-/-) syngeneic tumor models. Importantly, such enhanced activity was abolished in a syngeneic tumor model established in Trp53 knockout mice. Despite differential changes in tumor-infiltrating leukocytes (TILs), including the increases in infiltrated cytotoxic CD8+ T cells in Trp53wt tumors and M1 macrophages in Trp53mut tumors, a decrease in the proportion of M2 macrophages consistently occurred in both Trp53wt and Trp53mut tumors upon combination treatment. CONCLUSION: Our results demonstrate that p53 activation mediated by APG-115 promotes antitumor immunity in the tumor microenvironment (TME) regardless of the Trp53 status of tumors per se. Instead, such an effect depends on p53 activation in Trp53 wild-type immune cells in the TME. Based on the data, a phase 1b clinical trial has been launched for the evaluation of APG-115 in combination with pembrolizumab in solid tumor patients including those with TP53mut tumors.

5.
Pancreas ; 48(9): 1195-1203, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593021

RESUMO

OBJECTIVE: The objective of this study was to explore the exact relationship between the arterial radiomics score (rad-score) and lymph node (LN) metastasis in pancreatic ductal adenocarcinoma (PDAC). METHODS: A total of 225 patients with pathologically confirmed PDAC who underwent multislice computed tomography within 1 month of resection from December 2016 to August 2017 were retrospectively studied. For each patient, 1029 radiomics features of arterial phase were extracted, which were reduced using the least absolute shrinkage and selection operator logistic regression algorithm. Multivariate logistic regression models were used to analyze the association between the arterial rad-score and LN metastasis. RESULTS: Lymph node-negative and LN-positive patients accounted for 107 (47.56%) and 118 (52.44%) of the cohort, respectively. The rad-score, which consisted of 12 selected features of the arterial phase, was significantly associated with LN status (P < 0.05). Univariate analysis revealed that the arterial rad-score and T stage were independently and positively associated with risk of LN metastasis (P < 0.05). Multivariate analyses revealed a significant association between the arterial rad-score and the LN metastasis (P < 0.0001). Higher arterial rad-score was associated with LN metastasis (P for trend <0.0001). CONCLUSIONS: The arterial rad-score is independently and positively associated with the risk of LN metastasis in PDAC.

6.
Plant Physiol ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31659126

RESUMO

Gibberellin (GA) is known to play an important role in low red/far-red (R:FR) light ratio-mediated hypocotyl and petiole elongation in Arabidopsis. However, the regulatory relationship between low R:FR and GAs remains unclear, especially in gymnosperms. To increase our understanding of the molecular basis of low R:FR-mediated shoot elongation in pines and to determine whether there is an association between low R:FR and GAs action, we explored the morphological and transcriptomic changes triggered by low R:FR, GAs, and paclobutrazol (PAC), a GAs biosynthesis inhibitor, in Pinus tabuliformis seedlings. Transcriptome profiles revealed that low R:FR conditions and GAs have a common set of transcriptional targets in P. tabuliformis. We provide evidence that the effect of low R:FR on shoot elongation in P. tabuliformis is at least partially modulated by GAs accumulation, which can be largely attenuated by PAC. GAs are also involved in the crosstalk between different phytohormones in the low R:FR response. A GA biosynthesis gene, encoding ent-kaurenoic acid oxidase (KAO), was strongly stimulated by low R:FR without being affected by GAs feedback regulation or the photoperiod. We show that GA signaling is required for low R:FR-induced shoot elongation in P. tabuliformis seedlings, and that there are different regulatory targets for low R:FR-mediated GA biosynthesis between conifers and angiosperms.

