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This study presents a novel approach to enhance the catalytic activity of composite materials by promoting active surface exposure and improving hydrogen transfer performance. Through a self-assembly route involving tailored gas-solid and galvanic replacement reactions, Pt-WC/CNT catalysts with superhydrophilicity and coronavirus-like structure are synthesized. These unique structural features contribute to a remarkable enhancement in the electrocatalytic performance of the hydrogen evolution reaction (HER). Notably, the Pt-WC/CNT catalyst exhibits an outstanding intrinsic activity and efficient bubble transfer properties, leading to a high turnover frequency of 34.97 H2·s-1 at an overpotential of 100 mV. This value is 4.8 times higher than that achieved by commercial Pt/C catalysts (7.30 H2·s-1), establishing Pt-WC/CNT as one of the most active catalysts reported to date. Moreover, the combination of gas-solid and galvanic replacement reactions in the synthesis process offers a scalable route for the production of Pt-loading controllable composite catalysts, thus challenging the dominance of commercial Pt/C catalysts.
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Photocatalytic lignocellulose reforming for H2 production presents a compelling solution to solve environmental and energy issues. However, achieving scalable conversion under benign conditions faces consistent challenges including insufficient active sites for H2 evolution reaction (HER) and inefficient lignocellulose oxidation directly by photogenerated holes. Herein, it is found that Pt single atom-loaded CdS nanosheet (PtSA-CdS) would be an active photocatalyst for lignocellulose-to-H2 conversion. Theoretical and experimental analyses confirm that the valence band of CdS shifts downward after depositing isolated Pt atoms, and the slope of valence band potential on pH for PtSA-CdS is more positive than Nernstian equation. These characteristics allow PtSA-CdS to generate large amounts of â¢OH radicals even at pH 14, while the capacity is lacking with CdS alone. The employment of â¢OH/OH- redox shuttle succeeds in relaying photoexcited holes from the surface of photocatalyst, and the â¢OH radicals can diffuse away to decompose lignocellulose efficiently. Simultaneously, surface Pt atoms, featured with a thermoneutral Δ G H ∗ $\Delta G_{\mathrm{H}}^{\mathrm{*}}$ , would collect electrons to expedite HER. Consequently, PtSA-CdS performs a H2 evolution rate of 10.14 µmol h-1 in 1 m KOH aqueous solution, showcasing a remarkable 37.1-fold enhancement compared to CdS. This work provides a feasible approach to transform waste biomass into valuable sources.
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Dietary fiber metabolism by gut microorganisms plays important roles in host physiology and health. Alginate, the major dietary fiber of daily diet seaweeds, is drawing more attention because of multiple biological activities. To advance the understanding of alginate assimilation mechanism in the gut, we show the presence of unsaturated alginate oligosaccharides (uAOS)-specific alginate utilization loci (AUL) in human gut microbiome. As a representative example, a working model of the AUL from the gut microorganism Bacteroides clarus was reconstructed from biochemistry and transcriptome data. The fermentation of resulting monosaccharides through Entner-Doudoroff pathway tunes the metabolism of short-chain fatty acids and amino acids. Furthermore, we show that uAOS feeding protects the mice against dextran sulfate sodium-induced acute colitis probably by remodeling gut microbiota and metabolome. IMPORTANCE: Alginate has been included in traditional Chinese medicine and daily diet for centuries. Recently discovered biological activities suggested that alginate-derived alginate oligosaccharides (AOS) might be an active ingredient in traditional Chinese medicine, but how these AOS are metabolized in the gut and how it affects health need more information. The study on the working mechanism of alginate utilization loci (AUL) by the gut microorganism uncovers the role of unsaturated alginate oligosaccharides (uAOS) assimilation in tuning short-chain fatty acids and amino acids metabolism and demonstrates that uAOS metabolism by gut microorganisms results in a variation of cell metabolites, which potentially contributes to the physiology and health of gut.
