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1.
Math Biosci Eng ; 16(6): 6794-6804, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31698588

RESUMO

PURPOSE: Inflammatory myofibroblastic tumors (IMT) was a rare kind of tumor defined by WHO since 2012. Little was known about this disease. There were controversies about IMT's behavior, predilection site, age distribution, and the best treatment methods. Here we provided a systematic overview on tumor demographical, clinical, biological features as well as treatment efficacy based on real cases from Surveillance, Epidemiology, and End Results (SEER) database. METHODS: 92 patients diagnosed with IMT by histopathology were drawn from SEER database between 2002 and 2014. Patient demographics, clinical features and treatment information were analyzed. RESULTS: The mean age of onset was 47.4 ± 22.4 years (0 to 83y) and the ages prone to this disease are middle-aged (from 41y to 64y), accounting for 1/3 of all patients. Three peak ages of onsets were 0-4y, 36-40y and more than 50y. 42% of the tumors were located in the soft tissues of limbs, hip, shoulder, head, face and neck. The average tumor sizes were 6.5 ± 5.3cm (1cm to 25cm). Survival in the group of tumor size smaller than 6.5cm was better compared to group of tumor size larger than 6.5cm (P < 0.05). Most of the tumors were malignant or malignant potential (89%), though local and distant metastasis rate were low (5%). Surgery was the most common treatment. However, the survival benefit was still uncertain compared to adjuvant chemotherapy or radiotherapy. Multivariate regression analysis demonstrated that young patients had better survival than old ones. CONCLUSIONS: IMT was a malignant tumor with low risk of local and distant metastasis. The peak ages were 0-4y, 36-40y and more than 50y. The prone sites were the soft tissues of the limbs, hip, shoulder, head, face and neck. Tumor sizes and ages were the factors correlated with survival time.

2.
Ann Vasc Surg ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31669477

RESUMO

Venous cystic adventitial disease (CAD) is an uncommon vascular anomaly that most frequently affects the common femoral vein. Transluminal or transadventitial evacuation followed by cyst excision is considered an effective treatment for this condition, although the recurrence rate is relatively high. Herein, we report a case of a 59-year-old man with venous CAD that was successfully treated with saphenous vein patch angioplasty after mucoid evacuation and cyst excision, and we discuss the options for treating venous CAD.

3.
Biomed Pharmacother ; 121: 109599, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31707345

RESUMO

Diabetic nephropathy (DN) is a common but intractable diabetic microvascular complication. Tripterygium, a Chinses herb, has been proven to be effective for DN treatment. In this review, the efficacy and pharmacological mechanism of tripterygium and its extracts on DN is elucidated. Tripterygium and its extracts could effectively reduce urine protein and protect renal function. Its pharmacological mechanism involves anti-inflammation, anti-oxidation, anti-glomerulosclerosis and anti-fibrosis, which is achieved by balancing the Th1/Th2 cells, regulating macrophage infiltration, and regulating the following pathways: p38 MAPK, NF-κB, TGF-ß, Wnt/ß-catenin, Akt and Notch1. Although tripterygium and its extracts may result in some adverse effects, including liver-function damage, gastrointestinal reaction, menstrual disorders, and reproductive problems, they are considered good alternative medicines for DN if used with caution and in the proper manner.

4.
Luminescence ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31667940

RESUMO

The emission wavelength of organic-inorganic hybrid perovskite quantum dots (QDs) can be tuned by controlling reaction time relevant to the halide exchange. It is because halide exchange with different time would lead to different molar ratio of halides in perovskite QDs such as Cl and Br. Here, to research the ligand's effect on the halide exchange, this work synthesized 3-mercaptopropionic acid (MPA)-capped CH3 NH3 PbBrx Cl3-x QDs. It was found that SH- of MPA appeared to inhibit the halide exchange during the reation. Moreover, although the MPA-capped CH3 NH3 PbBrx Cl3-x QDs did not contain the chiral centre, they exhibit the optical rotation. This may provide a method for chirality manipulation of perovskite.

