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1.
Environ Microbiol ; 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32114703

RESUMO

Colistin resistance has attracted substantial attention after colistin was considered as a last-resort drug for the treatment of infections caused by carbapenem-resistant and/or multidrug-resistant (MDR) Gram-negative bacteria in clinical settings. However, with the discovery of highly mobile colistin resistance (mcr) genes, colistin resistance has become an increasingly urgent issue worldwide. Despite many reviews, which summarized the prevalence, mechanisms, and structures of these genes in bacteria of human and animal origin, studies on the prevalence of mobile colistin resistance genes in aquaculture and their transmission between animals and humans remain scarce. Herein, we review recent reports on the prevalence of colistin resistance genes in animals, especially wildlife and aquaculture, and their possibility of transmission to humans via the food chain. This review also gives some insights into the routine surveillance, changing policy and replacement of polymyxins by polymyxin derivatives, molecular inhibitors, and traditional Chinese medicine to tackle colistin resistance.

2.
Med Sci Monit ; 26: e921540, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32123154

RESUMO

BACKGROUND Our objective was to establish and compare three-dimensional models of knee joints of mini-pigs and sheep, the 2 most commonly used animal models of osteoarthritis. MATERIAL AND METHODS Three-dimensional geometric models of knee joints were used to assess their biomechanical properties by analysis of the three-dimensional finite element stress load for flexion at 30° and 60°. RESULTS Analysis of multiple tissues indicated that the sheep knee had greater stress peaks than the mini-pig knee at 30° flexion (range: 12.5 to 30.4 Mpa for sheep vs. 11.1 to 20.2 Mpa for mini-pig) and at 60° flexion (range: 17.9 to 43.5 Mpa for sheep vs. 15.9 to 28.9 Mpa for mini-pig). In addition, there was uneven distribution of stress loads in the surrounding ligaments during flexion. CONCLUSIONS Our three-dimensional finite element analysis indicated that the mini-pig knee joint had stress values and changes of cartilage, meniscus, and peripheral ligaments that were similar to those of the human knee.

3.
mBio ; 11(2)2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32156810

RESUMO

Although the pathogen recognition receptor pathways that activate cell-intrinsic antiviral responses are well delineated, less is known about how the host regulates this response to prevent sustained signaling and possible immune-mediated damage. Using a genome-wide CRISPR-Cas9 screening approach to identify host factors that modulate interferon-stimulated gene (ISG) expression, we identified the DNA binding protein Barrier-to-autointegration factor 1 (Banf1), a previously described inhibitor of retrovirus integration, as a modulator of basal cell-intrinsic immunity. Ablation of Banf1 by gene editing resulted in chromatin activation near host defense genes with associated increased expression of ISGs, including Oas2, Rsad2 (viperin), Ifit1, and ISG15 The phenotype in Banf1-deficient cells occurred through a cGAS-, STING-, and IRF3-dependent signaling axis, was associated with reduced infection of RNA and DNA viruses, and was reversed in Banf1 complemented cells. Confocal microscopy and biochemical studies revealed that a loss of Banf1 expression resulted in higher level of cytosolic double-stranded DNA at baseline. Our study identifies an undescribed role for Banf1 in regulating the levels of cytoplasmic DNA and cGAS-dependent ISG homeostasis and suggests possible therapeutic directions for promoting or inhibiting cell-intrinsic innate immune responses.IMPORTANCE Although the interferon (IFN) signaling pathway is a key host mechanism to restrict infection of a diverse range of viral pathogens, its unrestrained activity either at baseline or in the context of an immune response can result in host cell damage and injury. Here, we used a genome-wide CRISPR-Cas9 screen and identified the DNA binding protein Barrier-to-autointegration factor 1 (Banf1) as a modulator of basal cell-intrinsic immunity. A loss of Banf1 expression resulted in higher level of cytosolic double-stranded DNA at baseline, which triggered IFN-stimulated gene expression via a cGAS-STING-IRF3 axis that did not require type I IFN or STAT1 signaling. Our experiments define a regulatory network in which Banf1 limits basal inflammation by preventing self DNA accumulation in the cytosol.

