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The emerging and global spread of a novel plasmid-mediated colistin resistance gene, mcr-1, threatens human health. Expression of the MCR-1 protein affects bacterial fitness and this cost correlates with lipid A perturbation. However, the exact molecular mechanism remains unclear. Here, we identified the MCR-1 M6 variant carrying two-point mutations that conferred co-resistance to ß-lactam antibiotics. Compared to wild-type (WT) MCR-1, this variant caused severe disturbance in lipid A, resulting in up-regulation of L, D-transpeptidases (LDTs) pathway, which explains co-resistance to ß-lactams. Moreover, we show that a lipid A loading pocket is localized at the linker domain of MCR-1 where these 2 mutations are located. This pocket governs colistin resistance and bacterial membrane permeability, and the mutated pocket in M6 enhances the binding affinity towards lipid A. Based on this new information, we also designed synthetic peptides derived from M6 that exhibit broad-spectrum antimicrobial activity, exposing a potential vulnerability that could be exploited for future antimicrobial drug design.
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Colistina , Proteínas de Escherichia coli , Humanos , Colistina/farmacologia , Antibacterianos/farmacologia , Antibióticos beta Lactam , Lipídeo A , Peptídeos Antimicrobianos , Monobactamas , Plasmídeos , Farmacorresistência Bacteriana/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Testes de Sensibilidade MicrobianaRESUMO
Gene duplications have long been recognized as a driving force in the evolution of genes, giving rise to novel functions. The soybean (Glycine max) genome is characterized by a large number of duplicated genes. However, the extent and mechanisms of functional divergence among these duplicated genes in soybean remain poorly understood. In this study, we revealed that 4 MYB genes (GmMYBA5, GmMYBA2, GmMYBA1, and Glyma.09g235000)-presumably generated by tandem duplication specifically in the Phaseoleae lineage-exhibited a stronger purifying selection in soybean compared to common bean (Phaseolus vulgaris). To gain insights into the diverse functions of these tandemly duplicated MYB genes in anthocyanin biosynthesis, we examined the expression, transcriptional activity, induced metabolites, and evolutionary history of these 4 MYB genes. Our data revealed that Glyma.09g235000 is a pseudogene, while the remaining 3 MYB genes exhibit strong transcriptional activation activity, promoting anthocyanin biosynthesis in different soybean tissues. GmMYBA5, GmMYBA2, and GmMYBA1 induced anthocyanin accumulation by upregulating the expression of anthocyanin pathway-related genes. Notably, GmMYBA5 showed a lower capacity for gene induction compared to GmMYBA2 and GmMYBA1. Metabolomics analysis further demonstrated that GmMYBA5 induced distinct anthocyanin accumulation in Nicotiana benthamiana leaves and soybean hairy roots compared to GmMYBA2 and GmMYBA1, suggesting their functional divergence leading to the accumulation of different metabolites accumulation following gene duplication. Together, our data provide evidence of functional divergence within the MYB gene cluster following tandem duplication, which sheds light on the potential evolutionary directions of gene duplications during legume evolution.
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Genes myb , Glycine max , Glycine max/genética , Antocianinas/genética , Duplicação Gênica , Família Multigênica , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
The structural exploration of three-dimensional covalent organic frameworks (3D COFs) is of great significance to the development of COF materials. Different from structurally diverse MOFs, which have a variety of connectivity (3-24), now the valency of 3D COFs is limited to only 4, 6, and 8. Therefore, the exploration of organic building blocks with higher connectivity is a necessary path to broaden the scope of 3D COF structures. Herein, for the first time, we have designed and synthesized a 12-connected triptycene-based precursor (triptycene-12-CHO) with 12 symmetrical distributions of aldehyde groups, which is also the highest valency reported until now. Based on this unique 12-connected structure, we have successfully prepared a novel 3D COF with lnj topology (termed 3D-lnj-COF). The as-synthesized 3D COF exhibits honeycomb main pores and permanent porosity with a Brunauer-Emmett-Teller surface area of 1159.6 m2 g-1. This work not only provides a strategy for synthesizing precursors with a high connectivity but also provides inspiration for enriching the variety of 3D COFs.
