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BACKGROUND: The aim of this study was to explore the molecular mechanism of quercetin in the treatment of intracerebral hemorrhage. METHODS: Quercetin target genes and intracerebral hemorrhage target genes were collected from 5 databases. After standardized conversion of the obtained target genes through uniprot database, cross genes of the 2 were obtained using Venny 2.1 online tool. Further, protein interaction relationships were obtained in the String database, and then core target genes were screened and visualized by Cytoscape software, and cross genes were enriched by GO and KEGG pathways. Finally, the active drug ingredients and target proteins were verified and visualized by computer. RESULTS: In this study, 197 quercetin targets were identified as potential targets for the treatment of intracerebral hemorrhage, and 7 core target genes (TP53, STAT3, AKT1, SRC, JUN, TNF, and IL6) were screened. The GO and KEGG analyses further shed light on the molecular mechanisms underlying quercetin's treatment of intracerebral hemorrhage, involving multiple biological processes and signaling pathways (such as cancer pathways, lipids, and atherosclerosis). The stable binding of quercetin to these 7 key targets was confirmed by molecular docking simulation. CONCLUSION: Quercetin may treat intracerebral hemorrhage through multi-target-multi-pathway mechanisms, including regulating apoptosis, inhibiting inflammatory response, inhibiting iron death, and regulating angiogenesis, which can help alleviate nerve damage caused by intracerebral hemorrhage.
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Hemorragia Cerebral , Simulação de Acoplamento Molecular , Farmacologia em Rede , Quercetina , Quercetina/farmacologia , Quercetina/uso terapêutico , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/metabolismo , Humanos , Farmacologia em Rede/métodos , Mapas de Interação de Proteínas , Transdução de Sinais/efeitos dos fármacosRESUMO
Hybrid-wetting surfaces with hydrophilic spots reduced from the micrometer to nanometer scale have been confirmed to enhance vapor nucleation while simultaneously minimizing droplet pinning. Given that surface topography also plays a critical role in influencing nucleation characteristics, the effect of competition between intrinsic wettability and topography on nucleation remains unclear when both surface topography and hydrophilic regions approach the critical nucleation size. This work investigated vapor nucleation on two types of hybrid-wetting nanoconvex surfaces. On random hybrid-wetting convex surfaces, the most negative potential energy sites were located at the sides of the convex structures, leading vapor to preferentially nucleate at these locations, consistent with observations on homogeneous surfaces. Despite similar average potential energy values across the surface, wettability variations in hydrophilic and hydrophobic atoms significantly alter the surface energy distribution. As the wettability difference between hydrophilic and hydrophobic atoms increases, stronger hydrophilic atoms generate relatively higher local energy regions, promoting vapor rapid nucleation. The edge effect still exists at a hydrophilic atom ratio of 10%, and competition among hydrophilic spots impedes vapor nucleation and growth. However, when the ratio increases to 40%, the increased surface average potential energy promotes the probability of vapor contacting the surface, leading to rapid vapor nucleation on the sides of the convex structures. In addition, surface potential energy analysis and the Monte Carlo method revealed that nucleation locations on nanoconvex surfaces are governed by the competition between intrinsic wettability and topography. When the magnitude of the potential energy generated by the hydrophilic atoms exceeds that from the topography, stronger solid-liquid interactions at the top of the convex structure increase the likelihood of vapor contacting the surface, resulting in nucleation at the top. Conversely, when the magnitude of the potential energy generated by hydrophilic atoms is lower than that from topography, nucleation preferentially still occurs on the sides.
