RESUMEN
The peptidoglycan (PG) layer is a critical component of the bacterial cell wall and serves as an important target for antibiotics in both gram-negative and gram-positive bacteria. The hydrolysis of septal PG (sPG) is a crucial step of bacterial cell division, facilitated by FtsEX through an amidase activation system. In this study, we present the cryo-EM structures of Escherichia coli FtsEX and FtsEX-EnvC in the ATP-bound state at resolutions of 3.05 Å and 3.11 Å, respectively. Our PG degradation assays in E. coli reveal that the ATP-bound conformation of FtsEX activates sPG hydrolysis of EnvC-AmiB, whereas EnvC-AmiB alone exhibits autoinhibition. Structural analyses indicate that ATP binding induces conformational changes in FtsEX-EnvC, leading to significant differences from the apo state. Furthermore, PG degradation assays of AmiB mutants confirm that the regulation of AmiB by FtsEX-EnvC is achieved through the interaction between EnvC-AmiB. These findings not only provide structural insight into the mechanism of sPG hydrolysis and bacterial cell division, but also have implications for the development of novel therapeutics targeting drug-resistant bacteria.
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Adenosina Trifosfato , División Celular , Proteínas de Escherichia coli , Escherichia coli , Peptidoglicano , Peptidoglicano/metabolismo , Hidrólisis , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/química , Escherichia coli/metabolismo , Escherichia coli/genética , Adenosina Trifosfato/metabolismo , Microscopía por Crioelectrón , Pared Celular/metabolismo , Conformación Proteica , Modelos Moleculares , N-Acetil Muramoil-L-Alanina Amidasa/metabolismo , N-Acetil Muramoil-L-Alanina Amidasa/genética , Proteínas de la Membrana Bacteriana Externa , Transportadoras de Casetes de Unión a ATP , Regulador de Conductancia de Transmembrana de Fibrosis Quística , Lipoproteínas , Proteínas de Ciclo CelularRESUMEN
BACKGROUND: The influence of native secondary succession associated with anthropogenic disturbance on the biodiversity of the forests in subtropical China remains uncertain. In particular, the evolutionary response of small understory shrubs, particularly pioneer species inhabiting continuously disturbed habitats, to topographic heterogeneity and climate change is poorly understood. This study aimed to address this knowledge gap by focusing on the Gaultheria crenulata group, a clade of small pioneer shrubs in subtropical China. RESULTS: We examined the genetic structure and demographic history of all five species of the G. crenulata group with two maternally inherited chloroplast DNA (cpDNA) fragments and two biparentally inherited low-copy nuclear genes (LCG) over 89 natural populations. We found that the genetic differentiation of this group was influenced by the geomorphological boundary between different regions of China in association with Quaternary climatic events. Despite low overall genetic diversity, we observed an isolation-by-distance (IBD) pattern at a regional scale, rather than isolation-by-environment (IBE), which was attributed to ongoing human disturbance in the region. CONCLUSION: Our findings suggest that the genetic structure of the G. crenulata group reflects the interplay of geological topography, historical climates, and anthropogenic disturbance during the Pliocene-Pleistocene-Holocene periods in subtropical China. The observed IBD pattern, particularly prominent in western China, highlights the role of limited dispersal and gene flow, possibly influenced by physical barriers or decreased connectivity over geographic distance. Furthermore, the east-to-west trend of gene flow, potentially facilitated by the East Asian monsoon system, underscores the complex interplay of biotic and abiotic factors shaping the genetic dynamics of pioneer species in subtropical China's secondary forests. These findings can be used to assess the impact of environmental changes on the adaptation and persistence of biodiversity in subtropical forest ecosystems.