5.
J Transl Med ; 17(1): 382, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747915

RESUMO

BACKGROUND: In the process of drug development, computational drug repositioning is effective and resource-saving with regards to its important functions on identifying new drug-disease associations. Recent years have witnessed a great progression in the field of data mining with the advent of deep learning. An increasing number of deep learning-based techniques have been proposed to develop computational tools in bioinformatics. METHODS: Along this promising direction, we here propose a drug repositioning computational method combining the techniques of Sigmoid Kernel and Convolutional Neural Network (SKCNN) which is able to learn new features effectively representing drug-disease associations via its hidden layers. Specifically, we first construct similarity metric of drugs using drug sigmoid similarity and drug structural similarity, and that of disease using disease sigmoid similarity and disease semantic similarity. Based on the combined similarities of drugs and diseases, we then use SKCNN to learn hidden representations for each drug-disease pair whose labels are finally predicted by a classifier based on random forest. RESULTS: A series of experiments were implemented for performance evaluation and their results show that the proposed SKCNN improves the prediction accuracy compared with other state-of-the-art approaches. Case studies of two selected disease are also conducted through which we prove the superior performance of our method in terms of the actual discovery of potential drug indications. CONCLUSION: The aim of this study was to establish an effective predictive model for finding new drug-disease associations. These experimental results show that SKCNN can effectively predict the association between drugs and diseases.

6.
Water Res ; 170: 115298, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31751893

RESUMO

Handling excess sludge produced by wastewater treatment is a common problem worldwide. Due to limited space available in landfills, as well as difficulties involved in using excess sludge in agriculture, there is a need for alternative disposal methods. Although anaerobic digestion (AD) is widely used in processing sludge, only partial energy recovery from methane and sludge volume reduction can be achieved, resulting in a substantial amount of sludge remaining, which needs to be disposed of. Direct incineration after sludge drying is one possible option, a practice that is already in place in some cities in China. A comparison between direct incineration and conventional AD (with or without pretreatment by thermal hydrolysis) has to be made with respect to the energy balance and investment & operational (I & O) costs. This comparison reveals direct incineration to have the lowest energy deficit and I & O costs. Therefore, it is expected that direct incineration without AD will become the preferred sustainable approach to handling sludge.

7.
BMC Genomics ; 20(1): 780, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31655539

RESUMO

BACKGROUND: Our previous study finds that male sterility in Salvia miltiorrhiza could result in stunted growth and reduced biomass, but their molecular mechanisms have not yet been revealed. In this article, we investigate the underlying mechanism of male sterility and its impact on plant growth and metabolic yield by using physiological analysis and mRNA sequencing (RNA-Seq). RESULTS: In this study, transcriptomic and physiological analysis were performed to identify the mechanism of male sterility in mutants and its impact on plant growth and metabolic yield. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, it is found that the pathways are mainly enriched in processes including organ development, primary metabolic process and secondary metabolic process. Physiological analysis show that the chloroplast structure of male sterile mutants of S. miltiorrhiza is abnormally developed, which could result in decrease in leaf gas exchange (A, E and gs), chlorophyll fluorescence (Fv, Fm and Fv/Fm), and the chlorophyll content. Expression level of 7 differentially expressed genes involved in photosynthesis-related pathways is downregulated in male sterile lines of S. miltiorrhiza, which could explain the corresponding phenotypic changes in chlorophyll fluorescence, chlorophyll content and leaf gas exchange. Transcriptomic analysis establishes the role of disproportionating enzyme 1 (DPE1) as catalyzing the degradation of starch, and the role of sucrose synthase 3 (SUS3) and cytosolic invertase 2 (CINV2) as catalyzing the degradation of sucrose in the S. miltiorrhiza mutants. The results also confirm that phenylalanine ammonialyase (PAL) is involved in the biosynthesis of rosmarinic acid and salvianolic acid B, and flavone synthase (FLS) is an important enzyme catalyzing steps of flavonoid biosynthesis. CONCLUSIONS: Our results from the physiological and transcriptome analysis reveal underlying mechanism of plant growth and metabolic yield in male sterile mutants, and provide insight into the crop yield of S. miltiorrhiza.

