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1.
Phys Chem Chem Phys ; 22(43): 24964-24973, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33140766

RESUMO

Dipole-phonon quantum logic (DPQL) leverages the interaction between polar molecular ions and the motional modes of a trapped-ion Coulomb crystal to provide a potentially scalable route to quantum information science. Here, we study a class of candidate molecular ions for DPQL, the cationic alkaline-earth monoxides and monosulfides, which possess suitable structure for DPQL and can be produced in existing atomic ion experiments with little additional complexity. We present calculations of DPQL operations for one of these molecules, CaO+, and discuss progress towards experimental realization. We also further develop the theory of DPQL to include state preparation and measurement and entanglement of multiple molecular ions.

3.
Free Radic Biol Med ; 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33137468

RESUMO

BACKGROUND: Presently, few small molecule compounds are used as targeted therapy drugs in the treatment of colorectal cancer (CRC). It is important to identify new small molecule compounds, which can be used in the treatment of CRC. METHODS: In this study, we selected four protein molecules as drug targets: PRL-3 (Phosphatase of regenerating liver 3), CLIC4 (Chloride intracellular channel 4), THBS2 (Thrombospondin 2), and BGN (Biglycan). These protein molecules were associated with the growth and metastasis of CRC cells. Small molecular compounds were screened on the basis of their target structures. Thus, five small molecule compounds were screened from each target structure, and three small molecule compounds (macrocarpal I, sildenafil, and neoandrographolide) were found to bind with two drug targets at the same time. Further experiments revealed that the inhibition rate of macrocarpal I was the highest in CRC cells. Therefore, we determined the effects of macrocarpal I on proliferation, apoptosis, cytoskeleton of CRC cells, and subcutaneous tumorigenesis in nude mice. Furthermore, RNA-seq analysis was performed to determine the molecular mechanism through which macrocarpal I inhibited the progression of CRC. RESULTS: We found that macrocarpal I could effectively inhibit proliferation, colony formation of CRC cells, and subcutaneous tumorigenesis in nude mice. Moreover, it also destroyed the cytoskeleton of CRC cells and promoted apoptosis. The effects on kinase activity, cytoskeleton, and DNA repair is the mechanism of macrocarpal I to inhibiting CRC growth. CONCLUSION: Macrocarpal I is a small molecule compound that can effectively inhibit the progression of CRC. Thus, macrocarpal I is a therapeutic compound that shows promising results in the treatment of advanced CRC.

4.
Arch Biochem Biophys ; 695: 108644, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33098869

RESUMO

BACKGROUND: Colorectal cancer is a common malignant tumor of the digestive tract. In recent years, the incidence rate has increased year by year and is showing a younger trend. The application of Chinese herbal medicine (CHM) is one of the important methods for the treatment of colorectal cancer. CHM refers to the main therapeutic drugs based on traditional Chinese medicine (TCM), which is still valued. Many effective anticancer small-molecule compounds are derived from CHMs, and their effective anticancer ingredients and targets must be clarified and to further understand the molecular mechanisms by which CHM affects cancer. METHODS: We analyzed the ingredients in CHM that were found to be effective against colorectal cancer and constructed an interaction network among these ingredients and the target protein. By analyzing the number of connections in the network and their type of interaction, we identified the key target protein Corticosteroid 11-beta-dehydrogenase isozyme 2, the enzyme encoded by HSD11B2. Analyses of HSD11B2 expression, survival curve, and co-expressed genes helped clarify the correlation between HSD11B2 and colorectal cancer as well as its underlying molecular mechanism. RESULTS: We determined that the anticancer ingredients contained in Sanguisorba officinalis, Patrinia scabiosaefolia, and Smilax china had more connections to the target proteins found in colorectal cancer. In the interaction network, eight small-molecule compounds had an activating effect on HSD11B2. The expression of the HSD11B2 was markedly decreased in colorectal cancer tissues and was positively correlated with the overall survival time of patients. In addition, co-expression analyses showed a close relationship between HSD11B2 and tissue-specific genes in colorectal tissues. The expression levels of HSD11B2 in well-, moderately, and poorly differentiated tissues progressively decreased. CONCLUSION: The HSD11B2 protein was a key CHM target for treating colorectal cancer. The key role of CHM may lie in activating HSD11B2 and further promoting tissue differentiation in colorectal cancer.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33107573