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The objective of this study is to investigate the dynamic mechanical properties of coal and rock under deep water conditions. The research employs an enhanced Split Hopkinson Pressure Bar (SHPB) testing system. Five sets of dynamic impact experiments were conducted on coal samples under varying loading conditions to analyse the changes in dynamic strength, energy dissipation, fractal dimension and other characteristics of coal samples under different water content states were analyzed. The experimental results demonstrate that: (1) Under specific strain rate conditions, the dynamic strength of saturated coal samples is lower than that of natural coal samples. As the strain rate gradually increases, the bonding force generated by free water and the Stefan effect jointly act, and the peak strength of saturated coal samples under high strain rate loading conditions is higher than that of natural coal samples. (2) Under certain strain rate conditions, the absorption energy of saturated coal samples is approximately 10% to30% lower than that of natural coal samples, and deformation hysteresis phenomenon occurs in natural coal samples, thereby improving the dynamic strength of natural coal samples relative to saturated coal samples; (3) The fractal dimension of saturated coal samples with a specific strain rate under three-dimensional dynamic static combination loading is higher than that of natural coal samples, and the percentage of small particle coal samples with debris is higher than that of natural coal samples; Finally, based on the HJC model, some coal samples were selected to simulate the coal rock failure characteristics during the triaxial loading process using ANSYS/LS-DYNA, and their stress-strain curves and failure morphology diagrams were obtained. The discrepancy between the numerical simulation and the experimental results was less than 10%, thereby further elucidating and corroborating the coal failure process and dynamic mechanical characteristics.
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Gene transcription is a stochastic process that occurs in all organisms. Transcriptional bursting, a critical molecular dynamics mechanism, creates significant heterogeneity in mRNA and protein levels. This heterogeneity drives cellular phenotypic diversity. Currently, the lack of a comprehensive quantitative model limits the research on transcriptional bursting. This review examines various gene expression models and compares their strengths and weaknesses to guide researchers in selecting the most suitable model for their research context. We also provide a detailed summary of the key metrics related to transcriptional bursting. We compared the temporal dynamics of transcriptional bursting across species and the molecular mechanisms influencing these bursts, and highlighted the spatiotemporal patterns of gene expression differences by utilizing metrics such as burst size and burst frequency. We summarized the strategies for modeling gene expression from both biostatistical and biochemical reaction network perspectives. Single-cell sequencing data and integrated multiomics approaches drive our exploration of cutting-edge trends in transcriptional bursting mechanisms. Moreover, we examined classical methods for parameter estimation that help capture dynamic parameters in gene expression data, assessing their merits and limitations to facilitate optimal parameter estimation. Our comprehensive summary and review of the current transcriptional burst dynamics theories provide deeper insights for promoting research on the nature of cell processes, cell fate determination, and cancer diagnosis.
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Chinese Baijiu is a famous fermented alcoholic beverage in China. Interactions between key microorganisms, i.e., Saccharomyces cerevisiae and Lactiplantibacillus plantarum, have recently been reported at specific temperatures. However, empirical evidence of their interactions at various temperatures during fermentation is lacking. The results of this study demonstrated that S. cerevisiae significantly suppressed the viability and lactic acid yield of L. plantarum when they were cocultured above 15 °C. On the other hand, L. plantarum had no pronounced effect on the growth and ethanol yield of S. cerevisiae in coculture systems. S. cerevisiae was the main reducing sugar consumer. Inhibition of lactic acid production was also observed when elevated cell density of L. plantarum was introduced into the coculture system. A proteomic analysis indicated that the enzymes involved in glycolysis, lactate dehydrogenase, and proteins related to phosphoribosyl diphosphate, ribosome, and aminoacyl-tRNA biosynthesis in L. plantarum were less abundant in the coculture system. Collectively, our data demonstrated the antagonistic effect of S. cerevisiae on L. plantarum and provided insights for effective process management in light-flavor Baijiu fermentation.
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Two researchers independently assessed studies published up to February 5, 2023, across PubMed, Web of Science, Embase, and Cochrane Library, to investigate the associations of sleep traits with cardiometabolic risk factors, as well as with cardiovascular diseases. Fourteen systematic reviews consisting of 23 meta-analyses, and 11 Mendelian randomization (MR) studies were included in this study. Short sleep duration was associated with a higher risk of obesity, type 2 diabetes (T2D), hypertension, stroke, and coronary heart disease (CHD) in observational studies, while a causal role was only demonstrated in obesity, hypertension, and CHD by MR. Similarly, long sleep duration showed connections with a higher risk of obesity, T2D, hypertension, stroke, and CHD in observational studies, none was supported by MR analysis. Both observational and MR studies indicated heightened risks of hypertension, stroke, and CHD in relation to insomnia. Napping was linked to elevated risks of T2D and CHD in observational studies, with MR analysis confirming a causal role in T2D. Additionally, snoring was correlated with increased risks of stroke and CHD in both observational and MR studies. This work consolidates existing evidence on a causal relationship between sleep characteristics and cardiometabolic risk factors, as well as cardiovascular diseases.
