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BACKGROUND: Severe burns may alter the stability of the intestinal flora and affect the patient's recovery process. Understanding the characteristics of the gut microbiota in the acute phase of burns and their association with phenotype can help to accurately assess the progression of the disease and identify potential microbiota markers. METHODS: We established mouse models of partial thickness deep III degree burns and collected faecal samples for 16 S rRNA amplification and high throughput sequencing at two time points in the acute phase for independent bioinformatic analysis. RESULTS: We analysed the sequencing results using alpha diversity, beta diversity and machine learning methods. At both time points, 4 and 6 h after burning, the Firmicutes phylum content decreased and the content of the Bacteroidetes phylum content increased, showing a significant decrease in the Firmicutes/Bacteroidetes ratio compared to the control group. Nine bacterial genera changed significantly during the acute phase and occupied the top six positions in the Random Forest significance ranking. Clustering results also clearly showed that there was a clear boundary between the communities of burned and control mice. Functional analyses showed that during the acute phase of burn, gut bacteria increased lipoic acid metabolism, seleno-compound metabolism, TCA cycling, and carbon fixation, while decreasing galactose metabolism and triglyceride metabolism. Based on the abundance characteristics of the six significantly different bacterial genera, both the XGboost and Random Forest models were able to discriminate between the burn and control groups with 100% accuracy, while both the Random Forest and Support Vector Machine models were able to classify samples from the 4-hour and 6-hour burn groups with 86.7% accuracy. CONCLUSIONS: Our study shows an increase in gut microbiota diversity in the acute phase of deep burn injury, rather than a decrease as is commonly believed. Severe burns result in a severe imbalance of the gut flora, with a decrease in probiotics and an increase in microorganisms that trigger inflammation and cognitive deficits, and multiple pathways of metabolism and substance synthesis are affected. Simple machine learning model testing suggests several bacterial genera as potential biomarkers of severe burn phenotypes.
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Queimaduras , Microbioma Gastrointestinal , Microbiota , Humanos , Animais , Camundongos , Bactérias/genética , Firmicutes/genética , RNA Ribossômico 16S/genéticaRESUMO
Transition metal ions are served as disinfectant thousand years ago. However, the in vivo antibacterial application of metal ions is strongly restricted due to its high affinity with proteins and lack of appropriate bacterial targeting method. Herein, for the first time, Zn2+ -gallic acid nanoflowers (ZGNFs) are synthesized by a facile one-pot method without additional stabilizing agents. ZGNFs are stable in aqueous solution while can be easily decomposed in acidic environments. Besides, ZGNFs can specifically adhere onto Gram-positive bacteria, which is mediated by the interaction of quinone from ZGNFs and amino groups from teichoic acid of Gram-positive bacteria. ZGNFs exhibit high bactericidal effect toward various Gram-positive bacteria in multiple environments, which can be ascribed to the in situ Zn2+ release on bacterial surface. Transcriptome studies reveal that ZGNFs can disorder basic metabolic processes of Methicillin-resistant Staphylococcus aureus (MRSA). Moreover, in a MRSA-induced keratitis model, ZGNFs exhibit long-term retention in the infected corneal site and prominent MRSA elimination efficacy due to the self-targeting ability. This research not only reports an innovative method to prepare metal-polyphenol nanoparticles, but also provides a novel nanoplatform for targeted delivery of Zn2+ in combating Gram-positive bacterial infections.
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Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias Gram-Positivas , Íons , Zinco/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
When grating patterns are simultaneously projected by a dual-projection structured-light system, interference-like blur and brightness overexposure in the superposed area often cause miscalculation of the phase of the grating pattern. In this study, we proposed a novel method, to the best of our knowledge, that utilizes orthogonal grating encoding to retrieve the phases of superposed grating patterns. Specifically, we determined the frequency of the dual-projection pattern based on the condition that enabled the separation of superposed orthogonal signals in wireless communication. Additionally, the maximum intensity of the projected pattern was determined using the intensity-saturation relationship. By performing a discrete Fourier transform on a series of superposed grating patterns, we obtained the wrapped phase of the corresponding projected grating patterns in the space-time dimension. Finally, we reconstructed the measured object by fusing the point clouds obtained from the dual-projection structured-light system. The experimental results demonstrated that the encoded orthogonal grating patterns could eliminate interference-like blurring and brightness overexposure during superposition and obtain high-precision phase maps and 3D reconstruction results, which provides the possibility for the simultaneous reconstruction of multiprojection structured light.
