Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 855
Filtrar
1.
Nucleic Acids Res ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32009146

RESUMO

Family with sequence similarity (FAM46) proteins are newly identified metazoan-specific poly(A) polymerases (PAPs). Although predicted as Gld-2-like eukaryotic non-canonical PAPs, the detailed architecture of FAM46 proteins is still unclear. Exact biological functions for most of FAM46 proteins also remain largely unknown. Here, we report the first crystal structure of a FAM46 protein, FAM46B. FAM46B is composed of a prominently larger N-terminal catalytic domain as compared to known eukaryotic PAPs, and a C-terminal helical domain. FAM46B resembles prokaryotic PAP/CCA-adding enzymes in overall folding as well as certain inter-domain connections, which distinguishes FAM46B from other eukaryotic non-canonical PAPs. Biochemical analysis reveals that FAM46B is an active PAP, and prefers adenosine-rich substrate RNAs. FAM46B is uniquely and highly expressed in human pre-implantation embryos and pluripotent stem cells, but sharply down-regulated following differentiation. FAM46B is localized to both cell nucleus and cytosol, and is indispensable for the viability of human embryonic stem cells. Knock-out of FAM46B is lethal. Knock-down of FAM46B induces apoptosis and restricts protein synthesis. The identification of the bacterial-like FAM46B, as a pluripotent stem cell-specific PAP involved in the maintenance of translational efficiency, provides important clues for further functional studies of this PAP in the early embryonic development of high eukaryotes.

2.
Chem Commun (Camb) ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32016195

RESUMO

One-dimensional zig-zag chain and two-dimensional network dysprosium(iii) single-molecule toroics with anisotropy barriers of about 5 and 31 cm-1 under a zero dc field are reported. These are the first one- and two- dimensional homometallic single-molecule toroics reported to date. Furthermore, the two complexes also display white-light emission under UV-light irradiation.

3.
Sci Rep ; 10(1): 2647, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060351

RESUMO

With the booming economy in China, many researches have pointed out that the improvement of regional transportation infrastructure among other factors had an important effect on economic growth. Utilizing a large-scale dataset which includes 3.5 billion entry and exit records of vehicles along highways generated from toll collection systems, we attempt to establish the relevance of mid-distance land transport patterns to regional economic status through transportation network analyses. We apply standard measurements of complex networks to analyze the highway transportation networks. A set of traffic flow features are computed and correlated to the regional economic development indicator. The multi-linear regression models explain about 89% to 96% of the variation of cities' GDP across three provinces in China. We then fit gravity models using annual traffic volumes of cars, buses, and freight trucks between pairs of cities for each province separately as well as for the whole dataset. We find the temporal changes of distance-decay effects on spatial interactions between cities in transportation networks, which link to the economic development patterns of each province. We conclude that transportation big data reveal the status of regional economic development and contain valuable information of human mobility, production linkages, and logistics for regional management and planning. Our research offers insights into the investigation of regional economic development status using highway transportation big data.

4.
Vascul Pharmacol ; : 106651, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32044414

RESUMO

Aspirin is a widely used drug with anti-coagulating and anti-inflammatory effects on atherosclerotic vascular disease. The goal of this study was to investigate expression of microRNA (miR) in association with changes in arachidonic acid (AA) metabolism in cardiac and surrounding fat mesenchymal stem cells (MSCs) treated with or without aspirin. Aspirin-targeted endogenous lipid metabolites that impact specific miRNA expression were examined by mass spectrometry. The pattern of miR expression was characterized using a microarray of 1100 miRs. There were a dozen miRs expressed differentially in MSCs from human myocardium and peri-myocardial fat tissue at baseline, including hsa-miR-1307-3p, 765, 4739, 3613-3p, 4281, 6816-5p, 2861, and 146b-5p. After exposure to aspirin, cardiac MSCs expressed an array of of miRs (eg, hsa-miR-4734, 10a-5p, 4267, 3197, and 3182), while generation of their endogenous AA metabolites was depressed. However, in the peri-cardiac adipose tissue-derived MSCs, treatment with the same doses of aspirin caused mild changes in the miR expression levels. In conclusion, MSCs from human myocardium and peri-myocardial fat tissue respond differentially to aspirin treatment by alterations in miR expression and AA metabolism. The study further raises an intriguing issue as to whether the copious amounts of aspirin taken worldwide by patients with cardiovascular disease may have direct impacts on their heart repair processes by regulation of stromal cell miR expression and AA metabolism.

