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1.
Cell ; 184(3): 723-740.e21, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33508230

RESUMO

Elucidating the regulatory mechanisms of human brain evolution is essential to understanding human cognition and mental disorders. We generated multi-omics profiles and constructed a high-resolution map of 3D genome architecture of rhesus macaque during corticogenesis. By comparing the 3D genomes of human, macaque, and mouse brains, we identified many human-specific chromatin structure changes, including 499 topologically associating domains (TADs) and 1,266 chromatin loops. The human-specific loops are significantly enriched in enhancer-enhancer interactions, and the regulated genes show human-specific expression changes in the subplate, a transient zone of the developing brain critical for neural circuit formation and plasticity. Notably, many human-specific sequence changes are located in the human-specific TAD boundaries and loop anchors, which may generate new transcription factor binding sites and chromatin structures in human. Collectively, the presented data highlight the value of comparative 3D genome analyses in dissecting the regulatory mechanisms of brain development and evolution.


Assuntos
Encéfalo/embriologia , Evolução Molecular , Feto/embriologia , Genoma , Organogênese/genética , Animais , Sequência de Bases , Cromatina/metabolismo , Elementos de DNA Transponíveis/genética , Elementos Facilitadores Genéticos/genética , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Macaca mulatta , Camundongos , Especificidade da Espécie , Sintenia/genética , Fatores de Transcrição/metabolismo
2.
Int J Obes (Lond) ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39313560

RESUMO

OBJECTIVE: It is critical to accurately determine the level of obesity and health status since overweight/obesity has become a main global public health problem. This systematic review attempted to evaluate the consistency and correlation between body composition measurement indicators and body mass index (BMI) in childhood and adolescence. METHODS: Seven electronic databases (Web of Science, PubMed, Cochrane Library, Embase, CNKI, WANFANG DATA, SinoMed) were searched to collect the literature published since 1999 with the focus on the relationship between body composition measurement indicators and BMI to measure obesity in childhood and adolescence. RESULTS: Among the 28 articles included, 13 articles reported a moderate to very strong correlation between %BF and BMI in obesity measurement (range: 0.49-0.907), while two articles reported a strong to very strong correlation between FM and BMI (range: 0.60-0.86). Six articles reported good to excellent obesity measurement consistency between %BF and BMI (range: 0.441-0.876), one article reported WC (0.58) and WHtR (0.46) in the moderate consistency with BMI, and one article reported a relatively poor to fair consistency between FM and BMI (range: 0.167-0.409). WC, WHtR, and BMI showed the moderate consistency in pre-adolescent children. In pre-adolescence and adolescence, the measurement consistency between %BF and BMI was higher than that between FM and BMI. Gender difference existed in the consistency between %BF and BMI during adolescence. CONCLUSION: A range of body composition indicators such as %BF, WC, WHtR, and FM could provide valuable body composition measurements, complement BMI for obesity assessment in children and adolescents, and facilitate efficient and comprehensive surveillance of childhood obesity. REGISTRATION: PROSPERO CRD42024506932.

3.
Entropy (Basel) ; 26(6)2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38920514

RESUMO

The code of industrial management software typically features few system API calls and a high number of customized variables and structures. This makes the similarity of such codes difficult to compute using text features or traditional neural network methods. In this paper, we propose an FSPS-GNN model, which is based on graph neural networks (GNNs), to address this problem. The model categorizes code features into two types, outer graph and inner graph, and conducts training and prediction with four stages-feature embedding, feature enhancement, feature fusion, and similarity prediction. Moreover, differently structured GNNs were used in the embedding and enhancement stages, respectively, to increase the interaction of code features. Experiments with code from three open-source projects demonstrate that the model achieves an average precision of 87.57% and an F0.5 Score of 89.12%. Compared to existing similarity-computation models based on GNNs, this model exhibits a Mean Squared Error (MSE) that is approximately 0.0041 to 0.0266 lower and an F0.5 Score that is 3.3259% to 6.4392% higher. It broadens the application scope of GNNs and offers additional insights for the study of code-similarity issues.