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The advanced oxidation process of the photo-Fenton reaction can produce hydroxyl radicals with extremely strong oxidizing properties for the efficient and green degradation of various chemical and microbial pollutants. Herein, we report an approach to fabricating heterogeneous Fenton catalysts of ß-FeOOH nanorods on porous substrates triggered by mussel-inspired coatings of levodopa (3,4-dihydroxy-phenyl-l-alanine, l-DOPA) and polyethylenimine (PEI) for efficient photocatalytic dyes' degradation and sterilization. The l-DOPA-based coatings not only promote the formation and immobilization of ß-FeOOH nanorods on the porous substrates by strong coordination between catechol/carboxyl groups and Fe3+ but also improve the energy band structure of the Fenton catalysts through a valence band blue shift and band gap narrowing. The photo-Fenton catalysts prepared by the l-DOPA-based coatings exhibit high electron transport efficiency and improved utilization of sunlight. Only 2 h of mineralization is needed to fabricate these catalysts with excellent photocatalytic efficiency, in which the degradation efficiency of methylene blue can reach 99% within 30 min, whereas the sterilization efficiency of E. coli/S. aureus can reach 93%/94% within 20 min of the photo-Fenton reaction. Additionally, the prepared catalysts reveal a high photodegradation performance for various dyes including methylene blue, methyl blue, methyl orange, direct yellow, and rhodamine B. Furthermore, the catalysts retain high dye degradation efficiencies of above 90% after five photodegradation cycles, indicating cycling performance and good stability.
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Corantes , Levodopa , Corantes/química , Escherichia coli , Peróxido de Hidrogênio/química , Ferro/química , Azul de Metileno , Porosidade , Staphylococcus aureus , EsterilizaçãoRESUMO
In phase-measurement profilometry (PMP), the gamma effect can cause severe nonlinear distortion of the phase pattern (i.e., water ripples on the surface profile). Gamma correction is an effective method to eliminate the gamma effects of commercial projectors. However, projector defocusing on the suppression of higher harmonics inevitably results in an estimated gamma deviation from the true value. In this study, gamma mapping is constructed using the duty ratio (DR) to code the chord distribution of the simulated distorted phase while considering projector defocusing. With the known gamma mapping, the accurate gamma is calculated by DR coding of the actual distorted phase under projector defocusing. Simulated experiments verified that the relative errors of the gamma calculated by the proposed method under different degrees of defocus were less than 3.5%. Furthermore, the experimental results demonstrate that the proposed gamma calculation method is robust to the defocus effect of the projector and that a smoother surface can be reconstructed after gamma correction.