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As a common malignant tumor, esophageal squamous cell carcinoma (ESCC) is occasionally seen in clinical practice. This type of disease has low incidence rate and mortality. The post-translational modification of small ubiquitin like modifiers (SUMO) can play a crucial role in regulating protein function, and can significantly impact the occurrence and development of diseases. SUMO-specific peptidase (SENP) affects cell activity by regulating the biological function of SUMO. SENP3 belongs to the SENP family, and available data indicate that many malignancies are associated with SENPs, it is currently unclear its role in ESCC. This study indicates that there is a high level of SENP3 expression in ESCC tumor cells. If the expression level of this gene is high, it can have a significant impact on ESCC cell lines and affect physiological activities such as invasion of KYSE170 cells. If the gene is knocked out, this situation will not occur. There is also research data indicating that this gene can effectively activate related signaling pathways, thereby promoting the physiological activities of malignant tumor cells. In a nude mouse xenograft tumor model, KYSE170 cells with SENP3 expression knockdown induced a smaller volume and weight of tumor tissue. Therefore, it can be clearly stated that SENP3 can enable Wnt/ ß- The catenin signaling pathway is stimulated, which in turn affects the physiological activities of ESCC cells, including the invasion process. The results of this article lay the foundation for clinical staff to carry out clinical management.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Animais , Humanos , Camundongos , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , Via de Sinalização Wnt/genéticaRESUMO
BACKGROUND: The long non-coding RNA X-inactive specific transcript (XIST) plays a crucial role in transcriptional silencing of the X chromosome. Zinc finger E-box-binding homeobox 1 (ZEB1) is a transcription factor involved in epithelial-mesenchymal transition (EMT) regulation. AIMS: This study aimed to investigate the impact of XIST on esophageal squamous cell carcinoma (ESCC) progression and its underlying mechanism involving the miR-34a/ZEB1/E-cadherin/EMT pathway. METHODS: XIST and ZEB1 expression were analyzed using quantitative PCR and immunohistochemistry. XIST knockdown was achieved in KYSE150 ESCC cells using siRNA or shRNA lentivirus transfection. Proliferation, migration, and invasion abilities were assessed, and luciferase reporter assays were performed to confirm XIST-miR-34a-ZEB1 interactions. In vivo ESCC growth was evaluated using a xenograft mouse model. RESULTS: XIST and ZEB1 were upregulated in tumor tissues, correlating with metastasis and reduced survival. XIST knockdown inhibited proliferation, migration, and invasion of KYSE150 cells. It decreased ZEB1 expression, increased E-cadherin and miR-34a levels. Luciferase reporter assays confirmed miR-34a binding to XIST and ZEB1. XIST knockdown suppressed xenograft tumor growth. CONCLUSION: XIST promotes ESCC progression via the miR-34a/ZEB1/E-cadherin/EMT pathway. Targeting the XIST/miR-34a/ZEB1 axis holds therapeutic potential and serves as a prognostic biomarker in ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , MicroRNAs , RNA Longo não Codificante , Animais , Humanos , Camundongos , Caderinas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , Luciferases/genética , Luciferases/metabolismo , MicroRNAs/genética , Invasividade Neoplásica/genética , RNA Longo não Codificante/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismoRESUMO
Maintaining security in communication networks has long been a major concern. This issue has become increasingly crucial due to the emergence of new communication architectures like the Internet of Things (IoT) and the advancement and complexity of infiltration techniques. For usage in networks based on the Internet of Things, previous intrusion detection systems (IDSs), which often use a centralized design to identify threats, are now ineffective. For the resolution of these issues, this study presents a novel and cooperative approach to IoT intrusion detection that may be useful in resolving certain current security issues. The suggested approach chooses the most important attributes that best describe the communication between objects by using Black Hole Optimization (BHO). Additionally, a novel method for describing the network's matrix-based communication properties is put forward. The inputs of the suggested intrusion detection model consist of these two feature sets. The suggested technique splits the network into a number of subnets using the software-defined network (SDN). Monitoring of each subnet is done by a controller node, which uses a parallel combination of convolutional neural networks (PCNN) to determine the presence of security threats in the traffic passing through its subnet. The proposed method also uses the majority voting approach for the cooperation of controller nodes in order to more accurately detect attacks. The findings demonstrate that, in comparison to the prior approaches, the suggested cooperative strategy can detect assaults in the NSLKDD and NSW-NB15 datasets with an accuracy of 99.89 and 97.72 percent, respectively. This is a minimum 0.6 percent improvement.
