Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 568
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-38581330

RESUMO

Objective: Metabolism, a basic need and biochemical process for cell survival and proliferation, is closely connected with the pathogenesis and progression of prostate cancer. Methods: A four-gene signature construct that includes CKM (CKM), CD38, Enoyl Coenzyme A(EHHADH), and Arginase 2(ARG2) was created by bioinformatics. Finally, hub genes were validated by IHC and in vitro experiments. Results: The results showed the AUCs of the logistic regression and neural networks diagnostic model for the diagnosis of two subtypes were 0.920 and 0.936, respectively. The risk score demonstrated by univariable and multivariable Cox analysis is an independent predictive component of the prognostic signature for DFS. According to immunohistochemical analyses, ARG2 and CD38 expression levels were considerably under-expressed, but CKM and EHHADH expression levels were significantly overexpressed. Furthermore, The expression of ARG2 was significantly down-regulated in the late Gleason score. Finally, we found that ARG2 is lowly expressed in prostate cancer cells. Furthermore, based on the effect of ARG2 on the malignant phenotype of PCa in vitro, we also found that ARG2 may be a tumor suppressor that plays an important role in inhibiting proliferation, migration, and invasion. Conclusions: These findings suggest that ARG2 has been tentatively identified as a new target for research into how PCa develops in metabolism and for the development of innovative targeted treatments.

2.
Environ Int ; 186: 108626, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38626493

RESUMO

The relationship of fine particulate matter (PM2.5) exposure and insulin resistance remains inclusive. Our study aimed to investigate this association in the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR). Specifically, we examined the associations between long-term PM2.5 exposure and three surrogate indicators of insulin resistance: the triglyceride-glucose index (TyG), TyG with waist circumference (TyG-WC) and metabolic score for insulin resistance (METS-IR). Additionally, we explored potential effect modification of dietary intake and components. Generalized estimating equations were used to evaluate the associations between PM2.5 and the indicators with an unbalanced repeated measurement design. Our analysis incorporated a total of 162,060 observations from 99,329 participants. Each 10 µg/m3 increment of PM2.5 was associated with an increase of 0.22 % [95 % confidence interval (CI): 0.20 %, 0.25 %], 1.60 % (95 % CI: 1.53 %, 1.67 %), and 2.05 % (95 % CI: 1.96 %, 2.14 %) in TyG, TyG-WC, and METS-IR, respectively. These associations were attenuated among participants with a healthy diet, particularly those with sufficient intake of fruit and vegetable, fish or tea (pinteraction < 0.0028). For instance, among participants with a healthy diet, TyG increased by 0.11 % (95 % CI: 0.08 %, 0.15 %) per 10 µg/m3 PM2.5 increment, significantly lower than the association observed in those with an unhealthy diet. The findings of this study emphasize the potential of a healthy diet to mitigate these associations, highlighting the urgency for improving air quality and implementing dietary interventions among susceptible populations in China.


Assuntos
Exposição Ambiental , Resistência à Insulina , Material Particulado , Material Particulado/análise , Humanos , Masculino , Pessoa de Meia-Idade , China , Feminino , Exposição Ambiental/estatística & dados numéricos , Poluentes Atmosféricos/análise , Adulto , Dieta/estatística & dados numéricos , Idoso , Glicemia/análise , Triglicerídeos/sangue
3.
Food Funct ; 15(6): 3199-3213, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38445897

