Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 672
Filtrar
1.
Molecules ; 26(5)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652818

RESUMO

Glaesserella parasuis (G. parasuis) causes inflammation and damage to piglets. Whether polyserositis caused by G. parasuis is due to tight junctions damage and the protective effect of baicalin on it have not been examined. Therefore, this study aims to investigate the effects of baicalin on peritoneal tight junctions of piglets challenged with G. parasuis and its underlying molecular mechanisms. Piglets were challenged with G. parasuis and treated with or without baicalin. RT-PCR was performed to examine the expression of peritoneal tight junctions genes. Immunofluorescence was carried out to detect the distribution patterns of tight junctions proteins. Western blot assays were carried out to determine the involved signaling pathways. Our data showed that G. parasuis infection can down-regulate the tight junctions expression and disrupt the distribution of tight junctions proteins. Baicalin can alleviate the down-regulation of tight junctions mRNA in peritoneum, prevent the abnormalities and maintain the continuous organization of tight junctions. Our results provide novel evidence to support that baicalin has the capacity to protect peritoneal tight junctions from G. parasuis-induced inflammation. The protective mechanisms of baicalin could be associated with inhibition of the activation of PKC and MLCK/MLC signaling pathway. Taken together, these data demonstrated that baicalin is a promising natural agent for the prevention and treatment of G. parasuis infection.

2.
Br J Clin Pharmacol ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33533507

RESUMO

AIM: GSK3640254, a novel, next-generation maturation inhibitor effective against a range of HIV polymorphisms with no cross-resistance to current antiretroviral therapy, could potentially be coadministered with dolutegravir as a two-drug regimen. In this phase I study, pharmacokinetics and tolerability of GSK3640254 plus dolutegravir were assessed. METHODS: Healthy participants received dolutegravir 50 mg once daily (QD) on Days 1-5 in period 1, GSK3640254 200 mg QD on Days 1-7 in period 2, and dolutegravir 50 mg plus GSK3640254 200 mg QD on Days 1-7 in period 3. All treatments were administered with a moderate-fat meal 30 minutes prior to dosing. Pharmacokinetics parameters were derived by noncompartmental methods, and geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were derived using linear mixed effects models. Adverse events, laboratory measurements, electrocardiography, and vital signs were monitored. RESULTS: Sixteen participants completed the study. GMRs (90% CI) for dolutegravir area under the plasma concentration-time curve from time 0 to the end of the dosing interval at steady state (AUC0-t ), maximum observed concentration (Cmax ), and plasma concentration at the end of the dosing interval (Ct ) were 1.17 (1.118-1.233), 1.09 (1.044-1.138), and 1.24 (1.160-1.315), respectively. GMRs (90% CI) for GSK3640254 AUC0-t , Cmax , and Ct were 1.04 (0.992-1.094), 0.99 (0.923-1.065), and 0.10 (0.939-1.056), respectively. Dolutegravir plus GSK3640254 coadministration did not meaningfully alter steady-state exposure to dolutegravir or GSK3640254. No clinically significant trends in tolerability or safety were observed. CONCLUSION: Coadministration of GSK3640254 with dolutegravir did not result in clinically significant drug interaction and was well tolerated.

4.
Chin J Integr Med ; 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33609233

RESUMO

OBJECTIVE: To compare the therapeutic effect of different animal bile powders on lipid metabolism disorders induced by high-fat diet in rats, and analyze the bioactive components of each animal bile powder. METHODS: Sixty Sprague-Dawley rats were randomly divided into 6 groups (n=10): normal diet control group, high-fat diet model group, high-fat diet groups orally treated with bear, pig, cow and chicken bile powders, respectively. Serum biochemical markers from the abdominal aorta in each group were analyzed. Changes in the body weight and liver weight were recorded. Pathohistological changes in the livers were examined. High performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was used to determine the composition of bioactive components in each animal bile powder. RESULTS: Treatment with different types of animal bile powders had different inhibitory effects on high-fat diet-induced increase of body weight and/or liver weight in rats, most notably in bear and pig bile powders (P<0.05). High-fat diet induced lipid metabolism disorder in rats, which could be reversed by treatment with all kinds of bile powders. Bear bile and chicken bile showed the most potent therapeutic effect against lipid metabolism disorder. Cow and bear bile effectively alleviated high-fat diet induced liver enlargement and discoloration, hepatocyte swelling, infiltration of inflammatory cells and formation of lipid vacuoles. Bioactive component analysis revealed that there were significant differences in the relative content of taurocholic acid, taurodeoxycholic acid and ursodeoxycholic acid among different types of animal bile. Interestingly, a unique component with molecular weight of 496.2738 Da, whose function has not yet been reported, was identified only in bear bile powder. CONCLUSIONS: Different animal bile powders had varying therapeutic effect against lipid metabolism disorders induced by high-fat diet, and bear bile powder demonstrated the most effective benefits. Bioactive compositions were different in different types of animal bile with a novel compound identified only in bear bile powder.

