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1.
Bioinformatics ; 40(5)2024 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-38741151

RESUMO

MOTIVATION: Systems biology aims to better understand living systems through mathematical modelling of experimental and clinical data. A pervasive challenge in quantitative dynamical modelling is the integration of time series measurements, which often have high variability and low sampling resolution. Approaches are required to utilize such information while consistently handling uncertainties. RESULTS: We present BayModTS (Bayesian modelling of time series data), a new FAIR (findable, accessible, interoperable, and reusable) workflow for processing and analysing sparse and highly variable time series data. BayModTS consistently transfers uncertainties from data to model predictions, including process knowledge via parameterized models. Further, credible differences in the dynamics of different conditions can be identified by filtering noise. To demonstrate the power and versatility of BayModTS, we applied it to three hepatic datasets gathered from three different species and with different measurement techniques: (i) blood perfusion measurements by magnetic resonance imaging in rat livers after portal vein ligation, (ii) pharmacokinetic time series of different drugs in normal and steatotic mice, and (iii) CT-based volumetric assessment of human liver remnants after clinical liver resection. AVAILABILITY AND IMPLEMENTATION: The BayModTS codebase is available on GitHub at https://github.com/Systems-Theory-in-Systems-Biology/BayModTS. The repository contains a Python script for the executable BayModTS workflow and a widely applicable SBML (systems biology markup language) model for retarded transient functions. In addition, all examples from the paper are included in the repository. Data and code of the application examples are stored on DaRUS: https://doi.org/10.18419/darus-3876. The raw MRI ROI voxel data were uploaded to DaRUS: https://doi.org/10.18419/darus-3878. The steatosis metabolite data are published on FairdomHub: 10.15490/fairdomhub.1.study.1070.1.


Assuntos
Teorema de Bayes , Fluxo de Trabalho , Animais , Ratos , Humanos , Camundongos , Biologia de Sistemas/métodos , Fígado/metabolismo , Software , Imageamento por Ressonância Magnética/métodos
2.
Glia ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39310943

RESUMO

Neurotoxic A1 reactive astrocytes are induced by inflammatory stimuli. Leptin has been confirmed to have neuroprotective properties. However, its effect on the activation of A1 astrocytes in infectious inflammation is unclear. In the current study, astrocytes cultured from postnatal day 1 Sprague-Dawley rats were stimulated with lipopolysaccharide (LPS) to induce an acute in vitro inflammatory response. Leptin was applied 6 h later to observe its protective effects. The viability of the astrocytes was assessed. A1 astrocyte activation was determined by analyzing the gene expression of C3, H2-D1, H2-T23, and Serping 1 and secretion of pro-inflammatory cytokines IL-6 and TNF-α. The levels of phospho-p38 (pp38) and nuclear factor-κB (NF-κB) phosphor-p65 (pp65) were measured to explore the possible signaling pathways. Additionally, an LPS-induced inflammatory animal model was established to investigate the in vivo effects of leptin on A1 astrocytic activation. Results showed that in the in vitro culture system, LPS stimulation caused elevated expression of A1 astrocyte-specific genes and the secretion of pro-inflammatory cytokines, indicating the activation of A1 astrocytes. Leptin treatment significantly reversed the LPS induced upregulation in a dose-dependent manner. Similarly, LPS upregulated pp38, NF-κB pp65 protein and inflammatory cytokines were successfully reduced by leptin. In the LPS-induced animal model, the amelioratory effect of leptin on A1 astrocyte activation and inflammation was further confirmed, showed by the reduced sickness behaviors, A1 astrocyte genesis and inflammatory cytokines in vivo. Our results demonstrate that leptin efficiently inhibits LPS-induced neurotoxic activation of A1 astrocytes and neuroinflammation by suppressing p38-MAPK signaling pathway.

