Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 328
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-32139120

RESUMO

The levels of the anti-aging protein α-Klotho, in its soluble form (s-Klotho), are depressed in the circulation of patients with type 1 diabetes (T1D) or type 2 diabetes (T2D). Gene transfer experiments have suggested a protective role for ß-cell specific expression of α-Klotho in murine models of T1D and T1D, but these approaches are not easily translatable to clinical therapy. It is unknown whether systemic s-Klotho protein treatment ameliorates disease in T1D, which is characterized by autoimmune destruction of ß cells. We previously reported from in vitro experiments with ß cells that s-Klotho increases insulin secretion, reduces cells death and promotes ß-cell replication. Here, we investigated s-Klotho protein therapy in NOD mice, which have autoimmune T1D. We observed that diabetic NOD mice have significantly lower plasma levels of s-Klotho, compared to their non-diabetic counterparts. To examine in vivo effects of Klotho, we treated NOD mice with s-Klotho protein, or with a Klotho blocking antibody. Systemic treatment with s-Klotho ameliorated diabetes; notably increasing ß-cell replication and total ß-cell mass. Klotho expression was increased locally in the islets. s-Klotho also markedly reduced immune-cell infiltration of islets (insulitis). In contrast, administration of the Klotho antibody was detrimental, and aggravated the loss of ß-cell mass. Thus, s-Klotho has protective effects in this model of T1D, and this appears to depend on a combination of increased ß-cell replication and reduced insulitis. These findings suggest that s-Klotho might be effective as a new therapeutic agent for T1D.

2.
BMC Neurol ; 20(1): 76, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32126984

RESUMO

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant disorder arising from mutations of the MEN1 tumor suppressor gene on chromosome 11q13; MEN1 is characterized by the development of neuroendocrine tumors, including those of the parathyroid, gastrointestinal endocrine tissue and anterior pituitary. Additionally, thymic neuroendocrine tumors in MEN1 are also rarely reported. CASE PRESENTATION: This case report observed a family that presented with MEN1 p.L105Vfs mutation, and two of the family members had been diagnosed with thymic neuroendocrine tumor combined with MEN1. To the best of our knowledge, this is the first time such a mutation in the MEN1 gene has been reported. The proband presented with thymic neuroendocrine tumor, parathyroid adenoma and rectum adenocarcinoma. The son of the proband presented with thymic neuroendocrine tumor, gastrinoma, hypophysoma and parathyroid adenoma. Genetic testing revealed the frameshift mutation p.L105Vfs, leading to the identification of one carrier in the pedigree (the patient's younger sister). The proband then underwent parathyroidectomy at the age of 26 years (in 1980) for a parathyroid adenoma. Subsequently, the patient underwent thymectomy, radiotherapy and chemotherapy. The patient is now 64 years old, still alive and still undergoing Lanreotide therapy. CONCLUSION: Thymic neuroendocrine MEN1 is rare, but it accounts for almost 20% of MEN1-associated mortality. Consequently, we should focus on regular clinical screening of the thymus in MEN1 patients.

3.
Stem Cells Dev ; 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111146

RESUMO

Neuroinflammation is associated with the pathogenesis of all types of neurological disease, in which microglial cells play a critical role. In response to disturbances in the microenvironment, microglia become activated and differentiate into either an M1 phenotype, which has a pro-inflammatory, damaging effect, or an M2 phenotype, which plays an anti-inflammatory and reparative role. Thus, modulating microglial polarization is a suitable strategy to treat neuroinflammatory disorders. Glial cell-derived neurotrophic factor (GDNF) is a neurotrophic mediator that exerts neuroprotective effects during neurological diseases. In this study, we predicted that adipose-derived stem cells (ADSCs) could produce GDNF and investigated the effects of GDNF on microglial M1/M2 polarization. Furthermore, we determined whether GDNF modulates microglial activation and polarization via the PI3K/AKT signaling pathway. We found that the secretion of inflammatory cytokines in lipopolysaccharide-stimulated microglia was downgrated, while the anti-inflammatory mediators in interleukin-4-stimulated microglia were upgrated obviously, following pretreatment with ADSCs or GDNF. In addition, GDNF produced by ADSCs inhibited the microglia M1 phenotype and promoted the M2 phenotype by upregulating the PI3K/ATK pathway. These results reveal that GDNF produced by ADSCs might be useful for the treatment of neuroinflammatory diseases.

