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1.
Environ Sci Technol ; 58(20): 8643-8653, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38676641

RESUMO

Antimicrobial nanomaterials frequently induce inflammatory reactions within lung tissues and prompt apoptosis in lung cells, yielding a paradox due to the inherent anti-inflammatory character of apoptosis. This paradox accentuates the elusive nature of the signaling cascade underlying nanoparticle (NP)-induced pulmonary inflammation. In this study, we unveil the pivotal role of nano-microflora interactions, serving as the crucial instigator in the signaling axis of NP-induced lung inflammation. Employing pulmonary microflora-deficient mice, we provide compelling evidence that a representative antimicrobial nanomaterial, silver (Ag) NPs, triggers substantial motility impairment, disrupts quorum sensing, and incites DNA leakage from pulmonary microflora. Subsequently, the liberated DNA molecules recruit caspase-1, precipitating the release of proinflammatory cytokines and activating N-terminal gasdermin D (GSDMD) to initiate pyroptosis in macrophages. This pyroptotic cascade culminates in the emergence of severe pulmonary inflammation. Our exploration establishes a comprehensive mechanistic axis that interlinks the antimicrobial activity of Ag NPs, perturbations in pulmonary microflora, bacterial DNA release, macrophage pyroptosis, and consequent lung inflammation, which helps to gain an in-depth understanding of the toxic effects triggered by environmental NPs.


Assuntos
Pneumonia , Piroptose , Piroptose/efeitos dos fármacos , Camundongos , Animais , Pneumonia/induzido quimicamente , Pneumonia/patologia , Prata/toxicidade , Nanopartículas Metálicas/toxicidade , Macrófagos/efeitos dos fármacos , Inflamação
2.
J Nanobiotechnology ; 22(1): 19, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178140

RESUMO

Periodontitis is a chronic inflammatory disease caused by the local microbiome and the host immune response, resulting in periodontal structure damage and even tooth loss. Scaling and root planning combined with antibiotics are the conventional means of nonsurgical treatment of periodontitis, but they are insufficient to fully heal periodontitis due to intractable bacterial attachment and drug resistance. Novel and effective therapeutic options in clinical drug therapy remain scarce. Nanotherapeutics achieve stable cell targeting, oral retention and smart release by great flexibility in changing the chemical composition or physical characteristics of nanoparticles. Meanwhile, the protectiveness and high surface area to volume ratio of nanoparticles enable high drug loading, ensuring a remarkable therapeutic efficacy. Currently, the combination of advanced nanoparticles and novel therapeutic strategies is the most active research area in periodontitis treatment. In this review, we first introduce the pathogenesis of periodontitis, and then summarize the state-of-the-art nanotherapeutic strategies based on the triple concerto of antibacterial activity, immunomodulation and periodontium regeneration, particularly focusing on the therapeutic mechanism and ingenious design of nanomedicines. Finally, the challenges and prospects of nano therapy for periodontitis are discussed from the perspective of current treatment problems and future development trends.


Assuntos
Periodontite , Humanos , Periodontite/tratamento farmacológico , Periodonto , Antibacterianos/uso terapêutico , Regeneração , Imunomodulação , Imunidade
3.
Brief Bioinform ; 22(5)2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-33479731

RESUMO

Translation elongation is a crucial phase during protein biosynthesis. In this study, we develop a novel deep reinforcement learning-based framework, named Riboexp, to model the determinants of the uneven distribution of ribosomes on mRNA transcripts during translation elongation. In particular, our model employs a policy network to perform a context-dependent feature selection in the setting of ribosome density prediction. Our extensive tests demonstrated that Riboexp can significantly outperform the state-of-the-art methods in predicting ribosome density by up to 5.9% in terms of per-gene Pearson correlation coefficient on the datasets from three species. In addition, Riboexp can indicate more informative sequence features for the prediction task than other commonly used attribution methods in deep learning. In-depth analyses also revealed the meaningful biological insights generated by the Riboexp framework. Moreover, the application of Riboexp in codon optimization resulted in an increase of protein production by around 31% over the previous state-of-the-art method that models ribosome density. These results have established Riboexp as a powerful and useful computational tool in the studies of translation dynamics and protein synthesis. Availability: The data and code of this study are available on GitHub: https://github.com/Liuxg16/Riboexp. Contact:zengjy321@tsinghua.edu.cn; songsen@tsinghua.edu.cn.