3.
Eur Radiol ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38992110

RESUMO

OBJECTIVES: This study aims to evaluate image quality and regional lymph node metastasis (LNM) in patients with rectal cancer (RC) on multi-b-value diffusion-weighted imaging (DWI). METHODS: This retrospective study included 199 patients with RC who had undergone multi-b-value DWI. Subjective (five-point Likert scale) and objective assessments of quality images were performed on DWIb1000, DWIb2000, and DWIb3000. Patients were randomly divided into a training (n = 140) or validation cohort (n = 59). Radiomics features were extracted within the whole volume tumor on ADC maps (b = 0, 1000 s/mm2), DWIb1000, DWIb2000, and DWIb3000, respectively. Five prediction models based on selected features were developed using logistic regression analysis. The performance of radiomics models was evaluated with a receiver operating characteristic curve, calibration, and decision curve analysis (DCA). RESULTS: The mean signal intensity of the tumor (SItumor), signal-to-noise ratio (SNR), and artifact and anatomic differentiability score gradually were decreased as the b-value increased. However, the contrast-to-noise (CNR) on DWIb2000 was superior to those of DWIb1000 and DWIb3000 (4.58 ± 0.86, 3.82 ± 0.77, 4.18 ± 0.84, p < 0.001, respectively). The overall image quality score of DWIb2000 was higher than that of DWIb3000 (p < 0.001) and showed no significant difference between DWIb1000 and DWIb2000 (p = 0.059). The area under curve (AUC) value of the radiomics model based on DWIb2000 (0.728) was higher than conventional ADC maps (0.690), DWIb1000 (0.699), and DWIb3000 (0.707), but inferior to multi-b-value DWI (0.739) in predicting LNM. CONCLUSION: DWIb2000 provides better lesion conspicuity and LNM prediction than DWIb1000 and DWIb3000 in RC. CLINICAL RELEVANCE STATEMENT: DWIb2000 offers satisfactory visualization of lesions. Radiomics features based on DWIb2000 can be applied for preoperatively predicting regional lymph node metastasis in rectal cancer, thereby benefiting the stratified treatment strategy. KEY POINTS: Lymph node staging is required to determine the best treatment plan for rectal cancer. DWIb2000 provides superior contrast-to-noise ratio and lesion conspicuity and its derived radiomics best predict lymph node metastasis. DWIb2000 may be recommended as the optimal b-value in rectal MRI protocol.

4.
J Magn Reson Imaging ; 58(6): 1954-1963, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37026419

RESUMO

BACKGROUND: Preventing sepsis-associated acute kidney injury (S-AKI) can be challenging because it develops rapidly and is often asymptomatic. Probability assessment of disease progression for therapeutic follow-up and outcome are important to intervene and prevent further damage. PURPOSE: To establish a noninvasive multiparametric MRI (mpMRI) tool, including T1 , T2 , and perfusion mapping, for probability assessment of the outcome of S-AKI. STUDY TYPE: Preclinical randomized prospective study. ANIMAL MODEL: One hundred and forty adult female SD rats (65 control and 75 sepsis). FIELD STRENGTH/SEQUENCE: 9.4T; T1 and perfusion map (FAIR-EPI) and T2 map (multiecho RARE). ASSESSMENT: Experiment 1: To identify renal injury in relation to sepsis severity, serum creatinine levels were determined (31 control and 35 sepsis). Experiment 2: Animals underwent mpMRI (T1 , T2 , perfusion) 18 hours postsepsis. A subgroup of animals was immediately sacrificed for histology examination (nine control and seven sepsis). Result of mpMRI in follow-up subgroup (25 control and 33 sepsis) was used to predict survival outcomes at 96 hours. STATISTICAL TESTS: Mann-Whitney U test, Spearman/Pearson correlation (r), P < 0.05 was considered statistically significant. RESULTS: Severely ill septic animals exhibited significantly increased serum creatinine levels compared to controls (70 ± 30 vs. 34 ± 9 µmol/L, P < 0.0001). Cortical perfusion (480 ± 80 vs. 330 ± 140 mL/100 g tissue/min, P < 0.005), and cortical and medullary T2 relaxation time constants were significantly reduced compared to controls (41 ± 4 vs. 37 ± 5 msec in cortex, P < 0.05, 52 ± 7 vs. 45 ± 6 msec in medulla, P < 0.05). The combination of cortical T2 relaxation time constants and perfusion results at 18 hours could predict survival outcomes at 96 hours with high sensitivity (80%) and specificity (73%) (area under curve of ROC = 0.8, Jmax = 0.52). DATA CONCLUSION: This preclinical study suggests combined T2 relaxation time and perfusion mapping as first line diagnostic tool for treatment planning. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.


