RESUMO
Programmed cell death and caspase proteins play a pivotal role in host innate immune response combating pathogen infections. Blocking cell death is employed by many bacterial pathogens as a universal virulence strategy. CopC family type III effectors, including CopC from an environmental pathogen Chromobacterium violaceum, utilize calmodulin (CaM) as a co-factor to inactivate caspases by arginine ADPR deacylization. However, the molecular basis of the catalytic and substrate/co-factor binding mechanism is unknown. Here, we determine successive cryo-EM structures of CaM-CopC-caspase-3 ternary complex in pre-reaction, transition, and post-reaction states, which elucidate a multistep enzymatic mechanism of CopC-catalyzed ADPR deacylization. Moreover, we capture a snapshot of the detachment of modified caspase-3 from CopC. These structural insights are validated by mutagenesis analyses of CopC-mediated ADPR deacylization in vitro and animal infection in vivo. Our study offers a structural framework for understanding the molecular basis of arginine ADPR deacylization catalyzed by the CopC family.
Assuntos
Calmodulina , Caspases , Animais , Calmodulina/genética , Calmodulina/metabolismo , Caspases/metabolismo , Caspase 3/metabolismo , Arginina , Catálise , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismoRESUMO
The widespread use of biogas slurry could potentially raise the environmental risk of antibiotics. Dissolved organic matter (DOM), as the most active part of biogas slurry, was able to interact with antibiotics and play a crucial role in the structure and function of soil and aquatic ecosystems. The recent shifts in global climate patterns have garnered significant attention due to their substantial impact on temperature, thereby exerting a direct influence on the characteristics of DOM and subsequently on the environmental behavior of antibiotics. However, there is limited research concerning the impact of temperature on the binding of DOM and antibiotics. Thus, this study aimed to explore the temperature-dependent structural transformation and driving factors of biogas slurry-derived DOM (BSDOM). Additionally, the binding characteristics between BSDOM and the commonly used antibiotic norfloxacin (NOR) at different temperatures were studied by using multi spectroscopic methods and two-dimensional correlation spectroscopy (2D-COS) analysis. The results suggested that the temperature-dependent structural transformation of BSDOM was reversible, with a slight lag in the transition temperature under cooling (13 °C for heating and 17 °C for cooling). Heating promoted the conversion of protein-like to humic-like substances while cooling favored the decomposition of humic-like substances. BSDOM and NOR were static quenching, with oxygen-containing functional groups such as C-O and -OH playing an important role. Temperature influenced the order of binding, the activity of the protein fraction, and its associated functional groups. At temperatures of 25 °C and 40 °C, the fluorescent components were observed to exhibit consistent binding preferences, whereby the humic-like component demonstrated a greater affinity for NOR compared to the protein-like component. However, the functional group binding order exhibited an opposite trend. At 10 °C, a new protein-like component appeared and bound preferentially to NOR, when no C-O stretch corresponding to the amide was observed. The finding will contribute to a comprehensive understanding of the interaction mechanisms between DOM and antibiotics under climate change, as well as providing a theoretical basis to reduce the environmental risks of biogas slurry and antibiotics.
Assuntos
Matéria Orgânica Dissolvida , Norfloxacino , Temperatura , Biocombustíveis , Ecossistema , Espectrometria de Fluorescência/métodos , Substâncias Húmicas/análise , Antibacterianos , ProteínasRESUMO
Legionella pneumophila, a bacterial pathogen that causes a severe pneumonia known as Legionnaires' disease, extensively exploits the ubiquitin (Ub) pathway in the infected host cells through certain virulence effectors excreted by the Dot/Icm system. To date, several Dot/Icm effectors have been found to act as Ub ligases, and four effectors, including LotA, LotB, LotC, and Ceg7, have been identified as deubiquitinases (DUBs) from the ovarian tumor (OTU) domain family. LotA is unique among other OTU DUBs because it possesses two distinct DUB domains and exclusively exhibits catalytic activity against K6-linked diUb and polyUb chains. However, the structure of LotA and the molecular mechanism for the dual DUB activity remains elusive. In this study, we solved the structure of LotA in complex with proximally bound Ub and distal covalently bound Ub. Both Ub molecules are bound to the DUB1 domain and mimic a K6-linked diUb. Structural analysis reveals that the DUB1 domain utilizes a distinct mechanism for recognition of the K6-linked diUb within a large S1' binding site that is uncommon to OTU DUBs. Structural fold of the LotA DUB2 domain closely resembles LotB and LotC, similarly containing an extra α-helix lobe that has been demonstrated to play an important role in Ub binding. Collectively, our study uncovers the structural basis for the dual catalytic activity of the unique OTU family DUB LotA.