RESUMO

Ageing is defined as the degeneration of physiological functions in numerous tissues and organs of an organism, which occurs with age. As we age, the gut undergoes a series of changes and weaknesses that may contribute to overall ageing. Emerging evidence suggests that ß-nicotinamide mononucleotide (NMN) plays a role in regulating intestinal function, but there is still a lack of literature on its role in maintaining the colon health of ageing mice. In our research, Zmpste24-/- mice proved that NMN prolonged their life span and delayed senescence. This study was designed to investigate the effects of long-term intervention on regulating colon function in ageing mice. Our results indicated that NMN improved the pathology of intestinal epithelial cells and intestinal permeability by upregulating the expression of intestinal tight junction proteins and the number of goblet cells, increasing the release of anti-inflammatory factors, and increasing beneficial intestinal bacteria. NMN increased the expression of the proteins SIRT1, NMNAT2, and NMNAT3 and decreased the expression of the protein P53. It also regulated the activity of ISCs by increasing Wnt/ß-catenin and Lgr5. Our findings also revealed that NMN caused a significant increase in the relative abundance of Akkermansia muciniphila and Bifidobacterium pseudolongum and notable differences in metabolic pathways related to choline metabolism in cancer. In summary, NMN supplementation can delay frailty in old age, aid healthy ageing, and delay gut ageing.


Assuntos
Longevidade , Mononucleotídeo de Nicotinamida , Camundongos , Animais , Mononucleotídeo de Nicotinamida/metabolismo , Mononucleotídeo de Nicotinamida/farmacologia , Envelhecimento , Suplementos Nutricionais , Colo/metabolismo
4.
Environ Sci Pollut Res Int ; 31(16): 23876-23895, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38430442

RESUMO

Digital finance is a product of emerging technology-enabled innovation in financial services and has a critical impact on the green transformation of the manufacturing industry. We propose a new efficiency measurement model based on the slacks-based measure (SBM) to measure the efficiency of green transformation on regional manufacturing. Chinese interprovincial data from 2010 to 2019 were obtained for the study. In addition, we estimated the effect of digital finance on green transformation of manufacturing using a benchmark panel model. Finally, considering the regional heterogeneity and spatial effects of green transformation efficiency in the manufacturing industry, we constructed a spatial Durbin model based on an economic-geographic nested spatial weight matrix to analyze the spatial influence of digital finance on green transformation in the manufacturing industry. The results show that the green transformation of the manufacturing industry has significant positive spatial spillover effects owing to the existence of competition, demonstration, and economic correlation effects among regions.


Assuntos
Indústria Manufatureira , China , Comércio , Desenvolvimento Econômico
5.
Diabetes Obes Metab ; 26(5): 1919-1928, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38418401

RESUMO

AIMS: To identify the trajectories of body mass index (BMI) and waist circumference (WC), and assess the associations of BMI trajectory, WC trajectory, or the two combined, with type 2 diabetes mellitus (T2DM) risk in Chinese adults. MATERIALS AND METHODS: This study was based on a prospective project-the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR). A total of 54 434 participants (39.21% men) who were measured on at least two occasions were included. Three slowly increasing trajectory patterns were identified for BMI, and four for WC, by latent mixed modelling. A nine-category variable was derived by combining the WC trajectory (low, moderate, moderate-high/high) and the BMI trajectory (low, moderate, high). Logistic regression models were applied to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The risk of developing T2DM increased with elevated BMI or WC trajectory levels (all ptrend <0.001). The risks were 2.85 (2.59-3.14) for high BMI trajectory and 4.34 (3.78-4.99) for high WC trajectory versus low trajectory groups, respectively. The association was more pronounced among younger individuals (pinteraction <0.001). In the joint analysis, compared to participants with low WC and BMI trajectory, those with moderate-high/high WC combined with high BMI trajectory had the highest risk of T2DM (OR 3.96, 95% CI 3.48-4.50); even those who maintained moderate-high/high WC but low BMI trajectory showed a higher T2DM risk (OR 3.00, 95% CI 2.31-3.91). CONCLUSIONS: This study suggests that simultaneous dynamic and continuous monitoring of BMI and WC may contribute more than single measurements to predicting T2DM risk and determining preventive strategies.


