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1.
Artigo em Inglês | MEDLINE | ID: mdl-32051251

RESUMO

Integration of electroactive bacteria into electrodes combines strengths of intracellular biochemistry with electrochemistry for energy conversion and chemical synthesis. However, such biohybrid systems are often plagued with suboptimal electrodes, which limits the incorporation and productivity of the bacterial colony. Here, we show that an inverse opal-indium tin oxide electrode hosts a large population of current-producing Geobacter and attains a current density of 3 mA cm-2 stemming from bacterial respiration. Differential gene expression analysis revealed Geobacter's transcriptional regulations to express more electron-relaying proteins when interfaced with electrodes. The electrode also allows coculturing with Shewanella for syntrophic electrogenesis, which grants the system additional flexibility in converting electron donors. The biohybrid electrode containing Geobacter can also catalyze the reduction of soluble fumarate and heterogenous graphene oxide, with electrons from an external power source or an irradiated photoanode. This biohybrid electrode represents a platform to employ live cells for sustainable power generation and biosynthesis.

2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(2): 159-161, 2020 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-32034745

RESUMO

OBJECTIVE: To analyze INS gene variant in a patient with maturity-onset diabetes of the young type 10. METHODS: High-throughput sequencing was used to screen for the variants. Suspected variant was verified by Sanger sequencing. RESULTS: Genetic testing indicated that the patient and his mother have both carried a heterozygous c.130G>A (p.Gly44Arg) variant in exon 1 of the INS gene. Prediction of protein structure suggested the variant to be pathogenic. CONCLUSION: The c.130G>A (p.Gly44Arg) variant of the INS gene probably underlies the disease in this patient.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32015109

RESUMO

High levels of ultrafine particles (UFPs; diameter of less than 50 nm) are frequently produced from new particle formation under urban conditions, with profound implications on human health, weather, and climate. However, the fundamental mechanisms of new particle formation remain elusive, and few experimental studies have realistically replicated the relevant atmospheric conditions. Previous experimental studies simulated oxidation of one compound or a mixture of a few compounds, and extrapolation of the laboratory results to chemically complex air was uncertain. Here, we show striking formation of UFPs in urban air from combining ambient and chamber measurements. By capturing the ambient conditions (i.e., temperature, relative humidity, sunlight, and the types and abundances of chemical species), we elucidate the roles of existing particles, photochemistry, and synergy of multipollutants in new particle formation. Aerosol nucleation in urban air is limited by existing particles but negligibly by nitrogen oxides. Photooxidation of vehicular exhaust yields abundant precursors, and organics, rather than sulfuric acid or base species, dominate formation of UFPs under urban conditions. Recognition of this source of UFPs is essential to assessing their impacts and developing mitigation policies. Our results imply that reduction of primary particles or removal of existing particles without simultaneously limiting organics from automobile emissions is ineffective and can even exacerbate this problem.

5.
Nat Chem Biol ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932723

RESUMO

In plants, lineage-specific metabolites can be created by activities derived from the catalytic promiscuity of ancestral proteins, although examples of recruiting detoxification systems to biosynthetic pathways are scarce. The ubiquitous glyoxalase (GLX) system scavenges the cytotoxic methylglyoxal, in which GLXI isomerizes the α-hydroxy carbonyl in the methylglyoxal-glutathione adduct for subsequent hydrolysis. We show that GLXIs across kingdoms are more promiscuous than recognized previously and can act as aromatases without cofactors. In cotton, a specialized GLXI variant, SPG, has lost its GSH-binding sites and organelle-targeting signal, and evolved to aromatize cyclic sesquiterpenes bearing α-hydroxyketones to synthesize defense compounds in the cytosol. Notably, SPG is able to transform acetylated deoxynivalenol, the prevalent mycotoxin contaminating cereals and foods. We propose that detoxification enzymes are a valuable source of new catalytic functions and SPG, a standalone enzyme catalyzing complex reactions, has potential for toxin degradation, crop engineering and design of novel aromatics.

7.
Br J Pharmacol ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31976546

RESUMO

BACKGROUND AND PURPOSE: Despite recent advances in understanding its pathophysiology, treatment of acute kidney injury (AKI) remains a major unmet medical need, and novel therapeutic strategies are needed. Cathelicidin-related antimicrobial peptide (CRAMP) with immunomodulatory properties has an emerging role in various disease contexts. Here, we aimed to investigate the role of CRAMP and its underlying mechanisms in AKI. EXPERIMENTAL APPROACH: The human homologue LL-37 and CRAMP were measured in blood samples of AKI patients and in experimental AKI mice respectively. Experimental AKI was induced in wild-type and CRAMP-deficient (Cnlp-/- ) mice by ischaemia/reperfusion (I/R). Therapeutic evaluation of CRAMP was performed with exogenous CRAMP (5 mg·kg-1 , i.p.) treatment. KEY RESULTS: Cathelicidin expression was inversely related to clinical signs in patients and down-regulated in renal I/R-induced injury in mice. Cnlp-/- mice exhibited exacerbated I/R-induced renal dysfunction, aggravated inflammatory responses and apoptosis. Moreover, over-activation of the NLRP3 inflammasome in Cnlp-/- mice was associated with I/R-induced renal injury. Exogenous CRAMP treatment markedly attenuated I/R-induced renal dysfunction, inflammatory response and apoptosis, correlated with modulation of immune cell infiltration and phenotype. Consistent with Cnlp-/- mouse data, CRAMP administration suppressed renal I/R-induced NLRP3 inflammasome activation, and its renal protective effects were mimicked by a specific NLRP3 inhibitor CY-09. The reno-protective and NLRP3 inhibitory effects of CRAMP required the EGF receptor. CONCLUSION AND IMPLICATIONS: Our results suggest that CRAMP acts as a novel immunomodulatory mediator of AKI and modulation of CRAMP may represent a potential therapeutic strategy.

8.
Sci Total Environ ; 710: 135755, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-31918183

RESUMO

Satellite-based mapping has been proven to be an effective method to reveal the spatiotemporal variations of PM2.5 distributions. However, most satellite AOD (aerosol optical depth) statistical models suffer from unstable accuracy over long time spans. This study thus aims to propose an accurate and stable method for PM2.5 concentration estimations in time series. Specifically, a three-step residual variance constraint method (RVCM) is developed to simulate PM2.5 concentrations from January 2013 to December 2017 with the aid of AODs and other auxiliary data. Results show that the five-year fitting R2 and cross-validation R2 of RVCMs improved from 0.77 to 0.88 and 0.71 to 0.84, respectively, compared to those models without residual variance constraint (WO-RVCM). Additionally, RVCM demonstrated more stable performance on time series simulation of PM2.5 concentrations than WO-RVCM, with the yearly fitting R2 of 0.89, 0.88, 0.85, 0.87 and 0.88, and corresponding cross validation R2 of 0.85, 0.84, 0.80, 0.82 and 0.83, respectively. Furthermore, accuracy verification of removed outliers in residual variance constraint modeling confirmed the credibility of RVCM in outliers' simulation compared to WO-RVCM models. Finally, RVCM-aided estimations of time series PM2.5 concentrations and associated premature deaths in the study area (east and southeast mainland China) revealed their total decrease rates were 35.21% and 21.57%, and excellent air quality days increased from 7% to 35%. These findings suggest that residual variance constraint is effective and could be a reliable solution to providing time series AOD-PM2.5 modeling with stable accuracy over long time spans.

9.
J Diabetes Complications ; 34(1): 107468, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31761418

RESUMO

AIMS: To investigate the effect of multifactorial intervention on the urinary albumin to creatinine ratio (UACR) and the estimated glomerular filtration rate (eGFR) in short-duration type 2 diabetes. METHODS: A total of 150 type 2 diabetes patients, with disease duration <1 year and with no evidence of atherosclerosis were randomized to either the intensive intervention group (IG, n = 75), or the conventional group (CG, n = 75) for 7 years. The predefined endpoint of microvascular complications was the progression of renal impairments (the development of albuminuria and the change of eGFR). RESULTS: The incidence of progression to albuminuria (UACR ≥30 mg/g) was 12% in IG and 28% in CG (HR 0.37, 95% CI: 0.19-0.70, P = .0025). eGFR was significantly lower in IG than that in CG in the year 2 (P = .043) and 3 (P = .032) follow-up. Sex, fasting plasma glucose (FPG), HbA1c, and systolic blood pressure (SBP) were independently associated with the UACR (ß = -5.112, P = .015; ß = 0.908, P = .045; ß = 2.087, P = .038; and ß = 2.787, P = .002, respectively); aging was independently associated with eGFR (ß = -0.447, P = .000). CONCLUSIONS: Intensive multifactorial intervention delayed the progression to albuminuria, and reduced eGFR rapidly in early stage of intervention in short-duration type 2 diabetes. FPG, HbA1c, and SBP were risk factors for UACR increase; aging was a risk factor for eGFR decline.

11.
Brain Res ; 1727: 146511, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31672472

RESUMO

Isoflurane anesthesia is reported to induce insulin resistance (IR) in the peripheral tissues. However, researches on the impact of isoflurane on insulin-related metabolism in the central nervous system, especially in type 2 diabetes mellitus (T2DM), are scarce. This study sought to explore whether isoflurane anesthesia had a negative effect on insulin sensitivity both in peripheral and central tissues. Moreover, the possible role of isoflurane anesthesia in T2DM mice with pre-existing IR was analyzed. T2DM model in C57BL/6J mice was established by high fat diet (HFD) and single intraperitoneal injection of streptozotocin (STZ, 60 mg/kg). Both HFD/STZ-induced T2DM mice and normal mice received 6 h isoflurane exposure. Blood glucose level and serum insulin concentration were detected and the homeostasis model assessment of IR (HOMA-IR) index was calculated to estimate peripheral IR. Relative levels of genes and proteins in the insulin-dependent signaling pathway in mouse prefrontal cortex and hippocampus were determined to measure central IR. Results indicated that 6 h isoflurane exposure induced hyperglycemia, hyperinsulinemia and raised HOMA-IR index. Meanwhile, phosphorylated insulin receptor substrate-1 (pIRS1) (Ser639) and phosphorylated insulin receptor substrate-2 (pIRS2) (Ser731) were upregulated, while phosphorylated protein kinase B (pAKT) (Ser473) and phosphorylated glycogen synthase kinase-3 beta (pGSK3ß) (Ser9) were downregulated in the prefrontal cortex and hippocampus of anesthetized mice. Notably, isoflurane anesthesia significantly aggravated the degree of central IR in the aspects of gene transcriptions and protein expressions in HFD/STZ-induced T2DM mice with pre-existing IR. This study suggested that isoflurane anesthesia induced peripheral and central IR and aggravated pre-existing insulin resistance in T2DM mice.

12.
Ann Surg ; 271(1): 140-146, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30048321

RESUMO

OBJECTIVE: To ascertain whether regular ß-blocker exposure can improve short- and long-term outcomes after rectal cancer surgery. BACKGROUND: Surgery for rectal cancer is associated with substantial morbidity and mortality. There is increasing evidence to suggest that there is a survival benefit in patients exposed to ß-blockers undergoing non-cardiac surgery. Studies investigating the effects on outcomes in patients subjected to surgery for rectal cancer are lacking. METHODS: All adult patients undergoing elective abdominal resection for rectal cancer over a 10-year period were recruited from the prospectively collected Swedish Colorectal Cancer Registry. Patients were subdivided according to preoperative ß-blocker exposure status. Outcomes of interest were 30-day complications, 30-day cause-specific mortality, and 1-year all-cause mortality. The association between ß-blocker use and outcomes were analyzed using Poisson regression model with robust standard errors for 30-day complications and cause-specific mortality. One-year survival was assessed using Cox proportional hazards regression model. RESULTS: A total of 11,966 patients were included in the current study, of whom 3513 (29.36%) were exposed to regular preoperative ß-blockers. A significant decrease in 30-day mortality was detected (incidence rate ratio = 0.06, 95% confidence interval: 0.03-0.13, P < 0.001). Deaths of cardiovascular nature, respiratory origin, sepsis, and multiorgan failure were significantly lower in ß-blocker users, as were the incidences in postoperative infection and anastomotic failure. The ß-blocker positive group had significantly better survival up to 1 year postoperatively with a risk reduction of 57% (hazard ratio = 0.43, 95% confidence interval: 0.37-0.52, P < 0.001). CONCLUSIONS: Preoperative ß-blocker use is strongly associated with improved survival and morbidity after abdominal resection for rectal cancer.

13.
Crit Rev Food Sci Nutr ; 60(4): 684-694, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30570346

RESUMO

Current evidence on selenium and its effects on cancer is conflicting. This study aimed at assessing the association between dietary intake of selenium and incidence of cancers by performing systematic review and meta-analysis of population-based prospective studies. We systematically searched for articles in Medline (Ovid), Embase, Web of Science (Thomson Reuters), China National Knowledge Infrastructure, Wanfang Database and VIP Chinese Scientific Journals. Analysis was performed in Stata version 14.2. Of the 2,564 articles obtained from the databases, 39 met our inclusion criteria, 37 were included in the final analysis. Selenium at recommended daily allowance levels of ≥55 µg/day decreased the risk of cancer [relative risk (RR) = 0.94, 95% confidence interval (CI): 0.90-0.98]. A protective effect was found in men at levels ≥55 µg/day (RR = 0.97, 95% CI: 0.94-0.99). Extra selenium intake from supplements was protective at levels ≥55 µg/day (RR = 0.89, 95% CI: 0.82-0.97). There was an inverse relationship (p value = 0.020) between selenium intake and overall cancer risk after adjusting for age, body mass index, and smoking but there was no evidence of nonlinear relationship (p value = 0.261). The findings in this study suggest that selenium is protective against cancer however the effects vary with different cancers.