Assuntos
Proteínas de Bactérias , Enzimas Desubiquitinantes , Legionella pneumophila , Proteínas de Bactérias/química , Enzimas Desubiquitinantes/química , Legionella pneumophila/enzimologia , Ubiquitina/metabolismo , Catálise , Domínios Proteicos , Conformação Proteica em alfa-HéliceRESUMO
As extremely active sites processing terrestrially derived dissolved organic matter (DOM), lakes deserve sufficient attention. Because of high-complexity interactions between DOM and the surrounding environment, the natural and anthropogenic drivers controlling the composition and chemodiversity of DOM molecules in lakes remain unclear. Here, 13,952 DOM molecules were identified and assessed in 45 lakes across China via ultrahigh-resolution mass spectrometry. Furthermore, the effects of both natural and anthropogenic factors on the DOM composition, DOM chemodiversity, and greenhouse gas emissions were investigated. The majority of the variations in DOM chemical composition could be attributed to the differences in the hydrology and nutrient concentrations of the lakes, and human activities also played a role, mainly through atmospheric pollution. Environmental factors mainly influenced DOM chemodiversity in the form of S-containing compounds. N-containing compounds exhibited a positive correlation with CO2 emissions, while N- and S-free compounds exhibited a positive correlation with N2O emissions. These results facilitate a comprehensive understanding of the interactions between lake DOM and the surrounding environment, thereby providing a reference for the formulation of strategies aimed at the harmonious development of human and natural environments.
Assuntos
Lagos , Efeitos Antropogênicos , Matéria Orgânica Dissolvida , Atividades Humanas , Humanos , Lagos/química , Espectrometria de MassasRESUMO
BACKGROUND: Antibiotic-impregnated calcium sulfate has excellent curative efficacy in chronic osteomyelitis. However, its curative efficacy in pediatric hematogenous osteomyelitis has not been sufficiently studied. The purpose of this study was to evaluate the curative effects of antibiotic-impregnated calcium sulfate in the treatment of pediatric hematogenous osteomyelitis. METHODS: Overall, twenty-one pediatric patients with hematogenous osteomyelitis treated at our hospital between 2013 and 2018 were included for assessment. The clinical history, clinical manifestation, infection recurrence rate, sinus leakage, incision leakage, pathological fractures, bone growth and surgical procedures were analyzed. RESULTS: The infection recurrence rate was 0% (0/21) at a minimum of 31 months (range 31 to 91 months) of follow-up. Postoperative incision leakage was found in one pediatric patient. Osteolysis was found in one pediatric patient. Acceleration of bone growth occurred in one pediatric patient. Retardation of bone growth occurred in one pediatric patient. Genu valgus deformity occurred in one pediatric patient. CONCLUSIONS: Although noninfectious complications occurred, the curative effect of antibiotic-impregnated calcium sulfate in pediatric hematogenous osteomyelitis was satisfactory.