5.
J Am Heart Assoc ; 10(5): e019459, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33586478

RESUMO

Background Asymptomatic proximal deep vein thrombosis (DVT) is an end point frequently used to evaluate the efficacy of anticoagulant thromboprophylaxis in medical patients. Recently, the clinical relevance of asymptomatic DVT has been challenged. Methods and Results The objective of this study was to evaluate the relationship between asymptomatic proximal DVT and all-cause mortality (ACM) using a cohort analysis of a randomized trial for the prevention of venous thromboembolism (VTE) in acutely ill medical patients. Patients who received at least 1 dose of study drug and had an adequate compression ultrasound examination of the legs on either day 10 or day 35 were categorized into 1 of 3 cohorts: no VTE, asymptomatic proximal DVT, or symptomatic DVT. Cox proportional hazards model, with adjustment for significant independent predictors of mortality, were used to compare the incidences of ACM. Of the 7036 patients, 6776 had no VTE, 236 had asymptomatic DVT, and 24 had symptomatic VTE. The incidence of ACM was 4.8% in patients without VTE. Both asymptomatic proximal DVT (mortality, 11.4%; hazard ratio [HR], 2.31; 95% CI, 1.52-3.51; P<0.0001) and symptomatic VTE (mortality, 29.2%; HR, 9.42; 95% CI, 4.18-21.20; P<0.0001) were independently associated with significant increases in ACM. The analysis was post hoc, and ultrasound results were not available for all patients. Adjustment for baseline variables significantly associated with ACM may not fully compensate for differences. Conclusions Asymptomatic proximal DVT is associated with higher ACM than no VTE and remains a relevant end point to evaluate the efficacy of anticoagulant thromboprophylaxis in medical patients. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00571649.

6.
BMC Gastroenterol ; 21(1): 65, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579203

RESUMO

BACKGROUND: Single nucleotide polymorphism (SNP)-based polygenic risk scoring is predictive of colorectal cancer (CRC) risk. However, few studies have investigated the association of genetic risk score (GRS) with detection of adenomatous polyps at screening colonoscopy. METHODS: We randomly selected 1769 Caucasian subjects who underwent screening colonoscopy from the Genomic Health Initiative (GHI), a biobank of NorthShore University HealthSystem. Outcomes from initial screening colonoscopy were recorded. Twenty-two CRC risk-associated SNPs were obtained from the Affymetrix™ SNP array and used to calculate an odds ratio (OR)-weighted and population-standardized GRS. Subjects with GRS of < 0.5, 0.5-1.5, and > 1.5 were categorized as low, average and elevated risk. RESULTS: Among 1,769 subjects, 520 (29%) had 1 or more adenomatous polyps. GRS was significantly higher in subjects with adenomatous polyps than those without; mean (95% confidence interval) was 1.02 (1.00-1.05) and 0.97 (0.95-0.99), respectively, p < 0.001. The association remained significant after adjusting for age, gender, body mass index, and family history, p < 0.001. The detection rate of adenomatous polyps was 10.8%, 29.0% and 39.7% in subjects with low, average and elevated GRS, respectively, p-trend < 0.001. Higher GRS was also associated with early age diagnosis of adenomatous polyps, p < 0.001. In contrast, positive family history was not associated with risk and age of adenomatous polyps. CONCLUSIONS: GRS was significantly associated with adenomatous polyps in subjects undergoing screening colonoscopy. This result may help in stratifying average risk patients and facilitating personalized colonoscopy screening strategies.

