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1.
Sci Total Environ ; 754: 141948, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32916488

RESUMO

There is a rising concern regarding the accumulation of microplastics in the aquatic ecosystems. However, compared to the marine environment, the occurrence, transport, and diffusion of microplastics in freshwater sediment are still open questions. This paper summarizes and compares the methods used in previous studies and provides suggestions for sampling and analysis of microplastics in freshwater sediment. This paper also reviews the findings on microplastics in freshwater sediment, including abundance, morphological characteristics, polymer types, sources, and factors affecting the abundance of microplastics in freshwater sediment. The results show that microplastics are ubiquitous in the investigated sediment of rivers, lakes, and reservoirs, with an abundance of 2-5 orders of magnitude across different regions. Low microplastics concentration was observed in the Ciwalengke River with an average abundance of 30.3 ± 15.9 items/kg. In particular, an extremely high abundance of microplastics was recorded in the urban recipient in Norway reaching 12,000-200,000 items/kg. Fibers with particle size less than 1 mm are the dominant shape for microplastics in freshwater sediment. In addition, the most frequently recorded colors and types are white/transparent, and PE/PS, respectively. Finally, we conclude that the consistency of morphological characteristics and components of microplastics between the beach or marine sediments and freshwater sediments may be an indicator of these interlinkages and source-pathways. Microplastics in freshwater sediment need further research and exploration to identify its spatial and temporal variations and driving force through further field sampling and implementation of standard and uniform analytical methodologies.

2.
Sci Rep ; 10(1): 19507, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33177548

RESUMO

Exhaled carbon monoxide (COex) level has been proposed as a noninvasive and easily-obtainable cardiovascular risk marker, however, with limited prospective evidence, and its association with stroke risk has been rarely explored. Measurements of COex were performed during 2004-2008 baseline examinations in the China Kadoorie Biobank study among 512,891 adults aged 30-79 years from 10 diverse study areas. After excluding participants with baseline cardiopulmonary diseases, stroke and cancer, 178,485 men and 267,202 women remained. Cox regression yielded hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of cardio-cerebral-vascular disease (CCVD) associated with COex levels, with sequential addition of adjustment for proxy variables for CO exposure, including study area indexing ambient CO variations at large, and smoking and solid fuel use, apart from adjusting for traditional cardiovascular risk factors. During 7-year follow-up, we documented 1744 and 1430 major coronary events (myocardial infarction plus fatal ischemic heart disease), 8849 and 10,922 ischemic strokes, and 2492 and 2363 hemorrhagic strokes among men and women, respectively. The HRs with 95% CIs comparing the highest with lowest COex quintile were 2.15 [1.72, 2.69] for major coronary events, 1.65 [1.50, 1.80] for ischemic stroke, and 1.35 [1.13, 1.61] for hemorrhagic stroke among men, while among women higher associated risk was only observed for major coronary events (1.64 [1.35, 2.00]) and ischemic stroke (1.87 [1.73, 2.01]). The elevated risks were consistent when COex level was over 3 ppm. However, these associations were all attenuated until null by sequential addition of stratification by study areas, and adjustments of smoking and solid fuel use. Nevertheless, the association with ischemic stroke was maintained among the subgroup of male smokers even with adjustment for the depth and amount of cigarette smoking (HR [95% CI]: 1.37 [1.06, 1.77]), while a negative association with hemorrhagic stroke also appeared within this subgroup. Higher COex level (over 3 ppm) was associated with elevated risk of ischemic CCVD, but not independently of CO exposure. Our finding suggests that, though not an independent risk factor, COex could potentially provide a cost-effective biomarker for ischemic cardio-cerebral-vascular risk, given that CO exposure is ubiquitous.