4.
BMC Musculoskelet Disord ; 21(1): 68, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013945

RESUMO

BACKGROUND: The objective of this study was to evaluate the clinical effect and correlation between preoperative imaging parameters and the clinical effect of endoscopic transforaminal decompression for lumbar spinal stenosis. METHODS: In this prospective study, 87 patients from Shanxi Province People's Hospital met the criteria for lumbar spinal stenosis and were recruited from June 2014 to January 2016. These patients underwent endoscopic transforaminal decompression. The clinical symptoms were evaluated by VAS, ODI, and claudication at 3 and 6 months after surgery. The overall clinical efficacy was evaluated using the MacNab score. Yellow ligament thickness and area of the dural sac were examined by MRI. Bony vertebral canal area, real spinal canal area, nerve root canal bony area, nerve root canal real area, distance between the articular joints, and vertebral canal sagittal diameter were examined by CT. The soft tissue invasion ratio of the vertebral canal and the invasion ratio of the nerve root canal were calculated. Correlations between imaging parameters and age, sex, and clinical efficacy were examined. RESULTS: The MacNab scores were excellent in 47% of cases, good in 34%, generally good in 8%, and poor in 11%. VAS, ODI, and claudication were significantly improved compared with the preoperative values (P < 0.01). A significant difference was observed between the 71-81 year age group and the other age groups (P < 0.05). There were good correlations between clinical efficacy and vertebral canal sagittal diameter, distance between the articular joints, soft tissue invasion ratio of the vertebral canal, and invasion ratio of the nerve root canal. CONCLUSION: Treatment of lumbar spinal stenosis by endoscopic transforaminal decompression can achieve good clinical results. This operation is less effective in patients older than 71 years of age. There were positive correlations between clinical efficacy and the vertebral canal sagittal diameter, the articular joints, soft tissue invasion ratio of the vertebral canal, and invasion ratio of the nerve root canal.

5.
Aging (Albany NY) ; 12(4): 3312-3339, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32091408

RESUMO

Immune checkpoint blockade (ICB) therapies have revolutionized the treatment of human cancers including lung adenocarcinoma (LUAD). However, our understanding of the immune subtyping of LUAD and its association with clinical response of immune checkpoint inhibitor remains incomplete. Here we performed molecular subtyping and association analysis of LUAD from the Cancer Genome Atlas (TCGA) and validated findings from TCGA cohort in 9 independent validation cohorts. We conducted consensus molecular subtyping with nonnegative matrix factorization (NMF). Potential response of ICB therapy was estimated with Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. We identified 2 distinct subtypes of LUAD in TCGA cohort that were characterized by significantly different survival outcomes (i.e., high- and low-risk subtypes). The high-risk subtype was featured by lower TIDE score, upregulation of programmed death-ligand 1 (PD-L1) expression, and higher tumor mutation burden (TMB). The high-risk subtype also harbored significantly elevated cell cycle modulators CDK4/CDK6 and TP53 mutation. These observations were validated in 9 independent LUAD cohorts. Our findings suggest that immune checkpoint blockade therapy may be efficacious for high-risk subtype of LUAD patients.