5.
BMC Plant Biol ; 20(1): 78, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066376

RESUMO

BACKGROUND: The optimized illumination of plants using light-emitting diodes (LEDs) is beneficial to their photosynthetic performance, and in recent years, LEDs have been widely used in horticultural facilities. However, there are significant differences in the responses of different crops to different wavelengths of light. Thus, the influence of artificial light on photosynthesis requires further investigation to provide theoretical guidelines for the light environments used in industrial crop production. In this study, we tested the effects of different LEDs (white, W; blue, B; green, G; yellow, Y; and red, R) with the same photon flux density (300 µmol/m2·s) on the growth, development, photosynthesis, chlorophyll fluorescence characteristics, leaf structure, and chloroplast ultrastructure of Welsh onion (Allium fistulosum L.) plants. RESULTS: Plants in the W and B treatments had significantly higher height, leaf area, and fresh weight than those in the other treatments. The photosynthetic pigment content and net photosynthetic rate (Pn) in the W treatment were significantly higher than those in the monochromatic light treatments, the transpiration rate (E) and stomatal conductance (Gs) were the highest in the B treatment, and the intercellular CO2 concentration (Ci) was the highest in the Y treatment. The non-photochemical quenching coefficient (NPQ) was the highest in the Y treatment, but the other chlorophyll fluorescence characteristics differed among treatments in the following order: W > B > R > G > Y. This includes the maximum photochemical efficiency of photosystem II (PSII) under dark adaptation (Fv/Fm), maximum photochemical efficiency of PSII under light adaptation (Fv'/Fm'), photochemical quenching coefficient (qP), actual photochemical efficiency (ΦPSII), and apparent electron transport rate (ETR). Finally, the leaf structure and chloroplast ultrastructure showed the most complete development in the B treatment. CONCLUSIONS: White and blue light significantly improved the photosynthetic efficiency of Welsh onions, whereas yellow light reduced the photosynthetic efficiency.

6.
AAPS PharmSciTech ; 21(2): 38, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31897797

RESUMO

In the study, we developed a novel oral dosage form of Compound Danshen to resolve the problems of low bioavailability, disequilibrium in drug release, and stomach degradation of active components of Compound Danshen in conventional formulas. A colon-specific osmotic pump capsule (COPC) of Compound Danshen was prepared using a semipermeable shell with the core components. Using a single-factor method, we obtained the optimal formulation that consisted of Salvia miltiorrhiza extract, Panax notoginseng extract, Borneol, sodium chloride, polyethylene oxide wsr-N10, hydroxypropyl-ß-cyclodextrin, and ludipress. Moreover, in vitro dissolution test showed simultaneous releases of active ingredients from Compound Danshen COPC over 12 h at pH 7.8, displaying zero-order release characteristics. The impetus of drug release mainly depended on the difference in osmotic pressure across the capsule shell. Next, scanning electron microscopy showed morphological changes in the capsule shell during the dissolution test. More importantly, pharmacokinetic study in beagle dogs indicated that relative bioavailability was 330.58% and retention time was greatly prolonged in Compound Danshen COPC, compared with those in marketed Compound Danshen tablet products. Finally, in vivo imaging studies in beagle dogs showed that COPC was stable in gastrointestinal tract and the drug was specifically released in the colon region. A colon-specific osmotic pump capsule (COPC) of Compound Danshen was developed and optimized to achieve simultaneous zero-order release of multiple active components of Compound Danshen in the colon. More importantly, the COPC have proved to improve the bioavailability and prolong the retention time of Compound Danshen, compared with those in a marketed product.