4.
Radiat Oncol ; 15(1): 65, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32169088

RESUMO

BACKGROUND AND PURPOSE: We evaluated the relationship between patient-, tumor-, and treatment-related features and radiation-induced lymphopenia (RIL) and evaluated the correlation between RIL and survival outcome in NPC patients to help improve the treatment strategy. METHODS: This retrospective study included 374 patients with stage II-IVa NPC who had been treated with definitive RT and were enrolled from 2004 to 2015; The associations between the G3-4 RIL (absolute lymphocyte count, ALC <  0.5 × 109 cells/L) during RT and patient-, tumor-, and treatment-related factors were assessed using Cox regression analyses. The correlation between ALC nadir and survival was examined using a Kaplan-Meier analysis, compared with the log-rank test, and confirmed by a Cox proportional hazards analysis. RESULTS: In the multivariate analysis, lower baseline ALC and intensity modulated radiation therapy (IMRT) (vs. 2 dimensional-conformal radiation therapy,2D-CRT) were identified as 2 independent factors that were associated with G3-4 RIL. In the multivariate survival analysis, patients with G3-4 ALC nadir had longer local recurrence-free survival durations (LRFS) (vs. G0-2 nadir, HR = 0.548, P = 0.005) and longer progression-free survival durations (PFS) (vs. G0-2 nadir, HR = 0.676, P = 0.022), while patients with G4 ALC nadir had a shorter distant-metastasis-free survival duration (DMFS) (vs. G0-2 nadir, hazard ratio [HR] = 2.567, P = 0.037). CONCLUSIONS: In the study, lymphopenia during RT were affected by baseline ALC and RT modality independently. Moreover, G3-4 ALC nadir was independently linked with longer PFS and LRFS durations, while G4 ALC nadir was independently linked with a shorter DMFS duration.

5.
Food Funct ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32190865

RESUMO

Two novel effective antioxidative tripeptides GWY and QWY were designed based on 3D-QSAR models. Their activities were confirmed by an improved TEAC assay. The experimental results showed that GWY and QWY possessed good antioxidant activity, equaling 3.32 mM TE and 2.97 mM TE respectively. This indicated that 3D-QSAR models possessed significant predictive capacity for drug design. In addition, molecular docking and molecular dynamics simulation were applied to reveal the potential molecular mechanism of antioxidant peptides. The result showed that GWY and QWY could enhance the stability of Keap1 by interacting with the key residues Arg415, Arg483, Arg380 and Ser555 in the active sites. Interestingly, the key residues were exactly the binding site of Nrf2 in the active pocket of Keap1. Thus, GWY and QWY could compete with Nrf2 for binding to Keap1. This demonstrated that the new tripeptides might have the ability to activate the signaling pathway Keap1-Nrf2-ARE and improve the antioxidant defense system of the body as well.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32184192

RESUMO

Interleukin-6 (IL-6) is a pleiotropic cytokine with crucial immunoregulatory functions in both innate and adaptive immune responses. However, the IL-6 sequence and function remain unknown in sturgeon, one chondrostean fish. In the present study, we identified an interleukin-6 homolog from Siberian sturgeon (Acipenser baeri), named AbIL-6. Its open reading frame (ORF) was 657 nucleotides in length, encoding a polypeptide of 218 amino acids, which contains a signal peptide and the IL-6 family domain. Phylogenetic analysis showed that sturgeon IL-6 had close relationship with both teleost and chondrichthyes IL-6s. Abil-6 mRNA was highly expressed in spleen, brain and liver tissues of healthy sturgeon, and significantly up-regulated in the spleen, head kidney and liver by A.hydrophila (A.h) challenge. Heat-killed A.h and LPS effectively stimulated Abil-6 transcripts in primary spleen cells in vitro. In order to understand the bioactivity and influence of AbIL-6 on immune responses, recombinant AbIL-6 (rAbIL-6) was synthesized by prokaryotes and demonstrated to promote the proliferation of spleen cells and head kidney cells in vitro. Additionally, intraperitoneal injection of rAbIL-6 induced significantly higher expression of four immuno-related genes including il-1ß, cxcl10, mhcIIß and igm. rAbIL-6 improved the survival rate and reduced the tissue bacterial load after A.h infection. Taken together, these results suggest that AbIL-6 plays an important role in inflammatory responses and immune defense against bacterial infection of sturgeon.

7.
Spectrochim Acta A Mol Biomol Spectrosc ; 234: 118251, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32193157

RESUMO

Herein, nitrogen-doped carbon dots (N-CDs) emitting blue fluorescence were prepared using L-tartaric acid and triethylenetetramine through a simple and quick microwave-assisted method. The synthesized N-CDs displayed excitation-dependent fluorescence behavior, and their maximum excitation and emission wavelengths were 350 and 425 nm, respectively. The obtained N-CDs, which featured excellent fluorescence properties with a high fluorescence quantum yield of 31%, were applied to detect metronidazole (MNZ), which can effectively quench the fluorescence intensity of N-CDs due to the inner filter effect. This phenomenon was used as basis to develop a label-free fluorescent method for rapid MNZ determination, with the limit of detection of 0.22 µM and corresponding linear range of 0.5-22 µM. Hence, we had established a fluorescence method for MNZ detection and applied it to detect MNZ in real samples with satisfactory results. Finally, N-CDs with superior biocompatibility were applied for cell imaging and MNZ detection by the changes in fluorescence intensity.