6.
Nat Plants ; 6(2): 107-118, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32042158

RESUMO

Hornworts, liverworts and mosses are three early diverging clades of land plants, and together comprise the bryophytes. Here, we report the draft genome sequence of the hornwort Anthoceros angustus. Phylogenomic inferences confirm the monophyly of bryophytes, with hornworts sister to liverworts and mosses. The simple morphology of hornworts correlates with low genetic redundancy in plant body plan, while the basic transcriptional regulation toolkit for plant development has already been established in this early land plant lineage. Although the Anthoceros genome is small and characterized by minimal redundancy, expansions are observed in gene families related to RNA editing, UV protection and desiccation tolerance. The genome of A. angustus bears the signatures of horizontally transferred genes from bacteria and fungi, in particular of genes operating in stress-response and metabolic pathways. Our study provides insight into the unique features of hornworts and their molecular adaptations to live on land.

7.
Behav Neurol ; 2020: 2476861, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32089749

RESUMO

Background: The aim of this study was to explore the role of hesperadin in intracerebral hemorrhage (ICH) mice, with the involvement of the mammalian ste20-like kinase 4 (MST4)/AKT signaling pathway. Methods: All mice were divided into four groups: sham group, sham+hesperidin group, ICH group, and ICH+hesperadin group. The effects of hesperadin were assessed on the basis of brain edema and neurobehavioral function. Furthermore, we observed MST4, AKT, phosphorylation of AKT (pAKT), and microtubule-associated protein light chain 3 (LC3) by western blotting. Protein localization of MST4 and LC3 was determined by immunofluorescence. Results: The expression of MST4 was upregulated at 12 h and 24 h after ICH. Brain edema was significantly decreased and neurological function was improved in the hesperadin treatment group compared to the ICH group (P < 0.05). Hesperadin decreases the expressions of MST and increases pAKT after ICH. Autophagy significantly increased in the ICH group, while hesperadin reduced this increase. Conclusion: Hesperadin provides neuroprotection against ICH by inhibiting the MST4/AKT signaling pathway.

8.
J Chem Theory Comput ; 16(2): 1359-1366, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31935088

RESUMO

Protein backbone torsion angles (Phi and Psi) are crucial for protein local conformation description. In this paper, we propose a general postprocessing method for all prediction methods, namely, OPUS-Refine, which may contribute to the field in a different way. OPUS-Refine is a sampling-based method, therefore, the results of other prediction methods can be used as its constraints. After OPUS-Refine refinement, for instance, the accuracy of Phi/Psi predicted by SPIDER3 and SPOT-1D are both increased. In addition, to facilitate the sampling efficiency, we construct a neighbor-dependent statistical torsion angles sampling database, namely, OPUS-TA, which may be useful for other sampling-based methods. Furthermore, we also introduce the contact map predicted by RaptorX to OPUS-Refine as a global structural constraint. After refinement, compared to the predicted structures obtained from RaptorX online server, the accuracy of both global structural configurations (measured by TM-score and RMSD) and local structural configurations (measured by Phi/Psi) results are improved. OPUS-Refine is a highly efficient framework, it takes only about 4 s to refine the torsion angles and 30 s to refine the global structure of a protein with 100 residues in length on a typical desktop personal computer. Therefore, the sampling-based feature and the efficiency of OPUS-Refine offer greater potentiality for it to take advantage of any other method to achieve better performance.


Assuntos
Simulação por Computador , Bases de Dados de Compostos Químicos , Modelos Químicos , Proteínas/química , Modelos Moleculares , Conformação Proteica
9.
Mol Pharm ; 17(1): 145-154, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31800255

RESUMO

Cryptococcus neoformans (C. neoformans) is one of the most well-known zoonotic fungal pathogens. Cryptococcal encephalitis remains a major cause of morbidity and mortality in immunocompromised hosts. Effective and targeting killing of C. neoformans in the brain is an essential approach to prevent and treat cryptococcal encephalitis. In this study, a fluorescent polypyridyl ruthenium complex RC-7, {[phen2Ru(bpy-dinonyl)](PF6)2 (phen = 1,10-phenanthroline, bpy-dinonyl = 4,4'-dinonyl-2,2'-bipyridine)}, was screened out, which showed a highly fungicidal effect on C. neoformans. The values of minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) in antifungal activities were significantly lower than fluconazole as the control. Moreover, RC-7 was prepared as a brain-targeting nanoliposome (RDP-liposome; RDP is a peptide derived from rabies virus glycoprotein) for in vivo application. The results revealed that the liposomes could accumulate in the encephalitis brain and play an antifungal role. Compared with the cryptococcal encephalitis model mice, the RDP-liposomes remarkably prolonged the survival days of the encephalitis-bearing mice from 10 days to 24 days. Here, we introduce a polypyridyl ruthenium complex that could be used as a novel antifungal agent, and this study may have a broad impact on the development of targeted delivery based on ruthenium complex-loaded liposomes for theranostics of cryptococcal encephalitis.