7.
Vet Microbiol ; 241: 108555, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31928702

RESUMO

Avian pathogenic Escherichia coli (APEC) causes avian colibacillosis in poultry, which is characterized by systemic infections such as septicemia, air sacculitis, and pericarditis. APEC uses two-component regulatory systems (TCSs) to handle the stressful environments present in infected hosts. While many TCSs in E. coli have been well characterized, the RstA/RstB system in APEC has not been thoroughly investigated. The involvement of the RstA regulator in APEC pathogenesis was demonstrated during previous studies investigating its role in APEC persistence in chicken macrophages and respiratory infections. However, the mechanism underlying this phenomenon has not been clarified. Transcriptional analysis of the effect of rstAB deletion was therefore performed to improve the understanding of the RstA/RstB regulatory mechanism, and particularly its role in virulence. The transcriptomes of the rstAB mutant and the wild-type strain E058 were compared during their growth in the bloodstreams of challenged chickens. Overall, 198 differentially expressed (DE) genes were identified, and these indicated that RstA/RstB mainly regulates systems involved in nitrogen metabolism, iron acquisition, and acid resistance. Phenotypic assays indicated that the rstAB mutant responded more to an acidic pH than the wild-type strain did, possibly because of the repression of the acid-resistance operons hdeABD and gadABE by the deletion of rstAB. Based on the reported RstA box motif TACATNTNGTTACA, we identified four possible RstA target genes (hdeD, fadE, narG, and metE) among the DE genes. An electrophoretic mobility shift assay confirmed that RstA binds directly to the promoter of hdeD, and ß-galactosidase assays showed that hdeD expression was reduced by rstAB deletion, indicating that RstA directly regulates hdeD expression. The hdeD mutation resulted in virulence attenuation in both cultured chicken macrophages and experimentally infected chickens. In conclusion, our data suggest that RstA affects APEC E058 virulence partly by directly regulating the acidic resistance gene hdeD.

8.
Microb Pathog ; 141: 103990, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31978427

RESUMO

Extraintestinal pathogenic Escherichia coli (ExPEC) shows an enhanced ability to cause infection outside the intestinal tract. Avian pathogenic E. coli (APEC), one type of ExPEC, causes avian colibacillosis, a disease of significant economic importance to poultry producers worldwide that is characterized by systemic infection. Some ExPEC strains as well as other pathogenic enterobacteria produce enterobactin, a catecholate siderophore used to sequester iron during infection. Here, we showed that disruption of enterobactin efflux via outer membrane protein TolC significantly decreased the pathogenicity of APEC strain E058. Furthermore, colonization and persistence assays performed using a chicken infection model showed that the ΔtolC mutant was obviously attenuated (p˂0.001). In contrast, disruption of enterobactin synthesis gene entE and/or the inner membrane transporter gene entS had little effect on pathogenicity. Analysis of growth kinetics revealed a significant reduction in the growth of triple mutant strain E058ΔentEΔentSΔtolC in iron-deficient medium compared with the wild-type strain (p˂0.001), while no growth impairment was noted for the E058ΔtolC mutant in either Luria-Bertani broth or iron-deficient medium. The E058ΔentEΔentSΔtolC mutant also showed significantly decreased virulence compared with single mutant strain E058ΔtolC. Low-copy complementation of strains E058ΔtolC and E058ΔentEΔentSΔtolC with plasmid-borne tolC restored virulence to wild-type levels in the chicken infection model. Macrophage infection assays showed that ingestion of E058ΔtolC by macrophage cell line HD11 cells was reduced compared with ingestion of the E058ΔentEΔentSΔtolC mutant. However, no significant differences were observed between the mutants and the wild-type in a chicken serum resistance assay. Together, these results suggest that EntE, EntS and TolC synergistically contributed to the pathogenesis of APEC strain E058 in an iron-deficient environment.