RESUMO

BACKGROUND: Ultrasound guided thermal ablation plays an important role in the management of thyroid disease. The objective of this study was to evaluate the feasibility, efficacy, and safety of thermal ablation for patients with solitary T1bN0M0 PTC who are ineligible for or unwilling to undergo surgery. MATERIALS AND METHODS: Data pertaining to 172 patients (38 males and 134 females) who received thermal ablation therapy at 12 hospitals between April 2015 and March 2020 were retrospectively analyzed. The mean duration of follow-up was 24.9 ± 14.1 months (range, 12-60). The technical feasibility, technical success, efficacy, and safety of treatment were analyzed. Post-ablation tumor size at various time-points was compared with pre-ablation measurement. RESULTS: All patients selected for thermal ablation received enlarged ablation according to contrast-enhanced ultrasound post-ablation. The maximum diameter and volume of ablation zone at 6,12, 18, 24, 36, and 48 months post-ablation were significantly smaller than those recorded pre-ablation (P < 0.05 for all). At the most recent follow-up, 106 (61.6%) tumors had completely disappeared. The rate of lymph node metastasis (LNM) was 0.6% (1/172) and the incidence of new tumor was 1.2% (2/172). The overall complication rate was 5.2% (9/172) (major complications: 4.6% [8/172]; minor complications: 0.6% [1/172]). All major complications were relieved within four months post-ablation. CONCLUSION: Thermal ablation may be a feasible, effective, and safe treatment option for patients with solitary T1bN0M0 PTC who are ineligible for or unwilling to undergo surgery. It may provide a novel treatment option for selected patients.

6.
J Neuroinflammation ; 17(1): 288, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008395

RESUMO

BACKGROUND: Growing evidence has shown that alterations in the gut microbiota composition were associated with a variety of neuropsychiatric conditions. However, whether such associations reflect causality remains unknown. We aimed to reveal the causal relationships among gut microbiota, metabolites, and neuropsychiatric disorders including Alzheimer's disease (AD), major depressive disorder (MDD), and schizophrenia (SCZ). METHODS: A two-sample bi-directional Mendelian randomization analysis was performed by using genetic variants from genome-wide association studies as instrumental variables for gut microbiota, metabolites, AD, MDD, and SCZ, respectively. RESULTS: We found suggestive associations of host-genetic-driven increase in Blautia (OR, 0.88; 95%CI, 0.79-0.99; P = 0.028) and elevated γ-aminobutyric acid (GABA) (0.96; 0.92-1.00; P = 0.034), a downstream product of Blautia-dependent arginine metabolism, with a lower risk of AD. Genetically increased Enterobacteriaceae family and Enterobacteriales order were potentially associated with a higher risk of SCZ (1.09; 1.00-1.18; P = 0.048), while Gammaproteobacteria class (0.90; 0.83-0.98; P = 0.011) was related to a lower risk for SCZ. Gut production of serotonin was potentially associated with an increased risk of SCZ (1.07; 1.00-1.15; P = 0.047). Furthermore, genetically increased Bacilli class was related to a higher risk of MDD (1.07; 1.02-1.12; P = 0.010). In the other direction, neuropsychiatric disorders altered gut microbiota composition. CONCLUSIONS: These data for the first time provide evidence of potential causal links between gut microbiome and AD, MDD, and SCZ. GABA and serotonin may play an important role in gut microbiota-host crosstalk in AD and SCZ, respectively. Further investigations in understanding the underlying mechanisms of associations between gut microbiota and AD, MDD, and SCZ are required.