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BACKGROUND: Cities such as Shenzhen in southern China have large immigrant populations, and the reproductive health issues of pregnant women in these populations have not received sufficient attention. Stillbirth seriously threatens their health and is becoming a social issue worthy of attention. We conducted this study to estimate the trend in stillbirths at 28 or more gestational weeks and the related sociodemographic characteristics of pregnant women among a large internal migrant population in South China. METHODS: A stillbirth is defined as a baby born with no signs of life after a given threshold, and are restricted to births of 28 weeks of gestation or longer, with a birth weight of at least 1000 g for international comparison. A population-based retrospective cohort of all births from January 2010 to December 2019 in Baoan, Shenzhen, was conducted using the Shenzhen Birth Registry Database. The overall stillbirth rate and year-specific stillbirth rate were calculated as the number of foetal deaths ≥28 gestational weeks or a birth weight ≥ 1000 g divided by the number of births over the last decade or in each year, respectively. The associations between the risk of stillbirth and maternal sociodemographic status were assessed using logistic regression. Spearman's rank correlation was calculated to evaluate the correlation between the economic status of the maternal birthplace and the stillbirth. RESULTS: An overall stillbirth rate of 4.5 per 1000 births was estimated in a total of 492,184 births in our final analysis. Migrant women accounted for 87% of the total population but had a higher stillbirth rate (4.8 per 1000 births) than the permanent population (2.8 per 1000 births). The stillbirth rate varied by region of maternal birthplace, from 4.1 per 1000 births in women from East China to 5.7 per 1000 births in women from West China. The GDP per capita of the maternal birthplace was strongly correlated with the stillbirth rate. CONCLUSIONS: Large disparities in the stillbirth rate exist between migrant and permanent populations and among regions of maternal birthplace in China. Strategies targeting migrant women based on their maternal birthplace are needed to further reduce the burden of stillbirth.
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Natimorto , Migrantes , Peso ao Nascer , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Fatores de Risco , Natimorto/epidemiologiaRESUMO
Ozone pollution has been associated with several adverse effects, including memory impairment, intellectual retardation, emotional disturbances. However, the potential mechanisms remain uncertain. The present study aimed to investigate whether ozone (O3) regulates synaptic plasticity through PI3K/Akt/GSK3ß signaling pathway and induces neurobehavioral modifications among the young rats. In vivo, the newborn rats were used to construct the animal model of early postnatal O3 treatment. In vitro, this study measured the effect of different concentrations of serum from O3 treated rats on the viability of the PC12 cells, and investigated the modifications of synaptic plasticity and PI3K/Akt/GSK3ß signaling pathway in the hippocampus and PC12 cells after O3 treated. The results revealed significant depression-like behavior and increased hippocampal histopathological damage in the young rats after O3 treated. Compared with the control group, the expression levels of synaptic related proteins including Drebrin, PSD95, Synaptophysin and PIK3R1, p-Akt, and p-GSK3ß were decreased in the O3 treated group. In vitro assays, a significant reduction in Drebrin, PSD95, Synaptophysin, PIK3R1, p-Akt, and p-GSK3ß was found in PC12 cells after O3 serum treated. While 740Y-P (a specific PI3K activator) administered, the expression levels of Drebrin, PSD95, Synaptophysin, PIK3R1, p-Akt, and p-GSK3ß in the 740Y-P + O3 group were significantly elevated in vivo and vitro compared with the O3-only group. In addition, miRNAs modulating PIK3R1 were screened on bioinformatics website, the study found aberrant expression of miR-221-3p in the hippocampus and serum of O3 treated group. Inhibition of miR-221-3p expression effectively reversed the reduction of Drebrin, PSD95, Synaptophysin, PIK3R1, p-Akt, and p-GSK3ß in PC12 cells induced by O3 treatment. Altogether, these studies indicate that O3 restrained the expression of PI3K/Akt/GSK3ß signaling pathway and impaired synaptic plasticity that resulted in depressive-like behavior in young rats. Moreover, miR-221-3p plays an important role in this procedure by regulating PIK3R1.