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Bosques , Variación Genética , China , ADN de Cloroplastos/genética , Dinámica Poblacional , Biodiversidad , Flujo GénicoRESUMEN
BACKGROUND: Glioblastoma (GBM) is a highly heterogeneous, recurrent and aggressively invasive primary malignant brain tumor. The heterogeneity of GBM results in poor targeted therapy. Therefore, the aim of this study is to depict the cellular landscape of GBM and its peritumor from a single-cell perspective. Discovering new cell subtypes and biomarkers, and providing a theoretical basis for precision therapy. METHODS: We collected 8 tissue samples from 4 GBM patients to perform 10 × single-cell transcriptome sequencing. Quality control and filtering of data by Seurat package for clustering. Inferring copy number variations to identify malignant cells via the infercnv package. Functional enrichment analysis was performed by GSVA and clusterProfiler packages. STRING database and Cytoscape software were used to construct protein interaction networks. Inferring transcription factors by pySCENIC. Building cell differentiation trajectories via the monocle package. To infer intercellular communication networks by CellPhoneDB software. RESULTS: We observed that the tumor microenvironment (TME) varies among different locations and different GBM patients. We identified a proliferative cluster of oligodendrocytes with high expression of mitochondrial genes. We also identified two clusters of myeloid cells, one primarily located in the peritumor exhibiting an M1 phenotype with elevated TNFAIP8L3 expression, and another in the tumor and peritumor showing a proliferative tendency towards an M2 phenotype with increased DTL expression. We identified XIST, KCNH7, SYT1 and DIAPH3 as potential factors associated with the proliferation of malignant cells in GBM. CONCLUSIONS: These biomarkers and cell clusters we discovered may serve as targets for treatment. Targeted drugs developed against these biomarkers and cell clusters may enhance treatment efficacy, optimize immune therapy strategies, and improve the response rates of GBM patients to immunotherapy. Our findings provide a theoretical basis for the development of individualized treatment and precision medicine for GBM, which may be used to improve the survival of GBM patients.
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Biomarcadores de Tumor , Glioblastoma , Análisis de la Célula Individual , Microambiente Tumoral , Humanos , Glioblastoma/patología , Glioblastoma/genética , Glioblastoma/metabolismo , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Análisis por Conglomerados , Mapas de Interacción de Proteínas , Variaciones en el Número de Copia de ADN/genética , Agregación Celular , Perfilación de la Expresión GénicaRESUMEN
OBJECTIVES: Staphylococcus aureus (S. aureus) spreads worldwide and occurrence of mastitis caused by it holds significant implications for public health. We aim to reveal the molecular typing, antibiotic resistance and virulence gene profile of S. aureus causing mastitis through investigation. METHODS: A total of 200 isolates of S. aureus were collected from outpatients infected with mastitis in a hospital in Beijing from 2020.7 to 2021.7. The molecular characteristics were analyzed by MLST and spa typing, virulence genes were screened by PCR, antibiotic susceptible test was performed by VITEK® 2 Compact system and phylogenetic analysis was performed by MEGA11 and iTOL. RESULTS: Nineteen sequence types (STs) belonging to 9 clone complexes (CCs) were identified. ST22 was the most dominant clone (77.0%, 154/200). MRSA accounted for 19.0% (38/200) and 89.5% (34/38) of MRSA isolates belonged to CC22 and CC59. The isolates had relatively low levels of antibiotic resistance, with the exception of ß-lactams and macrolides with resistance rates above 50.0%. The carrying rate of pvl in the ST22-MRSA strains were 84.2% and the detection rates of seb and pvl in the MRSA isolates were significantly higher than those in the MSSA isolates, while the hlg, fnbA and sdrD showed opposite results. Whole genome sequenced specimens of MRSA strains X4 and B5 show the same evolutionary origin as ST22 EMRSA-15 (HE681097), which is popular in Europe. CONCLUSIONS: The method based on molecular epidemiology is an important tool for tracking the spread of S. aureus infections. We need to be alert to the major MRSA clones CC22 and CC59 in the region and be vigilant to the possible pandemic and spread of ST22 EMRSA-15.