10.
Nucleic Acids Res ; 48(D1): D762-D767, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31642470

RESUMO

WormBase (https://wormbase.org/) is a mature Model Organism Information Resource supporting researchers using the nematode Caenorhabditis elegans as a model system for studies across a broad range of basic biological processes. Toward this mission, WormBase efforts are arranged in three primary facets: curation, user interface and architecture. In this update, we describe progress in each of these three areas. In particular, we discuss the status of literature curation and recently added data, detail new features of the web interface and options for users wishing to conduct data mining workflows, and discuss our efforts to build a robust and scalable architecture by leveraging commercial cloud offerings. We conclude with a description of WormBase's role as a founding member of the nascent Alliance of Genome Resources.

11.
Sci Total Environ ; 698: 134315, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31783453

RESUMO

Bioaerosol in the atmosphere plays a very important role in environment and public health. To forecast the bioaerosol concentration, the correlation between bioaerosol concentration and meteorological factors was discussed, and a Back Propagation (BP) neural network with Principal Component Analysis (PCA) method was utilized in this study. The proposed method works in three steps. The first step is to compute the correlation between bioaerosol concentration and meteorological factors, which consists of analyzing correlation and selecting meteorological factors applied to the study of forecast model. The second step is to use PCA analysis to reduce the dimensions of meteorological dataset. The third step is to use BP neural network, setting up, training BP neural network and proving the feasibility of forecast model included. The results of our model in forecasting bioaerosol concentration show 10.55% of average relative error, 2.80 pieces/L (pcs/L) of average absolute error, and 84.01 grade of forecast accuracy, providing a promising model for the forecasting of bioaerosol concentration.


Assuntos
Aerossóis/análise , Poluição do Ar/estatística & dados numéricos , Monitoramento Ambiental/métodos , Atmosfera , Conceitos Meteorológicos
12.
Int J Med Inform ; 132: 103986, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31629312

RESUMO

BACKGROUND AND PURPOSE: Pneumonia is a common complication after stroke, causing an increased length of hospital stay and death. Therefore, the timely and accurate prediction of post-stroke pneumonia would be highly valuable in clinical practice. Previous pneumonia risk score models were often built on simple statistical methods such as logistic regression. This study aims to investigate post-stroke pneumonia prediction models using more advanced machine learning algorithms, specifically deep learning approaches. METHODS: Using a hospital's electronic health record(EHR) data from 2007-2017, 13,930 eligible patients with acute ischaemic stroke (AIS) were identified to build and evaluate the models (85% of the patients were used for training, and 15% were used for testing). In total, 1012 patients (7.23%) contracted pneumonia during hospitalization. A number of machine learning methods were developed and compared to predict pneumonia in the stroke population in China. In addition to the classic methods (i.e., logistic regression (LR), support vector machines (SVMs), extreme gradient boosting (XGBoost)), methods based on multiple layer perceptron (MLP) neural networks and recurrent neural network (RNNs) (i.e., attention-augmented gated recurrent unit (GRU)) are also implemented to make use of the temporal sequence information in electronic health record (EHR) systems. Prediction models for pneumonia were built for two time windows, i.e., within 7 days and within 14 days after stroke onset. In particular, pneumonia occurring within the 7-day window is considered highly associated with stroke (stroke-associated pneumonia, SAP). MAIN FINDINGS: The attention-augmented GRU model achieved the best performance based on an area under the receiver operating characteristic curve (AUC) of 0.928 for pneumonia prediction within 7 days and an AUC of 0.905 for pneumonia prediction within 14 days. This method outperformed the other machine learning-based methods and previously published pneumonia risk score models. Considering that pneumonia prediction after stroke requires a high sensitivity to facilitate its prevention at a relatively low cost (i.e., increasing the nursing level), we also compared the prediction performance using other evaluation criteria by setting the sensitivity to 0.90. The attention-augmented GRU achieved the optimal performance, with a specificity of 0.85, a positive predictive value (PPV) of 0.32 and a negative predictive value (NPV) of 0.99 for pneumonia within 7 days and a specificity of 0.82, a PPV of 0.29 and an NPV of 0.99 for pneumonia within 14 days. CONCLUSIONS: The deep learning-based predictive model is feasible for stroke patient management and achieves the optimal performance compared to many classic machine learning methods.