9.
Inflamm Res ; 69(1): 131-137, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31797003

RESUMO

OBJECTIVE: This study sought to evaluate short-term treatment with COX-2 inhibitors and acute changes in colonic PGE2 levels as predictors of long-term efficacy in a genetic model of colorectal cancer. METHODS: Celecoxib oral suspension (40 mg/kg BID) was dosed to Apc-mutant Pirc (F344/NTac-Apcam1137) rats for 4 days (short-term group), or the equivalent dose of 1500 ppm celecoxib was administered in the diet for 4 months (long-term group). Percent inhibition of colonic PGE2 was calculated, and the reduction in colonic PGE2 was assessed in relation to suppression of adenomatous colon polyps. RESULTS: Colonic mucosa PGE2 was fourfold higher in Pirc than in F344 wild-type rats (21 vs. 5.6 pg/mg epithelial tissue), due at least in part to higher COX-2 expression, and this was confirmed by elevated PGE2-d11 levels in Pirc colonic S9 incubations. In the 4-day study, dose-dependent reductions in PGE2 were observed in colonic epithelium (-33% (P>0.05) and -57% (P=0.0012)), after low- and high-dose celecoxib treatments of 4 mg/kg and 40 mg/kg (bid), respectively. In the 4-month study, 1500 ppm celecoxib suppressed colonic epithelium PGE2 by 43.5%, and tumor multiplicity by 80% (P<0.0015). Suppression of plasma 6-keto PGF1α also was corroborated following long-term treatment with 1500 ppm celecoxib (P<0.05). CONCLUSIONS: Acute changes in colonic mucosa PGE2 provided a rapid means of predicting long-term chemopreventive effects from celecoxib, and might be useful for screening of new COX-2 inhibitor compounds.

10.
Small ; 16(2): e1905075, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31814261

RESUMO

Transition-metal phosphides have flourished as promising candidates for oxygen evolution reaction (OER) electrocatalysts. Herein, it is demonstrated that the electrocatalytic OER performance of CoP can be greatly improved by constructing a hybrid CoP/TiOx heterostructure. The CoP/TiOx heterostructure is fabricated using metal-organic framework nanocrystals as templates, which leads to unique hollow structures and uniformly distributed CoP nanoparticles on TiOx . The strong interactions between CoP and TiOx in the CoP/TiOx heterostructure and the conductive nature of TiOx with Ti3+ sites endow the CoP-TiOx hybrid material with high OER activity comparable to the state-of-the-art IrO2 or RuO2 OER electrocatalysts. In combination with theoretical calculations, this work reveals that the formation of CoP/TiOx heterostructure can generate a pathway for facile electron transport and optimize the water adsorption energy, thus promoting the OER electrocatalysis.