7.
Nephrology (Carlton) ; 26(3): 227-233, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33484075

RESUMO

BACKGROUND: The causal relationship between adiponectin (ADPN) and estimated glomerular filtration rate (eGFR) is unclear. This study adopts a two-sample bidirectional Mendelian randomization (MR) study to explore the causal relationship between ADPN and eGFR. METHODS: Using eight single nucleotide polymorphisms (SNP) of ADPN and 26 SNP of eGFR as instrumental variables, the study performs a two-sample bidirectional MR study using MR inverse-variance weighted (IVW), MR-Egger and weighted median approach to evaluate the causal relationship between ADPN and eGFR. Using the genetic risk score (GRS) of ADPN and eGFR as instrumental variables, the study performs a second MR analysis to assess the association between ADPN and eGFR. RESULTS: In ADPN to eGFR MR analysis, the IVW, weighted median and GRS analysis all showed that ADPN had a causal effect on eGFR after removing potential confounders of the ADPN-eGFR relation (IVW: ß = .016, P = .002; weighted median: ß = .012, P = .022; GRS: ß = .016, P = 1.48E-05). As both ADPN and eGFR were natural log-transformed in the corresponding GWAS, eGFR increased by 0.15% for any 10% increase in ADPN. In eGFR to ADPN MR analysis, eGFR had no causal effect on ADPN after removing potential confounders of the eGFR-ADPN relation (All P values > 0.05). The heterogeneity test and sensitivity analysis indicated some heterogeneity, but no directional pleiotropy. CONCLUSION: Adiponectin has a causal effect on eGFR, while eGFR has no causal effect on ADPN. ADPN may be a clinical target for improving eGFR and treating chronic kidney disease caused by decreased eGFR.

8.
Nat Commun ; 12(1): 400, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452255

RESUMO

Promoter DNA methylation is a well-established mechanism of transcription repression, though its global correlation with gene expression is weak. This weak correlation can be attributed to the failure of current methylation quantification methods to consider the heterogeneity among sequenced bulk cells. Here, we introduce Cell Heterogeneity-Adjusted cLonal Methylation (CHALM) as a methylation quantification method. CHALM improves understanding of the functional consequences of DNA methylation, including its correlations with gene expression and H3K4me3. When applied to different methylation datasets, the CHALM method enables detection of differentially methylated genes that exhibit distinct biological functions supporting underlying mechanisms.


Assuntos
Metilação de DNA , Epigênese Genética , Epigenômica/métodos , Regiões Promotoras Genéticas/genética , Sequenciamento de Cromatina por Imunoprecipitação , Ilhas de CpG/genética , Conjuntos de Dados como Assunto , Aprendizado Profundo , Histonas , Humanos , RNA-Seq
9.
J Transl Med ; 19(1): 41, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33482857

RESUMO

BACKGROUND: Genome-wide association studies have identified thousands of disease-associated single nucleotide polymorphisms (SNPs). A subset of these SNPs may be additively combined to generate genetic risk scores (GRSs) that confer risk for a specific disease. Although the clinical validity of GRSs to predict risk of specific diseases has been well established, there is still a great need to determine their clinical utility by applying GRSs in primary care for cancer risk assessment and targeted intervention. METHODS: This clinical study involved 281 primary care patients without a personal history of breast, prostate or colorectal cancer who were 40-70 years old. DNA was obtained from a pre-existing biobank at NorthShore University HealthSystem. GRSs for colorectal cancer and breast or prostate cancer were calculated and shared with participants through their primary care provider. Additional data was gathered using questionnaires as well as electronic medical record information. A t-test or Chi-square test was applied for comparison of demographic and key clinical variables among different groups. RESULTS: The median age of the 281 participants was 58 years and the majority were female (66.6%). One hundred one (36.9%) participants received 2 low risk scores, 99 (35.2%) received 1 low risk and 1 average risk score, 37 (13.2%) received 1 low risk and 1 high risk score, 23 (8.2%) received 2 average risk scores, 21 (7.5%) received 1 average risk and 1 high risk score, and no one received 2 high risk scores. Before receiving GRSs, younger patients and women reported significantly more worry about risk of developing cancer. After receiving GRSs, those who received at least one high GRS reported significantly more worry about developing cancer. There were no significant differences found between gender, age, or GRS with regards to participants' reported optimism about their future health neither before nor after receiving GRS results. CONCLUSIONS: Genetic risk scores that quantify an individual's risk of developing breast, prostate and colorectal cancers as compared with a race-defined population average risk have potential clinical utility as a tool for risk stratification and to guide cancer screening in a primary care setting.

10.
Scand J Clin Lab Invest ; 81(1): 59-64, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33315479

RESUMO

Hemoglobin (Hb) variants, characterized by structural abnormalities in the globin chains, are among the most common inherited disorders. It has been shown that Hb variant remains an important cause of erroneous HbA1c results. Thus, it is important to be aware of the extent of the interference of each Hb variant encountered to avoid reporting unreliable results. However, the effects of many types of Hb variants on the measurement of HbA1c remain unclear. Here, we describe three rare Hb variants, Hb J-Tashikuergan [HBA2: c.59 C > A], Hb Pyrgos [HBB: c.251G > A], and Hb Hope [HBB: c.410 G > A], which lead to extremely high values (>25%) determined by Variant II Turbo 2.0. We further investigated their effects on HbA1c measurement by an HPLC system (Bio-Rad D100), a CE system (Sebia Capillarys 3 TERA), a boronate affinity chromatography system (Premier Hb9210), and an immunoassay method (Roche Diagnostics), and found that these Hb variants severely interfered with HbA1c measurement by Variant II Turbo 2.0 and Bio-Rad D100. This study demonstrates that patients with abnormally high HbA1c levels should be highly suspected of carrying Hb variants. When the HbA1c results are considered unreliable, other indicators such as glycated albumin may be a possible alternative to HbA1c in diabetic patients.

11.
Eur Urol ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33257031

RESUMO

BACKGROUND: Single nucleotide polymorphism-based genetic risk score (GRS) has been developed and validated for prostate cancer (PCa) risk assessment. As GRS is population standardized, its value can be interpreted as a relative risk to the general population. OBJECTIVE: To compare the performance of GRS with two guideline-recommended inherited risk measures, family history (FH) and rare pathogenic mutations (RPMs), for predicting PCa incidence and mortality. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort was derived from the UK Biobank where 208 685 PCa diagnosis-free participants at recruitment were followed via the UK cancer and death registries. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Rate ratios (RRs) of PCa incidence and mortality for FH (positive vs negative), RPMs (carriers vs noncarriers), and GRS (top vs bottom quartile) were measured. RESULTS AND LIMITATIONS: After a median follow-up of 9.67 yr, 6890 incident PCa cases (419 died of PCa) were identified. Each of the three measures was significantly associated with PCa incidence in univariate analyses; RR (95 % confidence interval [CI]) values were 1.88 (1.75-2.01) for FH, 2.89 (1.89-4.25) for RPMs, and 1.97(1.87-2.07) for GRS (all p < 0.001). The associations were independent in multivariable analyses. While FH and RPMs identified 11 % of men at higher PCa risk, addition of GRS identified an additional 22 % of men at higher PCa risk, and increases in C-statistic from 0.58 to 0.67 for differentiating incidence (p < 0.001) and from 0.65 to 0.71 for differentiating mortality (p = 0.002). Limitations were a small number of minority patients and short mortality follow-up. CONCLUSIONS: This population-based prospective study suggests that GRS complements two guideline-recommended inherited risk measures (FH and RPMs) for stratifying the risk of PCa incidence and mortality. PATIENT SUMMARY: In a large population-based prostate cancer (PCa) prospective study derived from UK Biobank, genetic risk score (GRS) complements two guideline-recommended inherited risk measures (family history and rare pathogenic mutations) in predicting PCa incidence and mortality. These results provide critical data for including GRS in PCa risk assessment.