Assuntos
Injúria Renal Aguda , Sepse , Feminino , Ratos , Animais , Estudos Prospectivos , Creatinina , Ratos Sprague-Dawley , Injúria Renal Aguda/diagnóstico por imagem , Injúria Renal Aguda/patologia , Imageamento por Ressonância Magnética , Perfusão , Sepse/complicações , Sepse/diagnóstico por imagem
5.
Angew Chem Int Ed Engl ; 62(52): e202314303, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-37942727

RESUMO

Transition metal single atom electrocatalysts (SACs) with metal-nitrogen-carbon (M-N-C) configuration show great potential in oxygen evolution reaction (OER), whereby the spin-dependent electrons must be allowed to transfer along reactants (OH- /H2 O, singlet spin state) and products (O2 , triplet spin state). Therefore, it is imperative to modulate the spin configuration in M-N-C to enhance the spin-sensitive OER energetics, which however remains a significant challenge. Herein, we report a local field distortion induced intermediate to low spin transition by introducing a main-group element (Mg) into the Fe-N-C architecture, and decode the underlying origin of the enhanced OER activity. We unveil that, the large ionic radii mismatch between Mg2+ and Fe2+ can cause a FeN4 in-plane square local field deformation, which triggers a favorable spin transition of Fe2+ from intermediate (dxy 2 dxz 2 dyz 1 dz2 1 , 2.96 µB ) to low spin (dxy 2 dxz 2 dyz 2 , 0.95 µB ), and consequently regulate the thermodyna-mics of the elementary step with desired Gibbs free energies. The as-obtained Mg/Fe dual-site catalyst demonstrates a superior OER activity with an overpotential of 224 mV at 10 mA cm-2 and an electrolysis voltage of only 1.542 V at 10 mA cm-2 in the overall water splitting, which outperforms those of the state-of-the-art transition metal SACs.

6.
Ophthalmology ; 127(12): 1612-1624, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32428537

RESUMO

PURPOSE: To identify novel susceptibility loci for high myopia. DESIGN: Genome-wide association study (GWAS) followed by replication and meta-analysis. PARTICIPANTS: A total of 14 096 samples from East and Southeast Asian populations (2549 patients with high myopia and 11 547 healthy controls). METHODS: We performed a GWAS in 3269 Japanese individuals (1668 with high myopia and 1601 control participants), followed by replication analysis in a total of 10 827 additional samples (881 with high myopia and 9946 control participants) from Japan, Singapore, and Taiwan. To confirm the biological role of the identified loci in the pathogenesis of high myopia, we performed functional annotation and Gene Ontology (GO) analyses. MAIN OUTCOME MEASURES: We evaluated the association of single nucleotide polymorphisms with high myopia and GO terms enriched among genes identified in the current study. RESULTS: We identified 9 loci with genome-wide significance (P < 5.0 × 10-8). Three loci were previously reported myopia-related loci (ZC3H11B on 1q41, GJD2 on 15q14, and RASGRF1 on 15q25.1), and the other 6 were novel (HIVEP3 on 1p34.2, NFASC/CNTN2 on 1q32.1, CNTN4/CNTN6 on 3p26.3, FRMD4B on 3p14.1, LINC02418 on 12q24.33, and AKAP13 on 15q25.3). The GO analysis revealed a significant role of the nervous system related to synaptic signaling, neuronal development, and Ras/Rho signaling in the pathogenesis of high myopia. CONCLUSIONS: The current study identified 6 novel loci associated with high myopia and demonstrated an important role of the nervous system in the disease pathogenesis. Our findings give new insight into the genetic factors underlying myopia, including high myopia, by connecting previous findings and allowing for a clarified interpretation of the cause and pathophysiologic features of myopia at the molecular level.


Assuntos
Povo Asiático/genética , Loci Gênicos , Predisposição Genética para Doença/genética , Miopia Degenerativa/genética , Doenças do Sistema Nervoso/genética , Polimorfismo de Nucleotídeo Único , Feminino , Estudo de Associação Genômica Ampla , Técnicas de Genotipagem , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Singapura , Taiwan
7.
Hum Mol Genet ; 26(2): 438-453, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-28073927

RESUMO

Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increased risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup-disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed so far. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a. In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG risk.