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Alginatos , Microbioma Gastrointestinal , Oligossacarídeos , Alginatos/metabolismo , Oligossacarídeos/metabolismo , Camundongos , Animais , Humanos , Colite/microbiologia , Colite/induzido quimicamente , Camundongos Endogâmicos C57BL , Ácidos Graxos Voláteis/metabolismo , Inflamação/metabolismo , Sulfato de Dextrana , Fibras na Dieta/metabolismoRESUMO
BACKGROUND: Vibrio parahaemolyticus is the predominant etiological agent of seafood-associated foodborne illnesses on a global scale. It is essential to elucidate the mechanisms by which this pathogen disseminates. Given the existing research predominantly concentrates on localized outbreaks, there is a pressing necessity for a comprehensive investigation to capture strains of V. parahaemolyticus cross borders. RESULTS: This study examined the frequency and genetic attributes of imported V. parahaemolyticus strains among travelers entering Shanghai Port, China, between 2017 and 2019.Through the collection of 21 strains from diverse countries and regions, Southeast Asia was pinpointed as a significant source for the emergence of V. parahaemolyticus. Phylogenetic analysis revealed clear delineation between strains originating from human and environmental sources, emphasizing that underlying genome data of foodborne pathogens is essential for environmental monitoring, food safety and early diagnosis of diseases. Furthermore, our study identified the presence of virulence genes (tdh and tlh) and approximately 120 antibiotic resistance-related genes in the majority of isolates, highlighting their crucial involvement in the pathogenesis of V. parahaemolyticus. CONCLUSIONS: This research enhanced our comprehension of the worldwide transmission of V. parahaemolyticus and its antimicrobial resistance patterns. The findings have important implications for public health interventions and antimicrobial stewardship strategies, underscoring the necessity for epidemiological surveillance of pathogen at international travel hubs.
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Doenças Transmitidas por Alimentos , Filogenia , Vibrioses , Vibrio parahaemolyticus , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/isolamento & purificação , Vibrio parahaemolyticus/classificação , Vibrio parahaemolyticus/patogenicidade , Vibrio parahaemolyticus/efeitos dos fármacos , Humanos , China/epidemiologia , Vibrioses/microbiologia , Vibrioses/epidemiologia , Doenças Transmitidas por Alimentos/microbiologia , Doenças Transmitidas por Alimentos/epidemiologia , Genoma Bacteriano/genética , Viagem , Fatores de Virulência/genética , Genômica , Farmacorresistência Bacteriana/genética , Antibacterianos/farmacologia , Alimentos Marinhos/microbiologiaRESUMO
Eukaryotic genomes are generally organized in multiple chromosomes. Here we have created a functional single-chromosome yeast from a Saccharomyces cerevisiae haploid cell containing sixteen linear chromosomes, by successive end-to-end chromosome fusions and centromere deletions. The fusion of sixteen native linear chromosomes into a single chromosome results in marked changes to the global three-dimensional structure of the chromosome due to the loss of all centromere-associated inter-chromosomal interactions, most telomere-associated inter-chromosomal interactions and 67.4% of intra-chromosomal interactions. However, the single-chromosome and wild-type yeast cells have nearly identical transcriptome and similar phenome profiles. The giant single chromosome can support cell life, although this strain shows reduced growth across environments, competitiveness, gamete production and viability. This synthetic biology study demonstrates an approach to exploration of eukaryote evolution with respect to chromosome structure and function.