Assuntos
Diabetes Mellitus Tipo 2 , Adulto , Masculino , Humanos , Feminino , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Fatores de Risco , Índice de Massa Corporal , Circunferência da Cintura , Estudos Prospectivos , China/epidemiologia
6.
Sci Rep ; 14(1): 4524, 2024 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402299

RESUMO

The universally poor clinical outcome makes gastric cancer (GC) still a significant public health threat, the main goal of our research is to develop a prognostic signature that can forecast the outcomes and immunological characteristics of GC via integrating single-cell and bulk RNA-sequencing. The CD8+ T cell feature genes were screened out by exploring single-cell RNA-sequencing (scRNA-seq) profiles retrieved from the TISCH2 database. Then, Cox and LASSO regressions were exploited for constructing a prognostic model in TCGA cohort based on these CD8+ T cell feature genes. Survival analysis was conducted to investigate the predictive capability of the signature for the clinical outcome of GC patients in TCGA and GEO cohorts. Additionally, we further examined the correlations between the risk signature and tumor immunotherapeutic response from the perspectives of immune infiltration, tumor mutation burden (TMB), immune checkpoint biomarker (ICB) expression, tumor microenvironment (TME), microsatellite instability (MSI), TIDE, and TCIA scores. In total, 703 CD8+ T cell feature genes were identified, eight of which were selected for constructing a prognostic signature. GC patients who possess high-risk score had significantly poorer survival outcomes than those who possess low-risk score in TCGA and GEO cohorts. Immune infiltration analysis proved that the risk score was negatively connected with the infiltration abundance of CD8+ T cells. Then, our findings demonstrated that GC patients in the high-risk subgroup possess a higher proportion of MSI-L/MSS, lower immune checkpoint biomarker expression, lower TMB, higher TIDE scores and lower TCIA scores compared to those in the low-risk subgroup. What's more, immunotherapy cohort analysis confirmed that patients who possess high-risk score are not sensitive to anti-cancer immunotherapy. Our study developed a reliable prognostic signature for GC that was significantly correlated with the immune landscape and immunotherapeutic responsiveness. The risk signature may guide clinicians to adopt more accurate and personalized treatment strategies for GC patients.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Prognóstico , Linfócitos T CD8-Positivos , Biomarcadores , RNA , Microambiente Tumoral/genética
7.
Genes (Basel) ; 15(2)2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38397246

RESUMO

Mercury (Hg) pollution not only poses a threat to the environment but also adversely affects the growth and development of plants, with potential repercussions for animals and humans through bioaccumulation in the food chain. Maize, a crucial source of food, industrial materials, and livestock feed, requires special attention in understanding the genetic factors influencing mercury accumulation. Developing maize varieties with low mercury accumulation is vital for both maize production and human health. In this study, a comprehensive genome-wide association study (GWAS) was conducted using an enlarged SNP panel comprising 1.25 million single nucleotide polymorphisms (SNPs) in 230 maize inbred lines across three environments. The analysis identified 111 significant SNPs within 78 quantitative trait loci (QTL), involving 169 candidate genes under the Q model. Compared to the previous study, the increased marker density and optimized statistical model led to the discovery of 74 additional QTL, demonstrating improved statistical power. Gene ontology (GO) enrichment analysis revealed that most genes participate in arsenate reduction and stress responses. Notably, GRMZM2G440968, which has been reported in previous studies, is associated with the significant SNP chr6.S_155668107 in axis tissue. It encodes a cysteine proteinase inhibitor, implying its potential role in mitigating mercury toxicity by inhibiting cysteine. Haplotype analyses provided further insights, indicating that lines carrying hap3 exhibited the lowest mercury content compared to other haplotypes. In summary, our study significantly enhances the statistical power of GWAS, identifying additional genes related to mercury accumulation and metabolism. These findings offer valuable insights into unraveling the genetic basis of mercury content in maize and contribute to the development of maize varieties with low mercury accumulation.