Assuntos
Códon/metabolismo , Biologia Computacional , Modelos Biológicos , Biossíntese de Proteínas , Ribossomos/metabolismo
4.
PLoS Biol ; 18(3): e3000686, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32226015

RESUMO

Compact CRISPR/Cas9 systems that can be packaged into an adeno-associated virus (AAV) hold great promise for gene therapy. Unfortunately, currently available small Cas9 nucleases either display low activity or require a long protospacer adjacent motif (PAM) sequence, limiting their extensive applications. Here, we screened a panel of Cas9 nucleases and identified a small Cas9 ortholog from Staphylococcus auricularis (SauriCas9), which recognizes a simple NNGG PAM, displays high activity for genome editing, and is compact enough to be packaged into an AAV for genome editing. Moreover, the conversion of adenine and cytosine bases can be achieved by fusing SauriCas9 to the cytidine and adenine deaminase. Therefore, SauriCas9 holds great potential for both basic research and clinical applications.


Assuntos
Proteína 9 Associada à CRISPR/metabolismo , DNA/metabolismo , Edição de Genes/métodos , Staphylococcus/enzimologia , Sequência de Aminoácidos , Proteína 9 Associada à CRISPR/química , Proteína 9 Associada à CRISPR/genética , Sistemas CRISPR-Cas , DNA/química , DNA/genética , Dependovirus/genética , Células HEK293 , Humanos , Motivos de Nucleotídeos , Engenharia de Proteínas , Staphylococcus/genética , Especificidade por Substrato
5.
Phys Chem Chem Phys ; 25(6): 5291, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36723146

RESUMO

Correction for 'Mixing behavior of p-terphenyl-3,5,3',5'-tetracarboxylic acid with trimesic acid at the solid-liquid interface' by Wei Li et al., Phys. Chem. Chem. Phys., 2021, 23, 25896-25900, https://doi.org/10.1039/D1CP04770A.

6.
Nucleic Acids Res ; 49(7): 4008-4019, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33721016

RESUMO

The compact CRISPR/Cas9 system, which can be delivered with their gRNA and a full-length promoter for expression by a single adeno-associated virus (AAV), is a promising platform for therapeutic applications. We previously identified a compact SauriCas9 that displays high activity and requires a simple NNGG PAM, but the specificity is moderate. Here, we identified three compact Cas9 orthologs, Staphylococcus lugdunensis Cas9 (SlugCas9), Staphylococcus lutrae Cas9 (SlutrCas9) and Staphylococcus haemolyticus Cas9 (ShaCas9), for mammalian genome editing. Of these three Cas9 orthologs, SlugCas9 recognizes a simple NNGG PAM and displays comparable activity to SaCas9. Importantly, we generated a SlugCas9-SaCas9 chimeric nuclease, which has both high specificity and high activity. We finally engineered SlugCas9 with mutations to generate a high-fidelity variant that maintains high specificity without compromising on-target editing efficiency. Our study offers important minimal Cas9 tools that are ideal for both basic research and clinical applications.


Assuntos
Proteínas de Bactérias , Proteína 9 Associada à CRISPR/genética , Sistemas CRISPR-Cas , Staphylococcus , Proteínas de Bactérias/genética , Fibroblastos , Edição de Genes , Células HEK293 , Células HeLa , Humanos , Staphylococcus/genética
7.
BMC Musculoskelet Disord ; 24(1): 826, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37858123