3.
Dalton Trans ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33200757

RESUMO

The development of fluorescent sensors based on lanthanide-doped luminescent nanoparticles has increased their application in biomarker detection. Lanthanide-doped upconversion nanoparticles (UCNPs) have been explored as one of the most promising sensors owing to their merits such as excellent photostability, zero background auto-fluorescence, and reduced side effects of near-infrared triggered treatments. However, traditional upconversion luminescence assay based on direct Fluorescence Resonance Energy Transfer (FRET) between the target molecules and surface of UCNPs encounters low detection accuracy due to superficial adsorption interactions. In this work, we use a molecularly imprinting technique to achieve the specific interaction between UCNPs and molecules for accurate sensing. We demonstrate this by synthesizing a nanostructure with a molecularly imprinted polymer at the surface of UCNPs, in which the imprinted cavities can specifically capture the target molecule of rhodamine B. The upconversion signal changes in relation to the molecule concentration due to FRET. Quantitative analysis shows that the fluorescence-quenching rate is consistent with the Stern-Volmer equation, resulting in a limit of detection of 6.27 µg mL-1. Our fluorescence sensing approach integrates the advantages of both nonlinear upconversion and molecular imprinting technologies, showing great potential for the detection of specific molecules.

4.
PLoS One ; 15(11): e0241540, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33152004

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread to the world. Whether there is an association between lifestyle behaviors and the acquisition of COVID-19 remains unclear. METHODS: In this case-control study, we recruited 105 patients with SARS-CoV-2 infection as a case group from the Wuhan Tongji Hospital (Wuhan, China). For each case two control subjects were recruited. Participants were randomly selected from communities in Wuhan and matched for sex, age (± 2yrs), and pre-existing comorbidities (hypertension and diabetes). RESULTS: A total of 105 patients diagnosed with COVID-19 and 210 controls were included. Compared with control group, the case group had higher proportions of lack of sleep (30.5% vs. 14.8%, P = 0.001) and increased physical activities (56.2% vs. 32.9%, P < 0.001). And patients in the case group were more likely to have alopecia (28.6% vs. 10.0%, P < 0.001) than people from the control group. Overall, we found that lack of sleep [adjusted odds ratio (OR) 1.56, 95% confidence interval (CI) 1.03-2.39)], physical activities (≥ 5 times a week) (adjusted OR 2.05, 95%CI 1.39-3.02) and alopecia (adjusted OR 1.73, 95%CI 1.13-2.66) were independent risk factors for COVID-19 infection. Conversely, low-dose alcohol intake (<100g alcohol per week), hand hygiene, and fruits intake (daily) were significantly associated with a decrease in morbidity. CONCLUSIONS: Individual lifestyle behaviors and health status can affect the occurrence of COVID-19.


Assuntos
Infecções por Coronavirus/epidemiologia , Nível de Saúde , Estilo de Vida , Pneumonia Viral/epidemiologia , Adulto , Idoso , Consumo de Bebidas Alcoólicas , Betacoronavirus , Estudos de Casos e Controles , China , Comorbidade , Exercício Físico , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias , Fatores de Risco , Sono
5.
Transl Oncol ; 14(1): 100945, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33190041

RESUMO

The mutation in postoperative plasma (molecular residues) was an independently prognostic factor in colorectal cancer (CRC). The status of postoperative plasma mutation of microsatellite instability (MSI) CRC has not been systematically examined. In this study, we enrolled 30 MSI and 46 microsatellite stability (MSS) CRCs, and performed next generation sequencing on surgical tissues, postoperative plasma, and plasma during follow-up. Compared with MSS, MSI tumors had dissimilar genomic profiles, higher tumor mutation burden (TMB), and more frameshift mutations. In the postoperative plasma, more MSI CRCs were detected with tumor-derived mutations (77% in MSI vs 33% in MSS, p < 0.001). The numbers of postoperative mutations were proportional to MSI tissues (Spearman r = 0.47, p = 0.023), while not for MSS. More proportion of postoperative plasma samples of MSI CRCs harbored frameshift mutations than MSS (p = 0.007). For the follow-up plasma, 93% (14 out of 15) MSI CRCs harbored tumor-derived mutations; 33% (4/12) MSS were mutation-positive, lower than MSI (p = 0.003). Thus, considering that MSI CRC had extremely distinct mutational characteristics in tumor and postoperative plasma compared with MSS CRC, we propose that the prognostic value of molecular residue identification in postoperative plasma needs to be independently evaluated in MSI and MSS CRCs.

