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1.
Nano Lett ; 24(17): 5324-5331, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38624236

RESUMEN

Phase transformation offers an alternative strategy for the synthesis of nanomaterials with unconventional phases, allowing us to further explore their unique properties and promising applications. Herein, we first observed the amorphization of Pt nanoparticles on the RuO2 surface by in situ scanning transmission electron microscopy. Density functional theory calculations demonstrate the low energy barrier and thermodynamic driving force for Pt atoms transferring from the Pt cluster to the RuO2 surface to form amorphous Pt. Remarkably, the as-synthesized amorphous Pt/RuO2 exhibits 14.2 times enhanced mass activity compared to commercial RuO2 catalysts for the oxygen evolution reaction (OER). Water electrolyzer with amorphous Pt/RuO2 achieves 1.0 A cm-2 at 1.70 V and remains stable at 200 mA cm-2 for over 80 h. The amorphous Pt layer not only optimized the *O binding but also enhanced the antioxidation ability of amorphous Pt/RuO2, thereby boosting the activity and stability for the OER.

2.
Plant Biotechnol J ; 22(5): 1269-1281, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38073308

RESUMEN

A fast evolution within mitochondria genome(s) often generates discords between nuclear and mitochondria, which is manifested as cytoplasmic male sterility (CMS) and fertility restoration (Rf) system. The maize CMS-C trait is regulated by the chimeric mitochondrial gene, atp6c, and can be recovered by the restorer gene ZmRf5. Through positional cloning in this study, we identified the nuclear restorer gene, ZmRf5, which encodes a P-type pentatricopeptide repeat (PPR) family protein. The over-expression of ZmRf5 brought back the fertility to CMS-C plants, whereas its genomic editing by CRISPR/Cas9 induced abortive pollens in the restorer line. ZmRF5 is sorted to mitochondria, and recruited RS31A, a splicing factor, through MORF8 to form a cleaving/restoring complex, which promoted the cleaving of the CMS-associated transcripts atp6c by shifting the major cleavage site from 480th nt to 344 th nt for fast degradation, and preserved just right amount of atp6c RNA for protein translation, providing adequate ATP6C to assembly complex V, thus restoring male fertility. Interestingly, ATP6C in the sterile line CMo17A, with similar cytology and physiology changes to YU87-1A, was accumulated much less than it in NMo17B, exhibiting a contrary trend in the YU87-1 nuclear genome previously reported, and was restored to normal level in the presence of ZmRF5. Collectively these findings unveil a new molecular mechanism underlying fertility restoration by which ZmRF5 cooperates with MORF8 and RS31A to restore CMS-C fertility in maize, complemented and perfected the sterility mechanism, and enrich the perspectives on communications between nucleus and mitochondria.


Asunto(s)
Fertilidad , Zea mays , Zea mays/genética , Factores de Empalme de ARN , Citoplasma/genética , Fertilidad/genética , Mitocondrias/genética , Infertilidad Vegetal/genética
3.
Hortic Res ; 10(11): uhad212, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38046852

RESUMEN

Heterophylly is regard as an important adaptive mechanism in response to different environments within plants. However, the genetic mechanisms responsible for heterophylly in woody plants are still poorly understood. Herein, the divergence of heterophyllous leaves was investigated at morphogenesis and using microdissection and physiological indexes in paper mulberry, and the genetic basis of heterophylly was further revealed combined with genome-wide association study (GWAS), transcriptome analysis and weighted gene coexpression network analysis (WGCNA). Our results revealed that the flavonoid content and antioxidant activity increased gradually from the entire leaf to the palmatisect leaf, while the hormone content and net photosynthetic rate decreased. Through GWAS and transcriptome analysis, a total of 98 candidate genes and 2338 differentially expressed genes associated with heterophylly were identified. Importantly, we uncovered critical variations in the candidate genes Bp07g0981 (WOX) and Bp07g0920 (HHO), along with significant differences in haplotypes and expression levels among heterophyllous leaves. Our results also suggested that the genes involved in hormone signaling pathways, antioxidant activity, and flavonoid metabolism might be closely related to the heterophylly of paper mulberry, which could account for the physiological data. Indeed, CR-wox mutant lines showed significant changes in leaf phenotypes, and differential expression profile analysis also highlighted the expression of genes related to phytohormones and transcription factors. Together, the genetic variations and candidate genes detected in this study provide novel insights into the genetic mechanism of heterophylly, and would improve the understanding of eco-adaptability in heterophyllous woody plants.