4.
Anal Biochem ; 668: 115116, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36925055

RESUMO

Acute enteritis (AE) is a type of digestive disease caused by biochemical factors that irritate the intestinal tract or pathogenic bacteria that infect it. In China, Ma-Mu-Ran Antidiarrheal Capsules (MMRAC) have been applied against diarrhea caused by AE and bacillary dysentery for many years, but the underlying mechanisms of their beneficial effects are not known. In the present study, network pharmacology and metabolomics were performed to clarify the active ingredients of MMRAC and explore the specific mechanism of MMRAC on AE mice. A total of 43 active components of MMRAC with 87 anti-AE target genes were identified, and these target genes were enriched in IL-17 and HIF-1 signaling pathways. Integration analysis revealed that purine metabolism was the critical metabolic pathway by which MMRAC exerted its therapeutic effect against AE. Specifically, MAPK14, MMP9, PTGS2, HIF1A, EGLN1, NOS2 were the pivotal targets of MMRAC for the treatment of AE, and Western blot analysis revealed MMRAC to decrease protein levels of these pro-inflammatory signaling molecules. According to molecular docking, these key targets have a strong affinity with the MMRAC compounds. Collectively, MMRAC relieved the colon inflammation of AE mice via regulating inflammatory signaling pathways to reduce hypoxia and improved energy metabolism.


Assuntos
Medicamentos de Ervas Chinesas , Enterite , Animais , Camundongos , Antidiarreicos/farmacologia , Antidiarreicos/uso terapêutico , Farmacologia em Rede , Simulação de Acoplamento Molecular , Metabolômica , Enterite/tratamento farmacológico , Cápsulas , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
5.
Biomed Chromatogr ; 37(11): e5732, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37732359

RESUMO

The current study utilizes a comprehensive network pharmacology and metabolomics analysis to investigate the mechanism of action of Ma-Mu-Ran Antidiarrheal Capsules (MMRAC) for the treatment of ulcerative colitis (UC). In this study, we established a mouse model of UC using dextran sulfate sodium. Colonic tissues were collected from mice and then subjected to hematoxylin and eosin staining, as well as histopathological analysis, to assess the therapeutic effect of MMRAC. Furthermore, we assessed the mechanisms through which MMRAC combats UC by employing integrated metabolomics and network pharmacology strategies. Lastly, we validated the key targets identified through western blot and molecular docking. An integrated network of metabolomics and network pharmacology was constructed using Cytoscape to identify eight endogenous metabolites involved in the therapeutic action of MMRAC on UC. Further comprehensive analyses were focused on four key targets and their associated core metabolites and pathways. The results of western blot and molecular docking demonstrated that MMRAC could modulate key targets and their expression levels. The cumulative results indicated that MMRAC restored intestinal function in UC, reduced inflammatory responses, and alleviated oxidative stress by influencing the methionine and cysteine metabolic pathways, as well as the urea cycle. In addition, it had an impact on arginine, proline, glutamate, aspartate, and asparagine metabolic pathways and their associated targets.