7.
Food Chem Toxicol ; : 111867, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33217525

RESUMO

Patulin (PAT), a kind of mycotoxin, is produced by many common fungi in fruit and vegetable-based products. It has been shown to cause hepatotoxicity. However, the possible mechanisms are not completely elucidated. The present study aimed to characterize the role of autophagic-inflammasomal pathway on pyroptosis induced by PAT. In mouse livers, PAT induced pyroptosis, and increased inflammation through the activation of NLRP3 inflammasome. In liver cells, we noticed that PAT induced pyroptotic cell death, which was confirmed by the activation of GSDMD, caspase-1, the release of LDH, and the result of PI/Hoechst assay. In addition, PAT-induced pyroptosis was dependent upon the activation of NLRP3 inflammasome and the release of cathepsin B. Cells had less expression of caspase-1 and IL-1ß protein levels after treated by NLRP3 inhibitor MCC950 or cathepsin B inhibitor CA-074Me. The expression of GSDMD and IL-1ß protein levels were also decrease after treated by caspase-1 inhibitor Ac-YVAD-cmk. Moreover, autophagy inhibitor 3-methyladenine (3MA) attenuated PAT-induced increase in cytoplasmic cathepsin B expression, and subsequent LDH release, the activation of NLRP3 inflamosomes, pyroptotic cell death, and inflammation. These findings suggested that PAT-induced pyroptosis maybe through autophagy-cathepsin B-inflammasomal pathway in the liver. These results provide new mechanistic insights into PAT-induced hepatotoxicity.

8.
Reprod Biol ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33158780

RESUMO

Toll-like receptors (TLRs) participates in regulation of the maternal immune tolerance during pregnancy, and the thymus is critical for the adaptive immune system. This study hypothesized whether early pregnancy affected the expression of toll-like receptor pathway in the thymus of ewes. In this study, expression of TLRs, tumor necrosis factor receptor associated factor 6 (TRAF6), interleukin 1 receptor associated kinase 1 (IRAK1) and myeloid differentiation primary response gene 88 (MyD88) was detected in maternal thymus during early pregnancy in sheep. Ovine thymuses were collected on day 16 of the estrous cycle, and days 13, 16 and 25 of pregnancy, and expression of TLR members was analyzed by real-time quantitative PCR, western blot and immunohistochemistry analysis. The results revealed that there were decreases in the expression of the mRNA and proteins of TLR2, IRAK1, TRAF6 and MyD88, but increase in TLR5 mRNA and protein. Furthermore, expression of TLR3 and TLR4 proteins peaked at days 13 and 16 of gestation, and MyD88 protein was located in the epithelial reticular cells and thymic corpuscles. In summary, TLR signaling is implicated in regulation of maternal thymic immune, which may be via downregulation of TLR2, IRAK1, TRAF6 and MyD88 during early pregnancy in sheep.

9.
Int J Food Sci Nutr ; : 1-8, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33207985

RESUMO

This study aimed to describe the characteristics and lifestyle differences of spicy food consumption in 0.5 million adults. Participants were recruited from 2004 to 2008 in the baseline research of the CKB study. Higher frequency and stronger pungency degree in spicy food positively correlated with preference for salty taste, eating snacks/deep-fried foods, tea/alcohol drinking and tobacco smoking. Among weekly tea/alcohol drinkers and current regular smokers, participants with a higher frequency of spicy food consumption or preference for stronger pungency degree were more likely to prefer strong tea, drink alcohol exceed the healthy amount, drink alcohol in the morning every day, smoke ≥ 40 cigarettes per day, consume a larger amount of tea leaves, alcohol and cigarettes each day, and start habitual tea/alcohol drinking or smoking at an earlier age. Differences existed in lifestyle factors related to major chronic diseases according to spicy food consumption frequency and pungency degree among the Chinese population.