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Cromossomos Artificiais de Levedura/genética , Engenharia Genética/métodos , Aptidão Genética/genética , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/genética , Biologia Sintética/métodos , Fusão Gênica Artificial/métodos , Centrômero/genética , Evolução Molecular , Meiose , Viabilidade Microbiana/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Esporos Fúngicos/genética , Telômero/genética , TranscriptomaRESUMO
Prenatal exposure to per- and polyfluoroalkyl substances (PFASs) has been reported to be linked to a series of adverse health outcomes in mothers and their children. As the gut microbiota is a sensitive biomarker for assessing the toxicity of environmental contaminants, this study attempted to investigate whether prenatal PFASs exposure was associated with the gut microbiota of infants. Based on the Shanghai-Minhang Birth Cohort Study, this prospective cohort study included 69 mother-infant pairs. Fasting blood samples were collected from pregnant women for the PFASs assay. We collected fecal samples of infants at 1 year of age and analyzed the V3-V4 hypervariable region of the bacterial 16 S rRNA gene by high-throughput sequencing. Among the detected 11 PFASs, the concentration of perfluorooctanoic acid (22.19 ng/mL) was the highest, followed by perfluorooctane sulfonic acid (12.08 ng/mL). Compared with infants whose mothers' total PFASs concentrations during pregnancy were at the 40th percentile or lower (reference group), the species richness and diversity of microbiota were lower in infants prenatally exposed to a high level of PFASs (the sum of PFASs concentrations above the 60th percentile). Prenatal exposure to PFASs was associated with a higher proportion of Acidaminococcaceae, Acidaminococcus, Megamonas, Megasphaera micronuciformis and Megamonas funiformis in infants. The changes of the species have been suggested to be associated with immune and metabolic dysfunction in humans. Functional alterations of gut microbiota due to PFASs exposure were dominated by an enrichment of butanoate metabolism. Our preliminary findings may shed light on the potential role of the microbiota underlying the well-known impact of prenatal PFASs exposure on health outcomes of humans in later life.
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Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Microbioma Gastrointestinal , Efeitos Tardios da Exposição Pré-Natal , Feminino , Humanos , Lactente , Gravidez , Ácidos Alcanossulfônicos/toxicidade , China , Estudos de Coortes , Fluorocarbonos/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Estudos Prospectivos , VitaminasRESUMO
BACKGROUND: Adding ZaoShao liquor (high-concentration liquor) is one of the most important steps in the brewing process of Shaoxing Jiafan wine, a product protected by Chinese geographical indications. The focus of this study is the effect of different additive amounts of liquor on the flavor of end products. RESULTS: In this study, four kinds of Shaoxing Jiafan wine were brewed by changing the amount of ZaoShao liquor. Headspace solid-phase microextraction and gas chromatography-mass spectrometry were used to detect the flavor substances of four kinds of Jiafan wine. The difference in flavor of four kinds of Jiafan wine was evaluated by electronic nose analysis technology and verified by sensory evaluation. Finally, the reliability of the experimental results was verified through an aroma reconstruction experiment of rice wine. In this study, the differences in flavoring substances under different amounts of ZaoShao liquor were verified from various angles. The results showed that the flavors of the four kinds of wines were significantly different. CONCLUSION: The composition of flavor substances in Shaoxing rice wine varies with the amount of ZaoShao liquor. This study provided a scientific basis for the improvement of production technology of Shaoxing wine. © 2024 Society of Chemical Industry.
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Aromatizantes , Cromatografia Gasosa-Espectrometria de Massas , Odorantes , Paladar , Compostos Orgânicos Voláteis , Vinho , Vinho/análise , Aromatizantes/química , Aromatizantes/análise , Humanos , Odorantes/análise , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/química , Nariz Eletrônico , Microextração em Fase Sólida/métodos , Oryza/química , Vitis/química , Masculino , Adulto , Feminino , ChinaRESUMO
Three CoFe-bimetallic oxides with different compositions (termed as CoFeOx -A/N/H) are prepared by thermally treating metal-organic-framework (MOF) precursors under different atmospheres (air, N2, and NaBH4 /N2 ), respectively. With the aid of vast oxygen vacancies (Ov ), cobalt at tetrahedral sites (Co2+ (Th)) in spinel Co3 O4 is diffused into interstitial octahedral sites (Oh) to form rocksalt CoO and ternary oxide CoFe2 O4 has been induced to give the unique defective CoO/CoFe2 O4 heterostructure. The resultant CoFeOx -H exhibits superb electrocatalytic activity toward water oxidation: overpotential at 10 mA cm-2 is 192 mV, which is 122 mV smaller than that of CoFeOx -A. The smaller Tafel slope (42.53 mV dec-1 ) and higher turnover frequency (785.5 h-1 ) suggest fast reaction kinetics. X-ray absorption spectroscopy, ex situ characterizations, and theoretical calculations reveal that defect engineering effectively tunes the electronic configuration to a more active state, resulting in the greatly decreased binding energy of oxo intermediates, and consequently much lower catalytic overpotential. Moreover, the construction of hetero-interface in CoFeOx -H can provide rich active sites and promote efficient electron transfer. This work may shed light on a comprehensive understanding of the modulation of electron configuration of bimetallic oxides and inspire the smart design of high-performance electrocatalysts.