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Antibacterianos , Infecciones Comunitarias Adquiridas , Mastitis , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Filogenia , Infecciones Estafilocócicas , Staphylococcus aureus , Factores de Virulencia , Humanos , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/epidemiología , Femenino , Beijing/epidemiología , Staphylococcus aureus/genética , Staphylococcus aureus/aislamiento & purificación , Staphylococcus aureus/clasificación , Staphylococcus aureus/efectos de los fármacos , Prevalencia , Factores de Virulencia/genética , Mastitis/microbiología , Mastitis/epidemiología , Antibacterianos/farmacología , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/epidemiología , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/clasificación , China/epidemiologíaRESUMEN
2-Methyl-1-butanol (2MB) and 3-Methyl-1-butanol (3MB) are microbial volatile organic compounds (VOCs) and found in indoor air. Here, we applied rice as a bioindicator to investigate the effects of these indoor microbial volatile pollutants. A remarkable decrease in germination percentage, shoot and root elongation, as well as lateral root numbers were observed in 3MB. Furthermore, ROS production increased by 2MB and 3MB, suggesting that pentanol isomers could induce cytotoxicity in rice seedlings. The enhancement of peroxidase (POD) and catalase (CAT) activity provided evidence that pentanol isomers activated the enzymatic antioxidant scavenging systems, with a more significant effect observed in 3MB. Furthermore, 3MB induced higher activity levels of glutathione (GSH), oxidized glutathione (GSSG), and the GSH/GSSG ratio in rice compared to the levels induced by 2MB. Additionally, qRT-PCR analysis showed more up-regulation in the expression of glutaredoxins (GRXs), peroxiredoxins (PRXs), thioredoxins (TRXs), and glutathione S-transferases (GSTUs) genes in 3MB. Taking the impacts of pentanol isomers together, the present study suggests that 3MB exhibits more cytotoxic than 2MB, as such has critical effects on germination and the early seedling stage of rice. Our results provide molecular insights into how isomeric indoor microbial volatile pollutants affect plant growth through airborne signals.
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Contaminantes Ambientales , Oryza , Antioxidantes/metabolismo , Plantones , Oryza/metabolismo , Pentanoles/metabolismo , Pentanoles/farmacología , 1-Butanol/metabolismo , 1-Butanol/farmacología , Contaminantes Ambientales/metabolismo , Disulfuro de Glutatión/metabolismo , Estrés Oxidativo , Glutatión/metabolismo , Raíces de Plantas/metabolismoRESUMEN
BACKGROUND: The comparison between prostaglandin E2 (PGE2) and oxytocin and for induction of labor (IOL) remains controversial. OBJECTIVE: The present study aimed to determine the safety and efficacy of these two agents in IOL. SEARCH STRATEGY: PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov. from the establishment of the database to April 23, 2023. SELECTION CRITERIA: A search was conducted with keywords "labor, induction, prostaglandin E2/PGE2/dinoprostone, and oxytocin". Only randomized clinical trials comparing oxytocin and vaginal dinoprostone in women who were at least late preterm (gestational age [GA] ≥34 weeks), singleton pregnant, and had intact membranes were enrolled for further meta-analysis. DATA COLLECTION AND ANALYSIS: We conducted both a descriptive analysis and a meta-analysis. In the meta-analysis, we utilized the Mantel-Haenszel random effects model to analyze dichotomous data, employing the relative risk (RR) as the effect measure along with 95% confidence intervals (CIs). The study quality was evaluated using Cochrane Collaboration's risk of bias assessment tool (RoB 2). A random-effects model was applied for the meta-analysis. MAIN RESULTS: After screening 3303 articles from five databases, a total of nine randomized controlled studies composed of 1071 patients were included. Our analysis included 534 patients in the PGE2 group and 537 patients in the oxytocin group. The pooled estimate of vaginal deliveries following PGE2 induction stood at 84.2%, while after oxytocin induction, it was 79.8%. The meta-analysis showed no statistical difference between the two groups in terms of the rate of vaginal delivery (pooled RR, 1.05; 95% CI: 0.95-1.16; P value for Q, 0.001; I2, 71.14%), cesarean section (pooled RR, 0.84; 95% CI: 0.52-1.35; P value for Q, 0.007; I2, 61.69%) and induction-delivery interval (pooled standard mean difference, 0.09; 95% CI: -0.67 to 0.85; P value for Q, 0.000; I2, 96.45%). Since the results for fetal distress and uterine hyperstimulation were consistent across all enrolled studies, no further meta-analysis was conducted. CONCLUSIONS: When amalgamating the available literature, it implies that oxytocin was found to have similar effects as PGE2 on delivery outcomes and safety concerns in pregnant women with GA ≥36 weeks. Although the uterine cervix was unfavorable, both low and high doses of oxytocin were feasible for IOL.