10.
J Chin Med Assoc ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33230060

RESUMO

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrythmia and increasing numbers of patients receiving AF ablation nowadays. So, in cardiology division, residents need to familiar with the AF ablation procedure-related knowledge for primary care. This study evaluated the baseline residents and patients self-efficacy to AF ablation procedure-related knowledge, developed the specific virtual reality (VR) informative aids, evaluated the effects of VR training and resident-led VR aids-based patient education on their self-efficacy, in the aspects of familiarity, confidence and anxiety, and satisfaction. METHODS: From 2019, April to 2020, April, this 1-year prospective pre- and post-study was undergone in cardiology division. Between 2019, April to 2019, December, the experienced physicians were invited to develop virtual reality (VR) informative aids for AF ablation procedure-related knowledge. Between January 2020 to April 2020, newly developed VR informative aids was implemented in educational program of training rotated residents for giving patient education. RESULTS: A total of 20 residents and 32 patients were enrolled. The baseline self-reported self-efficacy and knowledge score were relatively low among rotated residents and their patients. In addition to high level of satisfaction, self-efficacy and knowledge score of residents and their patients were increased after VR aids-based training and resident-led patient education. Higher degree of improvement in self-efficacy was noted among patients with depression/anxiety history than those without history. The follow-up assessments among residents showed that the positive effects of VR aids was sustained until 2 weeks later. CONCLUSION: Overall, residents and patients reported that the VR aids increase the effectiveness of patient education, achieve the purpose of a paperless environment, and motivate them to recommend it to others. Implementation of resident-to-patient education have a positive impact on trainees and patients understanding about AF ablation procedures-related knowledge.

11.
JAMA Netw Open ; 3(10): e2018721, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33006619

RESUMO

Importance: There is some support for the existence of genetic associations between adiposity and certain hepatobiliary diseases in Western populations. However, there is little evidence of such genetic associations in China, where the causes of these diseases may differ from those in Western populations and the mean body mass index (BMI) is much lower. Objectives: To compare the observational associations of BMI with hepatobiliary diseases and liver biomarkers with the genetic associations between BMI and these factors and to assess whether the genetic associations of BMI with liver diseases differed by hepatitis B virus infection status. Design, Setting, and Participants: This cohort study used data from the prospective China Kadoorie Biobank, including 473 938 adults aged 30 to 79 years without hepatobiliary diseases at baseline from 10 diverse areas in China from June 25, 2004, to July 15, 2008. A random sample of 75 736 participants with genotyping data was included in the Mendelian randomization analysis. Follow-up was completed January 1, 2017 (median [interquartile range] length of follow-up, 10.2 [9.2-11.1] years). Data were analyzed from January to October 2019. Exposures: Measured BMI obtained during the baseline survey and genetically instrumented BMI derived using 92 single-nucleotide variations. Main Outcomes and Measures: Incident cases of hepatobiliary diseases, liver enzymes, fatty liver index, and fibrosis score. Results: Among 473 938 individuals (276 041 [58.2%] women), the mean (SD) age was 52 (10.9) years and mean (SD) BMI was 23.8 (3.4). Baseline BMI was associated with higher risks of chronic liver disease (adjusted risk ratio per 1-SD increase, 1.14; 95% CI, 1.11 to 1.17) and gallbladder disease (adjusted risk ratio per 1-SD increase, 1.29; 95% CI, 1.27 to 1.31), with heterogeneity by disease subtype (P < .001). Genetically instrumented BMI was associated with higher risks of chronic liver disease (risk ratio per 1-SD increase, 1.55; 95% CI, 1.08 to 2.24) and gallbladder disease (risk ratio per 1-SD increase, 1.40; 95% CI, 1.11 to 1.76), with no heterogeneity between subtypes. A meta-analysis of the genetic associations in China Kadoorie Biobank and those calculated in UK Biobank gave a risk ratio of 1.55 (95% CI, 1.30 to 1.84) for chronic liver disease and 1.42 (95% CI, 1.22 to 1.64) for gallbladder disease. In the China Kadoorie Biobank study, there were positive genetic associations of BMI with liver enzymes, steatosis, and fibrosis scores, consistent with observational associations. The genetic associations of BMI with liver diseases and biomarkers did not differ by hepatitis B virus infection status. Conclusions and Relevance: In this cohort study of a relatively lean Chinese population, there were positive genetic associations of BMI with hepatobiliary diseases. These results suggest that maintaining a healthy weight through diet and physical activity may help prevent hepatobiliary diseases.