RESUMO

BACKGROUND: Most displaced femoral neck fractures can achieve satisfactory anatomical reduction by closed reduction, but there are still some that cannot reset satisfactorily after closed reduction, and open reduction are required. Such fractures that cannot be repositioned successfully by closed reduction are called irreducible displaced femoral neck fractures in this study. The objective of our study was to evaluate the efficacy of direct anterior incision with the Femoral Neck System in the treatment of irreducible displaced femoral fractures. METHODS: A total of 16 young and middle-aged patients with irreducible displaced femoral neck fractures involving Garden type III and IV were treated using Femoral Neck System fixation by open reduction through Direct Anterior Approach between January 2020 to September 2021. Functional outcomes and postoperative complications were assessed during follow-up. Clinical outcomes were evaluated by the Hip Harris score. The postoperative reduction was evaluated by the Garden Index. Observe postoperative complications. RESULTS: All patients were followed up with a mean follow-up time of 21.1(12-30) months, and according to radiological results, all patients achieved fracture healing, with a mean healing time of 4.25 months. All 16 patients received grade Garden I and II reductions, and there was no significant difference in the anteroposterior Garden reduction index between the first day after surgery (166.13 ± 5.61) and the 12th month after surgery(164.94 ± 4.49) (P>0.05) and no significant difference in lateral Garden index between the first day after surgery(171.06 ± 4.46) and the 12th month after surgery(169.38 ± 3.98) (P<0.05). According to the Hip Harris score scale, 13 patients received excellent and 3 patients received good. The postoperative Hip Harris Score(17.19 ± 4.8) was significantly higher than the preoperative score(92.19 ± 3.4), and the difference was statistically significant (P < 0.05). No or mild femoral neck shortness occurred in 12 (75%) patients, moderate shortening occurred in 3 (18.75%) patients, and severe shortening occurred in 1 (6.25%) patient. None of the patients experienced femoral head necrosis, fracture nonunion, or incision infection. One patient developed deep venous thrombosis of the lower extremity. CONCLUSIONS: The Direct Anterior Approach combined with Femoral Neck System is an excellent treatment for irreducible displaced femoral neck fracture and achieved good functional outcomes and anatomical reduction with low complications.


Assuntos
Fraturas do Colo Femoral , Colo do Fêmur , Pessoa de Meia-Idade , Humanos , Fixação Interna de Fraturas/métodos , Fraturas do Colo Femoral/diagnóstico por imagem , Fraturas do Colo Femoral/cirurgia , Redução Aberta , Infecção da Ferida Cirúrgica , Resultado do Tratamento , Estudos Retrospectivos
8.
J Environ Manage ; 328: 116985, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36527799

RESUMO

River stage fluctuation (RSF) induced by tides, dam releases, or storms may lead to enhanced nitrogen cycling (N cycling) in riparian zones (RZ). We conducted a laboratory water table manipulation experiment and applied a multiphase flow and transport model (TOUGHREACT) to investigate the role of RSF in N cycling in the RZ. Coupled nitrification and denitrification occur in the water table fluctuation zone under alternating aerobic and anaerobic conditions. Nitrate removal was enhanced in the saturated and unsaturated zones of the RZ. The net nitrate reduction rate in groundwater increased with the increasing number of RSF, as a result, the cumulative water influx. The RZ nitrate sink function became stronger with increasing RSF amplitude and soil organic matter (SOM) content, and weaker with increasing [NH4+]/[NO3-] ratio and mineralization rate. RSF generally creates a hot moment for net nitrate removal in the RZ. However, a hot moment for the nitrate source function might occur if the [NH4+]/[NO3-] ratio of groundwater is much greater than 1 and/or if a large pool of nitrate accumulates in the topsoil over a prolonged dry period. The absence of oxygen diffusion in the model would overestimate the nitrate removal capacity of the RZ.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Nitratos/análise , Rios , Nitrogênio/análise , Compostos Orgânicos , Solo , Monitoramento Ambiental , Poluentes Químicos da Água/análise
9.
Environ Sci Technol ; 56(8): 5090-5101, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35344362

RESUMO

Silver nanoparticles (AgNPs) are effective antimicrobial substances that show promise in combatting multidrug resistance. The potential application and release of AgNPs into the environment may neutralize the selective advantage of antibiotic resistance. Systemic knowledge regarding the effect of NPs on the evolution of antibiotic resistance is lacking. Our results showed that bacteria slowly developed adaptive tolerance to ciprofloxacin (CIP) under cyclic CIP and silver ion (Ag+) cotreatment, and no resistance/tolerance was discernible when CIP and AgNP exposure was alternated. In contrast, rapid CIP resistance was induced under continuous selection by treatment with only CIP. To combat the effects of CIP and Ag+, bacteria developed convergent evolutionary strategies with similar adaptive mechanisms, including anaerobic respiration transitioning (to reduce oxidative stress) and stringent response (to survive harsh environments). Alternating AgNP exposure impeded evolutionary resistance by accelerating B12-dependent folate and methionine cycles, which reestablished DNA synthesis and partially offset high oxidative stress levels, in contrast with the effect of CIP-directed evolutionary pressure. Nevertheless, CIP/AgNP treatment was ineffective in attenuating virulence, and CIP/Ag+ exposure even induced the virulence-critical type III secretion system. Our results increase the basic understanding of the impacts of NPs on evolutionary biology and suggest prospective nanotechnology applications for arresting evolutionary antibiotic resistance.