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MicroRNAs , Ozônio , Ratos , Animais , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Sinaptofisina , Ozônio/toxicidade , Plasticidade NeuronalRESUMO
OBJECTIVE: To explore the effects of acute paraquat (PQ) exposure on the phenotypic polarization of hippocampal microglia and its mechanism. METHODS: An acute PQ exposure rat model was established. Male SD rats were exposed to 0, 5, 25, and 50 mg/kg PQ, and brain hippocampal tissue was collected after 1, 3, and 7 days of exposure, respectively. Hippocampal pathological changes were examined by H&E staining, and immunohistochemistry (IHC) was used to detect changes in the number of Iba-1-positive cells, the average number of endpoints, and the average process length. The protein expression of Iba-1 was detected by western blotting. BV-2 microglia were treated with 0, 0.01, 0.025, 0.05, or 0.1 µmol/L PQ for 24 h. ELISA and western blotting assays were performed to detect the expression of TNF-α and IL-1ß in vivo and in vitro. The M1 microglia marker iNOS, the M2 microglia marker Arg-1, and the p-JAK2 and p-STAT3 protein were detected by western blotting. JAK2/STAT3 pathway activation role in regulating microglia phenotypic polarization was further validated in vivo and in vitro by JAK2-specific inhibitor AG490 administration. RESULTS: After acute PQ exposure, hippocampal neurons showed pathological changes such as loose arrangement and nuclear pyknosis, the number of Iba-1 positive cells and the expression of Iba-1 protein increased, and the average number of endpoints and average process length of microglia decreased. Histological examination revealed that compared with the control group, in the 50 mg/kg PQ group on the 3rd and 7th day, the expression of TNF-α, IL-1ß, and iNOS significantly increased, while that of Arg-1 significantly decreased. p-JAK2 and p-STAT3 expression significantly increased in the 50 mg/kg PQ group on the 1st, 3rd, and 7th day. In vitro, compared with the control group, the expression of TNF-α, IL-1ß, iNOS, p-JAK2, and p-STAT3 significantly increased, while Arg-1 expression was significantly reduced in the 0.025, 0.05, and 0.1 µmol/L PQ groups. After AG490 administration, the expression levels of p-JAK2, p-STAT3, iNOS, TNF-α, and IL-1ß in the AG490 +PQ group were significantly inhibited in vivo and in vitro compared with the PQ-only group. On the contrary, Arg-1 expression was significantly increased. CONCLUSION: Our results suggest that acute PQ exposure may induce M1-type polarization of hippocampal microglia by activating the JAK2/STAT3 pathway, which in turn releases pro-inflammatory factors such as TNF-α and IL-1ß, leading to hippocampal inflammatory damage.
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Various body indexes, especially body fat percentage (BFP), are widely used as effective indicators to measure our health. BFP is used in medicine to assess obesity, which is a body fat mass disorder accompanied with changes of the gut microbiota. However, the relationship between BFP and the gut microbiota has not been studied so far. To address this problem, we examined how gut microbiota and metabolome associated with body indices in healthy people. Microbial and metabolomics data based on 16S rDNA sequencing and LC-MS were obtained from stool samples of 20 healthy adults. Bioinformatics analysis was performed to explore the correlations between the body indices and gut microbial characteristics. Significantly different microbes were further validated via qPCR. Differential characteristics were filtered by building machine learning models to predict body status. Our data showed that abundance of Prevotella and the Prevotella/Bacteroides (P/B) ratio in the gut were markedly higher in high-BFP individuals than in low-BFP individuals. Microbial and metabolomics data consistently suggested significant differences in fatty acid metabolism in stool samples from the two groups. The P/B ratio and fatty acids are discriminative for people with different index levels by cross validation tests with machine learning models. These results suggest using Prevotella and fecal fatty acids as predictors may offer an alternative method for evaluating health status or weight loss. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12088-021-00989-5.
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Bacterial pathogens secrete numerous effector proteins via six secretion systems, type I to type VI secretion systems, to adapt to new environments or to promote virulence by bacterium-host interactions. Many computational approaches have been used in the identification of effector proteins before the subsequent experimental verification because they tolerate laborious biological procedures and are genome scale, automated and highly efficient. Prevalent examples include machine learning methods and statistical techniques. In this article, we summarize the computational progress toward predicting secreted effector proteins in bacteria, with an opening of an introduction of features that are used to discriminate effectors from non-effectors. The mechanism, contribution and deficiency of previous developed detection tools are presented, which are further benchmarked based on a curated testing data set. According to the results of benchmarking, potential improvements of the prediction performance are discussed, which include (1) more informative features for discriminating the effectors from non-effectors; (2) the construction of comprehensive training data set of the machine learning algorithms; (3) the advancement of reliable prediction methods and (4) a better interpretation of the mechanisms behind the molecular processes. The future of in silico identification of bacterial secreted effectors includes both opportunities and challenges.