Assuntos
Inibidor de Quinase Dependente de Ciclina p21/genética , Glaucoma de Ângulo Aberto/genética , Proteínas de Homeodomínio/genética , Doenças do Nervo Óptico/genética , Proteínas de Peixe-Zebra/genética , Feminino , Genoma Humano , Estudo de Associação Genômica Ampla , Glaucoma de Ângulo Aberto/patologia , Humanos , Pressão Intraocular/genética , Masculino , Pessoa de Meia-Idade , Disco Óptico/patologia , Doenças do Nervo Óptico/patologia , Tonometria Ocular
8.
Mol Vis ; 24: 127-142, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29422769

RESUMO

Purpose: To identify genes and genetic markers associated with corneal astigmatism. Methods: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. Results: The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08-1.16), p=5.55×10-9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans-claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). Conclusions: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.


Assuntos
Fosfatase Ácida/genética , Astigmatismo/genética , Claudinas/genética , Doenças da Córnea/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Povo Asiático , Astigmatismo/diagnóstico , Astigmatismo/etnologia , Astigmatismo/patologia , Estudos de Coortes , Córnea/metabolismo , Córnea/patologia , Doenças da Córnea/diagnóstico , Doenças da Córnea/etnologia , Doenças da Córnea/patologia , Expressão Gênica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único , Software , População Branca
9.
Int J Sports Med ; 39(5): 374-381, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29564847

RESUMO

The purpose of this study was to investigate the pleiotropic effects of 12 weeks of supervised exercise training at maximal fat oxidation (FATmax) intensity on body composition, lipid profile, glycemic control, insulin sensitivity and serum adipokine levels in older women with type 2 diabetes. Thirty-one women with type 2 diabetes, aged 60 to 69 years, were randomly allocated into exercise and control groups. Body composition, lipid profile, blood glucose, insulin resistance and serum leptin and adiponectin concentrations were measured before and after the intervention. Exercise group (n=16) walked at individualized FATmax intensities for 1 h/day for 3 days/week over 12 weeks. No dietary intervention was introduced during the experimental period. Maximal fat oxidation rate was 0.37±0.10 g/min, and occurred at 37.3±7.3% of the estimated VO2max. Within the exercise group, significant improvements were observed for most of the measured variables compared to non-exercising controls; in particular, the FATmax program reduced body fat% (p<0.001), visceral fat% (p<0.001), and insulin resistance (p<0.001). There was no significant change in daily energy intake for all participants during the intervention period. These results suggest that individualized FATmax training is an effective exercise training intensity for managing type 2 diabetes in older women.


Assuntos
Tecido Adiposo/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Adiponectina/sangue , Idoso , Glicemia/metabolismo , Composição Corporal/fisiologia , Diabetes Mellitus Tipo 2/sangue , Dieta , Feminino , Humanos , Resistência à Insulina , Leptina/sangue , Pessoa de Meia-Idade , Oxirredução , Consumo de Oxigênio/fisiologia , Cooperação do Paciente , Condicionamento Físico Humano
10.
Ophthalmology ; 124(9): 1271-1279, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28461014

RESUMO

PURPOSE: To investigate the difference in corneal hysteresis (CH) and corneal resistance factor (CRF) between Indian and Chinese populations. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Three hundred eighty-two Singaporean Indian persons and 764 Singaporean Chinese 50 years of age or older were included from the Singapore Indian Eye Study and Singapore Chinese Eye Study, respectively. METHODS: Participants underwent standardized systemic and ocular examinations and interviewer-administered questionnaires for risk factor assessment. The CH and CRF were measured with the Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, NY). Information on genetic ancestry was derived using principal component analysis. Linear regression models were used to investigate the association of CH and CRF with potential risk factors. MAIN OUTCOME MEASURES: Corneal hysteresis and CRF. RESULTS: After excluding participants with a history of intraocular surgery, a diagnosis of glaucoma suspect or glaucoma, refractive surgery, or presence of corneal abnormalities, CH and CRF readings were available for 382 Indian persons. For each Indian participant, 2 Chinese participants were selected and matched for age and gender (n = 764). There were no differences in the clinical measurements of CH (10.6±1.6 mmHg; P = 0.670) or CRF (10.3±1.7 mmHg; P = 0.103) between the ethnic groups. However, after adjusting for covariates, Indian persons had, on average, 0.18-mmHg higher CH levels than in Chinese (95% confidence interval [CI], 0.02-0.38; P = 0.031). Consistently, CH level was correlated significantly with genetic ancestry in the Southeast Asian population. Corneal resistance factor level was not associated independently with self-reported ethnicity (95% CI, -0.10 to 0.29; P = 0.335). CONCLUSIONS: Chinese have lower CH than Indian persons, and this disparity may reflect biomechanical differences of the cornea.


Assuntos
Povo Asiático/etnologia , Córnea/fisiologia , Elasticidade/fisiologia , Idoso , Povo Asiático/genética , Fenômenos Biomecânicos , Paquimetria Corneana , Estudos Transversais , Técnicas de Diagnóstico Oftalmológico/instrumentação , Feminino , Estudo de Associação Genômica Ampla , Humanos , Índia/epidemiologia , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Singapura/epidemiologia , Inquéritos e Questionários , Tonometria Ocular
11.
Ophthalmology ; 122(11): 2169-78, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26256834

RESUMO

PURPOSE: To determine the prevalence of age-related cataract and its ancestral and socioeconomic risk factors in a multi-ethnic Asian population. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 10 033 adults (3353 Chinese, 3280 Malays, and 3400 Indians) aged >40 years in the Singapore Epidemiology of Eye Diseases Study. METHODS: Study participants were invited for a structured interview and received a standardized comprehensive eye examination. Digital lens photographs were taken from eyes of each participant and graded for nuclear, cortical, and posterior subcapsular (PSC) cataract, following the Wisconsin Cataract Grading System. Prevalence data were compared with the Blue Mountains Eye Study (BMES) in Australia. Information on medical and lifestyle factors was collected using questionnaires and blood samples. To increase the precision of racial definition, genetic ancestry was derived from genome-wide single nucleotide polymorphism markers using principal component analysis. Regression models were used to investigate the association of cataract with socioeconomic factors (education and income) and genetic ancestry. MAIN OUTCOME MEASURES: Age-related cataract. RESULTS: A total of 8750 participants (94.0%) had gradable lens photographs. The age-standardized prevalence of cataract surgery in Chinese (16.0%), Malays (10.6%), and Indians (20.2%) was higher than in white subjects (4.1%). We found the age-standardized cataract prevalence in Chinese (30.4%), Malays (37.8%), and Indians (33.1%) was higher than in whites (18.5%). Cataract was 1.5 to 2 times more common in Asians and began 10 years earlier than in white subjects. Malays had significantly higher age-standardized prevalence of nuclear, cortical, and PSC cataract than Chinese (P<0.001). The severity of nuclear, cortical, and PSC cataract was significantly correlated with genetic ancestry in our South East Asian population. Less education and lower income were associated with cataract for Chinese and Indians but not Malays. The presence of visual impairment associated with cataract was higher in people aged ≥60 years and Malays. CONCLUSIONS: We showed that people of different Asian ethnicities had a higher prevalence and earlier age of onset of cataract than Europeans. People of Malay ancestry have a greater severity for all cataract subtypes than people of Chinese ancestry. Education and income were associated with cataract for certain Asian subgroups.


Assuntos
Povo Asiático/etnologia , Catarata/etnologia , Etnicidade , Classe Social , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Catarata/genética , Extração de Catarata/estatística & dados numéricos , Estudos Transversais , Escolaridade , Feminino , Humanos , Renda , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Singapura/epidemiologia , Inquéritos e Questionários , População Branca/etnologia
12.
PLoS Genet ; 8(7): e1002791, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22807686

RESUMO

Genome-wide association studies (GWAS) have recently identified KIF1B as susceptibility locus for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). To further identify novel susceptibility loci associated with HBV-related HCC and replicate the previously reported association, we performed a large three-stage GWAS in the Han Chinese population. 523,663 autosomal SNPs in 1,538 HBV-positive HCC patients and 1,465 chronic HBV carriers were genotyped for the discovery stage. Top candidate SNPs were genotyped in the initial validation samples of 2,112 HBV-positive HCC cases and 2,208 HBV carriers and then in the second validation samples of 1,021 cases and 1,491 HBV carriers. We discovered two novel associations at rs9272105 (HLA-DQA1/DRB1) on 6p21.32 (OR = 1.30, P = 1.13×10⁻¹9) and rs455804 (GRIK1) on 21q21.3 (OR = 0.84, P = 1.86×10⁻8), which were further replicated in the fourth independent sample of 1,298 cases and 1,026 controls (rs9272105: OR = 1.25, P = 1.71×10⁻4; rs455804: OR = 0.84, P = 6.92×10⁻³). We also revealed the associations of HLA-DRB1*0405 and 0901*0602, which could partially account for the association at rs9272105. The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV-related HCC, suggesting the involvement of glutamate signaling in the development of HBV-related HCC.