Assuntos
Algoritmos , Isquemia Encefálica/complicações , Registros Eletrônicos de Saúde/estatística & dados numéricos , Aprendizado de Máquina , Pneumonia/diagnóstico , Acidente Vascular Cerebral/complicações , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/epidemiologia , Pneumonia/etiologia , Valor Preditivo dos Testes , Curva ROC
13.
J Environ Manage ; 250: 109491, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31521034

RESUMO

Carbon source and influent COD/N (chemical oxygen demand: total nitrogen) pose distinct effects on nitrogen removal efficiency and microbial community structure of constructed wetlands. To investigate the interactive effect of carbon source with COD/N on nitrogen removal and microbial community structure in subsurface flow constructed wetlands, glucose (C6H12O6) and sodium acetate (C2H3NaO2) were used to determine five COD/N ratios in nine groups of constructed wetlands divided into glucose constructed wetlands and sodium acetate constructed wetlands. Results showed that efficiency in COD removal increased with COD/N, and peak value reached 92.7%. Interactive effect of carbon source with COD/N on system pH and ammonium removal was notably significant. Differences in ammonium removal performance between treatments were achieved by the variation of influent COD/N ratio and the change of system pH resulted from different carbon sources, and the result suggested that glucose was a better choice at high COD/N ratio. System microbial community structure was significantly affected by carbon source, influent COD/N ratio and their interaction. Microbial biomass in constructed wetlands significantly increased with increasing COD/N ratio. Higher density and diversity of fungus were observed in glucose constructed wetlands, particularly at COD/N ratio of 7 and 10.


Assuntos
Microbiota , Áreas Alagadas , Análise da Demanda Biológica de Oxigênio , Carbono , Desnitrificação , Nitrogênio
14.
Virus Genes ; 55(6): 843-847, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31560107

RESUMO

On 7 March 2019, African swine fever in a domestic pig farm was detected in Guangxi Province of China. The phylogenetic analysis showed that its causative strain contained two tandem repeat sequence insertions in the intergenic region between the I73R and the I329L genes, and was different from previously reported strains in China and other countries.


Assuntos
Vírus da Febre Suína Africana/genética , Febre Suína Africana/genética , Filogenia , Sequências de Repetição em Tandem/genética , Febre Suína Africana/virologia , Vírus da Febre Suína Africana/patogenicidade , Animais , China , Fazendas , Genótipo , Suínos/virologia
15.
J Food Biochem ; 43(9): e12981, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31489654