7.
Biotechnol Biofuels ; 12: 244, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31636703

RESUMO

Background: Trichoderma reesei is widely used for cellulase production and accepted as an example for cellulase research. Cre1-mediated carbon catabolite repression (CCR) can significantly inhibit the transcription of cellulase genes during cellulase fermentation in T. reesei. Early efforts have been undertaken to modify Cre1 for the release of CCR; however, this approach leads to arrested hyphal growth and decreased biomass accumulation, which negatively affects cellulase production. Results: In this study, novel fusion transcription factors (fTFs) were designed to release or attenuate CCR inhibition in cellulase transcription, while Cre1 was left intact to maintain normal hyphal growth. Four designed fTFs were introduced into the T. reesei genome, which generated several transformants, named Kuace3, Kuclr2, Kuace2, and Kuxyr1. No obvious differences in growth were observed between the parent and transformant strains. However, the transcription levels of cel7a, a major cellulase gene, were significantly elevated in all the transformants, particularly in Kuace2 and Kuxyr1, when grown on lactose as a carbon source. This suggested that CCR inhibition was released or attenuated in the transformant strains. The growth of Kuace2 and Kuxyr1 was approximately equivalent to that of the parent strain in fed-batch fermentation process. However, we observed a 3.2- and 2.1-fold increase in the pNPCase titers of the Kuace2 and Kuxyr1 strains, respectively, compared with that of the parent strain. Moreover, we observed a 6.1- and 3.9-fold increase in the pNPCase titers of the Kuace2 and Kuxyr1 strains, respectively, compared with that of Δcre1 strain. Conclusions: A new strategy based on fTFs was successfully established in T. reesei to improve cellulase titers without impairing fungal growth. This study will be valuable for lignocellulosic biorefining and for guiding the development of engineering strategies for producing other important biochemical compounds in fungal species.

8.
Front Microbiol ; 10: 2035, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31551972

RESUMO

Characterizing and engineering microbial communities for lignocellulosic biofuel production has received widespread attention. Previous research has established that Clostridium thermocellum JN4 and Thermoanaerobacterium thermosaccharolyticum GD17 coculture significantly improves overall cellulosic biofuel production efficiency. Here, we investigated this interaction and revealed the mechanism underlying the improved efficiency observed. In contrast to the previously reported mutualistic relationship, a harmful effect toward C. thermocellum JN4 was observed in these microbial consortia. Although T. thermosaccharolyticum GD17 relieves the carbon catabolite repression of C. thermocellum JN4 regarding obtaining more cellobiose or glucose released from lignocellulose, T. thermosaccharolyticum GD17 significantly hampers the growth of C. thermocellum JN4 in coculture. The increased formation of end products is due to the strong competitive metabolic advantage of T. thermosaccharolyticum GD17 over C. thermocellum JN4 in the conversion of glucose or cellobiose into final products. The possibility of controlling and rebalancing these microbial consortia to modulate cellulose degradation was achieved by adding T. thermosaccharolyticum GD17 stimulants into the system. As cellulolytic bacteria are usually at a metabolic disadvantage, these discoveries may apply to a large proportion of cellulosic biofuel-producing microbial consortia. These findings provide a reference for engineering efficient and modular microbial consortia for modulating cellulosic conversion.

9.
FEBS Open Bio ; 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31562747

RESUMO

The functional state (FS) of adult pancreatic islets is regulated by a large array of regulatory molecules including numerous transcription factors. Whether any islet structural molecules play such a role has not been well understood. Here, multiple technologies including bioinformatics analyses were used to explore such molecules. The tight junction family molecule claudin 4 (Cldn4) was the highest enriched amongst over 140 structural genes analysed. Cldn4 expression was ~75-fold higher in adult islets than in exocrine tissues and was mostly up-regulated during functional maturation of developing islet cells. Cldn4 was progressively down-regulated in functionally compromised, dedifferentiating insulin-secreting ß cells and in db/db type 2 diabetic islets. Furthermore, the genetic deletion of Cldn4 impaired significantly the FS without apparently affecting pancreas morphology, islet architectural structure and cellular distribution, and secretion of enteroendocrine hormones. Thus, we suggest a previously unidentified role for Cldn4 in regulating the FS of islets, with implications in translational research for better diabetes therapies.