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The antibiotic resistance crisis continues to threaten human health. Better predictions of the evolution of antibiotic resistance genes could contribute to the design of more sustainable treatment strategies. However, comprehensive prediction of antibiotic resistance gene evolution via laboratory approaches remains challenging. By combining site-specific integration and high-throughput sequencing, we quantified relative growth under the respective selection of cefotaxime or ceftazidime selection in â¼23,000 Escherichia coli MG1655 strains that each carried a unique, single-copy variant of the extended-spectrum ß-lactamase gene blaCTX-M-14 at the chromosomal att HK022 site. Significant synergistic pleiotropy was observed within four subgenic regions, suggesting key regions for the evolution of resistance to both antibiotics. Moreover, we propose PEARP and PEARR, two deep-learning models with strong clinical correlations, for the prospective and retrospective prediction of blaCTX-M-14 evolution, respectively. Single to quintuple mutations of blaCTX-M-14 predicted to confer resistance by PEARP were significantly enriched among the clinical isolates harboring blaCTX-M-14 variants, and the PEARR scores matched the minimal inhibitory concentrations obtained for the 31 intermediates in all hypothetical trajectories. Altogether, we conclude that the measurement of local fitness landscape enables prediction of the evolutionary trajectories of antibiotic resistance genes, which could be useful for a broad range of clinical applications, from resistance prediction to designing novel treatment strategies.
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Infecções por Escherichia coli , beta-Lactamases , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Resistência Microbiana a Medicamentos , Escherichia coli/genética , Infecções por Escherichia coli/tratamento farmacológico , Humanos , Estudos Prospectivos , Estudos Retrospectivos , beta-Lactamases/genéticaRESUMO
The interfacial effect is widely used to optimize the properties of ferroelectric nanocomposites, however, there is still a lack of direct evidence to understand its underlying mechanisms limited by the nano size and complex structures. Here, taking piezoelectricity, for example, the mechanism of interfacial polarization in barium titanate/poly(vinylidene fluoride-ran-trifluoroethylene) (BTO/P(VDF-TrFE)) nanocomposite is revealed at multiple scales by combining Kelvin probe force microscope (KPFM) with theoretical stimulation. The results prove that the mismatch of permittivity between matrix and filler leads to the accumulation of charges, which in turn induces local polarization in the interfacial region, and thus can promote piezoelectricity independently. Furthermore, the strategy of interfacial polarization to enhance piezoelectricity is extended and validated in other two similar nanocomposites. This work uncovers the mechanism of interfacial polarization and paves newfangled insights to boost performances in ferroelectric nanocomposites.
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BACKGROUND: Emerging functional imaging studies suggest that schizophrenia is associated with aberrant spatiotemporal interaction which may result in aberrant global and local dynamic properties. METHODS: We investigated the dynamic functional connectivity (FC) by using instantaneous phase method based on Hilbert transform to detect abnormal spatiotemporal interaction in schizophrenia. Based on resting-state functional magnetic resonance imaging, two independent datasets were included, with 114 subjects from COBRE [51 schizophrenia patients (SZ) and 63 healthy controls (HCs)] and 96 from OpenfMRI (36 SZ and 60 HCs). Phase differences and instantaneous coupling matrices were firstly calculated at all time points by extracting instantaneous parameters. Global [global synchrony and intertemporal closeness (ITC)] and local dynamic features [strength of FC (sFC) and variability of FC (vFC)] were compared between two groups. Support vector machine (SVM) was used to estimate the ability to discriminate two groups by using all aberrant features. RESULTS: We found SZ had lower global synchrony and ITC than HCs on both datasets. Furthermore, SZ had a significant decrease in sFC but an increase in vFC, which were mainly located at prefrontal cortex, anterior cingulate cortex, temporal cortex and visual cortex or temporal cortex and hippocampus, forming significant dynamic subnetworks. SVM analysis revealed a high degree of balanced accuracy (85.75%) on the basis of all aberrant dynamic features. CONCLUSIONS: SZ has worse overall spatiotemporal stability and extensive FC subnetwork lesions compared to HCs, which to some extent elucidates the pathophysiological mechanism of schizophrenia, providing insight into time-variation properties of patients with other mental illnesses.