4.
Angew Chem Int Ed Engl ; 62(35): e202308800, 2023 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-37428114

RESUMEN

Water electrolysis for H2 production is restricted by the sluggish oxygen evolution reaction (OER). Using the thermodynamically more favorable hydrazine oxidation reaction (HzOR) to replace OER has attracted ever-growing attention. Herein, we report a twisted NiCoP nanowire array immobilized with Ru single atoms (Ru1 -NiCoP) as superior bifunctional electrocatalyst toward both HzOR and hydrogen evolution reaction (HER), realizing an ultralow working potential of -60 mV and overpotential of 32 mV for a current density of 10 mA cm-2 , respectively. Inspiringly, two-electrode electrolyzer based on overall hydrazine splitting (OHzS) demonstrates outstanding activity with a record-high current density of 522 mA cm-2 at cell voltage of 0.3 V. DFT calculations elucidate the cooperative Ni(Co)-Ru-P sites in Ru1 -NiCoP optimize H* adsorption, and enhance adsorption of *N2 H2 to significantly lower the energy barrier for hydrazine dehydrogenation. Moreover, a self-powered H2 production system utilizing OHzS device driven by direct hydrazine fuel cell (DHzFC) achieve a satisfactory rate of 24.0 mol h-1 m-2 .

5.
Biotechnol Lett ; 45(1): 13-31, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36357714

RESUMEN

Most of the currently available disease resistance (R) genes have NBS (nucleotide-binding site) and LRR (leucine-rich-repeat) domain which belongs to the NBS-LRR gene family. The whole genome sequencing of Broussonetia papyrifera provides an important bioinformatics database for the study of the NBS-LRR gene family. In this study, 328 NBS-LRR family genes were identified and classified in B. papyrifera according to different classification schemes, where there are 92 N types, 47 CN type, 54 CNL type, 29 NL types, 55 TN type, and 51 TNL type. Subsequently, we conducted bioinformatics analysis of the NBS-LRR gene family. Classification, motif analysis of protein sequences, and phylogenetic tree studies of the NBS-LRR genes in B. papyrifera provide important basis for the functional study of NBS-LRR family genes. Additionally, we performed structural analysis of the chromosomal location, physicochemical properties, and sequences identified by genetic characterization. In addition, through the analysis of GO enrichment, it was found that NBS-LRR genes were involved in defense responses and were significantly enriched in biological stimulation, immune response, and abiotic stress. In addition, we found that Bp06g0955 was the most sensitive to low temperature and encoded the RPM1 protein by analyzing the low temperature transcriptome data of B. papyrifera. Quantitative results of gene expression after 48 h of Fusarium infection showed that Bp01g3293 increased 14 times after infection, which encodes RPM1 protein. The potential of NBS-LRR gene responsive to biotic and abiotic stresses can be exploited to improve the resistance of B. papyrifera.


Asunto(s)
Broussonetia , Filogenia , Proteínas/genética , Sitios de Unión/genética , Biología Computacional
6.
Int J Mol Sci ; 23(20)2022 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-36293375