10.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 31(3): 269-274, 2019 Aug 28.
Artigo em Chinês | MEDLINE | ID: mdl-31544405

RESUMO

OBJECTIVE: To explore the spatial-temporal clustering distribution of schistosomiasis transmission risk in Yunnan Province from 2004 to 2015, so as to provide scientific evidence for the future schistosomiasis control and consolidation of the control achievements. METHODS: All data pertaining to endemic situation of human and bovine schistosomiasis and snail survey at a township level in Yunnan Province from 2004 to 2015 were collected. A descriptive epidemiological method and Joinpoint model were used to describe the changing trends of Schistosoma japonicum infections in humans, bovine and snails, and the hotspots and clusters of schistosomiasis transmission risk were identified using spatial autocorrelation analysis, hotspots analysis and retrospective space-time scan statistic in Yunnan Province from 2004 to 2015. RESULTS: The prevalence of S. japonicum infections appeared a continuous decline in humans, bovine and snails in Yunnan Province from 2004 to 2015, and the estimated number of schistosomiasis cases reduced from 43 056 in 2004 to 756 in 2015, with a decline rate of 98.24%. There were no acute cases since 2008 and no infected snails since 2014 in Yunnan Province. There were significant differences in the changing trends of human and bovine S. japonicum infections in Yunnan Province between 2012 and 2015 and between 2013 and 2015, respectively using the Joinpoint model (P < 0.05). In addition, there was a spatial autocorrelation in human S. japonicum infections in Yunnan Province from 2004 to 2013 (P < 0.01), and the hotspots areas for human S. japonicum infections were mainly distributed in some townships from Dali City, Weishan County and Eryuan County. Retrospective spatial-temporal scanning revealed that S. japonicum human, bovine and snail infections were clustered in 23, 15, 4 townships from Dali City, Weishan County, Eryuan County, Nanjian County and Heqing County, respectively, with relative risks of 6.25 to 28.75 (P < 0.01), which was almost consistent with the cluster areas detected by hotspots analysis. CONCLUSIONS: The endemic situation of schistosomiasis significantly reduced in Yunnan Province from 2004 to 2015; however, there is still a risk of schistosomiasis transmission. The monitoring and control of schistosomiasis should be intensified in the future in Yunnan Province.


Assuntos
Esquistossomose Japônica , Esquistossomose , Animais , Bovinos , China , Humanos , Estudos Retrospectivos , Fatores de Risco , Esquistossomose/epidemiologia , Esquistossomose/prevenção & controle , Esquistossomose/transmissão , Caramujos , Análise Espaço-Temporal
11.
ACS Appl Mater Interfaces ; 11(36): 33356-33363, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31414790

RESUMO

The development of polymeric materials with a combination of excellent mechanical performance and room-temperature self-healing property is still a huge challenge. Here, we report a facile method for the fabrication of dual dynamic cross-linked polymer complexes that simultaneously possess multiple remarkable mechanical properties and room-temperature self-healability by simply mixing polymers that have complementary interactions in solutions. Thanks to the synergistic effects of electrostatic and hydrogen-bonding interactions within their networks, the complexes obtained a superhigh tensile strength of 27.4 MPa and toughness of 110.0 MJ/m3 when compared with other polymers that can self-heal at room temperature. More importantly, the complexes can repair a physical cut in an ∼90% relative humid environment at room temperature with a high healing efficiency of ∼96% because of the dynamic nature of the noncovalent interactions. This method is a simple, low-cost, and widely applicable strategy for the large-scale fabrication of room-temperature self-healing materials that possess superior and controllable mechanical performances.