RESUMO

The chemical constituents in Trifolium repens L. were comprehensively studied by UPLC in this work, and a total number of 308 compounds were detected with 169 ones identified. The possible fragmentation pathways were proposed and fragmentation rules were summarized. On the basis of the concluded strategies, the characterized compounds could be classified into organic acids and their derivatives, alkaloids, amino acids, peptides, flavonoids, oligosaccharides, coumarins, and other types of compounds. This approach provided a rapid way for the identification of constituents in T. repens L., and even in other complex analytes. Among the separation and identification of the constituents, three compounds of great amount were isolated and characterized by NMR. The expression of iNOS and COX-2 in LPS-induced RAW 264.7 cells was suppressed by the pretreatment with three isolated constituents. The results implied they may potentially serve as a remedy for the therapy of inflammation. PRACTICAL APPLICATIONS: This work provided a rapid method for the identification of the complex analyte, which could be used in TCM, natural food and so on. The summarized fragmentation rule could be applied for the analysis of several types of compounds, such as organic acids and their derivatives, alkaloids, amino acids and peptides, flavonoids, oligosaccharides, coumarins, and so on. Most of natural plants contain these kinds of compounds, so these rules could have wide applications. Except the phytochemical investigation, T. repens L. displayed anti-inflammation activity according to the reported literature, and the three isolated constituents may potentially serve as a remedy for the therapy of inflammation referring to the result of this research.

16.
BMC Med Educ ; 19(1): 341, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492136

RESUMO

BACKGROUND: Medical education is widely known to be a demanding process that may cause various mental health problems, such as burnout, which can lead to lowered levels of life satisfaction among medical students. Research shows that empathy is negatively correlated with burnout, but there are few studies on the relationship among empathy, burnout and life satisfaction in medical students. The objective of the present study is to explore the correlations of empathy and burnout with life satisfaction and the associated socio-demographic factors among Chinese undergraduate medical students. METHODS: In this cross-sectional study, 1271 undergraduate medical students (age 19.42 ± 1.34 years, 36% male) from 1st to 4th grades completed questionnaires including the Interpersonal Reactivity Index Chinese version (IRI-C), the Maslach Burnout Inventory Modified Chinese version (MBI-MC), the Satisfaction With Life Scale (SWLS) and socio-demographic characteristics. Statistical analyses included Student's t-test, one-way ANOVA, post hoc Bonferroni tests, hierarchical linear regression analysis and general linear model-univariate full factorial model. RESULTS: Over four academic years, medical students' empathy levels declined, but their burnout levels almost plateaued and their life satisfaction levels witnessed an initial fall before a rebound. Empathy was correlated with students' age and grade, and burnout was associated with students' maternal education. Significant differences in life satisfaction were detected with regard to medical students' age, academic year, the number of children in the family, place of residence and parents' educational levels. CONCLUSIONS: Empathy explained 0.6% of the variance in life satisfaction in contrast to 13.7% of the variance explained by burnout in life satisfaction. Although empathy did not have a main effect on life satisfaction, there was an interaction effect of empathy and burnout on life satisfaction among students of high and low empathy and burnout levels. Students with high levels of empathy and low levels of burnout were most satisfied with life. Medical institutions and related authorities need to find effective measures to enhance students' empathy levels and reduce burnout to improve their life satisfaction.

17.
Data Brief ; 25: 104338, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31485467

RESUMO

Dynamic microscale strain distributions with temporal resolution of 1 s in a smooth and a cracked Ti-6Al-4V alloys during one-cycle dwell fatigue tests are illustrated in videos (URL: https://drive.google.com/drive/folders/1pit_VV2apGOpETVfaJAAtL5Xl2CNOiJ3?usp=sharing). The tensile strain distributions were measured by the video sampling moiré method from the 1-µm-pitch grid images in a scanning electron microscope. The strain concentration factors of the smooth and the cracked specimens are 1.96 and 2.65, respectively. The plastic strain increment is 0.0007 during the displacement holding time of 591s in the smoothed specimen at maximum stress of 900 MPa., and 0.0008 during the displacement holding time of 593s in the cracked specimen at maximum stress of 870 MPa. The typical strain results are analyzed in 1-s-resolved strain mapping in Ti-6Al-4V alloys during dwell fatigue in SEM by video sampling moiré [1].

