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1.
Ultrasonics ; 138: 107213, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38056322

RESUMO

The initial discharge process of pulsed plasma electrolytic oxidation (PEO) on the 60% SiCp/2009 aluminum metal matrix composite (Al MMC) in silicate solution was monitored by acoustic emission (AE) technique. Parameters and correlations of AE signals on the Al MMC sample and under water were analyzed, and their generation mechanism was discussed. It was found that the peak amplitudes of AE signals and AE hits during the pulse time quickly increased with the increase of micro-discharge intensity, and the absolute energy of AE signals improved several orders of magnitude. Moreover, different from the peak amplitude, duration and rise time, the duration and count had a strong correlation. Elastic stress waves resulted from the microjet of plasma bubble collapse, the inner-surface friction inside discharge channel, the expansion-shrinkage process of plasma bubbles and micro-crack propagation during rapid solidification of melt are sources of AE signals on the Al MMC sample during the pulse time. However, the expansion-shrinkage process of plasma bubbles plays a key role in the generation of underwater AE signals. In the pause time of one pulse period, the bursting and moving of vapor bubbles result in weak AE signals. It is demonstrated that the AE technique can effectively characterize the features of micro-discharges within a pulse period.

2.
Aging Cell ; 22(12): e14028, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38015106

RESUMO

Human aging is invariably accompanied by a decline in renal function, a process potentially exacerbated by uremic toxins originating from gut microbes. Based on a registered household Chinese Guangxi longevity cohort (n = 151), we conducted comprehensive profiling of the gut microbiota and serum metabolome of individuals from 22 to 111 years of age and validated the findings in two independent East Asian aging cohorts (Japan aging cohort n = 330, Yunnan aging cohort n = 80), identifying unique age-dependent differences in the microbiota and serum metabolome. We discovered that the influence of the gut microbiota on serum metabolites intensifies with advancing age. Furthermore, mediation analyses unveiled putative causal relationships between the gut microbiota (Escherichia coli, Odoribacter splanchnicus, and Desulfovibrio piger) and serum metabolite markers related to impaired renal function (p-cresol, N-phenylacetylglutamine, 2-oxindole, and 4-aminohippuric acid) and aging. The fecal microbiota transplantation experiment demonstrated that the feces of elderly individuals could influence markers related to impaired renal function in the serum. Our findings reveal novel links between age-dependent alterations in the gut microbiota and serum metabolite markers of impaired renal function, providing novel insights into the effects of microbiota-metabolite interplay on renal function and healthy aging.


Assuntos
Microbioma Gastrointestinal , Humanos , Idoso , China , Metaboloma , Envelhecimento , Biomarcadores , Rim
3.
Rev Sci Instrum ; 94(6)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37862518

RESUMO

The initial discharge process of plasma electrolytic oxidation (PEO) on the 60 vol. % SiCP/2009 aluminum matrix composite in silicate solution was in situ monitored by sound and vibration measurement techniques. The underwater sound, airborne sound, and sample vibration signals were detected in the initial 120 s of the PEO process, and their generation mechanism was discussed. In terms of waveforms and spectrograms of the sound and vibration signals, the initial PEO process can be divided into five stages: conventional anodizing stage (I), glow discharge stage (Ⅱ), tiny spark discharge stage (Ⅲ), large spark discharge stage (Ⅳ), and strong spark discharge stage (Ⅴ). The sound and vibration signals during the PEO process are attributed to the evolution of bubbles, which are from the plasma discharge, electrochemical reactions, and vaporization of electrolyte under Joule heat. In stage I, these signals completely come from the bubbles produced by the evaporative electrolyte and electrochemical reactions. In stages Ⅱ-Ⅴ, the bubbles from the plasma discharge gradually become the main source of these signals with increasing discharge intensity. In addition, the spike peaks on the waveforms of these signals at stage Ⅴ are related to the strong discharge sparks. These results demonstrate that sound and vibration measurement techniques can effectively monitor the PEO discharge process.

4.
Sci Rep ; 12(1): 11037, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35773313

RESUMO

In order to adapt to the development of lightweight equipment, and further improve the wear resistance of ZL109 aluminum alloy, the influence of nickel-coated carbon nanotubes as an electrolyte additive on the preparation and wear resistance of microarc oxidation ceramic coatings on ZL109 aluminum alloy surface was investigated. In this work, 0.4 g/L, 0.8 g/L, 1.2 g/L, 1.6 g/L, and 2 g/L nickel-coated carbon nanotubes were added to the electrolyte respectively. The microarc oxidation ceramic coatings were prepared under bipolar pulse constant pressure mode, which were analyzed from the aspects of morphology, chemical composition, and wear resistance property. The results show that the nickel-coated carbon nanotubes possess a great influence on ceramic coatings. The morphology of ceramic coatings was significantly changed. In this work, the coating prepared by 1.2 g/L nickel-coated carbon nanotubes exhibits excellent wear resistance property.