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Fatores de Risco Cardiometabólico , Doenças Cardiovasculares , Análise da Randomização Mendeliana , Sono , Humanos , Sono/fisiologia , Diabetes Mellitus Tipo 2/genética , Estudos Observacionais como Assunto , Obesidade/complicações , Obesidade/genética , Hipertensão/genética , Acidente Vascular Cerebral , Fatores de RiscoRESUMO
The high incidence of bone defect-related diseases caused by trauma, infection, and tumor resection has greatly stimulated research in the field of bone regeneration. Generally, bone healing is a long and complicated process wherein manipulating the biological activity of interventional scaffolds to support long-term bone regeneration is significant for treating bone-related diseases. It has been reported that some physical cues can act as growth factor substitutes to promote osteogenesis through continuous activation of endogenous signaling pathways. This review focuses on the latest progress in bone repair by remote actuation and on-demand activation of biomaterials pre-incorporated with physical cues (heat, electricity, and magnetism). As an alternative method to treat bone defects, physical cues show many advantages, including effectiveness, noninvasiveness, and remote manipulation. First, we introduce the impact of different physical cues on bone repair and potential internal regulatory mechanisms. Subsequently, biomaterials that mediate various physical cues in bone repair and their respective characteristics are summarized. Additionally, challenges are discussed, aiming to provide new insights and suggestions for developing intelligent biomaterials to treat bone defects and promote clinical translation.
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Materiais Biocompatíveis , Regeneração Óssea , Alicerces Teciduais , Regeneração Óssea/efeitos dos fármacos , Materiais Biocompatíveis/química , Humanos , Animais , Alicerces Teciduais/química , Osteogênese/efeitos dos fármacos , Engenharia Tecidual/métodos , Osso e Ossos/metabolismoRESUMO
In order to investigate the composition and differences in volatile organic compounds (VOCs) in yak and cattle-yak meat and determine the key metabolites and metabolic pathways related to flavor formation. In this study, the VOCs and non-volatile metabolites in Longissimus dorsi muscle of two groups of samples were detected and analyzed by gas chromatography-ion migration spectrometry (GC-IMS) and gas chromatography-mass spectrometry (GC-MS). The results showed that 31 VOCs were identified by GC-IMS, including 5 alcohols, 5 ketones, 5 esters, 3 aldehydes, 2 furans, 2 hydrocarbons, 1 amine, 1 acid, 1 thiazole, 1 pyrazine, and 5 others. Most of them were alcohols, ketones, esters, and aldehydes. A total of 75 non-volatile metabolites with significant differences were obtained by GC-MS screening, among which amino acid contents such as serine, glycine, phenylalanine, and aspartic acid were significantly up-regulated in cattle-yak, and glutamic acid and tyrosine were significantly up-regulated in yak. The non-volatile differential metabolites in the two groups were significantly enriched in the metabolic pathways of arginine biosynthesis and oxidative phosphorylation. By combining GC-IMS and GC-MS, this study comprehensively and intuitively reflected the differences in VOCs between yak and cattle-yak meat, and clarified the metabolomic reasons for the differences in VOCs, so as to provide a theoretical basis for meat quality improvement.