11.
J Appl Clin Med Phys ; 21(1): 166-173, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31808307

RESUMO

BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) has gained popularity in radiation therapy simulation because it provides superior soft tissue contrast, which facilitates more accurate target delineation compared with computed tomography (CT) and does not expose the patient to ionizing radiation. However, image registration errors in commercial software have not been widely reported. Here we evaluated the accuracy of deformable image registration (DIR) by using a physical phantom for MRI. METHODS AND MATERIALS: We used the "Wuphantom" for end-to-end testing of DIR accuracy for MRI. This acrylic phantom is filled with water and includes several fillable inserts to simulate various tissue shapes and properties. Deformations and changes in anatomic locations are simulated by changing the rotations of the phantom and inserts. We used Varian Velocity DIR software (v4.0) and CT (head and neck protocol) and MR (T1- and T2-weighted head protocol) images to test DIR accuracy between image modalities (MRI vs CT) and within the same image modality (MRI vs MRI) in 11 rotation deformation scenarios. Large inserts filled with Mobil DTE oil were used to simulate fatty tissue, and small inserts filled with agarose gel were used to simulate tissues slightly denser than water (e.g., prostate). Contours of all inserts were generated before DIR to provide a baseline for contour size and shape. DIR was done with the MR Correctable Deformable DIR method, and all deformed contours were compared with the original contours. The Dice similarity coefficient (DSC) and mean distance to agreement (MDA) were used to quantitatively validate DIR accuracy. We also used large and small regions of interest (ROIs) during between-modality DIR tests to simulate validation of DIR accuracy for organs at risk (OARs) and propagation of individual clinical target volume (CTV) contours. RESULTS: No significant differences in DIR accuracy were found for T1:T1 and T2:T2 comparisons (P > 0.05). DIR was less accurate for between-modality comparisons than for same-modality comparisons, and was less accurate for T1 vs CT than for T2 vs CT (P < 0.001). For between-modality comparisons, use of a small ROI improved DIR accuracy for both T1 and T2 images. CONCLUSION: The simple design of the Wuphantom allows seamless testing of DIR; here we validated the accuracy of MRI DIR in end-to-end testing. T2 images had superior DIR accuracy compared with T1 images. Use of small ROIs improves DIR accuracy for target contour propagation.

12.
J Appl Clin Med Phys ; 21(1): 18-25, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31633877

RESUMO

Validate that a two-dimensional (2D) ionization chamber array (ICA) combined with a double-wedge plate (DWP) can track changes in electron beam energy well within 2.0 mms as recommended by TG-142 for monthly quality assurance (QA). Electron beam profiles of 4-22 MeV were measured for a 25 × 25 cm2 cone using an ICA with a DWP placed on top of it along one diagonal axis. The relationship between the full width half maximum (FWHM) field size created by DWP energy degradation across the field and the depth of 50% dose in water (R50 ) is calibrated for a given ICA/DWP combination in beams of know energies (R50 values). Once this relationship is established, the ICA/DWP system will report the R50 FWHM directly. We calibrated the ICA/DWP on a linear accelerator with energies of 6, 9, 12, 16, 20, and 22 MeV. The R50 FWHM values of these beams and eight other beams with different R50 values were measured and compared with the R50 measured in water, that is, R50 Water. Resolving changes of R50 up to 0.2 cm with ICA/DWP was tested by adding solid-water to shift the energy and was verified with R50 Water measurements. To check the long-term reproducibility of ICA/DWP we measured R50 FWHM on a monthly basis for a period of 3 yr. We proposed a universal calibration procedure considering the off-axis corrections and compared calibrations and measurements on three types of linacs (Varian TrueBeam, Varian C-series, and Elekta) with different nominal energies and R50 values. For all 38 beams on same type of linac with R50 values over a range of 2-8.8 cm, the R50 FWHM reported by the ICA/DWP system agreed with that measured in water within 0.01 ± 0.03 cm (mean ± 1σ) and maximum discrepancy of 0.07 cm. Long-term reproducibility results show the ICA/DWP system to be within 0.04 cm of their baseline over 3 yr. With the universal calibration the maximum discrepancy between R50 FWHM and R50 Water for different types of linac reduced from 0.25 to 0.06 cm. Comparison of R50 FWHM values and R50 Water values and long-term reproducibility of R50 FWHM values indicates that the ICA/DWP can be used for monitoring of electron beam energy constancy well within TG-142 recommended tolerance.