RESUMEN

Seeds directly determine the survival and population size of woody plants, but the genetic basis of seed weight in woody plants remain poorly explored. To identify genetic variations and candidate genes responsible for seed weight in natural woody populations, we investigated the hundred-seed weight of 198 paper mulberry individuals from different areas. Our results showed that the hundred-seed weight of paper mulberry was significantly associated with the bioclimatic variables of sampling sites, which increased from south to north along the latitudinal-temperature gradient. Using 2,414,978 high-quality SNPs from re-sequencing data, the genome-wide association analysis of the hundred-seed weight was performed under three models, which identified 148, 19 and 12 associated genes, respectively. Among them, 25 candidate genes were directly hit by the significant SNPs, including the WRKY transcription factor, fatty acid desaturase, F-box protein, etc. Most importantly, we identified three crucial genetic variations in the coding regions of candidate genes (Bp02g2123, Bp01g3291 and Bp10g1642), and significant differences in the hundred-seed weight were detected among the individuals carrying different genotypes. Further analysis revealed that Bp02g2123 encoding a fatty acid desaturase (FAD) might be a key factor affecting the seed weight and local climate adaptation of woody plants. Furthermore, the genome-wide investigation and expression analysis of FAD genes were performed, and the results suggested that BpFADs widely expressed in various tissues and responded to multiple phytohormone and stress treatments. Overall, our study identifies valuable genetic variations and candidate genes, and provides a better understanding of the genetic basis of seed weight in woody plants.


Asunto(s)
Proteínas F-Box , Morus , Humanos , Estudio de Asociación del Genoma Completo , Morus/genética , Reguladores del Crecimiento de las Plantas , Flavina-Adenina Dinucleótido/genética , Semillas/genética , Polimorfismo de Nucleótido Simple , Ácido Graso Desaturasas/genética , Proteínas F-Box/genética , Factores de Transcripción/genética
7.
BMC Public Health ; 22(1): 1411, 2022 07 25.
Artículo en Inglés | MEDLINE | ID: mdl-35879697

RESUMEN

BACKGROUND: As the fifth-largest global mortality risk factor, air pollution has caused nearly one-tenth of the world's deaths, with a death toll of 5 million. 21% of China's disease burden was related to environmental pollution, which is 8% higher than the US. Air pollution will increase the demand and utilisation of Chinese residents' health services, thereby placing a greater economic burden on the government. This study reveals the spatial impact of socioeconomic, health, policy and population factors combined with environmental factors on government health expenditure. METHODS: Spearman's correlation coefficient and GeoDetector were used to identify the determinants of government health expenditure. The GeoDetector consist of four detectors: factor detection, interaction detection, risk detection, and ecological detection. One hundred sixty-nine prefecture-level cities in China are studied. The data sources are the 2017 data from China's Economic and Social Big Data Research Platform and WorldPOP gridded population datasets. RESULTS: It is found that industrial sulfur dioxide attributed to government health expenditure, whose q value (explanatory power of X to Y) is 0.5283. The interaction between air pollution factors and other factors will increase the impact on government health expenditure, the interaction value (explanatory power of × 1âˆ©× 2 to Y) of GDP and industrial sulfur dioxide the largest, whose values is 0.9593. There are 96 simple high-risk areas in these 169 areas, but there are still high-risk areas affected by multiple factors. CONCLUSION: First, multiple factors influence the spatial heterogeneity of government health expenditure. Second, health and socio-economic factors are still the dominant factors leading to increased government health expenditure. Third, air pollution does have an important impact on government health expenditure. As a catalytic factor, combining with other factors, it will strengthen their impact on government health expenditure. Finally, an integrated approach should be adopted to synergisticly governance the high-risk areas with multi-risk factors.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , China/epidemiología , Ciudades , Gobierno , Gastos en Salud , Humanos , Material Particulado/análisis , Dióxido de Azufre
8.
Antibiotics (Basel) ; 11(3)2022 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-35326786

RESUMEN

Pseudomonas aeruginosa is a Gram-negative bacterium which is capable of developing a high level of antibiotic resistance. It has been placed on the WHO's critical priority pathogen list and it is commonly found in ventilator-associated pneumonia infections, blood stream infections and other largely hospital-acquired illnesses. These infections are difficult to effectively treat due to their increasing antibiotic resistance and as such patients are often treated with antibiotic combination regimens. METHODS: We conducted a systematic search with screening criteria using the Ovid search engine and the Embase, Ovid Medline, and APA PsycInfo databases. RESULTS: It was found that in many cases the combination therapies were able to match or outperform the monotherapies and none performed noticeably worse than the monotherapies. However, the clinical studies were mostly small, only a few were prospective randomized clinical trials and statistical significance was lacking. CONCLUSIONS: It was concluded that combination therapies have a place in the treatment of these highly resistant bacteria and, in some cases, there is some evidence to suggest that they provide a more effective treatment than monotherapies.