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Balanced fiber-reinforced rubber (FRR) pipes not only provide displacement compensation when transporting pressurized media but also prevent additional forces and displacements from being exerted on the connected pipeline system. Investigating the balanced performance of FRR pipes and the axial stiffness of balanced pipes is crucial for optimizing pipeline design and improving the reliability of pipeline systems. This paper develops a numerical model of FRR pipes that considers the nonlinearity of the rubber material and the interaction between the rubber matrix and fiber-reinforced layers. Using this model, the balanced performance of the pipe is calculated, and its axial stiffness under combined internal pressure and axial load is analyzed. Numerical results are compared with experimental data for validation. The results indicate that the pipe's balance is achieved through the combined effects of the elongation and rotation of the reinforcing fibers and the deformation of the rubber matrix, highlighting the significant impact of the rubber matrix on the mechanical performance of the FRR pipe. Furthermore, the pipe's balanced performance and axial stiffness are highly sensitive to the winding angle of reinforcing fibers. The proposed numerical model fills the gap in using numerical methods to evaluate the balanced performance of FRR pipes and provides valuable insights for their design and optimization.
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BACKGROUND: Pneumoconiosis mostly combines pulmonary and cardiovascular diseases, among which pulmonary heart disease (PHD) is of major concern due to its significant impact on the survival of pneumoconiosis patients. White cell count (WCC), red cell distribution width (RDW) and platelet parameters are thought to affect inflammatory responses and may be predictors of various cardiovascular diseases. However, very few studies have focused on PHD. OBJECTIVES: To examine the relationship between baseline complete blood count parameters (WCC, RDW, platelet parameters) and the risk of incident PHD in pneumoconiosis patients. DESIGN: A retrospective cohort study. SETTING: This was a single-centre, retrospective cohort study that used data from an Occupational Disease Hospital, Chengdu, Sichuan. PARTICIPANTS: A total of 946 pneumoconiosis patients from January 2012 to November 2021 were included in the study. Female patients and patients who had PHD, coronary heart disease, hypertensive heart disease, cardiomyopathy, heart failure, oncological disease, multiple organ dysfunction, AIDS at baseline and follow-up time of less than 6 months were also excluded. OUTCOME MEASURES: We identified PHD according to the patient's discharge diagnosis. We constructed Cox proportional hazard regression models to assess the HR of incident PHD in pneumoconiosis, as well as 95% CIs. RESULTS: In the multiple Cox proportional hazard regression analysis, platelet count (PLT) and plateletcrit (PCT) above the median at baseline were associated with an increased risk of PHD in pneumoconiosis with adjusted HR of 1.52 (95% CI 1.09 to 2.12) and 1.42 (95% CI 1.02 to 1.99), respectively. CONCLUSION: Higher baseline PLT and PCT are associated with a higher risk of PHD in pneumoconiosis.
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Pneumoconiose , Doença Cardiopulmonar , Humanos , Estudos Retrospectivos , Masculino , Pneumoconiose/sangue , Pneumoconiose/epidemiologia , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Idoso , Contagem de Células Sanguíneas , Doença Cardiopulmonar/sangue , Doença Cardiopulmonar/epidemiologia , Fatores de Risco , Índices de Eritrócitos , Modelos de Riscos Proporcionais , Contagem de Plaquetas , IncidênciaRESUMO
Previous studies have explored the effect of differing heat and relative humidity (RH) environments on the performance of multiple anaerobic high-intensity interval training (HIIT). Still, its impact on physiological responses and performance following aerobic HIIT has not been well studied. This study examined the effects of differing RH environments on physiological responses and performance in college football players following HIIT. Twelve college football completed HIIT under four different environmental conditions: (1) 25 °C/20% RH (Control group); (2) 35 °C/20% RH (H20 group); (3) 35 °C/40% RH (H40 group); (4) 35 °C/80% RH (H80 group). The heart rate (HR), mean arterial pressure (MAP), lactate, tympanic temperature (TT), skin temperature (TS), thermal sensation (TS), and rating of perceived exertion (RPE) were recorded continuously throughout the exercise. The heart rate variability (HRV): including root mean squared differences of the standard deviation (RMSSD)ãstandard deviation differences of the standard deviation (SDNN)ãhigh frequency (HF), low frequency (LF), squat jump height (SJH), cycling time to exhaustion (TTE), and sweat rate (SR) were monitored pre-exercise and post-exercise. The HR, MAP, lactate, TT, Ts, TS, and RPE in the 4 groups showed a trend of rapid increase, then decreased gradually. There was no significant difference in HR, MAP, TT, or RPE between the 4 groups at the same time point (p > 0.05), in addition to this, when compared to the C group, the lactate, Ts, TS in the other 3 groups significant differences were observed at the corresponding time points (p < 0.05). The RMSSD, SDNN, HF, and LF levels in the 4 groups before exercise were not significantly different. The RMSSD and HF in the H40 and H80 groups were significantly decreased and other HRV indicators showed no significant difference after exercise. In sports performance measurement, the SJH and TTE were significantly decreased, but there was no significant difference in the 4 groups. The SR was no significant difference in the 4 groups after exercise. In conclusion, heat and humidity environments elicited generally greater physiological effects compared with the normal environment but did not affect sports performance in college football players.