13.
Res Vet Sci ; 128: 16-23, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31707096

RESUMO

Pseudorabies has caused huge economic losses in China's pig industry and recurred on many large pig farms since late 2011. The disease is caused by highly pathogenic, antigenic variant pseudorabies virus (vPRV) strains. Therefore, the prevention and control of this recurrence of pseudorabies in China has been given priority. In a previous study, we showed that a suitable dose [1 × 106.3 50% tissue culture infectious dose (TCID50) per animal] of commercial Bartha-K61 vaccine protects growing pigs against lethal challenge by the emerging vPRV strain XJ5. In this study, different doses of the Bartha-K61 vaccine and our newly developed rPRV-gI-/gE-/TK- prototype vaccine derived from the vPRV strain XJ5 were used to evaluate immune protection against sublethal challenge by the vPRV strain XJ5. Pigs vaccinated with high doses of the Bartha-K61 vaccine or rPRV-gI-/gE-/TK- prototype vaccine showed no differences in their humoral immune responses, clinical symptoms, body weight gains, viral shedding, or gross and histological lesions after sublethal challenge by the vPRV strain XJ5. Therefore, we concluded that the Bartha-K61 vaccine at a dose of 1 × 105 TCID50 per animal protects pigs against sublethal challenge by the vPRV strain XJ5 and performs equally well as the same dose of the rPRV-gI-/gE-/TK- vaccine, whereas lower doses of the Bartha-K61 vaccine alone do not protect pigs from this challenge. These findings provide useful information for vaccination interventions and the ultimate eradication of pseudorabies caused by vPRV strains emerging in China.

14.
J Agric Food Chem ; 68(4): 1015-1021, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31690080

RESUMO

(2S)-Naringenin, a (2S)-flavanone, is widely used in the food, chemical, and pharmaceutical industries because of its diverse physiological activities. The production of (2S)-naringenin in microorganisms provides an ideal source that reduces the cost of the flavonoid. To achieve efficient production of (2S)-naringenin in Saccharomyces cerevisiae (S. cerevisiae), we constructed a biosynthetic pathway from p-coumaric acid, a cost-effective and more efficient precursor. The (2S)-naringenin synthesis pathway genes were integrated into the yeast genome to obtain a (2S)-naringenin production strain. After gene dosage experiments, the genes negatively regulating the shikimate pathway and inefficient chalcone synthase activity were verified as factors limiting (2S)-naringenin biosynthesis. With fed-batch process optimization of the engineered strain, the titer of (2S)-naringenin reached 648.63 mg/L from 2.5 g/L p-coumaric acid. Our results indicate that the constitutive production of (2S)-naringenin from p-coumaric acid in S. cerevisiae is highly promising.

15.
Mol Ther ; 28(1): 293-303, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31611143

RESUMO

Stargardt disease (STGD) is an autosomal recessive retinal disorder caused by a monogenic ABCA4 mutation. Currently, there is no effective therapy to cure Stargardt disease. The replacement of mutated ABCA4 with a functional gene remains an attractive strategy. In this study, we have developed a non-viral gene therapy using nanoparticles self-assembled by a multifunctional pH-sensitive amino lipid ECO and a therapeutic ABCA4 plasmid. The nanoparticles mediated efficient intracellular gene transduction in wild-type (WT) and Abca4-/- mice. Specific ABCA4 expression in the outer segment of photoreceptors was achieved by incorporating a rhodopsin promoter into the plasmids. The ECO/pRHO-ABCA4 nanoparticles induced substantial and specific ABCA4 expression for at least 8 months, 35% reduction in A2E accumulation on average, and a delayed Stargardt disease progression for at least 6 months in Abca4-/- mice. ECO/plasmid nanoparticles constitute a promising non-viral gene therapy platform for Stargardt disease and other visual dystrophies.

16.
Oncogene ; 39(3): 637-650, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31530934

RESUMO

Patients with stage II or III colorectal cancer (CRC) exhibit various clinical outcomes after radical treatments. The 5-year survival rate was between 50 and 87%. However, the underlying mechanisms of the variation remain unclear. Here we show that AMPKα1 is overexpressed in CRC patient specimens and the high expression is correlated with poor patient survival. We further reveal a previously unrecognized function of AMPKα1, which maintains high level of reduced glutathione to keep reduction-oxidation reaction (redox) homeostasis under stress conditions, thus promoting CRC cell survival under metabolic stress in vitro and enhancing tumorigenesis in vivo. Mechanistically, AMPKα1 regulate the glutathione reductase (GSR) phosphorylation possibly through residue Thr507 which enhances its activity. Suppression of AMPKα1 by using nano-sized polymeric vector induces a favorable therapeutic effect, especially when in combination with oxaliplatin. Our study uncovers a novel function of AMPKα1 in redox regulation and identifies a promising therapeutic strategy for treatment of CRC.