Assuntos
Nanopartículas Metálicas , Prata , Ciprofloxacina/farmacologia , Resistência Microbiana a Medicamentos , Íons , Estudos Prospectivos , Prata/farmacologia
10.
BMC Musculoskelet Disord ; 23(1): 370, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35443641

RESUMO

BACKGROUND: The surgical treatment of complex acetabular fractures is one of the most challenging procedures for orthopedic surgeons. The Pararectus approach, as a reasonable alternative to the existing surgical procedures, was performed for the treatment of acetabular fractures involving the anterior column. This study aimed to evaluate outcome using the Pararectus approach for acetabular fractures involving anterior columns. METHODS: Thirty-seven with displaced acetabular fractures involving anterior columns were treated between July 2016 and October 2019 using the Pararectus approach. The functional outcomes (using the Merle d Aubigné and Postel scoring system, WOMAC and modified Harris scoring), the quality of surgical reduction (using the Matta criteria), and postoperative complications were assessed during approximately 26 months follow-up period. RESULTS: Thirty-seven patients (mean age 53 years, range: 30-71; 28 male) underwent surgery. Mean intraoperative blood loss was 840 ml (rang: 400-2000 ml) and mean operating time was 210 min (rang: 140-500 min). The modified Merle d Aubigné score was excellent and good in 27 cases (73%), fair in 6 cases (16%), and poor in 3 cases (11%). The mean score was 88.5 (range:77-96) for the modified Harris Hip scores, and 22 (range:7-35) for the WOMAC scores after operation. Postoperative functional outcomes were significantly improved compared with preoperative outcomes (P < 0.0001). The quality of reduction was anatomical in 21 cases (57%), satisfactory in 9 cases (24%), and unsatisfactory in 7 cases (19%). At follow-up, four patients developed a DVT, and heterotopic bone formation was observed in one patient. The hip osteoarthritis was not observed. CONCLUSION: The Pararectus approach achieved good functional outcomes and anatomical reduction in the treatment of acetabular fractures involving anterior column with minimal access morbidity.


Assuntos
Fraturas Ósseas , Fraturas do Quadril , Lesões do Pescoço , Fraturas da Coluna Vertebral , Acetábulo/diagnóstico por imagem , Acetábulo/lesões , Acetábulo/cirurgia , Feminino , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Fraturas do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
11.
Phys Chem Chem Phys ; 23(45): 25896-25900, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34779445

RESUMO

The molecular self-assembly of carboxylic acid molecules on a solid surface plays an important role in understanding the nanoscale-precision construction of functional patterns. In this study, the mixing behavior of p-terphenyl-3,5,3',5'-tetracarboxylic acid (TPTC) and trimesic acid (TMA) on a highly oriented pyrolytic graphite surface was studied by scanning tunneling microscopy (STM). The STM images show how the presence of a small percentage of TPTC molecules adsorbed onto TMA molecules can drastically change the on-surface self-assembly behavior of aromatic tetracarboxylic acid by initiating the nucleation and growth of a different polymorph. Molecular mechanics and density functional theory simulations of the adsorption energy and the additional stabilizing energy, induced by hydrogen bonds during assembly formations, provide insights into the relative stability of different assembled structures. Moreover, STM-based "nanoshaving" was conducted to confirm that the template layer underneath the second layer is indeed a random network.

12.
Nucleic Acids Res ; 47(D1): D1090-D1101, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30407536

RESUMO

One important aspect of precision medicine aims to deliver the right medicine to the right patient at the right dose at the right time based on the unique 'omics' features of each individual patient, thus maximizing drug efficacy and minimizing adverse drug reactions. However, fragmentation and heterogeneity of available data makes it challenging to readily obtain first-hand information regarding some particular diseases, drugs, genes and variants of interest. Therefore, we developed the Precision Medicine Knowledgebase (PreMedKB) by seamlessly integrating the four fundamental components of precision medicine: diseases, genes, variants and drugs. PreMedKB allows for search of comprehensive information within each of the four components, the relationships between any two or more components, and importantly, the interpretation of the clinical meanings of a patient's genetic variants. PreMedKB is an efficient and user-friendly tool to assist researchers, clinicians or patients in interpreting a patient's genetic profile in terms of discovering potential pathogenic variants, recommending therapeutic regimens, designing panels for genetic testing kits, and matching patients for clinical trials. PreMedKB is freely accessible and available at http://www.fudan-pgx.org/premedkb/index.html#/home.