7.
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.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33051670

RESUMO

CONTEXT: Dietary fiber intake may relate to bone health. OBJECTIVE: To investigate whether dietary fiber intake is associated with bone mineral density (BMD), and the modification effect of genetic variations related to gut microbiota-derived short-chain fatty acids (SCFAs). DESIGN: The associations of dietary fiber intake with estimated BMD derived from heel ultrasound and fractures were assessed in 224,630 and 384,134 participants from UK Biobank. SETTING: UK Biobank. MAIN OUTCOME MEASURES: Estimated BMD derived from heel ultrasound. RESULTS: Higher dietary fiber intake (per standard deviation) was significantly associated with higher heel-BMD (ß [SE]=0.0047 [0.0003], P=1.10E-54). Similarly significant associations were observed for all the fiber subtypes including cereal, fruit (dried and raw), and vegetable (cooked and raw). (all P<0.05). The positive association was found in both women and men but more marked among men except for dietary fiber in cooked vegetables (All Pinteraction<0.05). A protective association was found between dietary fiber intake and hip fracture (HR, 95% CI: 0.94, 0.89-0.99; P=3.0E-02). In addition, the association between dietary fiber and heel-BMD was modified by genetically determined SCFA propionate production (Pinteraction=5.1E-03). The protective association between dietary fiber and heel-BMD was more pronounced among participants with lower genetically determined propionate production. CONCLUSIONS: Our results indicate that greater intakes of total dietary fiber and subtypes from various food sources are associated with higher heel-BMD. Participants with lower genetically determined propionate production may benefit more from taking more dietary fiber.

10.
Sci Rep ; 10(1): 15863, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985582

RESUMO

The aim of this study is to investigate the association between maternal gestational weight gain (GWG) and preterm birth according to pre-pregnancy body mass index (BMI) and maternal age. We did a cohort, hospital-based study in Quzhou, South China, from 1 Jan 2018 to 30 June 2019. We selected 4274 singleton live births in our analysis, 315 (7.4%) of which were preterm births. In the overall population, excess GWG was significantly associated with a decreased risk of preterm birth compared with adequate GWG (adjusted OR 0.81 [95% CI 0.72-0.91]), and the risk varied by increasing maternal age and pre-pregnancy BMI. Interestingly, underweight women who older than 35 years with excess GWG had significantly increased odds of preterm birth compared with adequate GWG in underweight women aged 20-29 years (2.26 [1.06-4.85]) and normal weight women older than 35 years (2.23 [1.13-4.39]). Additionally, low GWG was positively and significantly associated with preterm birth overall (1.92 [1.47-2.50]). Among normal weight women category, compared with adequate GWG women aged 20-29 years did, those older than 20 years with low GWG, had significantly higher odds of preterm birth, which increased with maternal age (1.80 [1.16-2.79] in 20-29 years, 2.19 [1.23-3.91] in 30-34 years, 3.30 [1.68-6.46] in ≫ 35 years). In conclusion, maternal GWG was significantly associated with the risk of preterm birth, but the risk varied by pre-pregnancy BMI and maternal age.

11.
Diabetes Metab ; 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32889114

RESUMO

AIM: Evidence of the lungs being a target organ of diabetes-related pathophysiology is increasing, and decreased pulmonary function increases the risk of diabetes after adjusting for demographic and metabolic factors. This systematic review and meta-analysis evaluates the bidirectional relationship between diabetes and pulmonary function. METHODS: MEDLINE, Embase, The Cochrane Library and Web of Science databases were searched, and all studies describing this bidirectional relationship were identified. Two reviewers independently extracted study characteristics and assessed the risk of bias. RESULTS: A total of 93 studies were included in the meta-analysis. The pooled weighted mean difference (WMD) between diabetes patients and non-diabetic participants for forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were -5.65% and -5.91%, respectively, of predicted values. Diabetes-related microvascular complications and poor glycaemic control were associated with poorer pulmonary function in those with diabetes. In addition, diabetes was associated with a restrictive spirometry pattern (RSP) in both cross-sectional studies [odds ratio (OR): 2.88, 95% confidence interval (CI): 2.18-3.81, I2 = 0.0%] and prospective cohort studies [hazard ratio (HR): 1.57, 95% CI: 1.04-2.36]. In five longitudinal studies, the conclusions were inconsistent as to whether or not diabetes accelerates pulmonary function decline. However, every 10% decrease in baseline predicted FVC value was associated with a 13% higher risk of incident diabetes (HR: 1.13, 95% CI: 1.09-1.17, I2 = 0.0%). CONCLUSION: There is a bidirectional relationship between diabetes and pulmonary function. However, further investigations into whether dynamic changes in glycaemic levels before and shortly after diabetes onset mediate the deleterious effects on pulmonary function, or vice versa, are now required.

