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1.
Ecotoxicol Environ Saf ; 198: 110623, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32361490

RESUMO

Humans are exposed to polybrominated diphenyl ethers (PBDEs) via ingestion of food, dust inhalation, and dermal absorption. Exposure to PBDEs via the placenta and breast milk is a special and important pathway in infants. This nested case-control study aimed to investigate the levels of PBDEs in maternal serum and colostrum, and to assess the association between the occurrence of fetal growth restriction (FGR) and prenatal exposure to PBDEs. We recruited 293 mother-newborn pairs, including 98 FGR cases and 195 healthy controls in Wenzhou, China. Maternal serum and colostrum samples were collected during pregnancy and after delivery, respectively, and the levels of PBDEs were measured by gas chromatography-tandem mass spectrometry. The total levels of PBDEs in maternal serum and colostrum were found to be in equilibrium, but congener profiles of PBDEs in these matrices were different. Increased BDE-207, BDE-209, ∑BDE196-209 and ∑PBDEs levels in maternal serum and BDE-99, ∑BDE17-154 and ∑PBDEs levels in colostrum were correlated with decreased birth weight Z score. Increased concentrations of higher brominated BDEs in maternal serum (odds ratio (OR) = 1.010, 95%CI = 1.003-1.018) and low-to moderately brominated BDEs in colostrum (OR = 1.004, 95%CI = 1.000-1.009) were associated with increased risk of FGR, which showed an exposure-response relationship. In addition, infants with FGR were more exposed to PBDEs in colostrum after birth than healthy infants. Longitudinal birth cohort studies are needed to determine the prolonged effect of PBDEs exposure on the growth of FGR infants in the future.

2.
Nucleic Acids Res ; 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32329779

RESUMO

Recent advances in genomic technologies have generated data on large-scale protein-DNA interactions and open chromatin regions for many eukaryotic species. How to identify condition-specific functions of transcription factors using these data has become a major challenge in genomic research. To solve this problem, we have developed a method called ConSReg, which provides a novel approach to integrate regulatory genomic data into predictive machine learning models of key regulatory genes. Using Arabidopsis as a model system, we tested our approach to identify regulatory genes in data sets from single cell gene expression and from abiotic stress treatments. Our results showed that ConSReg accurately predicted transcription factors that regulate differentially expressed genes with an average auROC of 0.84, which is 23.5-25% better than enrichment-based approaches. To further validate the performance of ConSReg, we analyzed an independent data set related to plant nitrogen responses. ConSReg provided better rankings of the correct transcription factors in 61.7% of cases, which is three times better than other plant tools. We applied ConSReg to Arabidopsis single cell RNA-seq data, successfully identifying candidate regulatory genes that control cell wall formation. Our methods provide a new approach to define candidate regulatory genes using integrated genomic data in plants.

3.
Dalton Trans ; 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32232276

RESUMO

Isostructural mixed alkali/alkaline-earth metal tellurite halides BaLiTe2O5X (X = Cl, Br) have been successfully synthesized by a mild hydrothermal method, which possess the [Te2O5]∞ chains formed by the corner-sharing connections of the TeO3 and TeO4 polyhedra. The [Te2O5]∞ chains are bridged via the LiO3 polyhedra to form the [LiTe2O5]∞ layers with 4- and 6-membered rings. The adjacent [LiTe2O5]∞ layers are linked via the BaO9 polyhedra to form the [BaLiTe2O5]∞ double layers, which are further connected via weak Ba-X-Li interactions to generate a 3D framework. Analysis of different lithium tellurites shows that the different arrangements of the Te-O and Li-O units in the lithium tellurites can be attributed to the cation-cation repulsion and lone-pair effect. Both compounds display good thermal stability, wide optical bandgaps (4.25 and 4.13 eV), and large birefringence. First-principles calculations indicate that the TeOn groups and X- determine the optical properties of BaLiTe2O5X (X = Cl, Br).