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Algoritmos , Proteínas de Bactérias/metabolismo , Sistemas de Secreção Bacterianos/metabolismo , Aprendizado de Máquina , Teorema de Bayes , Biologia Computacional , Simulação por Computador , Bases de Dados Factuais/estatística & dados numéricos , Interações entre Hospedeiro e Microrganismos , Humanos , Cadeias de Markov , Modelos Biológicos , Redes Neurais de Computação , Máquina de Vetores de Suporte , VirulênciaRESUMO
During the urbanization, human activities have brought great changes to marine biodiversity and microbial communities of coastal water. Shenzhen is a coastal city that has developed rapidly over the past four decades, but the microbial communities and metabolic potential in offshore water are still not well characterized. Here, 16S rRNA gene V4-V5 sequencing was conducted to determine the microbial components from coastal waters in twenty selected areas of Shenzhen. The results showed a significant difference on the microbial composition between the western and eastern waters. Samples from western coast had more abundant Burkholderiaceae, Sporichthyaceae, Aeromonadaceae, and Methylophilaceae compared to eastern coast, and at the genus level, Candidatus Aquiluna, Aeromonas, Arcobacter, Ottowia and Acidibacter were significantly higher in western waters. There was also a notable difference within the western sample group, suggesting the taxa-compositional heterogeneity. Moreover, analysis of environmental factors and water quality revealed that salinity, pH and dissolved oxygen were relatively decreased in western samples, while total nitrogen, total phosphorus, chemical oxygen demand, and harmful marine vibrio were significantly increased compared to eastern waters. The results suggest the coastal waters pollution is more serious in western Shenzhen than eastern Shenzhen and the microbial communities are altered, which can be associated with anthropogenic disturbances.
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Microbiota , Biodiversidade , Humanos , RNA Ribossômico 16S/genética , Salinidade , Água do Mar , Qualidade da ÁguaRESUMO
The prevalence of hyperuricemia has increased rapidly over the past decades. Bisphenol A (BPA) is an environmental endocrine disruptor. We investigated the effects of BPA on uric acid metabolism and its potential mechanisms. Experiments were performed in different animal models, cell cultures, and humans. In 3 different animal models, BPA exposure increased serum and hepatic uric acid with enhanced activity of xanthine oxidase (XO) in liver, whereas the excretion of uric acid was unchanged. Both in vivo and in vitro, BPA-induced uric acid production was decreased after treatment with allopurinol, which is a XO inhibitor. XO led to the accumulation of uric acid after xanthine was added, with the enzyme-catalyzed reaction, which was enhanced by BPA. Altered secondary structures of XO were found by circular dichroism analysis in the conditions of different BPA concentrations. Molecular docking portrayed Asp360 and Lys422 of XO to be the preferred binding sites for BPA. Mutation of both sites significantly blocked the effect of BPA on XO activity. In humans, patients with hyperuricemia exhibited higher levels of serum BPA than subjects without hyperuricemia. These findings demonstrate BPA promotes hyperuricemia by increasing hepatic uric acid synthesis via the activation of XO, probably through direct binding.-Ma, L., Hu, J., Li, J., Yang, Y., Zhang, L., Zou, L., Gao, R., Peng, C., Wang, Y., Luo, T., Xiang, X., Qing, H., Xiao, X., Wu, C., Wang, Z., He, J. C., Li, Q., Yang, S. Bisphenol A promotes hyperuricemia via activating xanthine oxidase.