Assuntos
Carcinoma Hepatocelular/genética , Cadeias alfa de HLA-DQ/genética , Neoplasias Hepáticas/genética , Receptores de Ácido Caínico/genética , Adulto , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Vírus da Hepatite B/genética , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
13.
Gut ; 63(1): 80-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23850713

RESUMO

OBJECTIVE: Crohn's disease (CD) is an intractable inflammatory bowel disease (IBD) of unknown cause. Recent meta-analysis of the genome-wide association studies (GWAS) and Immunochip data identified 163 susceptibility loci to IBD in Caucasians, however there are limited studies in other populations. METHODS: We performed a GWAS and two validation studies in the Korean population comprising a total of 2311 patients with CD and 2442 controls. RESULTS: We confirmed four previously reported loci: TNFSF15, IL23R, the major histocompatibility complex region, and the RNASET2-FGFR1OP-CCR6 region. We identified three new susceptibility loci at genome-wide significance: rs6856616 at 4p14 (OR=1.43, combined p=3.60×10(-14)), rs11195128 at 10q25 (OR=1.42, combined p=1.55×10(-10)) and rs11235667 at 11q13 (OR=1.46, combined p=7.15×10(-9)), implicating ATG16L2 and/or FCHSD2 as novel susceptibility genes for CD. Further analysis of the 11q13 locus revealed a non-synonymous single nucleotide polymorphism (SNP) (R220W/rs11235604) in the evolutionarily conserved region of ATG16L2 with stronger association (OR=1.61, combined p=2.44×10(-12)) than rs11235667, suggesting ATG16L2 as a novel susceptibility gene for CD and rs11235604 to be a potential causal variant of the association. Two of the three SNPs (rs6856616 (p=0.00024) and rs11195128 (p=5.32×10(-5))) showed consistent patterns of association in the International IBD Genetics Consortium dataset. Together, the novel and replicated loci accounted for 5.31% of the total genetic variance for CD risk in Koreans. CONCLUSIONS: Our study provides new biological insight to CD and supports the complementary value of genetic studies in different populations.


Assuntos
Povo Asiático/genética , Proteínas de Transporte/genética , Doença de Crohn/genética , Predisposição Genética para Doença/etnologia , Estudo de Associação Genômica Ampla , Adolescente , Adulto , Proteínas Relacionadas à Autofagia , Estudos de Casos e Controles , Doença de Crohn/etnologia , Fosfatases de Especificidade Dupla/genética , Feminino , Proteínas Ativadoras de GTPase/genética , Marcadores Genéticos , Técnicas de Genotipagem , Humanos , Fatores de Transcrição Kruppel-Like/genética , Modelos Logísticos , Masculino , Proteínas de Membrana/genética , Razão de Chances , Polimorfismo de Nucleotídeo Único , Fatores de Processamento de RNA , República da Coreia , Proteínas do Complexo SMN/genética , Adulto Jovem
14.
Small Methods ; 8(8): e2301378, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38326028

RESUMO

The improvement of photocatalytic activity of g-C3N4 is expected for its advanced applications but remains a challenge due to the limitations of current strategies, such as single function, inefficiency, and uneconomical. Herein, a modified g-C3N4 with improved interface properties is constructed through the modulation of the ionic microenvironment affected by ionic liquids (ILs) and exhibits a 2.3-fold enhanced photodegradation efficiency and a 3.5-fold enhanced reaction rate relative to pristine g-C3N4. It has demonstrated excellent performance in photo-therapy bacterial-infected wounds. Theoretical calculation indicated that the precursor can be regulated by designing the specific ILs microenvironment to form "ILs-Mel" clusters due to the diversity of interaction energy and electrostatic potential. The cluster results in uneven stress on the 2D plane, further inducing the reconstruction of the microstructure. The synergistic effect of cations and anions of ILs on regulating the interface properties of g-C3N4 due to the change of skeleton structure during thermolysis of ILs. The microstructure, surface, and optical-electrical properties can be adjusted by selecting different cations of ILs, and the custom-made band structure and wettability can be obtained by selecting different anions. This work provides a facile strategy to modulate the interface properties of g-C3N4 by building specific a microenvironment of precursor.


Assuntos
Líquidos Iônicos , Fotólise , Cicatrização , Líquidos Iônicos/química , Líquidos Iônicos/farmacologia , Cicatrização/efeitos dos fármacos , Compostos de Nitrogênio/química , Nitrilas/química , Nitrilas/farmacologia , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Humanos , Staphylococcus aureus/efeitos dos fármacos , Camundongos , Infecção dos Ferimentos/tratamento farmacológico , Grafite
15.
Front Psychiatry ; 15: 1382264, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827446

RESUMO

Objective: The aim of this study was to examine the correlation between the level of mobile phone dependence among college students and their experience of academic burnout. Additionally, the study sought to explore the potential mediating effect of study engagement and the moderating role of love. Methods: During October and December 2023, a cross-sectional study measuring mobile phone dependence, academic burnout, and study engagement among Chinese college students, using the UtrechtWork Engagement Scale-student (UWES-S), College Student Mobile Phone Dependence Questionnaire (CSMPDQ), and Academic Burnout Questionnaire (ABQ). To examine the hypothesis of mediating and moderating effect, SPSS PROCESS was utilized. Results: The predictive effect of mobile phone dependence on academic burnout was significant (ß = 0.410, t = 14.236, p < 0.001), and the predictive effect of mobile phone dependence on academic burnout remained significant when the mediating variable study engagement was introduced (ß = 0.308, t = 10.288, p < 0.001), mobile phone dependence had a significant predictive effect on study engagement (ß = -0.292, t = -11.639, p < 0.001), and study engagement had a significant positive predictive effect on academic burnout (ß = -0.270, t = -9.028, p < 0.001). Love significantly negatively predicted study engagement (ß = -0.564, t = -9.641, p < 0.001); and the interaction term for mobile phone dependence and love was significant (ß = -0.211, t = -3.688, p < 0.001), indicating a significant moderating effect of love between mobile phone dependence and study engagement. Conclusion: Mobile phones among college students has been found to have a direct correlation with academic burnout. It can also indirectly contribute to academic burnout by diminishing levels of academic engagement. This indirect relationship is further influenced by love. These findings can help researchers and educators better understand the underlying mechanisms between smartphone dependence and learning burnout in undergraduates.

16.
Food Sci Biotechnol ; 33(10): 2323-2331, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39145123

RESUMO

Red bell pepper (Capsicum annuum L.) is a popular and nutritious vegetable. In this study, oven cooking (OV), air-frying (AF), and infrared grilling (IR) were used to cook red bell peppers at different temperatures (170, 180, 190, and 200 °C). Changes in the total phenolic content, ascorbic acid content, antioxidant activity, and sugar and acrylamide content in red bell peppers were evaluated before and after cooking. The total phenolic and ascorbic acid contents decreased significantly after cooking (p < 0.05). Among the three evaluated methods, OV-cooked red bell peppers exhibited the highest antioxidant activity. The acrylamide content showed the lowest levels in OV 170 °C (93.67 ± 3.22 µg/kg dw) and the highest in AF 200 °C (1985.38 ± 76.39 µg/kg dw) samples. Compared to the AF and IR methods, OV was identified as the best way to preserve the antioxidant activity of red bell peppers while reducing acrylamide production. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01623-y.

17.
Environ Pollut ; 359: 124566, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39025292

RESUMO

Pharmaceuticals are widespread in aquatic environments and might contribute to the prevalence of antibiotic resistance. However, the co-effect of antibiotics and non-antibiotic pharmaceuticals on the gut microbiome of fish is poorly understood. In this study, we characterized the variation of the zebrafish gut microbiome and resistome after exposure to sulfamethoxazole (SMX) and aspirin under different treatments. SMX contributed to the significant increase in the antibiotic resistance genes (ARGs) richness and abundance with 46 unique ARGs and five mobile genetic elements (MGEs) detected. Combined exposure to SMX and aspirin enriched total ARGs abundance and rearranged microbiota under short-term exposure. Exposure time was more responsible for resistome and the gut microbiome than exposure concentrations. Perturbation of the gut microbiome contributed to the functional variation related to RNA processing and modification, cell motility, signal transduction mechanisms, and defense mechanisms. A strong significant positive correlation (R = 0.8955, p < 0.001) was observed between total ARGs and MGEs regardless of different treatments revealing the key role of MGEs in ARGs transmission. Network analysis indicated most of the potential ARGs host bacteria belonged to Proteobacteria. Our study suggested that co-occurrence of non-antibiotics and antibiotics could accelerate the spread of ARGs in gut microbial communities and MGEs played a key role.