5.
Artigo em Inglês | MEDLINE | ID: mdl-32249563

RESUMO

The grain boundaries of perovskite polycrystalline are regarded as a defect region that not only provides carrier recombination sites but also introduces device degradation pathways. Efforts to enlarging the grain size of a perovskite film and reducing its grain boundary are crucial for highly efficient and stable perovskite solar cells (PSCs). Some effective methods that facilitate grain growth are postdeposition thermal annealing and solvent vapor annealing. However, a detailed understanding of grain growth mechanisms in perovskite films is lacking. In this study, perovskite films were prepared by adding ethylamine hydrochloride (EACl) to the precursor solution. This additive strategy promotes a new grain growth mode, secondary grain growth, in perovskite films. Secondary grain growth leads to much larger grains with a high crystallographic orientation. These excellent properties lead to reduced grain boundaries and the densities of boundary defects. The improved film quality results in a prolonged charge-carrier lifetime and a significantly enhanced power conversion efficiency (PCE). Compared with the 18.42% PCE of the control device, the PCE of the device with EACl additives reaches 21.07%.

6.
Thyroid ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32245343

RESUMO

Background: The appropriate range of median urinary iodine concentration (MUI) in children has always been controversial. To prevent the occurrence of a goiter epidemic in Shanghai, we explored the appropriate range of MUI by integrating multiple monitoring results. Methods: This study summarized and analyzed the monitoring data from 1997, 1999, 2011, 2014, and 2017 of children living in Shanghai. In each monitoring year, the probability-proportional-to-size sampling technique was used to select 30 sampling units. In each sampling unit, one primary school was randomly selected. From each selected school, 40 children 8- to 10-year-old were randomly recruited to measure thyroid volume (Tvol) and their household salt iodine intake. Results: In 1997, 1999, 2011, 2014, and 2017, MUI of 8- to 10-year-old children was 228, 214, 182, 171, and 183 µg/L, and median Tvol (MTvol) was 2.9, 1.2, 1.0, 1.8, and 2.8 mL, respectively. There was a linear correlation between goiter rate and MTvol (r = 0.95, p = 0.014; 100 × goiter rate = 1.314 × MTvol -1.287). Generalized additive model (GAM) was used to predict MTvol as follows, MTvol = 0.60689 + 0.00302 MUI +0.999928 s (MUI) -0.05172 mean salt iodized concentrations (MSIs) +0.03481 × 100 × iodized salt coverage rate +0.00000969 per capita disposable income +0.271422 s (per capita disposable income) -0.38772 × monitoring year gap. The results revealed that the average relative error between predicted and actual value was 15.2%. GAM results showed that at 27-277 µg/L MUI, the goiter rate was <5%. Conclusions: Iodine status is appropriate in Shanghai. Under the existing economy and MSI, the optimal range of MUI should be 70-277 µg/L in 8- to 10-year-old children living in Shanghai.