12.
Adv Ther ; 37(11): 4660-4674, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32970315

RESUMO

INTRODUCTION: Simultaneous administration of acetylsalicylic acid (ASA) and clopidogrel has demonstrated efficacy in the treatment of acute coronary syndrome. Clopidogrel + ASA in a fixed-dose combination (FDC) provides a pharmaceutical option to enhance adherence to the coadministration of dual antiplatelet therapy (DAPT). Herein, we evaluate the bioequivalence of enteric ASA and clopidogrel in an FDC compared with simultaneous administration of the individual formulations. METHODS: This study is a randomized, single-center, open-label, three-sequence, three-period, two-treatment, crossover study conducted in healthy Chinese male and female subjects under fed conditions. Subjects were randomized to receive, in each period, a single dose of (1) a combination tablet containing 75-mg clopidogrel and 100-mg enteric ASA (test formulation) or (2) coadministration of one 75-mg clopidogrel tablet and one 100-mg enteric-coated ASA tablet (reference formulations) under fed conditions. Plasma samples were analyzed for ASA, salicylic acid, clopidogrel, and the clopidogrel metabolite SR26334. For ASA, the reference-scaled average bioequivalence (RSABE) analysis was conducted for Cmax of ASA because within-subject standard deviation (SDW) was ≥ 0.294 for log-transformed Cmax. RESULTS: The point estimate (test/reference geometric mean ratio) was between 0.80 and 1.25, and the upper one-sided 95% confidence interval (CI) for the scaled average bioequivalence metric was ≤ 0 (-0.08). AUC of ASA as SDW was < 0.294 for log-transformed AUClast and AUC. Estimates of 90% CIs for log-transformed AUClast and AUC ratios were within the bioequivalence range of 0.80 to 1.25 (0.98-1.08 and 1.00-1.10, respectively). For clopidogrel, the 90% CIs for the ratios comparing log-transformed Cmax, AUClast, and AUC ratios of clopidogrel following administration of test versus reference formulation were calculated using the ABE method and were well within the acceptable range of 0.80 to 1.25 (1.02-1.12, 0.92-0.99, and 0.92-0.98, respectively). CONCLUSION: FDC of ASA and clopidogrel was bioequivalent to the simultaneous administration of the individual formulations in healthy Chinese subjects under fed conditions. TRIAL REGISTRATION: CTR20190376.

13.
Cancer Discov ; 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978226

RESUMO

Chromosome copy number variations are a hallmark of cancers. Among them, the prevalent chromosome 17p deletions are associated with poor prognosis and can promote tumorigenesis more than TP53 loss. Here we utilize multiple functional genetic strategies and identify a new 17p tumor suppressor gene, PHD finger protein 23 (PHF23). Its deficiency impairs B cell differentiation and promotes immature B lymphoblastic malignancy. Mechanistically, we demonstrate that PHF23, an H3K4me3 reader, directly binds the SIN3-HDAC complex through its N-terminus and represses its deacetylation activity on H3K27ac. Thus, the PHF23-SIN3-HDAC (PSH) complex coordinates these two major active histone markers for the activation of downstream TSGs and differentiation-related genes. Further, dysregulation of the PSH complex is essential for the development and maintenance of PHF23 deficient and 17p deleted tumors. Hence, our study reveals a novel epigenetic regulatory mechanism that contributes to the pathology of 17p-deleted cancers and suggests novel susceptibility to this disease.