12.
Thyroid ; 29(10): 1447-1456, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31364476

RESUMO

Background: Inherited medullary thyroid carcinoma (MTC) is primarily caused by RET mutations that are commonly localized in exons 5, 8, 10, 11, and 13-16. In this study, we report pedigrees for individuals with MTC that harbor a germline S409Y variant within exon 6 of the RET proto-oncogene. Methods: Targeted sequencing was used to diagnose four apparently sporadic MTC index cases carrying the germline RET S409Y (c.1226 C>A) variant. Subsequently, 27 relatives of these individuals underwent clinical and genetic assessments and/or thyroid surgery. Furthermore, in silico analyses and in vitro assays were performed to predict or verify the potential oncogenic activity of the S409Y variant. Results: Overall, 15 of 31 participants were found to carry the RET S409Y variant. Of these, 6 presented with isolated MTC (mean age 50.2 years; range 41-75 years), of which 3 presented with neck lymph node metastases and 2 presented with distant liver or lung metastases. Among the remaining 9 carriers, 3 (mean age 56 years; range 41-76 years) had elevated serum calcium-stimulated calcitonin (sCtn) or concurrent marginally elevated serum calcitonin (Ctn) levels, whereas the other 6 (mean age 37.5 years; range 14-52 years) exhibited typical Ctn/sCtn levels (p < 0.05). None of the 15 carriers in these 4 families presented clinical evidence of pheochromocytoma, hyperparathyroidism, or Hirschsprung's disease. In silico analyses revealed that S409Y was a "possibly damaging" mutation that could affect the RET protein inter-domain interface. An in vitro assay revealed that the phosphorylation level of RET tyrosine 905 was relatively higher in the RET S409Y mutant than in wild-type (WT) RET. Moreover, transfection of HEK 293 cells with S409Y enhanced the phosphorylation activity of AKT, ERK pathways, and it increased cell proliferation compared with WT RET, but to a lesser degree than that for the RET C618Y and C634Y mutations. Conclusions: This study demonstrates that the novel germline RET S409Y variant is likely pathogenic and is associated with lower penetrance of MTC than that for the C618Y and C634Y mutations. Individuals with S409Y should be managed using a personalized approach, and additionally, "at-risk" family members should be evaluated. Additional studies are needed to elucidate the correlation between the S409Y mutation and multiple endocrine neoplasia type 2-specific tumors.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31334226

RESUMO

Tyrosol is extensively used in the pharmaceutical industry as an important natural product from plants. In this study, an exogenous pathway involved in catalyzing tyrosine to tyrosol was introduced into Saccharomyces cerevisiae. Furthermore, The pyruvate decarboxylase gene pdc1 was deleted to redirect the flux distribution at the pyruvate node, and a bifunctional NAD+-dependent fused chorismate mutase/prephenate dehydrogenase from E. coli (EcTyrA) and its' tyrosine inhibition resistant mutant (EcTyrAM53I/A354V) were heterologously expression in S. cerevisiae to tuning up the chorismate metabolism effectively directed the metabolic flux toward tyrosol production. Finally, the tyrosol yield of the engineered strain GFT-4 was improved to 126.74 ± 6.70 mg/g DCW at 48 h, increased 440 times compared with that of the control strain GFT-0 (0.28 ± 0.01 mg/g DCW). The new synergetic engineering strategy developed in this study can be further applied to increase the production of high value-added aromatic compounds derived from aromatic amino acid or shikimate in S. cerevisiae.

14.
Appl Microbiol Biotechnol ; 103(14): 5739-5750, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31152202

RESUMO

Auxiliary activity family 9 (AA9) lytic polysaccharide monooxygenases (LPMOs) show significant synergism with cellulase in cellulose degradation. In recent years, there have been many reports on AA9 LPMOs; however, the identification of efficient and thermostable AA9 LPMOs with broad potential for industrial applications remains necessary. In this study, a new AA9 LPMO from Talaromyces cellulolyticus, named TcAA9A, was identified. An analysis of the oxidation products of phosphoric acid-swollen cellulose categorized TcAA9A as a type 3 AA9 LPMO, and TcAA9A exhibited a better synergistic effect with cellulase from Trichoderma reesei than what is seen with TaAA9A, a well-studied AA9 LPMO from Thermoascus aurantiacus. Two AA9 LPMOs were successfully expressed in T. reesei, and the transformants were named TrTcAA9A and TrTaAA9A. The activities and thermostabilities of the AA9 LPMOs in TrTcAA9A were higher than those of the AA9 LPMOs in TrTaAA9A or the parent. The enzyme solution of TrTcAA9A was more efficient than that of the parent or TrTaAA9A for the degradation of Avicel and delignified corncob residue. Thus, TcAA9A showed a better performance than TaAA9A in T. reesei cellulase cocktails. This study may offer an innovative solution for improving enzyme cocktail activity for lignocellulosic degradation.