7.
Medicine (Baltimore) ; 99(17): e19480, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332600

RESUMO

BACKGROUND: The digestive tract malignancies are a series of malignant tumor with high morbidity and mortality. Traditional Chinese medicine (TCM) combined with chemotherapy drugs interventions have been applied for the treatment of malignant tumors in Asian countries for dacades. This study aimed to assess the effectiveness and safety on the combination of Kanglaite injection and fluorouracil-based chemotherapy for treating digestive tract malignancies. PURPOSE: To assess the effectiveness and safety on the combination of Kanglaite injection and fluorouracil-based chemotherapy for digestive tract malignancies. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed when conducting the meta-analysis. Randomized controlled trials (RCTs) of Kanglaite injection combined with fluorouracil-based chemotherapy in the treatment of digestive tract malignant tumors were selected and assessed for inclusion. RevMan 5.3 software (Cochrane Collaboration, Oxford, UK) was used for meta-analysis. The objective response rate (ORR) was defined as the primary endpoint, and the disease control rate (DCR), quality of life (QoL), and toxicities were the secondary outcomes. RESULTS: 20 RCTs enrolling 1339 patients with advanced digestive tract malignancies were included. The methodological quality of most included trials was low to moderate. Compared with fluorouracil-based chemotherapy alone, Kanglaite injection plus fluorouracil-based chemotherapy can improve DCR (risk ratio (RR) = 1.18, 95% confidence interval (CI) 1.11-1.25, P < .00001), ORR (RR = 1.35, 95% CI 1.18-1.54, P < .00001), QoL (RR = 1.58, 95% CI 1.35-1.85, P < .00001), and can reduce adverse drug reactions (ADRs) such as myelosuppression (RR = 0.33, 95% CI 0.25-0.43, P < .00001), leukopenia (RR = 0.31, 95% CI 0.22-0.43, P < .00001), thrombocytopenia (RR = 0.6, 95% CI 0.38-0.49, P = .03), neutropenia (RR = 0.26, 95% CI 0.12-0.55, P = .0005), anemia (RR = 0.41, 95% CI 0.23-0.75, P = .004), gastrointestinal reaction (RR = 0.35, 95% CI 0.27-0.46, P < .00001), nausea/vomiting (RR = 0.41, 95% CI 0.28-0.61, P < .00001), diarrhea (RR = 0.34, 95% CI 0.18-0.62, P = .0004), hepatotoxicity (RR = 0.28, 95% CI 0.17-0.47, P < .00001), neurotoxicity (RR = 0.58, 95% CI 0.41-0.82, P = .002), mucositis (RR = 0.59, 95% CI 0.29-1.21, P = .15). CONCLUSION: Kanglaite injection combined with fluorouracil-based chemotherapy could remarkably improve the clinical effectiveness and reduce the adverse effects in patients with advanced malignant tumors of the digestive tract which may provide evidence to judge whether TCM is an effective and safe intervention for the digestive tract malignancies.

8.
Stress ; : 1-8, 2020 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-32233890

RESUMO

Extensive evidence indicates that noradrenergic activation is essentially involved in mediating the enhancing effects of emotional arousal on memory consolidation. Our current understanding of the neurobiological mechanisms underlying the memory-modulatory effects of the noradrenergic system is primarily based on pharmacological studies in rats, employing targeted administration of noradrenergic drugs into specific brain regions. However, the further delineation of the specific neural circuitry involved would benefit from experimental tools that are currently more readily available in mice. Previous studies have not, as yet, investigated the effect of noradrenergic enhancement of memory in mice, which show different cognitive abilities and higher endogenous arousal levels induced by a training experience compared to rats. In the present study, we investigated the effect of posttraining noradrenergic activation in male C57BL/6J mice on the consolidation of object recognition and object location memory. We found that the noradrenergic stimulant yohimbine (0.3 or 1.0 mg/kg) administered systemically immediately after an object training experience dose-dependently enhanced 24-h memory of both the identity and location of the object. Thus, these findings indicate that noradrenergic activation also enhances memory consolidation processes in mice, paving the way for a systematic investigation of the neural circuitry underlying these emotional arousal effects on memory.LAY SUMMARY: The current study successfully validated the effect of noradrenergic activation on both object recognition and object location memory in mice. This study thereby provides a fundamental proof-of-principle for the investigation of the neural circuitry underlying noradrenergic and arousal effects on long-term memory in mice.