8.
Clin Exp Med ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664538

RESUMO

Value of hepatitis C virus (HCV) core antigen (cAg) test has been controversy in patients with low HCV loads for its lower sensitivity. We assessed correlation between HCV-cAg and HCV RNA in serum samples with low viral loads and analyzed the performance of HCV-cAg assay in determining diagnosis and treatment outcomes in chronic hepatitis C patients. Both HCV RNA and HCV-cAg were detected for 2298 serum samples. Correlation analysis was performed between the two tests. Receiver operating characteristics (ROC) curve was used to assess value of HCV-cAg test in determining diagnosis and response outcomes at the different HCV RNA thresholds. The two tests were correlated very well, and moreover, correlation in the low viral load group was higher than that in the high viral load group (r value: 0.901 and 0.517). Positive agreement of HCV-cAg ≥ 3 fmol/L was as high as 97.0% for HCV RNA ≥ 1000 IU/mL, and its negative agreement for HCV RNA < 15 IU/mL was up to 98.9% in all samples. Area under ROCs ranged from 0.939 to 0.992, regardless of HCV RNA thresholds. When lower limit of detection of HCV RNA was 15, 100 or 1000 IU/mL, positive predictive value of HCV-cAg was 96.8%, 98.8% or 92.4%, and its negative predictive value was 87.0%, 89.9% or 98.3%, respectively, on the basis of different cutoff values. High-sensitivity HCV-cAg detection may likely replace HCV RNA to confirm the existence of HCV and to guide the treatment of chronic HCV infection.

9.
Biomed Res Int ; 2019: 2426958, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534955

RESUMO

Computational drug repositioning, designed to identify new indications for existing drugs, significantly reduced the cost and time involved in drug development. Prediction of drug-disease associations is promising for drug repositioning. Recent years have witnessed an increasing number of machine learning-based methods for calculating drug repositioning. In this paper, a novel feature learning method based on Gaussian interaction profile kernel and autoencoder (GIPAE) is proposed for drug-disease association. In order to further reduce the computation cost, both batch normalization layer and the full-connected layer are introduced to reduce training complexity. The experimental results of 10-fold cross validation indicate that the proposed method achieves superior performance on Fdataset and Cdataset with the AUCs of 93.30% and 96.03%, respectively, which were higher than many previous computational models. To further assess the accuracy of GIPAE, we conducted case studies on two complex human diseases. The top 20 drugs predicted, 14 obesity-related drugs, and 11 drugs related to Alzheimer's disease were validated in the CTD database. The results of cross validation and case studies indicated that GIPAE is a reliable model for predicting drug-disease associations.

10.
J Atheroscler Thromb ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462616

RESUMO

AIM: Inflammation plays a significant role in the pathogenesis of human abdominal aortic aneurysm (AAA). AEBP1 can promote activation of the NF-κB pathway, subsequently affecting the expression of NF-κB target genes, including inflammatory cytokines and matrix metalloproteinases (MMPs). Our objective was to examine the role of AEBP1 in the development of AAA and characterize the underlying mechanism. METHODS: ITRAQ, RT-PCR, western blot, immunohistochemistry, and ELISA were used to compare different experimental groups with the controls and to determine the differentially expressed genes. We generated an AAA model using porcine pancreatic elastase in Sprague-Dawley rats and silenced their AEBP1 in vivo by adenoviruses injected intra-adventitially. We also silenced or overexpressed AEBP1 in human vascular smooth muscle cells in vitro in the presence and in the absence of NF-κB inhibitor BAY 11-7082. RESULTS: Proteome iTRAQ revealed a high expression of AEBP1 in AAA patients, which was verified by qRT-PCR, western blot, immunohistochemistry, and ELISA. The mean expression level of AEBP1 in AAA patients was higher than that in controls. Along with AEBP1 upregulation, we also verified mis-activation of NF-κB in human AAA samples. The in vivo studies indicated that AEBP1 knockdown suppressed AAA progression. Finally, the in vitro studies illustrated that AEBP1 promotes activation of the NF-κB pathway, subsequently upregulating pro-inflammatory factors and MMPs. CONCLUSIONS: Our results indicate a role of AEBP1 in the pathogenesis of AAA and provide a novel insight into how AEBP1 causes the development of AAA by activating the NF-κB pathway.