6.
Res Nurs Health ; 46(5): 515-526, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37525309

RESUMO

School bullying is a worldwide problem. Although previous studies examined the association between different lifestyle behaviors and bullying victimization, the complex co-occurrence of these behaviors was not identified, and their association with the risk of being bullied remains unclear. We aimed to identify the behavioral patterns of adolescents and to explore their association with bullying victimization. This cross-sectional study employed data from the "Surveillance for Common Diseases and Health Risk Factors among Students" project implemented in Jiangsu Province of China in 2019, and a total of 25,379 school-enrolled students were included. We used a latent class analysis to identify behavioral patterns and a regression mixture model to explore various demographic characteristics, such as age, sex, and family structure in relation to bullying victimization across different patterns. We considered respondents having targeted behaviors, including smoking, alcohol consumption, illicit drug use, sugar consumption, no fruit consumption, low physical activity, electronic media use, and insufficient sleep. Four behavioral patterns were identified, including the "adolescents without apparent targeted behaviors" (19.65%), "substance and electronic media users" (12.76%), "typical electronic media users" (54.49%), and "typical substance users" (8.10%). The risk of being bullied was the highest in the "substance and electronic media users" (probability: 0.33), tripled that in "adolescents without apparent targeted behaviors" (odds ratio: 3.60, 95% confidence interval: 3.01-4.30). Risk of being bullied was reduced for those "substance and electronic media users" living with a nuclear family. Behavioral patterns and their association with being bullied differ between groups of school-aged adolescents. To better inform decision-making based on the current real-world findings, the implementation of bullying prevention programs could target specific behavioral patterns.


Assuntos
Bullying , Vítimas de Crime , Humanos , Adolescente , Criança , Estudos Transversais , Análise de Classes Latentes , Fatores de Risco , Estilo de Vida
7.
Chem Biodivers ; 19(8): e202200471, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35774029

RESUMO

Dendrobium huoshanense flowers have been widely used for liver protection in China. This work was aimed to discover the natural products with activity of mitigating alcoholic hepatocyte injury from Dendrobium huoshanense flowers via bioactivity-guided isolation, and to clarify the underlying mechanisms of these natural products. As a result, three flavonoids, 3'-O-methylquercetin-3-O-ß-D-galactopyranoside (1), 3'-O-methylquercetin-3-O-ß-D-glucopyranoside (2) and quercetin-3-O-ß-D-glucopyranoside (3), were firstly isolated from D. huoshanense flowers. Results exhibited that flavonoids 1-3 could enhance the cell viability, decrease the expression of ALT and AST, inhibit the cell apoptosis, alleviate the oxidative stress, and mitigate the inflammatory response of alcohol-induced L02 cells. Mechanism study exhibited that flavonoids 1-3 could increase the expression of Nrf2 as well as its downstream antioxidation genes of alcohol-induced L02 cells, while ML-385 (Nrf2 inhibitor) could abolish the inhibitory effects of 1-3 on alcohol-induced hepatocyte injury. Flavonoids 1-3 could also reduce the phosphorylation levels of IκBα and NF-κB p65 of alcohol-induced L02 cells, while SC75741 (NF-κB inhibitor) could not enhance the inhibitory effects of 1-3 on alcohol-induced L02 cells injury. The data above indicated that flavonoids 1-3 could inhibit alcohol-induced hepatocyte injury, which might be attributed to alleviating oxidative stress and mitigating inflammatory response by activating Nrf2 and inhibiting NF-κB pathways.


Assuntos
Produtos Biológicos , Dendrobium , Produtos Biológicos/farmacologia , Etanol/farmacologia , Flavonoides/farmacologia , Flores/metabolismo , Hepatócitos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo
8.
Sensors (Basel) ; 22(12)2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35746140

RESUMO

Nowadays, accurate localization plays an essential role in many fields, such as target tracking and path planning. The challenges of indoor localization include inadequate localization accuracy, unreasonable anchor deployment in complex scenarios, lack of stability, and the high cost. So, the universal positioning technologies cannot meet the real application requirements scarcely. To overcome these shortcomings, a comprehensive ultra wide-band (UWB)-based real-time localization system (RTLS) is presented in this paper. We introduce the architecture of a real-time localization system, then propose a new wireless clock synchronization (WCS) scheme, and finally discuss the time difference of arrival (TDoA) algorithm. We define the time-base selection strategy for the TDoA algorithm, and we analyze the relationship between anchor deployment and positioning accuracy. The extended Kalman filter (EKF) method is presented for non-linear dynamic localization estimation, and it performs well in terms of stability and accuracy on moving targets.