Assuntos
Proteínas Fúngicas/metabolismo , Lignina/metabolismo , Oxigenases de Função Mista/metabolismo , Polissacarídeos/metabolismo , Thermoascus/enzimologia , Celulase/metabolismo , Celulose/metabolismo , Estabilidade Enzimática , Oxirredução , Temperatura Ambiente , Trichoderma/metabolismo
15.
Org Biomol Chem ; 17(20): 5075-5085, 2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-31066740

RESUMO

Oxacalix[4]arenes obtained from the highly efficient, one-pot SNAr reaction were post-macrocyclization functionalized through the reduction of nitro groups and hydrolysis of the ester groups to obtain several derivatives of desired solubility. The difficulties in basic hydrolysis of ester groups were overcome via developing an acid hydrolysis method for tert-butyl ester derivatives of this class. The synthesis of symmetrical oxacalix[4]arenes from an unsymmetrically substituted precursor was also explored via a multiple step fragment coupling approach. Compounds 17 & 18 adopted 1,3-alternate conformations in the solid state as most oxacalix[4]arenes did, and a chair (zigzag) conformation was revealed for tetraamido oxacalix[4]arene (6a) by X-ray single crystal analysis. The tetraureido oxacalixarene (7) showed strong association towards various anions such as F-, Cl-, Br-, I-, Ac-, and HSO4- with a 1 : 1 stoichiometry as revealed by 1H NMR analysis and UV-vis measurements.

16.
Tree Physiol ; 39(7): 1173-1186, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31073594

RESUMO

It has long been known that the pollen shedding time in pine trees is correlated with temperature, but the molecular basis for this has remained largely unknown. To better understand the mechanisms driving temperature response and to identify the hub regulators of pollen shedding time regulation in Pinus tabuliformis Carr., we identified a set of temperature-sensitive genes by carrying out a comparative transcriptome analysis using six early pollen shedding trees (EPs) and six late pollen shedding trees (LPs) during mid-winter and at three consecutive time points in early spring. We carried out a weighted gene co-expression network analysis and constructed a transcription factor (TF) collaborative network, merging the common but differentially expressed TFs of the EPs and LPs into a joint network. We found five hub genes in the core TF module whose expression was rapidly induced by low temperatures. The transcriptional activity of this TF module was strongly associated with pollen shedding time, and likely to produce the fine balance between cold hardiness and growth activity in early spring. We confirmed the key role of temperature in regulating flowering time and identified a transcription factor module associated with pollen shedding time in P. tabuliformis. This suggests that repression of growth activity by repressors is the main mechanism balancing growth and cold hardiness in pine trees in early spring. Our results provide new insights into the molecular mechanisms regulating seasonal flowering time in pines.

17.
Environ Sci Technol ; 53(10): 5717-5724, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31009209

RESUMO

Although strong in vivo-in vitro correlations (IVIVCs) between relative bioavailability (RBA) and bioaccessibility of soil Pb were well reported, knowledge on the fractions of bioaccessible Pb in simulated gastrointestinal (GI) fluids that are available for absorption into the systemic circulation is limited. Here, Pb-RBA in 14 Pb-contaminated soils were assessed using an in vivo mouse bioassay and compared to Pb bioaccessibility by the gastrointestinal phase of the UBM (Unified Bioaccessibility research group of Europe (BARGE) Method) in vitro assay with and without 0.45 µm filtration of GI fluid. Results showed good IVIVC between Pb-RBA and Pb bioaccessibility without filtration ( r 2 = 0.62), while Pb bioaccessibility with filtration provided a poor correlation with Pb-RBA ( r 2 = 0.16). This suggested that besides dissolved Pb ions, Pb-complexes formed in the UBM gastrointestinal fluid might also contribute to bioavailable Pb. To ascertain this, DGT (diffusive gradients in thin-films) devices which can measure both Pb2+ ions and labile inorganic and organic Pb-complexes were introduced to the UBM fluids to measure Pb DGT-bioaccessibility, which showed strong correlation to Pb-RBA ( r 2 = 0.71). With increasing diffusive gel thickness which could enhance release of Pb ions from Pb-complexes, Pb DGT-bioaccessibility increased by 3.4-5.7 times, while inclusion of dialysis membrane within DGT devices significantly decreased Pb DGT-bioaccessibility by inhibiting diffusion of Pb complexes to binding gel. These results confirmed the contribution of Pb-complexes to Pb bioavailability, providing new insights to Pb bioavailability.