18.
Sci Total Environ ; 694: 133687, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31382172

RESUMO

Four subsurface flow constructed wetlands (SFCWs) were constructed on the basis of the volume ratio of biochar in common gravel (0%, 10%, 20%, and 30%) for the evaluation of microbe and metabolite characteristics response to biochar addition. The results showed that the biochar added SFCWs provided higher removal efficiencies for ammonium (49.69%-63.51%) and total nitrogen (81.83%-86.36%), compared with pure gravel packed SFCWs for ammonium (47.40%) and total nitrogen (80.75%), respectively. Illumina MiSeq sequencing results revealed that the dominant phyla were Proteobacteria, Bacteroidetes, and Firmicutes. Biochar addition can improve the removal of nitrogen by altering microbial community and increasing the relative abundance of Thauera, Candidatus Competibacter, Dechloromonas, Desulfobulbus, Chlorobium, and Thiobacillus. Protein and humic substances were the primary components of extracellular polymeric substance (EPS) in SFCWs. The amount of total EPS considerably decreased with biochar addition, which caused a shift in the EPS functional groups including carbonyl of protein, amide, and hydroxyl groups. Moreover, biochar could enhance the high molecular weight compounds metabolized into low molecular compounds. The results can provide new insights into the use of biochar in the enhancement of nitrogen removal by microbial community and metabolic product characteristics.


Assuntos
Carvão Vegetal , Microbiologia da Água , Áreas Alagadas , Matriz Extracelular de Substâncias Poliméricas , Microbiota , Eliminação de Resíduos Líquidos/métodos
19.
J Cancer ; 10(18): 4178-4188, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413736

RESUMO

Gastric cancer (GC) is a leading global health problem as it is the fifth most common cancer type and the third most common cause of cancer-related deaths worldwide. In most areas of the world, the incidence rate of GC is 1.5- to 3-fold higher in males than in females. The androgen receptor (AR) is an independent adverse prognostic factor in patients with GC. However, the mechanism by which AR regulates the progression of GC remains unclear. In this study, we found that AR expression was upregulated in 6/8 GC cell lines, and this expression was higher than that in immortalized gastric cells. AR expression was also higher in GC tissues than in adjacent tissues. Moreover, the ectopic expression of AR promoted the colony formation ability, migration and invasion of GC cells. In contrast, AR knockdown had the opposite effects on GC cell lines. Remarkably, we found that AR regulated cell cycle-related kinase (CCRK) expression through transcriptional mechanisms. The AR-CCRK axis promoted GC development through the phosphorylation of GSK3ß and ß-catenin. Furthermore, TCGA data revealed that high expression of AR or CCRK was related to poor prognosis in GC patients. The prognosis was significantly worse in patients with concurrent high AR and CCRK expression than in patients with low AR and CCRK expression. In conclusion, our study demonstrated that AR and CCRK acted as oncogenes in GC progression. However, their clinical roles require further exploration.

20.
Oncoimmunology ; 8(8): 1608132, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413919

RESUMO

Immune checkpoint blockade (ICB) therapy has achieved remarkable clinical benefit in melanoma. However, our understanding of biomarkers that predict response to ICB remained obscure. Here we systematically analyzed the association between somatic mutations profile and clinicopathologic information from 336 melanoma patients treated by ICB (CTLA-4/PD-1). We identified eight new significantly mutated genes including COL5A1, SEMA3E, COL28A1, DGKG, RAPGEF5, GLDN, NCF2 and RCAN2. A mutational signature featured by enrichment of T > C mutations was identified to be associated with immune resistance (logistic regression model, OR, 2.59 [95%CI, 1.07 to 7.00], P = .043). High neoantigen quality was associated with prolonged immunotherapy survival (log-rank test, P = .009). This association remained significant after controlling for age, gender, stage and hypermutation (Cox proportional hazards model, HR, 0.56 [95%CI, 0.38 to 0.82], P = .003). Our findings shed new insights on biomarkers that are useful to predict melanoma patients who may benefit from ICB treatment; however, these biomarkers need to be validated in future studies.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA