4,5-Bis(4-meth­oxy­phen­oxy)phthalonitrile

The title compound, C22H16N2O4, was obtained unintentionally as the product of an attempted synthesis of a new phthalocyanine. The dihedral angles formed by the central benzene ring with the aromatic rings of the meth­oxy­phen­oxy groups are 85.39 (5) and 64.19 (5)°

Ketogenic Diet as a Treatment for Super-Refractory Status Epilepticus in Febrile Infection-Related Epilepsy Syndrome

Background: Febrile infection-related epilepsy syndrome (FIRES) is a fatal epileptic encephalopathy associated with super-refractory status epilepticus (SRSE). Several treatment strategies have been proposed for this condition although the clinical outcomes are poor. Huge efforts from neurointensivists have been focused on identifying the characteristics of FIRES and treatment to reduce the mortality associated with this condition. However, the role of ketogenic diet (KD) in FIRES is not fully understood.Methods: We performed a retrospective review of patients who met the diagnostic criteria of FIRES, SRSE, and were treated with KD between 2015 and 2018 at the Department of Pediatrics, Xiangya Hospital of Central South University. The following data were recorded: demographic features, clinical presentation, anticonvulsant treatment, timing and duration of KD and follow-up information. Electroencephalography recordings were reviewed and analyzed.Results: Seven patients with FIRES were put on KD (5 via enteral route, and 2 via intravenous line) for SRSE in the PICU. The median age was 8. Four patients were male and 3 were female. Although patients underwent treatment with a median of 4 antiepileptic drugs and 2 anesthetic agents, the status epilepticus (SE) persisted for 7–31 days before KD initiation. After KD initiation, all patients achieved ketosis and SE disappeared within an average of 5 days (IQR 3.5), although there were minor side effects. In 6 patients, a unique pattern was identified in the EEG recording at the peak period. After initiation of KD, the number of seizures reduced, the duration of seizure shortened, the background recovered and sleep architecture normalized in the EEG recordings. The early initiation of KD (at the onset of SE) in the acute phase of patients decreased the mRS score in the subsequent period (p = 0.012, r = 0.866).Conclusions: The characteristic EEG pattern in the acute phase promoted timely diagnosis of FIRES. Our data suggest that KD may be a safe and promising therapy for FIRES with SRSE, and that early initiation of KD produces a favorable prognosis. Therefore, KD should be applied earlier in the course of FIRES. Intravenous KD can be an effective alternative route of administration for patients who may not take KD enterally

A recombinant avian antibody against VP2 of infectious bursal disease virus protects chicken from viral infection

【Abstract】A stable cell-line was established that expressed the recombinant avian antibody (rAb) against the infectious bursal disease virus (IBDV). rAb exhibited neutralization activity to IBDV-B87 strain in DF1 cells. The minimum rAb concentration required for inhibition of the cytopathic effect (CPE) was 1.563 μg/mL. To test the efficacy of rAb, a 168-h cohabitation challenge experiment was performed to transmit the disease from the chickens challenged with vvIBDV (HLJ0504 strain) to three test groups of chickens, i.e. (1) chickens treated with rAb, (2) chickens treated with yolk antibody, and (3) non-treatment chickens. The survival rates of chickens treated with rAb, yolk antibody and without treatment were 73%, 67% and 20%, respectively. Another batch of chickens was challenged with IBDV (BC6/85 strain) and then injected with rAb (1.0 mg/kg) 6, 24 and 36 h post-challenge. Non-treatment chickens had 100% morbidity, whereas those administered with rAb exhibited only 20% morbidity. Morbidity was evaluated using clinical indicators and bursal histopathological section. This study provides a new approach to treating IBDV and the rAb represents a promising candidate for this IBDV therapy.This research was supported by Heilongjiang province project of applied technology research and development (2013GC13C105) and The National Natural Science Fund biologic science base improve program of research training and capacity (J1210069/J0124)

Selection for antimicrobial resistance is reduced when embedded in a natural microbial community

This is the final version. Available from Springer Nature via the DOI in this record.Antibiotic resistance has emerged as one of the most pressing, global threats to public health. In single-species experiments selection for antibiotic resistance occurs at very low antibiotic concentrations. However, it is unclear how far these findings can be extrapolated to natural environments, where species are embedded within complex communities. We competed isogenic strains of Escherichia coli, differing exclusively in a single chromosomal resistance determinant, in the presence and absence of a pig faecal microbial community across a gradient of antibiotic concentration for two relevant antibiotics: gentamicin and kanamycin. We show that the minimal selective concentration was increased by more than one order of magnitude for both antibiotics when embedded in the community. We identified two general mechanisms were responsible for the increase in minimal selective concentration: an increase in the cost of resistance and a protective effect of the community for the susceptible phenotype. These findings have implications for our understanding of the evolution and selection of antibiotic resistance, and can inform future risk assessment efforts on antibiotic concentrations.Medical Research Council (MRC)European Commissio

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Tracking antibiotic resistance gene pollution from different sources using machine-learning classification