17.
Eur Radiol ; 30(2): 1191-1201, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31493211

RESUMO

OBJECTIVES: To assess the value of 18F-FDG PET and MR-IVIM parameters before and during concurrent chemoradiotherapy (CCRT) for evaluating early treatment response and predicting tumor recurrence in patients with locally advanced cervical cancer (LACC) using a hybrid PET/MR scanner. METHODS: Fifty-one patients with LACC underwent pelvic PET/MR scans with an IVIM sequence at two time-points (pretreatment [pre] and midtreatment [mid]). Pre- and mid-PET parameters (SUVmax, MTV, TLG) and IVIM parameters (D, F, D*) and their percentage changes (Δ%SUVmax, Δ%MTV, Δ%TLG, Δ%D, Δ%F, Δ%D*) were calculated. We selected independent imaging parameters and built a combined prediction model incorporating imaging parameters and clinicopathological risk factors. The performance of the combinative evaluation for tumor early shrinkage rates (TESR) and the prediction model for tumor recurrence was assessed. RESULTS: Thirty-two patients were classified into the good response (GR) group with TESR ≥ 50%, and 19 patients were categorized into the poor response (PR) group with TESR < 50%. Δ%D (p = 0.013) and Δ%F (p = 0.006) are independently related to TESR with superior combined diagnostic ability (AUC = 0.901). Pre-TLG, Δ%D, and suspicious lymph node metastasis (SLNM) were selected for the construction of the combined prediction model. The model for identifying the patients with high risk of tumor recurrence reached a moderate predictive ability and good stability with c-index of 0.764 (95% CI, 0.672-0.855). CONCLUSION: The combined prediction model based on pretreatment PET metabolic parameter (pre-TLG), IVIM-D percentage changes, and LNs status provides great potential to identify the LACC patients with high risk of recurrence at early stage of CCRT. KEY POINTS: • PET/MR plus IVIM offers various complementary information for LACC. • IVIM-D and IVIM-F percentage changes are independently related to tumor early shrinkage rates. • The combined prediction model can help identify the LACC patients with high risk of tumor recurrence.

18.
Transbound Emerg Dis ; 67(1): 65-79, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31381232

RESUMO

A strain of porcine epidemic diarrhoea virus (PEDV), namely HLJBY, was isolated in Heilongjiang province, China. To provide insight into the understanding of the phylogenetic and the current epidemiological status of PEDV, PEDV HLJBY was compared with CV777 and other PEDV strains deposited in the GenBank. The homology between the entire genomic nucleotide sequences of PEDV HLJBY and CV777 was 97.7%. The homology of M gene was the highest (99.0%). However, the homology of ORF3 gene was 97.7%, and protein of ORF3 was 90.1%. In addition, HLJBY showed the highest nucleotide identity (99.9%) with PEDV-SX/China/2017 strain and lowest similarity (91.2%) to PEDV/Belgorod/dom/2008 strain. We analysed the changes in S gene and its protein of PEDV HLJBY with 65 historic PEDV strains. The highest nucleotide identity was 99.9% compared with PEDV-SX/China/2017 strain, and the lowest nucleotide identity was 60.0% compared with PEDV/Belgorod/dom/2008 strain. The length of deduced amino acid sequences of S proteins varied from 1,372 to 1,390 amino acids (aa). Compared with most aa sequences of S proteins, HLJBY exhibited 5 aa deletions (position 55, 59-61, 144). Analysis and comparison of open reading frame 3 (ORF3) proteins between HLJBY strain and other PEDV strains were also focused in this study. We revealed that the length of deduced amino acid sequences of ORF3 proteins was 80-224 aa among tested strains and the identity of HLJBY ORF3 amino acids with other PEDV strains was 71.4%-98.9%. ORF3 protein of both HLJBY strain and PEDV-SX/China/2017 strain consists of 91 aa, with 133 aa deletions at their C' end in relation to the other tested PEDV strains. The phylogenetic tree based on different proteins or genes resulted in different phylogenetic groups. For pathogenicity evaluation of PEDV HLJBY strain, colostrum deprivation piglets were challenged with PEDV HLJBY, and PEDV reference strain CV777 as a control, the results showed that animals challenged with either of these PEDV strains developed diarrhoea, and histopathological examination of small intestines of challenged animals showed acute viral enteritis with villous atrophy in either PEDV HLJBY-P10 or PEDV CV777-P8 inoculated piglets.