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Esquizofrenia , Humanos , Imageamento por Ressonância Magnética/métodos , Lobo Temporal/patologia , Giro do Cíngulo , Hipocampo/patologiaRESUMO
OBJECTIVES: Liver tumor in the caudate lobe is challenging to treat, partly due to its deep location. Endoscopic ultrasound-guided laser ablation (EUS-LA) is a new attractive option for tumors in high-risk or difficult-to-reach locations. This prospective study investigated the long-term efficacy of EUS-LA for tumors in the caudate lobe, and factors that predict outcomes. METHODS: From June 2016 to July 2021, twenty consecutive patients (aged 56.95 ± 10.06 years) with 25 caudate lobe tumors (15.64 ± 6.37 mm) underwent EUS-LA. Treatment outcomes were assessed and predictive factors were calculated via univariate and multivariate analyses. RESULTS: Twenty-five tumors achieved complete ablation after the first or second session of EUS-LA. The treatment effectiveness was 100%. During a median follow up of 27 months (3-60), four tumors (16%) developed local tumor progression and 15 patients (75%) experienced intrahepatic distant recurrence. According to univariate and multivariate analyses, the significant prognostic factor of local tumor progression was tumor size >2 cm (p = 0.047). Significant prognostic factors of intrahepatic distant recurrence were: tumor number, alpha-fetoprotein level, and total bilirubin level (p = 0.020, 0.019, 0.010, respectively). No adverse events related to EUS-LA were observed. CONCLUSION: EUS-LA is a viable, safe, and effective treatment option for patients with liver tumor in the caudate lobe. Tumor size >2 cm increases the risk of post-procedural local tumor progression. Intrahepatic tumor number, and pretreatment alpha-fetoprotein level and total bilirubin level are associated with intrahepatic distant recurrence. REGISTRATION: Clinicaltrials.gov, ID: NCT02816944(June 29, 2016).
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Carcinoma Hepatocelular , Ablação por Cateter , Terapia a Laser , Neoplasias Hepáticas , Humanos , Estudos Prospectivos , alfa-Fetoproteínas , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/etiologia , Resultado do Tratamento , Ultrassonografia de Intervenção , Bilirrubina , Estudos Retrospectivos , Ablação por Cateter/efeitos adversos , Carcinoma Hepatocelular/etiologiaRESUMO
BACKGROUND: Mobile colistin resistance like gene (mcr-like gene) is a new type of polymyxin resistance gene that can be horizontally transferred in the Enterobacteriaceae. This has brought great challenges to the treatment of multidrug-resistant Escherichia coli and K. pneumoniae. RESULTS: K. pneumoniae 16BU137 and E. coli 17MR471 were isolated from the bus and subway handrails in Guangzhou, China. K. pneumoniae 19PDR22 and KP20191015 were isolated from patients with urinary tract infection and severe pneumonia in Anhui, China. Sequence analysis indicated that the mcr-1.1 gene was present on the chromosome of E. coli 17MR471, and the gene was in the gene cassette containing pap2 and two copies of ISApl1.The mcr-1.1 was found in the putative IncX4 type plasmid p16BU137_mcr-1.1 of K. pneumoniae 16BU137, but ISApl1 was not found in its flanking sequence. Mcr-8 variants were found in the putative IncFIB/ IncFII plasmid pKP20191015_mcr-8 of K. pneumoniae KP20191015 and flanked by ISEcl1 and ISKpn26. CONCLUSION: This study provides timely information on Enterobacteriaceae bacteria carrying mcr-like genes, and provides a reference for studying the spread of mcr-1 in China and globally.
