Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 172
Filtrar
1.
BMC Med ; 19(1): 90, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33845843

RESUMO

BACKGROUND: The aim of this study was to quantitatively summarize the available evidence on the association of breastfeeding with the risk of childhood cancer. METHODS: A literature search of PubMed and Embase databases was performed to identify eligible observational studies published from inception to July 17, 2020. The categorical and dose-response meta-analysis was conducted by pooling relative risk (RR) or odds ratio (OR) estimates with 95% confidence intervals (CIs). Potential sources of heterogeneity were detected by meta-regression and stratification analysis. Sensitivity analysis and publication bias test were also carried out. RESULTS: Forty-five articles involving 475,579 individuals were included in the meta-analysis. Among the thirty-three studies on the association between breastfeeding and risk of childhood leukemia, the pooled risk estimates were 0.77 (95% CI, 0.65-0.91) and 0.77 (95% CI 0.63-0.94) for ever versus non/occasional breastfeeding and longest versus shortest breastfeeding duration group, respectively. There was clear indication for non-linear dose-response relationship between breastfeeding duration and the risk of childhood leukemia (P non-linear < 0.001). The most protective effect (OR, 0.66, 95% CI 0.62-0.70) was observed at a breastfeeding duration of 9.6 months. Four studies examined, the association between breastfeeding and risk of childhood neuroblastoma, and significant inverse associations were consistently observed in both the comparisons of ever breastfeeding versus non/occasional breastfeeding (OR = 0.59, 95% CI 0.44-0.81) and longest versus shortest breastfeeding (OR = 0.61, 95% CI 0.44-0.83). However, no associations of breastfeeding with risk of other cancers were found. CONCLUSIONS: Our study supports a protective role of breastfeeding on the risk of childhood leukemia, also suggesting a non-linear dose-response relationship. Further studies are warranted to confirm the association between breastfeeding and risk of childhood neuroblastoma.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33771786

RESUMO

Ulvan is an important marine polysaccharide. Bacterial ulvan lyases play important roles in ulvan degradation and marine carbon cycling. Until now, only a small number of ulvan lyases have been characterized. Here, a new ulvan lyase, Uly1, belonging to the polysaccharide lyase (PL) family 24 from the marine bacterium Catenovulum maritimum is characterized. The optimal temperature and pH for Uly1 to degrade ulvan are 40°C and pH 9.0, respectively. Uly1 degrades ulvan polysaccharides in the endolytic manner, mainly producing ΔRha3S, consisting of an unsaturated 4-deoxy-L-threo-hex-4-enopyranosiduronic acid and a 3-O-sulfated α-L-rhamnose. The structure of Uly1 was resolved at a 2.10 Å resolution. Uly1 adopts a seven-bladed ß-propeller architecture. Structural and site-directed mutagenesis analyses indicate that four highly conserved residues, H128, H149, Y223 and R239, are essential for catalysis. H128 functions as both the catalytic acid and base, H149 and R239 function as the neutralizers, and Y223 plays a supporting role in catalysis. Structural comparison and sequence alignment suggest that Uly1 and many other PL24 enzymes may directly bind the substrate near the catalytic residues for catalysis, different from the PL24 ulvan lyase LOR_107 adopting a two-stage substrate binding process. This study provides new insights into ulvan lyases and ulvan degradation.ImportanceUlvan is a major cell wall component of green algae of the genus Ulva. Many marine heterotrophic bacteria can produce extracellular ulvan lyases to degrade ulvan for carbon nutrient. In addition, ulvan has a range of physiological bioactivities based on its specific chemical structure. Ulvan lyase thus plays an important role in marine carbon cycling and has great potential in biotechnological applications. However, only a small number of ulvan lyases have been characterized over the past ten years. Here, based on biochemical and structural analyses, a new ulvan lyase of polysaccharide lyase family 24 is characterized and its substrate recognition and catalytic mechanisms are revealed. Moreover, a new substrate binding process adopted by PL24 ulvan lyases is proposed. This study offers a better understanding of bacterial ulvan lyases and is helpful for studying the application potentials of ulvan lyases.