5.
Environ Technol ; 43(4): 572-584, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32674672

RESUMO

In this work, we used cathodic microarc plasma electrolysis (CMPE) to degrade 2,4-dichlorophenol (2,4-DCP) in simulated wastewater. By investigating and comparing the removal efficiencies and chemical oxygen demand (COD) during the degradation process, higher bath voltage and alkaline condition were considered as more suitable for the 2,4-DCP decomposition. Higher initial 2,4-DCP concentration was attributed to the increase in the utilisation of the energy input. The plasma characteristics during CMPE were studied by optical emission spectroscopy (OES). It was found that the 2,4-DCP directly participated in the plasma discharge process. Furthermore, by studying the evolution of intermediate products at different experimental parameters, it was found that the existence of Cl- played an important role in the opening of benzene ring, which activated the ortho-substitutions of hydroxyl, meanwhile accelerated the p-substitutions. The instantaneous high temperature and high pressure and the Cl- that were generated and driven by cathodic plasma made the decomposition of 2,4-DCP much quicker.


Assuntos
Clorofenóis , Poluentes Químicos da Água , Eletrólise , Fenóis , Águas Residuárias
6.
Sci Rep ; 11(1): 11340, 2021 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059761

RESUMO

Exploiting a pure culture strategy to investigate the composition of the human gut microbiota, two novel anaerobes, designated strains AF52-21T and CM04-06T, were isolated from faeces of two healthy Chinese donors and characterized using a polyphasic approach. The two strains were observed to be gram-negative, non-motile, and rod-shaped. Both strains grew optimally at 37 °C and pH 7.0. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the two strains clustered with species of the genus Faecalibacterium and were most closely related to Faecalibacterium prausnitzii ATCC 27768T with sequence similarity of 97.18% and 96.87%, respectively. The two isolates shared a 16S rRNA gene sequence identity of 98.69%. Draft genome sequencing was performed for strains AF52-21T and CM04-06T, generating genome sizes of 2.85 Mbp and 3.01 Mbp. The calculated average nucleotide identity values between the genomes of the strains AF52-21T and CM04-06T compared to Faecalibacterium prausnitzii ATCC 27768T were 83.20% and 82.54%, respectively, and 90.09% when comparing AF52-21T and CM04-06T. Both values were below the previously proposed species threshold (95-96%), supporting their recognition as novel species in the genus Faecalibacterium. The genomic DNA G + C contents of strains AF52-21T and CM04-06T calculated from genome sequences were 57.77 mol% and 57.51 mol%, respectively. Based on the phenotypic, chemotaxonomic and phylogenetic characteristics, we conclude that both strains represent two new Faecalibacterium species, for which the names Faecalibacterium butyricigenerans sp. nov. (type strain AF52-21T = CGMCC 1.5206T = DSM 103434T) and Faecalibacterium longum sp. nov. (type strain CM04-06T = CGMCC 1.5208T = DSM 103432T) are proposed.


Assuntos
Faecalibacterium/genética , Faecalibacterium/isolamento & purificação , Adulto , Criança , Fezes/microbiologia , Feminino , Genoma Bacteriano , Humanos , Masculino , RNA Ribossômico 16S/genética
7.
Syst Appl Microbiol ; 44(3): 126201, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33892267