Assuntos
Mercúrio , Locos de Características Quantitativas , Humanos , Mapeamento Cromossômico , Zea mays/genética , Zea mays/metabolismo , Polimorfismo de Nucleotídeo Único , Estudo de Associação Genômica Ampla , Mercúrio/toxicidade , Mercúrio/metabolismo , Fenótipo
8.
Neural Netw ; 173: 106155, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38335793

RESUMO

Graph neural networks have become the primary graph representation learning paradigm, in which nodes update their embeddings by aggregating messages from their neighbors iteratively. However, current message passing based GNNs exploit the higher-order subgraph information other than 1st-order neighbors insufficiently. In contrast, the long-standing graph research has investigated various subgraphs such as motif, clique, core, and truss that contain important structural information to downstream tasks like node classification, which deserve to be preserved by GNNs. In this work, we propose to use the pre-mined subgraphs as priori knowledge to extend the receptive field of GNNs and enhance their expressive power to go beyond the 1st-order Weisfeiler-Lehman isomorphism test. For that, we introduce a general framework called PSA-GNN (Priori Subgraph Augmented Graph Neural Network), which augments each GNN layer by a pair of parallel convolution layers based on a bipartite graph between nodes and priori subgraphs. PSA-GNN intrinsically builds a hybrid receptive field by incorporating priori subgraphs as neighbors, while the embeddings and weights of subgraphs are trainable. Moreover, PSA-GNN can purify the noisy subgraphs both heuristically before training and deterministically during training based on a novel metric called homogeneity. Experimental results show that PSA-GNN achieves an improved performance compared with state-of-the-art message passing based GNN models.


Assuntos
Conhecimento , Antígeno Prostático Específico , Masculino , Humanos , Aprendizagem , Redes Neurais de Computação
9.
BMJ Open ; 14(2): e075257, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418236

RESUMO

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are prevalent respiratory diseases in China and impose significant burdens on the healthcare system. Moreover, the co-occurrence of COPD and OSA exacerbates clinical outcomes significantly. However, comprehensive epidemiological investigations in China remain scarce, and the defining characteristics of the population affected by COPD and OSA, alongside their intrinsic relationship, remain ambiguous. METHODS AND ANALYSIS: We present a protocol for a prospective, multicentre, observational cohort study based on a digital health management platform across three different healthcare tiers in five sites among Chinese patients with COPD. The study aims to establish predicative models to identify OSA among patients with COPD and to predict the prognosis of overlap syndrome (OS) and acute exacerbations of COPD through the Internet of Things (IoT). Moreover, it aims to evaluate the feasibility, effectiveness and cost-effectiveness of IoT in managing chronic diseases within clinical settings. Participants will undergo baseline assessment, physical examination and nocturnal oxygen saturation measuring. Specific questionnaires screening for OSA will also be administered. Diagnostic lung function tests and polysomnography will be performed to confirm COPD and OSA, respectively. All patients will undergo scheduled follow-ups for 12 months to record the changes in symptoms, lung functions and quality of life. Primary outcomes include the prevalence and characteristics of OS, while secondary outcomes encompass OS prognosis and the feasibility of the management model in clinical contexts. A total of 682 patients with COPD will be recruited over 12-24 months. ETHICS AND DISSEMINATION: The study has been approved by Peking University Third Hospital, and all study participants will provide written informed consent. Study results will be published in an appropriate journal and presented at national and international conferences, as well as relevant social media and various stakeholder engagement activities. TRIAL REGISTRATION NUMBER: NCT04833725.


Assuntos
Internet das Coisas , Doença Pulmonar Obstrutiva Crônica , Apneia Obstrutiva do Sono , Humanos , Estudos Prospectivos , Qualidade de Vida , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Atenção à Saúde , Estudos de Coortes , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/complicações , Estudos Observacionais como Assunto , Estudos Multicêntricos como Assunto
10.
Heliyon ; 10(2): e24739, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38304816

RESUMO

In order to overcome the poor dispersion of traditional inorganic zinc-rich coating, addressing the sedimentation and the agglomeration caused by high zinc powder content and improve the anti-corrosion performance of coatings. In this paper, the molybdate intercalated hydrotalcite flake zinc layer double hydroxide (ZnAl-NO3-/LDH) was synthesized by hydrothermal synthesis method at first, and the KH560 modified the Mo/LDH flake zinc powder was further obtained by ion exchange method. The results show that the samples have a layered structure of hydrotalcite with good crystal structure through X-ray diffraction (XRD) and Fourier transform infrared (FT-IR), and the molybdate corrosion inhibiting ions inserted successfully into the interlayer structure of hydrotalcite. Meanwhile, different contents of pigments and fillers were added into the inorganic zinc-rich coatings. It was found that the Nyquist radius of curvature and modulus value of the coating were the largest with a pigment and filler content of 40 %, the maximum corrosion potential was -0.017V, and the minimum corrosion current density was 3.377 × 10-7 A-cm-2. The result indicates that the coating has the best corrosion resistance with 40 % pigment content, which has good application prospects in the fields of cross-sea bridges, natural gas and oil pipelines et al.

11.
Heliyon ; 10(1): e23691, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38192771

RESUMO

It is long observed that females tend to live longer than males in nearly every country. However, the underlying mechanism remains elusive. In this study, we discovered that genetic associations with longevity are on average stronger in females than in males through bio-demographic analyses of genome-wide association studies (GWAS) dataset of 2178 centenarians and 2299 middle-age controls of Chinese Longitudinal Healthy Longevity Study (CLHLS). This discovery is replicated across North and South regions of China, and is further confirmed by North-South discovery/replication analyses of different and independent datasets of Chinese healthy aging candidate genes with CLHLS participants who are not in CLHLS GWAS, including 2972 centenarians and 1992 middle-age controls. Our polygenic risk score analyses of eight exclusive groups of sex-specific genes, analyses of sex-specific and not-sex-specific individual genes, and Genome-wide Complex Trait Analysis using all SNPs all reconfirm that genetic associations with longevity are on average stronger in females than in males. Our discovery/replication analyses are based on genetic datasets of in total 5150 centenarians and compatible middle-age controls, which comprises the worldwide largest sample of centenarians. The present study's findings may partially explain the well-known male-female health-survival paradox and suggest that genetic variants may be associated with different reactions between males and females to the same vaccine, drug treatment and/or nutritional intervention. Thus, our findings provide evidence to steer away from traditional view that "one-size-fits-all" for clinical interventions, and to consider sex differences for improving healthcare efficiency. We suggest future investigations focusing on effects of interactions between sex-specific genetic variants and environment on longevity as well as biological function.

12.
JAMA Cardiol ; 9(3): 233-242, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38198131

RESUMO

Importance: The genetic basis of coronary heart disease (CHD) has expanded from a germline to somatic genome, including clonal hematopoiesis of indeterminate potential (CHIP). How CHIP confers CHD risk in East Asian individuals, especially those with small clones (variant allele fraction [VAF] 0.5%-2%) and different genetic backgrounds, was completely unknown. Objective: To investigate the CHIP profile in a general Chinese cohort by deep sequencing and further explore the association between CHIP and incident CHD considering germline predisposition. Design, Setting, and Participants: This cohort study used data from 3 prospective cohorts in the project Prediction for Atherosclerotic Cardiovascular Disease Risk in China. Participants without cardiovascular disease or cancer at baseline were enrolled in 2001 and 2008 and had a median follow-up of 12.17 years extending into 2021. Exposures: CHIP mutations were detected by targeted sequencing (mean depth, 916×). A predefined CHD polygenic risk score (PRS) comprising 531 variants was used to evaluate germline predisposition. Main Outcomes and Measures: The main outcome was first incident CHD. Results: Among 6181 participants, the median (IQR) age was 53.83 years (45.35-62.39 years); 3082 participants (49.9%) were female, and 3099 (50.1%) were male. A total of 1100 individuals (17.80%) harbored 1372 CHIP mutations at baseline. CHIP was independently associated with incident CHD (hazard ratio [HR], 1.42; 95% CI, 1.18-1.72; P = 2.82 × 10-4) and presented a risk gradient with increasing VAF (P = 3.98 × 10-3 for trend). Notably, individuals with small clones, nearly half of CHIP carriers, also demonstrated a higher CHD risk compared with non-CHIP carriers (HR, 1.33; 95% CI, 1.02-1.74; P = .03) and were 4 years younger than those with VAF of 2% or greater (median age, 58.52 vs 62.70 years). Heightened CHD risk was not observed among CHIP carriers with low PRS (HR, 1.02; 95% CI, 0.64-1.64; P = .92), while high PRS and CHIP jointly contributed a 2.23-fold increase in risk (95% CI, 1.51-3.29; P = 6.29 × 10-5) compared with non-CHIP carriers with low PRS. Interestingly, the diversity in CHIP-related CHD risk within each PRS group was substantially diminished when removing variants in the inflammatory pathway from the PRS. Conclusions: This study revealed that elevated CHD risk attributed to CHIP was nonnegligible even for small clones. Inflammation genes involved in CHD could aggravate or abrogate CHIP-related CHD risk.


Assuntos
Doenças Cardiovasculares , Doença da Artéria Coronariana , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Doença da Artéria Coronariana/epidemiologia , Hematopoiese Clonal , Estudos de Coortes , Estudos Prospectivos , Células Germinativas
13.
Medicine (Baltimore) ; 103(4): e37026, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38277569

RESUMO

BACKGROUND: This study aims to investigate the safety and feasibility of preserving left colonic artery (LCA) in radical sigmoid and rectal cancer surgery. METHODS: Relevant articles were systematically searched on the PubMed, Embase, and Cochrane Library. The quality of included studies was evaluated using the Cochrane Handbook. A meta-analysis was conducted to assess the surgical outcomes and oncological outcomes by RevMan 5.4 software. RESULTS: Fifteen studies with a total of 5054 patients, including 2432 patients with LCA preservation and 2622 patients without LCA preservation, were included and analyzed in this study. The meta-analysis revealed that preserving LCA in radical surgery of sigmoid and rectal cancer has lower anastomotic leakage incidence (OR = 1.03, 95% confidence interval = 0.83-1.27, P < .0001). There were no significant differences in the operative time, intraoperative blood loss, number of dissected lymph nodes, postoperative complications as well as the oncological outcomes including systemic recurrence, local recurrence, 5-year overall survival rate, and 5-year disease-free survival rate. CONCLUSION SUBSECTIONS: This pooled analysis showed that preserving the LCA is safe and feasible in radical sigmoid and rectal cancer surgery.


Assuntos
Laparoscopia , Neoplasias Retais , Humanos , Artéria Mesentérica Inferior/cirurgia , Colo/patologia , Colo Sigmoide/patologia , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Artérias/cirurgia
14.
Stroke ; 55(1): 92-100, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38018834

RESUMO

BACKGROUND: Both genetic factors and environmental air pollution contribute to the risk of stroke. However, it is unknown whether the association between air pollution and stroke risk is influenced by the genetic susceptibilities of stroke and its risk factors. METHODS: This prospective cohort study included 40 827 Chinese adults without stroke history. Satellite-based monthly fine particulate matter (PM2.5) estimation at 1-km resolution was used for exposure assessment. Based on 534 identified genetic variants from genome-wide association studies in East Asians, we constructed 6 polygenic risk scores for stroke and its risk factors, including atrial fibrillation, blood pressure, type 2 diabetes, body mass index, and triglyceride. The Cox proportional hazards model was applied to evaluate the hazard ratios and 95% CIs for the associations of PM2.5 and polygenic risk score with incident stroke and the potential effect modifications. RESULTS: Over a median follow-up of 12.06 years, 3147 incident stroke cases were documented. Compared with the lowest quartile of PM2.5 exposure, the hazard ratio (95% CI) for stroke in the highest quartile group was 2.72 (2.42-3.06). Among individuals at high genetic risk, the relative risk of stroke was 57% (1.57; 1.40-1.76) higher than those at low genetic risk. Although no statistically significant interaction was found, participants with both the highest PM2.5 and high genetic risk showed the highest risk of stroke, with ≈4× that of the lowest PM2.5 and low genetic risk group (hazard ratio, 3.55 [95% CI, 2.84-4.44]). Similar upward gradients were observed in the risk of stroke when assessing the joint effects of PM2.5 and genetic risks of blood pressure, type 2 diabetes, body mass index, atrial fibrillation, and triglyceride. CONCLUSIONS: Long-term exposure to PM2.5 was associated with a higher risk of incident stroke across different genetic susceptibilities. Our findings highlighted the great importance of comprehensive assessment of air pollution and genetic risk in the prevention of stroke.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Fibrilação Atrial , Diabetes Mellitus Tipo 2 , Acidente Vascular Cerebral , Adulto , Humanos , Material Particulado/efeitos adversos , Material Particulado/análise , Estudos Prospectivos , Fibrilação Atrial/complicações , Estudo de Associação Genômica Ampla , Exposição Ambiental/efeitos adversos , Incidência , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/induzido quimicamente , Poluição do Ar/efeitos adversos , Fatores de Risco , Predisposição Genética para Doença , Triglicerídeos , Poluentes Atmosféricos/efeitos adversos
15.
Protein Expr Purif ; 215: 106408, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38008389

RESUMO

Hexokinases (HKs) play a vital role in glucose metabolism, which controls the first committed step catalyzing the production of glucose-6-phosphate from glucose. Two HKs (CGIHK1 and CGIHK2) from the Pacific oyster Crassostrea giga were cloned and characterized. CGIHK1 and CGIHK2 were recombinantly expressed in Escherichia coli and successfully purified by the Ni-NTA column. The optimum pH of the two enzymes was pH 8.0 and 8.5, respectively. The optimum temperature of the two enzymes was 42 °C and 50 °C, respectively. Both enzymes showed a clear requirement for divalent magnesium and were strongly inhibited by SDS. CGIHK1 exhibited highly strict substrate specificity to glucose, while CGIHK2 could also catalyze other 11 monosaccharide substrates. This is the first report on the in vitro biosynthesis of glucose-6-phosphate by the hexokinases from Crassostrea gigas. The facile expression and purification procedures combined with different substrate specificities make CGIHK1 and CGIHK2 candidates for the biosynthesis of glucose-6-phosphate and other sugar-phosphates.


Assuntos
Crassostrea , Hexoquinase , Animais , Hexoquinase/metabolismo , Crassostrea/genética , Glucose-6-Fosfato/metabolismo , Temperatura , Glucose/metabolismo
16.
Med Sci Sports Exerc ; 56(1): 103-109, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37703277

RESUMO

PURPOSE: Whether the association of sedentary behaviors with coronary artery disease (CAD) can be influenced by genetic susceptibility remains unclear. We aimed to investigate the joint and interplay effects between genetic risk and sedentary time (ST) and to further explore the extent to which the risk for CAD can be counteracted by reducing ST in different genetic groups. METHODS: This prospective cohort study included 39,164 Chinese adults without CAD history. Genetic susceptibility was quantified by a predefined polygenic risk score (PRS) with 540 genetic variants, and daily ST was assessed by questionnaire. We analyzed the modification effect of genetic risk on the association of ST with CAD using the Cox proportional hazards models. RESULTS: During a median follow-up of 11.60 yr, 1156 CAD events were documented. Higher ST and PRS were separately related to elevated CAD risk. Significant additive interaction was also observed (relative excess risk due to interaction: 0.77; 95% confidence interval [CI] = 0.27-1.28). Compared with participants with low genetic risk and low ST (<6 h·d -1 ), those with high genetic risk and high ST (≥10 h·d -1 ) had the highest CAD risk, with the hazard ratio (HR) and 95% CI of 4.22 (2.65-6.71). When stratified by genetic risks, participants with high ST had gradient increment of CAD risks across low, intermediate, and high genetic risk groups, with HR (95% CI) values of 1.21 (0.61-2.40), 1.57 (1.14-2.16), and 2.15 (1.40-3.31), respectively. For the absolute risk reduction, individuals with high genetic risk achieved the greatest benefit from low ST ( Ptrend = 0.024). CONCLUSIONS: Genetic susceptibility may synergistically interact with ST to increase CAD risk. Reducing ST could attenuate the CAD risk, especially among individuals with high genetic risk.