9.
Front Cell Infect Microbiol ; 12: 765445, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35155276

RESUMEN

Coxsackievirus A2 (CVA2) has recently been constantly detected, and is associated with viral myocarditis in children. Our previous study demonstrated that CVA2 led to heart damage in a neonatal murine model. However, the molecular mechanism of heart injury caused by CVA2 remains largely unknown. Emerging evidence suggests the significant functions of miRNAs in Coxsackievirus infection. To investigate potential miRNAs involved in heart injury caused by CVA2, our study, for the first time, conducted a RNA-seq in vivo employing infected mice hearts. In total, 87, 101 and 76 differentially expressed miRNAs were identified at 3 days post infection (dpi), 7 dpi and 7 dpi vs 3 dpi. Importantly, above 3 comparison strategies shared 34 differentially expressed miRNAs. These results were confirmed by quantitative PCR (qPCR). Next, we did GO, KEGG, and miRNA-mRNA integrated analysis of differential miRNAs. The dual-luciferase reporter assay confirmed the miRNA-mRNA pairs. To further confirm the above enriched pathways and processes, we did Western blotting and immunofluorescence staining. Our results suggest that inflammatory responses, T cell activation, apoptosis, autophagy, antiviral immunity, NK cell infiltration, and the disruption of tight junctions are involved in the pathogenesis of heart injury caused by CVA2. The dysregulated miRNAs and pathways recognized in the current study can improve the understanding of the intricate interactions between CVA2 and the heart injury, opening a novel avenue for the future study of CVA2 pathogenesis.


Asunto(s)
Infecciones por Coxsackievirus , Lesiones Cardíacas , MicroARNs , Animales , Apoptosis , Infecciones por Coxsackievirus/patología , Perfilación de la Expresión Génica , Ratones , MicroARNs/genética , MicroARNs/metabolismo , ARN Mensajero/genética
10.
J Antimicrob Chemother ; 76(9): 2302-2305, 2021 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-34120178

RESUMEN

OBJECTIVES: To investigate the efficacy of zidovudine in combination with carbapenems against NDM-1-producing Enterobacteriaceae. METHODS: MICs were determined using the broth microdilution method. The combinatory effects of zidovudine and carbapenems were examined using the chequerboard method and time-kill analysis. RESULTS: We found that the NDM-1-producing strains were resistant to all carbapenems tested. FIC index from chequerboard assay demonstrated that zidovudine synergized with carbapenems against all the NDM-1 strains. Time-kill analysis demonstrated significant synergistic activity when a low level of zidovudine was combined with meropenem. CONCLUSIONS: Zidovudine in combination with carbapenems produced synergistic activity against NDM-1 Enterobacteriaceae strains in vitro.


Asunto(s)
Carbapenémicos , Enterobacteriaceae , Antibacterianos/farmacología , Carbapenémicos/farmacología , Pruebas de Sensibilidad Microbiana , Zidovudina/farmacología , beta-Lactamasas
11.
Plant Mol Biol ; 105(6): 585-599, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33651261