12.
Clin Transl Sci ; 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-33278338

RESUMO

Malnutrition in gastric cancer patients with normal body mass index (BMI) is often ignored. This study aimed to explore the role of sarcopenia in predicting postoperative complication and long-term survival in gastric cancer patients with normal BMI. We included patients with normal BMI (18.5 kg/m2 ≤ BMI < 23 kg/m2 ) who underwent radical gastrectomy between July 2014 and December 2016. Sarcopenia was assessed by muscle mass, handgrip strength, and gait speed. Kaplan-Meier survival analysis was used to analyze the association between sarcopenia and the prognosis of gastric cancer patients. Univariate and multivariate analyses were used to identify risk factors contributing to postoperative complications and long-term survival. Overall, 267 gastric cancer patients with normal BMI were included in this study; of which, 49 (18.35%) patients were diagnosed with sarcopenia. Sarcopenia patients had higher incidence of a major postoperative complication, longer postoperative hospital stays, and greater hospital costs. The Kaplan-Meier survival analysis showed that sarcopenia patients had poorer overall survival than non-sarcopenia patients. Univariate and multivariate analyses showed that sarcopenia was an independent predictor for postoperative complication and long-term survival in such patients. Sarcopenia is an independent predictor for postoperative complication and long-term survival in patients with normal BMI after radical gastrectomy for gastric cancer. We recommend that patients with normal BMI should perform nutritional risk screening by sarcopenia.

13.
Prostate ; 80(15): 1314-1321, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33258481

RESUMO

BACKGROUND: Genome-wide association studies have identified over 100 single-nucleotide polymorphisms (SNPs) associated with prostate cancer (PrCa), and polygenic risk scores (PRS) based on their combined genotypes have been developed for risk stratification. We aimed to assess the contribution of PRS to PrCa risk in a large multisite study. METHODS: The sample included 1972 PrCa cases and 1919 unaffected controls. Next-generation sequencing was used to assess pathogenic variants in 14 PrCa-susceptibility genes and 72 validated PrCa-associated SNPs. We constructed a population-standardized PRS and tested its association with PrCa using logistic regression adjusted for age and family history of PrCa. RESULTS: The mean age of PrCa cases at diagnosis and age of controls at testing/last clinic visit was 59.5 ± 7.2 and 57.2 ± 13.0 years, respectively. Among 1740 cases with pathology data, 57.4% had Gleason score ≤ 6, while 42.6% had Gleason score ≥ 8. In addition, 39.6% cases and 20.1% controls had a family history of PrCa. The PRS was significantly higher in cases than controls (mean ± SD: 1.42 ± 1.11 vs 1.02 ± 0.76; P < .0001). Compared with men in the 1st quartile of age-adjusted PRS, those in the 2nd, 3rd, and 4th quartile were 1.58 (95% confidence interval [CI]: 1.31-1.90), 2.36 (95% CI: 1.96-2.84), and 3.98 (95% CI: 3.29-4.82) times as likely to have PrCa (all P < .0001). Adjustment for family history yielded similar results. PRS predictive performance was consistent with prior literature (area under the receiver operating curve = 0.64; 95% CI: 0.62-0.66). CONCLUSIONS: These data suggest that a 72-SNP PRS is predictive of PrCa, supporting its potential use in clinical risk assessment.

14.
Int J Cancer ; 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33300603

RESUMO

Cystic fibrosis (CF) carriers carrying one defective copy of a CFTR germline mutation are common in the general population. A recent study reported associations of CF carriers with risk for cancers of digestive organs and pancreatic cancer. In the current study, we assessed associations of CFTR F508del carriers with the risk for 54 types of cancers in the UK Biobank, a large population-based study. In Caucasians, compared to the carrier rate of 3.15% (12,357/392,274) in non-cancer subjects, the rate was significantly higher in cancer patients overall (2,621/79,619=3.29%), especially in patients with colorectal cancer (247/6,667=3.70%), cancers of gallbladder and biliary tract (21/351=5.98%), thyroid cancer (30/665=4.51%), and unspecified non-Hodgkin's lymphoma (74/1,805=4.10%), all P<=0.05. In contrast, the carrier rate in patients with cancers of lung and bronchus was significantly lower (89/3,463=2.57%), P=0.05. The association of CFTR F508del carriers with these types of cancer remained significant after adjusting for respective cancer-specific risk factors. For pancreatic cancer, although a higher carrier rate (38/1,004=3.78%) was found in patients with this cancer, the difference was not statistically significant (P=0.26). This null association was unlikely due to lack of statistical power; the large sample size of our study had >80% power, at a significance level of 0.05, to detect an association of >1.5-fold increased risk. In conclusion, the identified associations of CFTR F508del carriers with multiple types of cancer may have potential biological and clinical implications if confirmed in independent study populations. This article is protected by copyright. All rights reserved.

15.
Pharmacol Res Perspect ; 8(6): e00671, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33200887

RESUMO

Despite advances in HIV-1 management with antiretroviral therapy, drug resistance and toxicities with multidrug regimens can result in treatment failure. Hence, there is a continuing demand for antiretroviral agents (ARVs) with novel mechanisms of action. Maturation inhibitors inhibit HIV-1 replication via a unique mechanism of action and can be combined with other ARVs. Two phase I randomized clinical trials were conducted for a maturation inhibitor, GSK3640254, to determine safety, pharmacokinetics (NCT03231943), and relative bioavailability (NCT03575962) in healthy adults. The first trial was conducted in two parts. Part 1 was conducted in a two-cohort, interlocking, eight-period fashion in 20 participants with single ascending doses of GSK3640254 (1-700 mg) or placebo. In Part 2, 58 participants were randomized to receive GSK3640254 (n = 44) or placebo (n = 14). Four participants reported adverse events (AEs) leading to study discontinuation, with one adverse drug reaction (maculopapular rash). There was no relationship between frequency or severity of AEs and dose. Pharmacokinetic assessments showed that GSK3640254 was slowly absorbed, with time to maximum concentration (tmax) occurring between 3.5 and 4 hours and half-life of ~24 hours. In the relative bioavailability study of GSK3640254 mesylate salt vs bis-hydrochloride salt capsules in 14 healthy adults, the mesylate salt performed slightly better than the bis-hydrochloride formulation (12%-16% increase in area under the concentration-time curve and maximum concentration); tmax (5 hours) was similar between the formulations. Initial pharmacokinetic and safety data from these healthy-participant studies informed further development of GSK3640254 for once-daily dosing for the treatment of HIV-1 infection.

16.
Sci Total Environ ; : 143617, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33213921

RESUMO

The frequency of harmful algal blooms caused by eutrophication is increasing globally, posing serious threats to human health and economic development. Reservoir bays, affected by water environment and local watershed landscape, are more prone to eutrophication and algal blooms. The chlorophyll a (Chl a) concentration is an important indicator for the degree of eutrophication and algal bloom. Exploring the complex relationships between water environment and landscape background, and Chl a concentration in the reservoir bays are crucial for ensuring high-quality drinking water from reservoirs. In this study, we monitored Chl a concentrations of 66 bays in Danjiangkou Reservoir and the related water quality parameters (e.g., water temperature, turbidity, nutrients) in waterbodies of these reservoir bays in the storage and discharge periods from 2015 to 2018. Partial least squares-structural equation modeling (PLS-SEM) was used to quantify the relationship between water environmental factors and watershed landscapes, and Chl a concentrations in reservoir bays. The results showed that mean Chl a concentration was higher in storage period than that in discharge period. Two optimal PLS-SEMs explained 66.8% and 53.6% of Chl a concentration variation in the storage and discharge periods, respectively. The net effect of water chemistry on Chl a concentration was more pronounced during the discharge period (total effect = 0.61, 37% of the total effect on Chl a), while the net effect of land-use composition on Chl a concentration was more significant during the storage period (total effect = 0.57, 30% of the total effect on Chl a). The landscape pattern had significant indirect effects on Chl a concentration, especially during the discharge period (indirect effect = -0.31, 19% of the total effect on Chl a). Our results provide valuable information for managers to make rational decisions, thereby contributing to the prevention of eutrophication and algal blooms in reservoir bays.