8.
Nat Commun ; 11(1): 1427, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188862

RESUMO

Anthropogenic environments have been implicated in enrichment and exchange of antibiotic resistance genes and bacteria. Here we study the impact of confined and controlled swine farm environments on temporal changes in the gut microbiome and resistome of veterinary students with occupational exposure for 3 months. By analyzing 16S rRNA and whole metagenome shotgun sequencing data in tandem with culture-based methods, we show that farm exposure shapes the gut microbiome of students, resulting in enrichment of potentially pathogenic taxa and antimicrobial resistance genes. Comparison of students' gut microbiomes and resistomes to farm workers' and environmental samples revealed extensive sharing of resistance genes and bacteria following exposure and after three months of their visit. Notably, antibiotic resistance genes were found in similar genetic contexts in student samples and farm environmental samples. Dynamic Bayesian network modeling predicted that the observed changes partially reverse over a 4-6 month period. Our results indicate that acute changes in a human's living environment can persistently shape their gut microbiota and antibiotic resistome.

9.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(1): 0, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32207592

RESUMO

Since the corona virus disease 2019 (COVID-19) affects the cardio-pulmonary function of pregnant women, the anesthetic management in the cesarean section for the patients, as well as the protection for medical staff is significantly different from that in ordinary surgical operation. This paper reports a pregnant woman with COVID-19, for whom a cesarean section was successfully performed in our hospital on February 8, 2020. Anesthetic management, protection of medical staff and psychological intervention for the patients during the operation are discussed. Importance should be attached to the preoperative evaluation of pregnant women with COVID-19 and the implementation of anesthesia plan. For ordinary COVID-19 patients intraspinal anesthesia is preferred in cesarean section, and the influence on respiration and circulation in both maternal and infant should be reduced; while for severe or critically ill patients general anesthesia with endotracheal intubation should be adopted. The safety of medical environment should be ensured, and level-Ⅲ standard protection should be taken for anesthetists. Special attention and support should be given to maternal psychology. It is important to give full explanation before operation to reduce anxiety; to relieve the discomfort during operation to reduce tension; to avoid the bad mood of patients due to pain after operation.

10.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(1): 37-46, 2020 Feb 28.
Artigo em Chinês | MEDLINE | ID: mdl-32131938

RESUMO

Objective To study the gene expression of cardiac mesenchymal cells in patients with type 2 diabetes mellitus (T2DM)based on a whole-genome high-throughput sequencing dataset,screen differentially expressed genes,analyze the genetics signature of cardiac mesenchymal cells in T2DM patients by bioinformatics analysis,and explore the environmental chemicals related to the key differentially expressed genes. Methods The dataset GSE106177 was obtained from Gene Expression Omnibus (GEO) database.The dataset was pre-processed and analyzed by Network Analyst,Cytoscape 3.7.1,String11.0,CTD,and HMDD for screening for differentially expressed genes,enrichment analysis,establishment of protein-protein interaction (PPI) networks,and screening for relevant environmental chemicals. Results The gene expression pattern of cardiac mesenchymal cells in T2DM patients was significantly different from that in the control group.There were 135 differentially expressed genes,of which 58 (42.96%) were up-regulated and 77 (57.04%) were down-regulated.The differentially expressed genes mainly participated in biological processes such as multicellular organism development,anatomical structure development,and system development and were mainly involved in hepatocellular carcinoma,Cushing's syndrome,and cholesterol metabolism.PPI network showed that UBC was the core protein node.The microRNA-Gene interaction network showed that seven microRNAs,represented by hsa-mir-8485,interacted with the differentially expressed genes.Key T2DM related genes such as UBC,DNER,and CNTN1 interacted with bisphenol A. Conclusions The gene expression profile of cardiac mesenchymal cells markedly changes in T2DM patients,during which UBC may play an important biological role.Bisphenol A exposure may also affect the development and normal function of cardiac cells in T2DM patients.