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Desempenho Atlético , Frequência Cardíaca , Treinamento Intervalado de Alta Intensidade , Umidade , Humanos , Masculino , Treinamento Intervalado de Alta Intensidade/métodos , Frequência Cardíaca/fisiologia , Adulto Jovem , Desempenho Atlético/fisiologia , Exercício Físico/fisiologia , Universidades , Futebol Americano/fisiologia , Atletas , Ácido Láctico/sangue , Temperatura Corporal/fisiologiaRESUMO
BACKGROUND: The Ozaki technique demonstrated promising results in adults, but few studies reported on pediatric patients with limited follow-up time. This study aimed to evaluate the mid-term results of Ozaki technique compared with Ross operation for complex aortic valve (AV) diseases in children. MATERIALS AND METHODS: One hundred and seventeen children underwent either Ozaki (n = 64) or Ross (n = 53) operation from January 2017 to December 2023. The primary endpoint was incidence of moderate or severe regurgitation/stenosis (AR/AS) post procedure. RESULTS: No significant difference was observed in age (6.5±3.4 vs. 7.9±4.3 years) and weight (25.9±15.5 vs. 31.0±25.9 kgs) at surgery. The Ozaki group had significantly more patients in heart failure (20.3% vs. 1.9%, P = 0.003) before surgery and more patients needed ECMO installation (6.3% vs. 0, P = 0.125) after surgery. The Ozaki group were in worse status with more patients occurred heart failure (20.3% vs. 1.9%, P = 0.003) before surgery and needed ECMO installation (6.3% vs. 0, P = 0.125) after surgery. During follow up (20.4±17.3 vs. 22.7±22.8 months, P = 0.526), five patients (7.8%) in Ozaki group but no patients in Ross group required reoperations. The incidence of moderate or severe AR (28.1% vs. 3.1%) and AS (31.3% vs. 5.7%) were significantly higher than Ross group. Multivariate analysis identified lower age [HR:1.282 (95%CI:1.075-1.529), P = 0.006] and ECMO installation [HR:0.126 (0.018-0.887), P = 0.037] to be risk factors for moderate or severe AR, and higher aortic transvalvular gradient before discharge was confirmed as the only risk factor for moderate or severe AS (≥36 mmHg) at follow up in Ozaki group. CONCLUSION: Ozaki technique may be used as a palliative procedure for complex AV diseases in children, but its' mid-term results were not durable as Ross surgery, especially younger patients.
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Extracellular polymeric substances (EPS) have demonstrated significant benefits for reducing multivalent metal contamination. Using Achromobacter xylosoxidans BP1 isolated from a coal chemical site in China, this study elucidated the contribution of EPS production to Cr (VI) reduction and revealed its biological removal mechanism. BP1 grew at an optimum pH of 8 and the lowest inhibitory concentration of Cr(VI) was 300 mg/L. The spent medium completely removed Cr(VI), whereas resting cells were only able to remove 10.47 % and inactivated cells were nearly incapable of Cr(VI) removal. S-EPS and B-EPS reduced Cr(VI) by 98.59 % and 11.64 %, respectively. SEM-EDS analysis showed that the BP1 cells were stimulated to produce EPS under Cr stress. The XPS results showed that 29.63 % of Cr(VI) was enriched by intracellular bioaccumulation or biosorption and 70.37 % of Cr(VI) was reduced by extracellular enzymes to produce Cr(OH)3 and organic Cr(III) complexes. According to FTIR, EPS with -OH, COO-, and amide groups supplied binding sites and electrons for the reductive adsorption of Cr(VI). Genomic studies showed that BP1 primarily produces extracellular polysaccharides, metabolises sulphur and nitrogen, and reduces reactive oxygen species damage as a result of DNA repair proteases.