RESUMEN

KEY MESSAGE: Total of 14 SNPs associated with overwintering-related traits and 75 selective regions were detected. Important candidate genes were identified and a possible network of cold-stress responses in woody plants was proposed. Local adaptation to low temperature is essential for woody plants to against changeable climate and safely survive the winter. To uncover the specific molecular mechanism of low temperature adaptation in woody plants, we sequenced 134 core individuals selected from 494 paper mulberry (Broussonetia papyrifera), which naturally distributed in different climate zones and latitudes. The population structure analysis, PCA analysis and neighbor-joining tree analysis indicated that the individuals were classified into three clusters, which showed forceful geographic distribution patterns because of the adaptation to local climate. Using two overwintering phenotypic data collected at high latitudes of 40°N and one bioclimatic variable, genome-phenotype and genome-environment associations, and genome-wide scans were performed. We detected 75 selective regions which possibly undergone temperature selection and identified 14 trait-associated SNPs that corresponded to 16 candidate genes (including LRR-RLK, PP2A, BCS1, etc.). Meanwhile, low temperature adaptation was also supported by other three trait-associated SNPs which exhibiting significant differences in overwintering traits between alleles within three geographic groups. To sum up, a possible network of cold signal perception and responses in woody plants were proposed, including important genes that have been confirmed in previous studies while others could be key potential candidates of woody plants. Overall, our results highlighted the specific and complex molecular mechanism of low temperature adaptation and overwintering of woody plants.


Asunto(s)
Adaptación Fisiológica/genética , Frío , Fenómenos Fisiológicos de las Plantas , Plantas/genética , Alelos , Secuencia de Bases , Clima , Estudio de Asociación del Genoma Completo , Morus/genética , Morus/fisiología , Fenotipo , Polimorfismo de Nucleótido Simple , Temperatura
12.
Int J Antimicrob Agents ; 57(4): 106309, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33609719

RESUMEN

Infections caused by carbapenem-resistant Enterobacterales are difficult to treat. Colistin is the last-resort drug for the treatment of these infections, however colistin resistance has emerged in animals and humans. This study investigated the in vitro efficacy of mefloquine in combination with colistin against 114 antibiotic-resistant Enterobacterales isolates including NDM-1, extended-spectrum ß-lactamase (ESBL) and mcr-1 containing strains from a broad range of origins. The effect of the mefloquine and colistin combination was examined in vitro by chequerboard method and time-kill analysis and in vivo in a murine peritoneal infection model. The fractional inhibitory concentration index (FICI) of the combination indicated that synergy was detected for all NDM-1 and mcr-1 containing strains, 87.5% of ESBL producing Escherichia coli and 97.9% of ESBL producing Klebsiella pneumoniae strains. Time-kill curves demonstrated significant synergistic activity with low concentrations of colistin that were boosted by mefloquine. The combination showed enhanced activity against infection with NDM-1- or mcr-1 containing Enterobacteriaceae in mice at 4 h and 6 h after treatment. These findings suggest that the combination of mefloquine and colistin has the potential for rejuvenating the activity of colistin against multidrug-resistant Enterobacterales.


Asunto(s)
Antibacterianos/farmacología , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Colistina/farmacología , Escherichia coli/efectos de los fármacos , Klebsiella pneumoniae/efectos de los fármacos , Mefloquina/farmacología , Animales , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Farmacorresistencia Bacteriana Múltiple/genética , Sinergismo Farmacológico , Quimioterapia Combinada , Escherichia coli/genética , Femenino , Klebsiella pneumoniae/genética , Ratones , Ratones Endogámicos ICR , Pruebas de Sensibilidad Microbiana , beta-Lactamasas/genética
13.
Angew Chem Int Ed Engl ; 60(12): 6533-6538, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33350566

RESUMEN

Developing highly stable and efficient catalysts toward the oxygen reduction reaction is important for the long-term operation in proton exchange membrane fuel cells. Reported herein is a facile synthesis of two-dimensional coplanar Pt-carbon nanomeshes (NMs) that are composed of highly distorted Pt networks (neck width of 2.05±0.72 nm) and carbon. X-ray absorption fine structure spectroscopy demonstrated the metallic state of Pt in the coplanar Pt/C NMs. Fuel cell tests verified the excellent activity of the coplanar Pt/C NM catalyst with the peak power density of 1.21 W cm-2 and current density of 0.360 A cm-2 at 0.80 V in the H2 /O2 cell. Moreover, the coplanar Pt/C NM electrocatalysts showed superior stability against aggregation, with NM structures preserved intact for a long-term operation of over 30 000 cycles for electrode measurement, and the working voltage loss was negligible after 120 h in the H2 /O2 single cell operation. Density-functional theory analysis indicates the increased vacancy formation energy of Pt atoms for coplanar Pt/C NMs, restraining the tendency of Pt dissolution and aggregation.