17.
Nat Chem ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208896

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

18.
Nat Chem ; 12(11): 1023-1028, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33093680

RESUMO

Life is an out-of-equilibrium system sustained by a continuous supply of energy. In extant biology, the generation of the primary energy currency, adenosine 5'-triphosphate and its use in the synthesis of biomolecules require enzymes. Before their emergence, alternative energy sources, perhaps assisted by simple catalysts, must have mediated the activation of carboxylates and phosphates for condensation reactions. Here, we show that the chemical energy inherent to isonitriles can be harnessed to activate nucleoside phosphates and carboxylic acids through catalysis by acid and 4,5-dicyanoimidazole under mild aqueous conditions. Simultaneous activation of carboxylates and phosphates provides multiple pathways for the generation of reactive intermediates, including mixed carboxylic acid-phosphoric acid anhydrides, for the synthesis of peptidyl-RNAs, peptides, RNA oligomers and primordial phospholipids. Our results indicate that unified prebiotic activation chemistry could have enabled the joining of building blocks in aqueous solution from a common pool and enabled the progression of a system towards higher complexity, foreshadowing today's encapsulated peptide-nucleic acid system.

19.
Mol Cancer Res ; 18(12): 1815-1824, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33115829

RESUMO

We aim to understand, from acquired genetic alterations in tumors, why African American (AA) men are more likely to develop aggressive prostate cancer. By analyzing somatic mutations in 39 genes using deeper next-generation sequencing with an average depth of 2,522 reads for tumor DNA and genome-wide DNA copy-number alterations (CNA) in prostate cancer in a total of 171 AA/black men and comparing with those in 860 European American (EA)/white men, we here present several novel findings. First, >35% of AA men harbor damaging mutations in APC, ATM, BRCA2, KDM6A, KMT2C, KMT2D, MED12, ZFHX3, and ZMYM3, each with >1% of mutated copies. Second, among genes with >10% of mutated copies in tumor cells, ZMYM3 is the most frequently mutated gene in AA prostate cancer. In a patient's tumor with >96% frameshift mutations of ZMYM3, we find allelic imbalances in 10 chromosomes, including losses of five and gains of another four chromosomes, suggesting its role in maintaining genomic integrity. Third, when compared to prostate cancer in EA/white men, a higher frequency of CNAs of MYC, THADA, NEIL3, LRP1B, BUB1B, MAP3K7, BNIP3L and RB1, and a lower frequency of deletions of RYBP, TP53, and TMPRSS2-ERG are observed in AA/black men. Finally, for the above genes with higher frequency of CNAs in AA than in EA, deletion of MAP3K7, BNIP3L, NEIL3 or RB1, or gain of MYC significantly associates with both higher Gleason grade and advanced pathologic stage in AA/black men. Deletion of THADA associates with advanced pathologic stage only. IMPLICATIONS: A higher frequency of damaging mutation in ZMYM3 causing genomic instability along with higher frequency of altered genomic regions including deletions of MAP3K7, BNIP3L, RB1, and NEIL3, and gain of MYC appear to be distinct somatically acquired genetic alterations that may contribute to more aggressive prostate cancer in AA/black men.

20.
Carbohydr Polym ; 250: 116941, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33049853

RESUMO

Impregnated decorative paper was an important wood-based panel finishing material. However, traditional impregnated decorative paper was impregnated with melamine-formaldehyde resin, which will release formaldehyde and harm the human health. To solve this problem, small molecule polyacrylate-polyethylene glycol (PEG) adhesive was used to achieve the non-formaldehyde addition of the impregnation system. The dialdehyde modified CNF (D-CNF), modified by sodium periodate (NaIO4), and triethylenediamine were introduced to enhance the surface properties of the impregnated decorative paper. The results showed that the incorporation of D-CNF and triethylenediamine imparted excellent physical strength and surface properties to impregnated decorative paper. When the dosage of 0.3 wt% D-CNF and 3 mL/100 g triethylenediamine in the compound emulsion, the hardness, abrasion resistant value and surface bonding strength of impregnated decorative paper adhered fiberboard reached 3H, 330 r of damage and 1.13 MPa, respectively. Thus, it could be effectively used for making high-performance formaldehyde-free impregnated decorative paper.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...