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Achromobacter denitrificans , Biodegradação Ambiental , Cromo , Matriz Extracelular de Substâncias Poliméricas , Achromobacter denitrificans/metabolismo , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Cromo/metabolismo , China , OxirreduçãoRESUMO
Chirality on the molecular or nanometer scale is particularly significant in chemistry, materials science, and biomedicine. Chiral electrochemical reactions on solid surfaces are currently a hot research topic. Herein, a chiral solid surface is constructed in aqueous solutions by mixing chiral molecules, d- and l-glutamic, with γ-Fe2O3 and Fe3O4 nanoparticles (NPs) and MnFe2O4 colloidal nanocrystal assembly (CNA). Cyclic voltammetry and differential pulse voltammetry measurements are conducted in a phosphate buffer solution (PBS) containing ascorbic acid (AA) or isoascorbic acid (IAA), and a chiral effect appears on the electroreduction of ferric ions of amino acid-modified magnetic samples. A negative or positive potential shift is observed, respectively, for magnetic structures modified by l- and d-glutamic acid in aqueous AA electrolyte, while the opposite is observed for these samples in IAA electrolyte. The reduction peak current increases by 0.8-1.2 times for the electrodes modified with l- and d-glutamate molecules, improving the electron transport efficiency. The chiral effect is absent when the electrolytes contain achiral uric acid or dopamine, or even chiral l-/d-/ld-tartaric acid. The chiral recognition between d-/l-glutamic acid and AA/IAA at the electrochemical interface is suggested to be related to their spinal configurations. These observations will be helpful for the rational design of inorganic functional chiral micro/nanostructures.
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MAIN CONCLUSION: The SiMBR genes in foxtail millet were identified and studied. Heterologous expression of SiMBR2 in Arabidopsis can improve plant tolerance to drought stress by decreasing the level of reactive oxygen species. Foxtail millet (Setaria italica L.), a C4 crop recognized for its exceptional resistance to drought stress, presents an opportunity to improve the genetic resilience of other crops by examining its unique stress response genes and understanding the underlying molecular mechanisms of drought tolerance. In our previous study, we identified several genes linked to drought stress by transcriptome analysis, including SiMBR2 (Seita.7G226600), a member of the MED25 BINDING RING-H2 PROTEIN (MBR) gene family, which is related to protein ubiquitination. Here, we have identified ten SiMBR genes in foxtail millet and conducted analyses of their structural characteristics, chromosomal locations, cis-acting regulatory elements within their promoters, and predicted transcription patterns specific to various tissues or developmental stages using bioinformatic approaches. Further investigation of the stress response of SiMBR2 revealed that its transcription is induced by treatments with salicylic acid and gibberellic acid, as well as by salt and osmotic stresses, while exposure to high or low temperatures led to a decrease in its transcription levels. Heterologous expression of SiMBR2 in Arabidopsis thaliana enhanced the plant's tolerance to water deficit by reducing the accumulation of reactive oxygen species under drought stress. In summary, this study provides support for exploring the molecular mechanisms associated with drought resistance of SiMBR genes in foxtail millet and contributing to genetic improvement and molecular breeding in other crops.