RESUMO

A novel, non-motile, Gram-stain-positive, non-spore-forming, obligate anaerobic bacterium, designated strain TF01-11T, was isolated from human faeces. The isolate was characterized by phylogenetic and phenotypic properties, as well as by determination of its whole genome sequence. The growth temperature and pH ranges were 30-42 °C and 6.0-8.5, respectively. The end products of glucose fermentation were butyric acid and a small amount of acetic acid. The genome was estimated to be 3.61 Mbp with G + C content of 36.8 mol%. Genes related to biosynthesis of diaminopimelic acid, polar lipids, polyamines, teichoic and lipoteichoic acids were present. The predominant fatty acids were C16:0 (37.9%), C14:0 (16.4%), C13:0 OH/iso-C15:1H (11.1%) and C18:1ω9c (10.6%). Phylogenetic analyses based on 16S rRNA gene sequences demonstrated that the isolate was a member of family Lachnospiraceae, with the highest sequence similarity to the type strain of Roseburia intestinalis DSM 14610T (92.2%), followed by Acetivibrio ethanolgignens ATCC 33324T (92.0%). The average nucleotide identity (ANI) and average amino acid identity (AAI) values between strain TF01-11T and these closest relatives were less than 70.5% and 52.3%. Based on results of phenotypic characteristics and genotypic properties presented in this study, strain TF01-11T represents a novel species in a new genus, for which the name Butyribacter intestini gen. nov., sp. nov. is proposed. The type strain of the type species is TF01-11T (CGMCC 1.5203T = DSM 105140T). In addition, Acetivibrio ethanolgignens is proposed to be reclassified as Acetanaerobacter ethanolgignens gen. nov., comb. nov.


Assuntos
Ácido Butírico/metabolismo , Clostridiales/classificação , Firmicutes/classificação , Filogenia , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Fezes/microbiologia , Firmicutes/isolamento & purificação , Humanos , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
8.
Front Microbiol ; 12: 632361, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33692769

RESUMO

A Gram-staining-negative, non-spore-forming, short, straight rod, non-motile, and obligate anaerobic bacterial strain, AF73-05CM02T, was isolated from a fecal sample of a 30 years old healthy male living in Shenzhen, China. Colonies were approximately 0.2 mm in diameter, beige, and circular after 4 days of incubation on PYG agar under anaerobic conditions at 37°C. Strain AF73-05CM02T grew in a temperature range between 30 and 42°C and a pH range from 6.0 to 8.5, with optimum growth at 37-42°C and pH 7.0. 16S rRNA gene sequence analysis demonstrated that strain AF73-05CM02T belongs to the genus Christensenella and showed the highest level of sequence similarity (98.68%) with Christensenella minuta DSM 22607T. The predominant fatty acids of strain AF73-05CM02T were C10 : 0 (7.5%), iso-C11 : 0 (5.6%), C12 : 0 (7.2%), C14 : 0 (46.6%), iso-C15 : 0 (7.4%), C16 : 0 (9.7%), and C18 : 1 ω9c (6.9%). Acetic acid, formic acid, butyric acid, and lactic acid were the end products of glucose fermentation. The strain was negative for catalase, indole production, and hydrolysis of gelatin. Genomic relatedness analyses based on average nucleotide identity (ANI) indicated that strain AF73-05CM02T significantly differed from other species of the genus Christensenella, showing ANI values less than 82.89% with the phylogenetically closest species. The G + C content of the genomic DNA was 52.07 mol% from the genome sequence, which differs from that of Christensenella minuta. Several physiological, biochemical, and genotypic properties differentiated the novel bacterial strain from the related species, indicating that the strain represents a new species of the genus Christensenella for which the name Christensenella intestinihominis sp. nov. is proposed, with strain AF73-05CM02T ( = CGMCC 1.5207T = DSM 103477T ) being the type strain. The following study explored the cholesterol-lowering function of strains AF73-05CM02T and Christensenella minuta DSM 22067T and revealed that the two strains exhibit the capacity for removing cholesterol with efficiency rates of 36.6 and 54.3% and produce exopolysaccharide of 234 and 271 mg/L, respectively.

9.
Sci Rep ; 10(1): 15675, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32973281

RESUMO

A corrosion-resistant non-crystalline coating was fabricated by plasma electrolytic oxidation (PEO) on Q235 low carbon steel for ship pipes. The distribution and composition of chemical elements and phases of PEO coatings were analyzed by an orthogonal experiment, and the formation mechanism of PEO coatings was discussed. The corrosion current densities and corrosion potentials were measured. The results indicated that the formation of a transition layer mainly containing Fe3O4 was crucial for achieving an excellent coating quality. Furthermore, the corrosion current density of coated steel was reduced by 78% compared with the bare steel.