Assuntos
Poluentes do Solo , Animais , Bioensaio , Disponibilidade Biológica , Europa (Continente) , Camundongos , Diálise Renal , Solo
18.
Microbiol Resour Announc ; 8(13)2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30923241

RESUMO

Here, we describe the complete genome sequence of the Brevundimonas diminuta ATCC(B) 19146 strain, which contains 3,375 protein-coding genes and 61 RNAs within its 3,551,819-bp-long genome. The genome consists of a circular chromosome.

19.
Anal Chim Acta ; 1050: 88-94, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30661595

RESUMO

Analysis of organic pollutants is usually accomplished in centralized laboratories. However, the time-delayed and time-consuming process is insufficient and risky for precisely detection due to the contamination of vials, the losses of analytes during transportation and storage. Herein, a rapid and highly sensitive on-site detection approach was developed without using any vials by coupling an on-site pre-equilibrium solid phase microextraction (SPME) sampling method with a portable gas chromatography mass spectrometer (portable GC-MS), for the determination of three families of persistent organic pollutants (polychlorinated biphenyls, organochlorine pesticides and polycyclic aromatic hydrocarbons). Based on sampling-rate (SR) calibration method, the concentrations of target analytes in aquatic systems could be easily determined. Limits of detection (LODs) in the low parts-per-tillion levels (≤5.25 ng·L-1) were obtained for most of the investigated analytes with a total analysis time only ∼30 min. The proposed on-site detection approach was then successfully applied in the determination of persistent organic pollutants in real aquatic environment. A comparable result obtained by liquid extraction (LE) equipped with laboratorial GC-MS demonstrated the accuracy of the on-site detection method. In general, this study demonstrated a rapid and highly sensitive on-site approach, avoiding any risks of contamination during sampling and analysis, for determination of POPs as well as the potential applications for other organic pollutants in aquatic phase.

20.
JAMA Dermatol ; 155(3): 327-334, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30698628

RESUMO

Importance: It is necessary to determine whether psoriasis responds to methotrexate in the same manner in patients with and without psoriatic arthritis. Objective: To evaluate the effectiveness and safety of methotrexate in treating patients with psoriasis with and without psoriatic arthritis. Design, Setting, and Participants: In this prospective, single-arm, interventional study, a total of 235 patients with psoriasis, 107 without psoriatic arthritis and 128 with psoriatic arthritis who were receiving methotrexate therapy from April 1, 2015, to December 31, 2017, were recruited from the outpatient department of a hospital at a large Chinese university. There were no significant demographic or clinical differences between the subgroups with the exception of diabetes. Interventions: A 12-week course of low-dosage oral methotrexate (7.5-15 mg weekly). Main Outcomes and Measures: Changes in disease severity, adverse events, blood cell counts, and liver and renal function. Results: A total of 235 patients with psoriasis (166 male [66.0%]; mean [SD] age, 49.6 [15.1] years) received methotrexate treatment for 12 weeks. The 90% reduction from baseline Psoriasis Area Severity Index response was significantly lower in patients with psoriatic arthritis than in patients without psoriatic arthritis at week 8 (4 0f 128 [3.1%] vs 12 of 107 [11.2%]; P = .02) and week 12 (19 of 128 [14.8%] vs 27 of 107 [25.2%]; P = .049). Furthermore, the incidence of adverse events, including dizziness (12 of 128 [9.4%] vs 1 of 107 [0.9%]; P = .007), gastrointestinal symptoms (32 of 128 [25.0%] vs 13 of 107 [12.1%]; P = .01), and hepatoxicity (34 of 128 [26.6%] vs 16 of 107 [15.0%]; P = .04), was significantly higher in patients with psoriatic arthritis than in patients without psoriatic arthritis. Methotrexate-induced elevation of alanine aminotransferase levels was associated with body mass index (mean [SD] body mass index, 26 [4] in patients with [P = .04] vs 26 [4] in those without [P = .005] psoriatic arthritis) and smoking (17 of 34 [50.0%] in patients with [P = .02] vs 9 of 16 [56.3%] in those without [P = .04] psoriatic arthritis). Conclusions and Relevance: In this study, methotrexate was well tolerated and effective in treating psoriasis. It was more effective, with fewer adverse effects, in patients with psoriasis who did not have psoriatic arthritis than in patients who presented with both psoriasis and psoriatic arthritis. Therefore, methotrexate can be recommended as first-line treatment for psoriasis without arthritis.

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