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Compostos Benzidrílicos/toxicidade , Hiperuricemia , Fígado/enzimologia , Simulação de Acoplamento Molecular , Fenóis/toxicidade , Xantina Oxidase , Animais , Sítios de Ligação , Indução Enzimática/efeitos dos fármacos , Hiperuricemia/induzido quimicamente , Hiperuricemia/enzimologia , Masculino , Camundongos , Xantina Oxidase/biossíntese , Xantina Oxidase/químicaRESUMO
We recently found lytic action of the truncated yncE gene. When the truncated yncE gene of Salmonella enterica serovar Paratyphi A was expressed in Escherichia coli DH5α under the control of the Ara promoter, bacterial growth was markedly inhibited. In the present study, we characterized this lytic action. The N-terminal 103 aa of YncE, containing a signal peptide, was demonstrated to be essential for inhibition. Microscopic observation showed that the bacterial envelope of E. coli was damaged by the expression of truncated yncE, resulting in the release of cytoplasmic content and the formation of bacterial ghosts. The addition of MgSO4 or spermine, which is the stabilizer of bacterial membrane structure, dramatically reversed the cell lysis induced by the toxic truncated YncE. In contrast, the lytic action was significantly enhanced by the addition of SDS or EDTA. Our data indicated that the toxic truncated YncE could cause cell lysis by the disruption of the bacterial membrane.
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Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Escherichia coli/fisiologia , Animais , Membrana Celular , Clonagem Molecular , Escherichia coli/ultraestrutura , Proteínas de Escherichia coli/química , Dosagem de Genes , Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Ordem dos Genes , Vetores Genéticos/genética , Domínios e Motivos de Interação entre Proteínas , Sinais Direcionadores de Proteínas , Deleção de SequênciaRESUMO
It has been previously demonstrated that genistein exhibits anticancer activity against breast cancer. However, the precise mechanisms underlying the anticancer effect of genistein, in particular the epigenetic basis, remain unclear. In this study, we investigated whether genistein could modulate the DNA methylation status and expression of cancer-related genes in breast cancer cells. We treated MCF-7 and MDA-MB-231 human breast cancer cells with genistein in vitro. We found that genistein decreased the levels of global DNA methylation, DNA methyltransferase (DNMT) activity and expression of DNMT1. Yet, the expression of DNMT3A and DNMT3B showed no significant change. Using molecular modeling, we observed that genistein might directly interact with the catalytic domain of DNMT1, thus competitively inhibiting the binding of hemimethylated DNA to the catalytic domain of DNMT1. Furthermore, genistein decreased DNA methylation in the promoter region of multiple tumor suppressor genes (TSGs) such as ataxia telangiectasia mutated (ATM), adenomatous polyposis coli (APC), phosphatase and tensin homolog (PTEN), mammary serpin peptidase inhibitor (SERPINB5), and increased the mRNA expression of these genes. However, we detected no significant changes in the DNA methylation status or mRNA expression of stratifin (SFN). These results suggest that the anticancer effect of genistein on breast cancer may be partly due to its ability to demethylate and reactivate methylation-silenced TSGs through direct interaction with the DNMT1 catalytic domain and inhibition of DNMT1 expression.
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Antineoplásicos/farmacologia , Neoplasias da Mama/genética , Metilação de DNA/efeitos dos fármacos , Genes Supressores de Tumor , Genisteína/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Epigênese Genética , Feminino , Genoma Humano , Humanos , Modelos MolecularesRESUMO
BACKGROUND: Whole-genome sequencing is an important method to understand the genetic information, gene function, biological characteristics and survival mechanisms of organisms. Sequencing large genomes is very simple at present. However, we encountered a hard-to-sequence genome of Pseudomonas aeruginosa phage PaP1. Shotgun sequencing method failed to complete the sequence of this genome. RESULTS: After persevering for 10 years and going over three generations of sequencing techniques, we successfully completed the sequence of the PaP1 genome with a length of 91,715 bp. Single-molecule real-time sequencing results revealed that this genome contains 51 N-6-methyladenines and 152 N-4-methylcytosines. Three significant modified sequence motifs were predicted, but not all of the sites found in the genome were methylated in these motifs. Further investigations revealed a novel immune mechanism of bacteria, in which host bacteria can recognise and repel modified bases containing inserts in a large scale. This mechanism could be accounted for the failure of the shotgun method in PaP1 genome sequencing. This problem was resolved using the nfi- mutant of Escherichia coli DH5α as a host bacterium to construct a shotgun library. CONCLUSIONS: This work provided insights into the hard-to-sequence phage PaP1 genome and discovered a new mechanism of bacterial immunity. The methylome of phage PaP1 is responsible for the failure of shotgun sequencing and for bacterial immunity mediated by enzyme Endo V activity; this methylome also provides a valuable resource for future studies on PaP1 genome replication and modification, as well as on gene regulation and host interaction.