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Proteínas de Escherichia coli , Polimixinas , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Enterobacteriaceae/genética , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Genômica , Humanos , Polimixinas/farmacologiaRESUMO
BACKGROUND: Carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) causes serious infections with significant morbidity and mortality. However, the epidemiology and transmission mechanisms of CR-hvKP and the corresponding carbapenem-resistant plasmids require further investigation. Herein, we have characterized an ST11 K. pneumoniae strain EBSI041 from the blood sample encoding both hypervirulence and carbapenem resistance phenotypes from a patient in Egypt. RESULTS: K. pneumoniae strain EBSI041 showed multidrug-resistance phenotypes, where it was highly resistant to almost all tested antibiotics including carbapenems. And hypervirulence phenotypes of EBSI041 was confirmed by the model of Galleria mellonella infection. Whole-genome sequencing analysis showed that the hybrid plasmid pEBSI041-1 carried a set of virulence factors rmpA, rmpA2, iucABCD and iutA, and six resistance genes aph(3')-VI, armA, msr(E), mph(E), qnrS, and sul2. Besides, blaOXA-48 and blaSHV-12 were harboured in a novel conjugative IncL-type plasmid pEBSI041-2. The blaKPC-2-carrying plasmid pEBSI041-3, a non-conjugative plasmid lacking the conjugative transfer genes, could be transferred with the help of pEBSI041-2, and the two plasmids could fuse into a new plasmid during co-transfer. Moreover, the emergence of the p16HN-263_KPC-like plasmids is likely due to the integration of pEBSI041-3 and pEBSI041-4 via IS26-mediated rearrangement. CONCLUSION: To the best of our knowledge, this is the first report on the complete genome sequence of KPC-2- and OXA-48-coproducing hypervirulent K. pneumoniae from Egypt. These results give new insights into the adaptation and evolution of K. pneumoniae during nosocomial infections.
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Infecções por Klebsiella , Klebsiella pneumoniae , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , Egito , Humanos , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/genética , Plasmídeos/genética , beta-Lactamases/genéticaRESUMO
For children, there are very few published reviews focusing on severe acute pancreatitis (AP). PubMed, EMBASE, Web of Science, Scopus, Chinese National Knowledge Infrastructure (CNKI), Wanfang data, EBSCO, and Cochrane Library were searched from inception until March 2020. Meta-regression analyses were used to estimate the etiology, case fatality, recurrence, and severity of pediatric AP in different regions (North America, Asia, South America, Europe, and Oceania). Pooled data from 47 papers (48 studies) found that main causes of pediatric AP were gallstones in Asia; trauma in Oceania; and idiopathic in Europe, North America, and South America. The case-fatality rate (CFR) of pediatric AP is 4.7% (North America), 6.2% (Europe), 2.4% (Asia), 3.1% (South America), and 7.4% (Oceania). The incidence rates of recurrent acute pancreatitis (RAP) in children who have had an episode of acute pancreatitis in North American, Asia, and Europe were 15.3, 13.1, and 13.8%, respectively. The incidence of severe acute pancreatitis (SAP) in different regions was 30.3% (Oceania), 29.2% (South America), 20.8% (Europe), 15.8% (Asia), and 13.7% (North America). It suggests that physicians should notice the etiology of pediatric AP for the initial assessment, diagnosis, prediction of relapse, and appropriate treatment at a later stage. IMPACT: It indicates the etiology of pediatric acute pancreatitis for the initial assessment, diagnosis, and prediction of relapse. Main causes of pediatric AP were gallstones in Asia; trauma in Oceania; and idiopathic in Europe, North America, and South America. The case-fatality rate of pediatric AP is diverse worldwide. It suggests that physicians noticed the etiology of pediatric AP for the initial assessment, diagnosis, prediction of relapse, and appropriate treatment at a later stage.