11.
Clin Interv Aging ; 14: 1227-1241, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413553

RESUMO

Purpose: Abdominal aortic aneurysm (AAA) demonstrates many features of autoimmune diseases. Y chromosome, sex-determining region of the Y chromosome (SRY) gene, androgen receptor (AR) gene, and androgen appear as potential candidates for influence of the male immune function. This study investigated Y chromosome numbers, SRY gene, AR gene, and androgen levels in male AAAs. We also investigated the correlation between Y chromosome loss (LOY) ratio, SRY expression, androgen levels, and age. Patients and methods: We investigated LOY by fluorescence in situ hybridization (FISH) in 37 AAAs and compared with 12 patients with abdominal aortic atherosclerotic occlusive disease (AOD) and 91 healthy controls (HC). We investigated SRY and AR expression at mRNA level by real-time PCR in peripheral T lymphocytes in AAA compared with AOD and HC, and AR protein levels by immunohistochemistry (IHC) in AAA. LOY, SRY expression, androgen levels, and age were examined for correlations using the Spearman's rank correlation coefficient. Results: LOY ratio in peripheral T lymphocytes was significantly higher in the AAA group compared with the HC (9.11% vs 5.56%, P<0.001) and AOD groups (9.11% vs 6.42%, P=0.029). The SRY mRNA expression in peripheral T lymphocytes was 4.7-fold lower expressed in the AAA group than in the HC group (P<0.001). Free plasma testosterone levels were lower in the AAA group compared with the HC group (P=0.036), whereas sex hormone-binding globulin levels were higher (P=0.020). LOY ratio and expression of SRY mRNA level increased with age in the AAA group (R=0.402 and, R=0.366, respectively). A significant correlation between AR mRNA level (R=0.692) and aortic diameter was detected. Simultaneously, in AAA tissue, the rate of LOY increased with age (R=0.547) and also positively associated with LOY in peripheral blood T lymphocytes (R=0.661). Conclusion: This study identified a prominent Y chromosome loss in male AAAs, which is correlated to age, lower level of SRY expression and free testosterone, providing a new clue for the mechanisms of AAA.

12.
Mol Plant Microbe Interact ; 32(10): 1391-1401, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31408392

RESUMO

Salicylic acid (SA) is closely related to disease resistance of plants. WRKY transcription factors have been linked to the growth and development of plants, especially under stress conditions. However, the regulatory mechanism of WRKY proteins involved in SA production and disease resistance in apple is not clear. In this study, MdPBS3.1 responded to Botryosphaeria dothidea and enhanced resistance to B. dothidea. Electrophoretic mobility shift assays, yeast one-hybrid assays, and chromatin immunoprecipitation and quantitative PCR demonstrated that MdWRKY46 can directly bind to a W-box motif in the promoter of MdPBS3.1. Glucuronidase transactivation and luciferase analysis further showed that MdWRKY46 can activate the expression of MdPBS3.1. Finally, B. dothidea inoculation in transgenic apple calli and fruits revealed that MdWRKY46 improved resistance to B. dothidea by the transcriptional activation of MdPBS3.1. Viral vector-based transformation assays indicated that MdWRKY46 elevates SA content and transcription of SA-related genes, including MdPR1, MdPR5, and MdNPR1 in an MdPBS3.1-dependent way. These findings provide new insights into how MdWRKY46 regulates plant resistance to B. dothidea through the SA signaling pathway.


Assuntos
Ascomicetos , Resistência à Doença , Regulação da Expressão Gênica de Plantas , Malus , Proteínas de Plantas , Transdução de Sinais , Ascomicetos/fisiologia , Resistência à Doença/genética , Malus/genética , Malus/microbiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ácido Salicílico/metabolismo , Transdução de Sinais/genética
13.
Biomed Pharmacother ; 118: 109261, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31374355

RESUMO

Doxorubicin (DOX) as a first-line chemotherapeutic drug has been widely used for therapy of human cancers. However, side effects and chemo-resistance severely blocked its clinic application. Herein, natural borneol (NB) as a novel monoterpenoid chemosensitizer was found to have the potential to increase the blood brain barrier (BBB) permeability and intracellular uptake of DOX in vitro, and synergistically enhanced DOX-induced cytotoxicity in human glioma cells. NB treatment significantly potentiated DOX-induced G2/M cell cycle arrest by triggering reactive oxygen species (ROS)-mediated DNA damage. NB also enhanced DOX-induced dysfunction of MAPKs and PI3 K/AKT pathways. Furthermore, U251 human glioma xenograft growth in vivo was also effectively inhibited by combined treatment of DOX with NB through induction of G2/M-phase arrest and antiangiogenesis. Taken together, our finding validated that NB could act as novel chemosensitizer to enhance DOX-induced anticancer efficacy, and strategy of using NB and DOX could be a high efficient way in therapy of human cancers.