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Dinoprostona , Trabajo de Parto Inducido , Oxitócicos , Oxitocina , Humanos , Femenino , Oxitocina/administración & dosificación , Trabajo de Parto Inducido/métodos , Dinoprostona/administración & dosificación , Embarazo , Oxitócicos/administración & dosificación , Administración Intravaginal , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Introduction: Gastric cancer (GC) remains a major global health threat ranking as the fifth most prevalent cancer. Hypoxia, a characteristic feature of solid tumors, significantly contributes to the malignant progression of GC. Mitochondria are the major target of hypoxic injury that promotes mitochondrial dysfunction during the development of cancers including GC. However, the gene signature and prognostic model based on hypoxia- and mitochondrial dysfunction-related genes (HMDRGs) in the prediction of GC prognosis have not yet been established. Methods: The gene expression profile datasets of stomach cancer patients were retrieved from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Prognostic genes were selected using Least Absolute Shrinkage and Selection Operator Cox (LASSO-Cox) regression analysis to construct a prognostic model. Immune infiltration was evaluated through ESTIMATE, CIBERSORT, and ssGSEA analyses. Tumor immune dysfunction and exclusion (TIDE) and immunophenoscore (IPS) were utilized to explore implications for immunotherapy. Furthermore, in vitro experiments were conducted to validate the functional roles of HMDRGs in GC cell malignancy. Results: In this study, five HMDRGs (ZFP36, SERPINE1, DUSP1, CAV1, and AKAP12) were identified for developing a prognostic model in GC. This model stratifies GC patients into high- and low-risk groups based on median risk scores. A nomogram predicting overall survival (OS) was constructed and showed consistent results with observed OS. Immune infiltration analysis indicated that individuals in the high-risk group tend to exhibit increased immune cell infiltration. Additionally, analysis of cancer immunotherapy responses revealed that high-risk group patients exhibit poorer responses to cancer immunotherapy compared to the low-risk group. Immunohistochemistry (IHC) staining indicated that the expression levels of HMDRGs were remarkably correlated with GC, of which, SERPINE1 displayed the most pronounced up-regulation, while ZFP36 exhibited the most notable down-regulation in GC patients. Furthermore, in vitro investigation validated that SERPINE1 and ZFP36 contribute to the malignant processes of GC cells correlated with mitochondrial dysfunction. Conclusions: This study presents a novel and efficient approach to evaluate GC prognosis and immunotherapy efficacy, and also provides insights into understanding the pathogenesis of GC.
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Biomarcadores de Tumor , Mitocondrias , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/mortalidad , Pronóstico , Mitocondrias/metabolismo , Mitocondrias/genética , Biomarcadores de Tumor/genética , Análisis de la Célula Individual , Masculino , Regulación Neoplásica de la Expresión Génica , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Femenino , Transcriptoma , Perfilación de la Expresión Génica , Inhibidor 1 de Activador Plasminogénico/genética , Persona de Mediana Edad , Análisis de Secuencia de ARN , Línea Celular TumoralRESUMEN
Hematopoietic stem and progenitor cells (HSPCs) can give rise to all kinds of immune cells including neutrophils. Neutrophils are the first line of defense in the innate immune system with a short lifespan, due to which it is well-accepted that neutrophils have no immune memory. However, recent reports showed that the changes in HSPCs induced by primary stimulation could last a long time, which contributes to enhancing response to subsequent infection by generating more monocytes or macrophages equipped with stronger anti-bacterial function. Here, we used the reinfection mice model to reveal that primary infection could improve neutrophil-mediated host defense by training neutrophil progenitors in mammals, providing a new idea to enhance neutrophil number and improve neutrophil functions, which is pretty pivotal for patients with compromised or disordered immunity.