14.
Appl Environ Microbiol ; 86(18)2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32651209

RESUMEN

The genetic basis of plant local adaptation has been extensively studied, yet the interplay between local adaptation, plant genetic divergence, and the microbial community remains unclear. Our study used the restriction-site associated DNA sequencing (RAD-seq) approach to explore genetic divergence in Broussonetia papyrifera and used internal transcribed spacers (ITS) to characterize fungal community. RAD-seq results show that B. papyrifera individuals could be divided into three genotypes; this genotyping result was consistent with the classification of climate type at the sample site. Most of the 101 highly differentiated genes were related to stress resistance and the microbiome. Moreover, ß-diversity results indicated that genetic divergence had a significant effect on fungal community across all compartments (P < 0.01). At genus and operational taxonomic unit (OTU) level, Mortierella, Hannaella oryzae, OTU81578 (Mortierella), and OTU1665209 (H. oryzae) were found to be the major OTUs that contribute to differences in fungal community. The properties of cooccurrence networks vary greatly among three genotypes. The results of redundancy analysis (RDA) indicated that B. papyrifera-associated fungal community was significantly related to its local adaptability. Our findings suggest that genetic divergence of B. papyrifera is closely related to local adaptation, with significant effects on the associated fungal community, which in turn would enhance host local adaptability. This improves present understanding about the coevolution of microbial communities and the host plant.IMPORTANCE The coevolution of plants with the associated fungal community and its effect on plant adaptability are not clear, especially for native trees. This study focuses on the genetic basis of local adaptation in plants and the effect of genetic divergence of Broussonetia papyrifera on the associated fungal community. We identified genes related to the microbiome that are important for local adaptation of the host. Our results show that genetic divergence in B. papyrifera significantly affects the fungal community, which has a close connection with local adaptation. This helps us to understand the relationship between local adaptation, genetic divergence, and associated fungal communities. This study highlights the effect of plant genetic divergence on associated fungal community for native trees and establishes a close connection between this effect and local adaptability in the host. In addition, these observations lay a foundation for the research of coevolution of plants and their symbiotic microbiome through genome-wide association study (GWAS).


Asunto(s)
Broussonetia/genética , Broussonetia/microbiología , Hongos/aislamiento & purificación , Variación Genética , Micobioma , Adaptación Fisiológica , Simbiosis
15.
J Pharmacokinet Pharmacodyn ; 47(5): 421-430, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32488575

RESUMEN

Proper characterization of drug effects on Mycobacterium tuberculosis relies on the characterization of phenotypically resistant bacteria to correctly establish exposure-response relationships. The aim of this work was to evaluate the potential difference in phenotypic resistance in in vitro compared to murine in vivo models using CFU data alone or CFU together with most probable number (MPN) data following resuscitation with culture supernatant. Predictions of in vitro and in vivo phenotypic resistance i.e. persisters, using the Multistate Tuberculosis Pharmacometric (MTP) model framework was evaluated based on bacterial cultures grown with and without drug exposure using CFU alone or CFU plus MPN data. Phenotypic resistance and total bacterial number in in vitro natural growth observations, i.e. without drug, was well predicted by the MTP model using only CFU data. Capturing the murine in vivo total bacterial number and persisters during natural growth did however require re-estimation of model parameter using both the CFU and MPN observations implying that the ratio of persisters to total bacterial burden is different in vitro compared to murine in vivo. The evaluation of the in vitro rifampicin drug effect revealed that higher resolution in the persister drug effect was seen using CFU and MPN compared to CFU alone although drug effects on the other bacterial populations were well predicted using only CFU data. The ratio of persistent bacteria to total bacteria was predicted to be different between in vitro and murine in vivo. This difference could have implications for subsequent translational efforts in tuberculosis drug development.