14.
J Food Biochem ; 43(7): e12876, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31353718

RESUMO

This work was aimed at producing peptides containing iron-binding capabilities from scad (Decapterus maruadsi) processing by-product with alcalase hydrolysis. The chelating peptides were purified by ultrafiltration, immobilized-metal affinity chromatography, gel filtration chromatography, and reversed-phase high-performance liquid chromatography. A novel iron-binding peptide was purified with 1,386.63 Da molecular weight and amino acid sequence of QKGTYDDYVEGL. The peptide binds to iron mainly through carboxyl and hydroxyl oxygen bonds. The iron-binding peptide can significantly promote the absorption of inorganic iron in Caco-2 cells. These results have contributed to development of the peptide from scad processing by-products hydrolyzate in iron supplementations. PRACTICAL APPLICATIONS: Iron deficiency is one of the most common and widespread nutritional disorders in the world. Iron-peptide chelates may be suitable for iron-fortification. Our study shows that a peptide purified from scad processing by-product has iron-chelating activity, and significantly increases iron absorption by Caco-2 cells. Hence, this peptide has potential application as a novel carrier for enhancing iron absorption.

15.
Plant Mol Biol ; 101(1-2): 149-162, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31267255

RESUMO

KEY MESSAGE: Here we describe that the regulation of MdWRKY31 on MdHIR4 in transcription and translation levels associated with disease in apple. The phytohormone salicylic acid (SA) is a main factor in apple (Malus domestica) production due to its function in disease resistance. WRKY transcription factors play a vital role in response to stress. An RNA-seq analysis was conducted with 'Royal Gala' seedlings treated with SA to identify the WRKY regulatory mechanism of disease resistance in apple. The analysis indicated that MdWRKY31 was induced. A quantitative real-time polymerase chain reaction (qPCR) analysis demonstrated that the expression of MdWRKY31 was induced by SA and flg22. Ectopic expression of MdWRKY31 in Arabidopsis and Nicotiana benthamiana increased the resistance to flg22 and Pseudomonas syringae tomato (Pst DC3000). A yeast two-hybrid screen was conducted to further analyze the function of MdWRKY31. As a result, hypersensitive-induced reaction (HIR) protein MdHIR4 interacted with MdWRKY31. Biomolecular fluorescence complementation, yeast two-hybrid, and pull-down assays demonstrated the interaction. In our previous study, MdHIR4 conferred decreased resistance to Botryosphaeria dothidea (B. dothidea). A viral vector-based transformation assay indicated that MdWRKY31 evaluated the transcription of SA-related genes, including MdPR1, MdPR5, and MdNPR1 in an MdHIR4-dependent way. A GUS analysis demonstrated that the w-box, particularly w-box2, of the MdHIR4 promoter played a major role in the responses to SA and B. dothidea. Electrophoretic mobility shift assays, yeast one-hybrid assay, and chromatin immunoprecipitation-qPCR demonstrated that MdWRKY31 directly bound to the w-box2 motif in the MdHIR4 promoter. GUS staining activity and a protein intensity analysis further showed that MdWRKY31 repressed MdHIR4 expression. Taken together, our findings reveal that MdWRKY31 regulated plant resistance to B. dothidea through the SA signaling pathway by interacting with MdHIR4.