Assuntos
Antibacterianos , Osteomielite , Humanos , Criança , Antibacterianos/uso terapêutico , Sulfato de Cálcio/uso terapêutico , Sulfato de Cálcio/farmacologia , Osteomielite/tratamento farmacológico , Resultado do Tratamento , Desbridamento/efeitos adversos , Desbridamento/métodosRESUMO
BACKGROUND: Previous articles have focused on the diagnosis and treatment of acute hematogenous osteomyelitis. Here, we present a case of chronic hematogenous osteomyelitis in a 2-month-old girl. The diagnostic procedure was unusual and difficult due to negative culture results. CASE PRESENTATION: A girl aged 2 months and 23 days had fever and swelling in her right lower leg for 7 days. On the basis of her medical history, physical, and histological examination results; and radiologic and magnetic resonance imaging findings, a diagnosis of chronic osteomyelitis was made. The patient underwent surgical treatment and was discharged successfully. The patient showed good recovery and no sequelae at the 12-month follow-up. CONCLUSION: Hematogenous osteomyelitis in babyhood is different from that at any other age. Hematogenous osteomyelitis-related bone destruction in babyhood is more serious and occurs faster. The transition from acute hematogenous osteomyelitis to chronic hematogenous osteomyelitis takes only 7 days. To the best of our knowledge, this chronic hematogenous osteomyelitis patient is the youngest ever reported.
Assuntos
Osteomielite , Doença Aguda , Feminino , Humanos , Lactente , Perna (Membro) , Imageamento por Ressonância Magnética , Osteomielite/diagnóstico por imagem , Osteomielite/terapiaRESUMO
Mono- and co-sorption of the three antibiotics i.e., norfloxacin (NOR), sulfamerazine (SMR) and oxytetracycline (OTC), to raw and NH4+-modified cassava waste biochar added to aqueous solutions were investigated. The NH4+-modified biochar showed higher sorption affinity for both NOR and SMR than the raw biochar, while the raw biochar showed higher sorption affinity for OTC than the modified biochar. The highest sorption to both biochars in both the mono- and competitive sorption systems was found for OTC followed by NOR and SMR. Sorption equilibrium in all systems analyzed was reached within 15 h. Electrostatic interactions among the ionic antibiotics in the multicomponent solution increased NOR and SMR sorption to both biochars. Antibiotics' mono- and co-sorption to biochars decreased with increasing solution pH. The co-sorption of NOR and SMR to the two biochars was regulated by π-π electron-donor-acceptor (EDA) interactions; besides, electrostatic interactions and Hydrogen (H-) bonding played an important part. Cation bridging might have been a potential mechanism to contribute to SMR sorption to the raw biochar, and OTC sorption to the NH4+-modified biochar. These observations will improve our understanding of the simultaneous removal of multiple antibiotics from water or wastewater.
Assuntos
Compostos de Amônio , Manihot , Adsorção , Antibacterianos , Carvão Vegetal , ÁguaRESUMO
Recognition and prediction of dissolved organic matter (DOM) properties and greenhouse gas (GHG) emissions is critical to understanding climate change and the fate of carbon in aquatic ecosystems, but related data is challenging to interpret due to covariance in multiple natural and anthropogenic variables with high spatial and temporal heterogeneity. Here, machine learning modeling combined with environmental analysis reveals that urbanization (e.g., population density and artificial surfaces) rather than geography determines DOM composition and properties in lakes. The structure of the bacterial community is the dominant factor determining GHG emissions from lakes. Urbanization increases DOM bioavailability and decreases the DOM degradation index (Ideg), increasing the potential for DOM conversion into inorganic carbon in lakes. The traditional fossil fuel-based path (SSP5) scenario increases carbon emission potential. Land conversion from water bodies into artificial surfaces causes organic carbon burial. It is predicted that increased urbanization will accelerate the carbon cycle in lake ecosystems in the future, which deserves attention in climate models and in the management of global warming.