14.
Nutr Metab Cardiovasc Dis ; 30(11): 2077-2084, 2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-32819784

RESUMO

BACKGROUND AND AIMS: To examine the associations between history of gestational diabetes mellitus (GDM) and breastfeeding with branched-chain amino acids (BCAA) and their metabolites in later life. METHODS AND RESULTS: 638 women (mean age 48.0 y) who had participated in the Bogalusa Heart Study and substudies of pregnancy history had untargeted, ultrahigh performance liquid chromatography-tandem mass spectroscopy conducted by Metabolon© on serum samples. Metabolites were identified that were BCAA or associated with BCAA metabolic pathways. History of GDM at any pregnancy (self-reported, confirmed with medical records when possible) as well as breastfeeding were examined as predictors of BCAA using linear models, controlling for age, race, BMI, waist circumference, and menopausal status. None of the BCAA differed statistically by history of either GDM or breastfeeding, although absolute levels of each of the BCAA were higher with GDM and lower with breastfeeding. Of the 27 metabolites on the leucine, isoleucine and valine metabolism subpathway, 1-carboxyethylleucine, 1-carboxyethyvaline, and 3-hydroxy-2-ethylpropionate were higher in women with a history of GDM, but lower in women in women with a history of breastfeeding. Similar results were found for alpha-hydroxyisocaproate, 1-carboxyethylisoleucine, and N-acetylleucine. CONCLUSIONS: GDM and breastfeeding are associated in opposite directions with several metabolites on the BCAA metabolic pathway.

15.
Environ Int ; 143: 105973, 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32738765

RESUMO

Activated sludge processes with an ultra-short sludge retention time (ultra-short-SRT) are considered to have potential for energy and resource recovery from wastewater. The present study focused on the sludge characteristics, system performance and microbial kinetics in ultra-short-SRT activated sludge (USSAS) processes using typical domestic wastewater (SRT = 0.5, 1, 2, 3 and 4 d). The results showed that compared with the sludge in conventional activated sludge (CAS) processes, the sludge structure in USSAS system was looser (fractal dimension, D2P, 1.19-1.33), the boundary was rougher (pore boundary fractal dimension, DB, 1.44-1.59), the sludge concentration was lower, and the sludge volume index (SVI) was higher; bacteria such as Thiothrix and Trichococcus that cause sludge bulking, which poses an operation risk, were extensively detected, especially at SRTs of 0.5 d and 1.0 d. The performance in terms of total chemical oxygen demand (tCOD) and phosphorus removal increased with increasing SRT, and the highest removal rate (approximately 85% for tCOD and 90% for phosphorus) was observed when the SRT was 4 d. Both bioconversion and biosorption were responsible for the C/P separation, and their roles were different for different types of organic matter and phosphorus under different SRT conditions. The proportion of phosphate-accumulating organisms (PAO) reached 2.4% when the SRT was 3 d, resulting in highly effective biological phosphorus removal. The values of microbial kinetic parameters such as YH and KdH in USSAS systems were higher than those in CAS systems, indicating faster microbial community renewal. This study was helpful for understanding the characteristics of USSAS process.