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The ongoing coronavirus disease 2019 (COVID-19) pandemic, driven by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights the critical role of genomic surveillance in tracking rapidly spreading viruses and their evolving lineages. The emergence of the SARS-CoV-2 tiling array, a comprehensive tool capable of capturing the entire viral genome, has presented a promising avenue for variants. This study introduces the SARS-CoV-2 tiling array as a novel method for port inspection. Using next-generation sequencing as a benchmark, 35 positive samples underwent sequencing through both methodologies, including the Alpha variant (B.1.1.7), Delta variants (AY.120, AY.122, AY.23.1), and Omicron variants (BA.1, BA.2, BA.2.75, BA.4, BA.5, BE.1, BF.7, BN.1, BQ.1, XBB.1) within the sample set. The whole-genome tiling array demonstrated successful identification of various sublineages of SARS-CoV-2. The average sequencing coverage rates were 99.22% (96.82%-99.92%) for the whole-genome tiling array and 98.56% (92.81%-99.59%) for Illumina sequencing, respectively. The match rates of these two methods ranged from 92.81%-99.59%, with an average rate of 98.56%. Among the benefits of the whole-genome tiling array are its cost-effectiveness and equipment simplification, making it particularly suitable for identifying SARS-CoV-2 variants in the front-line inspection department. The aforementioned findings provide valuable insights into the surveillance of COVID-19 and present a pragmatic solution for improving quarantine measures at entry points.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , COVID-19/epidemiologia , China/epidemiologia , Genoma ViralRESUMO
OBJECTIVE AND DESIGN: An accumulating body of evidence has shown that gut microbiota is involved in regulating inflammation; however, it remains undetermined if and how gut microbiota plays an important role in modulating deep venous thrombosis (DVT), which is an inflammation-involved thrombotic event. SUBJECTS: Mice under different treatments were used in this study. METHODS AND TREATMENT: We induced stenosis DVT in mice by partially ligating the inferior vena cava. Mice were treated with antibiotics, prebiotics, probiotics, or inflammatory reagents to modulate inflammatory states, and their effects on the levels of circulating LPS and DVT were examined. RESULTS: Antibiotic-treated mice or germ-free mice exhibited compromised DVT. Treatment of mice with either prebiotics or probiotics effectively suppressed DVT, which was accompanied with the downregulation of circulating LPS. Restoration of circulating LPS in these mice with a low dose of LPS was able to restore DVT. LPS-induced DVT was blocked by a TLR4 antagonist. By performing proteomic analysis, we identified TSP1 as one of the downstream effectors of circulating LPS in DVT. CONCLUSION: These results suggest that gut microbiota may play a nonnegligible role in modulating DVT by leveraging the levels of LPS in circulation, thus shedding light on the development of gut microbiota-based strategies for preventing and treating DVT.
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BACKGROUND: Although the characteristics of the gut microbiota of children with autism spectrum disorder (ASD) have been well studied, those of young adults with ASD have seldom been reported. METHODS: Using 16S rRNA gene sequencing, we characterized the gut microbiota of 19 young adults with ASD and compared them with that of 19 healthy adults. A random forest prediction model was used to distinguish between the two groups at the genus level. RESULTS: The abundance levels of one phylum, seven families, and 18 genera in adults with ASD were significantly different from those of controls. The genus Phascolarctobacterium was significantly enriched in adults with ASD, which might elicit ASD-like behavior through production of propionate. In addition, a random forest model identified 15 genera that could distinguish adults with ASD from healthy controls with areas under the receiver operating curve of 92.86%, and ten of them were biomarkers identified by LEfSe. CONCLUSIONS: Our results identified specific gut bacteria associated with ASD, and the successful application of certain genera in the prediction model further supports the association between gut microbiota and ASD.
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Transtorno do Espectro Autista , Microbioma Gastrointestinal , Criança , Humanos , Adulto Jovem , RNA Ribossômico 16S/genética , Bactérias/genética , BiomarcadoresRESUMO
Exploration of high-performance photoanodes is considered as an essential challenge in photoelectrochemical (PEC) water splitting due to the complex four-electron reaction in water oxidation. Herein, the nano-structured WO3-Se heterojunction decorated by organic Nafion layer is designed. The optimized WO3-Se200-0.05Nafion photoanode shows a remarkable photocurrent of 1.40 mA cm-2at 1.23 V versus reversible hydrogen electrode, which is 2.5-fold higher than that of pure WO3nanosheets (WO3NS) photoelectrode. Remarkably, the photocurrent increments of WO3-Se200-0.05Nafion is larger than the increment sum of WO3-Se200 and WO3-0.05Nafion, which affirming the synergistic effect of Se nanospheres and Nafion layer. The improved PEC performances are attributed to the quick charge separation and transfer, the increased electric conductivity, and the excellent kinetics of oxygen evolution, which is derived from the strong interaction among WO3, Se and Nafion. Meanwhile, the better visible-light harvesting from Se nanospheres as photosensitizer and the induction of transparent Nafion as a passivation layer can explain this synergy. It hopes this heterostructure design with organic Nafion decoration can inspire to exploit outstanding performance photoanodes for PEC water splitting.
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Highly efficient and inexpensive electrocatalysts for oxygen evolution reaction (OER) are extensively studied for water splitting. Herein, a unique bimetallic nanocomposite CoNi(OH)2@NiCo2S4nanosheet arrays derived from metal-organic-frameworks (MOFs, CoNi-ZIF) is simply fabricated on Ni foam, endowing large specific surface area and outstanding electrical conductivity. Compared with their single-metallic counterparts, the bimetallic composite displays dramatically low overpotential and small Tafel slope as well as outstanding catalytic stability. The overpoptential at 20 mA cm-2for CoNi(OH)2@NiCo2S4is only 230 mV in comparison with Ni(OH)2@Ni3S2(266 mV), Co(OH)2@Co3S4(294 mV) and RuO2(η = 302 mV). First-principle calculations based on density functional theory (DFT) are carried out and reveal that the introduction of Ni in Co(OH)2helps lowered the energy difference of ΔGOOH*-ΔGO*, and thereby boosting the OER reactivity. This study provides an effective approach for the rational construction of low-cost metal hybrids.
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BACKGROUND: Secondary nosocomial infections, which are commonly caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) and vancomycin-resistant Enterococcus faecium (VRE), often develop in septic patients. This study aimed to identify the origin of secondary systemic pathogens and reveal the underlying mechanism of infection. METHODS: In this prospective, observational case-control study, a total of 34 septic patients, 33 non-septic intensive care unit (ICU) patients and 10 healthy individuals serving as controls were enrolled. Three hundred and twelve fecal samples were collected and subjected to 16S rRNA gene amplicon sequencing. Metagenome sequencing was performed to identify the homology between dominant CRKP or VRE in the intestine and pathogens isolated from secondary infectious sites. C57/BL mice were established as pseudo germ-free animal model by pretreatment with broad-spectrum antibiotics for two weeks. RESULTS: The abundance and diversity of the gut microbiota in septic patients was drastically decreased one week after ICU admission, potentially leading to the enrichment of antibiotic-resistant bacteria, such as CRKP. Furthermore, secondary bloodstream and abdominal infections caused by CRKP or VRE in septic patients occurred after intestinal colonization with the predominant bacterial species. Genomic analysis showed that bacteria isolated from secondary infection had high homology with the corresponding predominant intestinal opportunistic pathogens. In addition, animal model experiments validated the hypothesis that the administration of antibiotics caused the enrichment of CRKP and VRE among the intestinal microbiota, increasing the likelihood of permeation of other tissues and potentially causing subsequent systemic infection in pseudo germ-free mice. CONCLUSION: Our study indicated that the pathogens causing secondary infection in septic patients might originate from the intestinal colonization of pathogens following broad-spectrum antibiotic treatment.
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Coinfecção , Sepse , Animais , Estudos de Casos e Controles , Genótipo , Humanos , Camundongos , Estudos Prospectivos , RNA Ribossômico 16S/genética , Sepse/tratamento farmacológicoRESUMO
Schistosomiasis has been subjected to extensive control efforts in the People's Republic of China (China) which aims to eliminate the disease by 2030. We describe baseline results of a longitudinal cohort study undertaken in the Dongting and Poyang lakes areas of central China designed to determine the prevalence of Schistosoma japonicum in humans, animals (goats and bovines) and Oncomelania snails utilizing molecular diagnostics procedures. Data from the Chinese National Schistosomiasis Control Programme (CNSCP) were compared with the molecular results obtained.Sixteen villages from Hunan and Jiangxi provinces were surveyed; animals were only found in Hunan. The prevalence of schistosomiasis in humans was 1.8% in Jiangxi and 8.0% in Hunan determined by real-time polymerase chain reaction (PCR), while 18.3% of animals were positive by digital droplet PCR. The CNSCP data indicated that all villages harboured S. japonicum-infected individuals, detected serologically by indirect haemagglutination assay (IHA), but very few, if any, of these were subsequently positive by Kato-Katz (KK).Based on the outcome of the IHA and KK results, the CNSCP incorporates targeted human praziquantel chemotherapy but this approach can miss some infections as evidenced by the results reported here. Sensitive molecular diagnostics can play a key role in the elimination of schistosomiasis in China and inform control measures allowing for a more systematic approach to treatment.
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Schistosoma japonicum , Esquistossomose Japônica , Esquistossomose , Animais , Bovinos , China/epidemiologia , Humanos , Estudos Longitudinais , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Schistosoma japonicum/genética , Esquistossomose/epidemiologia , Esquistossomose Japônica/epidemiologia , Esquistossomose Japônica/veterinária , CaramujosRESUMO
BACKGROUND: Ethyl carbamate (EC) is a potential carcinogen existing in fermented foods such as Chinese rice wine (Huangjiu). Since urea is an important precursor of EC, the degradation of urea could be an effective way to reduce EC in foods. RESULTS: In this study, an Enterobacter sp. R-SYB082 with acid urea degradation characteristics was obtained through microbial screening. Further research isolated a new acid urea-degrading enzyme from R-SYB082 strain - ureidoglycolate amidohydrolase (UAH) - which could degrade EC directly. The cloning and expression of UAH in Escherichia coli BL21 (DE3) suggested that the activity of urea-degrading enzyme reached 3560 U L-1 , while urethanase activity reached 2883 U L-1 in the optimal fermentation condition. The enzyme had the dual ability of degrading substrate urea and product EC. The removal rate of EC in Chinese rice wine could reach 90.7%. CONCLUSION: This study provided a new method for the integrated control of EC in Chinese rice wine and other fermented foods. © 2022 Society of Chemical Industry.
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Oryza , Vinho , Ácidos , Amidoidrolases , China , Enterobacter/genética , Enterobacter/metabolismo , Escherichia coli/metabolismo , Fermentação , Oryza/metabolismo , Ureia/química , Uretana/metabolismo , Vinho/análiseRESUMO
Vascular remodeling and restenosis are common complications after percutaneous coronary intervention. Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) play important roles in intimal hyperplasia-induced vascular restenosis. NK2 Homeobox 3 (Nkx2-3), a critical member of Nkx family, is involved in tissue differentiation and organ development. However, the role of Nkx2-3 in VSMCs proliferation and migration remains unknown. In this study, we used carotid balloon injury model and platelet-derived growth factor-BB (PDGF)-treated VSMCs as in vivo and in vitro experimental models. EdU assay and CCK-8 assay were used to detect cell proliferation. Migration was measured by scratch test. Hematoxylin and eosin staining and immunohistochemistry staining were used to evaluate the intimal hyperplasia. The autophagy level was detected by fluorescent mRFP-GFP-LC3 in vitro and by transmission electron microscopy in vivo. It was shown that Nkx2-3 was upregulated both in balloon injured carotid arteries and PDGF-stimulated VSMCs. Adenovirus-mediated Nkx2-3 overexpression inhibited intimal hyperplasia after balloon injury, and suppressed VSMCs proliferation and migration induced by PDGF. Conversely, silencing of Nkx2-3 by small interfering RNA exaggerated proliferation and migration of VSMCs. Furthermore, we found that Nkx2-3 enhanced autophagy level, while the autophagy inhibitor 3-MA eliminated the inhibitory effect of Nkx2-3 on VSMCs proliferation and migration both in vivo and in vitro. Moreover, Nkx2-3 promoted autophagy in VSMCs by activating the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway. These results demonstrated for the first time that Nkx2-3 inhibited VSMCs proliferation and migration through AMPK/mTOR-mediated autophagy.
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Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia , Lesões das Artérias Carótidas/enzimologia , Movimento Celular , Proliferação de Células , Proteínas de Homeodomínio/fisiologia , Músculo Liso Vascular/enzimologia , Miócitos de Músculo Liso/enzimologia , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/fisiologia , Animais , Autofagia/efeitos dos fármacos , Becaplermina/farmacologia , Lesões das Artérias Carótidas/genética , Lesões das Artérias Carótidas/patologia , Lesões das Artérias Carótidas/prevenção & controle , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Proteínas de Homeodomínio/genética , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/ultraestrutura , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/ultraestrutura , Neointima , Ratos Sprague-Dawley , Transdução de Sinais , Fatores de Transcrição/genética , Remodelação VascularRESUMO
BACKGROUND: Acinetobacter baumannii is a common nosocomial pathogen that poses a huge threat to global health. Owing to the severity of A. baumannii infections, it became necessary to investigate the epidemiological characteristics of A. baumannii in Chinese hospitals and find the reasons for the high antibiotic resistance rate and mortality. This study aimed to investigate the epidemiologic and genetic characteristics of A. baumannii isolated from patients with hospital acquired pneumonia (HAP), bloodstream infection (BSI) and urinary tract infection (UTI) in China and uncover potential mechanisms for multi-drug resistance and virulence characteristics of A. baumannii isolates. RESULTS: All isolates were classified into two primary clades in core gene-based phylogenetic relationship. Clonal complex 208 (CC208) mainly consisted of ST195 (32 %) and ST208 (24.6 %). CC208 and non-CC208 isolates had carbapenem resistance rates of 96.2 and 9.1 %, respectively. Core genes were enriched in 'Amino acid transport and metabolism', 'Translation', 'Energy production and conversion', 'Transcription', 'Inorganic ion transport and metabolism' and 'Cell wall/membrane/envelope synthesis'. Most isolates possessed virulence factors related to polysaccharide biosynthesis, capsular polysaccharide synthesis and motility. Eleven isolates belong to ST369 or ST191 (oxford scheme) all had the virulence factor cap8E and it had a higher positive rate in UTI (35.3 %) than in BSI (18.9 %) and HAP (12.9 %). ABGRI1 antibiotic resistance islands were responsible for streptomycin, tetracycline and sulfonate resistance. The blaOXA-23 gene was the most probable cause for carbapenem resistance, although the blaOXA-66 gene with nonsynonymous SNPs (F82L, I129L) was not. CONCLUSIONS: A. baumannii is a genomically variable pathogen that has the potential to cause a range of infectious diseases. There is high proportion of carbapenem resistance in isolates from all three infection sites (HAP, BSI and UTI), which can be attributed to the blaOXA-23 gene. CC208 is the predominant clone in blaOXA-23-carrying A. baumannii that should be monitored. Virulence factors involving bacteria motility and polysaccharide biosynthesis which are widespread in clinical A. baumannii strains deserve our attention.