10.
Medicine (Baltimore) ; 98(26): e16122, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261530

RESUMO

BACKGROUND: The aim of this study was to assess the sensitivity and accuracy of magnetic resonance imaging-guided targeted biopsy (MRI-TB) in patients undergoing active surveillance (AS) procedure. METHODS: We searched databases to identify relevant studies which compared MRI-TB with systemic biopsy for diagnosing prostate cancer in patients on AS. Outcomes included sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the curve (AUC) and publication bias of AS group, confirmatory biopsy group and follow-up biopsy group. RESULTS: Fourteen articles involving 1693 patients were included. In AS group, the sensitivity was 0.62 (95% confidence interval [CI], 0.57-0.68), specificity was 0.89 (95% CI, 0.87-0.90), NLR was 0.43 (0.31-0.60), PLR was 4.90 (3.50-6.86), DOR was 12.75 (7.22-22.51), and AUC was 0.8645. In confirmatory biopsy group, the sensitivity was 0.67 (0.59-0.74), specificity was 0.89 (0.86-0.91), NLR was 0.42 (0.27-0.65), PLR was 4.94 (3.88-6.30), DOR was 14.54 (9.60-22.02), and AUC was 0.8812. In follow-up biopsy group, the sensitivity was 0.35 (0.22-0.51), specificity was 0.88 (0.82-0.92), NLR was 0.76 (0.52-1.11), PLR was 3.06 (1.71-5.50), DOR was 4.41 (2.15-9.03), and AUC was 0.8367. CONCLUSION: MRI-TB has a moderate-to-high diagnostic accuracy for diagnosing and reclassifying patients on AS with high specificity and AUC value under the SROC curve.


Assuntos
Biópsia Guiada por Imagem , Imagem por Ressonância Magnética Intervencionista , Neoplasias da Próstata/classificação , Neoplasias da Próstata/diagnóstico , Humanos , Masculino , Neoplasias da Próstata/patologia , Medição de Risco
11.
Cancer Med ; 8(6): 2971-2978, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31070304

RESUMO

PURPOSES: To investigate the value of prognostic nutritional index (PNI) in patients with upper tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy (RNU). PATIENTS AND METHODS: A total of 717 patients were included in our study from 2003 to 2016. PNI was calculated as 10 × serum albumin level (g/dL) + 0.005 × total lymphocyte count (per mm3 ). Kaplan-Meier analysis and Cox regression models were adapted to analyze the value of PNI on survival outcomes. RESULTS: The cutoff value of PNI was set as 46.91 and 298 patients (47.6%) had PNI <46.91. The median follow-up was 50 months. The results suggested that low PNI was significantly associated with worse pathologic features (all P < 0.001). Multivariable Cox regression analysis revealed that PNI < 46.91 was an independent predictor of poor overall survival (Hazard ratios [HR] = 1.777, 95% CI = 1.383-2.284, P < 0.001), cancer-specific survival (HR = 1.850, 95% CI = 1.399-2.445, P < 0.001), and recurrence-free survival (HR = 1.554, 95% CI = 1.229-1.964, P < 0.001). CONCLUSIONS: Low preoperative PNI was associated with worse survival outcomes in patients with UTUC. PNI could be an easily assessed blood-based biomarker to predict the prognosis in patients with UTUC treated with RNU.


Assuntos
Avaliação Nutricional , Neoplasias Urológicas/dietoterapia , Idoso , Feminino , Humanos , Masculino , Cuidados Pré-Operatórios , Prognóstico , Análise de Sobrevida , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia
12.
Nat Biotechnol ; 37(2): 179-185, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30718868

RESUMO

Reference genomes are essential for metagenomic analyses and functional characterization of the human gut microbiota. We present the Culturable Genome Reference (CGR), a collection of 1,520 nonredundant, high-quality draft genomes generated from >6,000 bacteria cultivated from fecal samples of healthy humans. Of the 1,520 genomes, which were chosen to cover all major bacterial phyla and genera in the human gut, 264 are not represented in existing reference genome catalogs. We show that this increase in the number of reference bacterial genomes improves the rate of mapping metagenomic sequencing reads from 50% to >70%, enabling higher-resolution descriptions of the human gut microbiome. We use the CGR genomes to annotate functions of 338 bacterial species, showing the utility of this resource for functional studies. We also carry out a pan-genome analysis of 38 important human gut species, which reveals the diversity and specificity of functional enrichment between their core and dispensable genomes.