16.
Diabetes Obes Metab ; 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32734691

RESUMO

AIM: To investigate whether the genetic risk score (GRS) for lean body mass (LBM) modified the effects of weight-loss diets on changes in appetite and adiposity among overweight and obese individuals. PARTICIPANTS AND METHODS: In the 2-year Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial, we included 692 adults who were randomly assigned to one of four diets varying in macronutrient intake. A GRS was calculated using five single nucleotide polymorphisms associated with LBM. RESULTS: The LBM-GRS was not associated with the baseline LBM measured by dual-energy x-ray absorptiometry in a subgroup (50%) of the study population. We found that the LBM-GRS had significantly different associations with changes in appetite from baseline to 6 months according to low- or high-fat diet group (P-interaction < 0.001, 0.021, 0.005 and 0.024 for total appetite score, hunger, fullness and prospective consumption, respectively). Lower LBM-GRS (indicating a greater genetic predisposition to LBM) was associated with greater decreases in the total appetite score (P < 0.001), hunger (P = 0.01), fullness (P = 0.001) and prospective consumption (P = 0.019) in participants in the low-fat diet group, whereas no significant associations with these appetite measures were observed in the high-fat diet group. In addition, lower LBM-GRS was associated with greater reduction in body weight (P = 0.003) and waist circumference (P = 0.011) among participants in the low-fat diet group, while no associations were observed in the high-fat diet group. The interactions attenuated, along with weight regain, from 6 months to 2 years. CONCLUSIONS: Our findings suggest that genetic variation in LBM may be differentially associated with appetite changes, and may subsequently be related to changes in body weight and waist circumference, according to dietary fat intake.

17.
Mayo Clin Proc ; 95(9): 1877-1887, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32861332

RESUMO

OBJECTIVE: To analyze the interactions between maternal gestational diabetes mellitus (GDM) and genetically determined maternal body mass index (BMI) during pregnancy on offspring childhood obesity. RESEARCH DESIGN AND METHODS: A total of 1114 Chinese mother-child pairs (560 GDM and 554 non-GDM) were included between August 2009 and July 2011. Maternal genetic risk score (GRS) of BMI during pregnancy was derived on the basis of 12 single nucleotide polymorphisms identified from a genome-wide association study. Offspring's BMI, BMI-for-age z score, weight, weight-for-age z score, waist circumference, sum of skinfolds, and body fat percentage during childhood were measured or calculated. RESULTS: Maternal GRS of BMI during pregnancy significantly interacted with maternal GDM status on childhood risks of overweight and obesity (all P for interaction <.05). After multivariable adjustment, per unit of GRS was associated with a 24% (P<.001) and a 28% (P<.001) increased risk of overweight and obesity among children of GDM mothers, whereas no significant associations were observed among children of mothers without GDM. In addition, per unit GRS of BMI during pregnancy was significantly associated with 0.16 kg/m2 higher BMI (P=.002), 0.09 higher BMI-for-age z score (P=.002), 0.24 kg higher weight (P=.04), 0.06 higher weight-for-age z score (P=.02), 0.28 cm higher waist circumference (P=.03), 0.94 mm higher sum of skinfolds (P=.004), and 0.37% higher body fat percentage (P=.03) among children of GDM mothers. There were no significant associations between maternal GRS of BMI during pregnancy and offspring's obesity-related outcomes among children of mothers without GDM. CONCLUSION: Our findings for the first time indicate that maternal GDM status may modify the relation between genetically determined maternal BMI during pregnancy and offspring's obesity risk during childhood.

18.
J Exp Clin Cancer Res ; 39(1): 168, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843066

RESUMO

BACKGROUND: cAMP responsive element binding protein 5 (CREB5) is a transcriptional activator in eukaryotic cells that can regulate gene expression. Previously, we found that CREB5 was involved in the occurrence and development of colorectal cancer (CRC) using bioinformatics analysis. However, the biological roles and underlying regulatory mechanism of CREB5 in CRC remain unclear. METHODS: Real-time PCR, western blotting, and immunohistochemistry were used to examine CREB5 expression. In vitro experiments including migration assay, wound-healing assay, chicken chorioallantoic membrane assay, and human umbilical vein endothelial cells tube formation assay were used to investigate the effects of CREB5 on CRC cell migration and tumor angiogenesis ability. Additionally, an orthotopic implantation assay was performed in nude mice to confirm the effects of CREB5 in vivo. Furthermore, gene set enrichment analysis was performed to explore the potential mechanism of CREB5 in CRC. RESULTS: We found that CREB5 expression was highly upregulated in CRC. CREB5 overexpression was positively correlated with advanced WHO stages and TNM stages and shorter survival in CRC patients. Moreover, CREB5 overexpression promoted while CREB5 silencing reduced the invasiveness and metastatic capacity of CRC cells both in vitro and in vivo. Furthermore, CREB5 directly interacted with the MET promoter and activated the hepatocyte growth factor-MET signalling pathway. Importantly, inhibition of MET reduced the invasion and metastasis of CREB5-overexpressing CRC cells, suggesting that CREB5 promotes metastasis mainly through activation of MET signalling. CONCLUSION: Our study demonstrates a crucial role for CREB5 in CRC metastasis by directly upregulating MET expression. CREB5 may be both a potential prognostic marker and a therapeutic target to effectively overcome metastasis in CRC.

19.
Diabetes Care ; 43(11): 2776-2784, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32847829

RESUMO

OBJECTIVE: Circulating vitamin D concentrations have been associated with the risk of type 2 diabetes (T2D), but the results are inconsistent. Emerging evidence suggests that vitamin D metabolism is linked to sleep behaviors. We investigated the prospective association between serum 25-hydroxyvitamin D (25OHD) and the risk of incident T2D and whether such association was modified by sleep behaviors. RESEARCH DESIGN AND METHODS: The study included 350,211 individuals free of diabetes in the UK Biobank. Serum 25OHD (nmol/L) concentrations were measured. Five sleep behaviors including sleep duration, insomnia, snoring, chronotype, and daytime sleepiness were included to generate overall sleep patterns, defined by healthy sleep scores. We also calculated genetic risk scores of sleep patterns. RESULTS: During a median follow-up of 8.1 years, we documented 6,940 case subjects with incident T2D. We found that serum 25OHD was significantly associated with a lower risk of incident T2D, and the multivariate adjusted hazard ratio (HR) (95% CI) per 10 nmol/L increase was 0.88 (0.87-0.90). We found a significant interaction between 25OHD and overall sleep patterns on the risk of incident T2D (P for interaction = 0.002). The inverse association between high 25OHD and T2D was more prominent among participants with healthier sleep patterns. Among the individual sleep behaviors, daytime sleepiness showed the strongest interaction with 25OHD (P for interaction = 0.0006). The reduced HR of T2D associated with high 25OHD appeared to be more evident among participants with no frequent daytime sleepiness compared with those with excessive daytime sleepiness. The genetic variations of the sleep patterns did not modify the relation between 25OHD and T2D. CONCLUSIONS: Our study indicates that higher serum 25OHD concentrations are associated with a lower risk of incident T2D, and such relations are modified by overall sleep patterns, with daytime sleepiness being the major contributor.

20.
Sci Rep ; 10(1): 12997, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32747656

RESUMO

Lipids in sewage sludge are considered to be high-class raw materials for biodiesel or other valuable products. We profiled the characteristics and assessed the reutilization potential of lipids from different sludge sources, including sludge from the primary sedimentation tank (PST sludge) and sludge from the secondary sedimentation tank in a conventional activated sludge system (CAS sludge), as well as sludge from ultrashort-sludge retention time (SRT) activated sludge systems with different SRTs (USAS sludge, with SRTs of 0.5, 1.0, 2.0, 3.0 and 4.0 d). The results showed that the lipids in the sludges were mainly composed of cellular lipids, free fatty acids (FFAs), wax and gum. The highest lipid content was found in the PST sludge (156.8 ± 11.9 mg/g, dry basis), followed by the USAS sludges (67.9 ± 11.0-132.2 ± 11.8 mg/g) and the CAS sludge (46.0 ± 16.5 mg/g). Lipid species such as Cer, So, PE, PC, and TG were abundant, comprising over 80% of the cellular lipids in the sludges. With higher lipid contents, the PST sludge and USAS sludge (0.5 d SRT) were suggested to have a higher reutilization potential for use in producing biodiesel. In addition, the CAS sludge was promising for resource reutilization and energy recovery due to the large amount of excess sludge.

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