Abstract Background Antimicrobial resistance (AMR) has been a worldwide public health concern. Current widespread AMR pollution has posed a big challenge in accurately disentangling source-sink relationship, which has been further confounded by point and non-point sources, as well as endogenous and exogenous cross-reactivity under complicated environmental conditions. Because of insufficient capability in identifying source-sink relationship within a quantitative framework, traditional antibiotic resistance gene (ARG) signatures-based source-tracking methods would hardly be a practical solution. Results By combining broad-spectrum ARG profiling with machine-learning classification SourceTracker, here we present a novel way to address the question in the era of high-throughput sequencing. Its potential in extensive application was firstly validated by 656 global-scale samples covering diverse environmental types (e.g., human/animal gut, wastewater, soil, ocean) and broad geographical regions (e.g., China, USA, Europe, Peru). Its potential and limitations in source prediction as well as effect of parameter adjustment were then rigorously evaluated by artificial configurations with representative source proportions. When applying SourceTracker in region-specific analysis, excellent performance was achieved by ARG profiles in two sample types with obvious different source compositions, i.e., influent and effluent of wastewater treatment plant. Two environmental metagenomic datasets of anthropogenic interference gradient further supported its potential in practical application. To complement general-profile-based source tracking in distinguishing continuous gradient pollution, a few generalist and specialist indicator ARGs across ecotypes were identified in this study. Conclusion We demonstrated for the first time that the developed source-tracking platform when coupling with proper experiment design and efficient metagenomic analysis tools will have significant implications for assessing AMR pollution. Following predicted source contribution status, risk ranking of different sources in ARG dissemination will be possible, thereby paving the way for establishing priority in mitigating ARG spread and designing effective control strategies

Polycyclic aromatic hydrocarbon (PAH) biodegradation capacity revealed by a genome-function relationship approach

Abstract Background Polycyclic aromatic hydrocarbon (PAH) contamination has been a worldwide environmental issue because of its impact on ecosystems and human health. Biodegradation plays an important role in PAH removal in natural environments. To date, many PAH-degrading strains and degradation genes have been reported. However, a comprehensive PAH-degrading gene database is still lacking, hindering a deep understanding of PAH degraders in the era of big data. Furthermore, the relationships between the PAH-catabolic genotype and phenotype remain unclear. Results Here, we established a bacterial PAH-degrading gene database and explored PAH biodegradation capability via a genome-function relationship approach. The investigation of functional genes in the experimentally verified PAH degraders indicated that genes encoding hydratase-aldolase could serve as a biomarker for preliminarily identifying potential degraders. Additionally, a genome-centric interpretation of PAH-degrading genes was performed in the public genome database, demonstrating that they were ubiquitous in Proteobacteria and Actinobacteria. Meanwhile, the global phylogenetic distribution was generally consistent with the culture-based evidence. Notably, a few strains affiliated with the genera without any previously known PAH degraders (Hyphomonas, Hoeflea, Henriciella, Saccharomonospora, Sciscionella, Tepidiphilus, and Xenophilus) also bore a complete PAH-catabolic gene cluster, implying their potential of PAH biodegradation. Moreover, a random forest analysis was applied to predict the PAH-degrading trait in the complete genome database, revealing 28 newly predicted PAH degraders, of which nine strains encoded a complete PAH-catabolic pathway. Conclusions Our results established a comprehensive PAH-degrading gene database and a genome-function relationship approach, which revealed several potential novel PAH-degrader lineages. Importantly, this genome-centric and function-oriented approach can overcome the bottleneck of conventional cultivation-based biodegradation research and substantially expand our current knowledge on the potential degraders of environmental pollutants

A novel chloroplastic isopentenyl diphosphate isomerase gene from Jatropha curcas: Cloning, characterization and subcellular localization

Background: Jatropha curcas is a rich reservoir of pharmaceutically active terpenoids. More than 25 terpenoids have been isolated from this plant, and their activities are anti-bacterial, anti-fungal, anti-cancer, insecticidal, rodenticidal, cytotoxic and molluscicidal. But not much is known about the pathway involved in the biosynthesis of terpenoids. The present investigation describes the cloning, characterization and subcellular localization of isopentenyl diphosphate isomerase (IPI) gene from J. curcas. IPI is one of the rate limiting enzymes in the biosynthesis of terpenoids, catalyzing the crucial interconversion of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Results: A full-length JcIPI cDNA consisting of 1355 bp was cloned. It encoded a protein of 305 amino acids. Analysis of deduced amino acid sequence predicted the presence of conserved active sites, metal binding sites and the NUDIX motif, which were consistent with other IPIs. Phylogenetic analysis indicated a significant evolutionary relatedness with Ricinus communis. Southern blot analysis showed the presence of an IPI multigene family in J. curcas. Comparative expression analysis of tissue specific JcIPI demonstrated the highest transcript level in flowers. Abiotic factors could induce the expression of JcIPI. Subcellular distribution showed that JcIPI was localized in chloroplasts. Conclusion: This is the first report of cloning and characterization of IPI from J. curcas. Our study will be of significant interest to understanding the regulatory role of IPI in the biosynthesis of terpenoids, although its function still needs further confirmation

Coupling Effects of pH and Dissolved Oxygen on the Corrosion Behavior and Mechanism of X80 Steel in Acidic Soil Simulated Solution

In an acidic red soil environment, the corrosion mechanism of X80 steel may be closely related to the pH value and oxygen content, but it has not yet formed a systematic understanding. In this paper, the coupling effects of pH and dissolved oxygen on the corrosion behavior and mechanism of X80 steel in an acidic soil simulated solution were further analyzed by electrochemical methods and three-dimensional video microscope. Results showed that the hydrogen reduction reaction was almost the only cathode process in the anoxic and low pH system, and small and dense pits were present on the electrode surface. pH value increased, the pits decreased, but the size of pits increased. In the oxygen-adequate system, oxygen-consuming (OC) corrosion preferentially occurred, and a protective corrosion product layer (including FeOOH, Fe3O4, etc.) might be formed accordingly, but the proportion of hydrogen evolution (HE) increased and the product layer had defects at a low pH environment. The specific corrosion mechanism of X80 steel in an acidic soil simulated solution is described in the relevant models