Assuntos
Doença da Artéria Coronariana , Adulto , Humanos , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Estudos Prospectivos , Comportamento Sedentário , Estudos de Coortes , Predisposição Genética para Doença , Fatores de Risco , China/epidemiologia
17.
J Agric Food Chem ; 71(49): 19804-19816, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38038649

RESUMO

Six new alkaloids (compounds 1-6) were isolated from Portulaca oleracea L. The compounds were triple pair (1 and 2, 3 and 4, and 5 and 6) enantiomers, with 1, 3, and 5 in the R-configuration and 2, 4, and 6 in the S-configuration, and all could bind to SUR1 according to molecular docking analysis. Treatment of STC-1 cells with each compound led to an influx of intracellular Ca2+, eventually leading to the secretion of glucagon-like peptide-1 (GLP-1), with compound 3 giving the highest secretion, resulting in 24.3 ± 7.03% more GLP-1 than nateglinide-treated cells, suggesting that these alkaloids may be able to reduce blood glucose based on their ability to stimulate the release of GLP-1. Furthermore, compound 3 also exhibited slightly faster absorption than nateglinide, as shown by pharmacokinetic analysis conducted in rats. Therefore, the results showed that some purslane alkaloids (such as compound 3) had good pharmacological activity in vivo and may have preventive and therapeutic effects on diabetes.


Assuntos
Alcaloides , Portulaca , Ratos , Animais , Portulaca/metabolismo , Nateglinida , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Simulação de Acoplamento Molecular , Alcaloides/farmacologia , Alcaloides/análise
18.
J Commun Healthc ; : 1-11, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38149652

RESUMO

BACKGROUND: The use of social media as a platform to access news and information has the potential to lead to the spread of fake news in Indonesia. This study aims to (1) understand the trust characteristics in information of Indonesians during COVID-19; (2) identify Indonesians' ability to detect COVID-19 fake news; and (3) analyze the relationship between people's trust characteristics in information with regard to COVID-19 information and their ability to detect fake news. METHOD: An online survey was conducted with 751 Indonesians who use social media to access information about COVID-19. Cultural theory is used to categorize people's trust characteristics in information, while signal detection theory is employed to identify people's ability to discriminate between fake and real news. RESULTS: The results showed that 61% of respondents were categorized as having hierarchy trust characteristics. Concerning the detectability of fake news, most respondents could discriminate between fake and real news. Lastly, there was a relationship between trust characteristics in information and bias tendencies in detecting fake news. CONCLUSIONS: The respondents have hierarchy trust characteristics, indicating they trusted government information related to COVID-19 issues. The respondents also have high ability to discriminate between fake and real news, even though they tended to miss more errors than identify false alarms when detecting fake news. The findings showed that respondents who had hierarchy and egalitarian characteristics tended to perceive real news as fake news and had a better ability to distinguish fake news compared to other trust characteristics in information.

19.
Opt Lett ; 48(24): 6428-6431, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38099765

RESUMO

Fizeau wavelength measurement plays an important role in the fields of laser technology, optical communication, and optical metrology. The accuracy of the traditional multistage Fizeau wavemeter is limited owing to the degradation of the stripe symmetry and finesse caused by variations in the cavity length. Herein, we propose a virtual Fizeau cavity (VFC) based on the principle of phase difference to address this issue. The principle analysis and simulation of this measurement system are presented, along with experiments that verified the feasibility and performance of the VFC method. The wavelength measurement accuracy of this system is superior to 60 MHz in the 350-1100 nm wavelength range. The design concept of "virtual-real combined" cavities first proposed in this paper to our knowledge introduces possibilities for the development of high-accuracy Fizeau wavelength measurements.

20.
J Geriatr Cardiol ; 20(11): 779-787, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38098467

RESUMO

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS: Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...