Assuntos
Antibacterianos , Aspirina , Resistência Microbiana a Medicamentos , Microbioma Gastrointestinal , Sulfonamidas , Peixe-Zebra , Peixe-Zebra/genética , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Sulfonamidas/farmacologia , Aspirina/farmacologia , Resistência Microbiana a Medicamentos/genética , Antibacterianos/farmacologia , Sulfametoxazol/farmacologia , Poluentes Químicos da Água , Bactérias/genética , Bactérias/efeitos dos fármacos
19.
Nanoscale Horiz ; 8(6): 812-826, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37016980

RESUMO

Exploring eco-friendly and cost-effective strategies for structure engineering at the nanoscale is important for boosting heterogeneous catalysis but still under a long-standing challenge. Herein, multifunctional polyphenol tannic acid, a low-cost natural biomass containing catechol and galloyl species, was employed as a green reducing agent, chelating agent, and stabilizer to prepare Au nanoparticles, which were dispersed on different-shaped CeO2 supports (e.g., rod, flower, cube, and octahedral). Systematic characterizations revealed that Au/CeO2-rod had the highest oxygen vacancy density and Ce(III) proportion, favoring the dispersion and stabilization of the metal active sites. Using isopropanol as a hydrogen-transfer reagent, deep insights into the structure-activity relationship of the Au/CeO2 catalysts with various morphologies of CeO2 in the catalytic nitrobenzene transfer hydrogenation reaction were gained. Notably, the catalytic performance followed the order: Au/CeO2-rod (110), (100), (111) > Au/CeO2-flower (100), (111) > Au/CeO2-cube (100) > Au/CeO2-octa (111). Au/CeO2-rod displayed the highest conversion of 100% nitrobenzene and excellent stability under optimal conditions. Moreover, DFT calculations indicated that nitrobenzene molecules had a suitable adsorption energy and better isopropanol dehydrogenation capacity on the Au/CeO2 (110) surface. A reaction pathway and the synergistic catalytic mechanism for catalytic nitrobenzene transfer hydrogenation are proposed based on the results. This work demonstrates that CeO2 structure engineering is an efficient strategy for fabricating advanced and environmentally benign materials for nitrobenzene hydrogenation.

20.
Breast Cancer Res ; 14(1): R25, 2012 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-22314178

RESUMO

INTRODUCTION: Over the last decade several breast cancer risk alleles have been identified which has led to an increased interest in individualised risk prediction for clinical purposes. METHODS: We investigate the performance of an up-to-date 18 breast cancer risk single-nucleotide polymorphisms (SNPs), together with mammographic percentage density (PD), body mass index (BMI) and clinical risk factors in predicting absolute risk of breast cancer, empirically, in a well characterised Swedish case-control study of postmenopausal women. We examined the efficiency of various prediction models at a population level for individualised screening by extending a recently proposed analytical approach for estimating number of cases captured. RESULTS: The performance of a risk prediction model based on an initial set of seven breast cancer risk SNPs is improved by additionally including eleven more recently established breast cancer risk SNPs (P = 4.69 × 10-4). Adding mammographic PD, BMI and all 18 SNPs to a Swedish Gail model improved the discriminatory accuracy (the AUC statistic) from 55% to 62%. The net reclassification improvement was used to assess improvement in classification of women into low, intermediate, and high categories of 5-year risk (P = 8.93 × 10-9). For scenarios we considered, we estimated that an individualised screening strategy based on risk models incorporating clinical risk factors, mammographic density and SNPs, captures 10% more cases than a screening strategy using the same resources, based on age alone. Estimates of numbers of cases captured by screening stratified by age provide insight into how individualised screening programs might appear in practice. CONCLUSIONS: Taken together, genetic risk factors and mammographic density offer moderate improvements to clinical risk factor models for predicting breast cancer.


Assuntos
Neoplasias da Mama/genética , Modelos Biológicos , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Área Sob a Curva , Densidade da Mama , Neoplasias da Mama/diagnóstico por imagem , Estudos de Casos e Controles , Detecção Precoce de Câncer , Feminino , Predisposição Genética para Doença , Humanos , Glândulas Mamárias Humanas/anormalidades , Mamografia , Pessoa de Meia-Idade , Pós-Menopausa , Medicina de Precisão , Curva ROC , Fatores de Risco
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