12.
Res Vet Sci ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33127092

RESUMO

The ketosis has negative effects on the high-yielding dairy cows during early lactation. Apolipoprotein A1 (APOA1) is a component of high-density lipoprotein. However, the association of APOA1 gene with ketosis, and the molecular mechanisms of expression of APOA1 gene are not fully understood in dairy cows. In this study, expression of APOA1 in the liver and blood was investigated by RT-qPCR and immunohistochemistry, and genetic variation in the 5'-flanking region of the AOPA1 gene was also screened and identified. In addition, correlation of the single nucleotide polymorphisms (SNPs) of APOA1 gene with blood ketone characters, and activity of APOA1 promoter were analyzed in dairy cows. The results showed that ApoA1 protein was expressed in the liver, and the mRNA level of APOA1 was significantly higher in the cows with ketosis comparing to the healthy cows. In addition, a novel SNP (g.-572 A > G) in the core promoter of the APOA1 gene was identified between base g.-714 and g.-68 through transient transfection in both HepG2 cell and FFb cell, and luciferase report assay. Moreover, there was lower concentration of blood ß-hydroxybutyrate in cows with genotype GG comparing to the cows with genotypes AA and AG. This study reported for the first time that the genetic variant g.-572 A > G in the core promoter region of APOA1 gene was associated with the ketosis in Chinese Holstein cows, and g.-572 A > G may be used as a genetic marker for ketosis prevention.

13.
Ecotoxicol Environ Saf ; 208: 111439, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33039874

RESUMO

Trichloroethylene (TCE) induced occupational medicamentosa-like dermatitis (OMLDT) in patients is accompanied, typically, by renal damage. But the role of C5b-9 and IL-1ß in TCE-sensitized mouse renal tubular damage is unclear. This study aimed to investigate whether TCE-sensitized mouse renal tubular epithelial cell damage was induced by NLRP3 inflammasome and whether NLRP3 inflammasome was activated by sublytic C5b-9. In total, 52 specific pathogen-free BALB/c female mice, 6- to 8-week-old, were used for establishing the TCE-sensitized mouse model. Renal tubular epithelial cells were isolated and used for determining the sublytic level of C5b-9. Kidney histological examination, serum neutrophil gelatinase associated lipocalin (NGAL) level were used for kidney damage evaluation. Renal protein levels of C5b-9, NLRP3, ASC, Caspase-1, IL-1ß, and IL-18 were measured. The renal lesions, serum NGAL level, renal NLRP3, ASC, Caspase-1 and IL-1ß protein levels all increased significantly in TCE sensitized positive group. However, pretreatment with recombinant protein sCD59-Cys inhibited the expression of C5b-9, NLRP3 inflammasome, IL-1ß, IL-18, and attenuated renal tubular epithelial cell damage. The sublytic C5b-9 activated NLRP3 inflammasome and aggravated renal tubular epithelial cell damage. Pretreatment with recombinant protein sCD59-Cys blocked the expression of the NLRP3 inflammasome by inhibiting the expression of C5b-9, and alleviating renal tubular epithelial cell damage.

14.
PeerJ ; 8: e9913, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33083108

RESUMO

The MPF and MAPK genes play crucial roles during oocyte maturation processes. However, the pattern of MPF and MAPK gene expression induced by melatonin (MT) and its correlation to oocyte maturation quality during the process of porcine oocyte maturation in vitro remains unexplored. To unravel it, in this study, we cultured the porcine oocytes in maturation medium supplemented with 0, 10-6, 10-9, and 10-12 mol/L melatonin. Later, we analyzed the MPF and MAPK gene expression levels by RT-PCR and determined the maturation index (survival and maturation rate of oocytes). The GSH content in the single oocyte, and cytoplasmic mitochondrial maturation distribution after porcine oocyte maturation in vitro was also evaluated. We also assessed the effects of these changes on parthenogenetic embryonic developmental potential. The oocytes cultured with 10-9mol/L melatonin concentration showed higher oocyte maturation rate, and MPF and MAPK genes expression levels along with better mitochondrial distribution than the 0, 10-6, and 10-12 mol/L melatonin concentrations (p < 0.05). No significant difference was observed in the survival rates when the oocytes were cultured with different melatonin concentrations. The expression of the MPF gene in the oocytes cultured with 10-6 mol/L melatonin was higher than with 10-12 and 0 mol/L melatonin, and the expression of the MAPK gene in 10-6 and 10-12 group was higher than the control (p < 0.05). As far as the embryonic developmental potential is concerned, the cleavage and blastocyst rate of oocytes cultured with 10-6 and 10-9 mol/L melatonin was significantly higher than the 10-12 mol/L melatonin and control. In conclusion, 10-9-10-6 mol/L melatonin significantly induced the MPF and MAPK gene expression; besides, it could also be correlated with GSH content of single oocyte, mitochondrial maturation distribution, and the first polar body expulsion. These changes were also found to be associated with parthenogenetic embryo developmental potential in vitro.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33078900

RESUMO

α-Haloboronates are useful organic synthons which can be converted to a diverse array of α-substituted alkyl borons. Methods to α-haloboronates are limiting and often suffer from harsh reaction conditions. Reported herein is a photochemical radical C-H halogenation of benzyl N -methyliminodiacetyl (MIDA) boronates. Fluorination, chlorination as well as bromination reactions were effective by using this protocol. Upon reaction with different nucleophiles, the C-Br bond in the brominated product could be readily transformed to a series of C-C, C-O, C-N, C-S, C-P and C-I bonds, some of which are difficult to forge with α-halo sp 2 -B boronate esters. An activation effect of B(MIDA) moiety was found.

16.
PLoS Med ; 17(10): e1003351, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33125374

RESUMO

BACKGROUND: Metabolically healthy obesity (MHO) and its transition to unhealthy metabolic status have been associated with risk of cardiovascular disease (CVD) in Western populations. However, it is unclear to what extent metabolic health changes over time and whether such transition affects risks of subtypes of CVD in Chinese adults. We aimed to examine the association of metabolic health status and its transition with risks of subtypes of vascular disease across body mass index (BMI) categories. METHODS AND FINDINGS: The China Kadoorie Biobank was conducted during 25 June 2004 to 15 July 2008 in 5 urban (Harbin, Qingdao, Suzhou, Liuzhou, and Haikou) and 5 rural (Henan, Gansu, Sichuan, Zhejiang, and Hunan) regions across China. BMI and metabolic health information were collected. We classified participants into BMI categories: normal weight (BMI 18.5-23.9 kg/m²), overweight (BMI 24.0-27.9 kg/m²), and obese (BMI ≥ 28 kg/m²). Metabolic health was defined as meeting less than 2 of the following 4 criteria (elevated waist circumference, hypertension, elevated plasma glucose level, and dyslipidemia). The changes in obesity and metabolic health status were defined from baseline to the second resurvey with combination of overweight and obesity. Among the 458,246 participants with complete information and no history of CVD and cancer, the mean age at baseline was 50.9 (SD 10.4) years, and 40.8% were men, and 29.0% were current smokers. During a median 10.0 years of follow-up, 52,251 major vascular events (MVEs), including 7,326 major coronary events (MCEs), 37,992 ischemic heart disease (IHD), and 42,951 strokes were recorded. Compared with metabolically healthy normal weight (MHN), baseline MHO was associated with higher hazard ratios (HRs) for all types of CVD; however, almost 40% of those participants transitioned to metabolically unhealthy status. Stable metabolically unhealthy overweight or obesity (MUOO) (HR 2.22, 95% confidence interval [CI] 2.00-2.47, p < 0.001) and transition from metabolically healthy to unhealthy status (HR 1.53, 1.34-1.75, p < 0.001) were associated with higher risk for MVE, compared with stable healthy normal weight. Similar patterns were observed for MCE, IHD, and stroke. Limitations of the analysis included lack of measurement of lipid components, fasting plasma glucose, and visceral fat, and there might be possible misclassification. CONCLUSIONS: Among Chinese adults, MHO individuals have increased risks of MVE. Obesity remains a risk factor for CVD independent of major metabolic factors. Our data further suggest that metabolic health is a transient state for a large proportion of Chinese adults, with the highest vascular risk among those remained MUOO.

17.
Lancet Oncol ; 21(10): 1378-1386, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33002439

RESUMO

BACKGROUND: Genetic variants and lifestyle factors have been associated with gastric cancer risk, but the extent to which an increased genetic risk can be offset by a healthy lifestyle remains unknown. We aimed to establish a genetic risk model for gastric cancer and assess the benefits of adhering to a healthy lifestyle in individuals with a high genetic risk. METHODS: In this meta-analysis and prospective cohort study, we first did a fixed-effects meta-analysis of the association between genetic variants and gastric cancer in six independent genome-wide association studies (GWAS) with a case-control study design. These GWAS comprised 21 168 Han Chinese individuals, of whom 10 254 had gastric cancer and 10 914 geographically matched controls did not. Using summary statistics from the meta-analysis, we constructed five polygenic risk scores in a range of thresholds (p=5 × 10-4 p=5 × 10-5 p=5 × 10-6 p=5 × 10-7, and p=5 × 10-8) for gastric cancer. We then applied these scores to an independent, prospective, nationwide cohort of 100 220 individuals from the China Kadoorie Biobank (CKB), with more than 10 years of follow-up. The relative and absolute risk of incident gastric cancer associated with healthy lifestyle factors (defined as not smoking, never consuming alcohol, the low consumption of preserved foods, and the frequent intake of fresh fruits and vegetables), was assessed and stratified by genetic risk (low [quintile 1 of the polygenic risk score], intermediate [quintile 2-4 of the polygenic risk score], and high [quintile 5 of the polygenic risk score]). Individuals with a favourable lifestyle were considered as those who adopted all four healthy lifestyle factors, those with an intermediate lifestyle adopted two or three factors, and those with an unfavourable lifestyle adopted none or one factor. FINDINGS: The polygenic risk score derived from 112 single-nucleotide polymorphisms (p<5 × 10-5) showed the strongest association with gastric cancer risk (p=7·56 × 10-10). When this polygenic risk score was applied to the CKB cohort, we found that there was a significant increase in the relative risk of incident gastric cancer across the quintiles of the polygenic risk score (ptrend<0·0001). Compared with individuals who had a low genetic risk, those with an intermediate genetic risk (hazard ratio [HR] 1·54 [95% CI 1·22-1·94], p=2·67 × 10-4) and a high genetic risk (2·08 [1·61-2·69], p<0·0001) had a greater risk of gastric cancer. A similar increase in the relative risk of incident gastric cancer was observed across the lifestyle categories (ptrend<0·0001), with a higher risk of gastric cancer in those with an unfavourable lifestyle than those with a favourable lifestyle (2·03 [1·46-2·83], p<0·0001). Participants with a high genetic risk and a favourable lifestyle had a lower risk of gastric cancer than those with a high genetic risk and an unfavourable lifestyle (0·53 [0·29-0·99], p=0·048), with an absolute risk reduction of 1·12% (95% CI 0·62-1·56). INTERPRETATION: Chinese individuals at an increased risk of incident gastric cancer could be identified by use of our newly developed polygenic risk score. Compared with individuals at a high genetic risk who adopt an unhealthy lifestyle, those who adopt a healthy lifestyle could substantially reduce their risk of incident gastric cancer. FUNDING: National Key R&D Program of China, National Natural Science Foundation of China, 333 High-Level Talents Cultivation Project of Jiangsu Province, and China Postdoctoral Science Foundation.


Assuntos
Predisposição Genética para Doença/genética , Estilo de Vida Saudável , Neoplasias Gástricas/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Feminino , Seguimentos , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/psicologia , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/psicologia
18.
Clin Cancer Res ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046514

RESUMO

PURPOSE: We investigated the value of circulating tumor DNA (ctDNA) in predicting tumor response to neoadjuvant chemoradiotherapy (nCRT), monitoring tumor burden, and prognosing survival in patients with locally advanced rectal cancer (LARC). EXPERIMENTAL DESIGN: This prospective multicenter trial recruited 106 LARC patients for treatment of nCRT followed by surgery. Serial ctDNA were analyzed by NGS at four time points: at baseline, during nCRT, pre-surgery and post-surgery. RESULTS: In total, 1098 mutations were identified in tumor tissues of the 104 patients being analyzed (median, 7 mutations per patient). ctDNA was detected in 75%, 15.6%, 10.5%, and 6.7% of cases at the four time points, respectively. None of the 29 patients with pathological complete response (ypCR) had preoperative ctDNA detected. Preoperative ctDNA positive rate was significantly lower in the well responded patients with pathological tumor regression grade of ypCAP 0-1 than ypCAP 2-3 group (P < 0.001), lower in ypCR than non-ypCR group (P = 0.02), and lower in ypT 0-2 than ypT 3-4 group (P = 0.002). With a median follow-up of 18.8 months, thirteen patients (12.5%) experienced distant metastasis. ctDNA positivity at all four time points was associated with a shorter metastasis-free survival (MFS) (P < 0.05). Multivariate analyses showed that the median VAF of mutations in baseline ctDNA was a strong independent predictor of MFS (HR=1.27, P < 0.001). CONCLUSIONS: We show that ctDNA is a real-time monitoring indicator that can accurately reflect the tumor burden. The median VAF of baseline ctDNA is a strong independent predictor of MFS.

19.
Infect Genet Evol ; 85: 104565, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32971249

RESUMO

This study aimed to characterize the antimicrobial susceptibility and genetic features of a heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) strain Guangzhou-SauVS2 recovered from a female patient in Guangzhou, representative of southern China. The genome of Guangzhou-SauVS2 was sequenced using Illumina HiSeq 2500 platform and assembled de novo using Velvet v1.2.08. Annotations and bioinformatics analysis were further performed. Results showed that Guangzhou-SauVS2 was susceptible and resistant to 7 and 11 antibiotic drugs, respectively, and exhibited hVISA with a minimum inhibitory concentration of vancomycin as 4 µg/mL. Its genome is 2,883,941 bp in length and contains 2934 predicted genes with an average G + C content of 32.9%. Besides, a total of 38 virulence factors and 4 antibiotic-resistant genes were identified. These results can be employed to further study the pathogenic and antimicrobial mechanisms of hVISA.

20.
J Biol Inorg Chem ; 25(7): 1023-1034, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32945939

RESUMO

The metallo-ß-lactamase (MßL) superfamily, which is intriguing due to its enzyme promiscuity, is a good model enzyme superfamily for studies of catalytic function evolution. Our previous study traced the evolution of the phosphotriesterase activity of the MßL superfamily and found that MßLs go through three typical active-site structures in the development of phosphotriesterase activity. In the present study, taking the three typical active-site structures as class labels, the classification and prediction models, which were established by support vector machine and amino acid composition, classified the MßL members into three classes. The indispensable amino acid compositions showed a surprising performance that was remarkably better than the performance of the dispensable amino acid compositions and even equal to the performance of the 20 native amino acids. We further traced the origin of the classification error and found that there was one subclass adopting a type of active-site structure that was the evolutionary transition between these classes. After that, our classification and prediction models were successfully used to predict several MßL active-site structures that lost the dinuclear structures during crystallization. In summary, our studies established a classification and prediction system for active-site structures that well compensated for experimental methods that recognize protein structure details and suggest that the indispensable amino acids contain much more protein structure information than the dispensable amino acids.

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