11.
Small ; : e2001003, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32162848

RESUMO

Fluorescence in the second near-infrared window (NIR-II, 900-1700 nm) has drawn great interest for bioimaging, owing to its high tissue penetration depth and high spatiotemporal resolution. NIR-II fluorophores with high photoluminescence quantum yield (PLQY) and stability along with high biocompatibility are urgently pursued. In this work, a Ag-rich Ag2 Te quantum dots (QDs) surface with sulfur source is successfully engineered to prepare a larger bandgap of Ag2 S shell to passivate the Ag2 Te core via a facile colloidal route, which greatly enhances the PLQY of Ag2 Te QDs and significantly improves the stability of Ag2 Te QDs. This strategy works well with different sized core Ag2 Te QDs so that the NIR-II PL can be tuned in a wide range. In vivo imaging using the as-prepared Ag2 Te@Ag2 S QDs presents much higher spatial resolution images of organs and vascular structures as compared with the same dose of Ag2 Te nanoprobes administrated, suggesting the success of the core-shell synthetic strategy and the potential biomedical applications of core-shell NIR-II nanoprobes.

12.
Zhen Ci Yan Jiu ; 45(2): 169-72, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32144930

RESUMO

This article reviews the clinical studies on acupuncture in the treatment of asthma, chronic bronchitis, and acute exacerbation and stable phase of chronic obstructive pulmonary disease in China over the past 10 years, and the results suggest that acupuncture has a good clinical effect. At present, there are still several problems in related clinical studies, including lacking of standard operation procedure for acupuncture, unreasonable design of control group, and low quality of clinical research. Therefore, in the future, top-level design should be standardized and large-sample multicenter clinical studies should be conducted to provide stronger evidence of evidence-based medicine for acupuncture in the treatment of respiratory diseases.


Assuntos
Terapia por Acupuntura , Asma , Doença Pulmonar Obstrutiva Crônica , China , Humanos , Doença Pulmonar Obstrutiva Crônica/terapia
13.
Artigo em Inglês | MEDLINE | ID: mdl-32163336

RESUMO

Colletotrichum fructicola is a plant pathogenic fungus with a broad host range. It causes significant losses to important crops including apple, pear, strawberry and other Rosaceae and non-Rosaceae species. To date, two short-read based C. fructicola genomes are publicly available, but both are fragmented. In this study we re-sequenced the genome of C. fructicola using nanopore long read technology and refined the assembly with Hi-C map data. The resulting high-quality assembly is an important resource for further comparative and experimental studies with C. fructicola.

14.
Biologicals ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32165080

RESUMO

Immunoglobulin preparations are one of the promising drugs for Alzheimer's disease (AD). Anti-ß-amyloid (Aß) oligomers antibodies in immunoglobulin preparations are considered to be critical for the therapeutic effect against Alzheimer's disease. However, the antibodies content in immunoglobulin preparations varies greatly. In order to determine which factor contributes to the difference of the antibodies content, the content of anti-Aß oligomers antibodies in multiple batches of immunoglobulin preparations from two manufacturers were measured by enzyme-linked immunosorbent assay. The results showed that no significant difference was found in the antibodies content among different bathes of normal immunoglobulin preparations prepared by the same process from the same manufacturer, whereas significant difference was found in the antibodies content between normal immunoglobulin preparations prepared by ethanol fractionation and those by chromatography process from the same manufacturer. In addition, significant variation existed in the antibodies content between normal immunoglobulin preparations and specific immunoglobulin preparations that are produced by plasma pool of immunized donors. Based on analysis of these results, the preparation process and raw plasma could be the main contributing factors affecting the content of anti-Aß oligomers antibodies in immunoglobulin preparations. This finding might help to develop AD-specific immunoglobulin preparation containing higher content of anti-Aß oligomers antibodies.

15.
Stem Cells Dev ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32122257

RESUMO

This study was conducted to compare the in vitro proliferation and osteogenic differentiation potential of mesenchymal stem cells (MSCs) derived from mandibular (M-MSCs) or femur (F-MSCs) of rats. M-MSCs and F-MSCs cultures were isolated and established from the same rat. Cultures were observed for morphological by microscope and growth characteristics by CCK-8 and cloning assays. Cells' adhesion ability on culture plate and Titanium sheet were detected by staining with toluidine blue and hochest33258, respectively. The level of Ca, P and ALP levels serially during osteogenic differentiation were evaluated. Cultures were analysed for mineralization potential with Alizarin Red and ALP staining methods, and for differentiation markers with RT-PCR (ALP, Runx2 and OCN). M-MSCs and F-MSCs were successfully isolated from the same rat with uncontaminated cultured, and showed significant differences in morphology. The proliferation rate of M-MSCs was higher than F-MSCs in primary culture, but was significantly lower after passage. More colonies are formed from F-MSCs than from M-MSCs. M-MSCs showed a significantly higher mineralization and osteogenic differentiation potential, which might be of significance for the use in bone/dental tissue engineering. In vitro, cell passage will decrease the proliferation ability of M-MSCs. The higher mineralization and osteogenic differentiation potential of M-MSCs made it could be an approachable stem cell source for further applied in stem cell-based clinical therapies.