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Células Madre Hematopoyéticas , Neutrófilos , Animales , Neutrófilos/inmunología , Ratones , Células Madre Hematopoyéticas/inmunología , Ratones Endogámicos C57BL , Inmunidad Innata , Humanos , Reinfección/inmunología , Modelos Animales de EnfermedadRESUMEN
Infection caused by KPC and NDM carbapenemases co-producing Klebsiella pneumoniae (KPC_NDM_CRKP) poses serious public health concerns. Here, we elucidate the prevalence of a hypertransmissible lncM1 plasmid, pKPC_NDM, co-carrying blaKPC-2 and blaNDM-1 genes in sequence type 1049 K_locus 5 (ST1049-KL5) KPC_NDM_CRKP isolates. Genetic and clonal relatedness analyses using pulsed-field gel electrophoresis, single nucleotide polymorphism analysis and core genome multilocus sequence typing suggested clonal dissemination of ST1049-KL5 KPC_NDM_CRKP strains in our hospital. Whole genome sequencing identified an identical 76,517 bp- blaKPC-2 and blaNDM-1 genes co-carrying IncM1 plasmid pKPC_NDM and a pLVPK-like hypervirulent plasmid in all ST1049-KL5 KPC_NDM_CRKP isolates. pKPC_NDM shared 100% identity with a previously sequenced plasmid CRKP35_unnamed4, demonstrating high transferability in conjugation assay, with conjugation frequencies reaching 10-4 and 10-5 in Escherichia coli and K. pneumoniae recipients, respectively. It also maintained favorable stability and flexible compatibility, with retention rates exceeding 80% after 10 days of continuous passage, and could be compatible with pre-existing blaKPC- or blaNDM-carrying plasmids in recipient strains. This study summarizes the characteristics of KPC_NDM_CRKP outbreaks and highlights the importance of ongoing surveillance and infection control strategies to address the challenges posed by ST1049 K. pneumoniae strains.
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Infecciones por Klebsiella , Klebsiella pneumoniae , Plásmidos , beta-Lactamasas , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/aislamiento & purificación , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Plásmidos/genética , Infecciones por Klebsiella/epidemiología , Infecciones por Klebsiella/microbiología , Humanos , Prevalencia , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Enterobacteriaceae Resistentes a los Carbapenémicos/aislamiento & purificación , Antibacterianos/farmacología , Carbapenémicos/farmacología , Secuenciación Completa del Genoma , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Pruebas de Sensibilidad MicrobianaRESUMEN
Central China has been reported to be one of the most important endemic areas of zoonotic infection by spotted fever group rickettsiae (SFGR), severe fever with thrombocytopenia syndrome virus (SFTSV) and hantaan virus (HTNV). Due to similar clinical symptoms, it is challenging to make a definite diagnosis rapidly and accurately in the absence of microbiological tests. In the present study, an all-in-one real-time PCR assay was developed for the simultaneous detection of nucleic acids from SFGR, SFTSV and HTNV. Three linear standard curves for determining SFGR-ompA, SFTSV-L and HTNV-L were obtained within the range of 101-106 copies/µL, with the PCR amplification efficiencies ranging from 93.46% to 96.88% and the regression coefficients R2 of >0.99. The detection limit was 1.108 copies/µL for SFGR-ompA, 1.075 copies/µL for SFTSV-L and 1.006 copies/µL for HTNV-L, respectively. Both the within-run and within-laboratory coefficients of variation on the cycle threshold (Ct) values were within the range of 0.53%-2.15%. It was also found there was no statistical difference in the Ct values between single template and multiple templates (PSFGR-ompA = 0.186, PSFTSV-L = 0.612, PHTNV-L = 0.298). The sensitivity, specificity, positive and negative predictive value were all 100% for determining SFGR-ompA and SFTSV-L, 97%, 100%, 100% and 99.6% for HTNV-L, respectively. Therefore, the all-in-one real-time PCR assay appears to be a reliable, sensitive, rapid, high-throughput and low cost-effective method to diagnose the zoonotic infection by SFGR, SFTSV and HTNV.