Assuntos
Resistência à Doença , Malus/genética , Doenças das Plantas/imunologia , Reguladores de Crescimento de Planta/farmacologia , Proteínas de Plantas/metabolismo , Ácido Salicílico/farmacologia , Arabidopsis/genética , Arabidopsis/imunologia , Arabidopsis/microbiologia , Ascomicetos/fisiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Frutas/genética , Frutas/imunologia , Frutas/microbiologia , Regulação da Expressão Gênica de Plantas , Genes Reporter , Malus/imunologia , Malus/microbiologia , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Regiões Promotoras Genéticas/genética , Pseudomonas syringae/fisiologia , Plântula/genética , Plântula/imunologia , Plântula/microbiologia , Transdução de Sinais , Tabaco/genética , Tabaco/imunologia , Tabaco/microbiologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Técnicas do Sistema de Duplo-Híbrido
16.
BMC Neurol ; 19(1): 154, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286894

RESUMO

BACKGROUND: Alzheimer's disease has become a public health crisis globally due to its increasing incidence. The purpose of this study was to establish an early warning model using artificial neural network (ANN) for early diagnosis of AD and to explore early sensitive markers for AD. METHODS: A population based nested case-control study design was used. 89 new AD cases with good compliance who were willing to provide urine and blood specimen were selected from the cohort of 2482 community-dwelling elderly aged 60 years and over from 2013 to 2016. For each case, two controls living nearby were identified. Biomarkers for AD in urine and blood, neuropsychological functions and epidemiological parameters were included to analyze potential risk factors of AD. Compared with logistic regression, k-Nearest Neighbor (kNN) and support vector machine (SVM) model, back-propagation neural network of three-layer topology structures was applied to develop the early warning model. The performance of all models were measured by sensitivity, specificity, accuracy, positive prognostic value (PPV), negative prognostic value (NPV), the area under curve (AUC), and were validated using bootstrap resampling. RESULTS: The average age of AD group was about 5 years older than the non-AD controls (P < 0.001). Patients with AD included a significantly larger proportion of subjects with family history of dementia, compared with non-AD group. After adjusting for age and gender, the concentrations of urinary AD7c-NTP and aluminum in blood were significantly higher in AD group than non-AD group (2.01 ± 1.06 vs 1.03 ± 0.43, 1.74 ± 0.62 vs 1.24 ± 0.41 respectively), but the concentration of Selenium in AD group (2.26 ± 0.59) was significantly lower than that in non-AD group (2.61 ± 1.07). All the models were established using 18 variables that were significantly different between AD patients and controls as independent variables. The ANN model outperformed the other classifiers. The AUC for this ANN was 0.897 and the model obtained the accuracy of 92.13%, the sensitivity of 87.28% and the specificity of 94.74% on the average. CONCLUSIONS: Increased risk of AD may be associated with higher age among senior citizens in urban communities. Urinary AD7c-NTP is clinically valuable for the early diagnosis. The established ANN model obtained a high accuracy and diagnostic efficiency, which could be a low-cost practicable tool for the screening and diagnosis of AD for citizens.


Assuntos
Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/sangue , Proteínas do Tecido Nervoso/urina , Redes Neurais (Computação) , Fragmentos de Peptídeos/sangue , Oligoelementos/sangue , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Área Sob a Curva , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Diagnóstico Precoce , Feminino , Humanos , Masculino , Sensibilidade e Especificidade
17.
Nat Commun ; 10(1): 2544, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31186424

RESUMO

Cas13d, the type VI-D CRISPR-Cas effector, is an RNA-guided ribonuclease that has been repurposed to edit RNA in a programmable manner. Here we report the detailed structural and functional analysis of the uncultured Ruminococcus sp. Cas13d (UrCas13d)-crRNA complex. Two hydrated Mg2+ ions aid in stabilizing the conformation of the crRNA repeat region. Sequestration of divalent metal ions does not alter pre-crRNA processing, but abolishes target cleavage by UrCas13d. Notably, the pre-crRNA processing is executed by the HEPN-2 domain. Furthermore, both the structure and sequence of the nucleotides U(-8)-C(-1) within the repeat region are indispensable for target cleavage, and are specifically recognized by UrCas13d. Moreover, correct base pairings within two separate spacer regions (an internal and a 3'-end region) are essential for target cleavage. These findings provide a framework for the development of Cas13d into a tool for a wide range of applications.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas Associadas a CRISPR/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Ribonucleases/metabolismo , Ruminococcus/genética , Sequência de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas Associadas a CRISPR/química , Proteínas Associadas a CRISPR/metabolismo , Sistemas CRISPR-Cas , Conformação de Ácido Nucleico , Domínios Proteicos , Processamento Pós-Transcricional do RNA , RNA Bacteriano/genética , RNA Bacteriano/metabolismo , RNA Guia/genética , Ribonucleases/química , Ribonucleases/genética , Ruminococcus/enzimologia
18.
Water Res ; 161: 74-77, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31181448