Assuntos
Doença/genética , Variação Genética , Bases de Conhecimento , Farmacogenética/métodos , Medicina de Precisão/métodos , Biologia Computacional/métodos , Humanos , Armazenamento e Recuperação da Informação/métodos , Internet , Reprodutibilidade dos Testes
13.
Nano Lett ; 20(2): 1455-1460, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-31916445

RESUMO

The use of nanomaterials to regulate cell surface receptors is considered a novel strategy to manipulate cell behaviors. However, recognition is important to drive nanoparticle-cell complex formation. Here, we report a novel approach that uses graphene oxide (GO) as a chemoattractant to lure bacteria to nanosurface, facilitating complex formation. The amount of Escherichia coli (E. coli) cells attracted into capillaries containing 20 mg/L GO was more than 8.6-fold higher than that attracted into capillaries containing 20 mg/L glucose. The inherent mechanism involved interference with transmembrane chemoreceptors and activation of the chemotactic system via GO attachment and a subsequent increase in cell aggregation and migration via self-secreted quorum sensing molecules. The key feature of this strategy is the potential to improve the efficiency of the nanoparticle-cell recognition pattern and to expedite the development of surface-contact-related nanotechnology.


Assuntos
Fatores Quimiotáticos/farmacologia , Escherichia coli/efeitos dos fármacos , Grafite/química , Nanoestruturas/química , Antibacterianos/química , Antibacterianos/farmacologia , Fatores Quimiotáticos/química , Glucose/farmacologia , Nanopartículas/química , Receptores de Superfície Celular/antagonistas & inibidores , Receptores de Superfície Celular/química
14.
Glob Chang Biol ; 26(4): 2377-2389, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31943531

RESUMO

With the increasing intensity of global human activities, the ecosystem function, which is supported by the microbial community, will be dramatically changed and impaired. To investigate microbial resistance and resilience of microbial communities to human activities, we chose two typical types of human disturbances, urbanization, and reclamation under the higher intensity of human activities than the global average level. We examined microbial traits, including the abundance, diversity, phylogeny, and co-occurrence interactions in soil microbial communities, together with the nitrification activities observed in the subtropical coastal ecosystem of the Pearl River Estuary and in soil microcosm experiments. Microbial communities were less resistant to the environmental changes caused by urbanization than to those caused by reclamation, which was significantly reflected in the nitrogen and/or carbon-related patterns. However, most of the microbial traits could be recovered almost to the original level without significant differences in the microcosm after 40 days of incubation. The co-occurrence interactions between nitrifiers and other microbial communities were dramatically changed and could not be completely recovered, but this change did not affect their nitrification activities for balancing the ammonium in the soil to the original level during the recovery stage, suggesting that the interactions between microbial communities might have fewer effects on their activities than previously thought. This study quantitatively demonstrated that microbial communities as a whole can recover to a status similar to the original state in a short time after the removal of stress at a large ecosystem scale even under the higher intensity of human activities than global average level in coastal ecosystems, which implied a strong recovery capacity of soil microbial community even after intense human disturbance.