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Virus Hantaan , Phlebovirus , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad , Síndrome de Trombocitopenia Febril Grave , China/epidemiología , Virus Hantaan/genética , Virus Hantaan/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Phlebovirus/genética , Phlebovirus/aislamiento & purificación , Humanos , Síndrome de Trombocitopenia Febril Grave/diagnóstico , Rickettsia/aislamiento & purificación , Rickettsia/genética , Rickettsiosis Exantemáticas/diagnóstico , AnimalesRESUMEN
Central nervous system (CNS) infections are a leading cause of death in patients. Nanopore-targeted sequencing (NTS) has begun to be used for pathogenic microbial detection. This study aims to evaluate the ability of NTS in the detection of pathogens in cerebrospinal fluid (CSF) through a prospective study. Fifty CSF specimens collected from 50 patients with suspected CNS infections went through three methods including NTS, metagenomic next-generation sequencing (mNGS), and microbial culture in parallel. When there was an inconsistency between NTS results and the results of the mNGS, the 16S rDNA gene was amplified followed by Sanger sequencing to further verify pathogens detected by NTS. Among 50 CSF specimens, 76% were NTS-positive, which is lower than mNGS (94.0%), yet higher than microbial culture (16.0%). The overall validation rate, diagnostic accordance rate (DAR), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of NTS were 86.7%, 50.0%, 71.0%, 15.8%, 57.9%, and 25.0%, respectively. In the CSF total nucleated cell (TNC) number ≤10 cells/µL, DAR, specificity, and PPV were 20%, 11.1%, and 11.1%, whereas in that with CSF TNC number >10 cells/µL, DAR, sensitivity, specificity, PPV, and NPV were 57.5%, 70.0%, 20.0%, 72.4%, and 18.2%, respectively. Although NTS has a higher microbial detection rate than microbial culture, it should combine CSF TNC result to evaluate the value of NTS for the diagnosis of CNS infections. IMPORTANCE: This study aims to prospectively evaluate the ability of nanopore-targeted sequencing (NTS) in the detection of pathogens in cerebrospinal fluid (CSF). It was the first time combining mNGS and microbial culture to verify the NTS-positive results also using 16S rDNA amplification with Sanger sequencing. Although microbial culture was thought to be the gold standard for pathogens detection and diagnosis of infectious diseases, this study suggested that microbial culture of CSF is not the most appropriate way for diagnosing central nervous system (CNS) infection. NTS should be recommended to be used in CSF for diagnosing CNS infection. When evaluating the value of NTS for diagnosis of CNS infections, the results of CSF TNC should be combined, and NTS-positive result is observed to be more reliable in patients with CSF TNC level >10 cells/µL.
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Infecciones del Sistema Nervioso Central , Nanoporos , Humanos , Estudios Prospectivos , Infecciones del Sistema Nervioso Central/diagnóstico , Valor Predictivo de las Pruebas , Secuenciación de Nucleótidos de Alto Rendimiento , ADN Ribosómico/genética , Metagenómica/métodosRESUMEN
Paramyxoviruses are a group of single-stranded, negative-sense RNA viruses, some of which are responsible for acute human disease, including parainfluenza virus, measles virus, Nipah virus and Hendra virus. In recent years, a large number of novel paramyxoviruses, particularly members of the genus Jeilongvirus, have been discovered in wild mammals, suggesting that the diversity of paramyxoviruses may be underestimated. Here we used hemi-nested reverse transcription PCR to obtain 190 paramyxovirus sequences from 969 small mammals in Hubei Province, Central China. These newly identified paramyxoviruses were classified into four clades: genera Jeilongvirus, Morbillivirus, Henipavirus and Narmovirus, with most of them belonging to the genus Jeilongvirus. Using Illumina sequencing and Sanger sequencing, we successfully recovered six near-full-length genomes with different genomic organizations, revealing the more complex genome content of paramyxoviruses. Co-divergence analysis of jeilongviruses and their known hosts indicates that host-switching occurred more frequently in the evolutionary histories of the genus Jeilongvirus. Together, our findings demonstrate the high prevalence of paramyxoviruses in small mammals, especially jeilongviruses, and highlight the diversity of paramyxoviruses and their genome content, as well as the evolution of jeilongviruses.
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Infecciones por Paramyxoviridae , Paramyxovirinae , Paramyxovirinae/genética , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/veterinaria , Mamíferos , China , Filogenia , Genoma Viral , Especificidad del HuéspedRESUMEN
Graft availability from donation after circulatory death (DCD) is significantly limited by ischaemia reperfusion (IR) injury. Effective strategies to mitigate IR injury in DCD grafts are essential to improve graft quality and expand the donor pool. In this study, liver grafts from DCD pigs were preserved in the University of Wisconsin (UW) solution saturated with 0.1 nM dexmedetomidine (Dex) and various concentrations of noble gases Argon (Ar) and/or Xenon (Xe) at 4 °C for 24 or 72 h. The combined 50% Ar and Dex provided maximum protection to liver grafts by reducing morphological damage, apoptosis, necroptosis, ferroptosis, hepatocyte glycogen depletion, reticulin framework collapse, iron deposition, and oxidative stress. In vitro, human liver Hep G2 cells were preserved in the UW solution saturated with 0.1 nM Dex and 50% Ar in combination at 4 °C for 24 h, followed by recovery in medium at 37 °C for up to 48 h to mimic clinical IR injury. This treatment significantly increased the expression of anti-oxidative stress proteins by promoting the translocation of thioredoxin-interacting protein (TXNIP) to mitochondria, thereby inhibiting ferroptosis, increasing plasma membrane integrity, and maintaining cell viability.In summary, The combination of 0.1 nM Dex and 50% Ar may be a promising strategy to reduce ferroptosis and other form cell death, and preserve liver grafts.