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Arabidopsis , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Setaria (Planta) , Estresse Fisiológico , Setaria (Planta)/genética , Setaria (Planta)/fisiologia , Setaria (Planta)/efeitos dos fármacos , Arabidopsis/genética , Arabidopsis/fisiologia , Estresse Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Secas , Plantas Geneticamente Modificadas , Família Multigênica , Regiões Promotoras Genéticas/genética , Espécies Reativas de Oxigênio/metabolismoRESUMO
Nitrite plays a critical role in a variety of nitrification and denitrification processes in the nitrogen cycle. Due to the high surface energy, tendency to aggregate, and poor conductivity, current nitrite ZnS-based sensing platform could not meet the need of on-site nitrite detection in smart agriculture. In order to address these issues, the carboxylated carbon nanotube (CNT) was introduced to reduce the surface energy and prevented aggregation of ZnS, while ZnS-carboxylated CNT (ZnS-CNT) composite also provided excellent electrochemical conductivity. Furthermore, the introduction of phase transition BSA (PTB) created a three-dimensional porous conductive matrix without interfering with the mass transfer process of nitrite. The resulting sensing platform exhibited a linear detection range of 10 nM to 0.4 mM for nitrite, with a detection limit of 0.73 nM. And this sensing platform had the excellent antifouling ability to direct detection nitrite in real soil suspension. In addition, the sensing platform demonstrated remarkable resistance to interferences from pH variations, microbial presence, and organic pollutants that usually present in soil environment. Therefore, on-site detection of nitrite ions in soil environment was realized no needing complex pretreatments.
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While carotid intima-media thickness (cIMT) as a noninvasive surrogate measure of atherosclerosis is widely considered a risk factor for stroke, the intrinsic link underlying cIMT and stroke has not been fully understood. We aimed to evaluate the clinical value of cIMT in stroke through the investigation of phenotypic and genetic relationships between cIMT and stroke. We evaluated phenotypic associations using observational data from UK Biobank (N = 21,526). We then investigated genetic relationships leveraging genomic data conducted in predominantly European ancestry for cIMT (N = 45,185) and any stroke (AS, Ncase/Ncontrol=40,585/406,111). Observational analyses suggested an increased hazard of stroke per one standard deviation increase in cIMT (cIMTmax-AS: hazard ratio (HR) = 1.39, 95%CI = 1.09-1.79; cIMTmean-AS: HR = 1.39, 95%CI = 1.09-1.78; cIMTmin-AS: HR = 1.32, 95%CI = 1.04-1.68). A positive global genetic correlation was observed (cIMTmax-AS: [Formula: see text]=0.23, P=9.44 × 10-5; cIMTmean-AS: [Formula: see text]=0.21, P=3.00 × 10-4; cIMTmin-AS: [Formula: see text]=0.16, P=6.30 × 10-3). This was further substantiated by five shared independent loci and 15 shared expression-trait associations. Mendelian randomization analyses suggested no causal effect of cIMT on stroke (cIMTmax-AS: odds ratio (OR)=1.12, 95%CI=0.97-1.28; cIMTmean-AS: OR=1.09, 95%CI=0.93-1.26; cIMTmin-AS: OR=1.03, 95%CI = 0.90-1.17). A putative association was observed for genetically predicted stroke on cIMT (AS-cIMTmax: beta=0.07, 95%CI = 0.01-0.13; AS-cIMTmean: beta=0.08, 95%CI = 0.01-0.15; AS-cIMTmin: beta = 0.08, 95%CI = 0.01-0.16) in the reverse direction MR, which attenuated to non-significant in sensitivity analysis. Our work does not find evidence supporting causal associations between cIMT and stroke. The pronounced cIMT-stroke association is intrinsic, and mostly attributed to shared genetic components. The clinical value of cIMT as a surrogate marker for stroke risk in the general population is likely limited.