15.
Environ Sci Technol ; 54(19): 12412-12422, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32910654

RESUMO

Graphene oxide (GO), which has diverse antimicrobial mechanisms, is a promising material to address antibiotic resistance. Considering the emergence of antibiotic tolerance/resistance due to prolonged exposure to sublethal antibiotics, it is imperative to assess the microbiological effects and related adaptive mechanisms under chronic exposure to sublethal levels of GO, which have rarely been explored. After repetitive exposure to 5 mg/L GO for 200 subcultures (400 days), evolved Escherichia coli (E. coli) cells (EGO) differed significantly from their ancestor cells according to transcriptomic and metabolomic analyses. Contact with GO surfaces transformed E. coli by activating the Cpx envelope stress response (ESR), resulting in more than twofold greater extracellular protease release and biofilm formation. The ESR also modulated the envelope structure and function via increases in membrane fluidity, permeation, and lipopolysaccharide content to fulfill growth requirements and combat envelope stress. As a consequence of metabolic adjustment, EGO cells showed advantages of surviving in an acidic and oxidative environment, which resembles the cytosol of host cells. With these adaptive features, EGO cells exhibited higher pathogenicity than ancestor E. coli cells as evidenced by increased bacterial invasion and intracellular survival and a more severe inflammatory response in macrophage cells. To conclude, we seek to raise awareness of the possible occurrence of microbial adaptation to antimicrobial nanomaterials, which may be implicated in cross-adaptation to harsh environments and eventually the prevalence of virulence.


Assuntos
Proteínas de Escherichia coli , Grafite , Antibacterianos , Escherichia coli , Virulência
16.
Environ Sci Technol ; 54(20): 13186-13196, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-32960578

RESUMO

Due to daily exposure to nanostructured titanium dioxide (nTiO2) for various purposes, concerns have been raised regarding the potential health impact of this material. Few studies have researched the chronic effect of nTiO2 on commensal gut bacteria, and the exposure scenario is typified by long durations, low doses, and dark conditions. We repeatedly exposed Escherichia coli to 5 mg/L nTiO2 for 200 subcultures (400 days) in the dark. Adaptive morphogenesis (i.e., filamentation, thickening of the cell wall, and biofilm formation) was observed, which diminished the sensitivity of the cells to oxidative stress and multiple antibiotics. The bacterial mobility was enhanced by approximately 66%, which was ascribed to the significant increases in flagellar assembly and fimbria biosynthesis. These adaptive traits were associated with increased pathogenicity, as corroborated by a higher death rate of macrophages in vitro and more severe bacterial infection in mice in vivo. The adaptive evolution was attributed to hydroxyl radical production by 5 mg/L nTiO2 in the dark due to surface oxygen vacancies. Therefore, although nTiO2 is generally considered inert in the absence of light, additional precautions should be taken when it is applied in food and daily products considering its potential toxic effects on the commensal microbial community.


Assuntos
Escherichia coli , Nanopartículas , Animais , Camundongos , Estresse Oxidativo , Titânio/toxicidade
17.
Environ Sci Technol ; 53(6): 3277-3286, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30789710

RESUMO

The major concern regarding the biocide triclosan (TCS) stems from its potential coselection for antibiotic resistance. However, environmental impacts are often investigated using high concentrations and acute exposure, while predicted releases are typified by chronic low concentrations. Moreover, little information is available regarding the reversibility of TCS and derived antibiotic resistance with diminishing TCS usage. Here, the model Gram-negative bacterium Escherichia coli was exposed to 0.01 mg/L TCS continuously for more than 100 generations. The adapted cells gained considerable resistance to TCS as indicated by a significant increase in the minimal inhibitory concentration (MIC50) from 0.034 to 0.581 mg/L. This adaptive evolution was attributed to overexpression and mutation of target genes (i.e., fabI) as evidenced by transcriptomic and genomic analyses. However, only mild tolerance to various antibiotics was observed, possibly due to reduced membrane permeability and biofilm formation. After TCS exposure ceased, the adapted cells showed persistent resistance to TCS due to inheritable genetic mutations, whereas their antibiotic tolerance declined over time. Our results suggest that extensive use of TCS may promote the evolution and persistence of TCS-resistant bacterial pathogens. A quantitative definition of the conditions under which TCS selects for multidrug resistance in the environment is crucially needed.


Assuntos
Triclosan , Antibacterianos , Farmacorresistência Bacteriana , Escherichia coli , Testes de Sensibilidade Microbiana
18.
BMC Genomics ; 19(1): 807, 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30404602