9.
Environ Res ; 186: 109549, 2020 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-32325291

RESUMO

The frequent occurrence of toxin-producing cyanobacteria blooms driven by anthropogenic eutrophication has become a major threat to aquaculture ecosystems worldwide. In this study, the behavior of M. aeruginosa cells during flocs storage period of 6 days was first investigated after pre-oxidation and coagulation of Fe2+/PS. Fe2+/PS achieved a superior removal efficiency of 90.7% for OD680 and 90.4% for chl-a. The contents of extracellular MCs in the pre-oxidation and coagulation system were significantly (P < 0.05) lower than those in the control. A significant (P < 0.05) difference in intracellular protein between the control and the coagulated systems was observed. Three-dimensional fluorescence excitation emission matrix (EEM) was employed to investigate the variations in extracellular organic matter (EOM) during flocs storage. The results indicated the presence of four peaks, representing protein-like substances, intermediate dissolved microbial metabolites, fulvic and humic-like compounds in the Fe2+/PS process. And the intensities of four peaks were all decreased in the Fe2+/PS system compared to those in the control. A low level of accumulated residual Fe of 0.28 mg/L was observed without posing potential environmental risk. The results showed that the M. aeruginosa cells were under stressful conditions after 3-d storage due to the decomposition of extracellular polymeric substances (EPSs) and the insufficient supply of nutrients. However, SEM results indicated that no significant alteration in cell morphology was observed. Therefore, with high removal of M. aeruginosa, low MCs concentrations, and trivial cell damage, the Fe2+/PS preoxidation-coagulation was proved to be an environmental-friendly method for cyanobacteria removal without yielding serious secondary pollution. This work will contribute to better understanding and managing the cyanobacteria-laden aquaculture water after pre-oxidation and coagulation.

10.
J Cancer Res Clin Oncol ; 146(6): 1533-1543, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32281025

RESUMO

PURPOSE: To evaluate the efficacy of 177Lu-DOTA0-Tyr3-octreotate (177Lu-DOTATATE) radionuclide therapy in patients with inoperable or metastatic neuroendocrine tumours (NETs), (PROSPERO ID CRD42019130755). METHODS: All published clinical studies of NETs treated with 177Lu-DOTATATE were identified based on systematic searches in the PubMed, EMBASE, Cochrane Library, Web of Science and ClinicalTrials.gov databases up to January 2019. Among these studies, only the reports evaluated with the "Response Evaluation Criteria in Solid Tumours (RECIST)" or "Southwest Oncology Group (SWOG)" criteria or both were included. We analysed the disease response rate (DRR) and disease control rate (DCR) of each group to evaluate the efficacy of 177Lu-DOTATATE. RESULTS: Fifteen studies were selected from 715 references. The pooled effect in the RECIST group (13 studies) was 27.58% (95% confidence interval (CI) 21.03-35.27%) for the DRR and 79.14% (95% CI 75.83-82.1%) for the DCR. In the SWOG criteria group (7 studies), the pooled effect was 20.59% (95% CI 10.89-35.51%) for the DRR and 78.28% (95% CI 74.39-81.72%) for the DCR. Therefore, the RECIST and SWOG groups showed similar DRRs and DCRs after177Lu-DOTATATE treatment, indicating that 177Lu-DOTATATE treatment has excellent efficacy with a control rate of approximately 78-79%. Moreover, adverse effects of 177Lu-DOTATATE were minimal, including fatigue, nausea, vomiting and hormonal disorders. CONCLUSIONS: For patients with inoperable or metastatic NETs, 177Lu-DOTATATE is an effective treatment with minimal side effects.

11.
Biochem Biophys Res Commun ; 526(3): 764-771, 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32265032

RESUMO

BACKGROUND: Wnt/ß-catenin signaling is involved in glucose and lipid metabolism, but the mechanism is not clear yet. AIM: The objective is to study mechanisms of Wnt/ß-catenin signaling on regulating hepatocytes metabolism. METHODS: Real-time qPCR, Western blot, and Oil-red O staining methods were used. RESULTS: The Wnt/ß-catenin signaling was activated in hepatocytes by CP21R7, and the level of phosphorylated IRS-1 (Ser307) and TRB3 were significantly increased, while the levels of phosphorylated IRS-1 (Tyr612) and phosphorylated Akt were decreased. Moreover, the expression of FGF21, FAS, SCD1, PPARγ and ADRP was significantly increased. The expression of ATF4, ATF5, eIF2α, GRP78, CHOP and phosphorylated level of PERK were also increased. The expression of FGF21 and TRB3 was significantly down-regulated, and the lipid droplets were notably reduced after the ER stress was inhibited by TUDCA. The expression of FGF21 was significantly decreased when the IRE1 pathway of the UPR was inhibited by STF-083010. CONCLUSIONS: Activation of Wnt/ß-catenin signaling pathway could cause insulin resistance and lipogenesis in hepatocytes via regulation of the IRE1 pathway of the ER stress and UPR, providing new targets for the treatment of metabolic disorders.