Assuntos
Biologia Computacional/métodos , Microbioma Gastrointestinal , Metagenoma , Bactérias/classificação , Análise por Conglomerados , Sequência Conservada , Fezes , Genoma Bacteriano , Genômica , Humanos , Metagenômica , Filogenia , Polimorfismo de Nucleotídeo Único , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
13.
Environ Technol ; 40(8): 969-978, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29239691

RESUMO

In this paper, the cathodic microarc plasma electrolysis (CMPE) was tentatively performed to degrade the phenol in aqueous solution by vapor-gaseous envelope discharge around the Ti cathode. Degradation efficiency of phenol was measured and the intermediate products were evaluated. The suspended particles in solution were analyzed and the decomposition mechanism of phenol in the process of cathodic microarc plasma degradation was discussed. The instantaneous current efficiency reached a peak value firstly and then decreased with the discharge time. In the cathodic plasma region, the Cl substituted the hydrogen on benzene ring in the initial time, which was replaced by a hydroxyl immediately, then the polyhydroxy phenol was easily decomposed. In addition, optical emission spectroscopy was carried out to characterize the plasma features during the CMPE process. The temperature of electron around the microarc discharge envelope reached about 4000 K; thus the phenol was partly carbonized to become graphite particles. CMPE is a promising approach to degrade quickly the phenol in wastewater.


Assuntos
Fenol , Águas Residuárias , Eletroquímica , Eletrodos , Eletrólise , Oxirredução , Fenóis
15.
Int J Mol Sci ; 17(7)2016 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-27438826

RESUMO

The green alga Myrmecia incisa is one of the richest natural sources of arachidonic acid (ArA). To better understand the regulation of ArA biosynthesis in M. incisa, a novel gene putatively encoding the Δ9 fatty acid desaturase (FAD) was cloned and characterized for the first time. Rapid-amplification of cDNA ends (RACE) was employed to yield a full length cDNA designated as MiΔ9FAD, which is 2442 bp long in sequence. Comparing cDNA open reading frame (ORF) sequence to genomic sequence indicated that there are 8 introns interrupting the coding region. The deduced MiΔ9FAD protein is composed of 432 amino acids. It is soluble and localized in the chloroplast, as evidenced by the absence of transmembrane domains as well as the presence of a 61-amino acid chloroplast transit peptide. Multiple sequence alignment of amino acids revealed two conserved histidine-rich motifs, typical for Δ9 acyl-acyl carrier protein (ACP) desaturases. To determine the function of MiΔ9FAD, the gene was heterologously expressed in a Saccharomyces cerevisiae mutant strain with impaired desaturase activity. Results of GC-MS analysis indicated that MiΔ9FAD was able to restore the synthesis of monounsaturated fatty acids, generating palmitoleic acid and oleic acid through the addition of a double bond in the Δ9 position of palmitic acid and stearic acid, respectively.


Assuntos
Ácido Araquidônico/metabolismo , Ácidos Graxos Dessaturases/metabolismo , Microalgas/enzimologia , Saccharomyces cerevisiae/metabolismo , Sequência de Aminoácidos , Clonagem Molecular , Ácidos Graxos Dessaturases/genética , Cromatografia Gasosa-Espectrometria de Massas , Microalgas/genética , Microalgas/crescimento & desenvolvimento , Filogenia , Saccharomyces cerevisiae/genética , Homologia de Sequência de Aminoácidos , Estearoil-CoA Dessaturase
16.
Sci Rep ; 6: 25514, 2016 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-27156368

RESUMO

In situ device (ISD) and circular disposable device (CDD) are used for optimizing male circumcision (MC), but evidence to explore the characteristics of these two devices is insufficient. In order to explore this issue systematically and provide reliable evidence, ten published randomized controlled trials (RCTs) exploring the safety and efficacy of ISDs and CDDs were included (involving 4649 men). Moderate quality of the RCTs included was found after assessment. Pairwise meta-analyses and network meta-analyses were processed in stata 13.0 and AIDDS v1.16.6 respectively. According to the outcomes that were statistically significant in both pairwise and network meta-analyses, ISD was found to have less intraoperative blood loss (IB), less operative time (OT) and less incidence of wound bleeding (WB) than conventional circumcision (CC); ISD was found to have less WB but more wound healing time (WHT) than CDD; CDD was found to have less IB and less OT than CC. CDD tended to have the best wound healing condition and least pain experience; ISD tended to have the least IB, least OT, least WB, and highest satisfaction rate. With their own superiorities in many aspects, CDD and ISD are both safe and effective devices for optimizing MC.