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OBJECTIVES: The respiratory tract is the portal of entry for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although a variety of respiratory pathogens other than SARS-CoV-2 have been associated with severe cases of COVID-19 disease, the dynamics of the upper respiratory microbiota during disease the course of disease, and how they impact disease manifestation, remain uncertain. METHODS: We collected 349 longitudinal upper respiratory samples from a cohort of 65 COVID-19 patients (cohort 1), 28 samples from 28 recovered COVID-19 patients (cohort 2), and 59 samples from 59 healthy controls (cohort 3). All COVID-19 patients originated from the earliest stage of the epidemic in Wuhan. Based on a modified clinical scale, the disease course was divided into five clinical disease phases (pseudotimes): "Healthy" (pseudotime 0), "Incremental" (pseudotime 1), "Critical" (pseudotime 2), "Complicated" (pseudotime 3), "Convalescent" (pseudotime 4), and "Long-term follow-up" (pseudotime 5). Using meta-transcriptomics, we investigated the features and dynamics of transcriptionally active microbes in the upper respiratory tract (URT) over the course of COVID-19 disease, as well as its association with disease progression and clinical outcomes. RESULTS: Our results revealed that the URT microbiome exhibits substantial heterogeneity during disease course. Two clusters of microbial communities characterized by low alpha diversity and enrichment for multiple pathogens or potential pathobionts (including Acinetobacter and Candida) were associated with disease progression and a worse clinical outcome. We also identified a series of microbial indicators that classified disease progression into more severe stages. Longitudinal analysis revealed that although the microbiome exhibited complex and changing patterns during COVID-19, a restoration of URT microbiomes from early dysbiosis toward more diverse status in later disease stages was observed in most patients. In addition, a group of potential pathobionts were strongly associated with the concentration of inflammatory indicators and mortality. CONCLUSION: This study revealed strong links between URT microbiome dynamics and disease progression and clinical outcomes in COVID-19, implying that the treatment of severe disease should consider the full spectrum of microbial pathogens present.
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COVID-19 , Microbiota , Humanos , SARS-CoV-2 , Nariz , Progresión de la EnfermedadRESUMEN
ABSTRACT Background: The rate of methicillin-resistant Staphylococcus aureus (MRSA) among the total of S. aureus isolates decreased to 35.3% in 2017 in China. It is unclear whether the molecular characteristics of S. aureus isolates have changed as the rate decreased. Objective: This study aimed to investigate the molecular characteristics and virulence genes profile of S. aureus isolates causing bloodstream infection and analyze the correlation between the prevalence rates of the common sequence types and MRSA. Methods: A total of 112 S. aureus strains from eight hospitals of four cities, including 32 MRSA isolates, were identified and evaluated through multilocus sequence typing, spa typing, and determination of virulence genes. Results: Twenty-five STs were identified, of which ST5 (21.4%) was the most prevalent, whereas the prevalence of ST239 correlated with the rate of MRSA among all S. aureus isolates. Forty-six spa types were identified, of which t2460 (14.3%) was the most common. clfa, hla, seb, fnbA and hlb were the prevailing virulence genes. 81.3% MRSA and 45.0% methicillin-sensitive S. aureus (MSSA) isolates harbored six or more tested virulence genes. ST5-t2460, seldom noted in bloodborne S. aureus isolates in China, was the most common clone. The prevalence of harboring six or more virulence genes in ST5-t2460 and ST188-t189 were 93.8% and 8.3%, respectively. Conclusion: ST5-t2460 was the most common clone in S. aureus causing bloodstream infection followed by ST188-t189, which had never been noted in China before. Moreover, ST5-t2460 harbored more virulence genes than ST188-t189, and the prevalence of ST239 clone decreased with the proportion of MRSA among all S. aureus isolates.