Asunto(s)
Antituberculosos/farmacocinética , Modelos Biológicos , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis Pulmonar/tratamiento farmacológico , Animales , Antituberculosos/administración & dosificación , Recuento de Colonia Microbiana , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Farmacorresistencia Bacteriana , Humanos , Pulmón/microbiología , Pulmón/patología , Ratones , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/aislamiento & purificación , Rifampin/administración & dosificación , Rifampin/farmacocinética , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/patología
16.
Front Microbiol ; 11: 54, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32063896

RESUMEN

Antimicrobial susceptibility testing (AST) performed according to defined guidelines is important to identify resistance and to predict the clinical success or failure of specific antibiotic therapy. However, these guidelines do not cover all physiological conditions that can have a tremendous impact on in vivo resistance. In this study, we tested the susceptibility of thirteen mcr-1-positive Escherichia coli strains against colistin, one of the last resort antibiotics for treating multi-drug resistant pathogens, in media recommended for ASTs as well as - physiologically more relevant - in human serum and artificial urine (AU). Minimal inhibitory concentration (MIC) values in heat-inactivated human serum were similar to those in cation-adjusted Mueller-Hinton broth (CAMHB), but reduced in native serum for almost all strains that could grow in this media. In AU MIC values for mcr-1 positive E. coli were increased significantly up to 16-fold compared to that in CAMBH, which did not apply to the colistin-susceptible E. coli strains tested. Although different growth media could affect the MIC of colistin alone, their impact on the synergistic effect of the combination with the antiviral drug azidothymidine was minimal. The higher divalent cation concentration combined with acidic pH values is most likely responsible for the increased MIC values of the mcr-1 harboring E. coli strains tested against colistin in AU compared to that in CAMHB. Antimicrobial susceptibility screening procedures for colistin using CAMHB only could lead to an underestimation of resistance under different physiological conditions. Therefore, not only pharmacokinetic but also pharmacodynamic studies in urine are as important as in serum or plasma.

17.
Clin Pharmacol Ther ; 108(2): 274-286, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32080839

RESUMEN

The development of optimal treatment regimens in tuberculosis (TB) remains challenging due to the need of combination therapy and possibility of pharmacodynamic (PD) interactions. Preclinical information about PD interactions needs to be used more optimally when designing early bactericidal activity (EBA) studies. In this work, we developed a translational approach which can allow for forward translation to predict efficacy of drug combination in EBA studies using the Multistate Tuberculosis Pharmacometric (MTP) and the General Pharmacodynamic Interaction (GPDI) models informed by in vitro static time-kill data. These models were linked with translational factors to account for differences between the in vitro system and humans. Our translational MTP-GPDI model approach was able to predict the EBA0-2 days , EBA0-5 days , and EBA0-14 days from different EBA studies of rifampicin and isoniazid in monotherapy and combination. Our translational model approach can contribute to an optimal dose selection of drug combinations in early TB clinical trials.


Asunto(s)
Antibióticos Antituberculosos/administración & dosificación , Antituberculosos/administración & dosificación , Desarrollo de Medicamentos , Isoniazida/administración & dosificación , Mycobacterium tuberculosis/efectos de los fármacos , Rifampin/administración & dosificación , Investigación Biomédica Traslacional , Tuberculosis/tratamiento farmacológico , Antibióticos Antituberculosos/farmacocinética , Antituberculosos/farmacocinética , Carga Bacteriana , Ensayos Clínicos Fase II como Asunto , Cálculo de Dosificación de Drogas , Quimioterapia Combinada , Humanos , Isoniazida/farmacocinética , Pruebas de Sensibilidad Microbiana , Modelos Biológicos , Mycobacterium tuberculosis/crecimiento & desarrollo , Rifampin/farmacocinética , Tuberculosis/microbiología
18.
Appl Microbiol Biotechnol ; 104(8): 3627-3641, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32078018