RESUMO

BACKGROUND: Alfalfa (Medicago sativa) is a widely cultivated, essential commercial forage crop. The protein content in its leaves is the critical factor in determining the quality of alfalfa. Thus far, the understanding of the molecular mechanism of alfalfa defoliation traits remains unclear. The transcriptome database created by RNA-Seq is used to identify critical genes related to defoliation traits. RESULTS: In this study, we sequenced the transcriptomes of the Zhungeer variety (with easy leaf abscission) and WL319HQ variety (without easy leaf abscission). Among the identified 66,734 unigenes, 706 differentially expressed genes (DEGs) upregulated, and 392 unigenes downregulated in the Zhungeer vs WL319HQ leaf. KEGG pathway annotations showed that 8,414 unigenes were annotated to 87 pathways and contained 281 DEGs. Six DEGs belonging to the "Carotenoid biosynthesis", "Plant hormone signal transduction" and "Circadian rhythm-plant" pathways involved in defoliation traits were identified and validated by RT-qPCR analyses. CONCLUSIONS: This study used RNA-Seq to discover genes associated with defoliation traits between two alfalfa varieties. Our transcriptome data dramatically enriches alfalfa functional genomic studies. In addition, these data provide theoretical guidance for field production practice and genetic breeding, as well as references for future study of defoliation traits in alfalfa.


Assuntos
Regulação da Expressão Gênica de Plantas , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Medicago sativa/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/genética , Proteínas de Plantas/genética , Medicago sativa/classificação , Medicago sativa/crescimento & desenvolvimento , Melhoramento Vegetal , Locos de Características Quantitativas , Transcriptoma
19.
Environ Sci Technol ; 52(21): 12783-12791, 2018 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-30277752

RESUMO

Microbial reduction of graphene oxide (GO) under aerobic conditions is poorly understood despite its critical role in changing GO toxicity and environmental fate. Here we show that 20 mg/L GO interacts with the membrane-bound cytochrome c of E. coli in saline, shuttling electrons from the respiratory chain to extracellular molecular oxygen. This results in the formation of superoxide anions (O2•-), which in turn reduce GO in 30 min. The critical role of superoxide was demonstrated by impeding GO reduction upon addition of superoxide dismutase, or by carrying out experiments under strictly anaerobic conditions that preclude O2•- formation. Coating GO with bovine serum albumin also stopped GO reduction, which indicates the need for direct contact between GO and the cell membrane. Cell death was observed as a consequence of GO bioreduction. Apparently, electron shuttling by GO (via membrane contact) interrupts the respiratory chain and induces oxidative stress, as indicated by a 20% decrease in electron transport activity and an increase in intracellular reactive oxygen species. This novel antimicrobial mechanism could be relevant to assess GO stability and biocompatibility, and informs potential applications for microbial control.


Assuntos
Grafite , Escherichia coli , Óxidos , Espécies Reativas de Oxigênio , Superóxidos
20.
BMC Musculoskelet Disord ; 19(1): 108, 2018 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-29621984

RESUMO

BACKGROUND: Due to the intraarticular and complex nature of the coronal shear fracture of the humeral capitellum and its rarity, it has been difficult to formulate a universally accepted method of surgical management. The purpose of this study is to retrospectively evaluate the clinical outcomes of 15 patients with isolated coronal shear fractures of the capitellum treated by Herbert screw fixation through anterolateral approach, and to address the safety and tips for this surgical procedure. METHODS: This retrospective study included 15 isolated coronal shear fractures of the capitellum without posterior involvement, which were classified according to the Dubberley classification as 11 type 1A fractures and 4 type 3A fractures. All fractures were treated with Herbert screws fixation via the anterolateral approach. Clinical and radiographic evaluation was performed regularly, with a mean follow-up of 29 months. RESULTS: The mean operative time was 81 min. There were no wound healing problems or infection. One incomplete posterior interosseous nerve injury occurred, which recovered soon without residual compromise. All fractures healed well. At the final follow-up, the average range of motion was 134°in flexion-extension and 172°in supination-pronation. There was no significant difference between the affected and the unaffected elbows with regard to motion in flexion-extension or flexion-extension. The average Mayo Elbow Performance Index Score was 93 with 11 excellent and 4 good. No evidence of avascular necrosis, posttraumatic osteoarthritis, or heterotrophic ossification was found. CONCLUSION: Open reduction and internal fixation using Herbert screws through a anterolateral approach is a reliable and effective treatment for coronal shear fractures of capitellum, and able to achieve stable fixation and restoration of a functional range of motion.


Assuntos
Lesões no Cotovelo , Fixação Interna de Fraturas/métodos , Fraturas do Úmero/cirurgia , Adulto , Feminino , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
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