3.
Pharmacology ; : 1-9, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33780953

RESUMO

BACKGROUND: Hepatic fibrosis is an inflammatory liver disease, and there is no effective therapy at present. Astilbin is a bioactive ingredient found in many medicinal and food plants, with antioxidative, anti-inflammatory, and antitumor properties. OBJECTIVES: This study aimed to investigate the protective effect and related molecular mechanism of astilbin against carbon tetrachloride (CCl4)-induced liver fibrosis in rats. METHODS: Liver fibrosis was induced by injection of CCl4 in male Sprague-Dawley rats, and those rats were then treated with astilbin at different concentrations. Pathological changes, collagen production, inflammatory cytokine, and oxidative stress were evaluated to evaluate the effects of astilbin on CCl4-induced hepatic fibrosis. Real-time PCR and western blot were performed to detect the mRNA and protein expression of indicated genes. RESULTS: We discovered that CCl4 caused significant fibrosis damage in rat liver, and astilbin dose-dependently improved the liver functions and fibrosis degree. Astilbin treatment significantly decreased collagen production, inflammatory response, and oxidative stress in vivo. Mechanically, administration of astilbin obviously elevated the hepatic levels of Nrf2 and its downstream components, including NAD(P)H:quinone oxidoreductase 1 (Nqo1), heme oxygenase (HO-1), glutamate-cysteine ligase catalytic subunit, and glutamate cysteine ligase modifier. CONCLUSIONS: Taken together, these findings demonstrate that astilbin could protect against CCL4 induced-liver fibrosis in rats.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33765360

RESUMO

AIMS: To analyze lung cancer incidence and mortality rates from 2013 to 2017 in Qingdao, Shandong Province, China. METHODS: The lung cancer new cases and death data during 2013-2017 were collected from the Qingdao Cancer Surveillance System. The crude incidence and mortality rates were calculated by residential area and gender. The annual percentage change (APC) was determined to evaluate the incidence and mortality rate trends. RESULTS: Between 2013 and 2017, 31 653 new lung cancer cases and 24 965 deaths from lung cancer were retrieved. The age-standardized incidence rates by Chinese standard population (ASIRC) were 42.1 per 100 000. The crude incidence rates for men and women increased from 85.2 and 46.3 per 100 000 in 2013 to 124.0 and 67.4 per 100 000 in 2017, respectively. The APCs were 7.8% for men (P < .001) and 7.5% (P = .027) for women. The crude mortality rates increased from 56.3 per 100 000 in 2013 to 68.0 per 100 000 in 2017. The age-standardized mortality rates by ASIRC were 32.3 per 100 000. The APCs of mortality rates were higher in men than in women and were higher in rural than in urban areas. Age-specific incidence and mortality rates were lower in individuals aged <40 years, increased sharply in those aged >40 years, and were the highest in 80-year-old individuals. CONCLUSION: These data show different patterns of incidence and mortality rate according to gender and resident area during 2013-2017. Early screening and targeted prevention should be implemented to control the increased trend of lung cancer.

5.
Sensors (Basel) ; 21(4)2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33669528

RESUMO

There are three state estimation fusion methods for a class of strong nonlinear measurement systems, based on the characteristic function filter, namely the centralized filter, parallel filter, and sequential filter. Under ideal communication conditions, the centralized filter can obtain the best state estimation accuracy, and the parallel filter can simplify centralized calculation complexity and improve feasibility; in addition, the performance of the sequential filter is very close to that of the centralized filter and far better than that of the parallel filter. However, the sequential filter can tolerate non-ideal conditions, such as delay and packet loss, and the first two filters cannot operate normally online for delay and will be invalid for packet loss. The performance of the three designed fusion filters is illustrated by three typical cases, which are all better than that of the most popular Extended Kalman Filter (EKF) performance.

6.
J Nutr ; 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33693920

RESUMO

BACKGROUND: Observational epidemiological studies have reported an inconsistent relation between iron status and risk of systemic lupus erythematosus (SLE). Moreover, it remains uncertain whether the observed association is causal or due to confounding or reverse causality. OBJECTIVES: We aimed to investigate the association between serum iron status and risk of SLE using a 2-sample Mendelian randomization (MR) approach. METHODS: Genetic instruments for iron status including serum iron, log-transformed ferritin, transferrin saturation, and transferrin were identified from a large-scale genome-wide association study (GWAS) performed by the Genetics of Iron Status Consortium among 48,972 individuals of European ancestry (55% female). Three independent single nucleotide polymorphisms (rs1800562, rs1799945, and rs855791) concordantly related with 4 iron status biomarkers were selected as instrumental variables. Summary statistics of SLE were obtained from a publicly available GWAS of 4036 patients with SLE and 6959 controls of European descent. The MR study was conducted using the inverse-variance weighted (IVW) method, supplemented with MR-Egger regression and simple- and weighted-median methods. Leave-one-out analysis was further performed to test the robustness of our findings. ORs with 95% CIs were calculated. RESULTS: Genetically predicted iron status was associated with altered risk of SLE, with ORs of 0.79 (95% CI: 0.66, 0.94), 0.54 (95% CI: 0.34, 0.85), 0.82 (95% CI: 0.71, 0.94), and 1.36 (95% CI: 1.06, 1.76) per 1-SD increase in iron, log-transformed ferritin, transferrin saturation, and transferrin using the IVW method, respectively. MR-Egger regression did not indicate potential pleiotropic bias. Sensitivity analyses produced similar findings, suggesting the robustness of the association. CONCLUSIONS: Our study suggested that high iron status may be associated with a reduced risk of SLE among European populations. Further studies are warranted to elucidate the mechanism underlying the protective role of iron against susceptibility to SLE.

7.
Thorac Cancer ; 12(8): 1147-1153, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33586338

RESUMO

BACKGROUND: To investigate the uniportal video-assisted thoracoscopic surgery (VATS) technique and safety of non-small cell lung cancer (NSCLC) patients treated with uniportal and three-port VATS. METHODS: We retrospectively evaluated 146 consecutive patients with NSCLC who underwent VATS lobectomy between January 2018 and May 2018. The general clinical date, perioperative data and life quality were individually compared and analyzed between the two groups. RESULTS: Intraoperative blood loss was significantly lower in the uniportal than in the three-port group (p = 0.035), and significantly shorter chest tube drainage and postoperative hospital stay durations were found in the uniportal than in the three-port group (p = 0.022 and p = 0.008). The postoperative 24 and 72 h numerical rating scale (NRS) scores were significantly lower in the uniportal group than in the three-port group (p < 0.001 and p < 0.001). There were no significant differences between the two groups in the number or stations of total lymph node dissected (p = 0.222 and p = 0.159). There were no significant differences between the two groups in the postoperative total or respiratory complications (p = 0.917 and p = 0.930). CONCLUSIONS: Uniportal VATS is a safe and effective alternative for patients with NSCLC. It is a preferable option for appropriate cases as it is conducive to patients' postoperative recovery and quality of life.

8.
Medicine (Baltimore) ; 100(4): e23809, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530177

RESUMO

OBJECTIVE: To evaluate the clinical and radiographic outcomes of total knee arthroplasties (TKA) between using medial-pivot (MP) and posterior-stabilized (PS) prosthesis. Does MP prosthesis and PS prosthesis influence the clinical results of a TKA? METHODS: An electronic literature search of PubMed Medline and the Cochrane Library was performed from inception to October 1, 2019. A meta-analysis to compare postoperative outcomes of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Knee Society Score (KSS), range of motion (ROM), complications, and radiographic results between MP and PS prosthesis were conducted. RESULTS: Seven eligible studies involving 934 adult patients (MP group, n = 461; PS group, n = 473) were identified for analysis. This study showed no significant difference between the 2 groups in the WOMAC scores, KSS, ROM, and complications (P > .05). The differences of the femorotibial angle, position of implant, and patellar tilt were also not significant between the 2 groups (P > .05). CONCLUSION: The present meta-analysis has shown that patients with the MP prosthesis have similar clinical results as patients with PS prosthesis. Furthermore, the radiographic results, especially patella tilt angle, were also similar between the 2 groups. Therefore, surgeons should be aware that the types of prostheses are not a decisive factor to ensure successful operation.


Assuntos
Artroplastia do Joelho/instrumentação , Prótese do Joelho , Osteoartrite do Joelho/cirurgia , Desenho de Prótese , Artroplastia do Joelho/métodos , Humanos , Joelho/diagnóstico por imagem , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/fisiopatologia , Radiografia , Amplitude de Movimento Articular , Resultado do Tratamento
9.
J Hazard Mater ; 401: 123270, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-32645543

RESUMO

The increasing use of raw carbon-based nanomaterials (CBNs) will inevitably affect wastewater treatment systems. Constructed wetlands (CWs) are ecological wastewater treatment facilities and can intercept the vast particles pollutant, including CBNs. However, the impacts of CBNs on the treatment performance of CWs have no available knowledge. Therefore, we systematically inspected the effects of single-walled and multi-walled carbon nanotubes (SWCNTs and MWCNTs) and fullerene nanoparticles (C60) on CW performance under 180-day exposure to 0, 10 and 1000 µg/L concentrations. The results showed that CBNs had marginally adverse impacts on chemical oxygen demand (COD) and total phosphorus (TP) removal, whereas nitrogen removal declined by 24.1 %-42.7 % following long-term exposure to CBNs. MWCNTs had the greatest inhibition effect on nitrogen removal, followed by SWCNTs and C60. The CBNs also induced reactive oxygen species (ROS) overproduction as the increasing concentration, which confirmed that CBNs have biotoxic effects in CWs. The variation of functional microbial community and the inhibition of enzyme activities were the dominant reasons for the decline in nitrogen removal efficiency. Furthermore, predictive functional profiling showed that CBNs affected functional gene abundance, and caused a decline in the enzymes abundance connected to nitrogen removal by the end of the 180-day exposure period.

10.
Sci Total Environ ; 762: 144168, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33360457

RESUMO

The Earth is experiencing excessive nitrogen (N) input to its various ecosystems due to human activities. How to effectively and efficiently remove N from ecosystems has been, is and will be at the center of attention in N research. Hyporheic and riparian zones are widely acknowledged for their buffering capacity to reduce contaminants (especially N) transport downstream. However, these zones are usually misunderstood that they can remove N at all spots and at any moments. Here pathways of N removal from hyporheic and riparian zones are reviewed and summarized with an emphasize on their hot spots and hot moments. N is biogeochemically removed by denitrification, anammox, nitrifier denitrification, denitrifying anaerobic methane oxidation, Feammox and Sulfammox. Hot moments of N removal are mainly triggered by precipitation, fire and snowmelt. Finally, some research needs are outlined and discussed, such as developing approaches for multiscale sampling and monitoring, quantifying the effects of hot spots and hot moments at hyporheic and riparian zones and evaluating the impacts of human activities on hot spots and hot moments, to inspire more research on hot spots and hot moments of N removal. By this review, we hope to bring awareness of the heterogeneity of hyporheic and riparian zones to catchment managers and policy makers when tackling N pollution problems.


Assuntos
Desnitrificação , Nitrogênio , Ecossistema , Humanos
11.
J Infect ; 82(2): 253-260, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33359014

RESUMO

BACKGROUND: Herpes zoster (HZ) mainly affects elderly and immunocompromised individuals and is characterized by a painful vesicular rash. Data on the epidemiology of HZ, particularly in unvaccinated individuals aged ≥50 years, are still limited in China. Thus, this study aimed to evaluate the epidemiological features, disease burden, and associated risk factors of HZ in the population aged ≥50 years in China. METHODS: We evaluated HZ patients who were aged ≥50 years between January 1, 2015 and December 31, 2017 in the electronic health record database of Yinzhou district. HZ and its complications were identified using ICD-10 codes. In addition, post-herpetic neuralgia (PHN) as a complication of HZ was defined as pain occurring or persisting 90 days after rash onset. The disease burden was estimated according to the duration of hospitalization, frequency of visits, pharmacological treatment cost, and examination cost. Cox proportional hazards regression was used to investigate the associated risk factors for HZ. RESULTS: The overall incidence of HZ was 6.64 per 1000 person-years. Of the 4,313 initial episodes from 2015 to 2017, there were 99 recurrent cases. In total, 7.26% and 3.94% of the HZ patients had PHN and other complications, respectively. The average frequency of outpatient visits was significantly lower in patients with initial disease than that in patients with recurrence (3.6 vs. 6.7 per patient). The mean duration of hospital stay was longer in the recurrent episode than that in the initial episode (24.0 vs. 21.6 days). The inpatient and outpatient cost per new-onset HZ was approximately ¥8116.9 and ¥560.2 per patient, respectively. Age; female sex; suburban residency; and presence of immunocompromised disease, hypertension, or diabetes were significantly associated with the development of HZ. CONCLUSION: The incidence and recurrence rates of HZ showed different trends with increasing age. The presence of HZ-related complications increased the direct medical costs. Our findings help provide a basis for developing appropriate strategies for HZ prevention and control.

12.
Front Oncol ; 10: 545603, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33178578

RESUMO

Background: Inconsistent findings from observational studies have reported that C-reactive protein (CRP) is likely associated with risk of prostate cancer. Because conventional observational studies are susceptible to confounding and reverse causality, it remains unclear whether there is a causal relationship of CRP with risk of prostate cancer. Methods: In this study, we applied a two-sample Mendelian randomization (MR) approach to evaluate the potential causal association of circulating CRP levels with prostate cancer risk. Instrumental variables (IVs) and corresponding genetic association estimates for circulating CRP levels were obtained from a meta-analysis of genome-wide association studies (GWASs) including 204,402 participants of European descent. The genetic association estimates of these IVs with prostate cancer were obtained from a GWAS meta-analysis including 79,148 cases and 61,106 controls of European ancestry. The inverse-variance weighted (IVW) method was used as primary MR analyses, whereas in sensitivity analyses, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO) test were used to assess the presence of pleiotropy. Odd ratio (OR) and 95% CI were calculated. Results: Overall, 58 single-nucleotide polymorphisms were used as instruments for circulating CRP levels. MR analysis suggested that genetically determined CRP levels were not associated with prostate cancer risk (OR 1.06, 95% CI 0.96 to 1.16) using the IVW method. Sensitivity analyses using alternative MR methods produced similar results (OR 1.00, 95% CI 0.93 to 1.08 for the weighted-median method; OR 1.02, 95% CI 0.95 to 1.08 for MR-PRESSO test). MR-Egger regression did not suggest evidence of directional pleiotropy (P = 0.25). Conclusion: Our study found that genetically predicted circulating CRP levels were not associated with prostate cancer risk, suggesting that CRP is unlikely to be a causal factor in the development of prostate cancer.

13.
Environ Sci Technol ; 54(21): 14007-14016, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33092338

RESUMO

Nanosized plastics (nanoplastics) releasing into the wastewater may pose a potential threat to biological nitrogen removal. Constructed wetland (CW), a wastewater treatment or shore buffer system, is an important sink of nanoplastics, while it is unclear how nitrogen removal in CWs occurs in response to nanoplastics. Here, we investigated the effects of polystyrene (PS) nanoplastics (0, 10, and 1000 µg/L) on nitrogen removal for 180 days in CWs. The results revealed that total nitrogen removal efficiency decreased by 29.5-40.6%. We found that PS penetrated the cell membrane and destroyed both membrane integrity and reactive oxygen species balance. Furthermore, PS inhibited microbial activity in vivo, including enzyme (ammonia monooxygenase, nitrate reductase, and nitrite reductase) activities and electron transport system activity (ETSA). These adverse effects, accompanied by a decline in the relative abundance of nitrifiers (e.g., Nitrosomonas and Nitrospira) and denitrifiers (e.g., Thauera and Zoogloea), directly accounted for the strong deterioration observed in nitrogen removal. The decline in leaf and root activities decreased nitrogen uptake by plants, which is an important factor of deterioration in nitrogen removal. Overall, our results imply that the presence of nanoplastics in the aquatic environment is a hidden danger to the global nitrogen cycle and should receive more attention.

14.
J Biol Chem ; 295(48): 16380-16392, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-32967968

RESUMO

Alginate lyases play important roles in alginate degradation in the ocean. Although a large number of alginate lyases have been characterized, little is yet known about those in extremely cold polar environments, which may have unique mechanisms for environmental adaptation and for alginate degradation. Here, we report the characterization of a novel PL7 alginate lyase AlyC3 from Psychromonas sp. C-3 isolated from the Arctic brown alga Laminaria, including its phylogenetic classification, catalytic properties, and structure. We propose the establishment of a new PM-specific subfamily of PL7 (subfamily 6) represented by AlyC3 based on phylogenetic analysis and enzymatic properties. Structural and biochemical analyses showed that AlyC3 is a dimer, representing the first dimeric endo-alginate lyase structure. AlyC3 is activated by NaCl and adopts a novel salt-activated mechanism; that is, salinity adjusts the enzymatic activity by affecting its aggregation states. We further solved the structure of an inactive mutant H127A/Y244A in complex with a dimannuronate molecule and proposed the catalytic process of AlyC3 based on structural and biochemical analyses. We show that Arg82 and Tyr190 at the two ends of the catalytic canyon help the positioning of the repeated units of the substrate and that His127, Tyr244, Arg78, and Gln125 mediate the catalytic reaction. Our study uncovers, for the first time, the amino acid residues for alginate positioning in an alginate lyase and demonstrates that such residues involved in alginate positioning are conserved in other alginate lyases. This study provides a better understanding of the mechanisms of alginate degradation by alginate lyases.

15.
Brain Res Bull ; 165: 305-315, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32956770

RESUMO

Bone marrow mesenchymal stem cells (BMSCs) are involved in cancer initiation and metastasis, and sometimes mediate cell communication by releasing exosomes and delivering microRNAs (miRNAs). The study aims to investigate the effects of exosomal hsa-miR-23b-3p derived from human BMSCs on intracranial aneurysm (IA). Firstly, human BMSCs-derived exosomes were extracted by ultra-high speed centrifugation. After clinical specimen collection, imbalance of T helper (Th) 17/Treg was found in patients with IA. Then, basilar artery aneurysm models were established and BMSCs-derived exosomes were isolated and identified. The results showed that BMSCs-derived exosomes improved pathological remodeling of IA wall, upregulated the contractile phenotype and inhibited the secretory phenotype of smooth muscle cells and reduced the number of Th17 cells to maintain the balance of Th17/Treg. In addition, human BMSCs-derived exosomes inhibited the activation of the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt)/nuclear factor-kappa B (NF-κB) signaling pathway and maintained Th17/Treg balance, which in turn interfered with aneurysm formation. Finally, the targeting relationship between hsa-miR-23b-3p and KLF5 was confirmed. We further noted that BMSCs-derived exosomal hsa-miR-23b-3p inhibited IA formation by targeting KLF5 through suppression of the PI3k/Akt/NF-κB signaling pathway. All in all, our study concluded that BMSCs-derived exosomal hsa-miR-23b-3p could maintain Th17/Treg balance by targeting KLF5 through suppression of the PI3k/Akt/NF-κB signaling pathway, thus inhibit IA formation.

16.
J Phys Chem A ; 124(40): 8280-8291, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-32924506

RESUMO

The kinetic data of cyclopentadiene C5H6 oxidation reactions are significant for the construction of aromatics oxidation mechanism because cyclopentadiene C5H6 has been proved to be an important intermediate in the aromatics combustion. Kinetics for the elementary reactions on the potential energy surface (PES) relevant for the C5H6 + HO2 reaction are studied in this work. Stationary points on the PES are calculated by employing the CCSD(T)/cc-pVTZ//B3LYP/6-311G(d,p) level of theory. High-pressure limit and pressure-dependent rate constants for elementary reactions on this PES are calculated using conventional transition state theory (TST), variational transition-state theory (VTST) and Rice-Ramsberger-Kassel-Marcus/master equation (RRKM/ME) theory. In this work, the reaction channels for the C5H6 + HO2 reaction, which include H-abstraction channels from C5H6 by HO2 to form the C5H5 + H2O2 and the addition channels through well-skipping pathways to form the bimolecular products C5H7 + O2 or C5H6O + OH, or through C5H7O2 stabilization and its unimolecular decomposition to form the bimolecular products C5H7 + O2 or C5H6O + OH, namely sequential pathways, are studied. Also, the consuming reaction channels for the compounds C5H6O and C5H7 in the addition products are studied. The dominant reaction channels for these reactions are unraveled through comparing the energy barriers and rate constants of all elementary reactions and it is found: (1) HO2 addition to cyclopentadiene C5H6 is more important than direct H-abstraction. (2) in the HO2 addition channels, the well-skipping pathways and sequential pathways are competing and the well-skipping pathways will be favor in the higher pressures and the sequential pathways will be favor in the higher temperature. (3) The major consumption reaction channel for the five-member-ring compound C5H6O is the reaction channel to form C4H6 + CO and the major consumption reaction channel for the five-member-ring compound C5H7 is the reaction channel to form C3H5 + C2H2. High-pressure limit rate constants and pressure-dependent rate constants for elementary reactions on the PES are calculated, which will be useful in modeling the oxidation of aromatic compounds at low- and medium-temperatures.

17.
Sensors (Basel) ; 20(15)2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32752273

RESUMO

Gaussia luciferase (GLuc) is a secreted protein with significant potential for use as a reporter of gene expression in bacterial pathogenicity studies. To date there are relatively few examples of its use in bacteriology. In this study we show that GLuc can be functionally expressed in the human pathogen Staphylococcus aureus and furthermore show that it can be used as a biosensor for the agr quorum sensing (QS) system which employs autoinducing peptides to control virulence. GLuc was linked to the P3 promoter of the S. aureusagr operon. Biosensor strains were validated by evaluation of chemical agent-mediated activation and inhibition of agr. Use of GLuc enabled quantitative assessment of agr activity. This demonstrates the utility of Gaussia luciferase for in vitro monitoring of agr activation and inhibition.

18.
Genome Biol ; 21(1): 159, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32616020

RESUMO

BACKGROUND: Despite their regional economic importance and being increasingly reared globally, the origins and evolution of the llama and alpaca remain poorly understood. Here we report reference genomes for the llama, and for the guanaco and vicuña (their putative wild progenitors), compare these with the published alpaca genome, and resequence seven individuals of all four species to better understand domestication and introgression between the llama and alpaca. RESULTS: Phylogenomic analysis confirms that the llama was domesticated from the guanaco and the alpaca from the vicuña. Introgression was much higher in the alpaca genome (36%) than the llama (5%) and could be dated close to the time of the Spanish conquest, approximately 500 years ago. Introgression patterns are at their most variable on the X-chromosome of the alpaca, featuring 53 genes known to have deleterious X-linked phenotypes in humans. Strong genome-wide introgression signatures include olfactory receptor complexes into both species, hypertension resistance into alpaca, and fleece/fiber traits into llama. Genomic signatures of domestication in the llama include male reproductive traits, while in alpaca feature fleece characteristics, olfaction-related and hypoxia adaptation traits. Expression analysis of the introgressed region that is syntenic to human HSA4q21, a gene cluster previously associated with hypertension in humans under hypoxic conditions, shows a previously undocumented role for PRDM8 downregulation as a potential transcriptional regulation mechanism, analogous to that previously reported at high altitude for hypoxia-inducible factor 1α. CONCLUSIONS: The unprecedented introgression signatures within both domestic camelid genomes may reflect post-conquest changes in agriculture and the breakdown of traditional management practices.

19.
Nucleic Acids Res ; 48(16): 9109-9123, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32729622

RESUMO

Nuclear factor erythroid 2-related factor 2 (NRF2) is a well-characterized transcription factor that protects cells against oxidative and electrophilic stresses. Emerging evidence has suggested that NRF2 protects cells against DNA damage by mechanisms other than antioxidation, yet the mechanism remains poorly understood. Here, we demonstrate that knockout of NRF2 in cells results in hypersensitivity to ionizing radiation (IR) in the presence or absence of reactive oxygen species (ROS). Under ROS scavenging conditions, induction of DNA double-strand breaks (DSBs) increases the NRF2 protein level and recruits NRF2 to DNA damage sites where it interacts with ATR, resulting in activation of the ATR-CHK1-CDC2 signaling pathway. In turn, this leads to G2 cell cycle arrest and the promotion of homologous recombination repair of DSBs, thereby preserving genome stability. The inhibition of NRF2 by brusatol increased the radiosensitivity of tumor cells in xenografts by perturbing ATR and CHK1 activation. Collectively, our results reveal a novel function of NRF2 as an ATR activator in the regulation of the cellular response to DSBs. This shift in perspective should help furnish a more complete understanding of the function of NRF2 and the DNA damage response.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Fator 2 Relacionado a NF-E2/genética , Reparo de DNA por Recombinação/genética , Células A549 , Animais , Proteína Quinase CDC2/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Quinase 1 do Ponto de Checagem/genética , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Técnicas de Inativação de Genes , Xenoenxertos , Humanos , Camundongos , Quassinas/farmacologia , Tolerância a Radiação/efeitos dos fármacos , Radiação Ionizante , Reparo de DNA por Recombinação/efeitos dos fármacos , Reparo de DNA por Recombinação/efeitos da radiação , Transdução de Sinais/efeitos dos fármacos
20.
PLoS Med ; 17(7): e1003202, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32702001

RESUMO

BACKGROUND: Efforts to reduce unnecessary antibiotic prescribing have coincided with increasing awareness of sepsis. We aimed to estimate the probability of sepsis following infection consultations in primary care when antibiotics were or were not prescribed. METHODS AND FINDINGS: We conducted a cohort study including all registered patients at 706 general practices in the United Kingdom Clinical Practice Research Datalink, with 66.2 million person-years of follow-up from 2002 to 2017. There were 35,244 first episodes of sepsis (17,886, 51%, female; median age 71 years, interquartile range 57-82 years). Consultations for respiratory tract infection (RTI), skin or urinary tract infection (UTI), and antibiotic prescriptions were exposures. A Bayesian decision tree was used to estimate the probability (95% uncertainty intervals [UIs]) of sepsis following an infection consultation. Age, gender, and frailty were evaluated as association modifiers. The probability of sepsis was lower if an antibiotic was prescribed, but the number of antibiotic prescriptions required to prevent one episode of sepsis (number needed to treat [NNT]) decreased with age. At 0-4 years old, the NNT was 29,773 (95% UI 18,458-71,091) in boys and 27,014 (16,739-65,709) in girls; over 85 years old, NNT was 262 (236-293) in men and 385 (352-421) in women. Frailty was associated with greater risk of sepsis and lower NNT. For severely frail patients aged 55-64 years, the NNT was 247 (156-459) in men and 343 (234-556) in women. At all ages, the probability of sepsis was greatest for UTI, followed by skin infection, followed by RTI. At 65-74 years, the NNT following RTI was 1,257 (1,112-1,434) in men and 2,278 (1,966-2,686) in women; the NNT following skin infection was 503 (398-646) in men and 784 (602-1,051) in women; following UTI, the NNT was 121 (102-145) in men and 284 (241-342) in women. NNT values were generally smaller for the period from 2014 to 2017, when sepsis was diagnosed more frequently. Lack of random allocation to antibiotic therapy might have biased estimates; patients may sometimes experience sepsis or receive antibiotic prescriptions without these being recorded in primary care; recording of sepsis has increased over the study period. CONCLUSIONS: These stratified estimates of risk help to identify groups in which antibiotic prescribing may be more safely reduced. Risks of sepsis and benefits of antibiotics are more substantial among older adults, persons with more advanced frailty, or following UTIs.


Assuntos
Infecções/complicações , Sepse/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Prescrições de Medicamentos , Feminino , Idoso Fragilizado , Fragilidade , Humanos , Lactente , Recém-Nascido , Infecções/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Atenção Primária à Saúde , Probabilidade , Encaminhamento e Consulta , Infecções Respiratórias/complicações , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/epidemiologia , Reino Unido/epidemiologia , Infecções Urinárias/complicações , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...