Assuntos
Gases de Efeito Estufa , Lagos , Lagos/química , Ecossistema , Matéria Orgânica Dissolvida , Gases de Efeito Estufa/análise , Urbanização , Carbono/análiseRESUMO
Extracellular polymeric substances (EPS) secreted by organisms tend to encapsulate microplastics (MPs), forming an EPS-corona that affects the fate of MPs in marine ecosystems. However, the impact of the EPS-corona on the biotoxicity of MPs to marine organisms remains poorly understood. Herein, the effect of the EPS-corona on the toxicity of polystyrene (PS) MPs of different sizes (0.1 and 1 µm) to Skeletonema costatum (S. costatum) was investigated. The preferential adsorption of medium molecule weight (â¼55 kDa) proteins onto PS MPs mainly contributed to the EPS-corona formation, decreasing the surface charge negativity of small-sized PS MPs (0.1 µm) by 72.4 %. Nitrogen (N) and oxygen (O) moieties in polysaccharides and proteins were identified as the preferential adsorption sites in the EPS-PS MPs interaction. Density functional theory (DFT) calculations confirmed the nuclear magnetic resonance spectroscopy (NMR) results, revealing that the binding mode between EPS and PS MPs was mainly hydrogen bonding. In addition, EPS-corona increased the cell density of S. costatum by 35.5-36.0 % when exposed to small-sized PS MPs (0.1 µm, 25-50 mg/L). These findings provide new insights into how EPS-corona affects the environmental fate and ecological risks associated with micro- and nano-sized plastics in marine ecosystems.
Assuntos
Matriz Extracelular de Substâncias Poliméricas , Microplásticos , Poliestirenos , Poluentes Químicos da Água , Microplásticos/toxicidade , Microplásticos/química , Adsorção , Poliestirenos/toxicidade , Poliestirenos/química , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Matriz Extracelular de Substâncias Poliméricas/química , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/química , Proteínas/química , Proteínas/metabolismo , Peso Molecular , Diatomáceas/efeitos dos fármacos , Diatomáceas/metabolismo , Tamanho da PartículaRESUMO
Over the past decades, the accumulation of plastics in mangrove ecosystems has emerged as a significant environmental concern, primarily due to anthropogenic activities. Polypropylene (PP) films, one of the plastic types with the highest detection rate, tend to undergo intricate aging processes in mangrove ecosystems, leading to the release of dissolved organic matter (DOM) that may further influence the local bacterial communities. Yet, the specific effects of new and weathered (aged) plastic films and the associated leached DOM on bacterial consortia in mangrove sediments remain poorly understood. In this study, an incubation experiment was conducted to elucidate the immediate effects and mechanisms of the new and relatively short-term (45 or 90 days) aged PP films, as well as their leached DOM (PDOM), on characteristics of DOM and the bacterial community structure in mangrove sediments under different tidal conditions. Surface morphology and functional group analyses showed that both new and aged PP films exhibited comparable degradation profiles under different tidal conditions over the incubation period. As compared to the new PP film treatments, the introduction of the short-term aged PP films significantly affected the content of humic-like compounds in sediments, and such effects were partially ascribed to the release of PDOM during the incubation. Although the addition of PP films and PDOM showed minor effects on the overall diversity and composition of bacterial communities in the sediments, the abundance of some dominant phyla exhibited a growth or reduction tendency, possibly changing their ecological functions. This study was an effective attempt to investigate the relationship among plastic surface characteristics, sedimentary physicochemical properties, and bacterial communities in mangrove sediments. It revealed the ecological ramifications of new and short-term plastic pollution and its leachates in mangrove seedtimes, enhancing our understating of their potential impacts on the health of mangrove ecosystems.