Assuntos
Circuncisão Masculina/instrumentação , Ensaios Clínicos como Assunto , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Viés de Publicação
17.
Nat Med ; 21(8): 895-905, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26214836

RESUMO

We carried out metagenomic shotgun sequencing and a metagenome-wide association study (MGWAS) of fecal, dental and salivary samples from a cohort of individuals with rheumatoid arthritis (RA) and healthy controls. Concordance was observed between the gut and oral microbiomes, suggesting overlap in the abundance and function of species at different body sites. Dysbiosis was detected in the gut and oral microbiomes of RA patients, but it was partially resolved after RA treatment. Alterations in the gut, dental or saliva microbiome distinguished individuals with RA from healthy controls, were correlated with clinical measures and could be used to stratify individuals on the basis of their response to therapy. In particular, Haemophilus spp. were depleted in individuals with RA at all three sites and negatively correlated with levels of serum autoantibodies, whereas Lactobacillus salivarius was over-represented in individuals with RA at all three sites and was present in increased amounts in cases of very active RA. Functionally, the redox environment, transport and metabolism of iron, sulfur, zinc and arginine were altered in the microbiota of individuals with RA. Molecular mimicry of human antigens related to RA was also detectable. Our results establish specific alterations in the gut and oral microbiomes in individuals with RA and suggest potential ways of using microbiome composition for prognosis and diagnosis.


Assuntos
Artrite Reumatoide/microbiologia , Intestinos/microbiologia , Microbiota , Boca/microbiologia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Proteína C-Reativa/análise , Humanos , Metagenoma , Saliva/microbiologia
18.
Eur J Med Chem ; 95: 377-87, 2015 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-25828929

RESUMO

The mutant p53 proteins and their corresponding cellular response can be manipulated by novel quinazolinone derivatives 4-8 (a-i) in p53 mutant cancer cells. Of the two most potent compounds, 4a exhibited promising broad-spectrum anti-cancer effects, whereas 6c showed selective and exclusive inhibition activity in p53 mutant cancer cell lines but low toxicity to wild-type p53 cancer cell A375 and normal lung fibroblast WI-38 cells. Furthermore, 6c exhibited a more sophisticated mechanism for cell-destructive response by causing S/G2 phase arrest effect and cell size reduction. Compared with the cellular response of 6b and genetic background of cell lines studied, p53 mutation was found to be the key factor and main target for 6c evoked cell-destructive response. Molecular mechanism studies indicated that p53 phosphorylation and acetylation dual-targeting inhibitor 6c exerted anti-cancer activities with a special mechanism in evoking cell apoptosis by arresting mutant p53 function to trigger the deregulation of Cdk2 caused Bim-mediated apoptosis. To the best of our knowledge, 6c is the first quinazolinone derivative to dictate mutant p53 function for apoptotic cell death.


Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Mutação , Quinazolinonas/farmacologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Acetilação/efeitos dos fármacos , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Quinase 2 Dependente de Ciclina/metabolismo , Humanos , Fosforilação/efeitos dos fármacos , Quinazolinonas/química
19.
Nature ; 490(7418): 55-60, 2012 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-23023125

RESUMO

Assessment and characterization of gut microbiota has become a major research area in human disease, including type 2 diabetes, the most prevalent endocrine disease worldwide. To carry out analysis on gut microbial content in patients with type 2 diabetes, we developed a protocol for a metagenome-wide association study (MGWAS) and undertook a two-stage MGWAS based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. We identified and validated approximately 60,000 type-2-diabetes-associated markers and established the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance. An analysis of 23 additional individuals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/microbiologia , Estudo de Associação Genômica Ampla/métodos , Intestinos/microbiologia , Metagenoma/genética , Metagenômica/métodos , Povo Asiático , Butiratos/metabolismo , China/etnologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/classificação , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Fezes/microbiologia , Ligação Genética/genética , Marcadores Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Redes e Vias Metabólicas/genética , Infecções Oportunistas/complicações , Infecções Oportunistas/microbiologia , Padrões de Referência , Sulfatos/metabolismo
20.
Anal Chem ; 81(6): 2364-72, 2009 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-19206530

RESUMO

A simple and renewable four-band platinum electrode for in situ conductivity measurement of polymers is described. A model is developed to evaluate contact resistance between the electrode and polyaniline film and calibrate the film resistances obtained by two-probe and four-probe methods. The conductivity of the film is calculated from the calibrated resistance. By comparing the effects of band thickness, gap width, and film thickness, it is found that the ratio K of the middle gap width to the thickness of the internal two platinum bands is the most important parameter to characterize one four-band electrode. An ideal four-band electrode should have large K and wide middle gap as possible so long as the film can uniformly cover the electrode. Under this case, the influence of contact resistance on the four-probe measurement of film resistance is negligible. It is shown that contact resistance depends on the oxidation state of the film. It rises nonlinearly with increasing film resistance.

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