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Pancreatite/etiologia , Pancreatite/mortalidade , Criança , Humanos , Pancreatite/fisiopatologia , Recidiva , Índice de Gravidade de DoençaRESUMO
PURPOSE: This study aimed to explore the prevalence and distribution of mental disorders in the elderly population 5 years after the Lushan earthquake in Ya'an, China. METHODS: A multi-stage, group-matching random sampling method was adopted with 2579 elderly participants (≥ 60 years old) who were interviewed from January to May 2019. Preliminary screening was conducted using the scale by trained psychiatric nurses, followed by a diagnostic interview during the second stage using Chinese Version of the 5th edition of the Diagnostic and Statistical Manual of Mental Disorder by trained psychiatrists. RESULTS: A total of 2561 participants were included in this study with complete data. The weighted lifetime prevalence of all mental disorders in the elderly was 16.2% (95% CI 15.3-17.1), and the weighted 12-month prevalence was 15.2% (95% CI 13.4-17.0). Depressive disorders, anxiety disorders, substance-related and addictive disorders were the most common mental disorders. The 12-month prevalence of all mental disorders were significantly higher in the elderly living alone, with chronic somatic disease, and being poor (P < 0.05). The 12-month prevalence of posttraumatic stress disorder (PTSD) was significantly higher in the elderly in extremely severely earthquake-affected areas (P < 0.001). CONCLUSION: The results of this study show that mental health status of the elderly in Ya'an area differ by socio-economic development, geographical location, and natural disasters. The social and economic development characteristics, the impact of major natural disasters (e.g., earthquakes), and population characteristics should be combined to formulate strategies and interventions to promote the mental health of the elderly.
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Desastres , Terremotos , Transtornos Mentais , Transtornos de Estresse Pós-Traumáticos , Idoso , Humanos , Pessoa de Meia-Idade , Prevalência , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , China/epidemiologia , Fatores de Risco , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologiaRESUMO
Zeros in compositional data are very common and can be classified into rounded and essential zeros. The rounded zero refers to a small proportion or below detection limit value, while the essential zero refers to the complete absence of the component in the composition. In this article, we propose a new framework for analyzing compositional data with zero entries by introducing a stochastic representation. In particular, a new distribution, namely the Dirichlet composition distribution, is developed to accommodate the possible essential-zero feature in compositional data. We derive its distributional properties (e.g., its moments). The calculation of maximum likelihood estimates via the Expectation-Maximization (EM) algorithm will be proposed. The regression model based on the new Dirichlet composition distribution will be considered. Simulation studies are conducted to evaluate the performance of the proposed methodologies. Finally, our method is employed to analyze a dataset of fluorescence in situ hybridization (FISH) for chromosome detection.
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Algoritmos , Cromossomos , Simulação por Computador , Hibridização in Situ Fluorescente , Funções Verossimilhança , Distribuição de PoissonRESUMO
In response to the spread of colistin resistance gene mcr-1, China banned the use of colistin in livestock fodders. We used a time-series analysis of inpatient colonization data from 2011-2019 to accurately reveal the associated fluctuations of mcr-1 that occurred in inpatients in response to the ban.
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Farmacorresistência Bacteriana , Proteínas de Escherichia coli , Antibacterianos/farmacologia , China/epidemiologia , Escherichia coli , Humanos , Pacientes Internados , PrevalênciaRESUMO
Two multidrug-resistant (MDR) mcr-1-harboring Klebsiella pneumoniae isolates from patients with urinary tract infections and one MDR Klebsiella quasipneumoniae isolate from a patient with bloodstream infection were identified to carry tmexCD1-toprJ1 The addition of the efflux pump inhibitor reduced the tigecycline MIC against all three isolates by 8- to 16-fold. pKQBSI104-1 was transferred from K. quasipneumoniae to Escherichia coli J53 via conjugation. The tmexCD1-toprJ1-carrying plasmids pKP15ZE495-1 (102,569 bp) and pKQBSI104-1 (121,996 bp) were completely sequenced and analyzed.