Assuntos
Bactérias , Sedimentos Geológicos , Polipropilenos , Áreas Alagadas , Sedimentos Geológicos/química , Sedimentos Geológicos/microbiologia , Poluentes Químicos da Água/análise , MicrobiotaRESUMO
Antibiotics and nanoplastics are widely detected in the coastal ecosystem. However, the transcriptome mechanism elucidating the effect of antibiotics and nanoplastics co-exposure on the gene expression of aquatic organisms in coastal environment is still unclear. Here, single and joint effects of sulfamethoxazole (SMX) and polystyrene nanoplastics (PS-NPs) on the intestinal health and gene expression of medaka juveniles (Oryzias melastigma), which live in coastal environment, were investigated. The SMX and PS-NPs co-exposure decreased intestinal microbiota diversity compared to the PS-NPs, and caused more adverse effect on the intestinal microbiota composition and intestinal damage compared to the SMX, indicating that PS-NPs might enhance the toxicity of SMX on the medaka intestine. The increased abundance of Proteobacteria in the intestine was observed in the co-exposure group, which might induce the intestinal epithelium damage. In addition, the differentially expressed genes (DEGs) were mainly involved in the drug metabolism-other enzymes, drug metabolism-cytochrome P450, metabolism of xenobiotics by cytochrome P450 pathways in visceral tissue after the co-exposure. The expression of the host immune system genes (e.g., ifi30) could be associated with the increased pathogens in intestinal microbiota. This study is useful for understanding the toxicity effect of antibiotics and NPs on aquatic organisms in coastal ecosystem.
Assuntos
Oryzias , Poluentes Químicos da Água , Animais , Microplásticos/toxicidade , Microplásticos/metabolismo , Oryzias/metabolismo , Sulfametoxazol/toxicidade , Sulfametoxazol/metabolismo , Ecossistema , Poliestirenos/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Antibacterianos/metabolismo , Intestinos , Poluentes Químicos da Água/análiseRESUMO
Microplastics (MPs) and sulfamethoxazole (SMX) are ubiquitous in various aquatic environments, but little is known about their joint toxicity mechanism on marine organisms. This study investigated the individual and joint toxicity of SMX and five MPs, including polypropylene (PP), polyethylene (PE), polyethylene terephthalate (PET), polystyrene (PS) and bioplastic polylactic acid (PLA), on Skeletonema costatum. The inhibition rates (IR) of the single MPs systems (50 mg/L) followed the order of PP > PE > PLA > PS > PET, while the addition of 0.3 mg/L SMX significantly decreased the toxicity of PP, PE and PLA in the joint system due to the "shelter" effect from MPs adsorption. As for the PS and SMX joint system, the malondialdehyde (MDA), reactive oxygen species (ROS) levels and superoxide dismutase (SOD) activity were higher than those of the other joint systems. The metabolomic results showed that SMX downregulated glycerophospholipid and amino acid metabolism. PS caused the downregulation of glycerophospholipids, carbohydrates and amino acid via the hetero-aggregation with algae. The co-exposure of SMX and PS alleviated the perturbation of alanine, aspartate and glutamate metabolism of algae compared with SMX. These findings enhance our understanding of the potential mechanisms of the MPs and organic pollutants joint toxicity in the marine environment.
Assuntos
Diatomáceas , Poluentes Químicos da Água , Aminoácidos , Microplásticos/toxicidade , Plásticos/toxicidade , Poliésteres , Polietileno , Poliestirenos/toxicidade , Sulfametoxazol/farmacologia , Poluentes Químicos da Água/análiseRESUMO
Two-dimensional transition metal dichalcogenide (TMDC) nanomaterials have attracted tremendous research interest in various fields, but the effects of eco-corona formation on the transformation mechanisms and ecological risk of TMDCs remain largely unknown. The effect of eco-corona formation on TMDC reactivity was explored using extracellular polymeric substances (EPS) as the eco-corona constituents and single-layer molybdenum disulfide (SLMoS2) as the model TMDC. We found that EPS promoted lattice distortion and the formation of defects (sulfur vacancies and pores) on SLMoS2 after it was aged (precoated) with EPS under simulated visible-light irradiation. In addition, the EPS-corona induced higher free radical (especially hyperoxide radical) photogeneration by SLMoS2. Furthermore, compared to pristine SLMoS2, SLMoS2-EPS exhibited stronger developmental inhibition, oxidative stress, membrane damage, photosynthetic toxicity and metabolic perturbation effects on Chlorella vulgaris. However, the endocytosis pathway (especially macropinocytosis) of SLMoS2 entry into C. vulgaris was inhibited by EPS. Metabolic and transcriptomic analyses revealed that the enhanced toxicity of SLMoS2-EPS was associated with the downregulation of fatty acid metabolism and transcription related to photosynthesis, respectively. The present work provides mechanistic insights into the roles of the EPS-corona on the environmental transformation and phytotoxicity of TMDCs, which benefit environmental safety assessments and sustainable applications of engineered nanomaterials.