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Genoma Viral , Fagos de Pseudomonas/genética , Fagos de Pseudomonas/imunologia , Metilação de DNA , Biblioteca Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Dados de Sequência Molecular , Proteínas Associadas a Pancreatite , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/imunologia , Pseudomonas aeruginosa/virologia , Análise de Sequência de DNARESUMO
MOTIVATION: Various human pathogens secret effector proteins into hosts cells via the type IV secretion system (T4SS). These proteins play important roles in the interaction between bacteria and hosts. Computational methods for T4SS effector prediction have been developed for screening experimental targets in several isolated bacterial species; however, widely applicable prediction approaches are still unavailable RESULTS: In this work, four types of distinctive features, namely, amino acid composition, dipeptide composition, .position-specific scoring matrix composition and auto covariance transformation of position-specific scoring matrix, were calculated from primary sequences. A classifier, T4EffPred, was developed using the support vector machine with these features and their different combinations for effector prediction. Various theoretical tests were performed in a newly established dataset, and the results were measured with four indexes. We demonstrated that T4EffPred can discriminate IVA and IVB effectors in benchmark datasets with positive rates of 76.7% and 89.7%, respectively. The overall accuracy of 95.9% shows that the present method is accurate for distinguishing the T4SS effector in unidentified sequences. A classifier ensemble was designed to synthesize all single classifiers. Notable performance improvement was observed using this ensemble system in benchmark tests. To demonstrate the model's application, a genome-scale prediction of effectors was performed in Bartonella henselae, an important zoonotic pathogen. A number of putative candidates were distinguished. AVAILABILITY: A web server implementing the prediction method and the source code are both available at http://bioinfo.tmmu.edu.cn/T4EffPred.
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Aminoácidos/química , Proteínas de Bactérias/metabolismo , Sistemas de Secreção Bacterianos , Biologia Computacional , Regulação Bacteriana da Expressão Gênica , Matrizes de Pontuação de Posição Específica , Proteínas de Bactérias/classificação , Proteínas de Bactérias/genética , Infecções por Bartonella/genética , Infecções por Bartonella/microbiologia , Bartonella henselae/patogenicidade , Genoma Bacteriano , Máquina de Vetores de Suporte , Fatores de Virulência/metabolismoRESUMO
Increasing scientific evidences suggest that aerobic exercise may improve cancer-related fatigue in breast cancer patients, but many existing studies have yielded inconclusive results. This meta-analysis aimed to derive a more precise estimation of the effects of aerobic exercise on cancer-related fatigue in breast cancer patients receiving chemotherapy. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched from inception through July 1, 2013 without language restrictions. Crude standardized mean difference (SMD) with 95 % confidence interval (CI) was calculated. Twelve comparative studies were assessed with a total of 1,014 breast cancer patients receiving chemotherapy, including 522 patients in the aerobic exercise group (intervention group) and 492 patients in the usual care group (control group). The meta-analysis results revealed that the Revised Piper Fatigue Scale (RPFS) scores of breast cancer patients in the intervention group were significantly lower than those in the control group (SMD=-0.82, 95% CI=-1.04 â¼ -0.60, P<0.001). However, there was no significant difference in the Functional Assessment of Chronic Illness Treatment-Fatigue scale (FACIT-F) scores between the intervention and control groups (SMD=0.09, 95% CI=-0.07 â¼ 0.25, P=0.224). Subgroup analysis by ethnicity indicated that there were significant differences in RPFS and FACIT-F scores between the intervention and control groups among Asian populations (RPFS: SMD=-1.08, 95% CI=-1.35 â¼ -0.82, P<0.001; FACIT-F: SMD=1.20, 95 % CI=0.70 â¼1.71, P<0.001), but not among Caucasian populations (all P>0.05). The current meta-analysis indicates that aerobic exercise may improve cancer-related fatigue in breast cancer patients receiving chemotherapy, especially among Asian populations.