12.
Radiology ; : 200905, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32191588

RESUMO

Background Coronavirus disease has widely spread all over the world since the beginning of 2020. It is desirable to develop automatic and accurate detection of COVID-19 using chest CT. Purpose To develop a fully automatic framework to detect COVID-19 using chest CT and evaluate its performances. Materials and Methods In this retrospective and multi-center study, a deep learning model, COVID-19 detection neural network (COVNet), was developed to extract visual features from volumetric chest CT exams for the detection of COVID-19. Community acquired pneumonia (CAP) and other non-pneumonia CT exams were included to test the robustness of the model. The datasets were collected from 6 hospitals between August 2016 and February 2020. Diagnostic performance was assessed by the area under the receiver operating characteristic curve (AUC), sensitivity and specificity. Results The collected dataset consisted of 4356 chest CT exams from 3,322 patients. The average age is 49±15 years and there were slightly more male patients than female (1838 vs 1484; p-value=0.29). The per-exam sensitivity and specificity for detecting COVID-19 in the independent test set was 114 of 127 (90% [95% CI: 83%, 94%]) and 294 of 307 (96% [95% CI: 93%, 98%]), respectively, with an AUC of 0.96 (p-value<0.001). The per-exam sensitivity and specificity for detecting CAP in the independent test set was 87% (152 of 175) and 92% (239 of 259), respectively, with an AUC of 0.95 (95% CI: 0.93, 0.97). Conclusions A deep learning model can accurately detect COVID-19 and differentiate it from community acquired pneumonia and other lung diseases.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32219946

RESUMO

Organic solid-state semiconductor lasers are attracting ever-increasing interest for their potential application in future photonic circuits. Despite the great progress made in recent years, an organic laser from 3D chiral structures has not been achieved. Now, the first example of an organic nano-laser from the micro-helix structure of an achiral molecule is presented. Highly regular micro-helixes with left/right-handed helicity from a distyrylbenzene derivative (HM-DSB) were fabricated and characterized under microscope spectrometers. These chiral micro-helixes exhibit unique photonic properties, including helicity-dependent circularly polarized luminescence (CPL), periodic optical waveguiding, and length-dependent amplified spontaneous emission (ASE) behavior. The successful observation of laser behavior from the organic micro-helix extends our understanding to morphology chirality of organic photonic materials and provides a new design strategy towards chiral photonic circuits.

14.
Chemosphere ; 249: 126463, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32213388

RESUMO

The brown planthopper (BPH), Nilaparvata lugens, is a resurgent pest with an unexpected response to jinggangmycin (JGM), a broadly applied antibiotic used to control rice sheath blight disease. JGM stimulates BPH fecundity, but the underlining molecular mechanisms remain unclear. Here we report that JGM sprays led to increased glucose concentrations, photosynthesis and gene expression, specifically Rubsico, sucrose phosphate synthase, invertase 2 (INV2) and INV3 in rice plants. JGM sprays led to high-glucose rice plants. Feeding BPH on these plants led to increased insulin-like signaling and vitellogenin synthesis. Treating BPH with metformin, a gluconeogenesis inhibitor, reversed the influence of feeding on high-glucose rice, which was rescued by glucose injections. Silencing insulin-like peptide 2 using per os dsRNA led to reduction in juvenile hormone (JH) III titers and other fecundity parameters, which were reversed by topical applications of the JH analog, methoprene. We infer that JGM acts via two broad mechanisms, one through increasing rice plant sugar concentrations and a second by upregulating BPH insulin-like signaling.