Assuntos
Chlorella vulgaris , Nanoestruturas , Matriz Extracelular de Substâncias Poliméricas , Luz , Molibdênio/toxicidade , Nanoestruturas/toxicidadeRESUMO
Lakes are critical for biogeochemical and ecological processes and are sensitive and vulnerable to anthropogenic disturbances, but how and to what extent human activities disturb the biodiversity in lakes remain unknown. Here, we showed the microbial diversity in 46 lakes and assessed the influence of 27 anthropogenic factors. We found that the economic level (e.g., per capita gross domestic product) was strongly negatively correlated (r = -0.97) with bacterial diversity but positively correlated (r = 0.17) with fungal diversity in lakes. The composition of the microbial community significantly changed with increasing economic level. Bacteria are more sensitive than fungi to anthropogenic impacts. Expanding the population size and increasing the economic level may promote the development of fungal diversity but inhibit bacterial diversity. Air quality, urbanization and ozone were negatively correlated with bacterial diversity, and fisheries had a negative correlation with fungal diversity. The anti-interference ability of lake microorganisms in the middle economic level zones (45,000-90,000 yuan/person) was stronger than that in high-level (> 90,000 yuan/person) and low-level (> 45,000 yuan/person) economic zones. Overall, our investigation provides national-scale evidence that changes in the microbial diversity in lakes were related to economic levels.
Assuntos
Efeitos Antropogênicos , Biodiversidade , Lagos , Microbiota , Bactérias/classificação , Fungos/classificação , Lagos/microbiologiaRESUMO
Zeolitic imidazole frameworks (ZIFs) have attracted a considerable amount of attention for use in environmental applications (e.g., pollutant adsorption and photocatalysis in water treatments). The environmental stability and toxicity of ZIFs are key prerequisites for their practical applications, but information about these factors is largely lacking. The present work finds that pristine ZIFs (ZIF-8 and ZIF-67) photodegrade from frame structures into two-dimensional nanosheets and are oxidized to zinc carbonate (ZIF-8) and Co3O4 (ZIF-67) under visible-light irradiation. The photoinduced electrons, holes and free radicals promote dissolution of the metal cores and organic ligands, leading to collapse of the frame structure. The photodegradation of ZIF-8 alleviates developmental inhibition, oxidative stress, plasmolysis, and photosynthetic toxicity, while the photodegradation of ZIF-67 aggravates nanotoxicity. The integration of metabolomics and transcriptomics analysis reveals that unsaturated fatty acid biosynthesis and metal ion-binding transcription contribute to the altered toxicity of ZIF photodegradation. These findings highlight the roles of photodegradation in structural transformation and alteration of the toxicity of ZIFs, alarming the study of pristine metal-organic frameworks (MOFs).
Assuntos
Estruturas Metalorgânicas , Nanoestruturas , Zeolitas , Adsorção , Cobalto , Óxidos , Zeolitas/toxicidadeRESUMO
BACKGROUND: Hepatitis C virus (HCV) infection is an important health threat in China to which direct acting antivirals (DAAs) are very effective. In 2019, another novel DAA glecaprevir/pibrentasvir (GLE/PIB) was officially approved. Knowledge of its cost-effectiveness would be informative for clinical decision-making but has not been evaluated. This study aims to evaluate the cost-effectiveness of GLE/PIB to inform policy-making on drug reimbursement and HCV eradication. METHODS: Markov models were developed from the payers' perspective and simulated the lifetime experience of adult patients chronically infected with HCV genotype 1 or genotype 2. Two regimens, GLE/PIB and pegylated interferon (pegIFN) plus ribavirin (RBV), were compared in cost and quality adjusted life years (QALY) with both outcomes being discounted to 2020 values. The incremental cost-effectiveness ratio (ICER) was computed to reflect the incremental benefit of GLE/PIB versus pegIFN + RBV. The robustness of the model outcomes was examined using deterministic and probabilistic sensitivity analysis (PSA) to identify influential parameters and to assess the probability of GLE/PIB being cost-effective. The GDP per capita in China in 2019 ($10,275) was used as the threshold for cost-effectiveness. RESULTS: For the entire target population, GLE/PIB was the dominant regimen attaining a cost-saving of $255 and 1.17 more QALYs relative to pegIFN + RBV. The finding was more pronounced for HCV genotype 1 infection by saving $1,656 and creating 1.37 more QALYs. At the $10,275 threshold, the probability of GLE/PIB being cost-effective was 99.32% overall and 99.85% for HCV genotype 1 infection. The age of starting DAA treatment, price of pegIFN + RBV, cost of cirrhosis treatment and duration of the GLE/PIB regimen were the five most influential factors. For the patients with HCV genotype 2 infection, the ICER of GLE/PIB was $12,914/QALY with 95% confidence interval of $4,047/QALY to $37,640/QALY. The GLE/PIB regimen statistically cannot be ruled out as a cost-effective option for HCV genotype 2 infection. CONCLUSIONS: GLE/PIB is a cost-effective strategy to treat chronic HCV genotype 1 and HCV genotype 2 infection in China. This regimen should be initiated at a younger age to maximize its value. To achieve national eradication, it may be timely to consider replacing pegIFN + RBV with DAAs, such as GLE/PIB, as the first-line treatment.
Assuntos
Antivirais , Hepatite C Crônica , Adulto , Ácidos Aminoisobutíricos , Antivirais/uso terapêutico , Benzimidazóis , China , Análise Custo-Benefício , Ciclopropanos , Quimioterapia Combinada , Genótipo , Hepatite C Crônica/tratamento farmacológico , Humanos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Prolina/análogos & derivados , Pirrolidinas , Quinoxalinas , SulfonamidasRESUMO
Legionella pneumophila extensively modulates the host ubiquitin network to create the Legionella-containing vacuole (LCV) for its replication. Many of its virulence factors function as ubiquitin ligases or deubiquitinases (DUBs). Here, we identify Lem27 as a DUB that displays a preference for diubiquitin formed by K6, K11, or K48. Lem27 is associated with the LCV where it regulates Rab10 ubiquitination in concert with SidC and SdcA, two bacterial E3 ubiquitin ligases. Structural analysis of the complex formed by an active fragment of Lem27 and the substrate-based suicide inhibitor ubiquitin-propargylamide (PA) reveals that it harbors a fold resembling those in the OTU1 DUB subfamily with a Cys-His catalytic dyad and that it recognizes ubiquitin via extensive hydrogen bonding at six contact sites. Our results establish Lem27 as a DUB that functions to regulate protein ubiquitination on L. pneumophila phagosomes by counteracting the activity of bacterial ubiquitin E3 ligases.