RESUMO

In dealing with wastewater, chemical energy has traditionally been perceived as the only source of recoverable energy in moving towards the carbon-neutral operation of wastewater treatment plants. Based on an estimation of practically recoverable energy embedded in municipal wastewater, however, the potential for thermal energy (90% recovery from wastewater) is much higher than for chemical energy (COD, 10% recovery). The carrier of chemical energy (COD) has a high exergy value which should, from a sustainability point of view, be utilized to the greatest extent possible. Rather than being converted into methane (and subsequently into carbon dioxide), carbon (COD) contained in wastewater should be converted into highly valuable organic products. Thermal energy could be utilized for district heating/cooling, agricultural greenhouses, and even for drying dewatered sludge. In this way, thermal energy can indirectly offset the energy demand for wastewater treatment. The limitations in utilizing thermal energy are not generally based on technical difficulties; in fact, they can be mainly attributed to supply distances and governmental policies. It would, therefore, be greatly beneficial if municipal authorities would work together to jointly plan utilization of this thermal energy.


Assuntos
Eliminação de Resíduos Líquidos , Águas Residuárias , Anaerobiose , Reatores Biológicos , Temperatura Alta , Metano , Esgotos
19.
Plant Cell Physiol ; 60(10): 2129-2140, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31165159

RESUMO

Apple ring rot is a severe disease that affects the yield and quality of apple fruits worldwide. However, the underlying molecular mechanism that involved in this process still remains largely unexplored. Here, we report that apple POZ/BTB CONTAINING-PROTEIN 1 (MdPOB1), a BTB-BACK domain E3 ligase protein, functions to suppress apple pathogen defense against Botryosphaeria dothidea (B. dothidea). Both in vitro and in vivo assays indicated that MdPOB1 interacted directly with and degraded apple U-box E3 ligase MdPUB29, a well-established positive regulator of plant innate immunity, through the ubiquitin/26S proteasome pathway. A series of transgenic analyses in apple fruits demonstrated that MdPOB1 affected apple pathogen defense against B. dothidea at least partially, if not completely, via regulating MdPUB29. Additionally, it was found that the apple pathogen defense against B. dothidea was correlated with the H2O2 contents and the relative expression of salicylic acid (SA) synthesis- and SA signaling-related genes, which might be regulated via degradation of MdPUB29 by MdPOB1. Overall, our findings provide new insights into the mechanism of the MdPOB1 modulation of apple ring rot resistance, which occur by directly regulating potential downstream target protein MdPUB29 for proteasomal degradation in apple.

20.
Water Res ; 160: 268-277, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31154124

RESUMO

Conventional wastewater treatment plants (WWTPs) clean wastewater and minimize water pollution; but, while doing so, they also contribute to air pollution and need energy/material input with associated emissions. However, energy recovery (e.g. anaerobic digestion) and resource recovery (e.g. water reuse) allow us to offset the adverse environmental impacts of wastewater treatment. Life cycle assessments (LCA) have been used more and more to evaluate the environmental impacts of WWTPs and to suggest improvement options. There is a need to search for resource recovery applications that genuinely realize a net-zero impact on the total environment of WWTPs. In this work, a scheme with highly efficient energy and resource recovery (especially for thermal energy) is proposed and evaluated. The environmental impact of a conventional WWTP in comparison with the scheme proposed here, with energy/resource recovery included, was calculated, and discussed with reference to LCA methodology. In the process of using LCA, it was necessary to choose a regional situation to focus on. In this case, a Chinese situation was focused as a reference, but the qualitative information gained is of worldwide relevance. The results clearly revealed that conventional WWTP does not benefit the total environment as a whole while the new scheme benefited the total environment via resource/energy recovery-based processes. Among others, thermal energy recovery played a significant role towards a net-zero LCA analysis (contributing around 40%) which suggests that more attention and research should be focused on it.


Assuntos
Poluição do Ar , Purificação da Água , Meio Ambiente , Eliminação de Resíduos Líquidos , Águas Residuárias
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