16.
Behav Brain Res ; 383: 112516, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32006566

RESUMO

BACKGROUND: Depression is a debilitating condition with a profound influence on quality of life for millions of people globally. Physical exercise has been broadly recognized for its therapeutic effects on depression, but the mechanisms that underlie its benefits remain unknown. In the study, we investigated whether the physical exercise of could be a protection from stress-induced depression and its impact on the brain activity of Regional Homogeneity (ReHo) in mice. METHODS: Adult male C57BL/6 mice were assigned to one of the following groups: control group; exercise group, 2 h/day in a running wheel apparatus; chronic unpredictable mild stress (CUMS) group; CUMS + exercise group. rs-fMRI was applied to detect the changes of regional spontaneous activity. RESULTS: Firstly, CUMS-induced depressive behavior was significantly reduced by exercise. Base on the ReHo analysis, disorders of the regional spontaneous activity in the brain of CUMS mice, primarily in the limbic system, especially in the hippocampus and PFC, motor cortex, sensory cortex, visual cortex were found. While exercise remarkably prevented the CUMS-induced chaos of brain activity in parts of the above regions, such as cortex, hippocampus and corpus callosum. These results suggested physical exercise could prevent the dysfunction of mood-regulating circuit in CUMS model. Furthermore, exercise improved skeletal muscle PGC-1a and hippocampal BDNF levels in stress mice, and reduced IDO1 in skeletal muscle. CONCLUSIONS: These results suggested that exercise prevented CUMS induced depressive behaviors and brain regional spontaneous activity in mice, accompanied with the adjustment of skeletal muscle PGC-1a/IDO1 signals and hippocampal function.

17.
Plant Dis ; : PDIS07191559RE, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32027567

RESUMO

Apple core rot, an economically important disease worldwide, appears both before and during harvest. Current gaps in understanding of the infection cycle impede progress toward more effective management of this disease. The fungus Trichothecium roseum is the main pathogen of core rot on apple in China. In this study, we used fluorescent labeling to trace colonization of T. roseum in floral tissues, characterizing routes of penetration to the core of 'Fuji' apples. T. roseum infected petals, anthers, filaments, stigmas and separated styles of flowers, and floral debris served as inoculum for core infection. In field inoculations, T. roseum entered styles initially through stylar fissures and colonized pluricellular hairs of these fissures during early stages of fruit development. Subsequently, hyphae grew along the extending fissures, which are continuations of stylar fissures located between stylar bases and carpel cavities. The hyphae remained in the extending fissures from mid-June to late July. When fruit developed an open sinus in late July, the sinus eventually fused with extending fissures and carpel cavities in late August, hyphae invaded carpel cavities, and ultimately fruit flesh via cracks on carpel cavity walls. Our results revealed for the first time the routes by which T. roseum penetrates apple fruit, and provided significant insights for strategic management of core rot.

19.
Org Biomol Chem ; 18(10): 1933-1939, 2020 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-32101242

RESUMO

A novel and convenient photo-mediated halogenated spirocyclization of N-(p-methoxyaryl)propiolamides has been developed. The photolysis of phenyliodine bis(trifluoroacetate) (PIFA) as an iodination reagent led to iodinated ipso-cyclization under the irradiation of a xenon lamp, while brominated ipso-cyclization or chlorinated ipso-cyclization was achieved by irradiating a mixture of PIFA and KBr/KCl under a blue LED. The present protocol simply utilizes light as the safe and clean energy source and doesn't require any external photocatalyst providing various 3-halospiro[4,5]trienones in good to excellent yields (up to 93%).

20.
Org Biomol Chem ; 18(10): 1940-1948, 2020 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-32101246

RESUMO

A visible-light-promoted decarboxylative acyl radical acylation/cyclization cascade reaction of N-methacryloylbenzamides for accessing acylated isoquinoline-1,3(2H,4H)-dione derivatives was described. In this report, α-keto acids were used for generating acyl radicals and inducing radical acylations. This protocol features mild reaction conditions, operational practicality and a broad substrate scope.

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