Assuntos
Proteínas de Bactérias/metabolismo , Enzimas Desubiquitinantes/metabolismo , Legionella pneumophila/enzimologia , Fagossomos/enzimologia , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina/metabolismo , Motivos de Aminoácidos , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Enzimas Desubiquitinantes/genética , Legionella pneumophila/química , Legionella pneumophila/genética , Legionella pneumophila/metabolismo , Pargilina/análogos & derivados , Pargilina/metabolismo , Fagossomos/metabolismo , Propilaminas/metabolismo , Ubiquitina/química , Ubiquitina-Proteína Ligases/genética , Ubiquitinação , Vacúolos/enzimologia , Vacúolos/genética , Vacúolos/metabolismoRESUMO
BACKGROUND: The screw and cement technique is a convenient method used to rebuild medial tibial plateau defects in primary total knee arthroplasty (TKA). The objective of this study was to perform a finite element assessment to determine the effect of different numbers of screws on the stability of TKA and to determine whether differences exist between two different insertion angles. METHOD: Six tibial finite element models with defects filled with screws and cement and one model with defects filled only with cement were generated. Contact stresses on the surface of cancellous bone in different areas were calculated. RESULTS: Compared to the cement-only technique, the stress on the border of cancellous bone and bone cement decreased by 10% using the screw and cement technique. For bone defects with a 12% defect area and a 12-mm defect depth, the use of 1 screw achieved the greatest stability; for those with a 15% defect area and a 20-mm defect depth, 2 screws achieved the greatest stability. CONCLUSIONS: (1) The screw and cement technique is superior to the bone cement-only technique. For tibial defects in which the defect area comprises a large percentage but the depth is less than 5 mm, the screw and cement technique is recommended. (2) Vertical screws can achieve better stability than oblique screws. (3) Screws should be used in moderation for different defects; more is not always better.
Assuntos
Artroplastia do Joelho/métodos , Cimentos Ósseos/uso terapêutico , Parafusos Ósseos , Análise de Elementos Finitos , Humanos , Articulação do Joelho/cirurgia , Masculino , Tíbia/cirurgiaRESUMO
Biochar, can be used as a sorbent material to sequester organic contaminants in soils. In this study, the sorption-desorption behavior of atrazine (AT) was studied in latosol (L) supplemented with varying doses of cassava waste biochar (CW). Changes in the release of AT were assessed with varying aging time (0-60â¯days) and environmental factors (pH, ionic strength, solid-liquid ratio and disturbance intensity). Results indicate that the addition of 0.1%-5% (w/w) CW in L, promoted AT adsorption by 1.7- to 36-fold as compared with the natural soil control, after 60â¯days. The release of AT from biochar-amended soil was significantly affected by pH ranged from 3 to 9 and the amount of desorbed AT increased with increasing pH conditions. 0.05â¯mol/L Ca2+ enhanced AT sorption by biochar. The release of AT increased with increasing solid-liquid ratio (at the ratio of 1:10, 1:15, 1:20) and disturbance intensity, surface complexation and cation exchange were found to play important roles in sorption mechanisms.
Assuntos
Atrazina/análise , Carvão Vegetal/química , Herbicidas/análise , Modelos Químicos , Poluentes do Solo/análise , Recuperação e Remediação Ambiental , Manihot , SoloRESUMO
In this study, the impacts of various cations, cation strength and pH on ofloxacin (OFL) adsorption to cassava residue-derived biochars were determined. The associated adsorption mechanisms are discussed. The biochars were prepared at pyrolysis temperatures ranging from 350°C to 750°C, and labeled as CW350, CW450, CW550, CW650 and CW750. The Freundlich model provided the best fit to describe the adsorption capacity of OFL and the Freundlich coefficient (logKf) increased with increasing pyrolysis temperature. The inclusion of Zn2+ or Al3+ increased OFL sorption capacities of five biochars, while Cu2+ reduced sorption to CW450 and CW550. No significant impacts on OFL sorption were observed in the presence of K+ and Ca2+. The concentration of Ca2+ affected the adsorption capacity of CW550, but had no significant impact on other biochars. The pH of OFL solution, ranging from 3 to 9, had no significant changes on OFL adsorption by all the tested biochars. Results of FTIR spectra and zeta potential indicated that electrostatic interactions, cationic exchange, metal bridging and micropore filling could be the main sorption mechanism between OFL and biochars. These studies indicated that cassava residue can be converted into biochars that are effective adsorbents for removing OFL from aqueous solution.