19.
J Affect Disord ; 263: 60-63, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31818797

RESUMO

BACKGROUND: The high prevalence of depression in general population was related to its social-demographics and cognitive performance. However, no studies investigated the prevalence of depression, its social-demographic and cognitive correlates in psychiatric medical staff. Thus, the aims of this study investigated the prevalence, social-demographic and cognitive correlates of depression in Chinese psychiatric medical staff. METHODS: 186 Chinese psychiatric medical staff were enrolled in Wenzhou Kangning Hospital. Depressive symptom score was assessed by the Self-rating Depression Scale (SDS). Cognition was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RESULTS: The prevalence of depression was 17.74% in these medical staff. The RBANS total score in participants with depressive symptom was significantly lower than that in participants with not depressive symptom after controlling for the confounding variables. The Person correlation analysis found that the normal SDS score in these medical staff was significantly related to age, education, occupations, RBANS total score and subscale scores. Stepwise multivariate regression analysis further identified that age and RBANS total score were significantly associated with the normal SDS score in these medical staff. LIMITATIONS: The limitations included cross-sectional study design, the small sample size, and the self-rating scale of depression. CONCLUSIONS: The prevalence of depression in Chinese psychiatric medical staff was higher in comparison with Chinese general population, but lower in comparison with Chinese medical staff. Cognitive deficits might be considered a core feather of depression that should be a valuable target for future interventions. Age influenced depressive symptom in these medical staff .

20.
Br J Cancer ; 122(2): 209-220, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31819189

RESUMO

BACKGROUND: Mitochondrial dynamics plays an important role in tumour progression. However, how these dynamics integrate tumour metabolism in hepatocellular carcinoma (HCC) metastasis is still unclear. METHODS: The mitochondrial fusion protein mitofusin-1 (MFN1) expression and its prognostic value are detected in HCC. The effects and underlying mechanisms of MFN1 on HCC metastasis and metabolic reprogramming are analysed both in vitro and in vivo. RESULTS: Mitochondrial dynamics, represented by constant fission and fusion, are found to be associated with HCC metastasis. High metastatic HCC displays excessive mitochondrial fission. Among genes involved in mitochondrial dynamics, MFN1 is identified as a leading downregulated candidate that is closely associated with HCC metastasis and poor prognosis. While promoting mitochondrial fusion, MFN1 inhibits cell proliferation, invasion and migration capacity both in vitro and in vivo. Mechanistically, disruption of mitochondrial dynamics by depletion of MFN1 triggers the epithelial-to-mesenchymal transition (EMT) of HCC. Moreover, MFN1 modulates HCC metastasis by metabolic shift from aerobic glycolysis to oxidative phosphorylation. Treatment with glycolytic inhibitor 2-Deoxy-D-glucose (2-DG) significantly suppresses the effects induced by depletion of MFN1. CONCLUSIONS: Our results reveal a critical involvement of mitochondrial dynamics in HCC metastasis via modulating glucose metabolic reprogramming. MFN1 may serve as a novel potential therapeutic target for HCC.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA