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1.
Toxics ; 12(5)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38787101

RESUMO

To explore the contamination status and identify the source of the heavy metals in the sediments in the major inflow rivers of Dianchi Lake in China, sediment samples were collected and analyzed. Specifically, the distribution, source, water quality, and health risk assessment of the heavy metals were analyzed using correlation analysis (CA), principal component analysis (PCA), the heavy metal contamination factor (Cf), the pollution load index (PLI), and the potential ecological risk index (PERI). Additionally, the chemical fractions were analyzed for mobility characteristics. The results indicate that the average concentration of the heavy metals in the sediment ranked in the descending order of Zn > Cr > Cu > Pb > As > Ni > Cd > Hg, and most of the elements existed in less-mobile forms. The Cfwas in the order of Hg > Zn > Cd > As > Pb > Cr > Ni; the accumulation of Hg, Zn, Cd, and As was obvious. Although the spatial variability of the heavy metal contents was pronounced, the synthetical evaluation index of the PLI and PERI both reached a high pollution level. The PCA and CA results indicate that industrial, transportation, and agricultural emissions were the dominant factors causing heavy metal pollution. These results provide important data for improving water resource management efficiency and heavy metal pollution prevention in Dianchi Lake.

2.
Clin Microbiol Infect ; 30(7): 911-916, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38341143

RESUMO

OBJECTIVES: To investigate the short-term and long-term effectiveness of different levels of financial incentives on increasing the willingness to vaccinate and vaccine uptake. METHODS: A randomized controlled trial was conducted to investigate the effectiveness of financial incentives of three groups with monetary incentives (CNY 20, CNY 40, and CNY 60; 1 CNY = 0.13 EUR) vs. a control group-CNY 0-on influenza vaccine uptake among 720 older adults (≥60 years) in Beijing, China. The primary outcome was vaccine uptake, and the secondary outcomes were intention to vaccinate and length of time to immunization. RESULTS: Financial incentive significantly promoted higher intention to influenza vaccination (120/178 [67.42%] vs. 442/542 [81.55%]; Relative Risk [RR], 1.21; 95% CI, 1.02-1.42) and higher vaccination participation (74/178 [41.57%] vs. 316/542 [58.30%]; RR, 1.39; 95% CI, 1.10-1.75). CNY 60 had the largest impact on the intention to vaccinate (15.00% vs. 13.48% and 13.90%) and vaccination uptake (19.42% vs. 14.05% and 16.67%) compared with CNY 20 and CNY 40. Time to vaccination was significantly lower among participants receiving incentives than those without ([37.21 days; 95% CI, 34.33-39.99] vs. [48.27 days; 95% CI, 43.47-53.07]; Hazard Ratio [HR] 1.57, 95% CI 1.22-2.03). We found no long-term influence of financial incentives on vaccination decisions in the following year (217/542, 40.04% vs. 65/178, 36.52%; RR 1.08, 95% CI 0.82-1.42). DISCUSSION: Our study suggests that modest financial incentives will boost short-term influenza vaccination rates and shorten the length of time to immunization in China. No one single-time financial incentive had a long-term effect on future vaccination behaviours or helped establish regular vaccination behaviours.


Assuntos
Vacinas contra Influenza , Influenza Humana , Motivação , Vacinação , Humanos , Masculino , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/economia , Feminino , Influenza Humana/prevenção & controle , Influenza Humana/economia , Idoso , Vacinação/economia , Vacinação/estatística & dados numéricos , Vacinação/psicologia , China , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Idoso de 80 Anos ou mais , Intenção
3.
Res Sq ; 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37577579

RESUMO

In the context of the Critical Assessment of the Genome Interpretation, 6th edition (CAGI6), the Genetics of Neurodevelopmental Disorders Lab in Padua proposed a new ID-challenge to give the opportunity of developing computational methods for predicting patient's phenotype and the causal variants. Eight research teams and 30 models had access to the phenotype details and real genetic data, based on the sequences of 74 genes (VCF format) in 415 pediatric patients affected by Neurodevelopmental Disorders (NDDs). NDDs are clinically and genetically heterogeneous conditions, with onset in infant age. In this study we evaluate the ability and accuracy of computational methods to predict comorbid phenotypes based on clinical features described in each patient and causal variants. Finally, we asked to develop a method to find new possible genetic causes for patients without a genetic diagnosis. As already done for the CAGI5, seven clinical features (ID, ASD, ataxia, epilepsy, microcephaly, macrocephaly, hypotonia), and variants (causative, putative pathogenic and contributing factors) were provided. Considering the overall clinical manifestation of our cohort, we give out the variant data and phenotypic traits of the 150 patients from CAGI5 ID-Challenge as training and validation for the prediction methods development.

4.
Front Cardiovasc Med ; 10: 1102754, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37215555

RESUMO

Background: It has been well acknowledged that disordered intestinal microflora and their fermented products play crucial role during the development of hypertension (HTN). Aberrant profiles of fecal bacteria have been documented in subjects with isolated systolic HTN (ISH) and isolated diastolic HTN (IDH) previously. Nevertheless, evidence regarding the association of metabolic products in the bloodstream with ISH, IDH and combined systolic and diastolic HTN (SDH) remains scarce. Methods: We performed a cross-sectional study and conducted untargeted liquid chromatography-mass spectrometry (LC/MS) analysis on serum samples of 119 participants, including 13 subjects with normotension (SBP < 120/DBP < 80 mm Hg), 11 individuals with ISH (SBP ≥ 130/DBP < 80 mm Hg), 27 patients with IDH (SBP < 130/DBP ≥ 80 mm Hg), and 68 SDH patients (SBP ≥ 130, DBP ≥ 80 mm Hg). Results: Here, the results showed clearly separated clusters in PLS-DA and OPLS-DA score plots for patients suffering from ISH, IDH and SDH when compared with normotension controls. The ISH group was characterized by elevated levels of 3,5-tetradecadien carnitine and notable reduction of maleic acid. While IDH patients were enriched with metabolites in L-lactic acid and depleted in citric acid. Stearoylcarnitine was identified to be specifically enriched in SDH group. The differentially abundant metabolites between ISH and controls were involved in tyrosine metabolism pathways, and in biosynthesis of phenylalanine for those between SDH and controls. Potential linkages between the gut microbial and serum metabolic signatures were detected within ISH, IDH and SDH groups. Furthermore, we found the association of discriminatory metabolites with the characteristics of patients. Conclusion: Our findings demonstrate disparate blood metabolomics signatures across ISH, IDH and SDH, with differentially enriched metabolites and potential functional pathways identified, reveal the underlying microbiome and metabolome network in HTN subtypes, and provide potential targets for disease classification and therapeutic strategy in clinical practice.

5.
Genome Biol ; 24(1): 79, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37072822

RESUMO

A promising alternative to comprehensively performing genomics experiments is to, instead, perform a subset of experiments and use computational methods to impute the remainder. However, identifying the best imputation methods and what measures meaningfully evaluate performance are open questions. We address these questions by comprehensively analyzing 23 methods from the ENCODE Imputation Challenge. We find that imputation evaluations are challenging and confounded by distributional shifts from differences in data collection and processing over time, the amount of available data, and redundancy among performance measures. Our analyses suggest simple steps for overcoming these issues and promising directions for more robust research.


Assuntos
Algoritmos , Epigenômica , Genômica/métodos
6.
Diabetes Ther ; 14(1): 93-107, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36414806

RESUMO

OBJECTIVE: This study aimed to evaluate the long-term cost-effectiveness of once-weekly subcutaneous semaglutide versus polyethylene glycol loxenatide (PEG-loxenatide) in patients with type 2 diabetes uncontrolled on metformin, from a Chinese healthcare systems perspective. METHODS: The study applied the Swedish Institute of Health Economics Diabetes Cohort Model to evaluate the long-term clinical and economic outcomes of once-weekly treatment of semaglutide at 0.5 mg and 1.0 mg, respectively, versus PEG-loxenatide 0.2 mg, over a 40-year time horizon. Baseline cohort characteristics were collected from the SUSTAIN China trial. A network meta-analysis was conducted to obtain comparative treatment effects of once-weekly semaglutide and PEG-loxenatide based on two phase 3a clinical trials. Drug costs were sourced from the national bidding price of China. Outcomes were discounted at 5.0% per annum. One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to assess the uncertainty of the base-case results. RESULTS: When compared with PEG-loxenatide 0.2 mg, the projections of outcomes over the 40-year time horizon in patients with type 2 diabetes uncontrolled on metformin showed that treatment with once-weekly semaglutide 0.5 mg and 1.0 mg were associated with improved discounted life expectancy by 0.08 and 0.12 years, and improved discounted quality-adjusted life expectancy by 0.16 and 0.22 quality-adjusted life-years, respectively. Once-weekly semaglutide 0.5 mg and 1.0 mg were achieved at lifetime cost savings of 19,309 China Yuan (CNY) and 10,179 CNY, respectively. Sensitivity analyses verified the robustness of the results. CONCLUSION: From the perspective of Chinese healthcare systems, treatment with once-weekly subcutaneous semaglutide represents a dominant option versus PEG-loxenatide for patients with type 2 diabetes uncontrolled on metformin.

7.
Int J Biol Macromol ; 225: 255-265, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36334636

RESUMO

This study performed a comprehensive investigation of Hyperici Perforati Herba polysaccharide (HPHP) regarding the development and optimization of extraction methods, elucidation of structure and characteristics, and determination of antioxidant activities. An ultrasonic-assisted extraction method, which offered advantages in terms of the extraction yield and energy efficiency, was developed by response surface analysis. The following optimum conditions were determined: a crushing degree at 65 mesh, ultrasonic time at 50 min and temperature of 43 °C. Through enzyme-mediated deproteination via the Sevag method, activated carbon depigmentation, and DEAE-52 and Sephadex G-100 column elution, three HPHPs were obtained, and their monosaccharides mainly included mannose, galactose, glucose and arabinose. The molar weights were 8.347, 1.199 and 22.426 kDa, respectively. The HPHP structures were an amorphous aggregate of spherical-like shapes with a rough surface of pores and crevices, which presented characteristic Fourier transform infrared (FT-IR) and nuclear magnetic resonance (NMR) spectra of polysaccharides. Their main glucosidic linkage is the α-type configuration. Moreover, HPHPs exhibited strong scavenging activity for DPPH·, ABTS·+, OH· and O2·- radicals; good ferric reducing power; and effective protection against oxidative damage in human cells. Overall, the results of this work underpinned a fundamental understanding of HPHPs, thus providing a potential antioxidant for further research and development.


Assuntos
Antineoplásicos , Antioxidantes , Humanos , Antioxidantes/farmacologia , Antioxidantes/química , Ultrassom , Espectroscopia de Infravermelho com Transformada de Fourier , Polissacarídeos/farmacologia , Polissacarídeos/química
8.
Artigo em Inglês | MEDLINE | ID: mdl-36554630

RESUMO

Tax revenue is one of the essential means through which the government controls the macro-economy and plays a vital role in promoting environmental protection and sustainable development. This study takes Chinese panel data from 2004 to 2020 as sample observations, uses the SBM-GML index method to measure industrial green total factor productivity, and then uses econometric methods such as the two-way fixed effects model and instrumental variable method to analyze the impact of an environmental tax on industrial green transformation. It is found that the generalized environmental tax represented by vehicle and vessel tax, resource tax, and urban land use tax has a significant positive effect on industrial green transformation. After a series of robustness tests and the exclusion of endogeneity, this conclusion remains valid. The research shows that credit governance, the agglomeration of producer service, and their co-agglomeration with manufacturing are important adjustment mechanisms. Among them, credit management is special and compulsory, greatly restricting the environmental pollution behavior of industrial enterprises, and encourages enterprises to make green investments and to actively improve production processes.


Assuntos
Comércio , Indústrias , Humanos , China , Desenvolvimento Econômico , Poluição Ambiental , Governo
9.
Environ Dev Sustain ; : 1-25, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36124159

RESUMO

The government's development of eco-environmental policies can have a scientific foundation thanks to the fine particulate matter (PM2.5) medium- and long-term change forecast. This study develops a STRIPAT-Scenario analysis framework employing panel data from 11 cities in Zhejiang Province between 2006 and 2020 to predict the changing trend of PM2.5 concentrations under five alternative scenarios. The results reveal that: (1) urbanization development (P), economic development (A), technological innovation investment (T) and environmental regulation intensity have a significant inhibitory effect on PM2.5 concentration in Zhejiang Province, while industrial structure, industrial energy consumption and the number of motor vehicles (TR) have a significant increase on PM2.5 concentration. (2) Under any scenario, the PM2.5 concentration of 11 cities in Zhejiang Province can reach the constraint target set in the 14th Five-Year plan. The improvement in urban PM2.5 quality is most obviously impacted by the high-quality development scenario (S4). (3) Toward 2035, PM2.5 concentrations of 11 cities in Zhejiang Province can reach the National Class I level standard in most scenario models, among which Hangzhou, Jiaxing and Shaoxing are under high pressure to reduce emissions and are the key areas for PM2.5 management in Zhejiang Province. However, most cities cannot reach the 10 µg/m3 limit of WHO's AQG2005 version. Finally, this study makes recommendations for reducing PM2.5 in terms of enhancing industrial structure and funding science and technology innovation.

10.
Diabetes Ther ; 13(10): 1737-1753, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35934763

RESUMO

INTRODUCTION: The objective of the current study was to assess the long-term cost-effectiveness of once-weekly semaglutide 0.5 mg and 1.0 mg versus dulaglutide 1.5 mg for the treatment of patients with type 2 diabetes uncontrolled on metformin in the Chinese setting. METHODS: The Swedish Institute of Health Economics Diabetes Cohort Model (IHE-DCM) was used to evaluate the long-term health and economic outcomes of once-weekly semaglutide and dulaglutide. Analysis was conducted from the perspective of the Chinese healthcare systems over a time horizon of 40 years. Data on baseline cohort characteristics and treatment effects were sourced from the SUSTAIN 7 clinical trial. Costs included treatment costs and costs of complications. Projected health and economic outcomes were discounted at a rate of 5% annually. The robustness of the results was evaluated through one-way sensitivity analyses and probabilistic sensitivity analyses. RESULTS: Compared with dulaglutide 1.5 mg, once-weekly semaglutide 0.5 mg and 1.0 mg were associated with improvements in discounted life expectancy of 0.04 and 0.10 years, respectively, and improvements in discounted quality-adjusted life expectancy of 0.08 and 0.19 quality-adjusted life years (QALYs), respectively. Clinical benefits were achieved at reduced costs, with lifetime cost savings of 8355 Chinese Yuan (CNY) with once-weekly semaglutide 0.5 mg and 11,553 CNY with once-weekly semaglutide 1.0 mg. Sensitivity analyses verified the robustness of the research results. CONCLUSIONS: Once-weekly semaglutide was suggested to be dominant (more effective and less costly) versus dulaglutide 1.5 mg in patients with type 2 diabetes uncontrolled on metformin treatment in China.

11.
J Affect Disord ; 296: 434-442, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34606808

RESUMO

BACKGROUND: Preventive intervention can significantly reduce the human and economic costs of postpartum depression (PPD) compared with treatment post-diagnosis. However, identifying women with a high PPD risk and making a judgement as to the benefits of preventive intervention is a major challenge. METHODS: This is a retrospective study of parturients that underwent a cesarean delivery. Control group was used as development cohort and validation cohort to construct the risk prediction model of PPD and determine a risk threshold. Ketamine group and development cohort were used to verify the risk classification of parturients by evaluating whether the incidence of PPD decreased significantly after ketamine treatment in high-risk for PPD population. RESULTS: The AUC for the development cohort and validation cohort of the PPD prediction model were 0.751 (95%CI:0.700-0.802) and 0.748 (95%CI:0.680-0.816), respectively. A threshold of 19% PPD risk probability was determined, with a specificity and sensitivity in the validation cohort are 0.766 and 0.604, respectively. After matching the high-risk group and the low-risk group by propensity score, the results demonstrated that PPD incidence significantly reduced in the high-risk group following ketamine, versus non-ketamine, intervention (p < 0.01). In contrast, intervention in the low-risk group showed no significant difference in PPD outcomes (p > 0.01). LIMITATION: Randomized trials are needed to further verify the feasibility of the model and the thresholds proposed. CONCLUSION: This prediction model developed in this study shows utility in predicting PPD risk. Ketamine intervention significantly lowers PPD incidence in parturients with a risk classification threshold greater than 19%.


Assuntos
Depressão Pós-Parto , Cesárea , Estudos de Coortes , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/prevenção & controle , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
12.
Artigo em Inglês | MEDLINE | ID: mdl-34501979

RESUMO

Africa's PM2.5 pollution has become a security hazard, but the understanding of the varying effects of urbanization on driven mechanisms of PM2.5 concentrations under the rapid urbanization remains largely insufficient. Compared with the direct impact, the spillover effect of urbanization on PM2.5 concentrations in adjacent regions was underestimated. Urbanization is highly multi-dimensional phenomenon and previous studies have rarely distinguished the different driving influence and interactions of multi-dimensional urbanization on PM2.5 concentrations in Africa. This study combined grid and administrative units to explore the spatio-temporal change, spatial dependence patterns, and evolution trend of PM2.5 concentrations and multi-dimensional urbanization in Africa. The differential influence and interaction effects of multi-dimensional urbanization on PM2.5 concentrations under Africa's rapid urbanization was further analyzed. The results show that the positive spatial dependence of PM2.5 concentrations gradually increased over the study period 2000-2018. The areas with PM2.5 concentrations exceeding 35 µg/m3 increased by 2.2%, and 36.78% of the African continent had an increasing trend in Theil-Sen index. Urbanization was found to be the main driving factor causing PM2.5 concentrations changes, and economic urbanization had a stronger influence on air quality than land urbanization or population urbanization. Compared with the direct effect, the spillover effect of urbanization on PM2.5 concentrations in two adjacent regions was stronger, particularly in terms of economic urbanization. The spatial distribution of PM2.5 concentrations resulted from the interaction of multi-dimensional urbanization. The interaction of urbanization of any two different dimensions exhibited a nonlinear enhancement effect on PM2.5 concentrations. Given the differential impact of multi-dimensional urbanization on PM2.5 concentrations inside and outside the region, this research provides support for the cross-regional joint control strategies of air pollution in Africa. The findings also indicate that PM2.5 pollution control should not only focus on urban economic development strategies but should be an optimized integration of multiple mitigation strategies, such as improving residents' lifestyles, optimizing land spatial structure, and upgrading the industrial structure.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , África , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Cidades , Monitoramento Ambiental , Material Particulado/análise , Tecnologia de Sensoriamento Remoto , Urbanização
13.
J Am Chem Soc ; 143(8): 3256-3263, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33600160

RESUMO

Desaturation of unactivated alkanes remains a challenging yet desirable strategy to make olefins. The Illicium sesquiterpenes usually possess highly oxygenated cage-like architectures, and some of them exhibit prominent neurotrophic effects. Here, we disclose a unique photochemical desaturation strategy for the efficient, highly stereocontrolled total syntheses of five Illicium sesquiterpenes from inexpensive (R)-pulegone, featuring a 13-step gram-scale synthesis of (-)-merrilactone A. The efficiency of the syntheses derives from an expedient construction of a tetracyclic framework via two annulations, a site-specific photoinduced single-step desaturation in a complex hydrocarbon system, and diverse oxygenation manipulations around the resultant olefin intermediate. This work highlights how late-stage desaturation can dramatically streamline the synthesis of complex terpenes and diverse non-natural analogues for establishing the structure-activity relationship and elucidating their molecular mechanisms of bioactivity.


Assuntos
Illicium/química , Processos Fotoquímicos , Sesquiterpenos/química , Sesquiterpenos/síntese química , Técnicas de Química Sintética , Custos e Análise de Custo , Cinética , Oxigênio/química
14.
J Refract Surg ; 36(5): 308-316, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32396642

RESUMO

PURPOSE: To determine the incidence, management, outcomes, and risk factors of suction loss during femtosecond laser small incision lenticule extraction (SMILE) for the treatment of myopia and myopic astigmatism. METHODS: The study reviewed 12,057 consecutive eyes treated with SMILE. Eyes that developed suction loss (study group) or underwent uneventful SMILE (control group) were analyzed. Corneal topography, manifest refractions, and measurements of uncorrected (UDVA) and corrected (CDVA) distance visual acuities were evaluated preoperatively and postoperatively after 1 day and 12 months. Risk factors were determined for suction loss development. RESULTS: Twenty-seven of 12,057 eyes (0.22%) were enrolled in the study group and 50 eyes in the control group. Suction loss occurred in 14 eyes during the cutting of the refractive lenticule, 7 eyes during the cutting of the cap, and 6 eyes during the creation of the cap small incision. There was no statistically significant difference between the two groups in logMAR UDVA (P = .52) or CDVA (P = .59). A novel method of increasing cap thickness was applied to 8 eyes when suction loss occurred after more than 10% of the lenticule was cut. The eye being operated on first (the right eye) (P = .02) and a thinner lenticule (P = .006) were associated with a significantly higher risk of developing suction loss. CONCLUSIONS: The incidence of suction loss was low. The novel method achieved visual and refractive outcomes as favorable as those of uneventful SMILE procedures. The first eye that was operated on had a higher risk for the development of suction loss. [J Refract Surg. 2020;36(5):308-316.].


Assuntos
Astigmatismo/cirurgia , Substância Própria/cirurgia , Cirurgia da Córnea a Laser , Complicações Intraoperatórias , Miopia/cirurgia , Sucção , Adolescente , Adulto , Topografia da Córnea , Feminino , Humanos , Masculino , Microcirurgia , Estudos Prospectivos , Refração Ocular/fisiologia , Reoperação , Fatores de Risco , Resultado do Tratamento , Acuidade Visual/fisiologia , Adulto Jovem
15.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(3): 353-357, 2020 Mar 30.
Artigo em Chinês | MEDLINE | ID: mdl-32376587

RESUMO

In the setting of epidemics of communicable diseases, early initiation of epidemiological and clinical data collection and analysis and conducting relevant researches are essential to the success of epidemic containment. The coronavirus disease 2019 (COVID-19), starting initially as an epidemic in China in late 2019 and now becoming a pandemic globally, poses grave challenges to the global health care systems while also provides an opportunity for studying infectious diseases in the perspective of methodology. The authors propose the evaluation methods for case reports, randomized controlled trials (RCTs), real-world evidence studies and health economics researches during an epidemic. Case reports, which are of important value for health care workers during outbreaks of infectious diseases, should be written in standard format and style and published following a strict peer review process. RCTs provides the gold standard for evaluating the effectiveness of a given treatment for the patients from the outbreaks. We review the potential challenges faced in conducting RCTs during the outbreaks. The real-world data collected from the cases in designated hospitals allow the verification of the safety and effectiveness of the intervention measures. The data from health economics research also provide important support for optimizing communicable disease prevention and control strategies. Herein we summarize the health economics research methods, study design, and technical points during the outbreaks. We recommend that clinical research and health economics research be incorporated into the prevention and control plan and measures be taken to ensure both the standards and feasibility of these studies to improve the response capacity against outbreaks of communicable diseases.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , COVID-19 , China , Humanos , SARS-CoV-2
16.
PLoS Pathog ; 15(10): e1008032, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31589660

RESUMO

The intracellular pathogen Listeria monocytogenes is distinguished by its ability to invade and replicate within mammalian cells. Remarkably, of the 15 serovars within the genus, strains belonging to serovar 4b cause the majority of listeriosis clinical cases and outbreaks. The Listeria O-antigens are defined by subtle structural differences amongst the peptidoglycan-associated wall-teichoic acids (WTAs), and their specific glycosylation patterns. Here, we outline the genetic determinants required for WTA decoration in serovar 4b L. monocytogenes, and demonstrate the exact nature of the 4b-specific antigen. We show that challenge by bacteriophages selects for surviving clones that feature mutations in genes involved in teichoic acid glycosylation, leading to a loss of galactose from both wall teichoic acid and lipoteichoic acid molecules, and a switch from serovar 4b to 4d. Surprisingly, loss of this galactose decoration not only prevents phage adsorption, but leads to a complete loss of surface-associated Internalin B (InlB),the inability to form actin tails, and a virulence attenuation in vivo. We show that InlB specifically recognizes and attaches to galactosylated teichoic acid polymers, and is secreted upon loss of this modification, leading to a drastically reduced cellular invasiveness. Consequently, these phage-insensitive bacteria are unable to interact with cMet and gC1q-R host cell receptors, which normally trigger cellular uptake upon interaction with InlB. Collectively, we provide detailed mechanistic insight into the dual role of a surface antigen crucial for both phage adsorption and cellular invasiveness, demonstrating a trade-off between phage resistance and virulence in this opportunistic pathogen.


Assuntos
Proteínas de Bactérias/metabolismo , Bacteriófagos/patogenicidade , Parede Celular/metabolismo , Galactose/metabolismo , Listeria monocytogenes/virologia , Proteínas de Membrana/metabolismo , Ácidos Teicoicos/metabolismo , Virulência , Proteínas de Bactérias/genética , Bacteriófagos/genética , Células CACO-2 , Células Hep G2 , Humanos , Listeria monocytogenes/metabolismo , Proteínas de Membrana/genética , Mutação , Sorogrupo
17.
Hum Mutat ; 40(9): 1546-1556, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31294896

RESUMO

Testing for variation in BRCA1 and BRCA2 (commonly referred to as BRCA1/2), has emerged as a standard clinical practice and is helping countless women better understand and manage their heritable risk of breast and ovarian cancer. Yet the increased rate of BRCA1/2 testing has led to an increasing number of Variants of Uncertain Significance (VUS), and the rate of VUS discovery currently outpaces the rate of clinical variant interpretation. Computational prediction is a key component of the variant interpretation pipeline. In the CAGI5 ENIGMA Challenge, six prediction teams submitted predictions on 326 newly-interpreted variants from the ENIGMA Consortium. By evaluating these predictions against the new interpretations, we have gained a number of insights on the state of the art of variant prediction and specific steps to further advance this state of the art.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/diagnóstico , Biologia Computacional/métodos , Neoplasias Ovarianas/diagnóstico , Neoplasias da Mama/genética , Detecção Precoce de Câncer , Feminino , Predisposição Genética para Doença , Testes Genéticos , Variação Genética , Humanos , Modelos Genéticos , Neoplasias Ovarianas/genética
18.
J Phys Chem Lett ; 10(14): 3985-3990, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31241956

RESUMO

Trinucleotide repeat (TNR) sequences, which are responsible for several neurodegenerative genetic diseases, fold into hairpins that interfere with the protein machinery in replication or repair, thus leading to dynamic mutation -abnormal expansions of the genome. Despite their high thermodynamic stability, these hairpins can undergo configurational rearrangements, which may be crucial for continuous dynamic mutation. Here, we used CTG repeats as a model system to study their structural dynamics at the single-molecule level. A unique dynamic two-state configuration interchange was discovered over a wide range of odd-numbered CTG repeat sequences. Employing repeat-number-dependent kinetic analysis, we proposed a bulge translocation model, which is driven by the local instability and can be extended reasonably to longer (pathologically relevant) hairpins, implying the potential role in error accumulation in repeat expansion.


Assuntos
DNA/química , DNA/genética , Conformação de Ácido Nucleico , Repetições de Trinucleotídeos/genética , Simulação de Dinâmica Molecular , Método de Monte Carlo , Termodinâmica
19.
Light Sci Appl ; 8: 4, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30651979

RESUMO

For the rapid development of the hydrogen economy, a reliable and low-cost hydrogen sensor appears to be extremely important. Here, we first show that a palladium film deposited on polydimethylsiloxane (PDMS) can obtain an exceedingly high-reflectance contrast of 25.78 over the entire visible band upon exposure to 4 vol% hydrogen gas (H2) mixed with nitrogen gas. This high-reflectance contrast results from the surface deformation induced by the volume inflation after exposure to H2, leading to the transition of the near-specular surface to a diffusing surface. In addition, a change in brightness is readable by naked eye upon exposure to H2 with various concentrations from 0.6 to 1 vol% under the illumination of a fluorescent tube. Furthermore, this sensor possesses an excellent recyclability and quick response time of a few seconds. Compared with Pd nanostructure-based hydrogen sensors, this visual, high-contrast and low-cost sensor is of great potential for practical hydrogen sensing.

20.
Artigo em Inglês | MEDLINE | ID: mdl-30103386

RESUMO

Health literacy is an important determinant of health, and is one of the key indicators of a healthy city. Developing and improving methods to measure health literacy is prudent and necessary. This review summarizes the findings of published tools for assessing health literacy among the general population to provide a reference for establishing health literacy assessment tools in the future. In this systematic review, PubMed, Embase, and Web of Science were used to search articles regarding tools for assessing health literacy among the general population published up to 10 January 2018. Two researchers independently conducted literature screening, quality assessment of methodology, and data extraction according to preset inclusion and exclusion criteria. The quality assessment of the research was examined with the use of the specifications of the reporting guidelines for survey research (SURGE). Eleven articles met the inclusion criteria. All included instruments in monitoring the health literacy of the general population were presented through the form of questionnaires. The multistage process of making all the scales generally involved the following steps: item development, pre-testing, and evaluation of readability. However, the specific methods were different. Internal consistency for all the instruments was acceptable but with weak consistency among the subscales for some instruments. Most of the identified instruments derived from the definition of health literacy or were based on existing health literacy theory. Approximately 30% of the performed studies provided no description of the important features specified in the SURGE. This review indicates a trend in the increasing tools for assessing the health literacy of the general population by using multidimensional structures and comprehensive measurement approaches. However, no clear "consensus" was observed in the dimensions of health literacy tools.


Assuntos
Avaliação Educacional , Letramento em Saúde/estatística & dados numéricos , Bases de Dados Factuais , Pesquisa sobre Serviços de Saúde , Humanos , Garantia da Qualidade dos Cuidados de Saúde
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