RESUMEN

Plants associate with numerous microbes, but little is known about how microbiome components, especially fungi, adapt to specific plant compartments. The adaptability of microbial function to the plant compartment is also not clear especially for woody species. Here, we characterized the bacterial and fungal communities in root endosphere, stems, and rhizospheres of 33 Broussonetia papyrifera seedlings, based on amplification of 16S and ITS rRNA. Results showed that the α-diversity indexes of the bacterial community were significantly different in different plant compartments and they significantly increased from stem to root endosphere to the rhizosphere, whereas those of the fungal community were similar (p > 0.05). However, the result of constrained PCoA (CPCoA) and analysis of similarity (ANOSIM) showed that both bacterial and fungal compositions were significantly affected by plant compartments (p < 0.01). In detail, the operational taxonomic units (OTUs) distribution of the bacterial community was significantly different, but 249 of 252 fungal OTUs were shared in different plant compartments. Both the bacterial and fungal compositions were significantly influenced by plant compartments, based on the result on phyla, core OTUs, and indicator OTUs level. Further, 40 of 42 enriched KEGG pathways involving the bacteria also differed significantly among plant compartments (p < 0.01). This study provides an understanding of the influence of plant compartments on the microbiome and confirms that the disperse limitation of fungal OTUs across different plant compartments is smaller. This study sheds light on how the microbial community adapts to and thrives in different plant compartments.


Asunto(s)
Broussonetia/anatomía & histología , Broussonetia/microbiología , Microbiota , Rizosfera , Bacterias/clasificación , Bacterias/metabolismo , Hongos/clasificación , Hongos/fisiología , Raíces de Plantas/microbiología , Tallos de la Planta/microbiología
19.
Chemistry ; 26(18): 4019-4024, 2020 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-31571290

RESUMEN

Engineering noble metal nanostructures at the atomic level can significantly optimize their electrocatalytic performance and remarkably reduce their usage. We report the synthesis of atomically dispersed Pt on screw-like Pd/Au nanowires by using ultrafine Pd nanowires as seeds. Au can selectively grow on the surface of Pd nanowires by an island growth pattern to fabricate surface defect sites to load atomically dispersed Pt, which can be confirmed by X-ray absorption fine structure measurements and aberration corrected HRTEM images. The nanowires with 2.74 at % Pt exhibit superior HER properties in acidic solution with an overpotential of 20.6 mV at 10 mA cm-2 and enhanced alkaline ORR performance with a mass activity over 15 times greater than the commercial platinum/carbon (Pt/C) catalysts.

20.
Expert Rev Anti Infect Ther ; 18(1): 5-15, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31847614

RESUMEN

Introduction: Anti-Microbial Resistance (AMR) is a pandemic which threatens modern medicine. There is a lack of effective drug treatment due to the slow pace, high cost and low achievable sales prices of new antibiotic monotherapies. New hope comes in the shape of antibiotic combination therapy, which although used by mother nature, is under-explored and could provide the solution to AMR.Areas covered: We performed a search of Pubmed and Medline using the keywords 'combination therapy', 'antimicrobial resistance' for articles between 1930 and 2019, as supplemented with other relevant references to our knowledge. We have reviewed the theoretical considerations for combination development and examine the existing and future clinical indications of combination therapies. We have discussed the potential of antibiotic combinations to provide therapeutic synergy, rejuvenating the effectiveness of old antibiotics to which the bacteria had developed resistance previously. We have examined the current thinking and evidence on resistance reduction using combination therapies, with a review on toxicity and drug-drug antagonism.Expert opinion: Antibiotic combination therapy, exploiting synergies, old-drug rejuvenation and resistance reduction could provide the solution to AMR. The number of pharmaceutical companies in this area is likely to expand, bringing promising combinations to the bedside, to save millions of lives worldwide.


Asunto(s)
Antibacterianos/administración & dosificación , Infecciones Bacterianas/tratamiento farmacológico , Farmacorresistencia Bacteriana , Antibacterianos/efectos adversos , Antibacterianos/farmacología , Infecciones Bacterianas/microbiología , Antagonismo de Drogas , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos
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