Assuntos
Antibacterianos/farmacologia , Hemípteros/fisiologia , Inositol/análogos & derivados , Oryza/metabolismo , Animais , Fertilidade/efeitos dos fármacos , Inositol/farmacologia , Insulina/metabolismo , RNA de Cadeia Dupla , Açúcares/metabolismo
15.
Acad Radiol ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32061467

RESUMO

RATIONALE AND OBJECTIVES: To investigate the feasibility of apparent diffusion coefficient (ADC) histogram analysis of primary advanced high-grade serous ovarian cancer (HGSOC) to predict patient response to platinum-based chemotherapy. MATERIALS AND METHODS: A total of 70 patients with 102 advanced stage HGSOCs (International Federation of Gynecology and Obstetrics (FIGO) stages III-IV) who received standard treatment of primary debulking surgery followed by the first line of platinum-based chemotherapy were retrospectively enrolled. Patients were grouped as platinum-resistant and platinum-sensitive according to whether relapse occurred within 6 months. Clinical characteristics, including age, pretherapy CA125 level, International Federation of Gynecology and Obstetrics stage, residual tumor, and histogram parameters derived from whole tumor and solid component such as ADCmean; 10th, 20th, 25th, 30th, 40th, 50th, 60th, 70th, 75th, 80th, 90th percentiles; skewness and kurtosis, were compared between platinum-resistant and platinum-sensitive groups. RESULTS: No significantly different clinical characteristics were observed between platinum-sensitive and platinum-resistant patients. There were no significant differences in any whole-tumor histogram-derived parameters between the two groups. Significantly higher ADCmean and percentiles and significantly lower skewness and kurtosis from the solid-component histogram parameters were observed in the platinum-sensitive group when compared with the platinum-resistant group. ADCmean, skewness and kurtosis showed moderate prediction performances, with areas under the curve of 0.667, 0.733 and 0.616, respectively. Skewness was an independent risk factor for platinum resistance. CONCLUSION: Pretreatment ADC histogram analysis of primary tumors has the potential to allow prediction of response to platinum-based chemotherapy in patients with advanced HGSOC.

16.
Biosci Rep ; 40(1)2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31950990

RESUMO

Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide, and its underlying mechanism remains unclear. Accumulating evidence has highlighted that long non-coding RNA (lncRNA) acts as competitive endogenous RNA (ceRNA) and plays an important role in the occurrence and development of LUAD. Here, we comprehensively analyzed and provided an overview of the lncRNAs, miRNAs, and mRNAs associated with LUAD from The Cancer Genome Atlas (TCGA) database. Then, differentially expressed lncRNAs (DElncRNA), miRNAs (DEmiRNA), and mRNAs (DEmRNA) were used to construct a lncRNA-miRNA-mRNA regulatory network according to interaction information from miRcode, TargetScan, miRTarBase, and miRDB. Finally, the RNAs of the network were analyzed for survival and submitted for Cox regression analysis to construct prognostic indicators. A total of 1123 DElncRNAs, 95 DEmiRNAs, and 2296 DEmRNAs were identified (|log2FoldChange| (FC) > 2 and false discovery rate (FDR) or adjusted P value < 0.01). The ceRNA network was established based on this and included 102 lncRNAs, 19 miRNAs, and 33 mRNAs. The DEmRNAs in the ceRNA network were found to be enriched in various cancer-related biological processes and pathways. We detected 22 lncRNAs, 12 mRNAs, and 1 miRNA in the ceRNA network that were significantly associated with the overall survival of patients with LUAD (P < 0.05). We established three prognostic prediction models and calculated the area under the 1,3,5-year curve (AUC) values of lncRNA, mRNA, and miRNA, respectively. Among them, the prognostic index (PI) of lncRNA showed good predictive ability which was 0.737, 0.702 and 0.671 respectively, and eight lncRNAs can be used as candidate prognostic biomarkers for LUAD. In conclusion, our study provides a new perspective on the prognosis and diagnosis of LUAD on a genome-wide basis, and develops independent prognostic biomarkers for LUAD.