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Infecções por Klebsiella , Klebsiella pneumoniae , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , China , Humanos , Klebsiella , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana , Plasmídeos/genéticaRESUMO
BACKGROUND: Previous studies reported the prevalence of mcr-1 among clinical infected Salmonella isolates in China. However, the transmission dynamics of mcr-1 in different ecological niches were not well investigated. Our objective is to exhibit the transmission dynamics of mcr-1 in Salmonella. METHODS: 598 Salmonella isolates were recovered from ten hospitals; besides 936 pig faces and 167 pork samples were collected from January 2015 to December 2017 in Guangzhou, China. PCR and sequencing were used to identify mcr-1-positive Salmonella. Antimicrobial susceptibility testing was performed with 16 antimicrobials. Conjugation, S1-PFGE, and Southern blot were used to determine the transferability and location of mcr-1. Whole-genome sequencing was used to investigate pangenome, phylogeny, plasmid, and transposon. RESULTS: Eleven mcr-1-positive Salmonella isolates were identified from patients with infectious diarrhea. Five pig fecal samples and three pork samples contained mcr-1-positive Salmonella isolates. All isolates were multi-drug resistant. The mcr-1 genes were located on â¼210-250 kb IncHI2-pST3 plasmids, and 12 mcr-1 genes were transferable. All isolates were assigned to ST34 or its genetically closed STs. The distribution of the core-genome network was significantly correlated with source distributions. The accessory genes-based network demonstrated that the diverse clonal complexes could share highly similar accessory genomes. CONCLUSIONS: The prevalence of mcr-1-positive Salmonella among different sources was low. Clonal transmission could not be the main reason for the expansion of mcr-1-positive Salmonella, but be attributed to the horizontal transfer of IncHI2-pST3 plasmid. Continuous surveillance on Salmonella should be performed to investigate the response of colistin banning in food-producing animals by mcr-1-positive Salmonella populations.
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Antibacterianos , Salmonella typhimurium , Animais , Antibacterianos/farmacologia , China/epidemiologia , Diarreia/epidemiologia , Genômica , Humanos , Plasmídeos/genética , Prevalência , Salmonella typhimurium/genética , SuínosRESUMO
By adoption of a high permittivity ZrO2capping layer (ZOCL), enhanced ferroelectric properties were achieved in the Hf0.5Zr0.5O2(HZO) thin films. For HZO thin film with 10 Å ZOCL, the 2Prvalue can reach as high as â¼43.1µC cm-2under a sweep electric field of 3 MV cm-1. In addition, a reduced coercive field of 1.5 MV cm-1was observed, which is comparable to that of HZO with metallic CL. Furthermore, the homogeneity of ferroelectric orthorhombic phase in HZO films was observed to be clearly increased, as evidenced by nanoscale piezoelectric force microscopy measurements. These results demonstrate that ZOCL is very favorable for high performance ferroelectric HZO films and their future device applications.
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PURPOSE: Studies regarding the association between dietary fat intake and gestational diabetes mellitus (GDM) are limited and provide conflicting findings. Thus, the study aims to examine the association of dietary fat intake in the year preceding pregnancy and during pregnancy with the risk of GDM, taking the relevance of dietary protein intake on GDM into consideration. METHODS: A prospective study was conducted in 6299 singleton pregnancies, using the data from the Nutrition in Pregnancy and Growth in Southwest China (NPGSC). A validated food frequency questionnaire was used to assess dietary fat intake in the year preceding pregnancy and during the first and second trimesters of pregnancy. Logistic regression analysis was used to assess the prospective associations of dietary fat intake and the type and source of dietary fats in different time windows with GDM risk. RESULTS: Higher intake of total fat [OR (95% CI): 2.21 (1.19-4.20), P = 0.02] during 12-22 weeks of gestation was associated with higher GDM risk. However, adjustment for animal protein intake greatly attenuated this association [OR (95% CI): 1.81 (0.93, 3.64), P = 0.11]. Total fat intake neither in the year preceding pregnancy nor during the early pregnancy was associated with GDM risk. Moreover, insignificant associations were observed between intakes of vegetable fat, animal fat, cholesterol, saturated fatty acid, monounsaturated fatty acid and polyunsaturated fatty acid one year before pregnancy and during the first and second trimesters and GDM risk. CONCLUSION: Our study indicated that dietary fat intake one year before pregnancy and across the two pregnancy trimesters preceding the diagnosis of GDM has no relevance on GDM risk among Chinese women, particularly those with normal BMI, low, or normal calorie intake.