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Infecções por Acinetobacter , Acinetobacter baumannii , Doenças Transmissíveis , Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , China/epidemiologia , Farmacorresistência Bacteriana Múltipla , Genômica , Humanos , Testes de Sensibilidade Microbiana , Filogenia , beta-Lactamases/genéticaRESUMO
BACKGROUND: Cystic and alveolar echinococcosis caused by the tapeworms Echinococcus granulosus sensu stricto (s.s.) and E. multilocularis, respectively, are important zoonotic diseases. Protease inhibitors are crucial for the survival of both Echinococcus spp. Kunitz-type inhibitors play a regulatory role in the control of protease activity. In this study,we identified Kunitz-type domain protease inhibitors(KDPIs) present in the genomes of these two tapeworms and analyzed the gene sequences using computational, structural bioinformatics and phylogenetic approaches to evaluate the evolutionary relationships of these genes. Hi-seq transcriptome analysis showed that E. granulosus s.s. KDPIs were differentially expressed in the different developmental stages. We validated some of the genes expressed in adult worm, protoscolex and cyst germinal membrane of E. granulosus s.s. and E. multilocularis by quantitative PCR. RESULTS: A total of 19 genes from E. multilocularis and 23 genes from E. granulosus s.s. were predicted to be KDPIs with the most containing a single Kunitz-domain. A maximum likelihood method phylogenetic tree indicated that the E. granulosus s.s. and E. multilocularis Kunitz domain peptides were divided into three branches containing 9 clusters. The ratio of positively charged residues and neutral residues are different between E. multilocularis and E. granulosus s.s. KDPIs. We also found that E. multilocularis had higher percentage of sequences containing signal peptides (17/19, 89.47%) than that of E. granulosus s.s. (14/23, 60.87%). Transcript analysis showed all the E. granulosus s.s. KDPI genes were expressed differentially in four developmental stages of the worm. Transcription analysis showed that 9 KDPIs (including EG_07244,EGR_08716 and EGR_10096) were highly upregulated in adult worm, and 2 KDPIs (EG_09268 and EG_09490) were highly expressed in the cyst germinal membrane. Quantitative gene expression analysis(qPCR) of four genes confirmed the expression of these genes. EGR_08716 and its homologous gene (EmuJ_001137000) were highly and specifically expressed in adult worms of the two worms. CONCLUSIONS: A total 19 and 23 KDPIs were identified in the genomes of E. multilocularis and E. granulosus s.s. , respectively. The differential expression of these KDPIs in different stages may indicate their different roles in the different hosts. The difference in characterization of KDPIs may be associated with the different pathology of metacestode stage of these two parasites.
Assuntos
Echinococcus granulosus , Animais , Biologia Computacional , Echinococcus granulosus/genética , Filogenia , Inibidores de ProteasesRESUMO
Our current knowledge of the virosphere in deep-sea sediments remains rudimentary. Here we investigated viral diversity at both gene and genomic levels in deep-sea sediments of Southwest Indian Ocean. Analysis of 19 676 106 non-redundant genes from the metagenomic DNA sequences revealed a large number of unclassified viral groups in these samples. A total of 1106 high-confidence viral contigs were obtained after two runs of assemblies, and 217 of these contigs with sizes up to ~120 kb were shown to represent complete viral genomes. These contigs are clustered with no known viral genomes, and over 2/3 of the ORFs on the viral contigs encode no known functions. Furthermore, most of the complete viral contigs show limited similarity to known viral genomes in genome organization. Most of the classified viral contigs are derived from dsDNA viruses belonging to the order Caudovirales, including primarily members of the families Myoviridae, Podoviridae and Siphoviridae. Most of these viruses infect Proteobacteria and, less frequently, Planctomycetes, Firmicutes, Chloroflexi, etc. Auxiliary metabolic genes (AMGs), present in abundance on the viral contigs, appear to function in modulating the host ability to sense environmental gradients and community changes, and to uptake and metabolize nutrients.