17.
Comput Med Imaging Graph ; 80: 101688, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31926366

RESUMO

Extensive research has been devoted to the segmentation of the coronary artery. However, owing to its complex anatomical structure, it is extremely challenging to automatically segment the coronary artery from 3D coronary computed tomography angiography (CCTA). Inspired by recent ideas to use tree-structured long short-term memory (LSTM) to model the underlying tree structures for NLP tasks, we propose a novel tree-structured convolutional gated recurrent unit (ConvGRU) model to learn the anatomical structure of the coronary artery. However, unlike tree-structured LSTM proposed for semantic relatedness as well as sentiment classification in natural language processing, our tree-structured ConvGRU model considers the local spatial correlations in the input data as the convolutions are used for input-to-state as well as state-to-state transitions, thus more suitable for image analysis. To conduct voxel-wise segmentation, a tree-structured segmentation framework is presented. It consists of a fully convolutional network (FCN) for multi-scale discriminative feature extraction and the final prediction, and a tree-structured ConvGRU layer for anatomical structure modeling. The proposed framework is extensively evaluated on four large-scale 3D CCTA dataset (the largest to the best of our knowledge), and experiments show that our method is more accurate as well as efficient, compared with other coronary artery segmentation approaches.

18.
Front Med ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31901116

RESUMO

High-throughput metabolomics can clarify the underlying molecular mechanism of diseases via the qualitative and quantitative analysis of metabolites. This study used the established Yang Huang syndrome (YHS) mouse model to evaluate the efficacy of geniposide (GEN). Urine metabolic data were quantified by ultraperformance liquid chromatography-tandem mass spectrometry. The non-target screening of the massive biological information dataset was performed, and a total of 33 metabolites, including tyramine glucuronide, aurine, and L-cysteine, were identified relating to YHS. These differential metabolites directly participated in the disturbance of phase I reaction and hydrophilic transformation of bilirubin. Interestingly, they were completely reversed by GEN. While, as the auxiliary technical means, we also focused on the molecular prediction and docking results in network pharmacological and integrated analysis part. We used integrated analysis to communicate the multiple results of metabolomics and network pharmacology. This study is the first to report that GEN indirectly regulates the metabolite "tyramine glucuronide" through its direct effect on the target heme oxygenase 1 in vivo. Meanwhile, heme oxygenase-1, a prediction of network pharmacology, was the confirmed metabolic enzyme of phase I reaction in hepatocytes. Our study indicated that the combination of high-throughput metabolomics and network pharmacology is a robust combination for deciphering the pathogenesis of the traditional Chinese medicine (TCM) syndrome.

19.
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.

20.
Arch Insect Biochem Physiol ; 103(2): e21634, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31587360

RESUMO

Pteromalus puparum is a gregarious pupal endoparasitoid with a wide host range. It deposits eggs into pierid and papilionid butterfly pupae. Glutathione S-transferases (GSTs) are a family of multifunctional detoxification enzymes that act in xenobiotic metabolism in insects. Insect genome projects have facilitated identification and characterization of GST family members. We identified 20 putative GSTs in the P. puparum genome, including 19 cytosolic and one microsomal. Phylogenetic analysis showed that P. puparum GSTs are clustered into Hymenoptera-specific branches. Transcriptomic data of embryos, larvae, female pupae, male pupae, female adults, male adults, venom glands, carcass, salivary glands, and ovaries revealed stage-, sex-, and tissue-specific expression patterns of GSTs in P. puparum. This is the most comprehensive study of genome-wide identification, characterization, and expression profiling of GST family in hymenopterans. Our results provide valuable information for understanding the metabolic adaptation of this wasp.


Assuntos
Glutationa Transferase/genética , Proteínas de Insetos/genética , Vespas/genética , Sequência de Aminoácidos , Animais , Embrião não Mamífero/química , Embrião não Mamífero/metabolismo , Feminino , Perfilação da Expressão Gênica , Glutationa Transferase/química , Glutationa Transferase/metabolismo , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Larva/genética , Larva/metabolismo , Masculino , Filogenia , Pupa/genética , Pupa/metabolismo , Alinhamento de Sequência , Vespas/crescimento & desenvolvimento , Vespas/metabolismo
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