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Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Exercício Físico , Fadiga/prevenção & controle , Povo Asiático , Neoplasias da Mama/complicações , Neoplasias da Mama/psicologia , Estudos de Casos e Controles , Feminino , Humanos , Viés de Publicação , Qualidade de VidaRESUMO
Human extrachromosomal circular DNA, or eccDNA, has been the topic of extensive investigation in the last decade due to its prominent regulatory role in the development of disorders including cancer. With the rapid advancement of experimental, sequencing and computational technology, millions of eccDNA records are now accessible. Unfortunately, the literature and databases only provide snippets of this information, preventing us from fully understanding eccDNAs. Researchers frequently struggle with the process of selecting algorithms and tools to examine eccDNAs of interest. To explain the underlying formation mechanisms of the five basic classes of eccDNAs, we categorized their characteristics and functions and summarized eight biogenesis theories. Most significantly, we created a clear procedure to help in the selection of suitable techniques and tools and thoroughly examined the most recent experimental and bioinformatics methodologies and data resources for identifying, measuring and analyzing eccDNA sequences. In conclusion, we highlighted the current obstacles and prospective paths for eccDNA research, specifically discussing their probable uses in molecular diagnostics and clinical prediction, with an emphasis on the potential contribution of novel computational strategies.
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To reveal the key factors influencing the progression of severe COVID-19 to critical illness and death in the intensive care unit (ICU) and to accurately predict the risk, as well as to validate the efficacy of treatment using traditional Chinese medicine (TCM), thus providing valuable recommendations for the clinical management of patients. A total of 189 patients with COVID-19 in 25 ICUs in Chongqing, China, were enrolled, and 16 eventually died. Statistical models shown that factors influencing the progression of COVID-19 to critical illness include the severity of illness at diagnosis, the mode of respiratory support, and the use of TCM. Risk factors for death include a history of metabolic disease, the use of antiviral drugs and TCM, and invasive endotracheal intubation. The area under curve of the noncollinearity model predicted the risk of progression to critical illness and the risk of death reached 0.847 and 0.876, respectively. The use of TCM is an independent protective factor for the prevention of the progression of severe COVID-19, while uncorrectable hypoxemia and invasive respiratory support are independent risk factors, and antiviral drugs can help reduce mortality. The multifactorial prediction model can assess the risk of critical illness and death in ICU COVID-19 patients, and inform clinicians in choosing the treatment options and medications.
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COVID-19 , Humanos , COVID-19/terapia , Medicina Tradicional Chinesa , Estado Terminal/terapia , Unidades de Terapia Intensiva , AntiviraisRESUMO
SIGNIFICANCE: Inflammatory linear verrucous epidermal nevus (ILVEN) is an uncommon type of epidermal nevus and is refractory to therapy. We report the effectiveness of photodynamic therapy (PDT) for treating ILVEN with claudication in a young girl. ADDITIONAL CONTRIBUTIONS: We thank the patient for granting permission to publish this information. APPROACH: Aminolaevulinic Acid Hydrochloride (ALA) photodynamic therapy (PDT) was applied six times in 1-month interval. RESULTS: Most lesions and pruritus have subsided markedly, with mild scarring and a marked reduction in claudication. CONCLUSIONS: ALA PDT might be an effective and promising treatment for ILVEN in the future.