14.
Nat Protoc ; 15(1): 1-14, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31863076

RESUMO

Genome-scale models (GEMs) of bacterial strains' metabolism have been formulated and used over the past 20 years. Recently, with the number of genome sequences exponentially increasing, multi-strain GEMs have proved valuable to define the properties of a species. Here, through four major stages, we extend the original Protocol used to generate a GEM for a single strain to enable multi-strain GEMs: (i) obtain or generate a high-quality model of a reference strain; (ii) compare the genome sequence between a reference strain and target strains to generate a homology matrix; (iii) generate draft strain-specific models from the homology matrix; and (iv) manually curate draft models. These multi-strain GEMs can be used to study pan-metabolic capabilities and strain-specific differences across a species, thus providing insights into its range of lifestyles. Unlike the original Protocol, this procedure is scalable and can be partly automated with the Supplementary Jupyter notebook Tutorial. This Protocol Extension joins the ranks of other comparable methods for generating models such as CarveMe and KBase. This extension of the original Protocol takes on the order of weeks to multiple months to complete depending on the availability of a suitable reference model.

15.
Indoor Air ; 30(1): 126-136, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31797459

RESUMO

Cooking is one of the main sources of indoor air pollution in China. Given emerging evidence of a link between air pollutants and neurodevelopmental delays, we examined whether maternal experiences with cooking during gestation might increase their child's hyperactivity at 3 years of age. The participants involved 45 518 mothers of children who were newly enrolled at kindergarten in the Longhua District of Shenzhen from 2015 to 2017. The results show that maternal exposure to cooking fumes during pregnancy was related to an increased risk of their offspring having hyperactivity behaviors at the age of 3 years. Compared with pregnant mothers who never cooked, pregnant mothers who cooked sometimes, often, or always had children who showed a significantly higher hyperactivity risk. Households using cooking fuels such as coal, gas during the mothers' pregnancy, exhibited more hyperactivity behaviors in the young child when compared to those using electricity for cooking. In addition, poor ventilation during cooking, while mothers were pregnant, was found to be a significant risk factor for clinical levels of the offspring's hyperactive behaviors. Furthermore, the positive association with maternal cooking during pregnancy and their offsprings' hyperactivity was relatively consistent across strata defined by social class, education, and other covariates.

16.
Behav Brain Res ; 379: 112320, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31669345

RESUMO

There is a serious need for fast-acting drugs to treat post-traumatic stress disorder (PTSD). Our previous studies revealed that YL-IPA08, a novel small-molecule TSPO agonist, exerted significant anti-PTSD effects in various animal models. However, the onset time of YL-IPA08 and its underlying mechanisms remain unclear. In the present study, we first investigated the time course of YL-IPA08 compared to selective serotonin reuptake inhibitors (SSRIs) in the well-known time-dependent sensitization model of PTSD. YL-IPA08 required only 2-4 days of treatment to take effect in behavioural models of PTSD, whereas sertraline required 7-8 days. Furthermore, the mechanism study revealed that YL-IPA08 elicited anti-PTSD-like effects associated with increased GABA levels and allopregnanolone efflux in the hippocampus and prefrontal cortex and increased corticosterone levels in the serum after only 5 days of treatment, whereas sertraline required 9 days. Our results demonstrate that YL-IPA08 can exert fast-onset anti-PTSD-like effects, and its mechanisms may be related to the increased GABA levels, allopregnanolone efflux and the hypothalamic-pituitary-adrenal (HPA) axis function.

17.
Am J Trop Med Hyg ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31802738

RESUMO

Infection with Strongyloides stercoralis can cause life-threatening disease in immunocompromised patients. Strongyloidiasis is thought to be hyper-endemic in tropical Australia, but there are limited contemporary seroprevalence data to inform local elimination strategies. To define the temporospatial epidemiology of strongyloidiasis in Far North Queensland, tropical Australia, the serology results of 2,429 individuals tested for the infection between 2000 and 2018 were examined. The proportion of positive tests fell from 36/69 (52.2%) in 2000 to 18/222 (8.1%) in 2018 (P < 0.001). Indigenous patients were more likely to have a positive result (Odds Ratio [OR]: 3.9, 95% CI: 3.0-5.0); however, by the end of the study period, residence in a rural or remote location (OR 3.9 (95% CI: 1.2-13.0), P = 0.03) was a more important risk factor for seropositivity than Indigenous status (OR 1.1 (95% CI: 0.4-3.1) P = 0.91). Ivermectin prescription data were available for the period 2004-2018, with annual prescriptions increasing from 100 to 185 boxes (P = 0.01). The volume of ivermectin dispensed correlated negatively with seropositivity (Spearman's rho = -0.62, P = 0.02). An expanded environmental health program was implemented during the study period and likely contributed to the declining seroprevalence; however, the relative contributions of the individual components of this program are difficult to quantify. The seroprevalence of strongyloidiasis has declined markedly in this region of tropical Australia despite there being no targeted campaign to address the disease. Expanded prescription of ivermectin and public health interventions targeting the few remaining high-prevalence communities would be expected to expedite disease elimination.

18.
PLoS Comput Biol ; 15(12): e1007525, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31809503

RESUMO

Response to acid stress is critical for Escherichia coli to successfully complete its life-cycle by passing through the stomach to colonize the digestive tract. To develop a fundamental understanding of this response, we established a molecular mechanistic description of acid stress mitigation responses in E. coli and integrated them with a genome-scale model of its metabolism and macromolecular expression (ME-model). We considered three known mechanisms of acid stress mitigation: 1) change in membrane lipid fatty acid composition, 2) change in periplasmic protein stability over external pH and periplasmic chaperone protection mechanisms, and 3) change in the activities of membrane proteins. After integrating these mechanisms into an established ME-model, we could simulate their responses in the context of other cellular processes. We validated these simulations using RNA sequencing data obtained from five E. coli strains grown under external pH ranging from 5.5 to 7.0. We found: i) that for the differentially expressed genes accounted for in the ME-model, 80% of the upregulated genes were correctly predicted by the ME-model, and ii) that these genes are mainly involved in translation processes (45% of genes), membrane proteins and related processes (18% of genes), amino acid metabolism (12% of genes), and cofactor and prosthetic group biosynthesis (8% of genes). We also demonstrated several intervention strategies on acid tolerance that can be simulated by the ME-model. We thus established a quantitative framework that describes, on a genome-scale, the acid stress mitigation response of E. coli that has both scientific and practical uses.

19.
Small ; 15(52): e1905903, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31769588

RESUMO

Metal anodes, such as zinc and bismuth have been regarded as ideal materials for aqueous batteries due to high gravimetrical capacity, high abundance, low toxicity, and intrinsic safety. However, their translation into practical applications are hindered by the low mass loading (≈1 mg cm-2 ) of active materials. Here, the multiscale integrated structural engineering of 3D scaffold and active material, i.e., bismuth is in situ intercalated in reduced graphene oxide (rGO) wall of network, are reported. Tailoring the rapid charge transport on rGO 3D network and facile access to nano- and microscale bismuth, the rGO/Bi hybrid anode shows high utilization efficiency of 91.4% at effective high load density of ≈40 mg cm-2 , high areal capacity of 3.51 mAh cm-2 at the current density of 2 mA cm-2 and high reversibility of >10 000 cycles. The resulting Ni-Bi full battery exhibits high areal capacity of 3.13 mAh cm-2 at the current density of 2 mA cm-2 , far outperforming the other counterpart batteries. It represents a general and efficient strategy in enhancing the battery performance by designing hierarchically networked structure.

20.
J Asian Nat Prod Res ; : 1-12, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31755304

RESUMO

As part of our continuing efforts to discover structurally interesting bioactive phthalide derivatives, 23 of them with a structure incorporating thiophen or halogens were designed and synthesized, 17 of which are previously unreported. In vitro antiplatelet aggregation activity screening showed that 14b could significantly inhibit platelet aggregation induced by arachidonic acid, compared with edaravone (p < 0.01). Meanwhile, oxidative damage models using SH-SY5Y and PC12 cells induced by H2O2 were built to evaluate the antioxidant activity of the phthalide derivatives. In SH-SY5Y cells, compared with aspirin, 1a significantly increased the relative cell survival rate (p < 0.05). Compared with edaravone, 1a (p < 0.01) and 15b (p < 0.05) significantly increased the relative cell survival rate. In PC12 cells, 1a (p < 0.01), 15b (p < 0.01), and 12a (p < 0.05) remarkably increased the cell survival rate compared with edaravone. The present study identified lead structures to develop potential anti-ischemic stroke agents.

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