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Espessura Intima-Media Carotídea , Fenótipo , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/genética , Masculino , Feminino , Fatores de Risco , Pessoa de Meia-Idade , Idoso , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Aterosclerose/genética , Reino Unido/epidemiologia , Adulto , Análise da Randomização Mendeliana , Estudo de Associação Genômica AmplaRESUMO
Cholelithiasis is a common disease of the digestive system. The risk factors for cholelithiasis have been reported and summarized many times in the published literature, which primarily focused on cross-sectional studies. Due to the inherent limitations of the study design, the reported findings still need to be validated in additional longitudinal studies. Moreover, a number of new risk factors for cholelithiasis have been identified in recent years, such as bariatric surgery, hepatitis B virus infection, hepatitis C virus infection, kidney stones, colectomy, osteoporosis, etc. These new findings have not yet been included in published reviews. Herein, we reviewed the 101 cholelithiasis-associated risk factors identified through research based on longitudinal investigations, including cohort studies, randomized controlled trials, and nested case control studies. The risk factors associated with the pathogenesis of cholelithiasis were categorized as unmodifiable and modifiable factors. The unmodifiable factors consist of age, sex, race, and family history, while the modifiable factors include 37 biological environmental factors, 25 socioenvironmental factors, and 35 physiochemical environmental factors. This study provides thorough and comprehensive ideas for research concerning the pathogenesis of cholelithiasis, supplying the basis for identifying high-risk groups and formulating relevant prevention strategies.
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Colelitíase , Colelitíase/etiologia , Fatores de Risco , Humanos , Estudos Longitudinais , Hepatite B/complicaçõesRESUMO
OBJECTIVES: We examined the associations of self-reported exposures, and urinary metabolites related to household pesticide with cardiovascular disease (CVD) mortality in older adults based on the 2007 to 2014 waves of National Health and Nutrition Examination Survey (NHANES). METHODS: Information on application and urinary metabolites related to household pesticide exposure were collected. We estimated the risks of household pesticide exposure, urinary metabolites with subsequent incident CVD death using Cox proportional hazards regression models. The indirect effects of urinary metabolites and effect modifications were examined. RESULTS: The participants who reported exposure to household pesticide had a higher risk of incident CVD death (adjusted HR 1.40, 95% CI 1.08 to 1.81). Per 1-log10 increase in urinary N, N-diethyl-3-methylbenzamide (DEET) related to household insect repellents was associated with a higher risk of incident CVD death (adjusted HR 1.97, 95% CI 1.14 to 3.40). Urinary DEET explained 4.21% of the total association between household pesticide exposure and CVD death risk. The participants who persisted a low level of health diet exhibited pronounced CVD death risks with household pesticide exposures. CONCLUSIONS: Exposure to household pesticide, especially household insect repellents, was consistently associated with an elevated CVD death risk in older adults. A heatlhy diet could partly attenuate the associations.
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Doenças Cardiovasculares , Exposição Ambiental , Praguicidas , Humanos , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/urina , Masculino , Feminino , Idoso , Estudos Prospectivos , Exposição Ambiental/análise , Exposição Ambiental/efeitos adversos , Praguicidas/urina , Praguicidas/toxicidade , Pessoa de Meia-Idade , Inquéritos Nutricionais , Repelentes de Insetos , DEET/urina , Idoso de 80 Anos ou maisRESUMO
Background: Exercise has been reported to be associated with a reduced risk of nonalcoholic fatty liver disease (NAFLD), but there is no consensus on the role of weight changes in this association. This study aims to investigate whether the impact of exercise on NAFLD is mainly dependent on weight changes or is inherent to exercise itself. Methods: The study recruited 1671 Chinese NAFLD-free adults in 2019, and collected their exercise habits as well as 3 years of medical examination data including anthropometric measurements, blood biochemistry parameters, and liver ultrasound results. Univariate and multivariate logistic regression models were employed to examine the impact of exercise habits on NAFLD risk, with mediation analysis utilized to estimate the magnitude of the role of weight maintenance in the association between exercise and NAFLD. Results: After adjusting for confounders, moderate to high-intensity exercisers were 1.56 times (95% CIs = 1.09-2.22) more likely to successfully control their body weight, and therefore the weight-controlled group had a lower NAFLD risk of 34.9% (95% CIs = 21.8%-56.0%) compared to the weight-gain group. Mediation analysis reveals that exercise can significantly reduce the risk of NAFLD both through weight maintenance (37.1%) and independent of weight maintenance (62.9%). Conclusion: It might be more crucial to emphasize the adoption of regular moderate to high-intensity exercise for preventing NAFLD in the general population, rather than solely focusing on weight maintenance.