Assuntos
Algoritmos , Fenômenos Biológicos , Sistemas Computacionais
9.
J Sci Food Agric ; 102(15): 6889-6898, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35647671

RESUMO

BACKGROUND: Improving irrigation water productivity is vital for sustaining high maize yield in Hetao irrigated area of northwest China. Whether ridge cropping and furrow irrigation systems (planting both on ridges and in furrows) fulfill water-saving and maize yield-increasing is unclear. A 2-year trial was conducted to reveal the influence of irrigation with three levels (270, 225, 180 mm, represented as I270 , I225 , I180 , respectively) under two planting systems [traditional flat planting system (TFI) and ridge cropping and furrow irrigation system (RFI)] on maize growth, grain yield, water use efficiency (WUE) and irrigation water use efficiency (IUE). RESULTS: RFI system increased soil water storage in 0-100 cm layer (P < 0.05), but did not cause excess water consumption, compared to TFI system. Logistic equation simulation showed that RFI system advanced the time of maximum dry matter growth rate (Tmax , 2.6-4.9 days) and prolonged the duration of dry matter accumulation (Td , 3.2-4.7 days), ultimately obtained a 4.2-9.5% improvement of dry matter. Compared with TFI system, RFI system increased WUE by 8.0-21.2%, IUE by 8.3-20.5% and grain yield increased by 9.4-21.4%. RFI225 satisfied water-saving by 16.6% and yield-increasing by 3.6-14.7%. CONCLUSION: Ridge cropping and furrow irrigation systems brought an improvement of soil water storage and dry matter accumulation and kernel per spike, and ultimately obtained an increase of grain yield and water productivity. © 2022 Society of Chemical Industry.


Assuntos
Água , Zea mays , Água/análise , Agricultura , Solo , Estações do Ano , China , Irrigação Agrícola , Biomassa
10.
Environ Res ; 195: 110804, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33513381

RESUMO

Studies have shown that ambient air pollution is associated with obesity in adults, but epidemiological evidence is scarce for children and adolescents. This study sought to examine the association between long-term exposure to ambient air pollution and obesity in a large population of children and adolescents in China. A cross-sectional analysis was performed from a school-based health lifestyles intervention project between September 1, 2019 and November 31, 2019, including 36,456 participants aged 9-17 years in Jiangsu province of China. Exposure to air pollutants (nitrogen dioxide (NO2), ozone (O3), particulate matter with aerodynamic diameters ≤10 µm (PM10), and ≤2.5 µm (PM2.5)) were measured based on the nearest air monitoring station for each selected school. Data on each participant's weight and height was also recorded. Demographic and obesity-related behavioral information was collected using a self-reported questionnaire. We used the multivariate regression model to estimate the effects of three-year (2016-2018) average concentrations and the exceedance concentration days (ECD) of air pollutants on obesity after adjusting potential confounders. The ECD was defined as daily concentration exceeding the Chinese National Ambient Air Quality Standard and World Health Organization Ambient Air Quality Guidelines. We observed that higher concentrations of PM2.5, NO2, and O3 were associated with elevated likelihood of obesity. For each 10 µg/m3 increment in concentration, odds ratio of obesity was 1.185 (95% confidence interval (CI): 1.054, 1.333) for PM2.5, 1.127 (95%CI: 1.042, 1.219) for NO2, and 1.041 (95%CI: 1.001, 1.082) for O3, respectively. A significant association between the ECD and obesity was also found for PM2.5 and O3. Effects of air pollutants on obesity were stronger in males, low economic level regions, and age subgroups of 9-11 and 15-17 years. Our findings suggest that long-term exposures to PM2.5, NO2, and O3 were associated with higher prevalence of obesity in children and adolescents. Continuous efforts to reduce air pollution level could help ease the increasing prevalence of obesity within a region.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Obesidade Infantil , Adolescente , Adulto , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Criança , China/epidemiologia , Estudos Transversais , Exposição Ambiental/análise , Humanos , Masculino , Dióxido de Nitrogênio/análise , Material Particulado/análise , Obesidade Infantil/epidemiologia , Obesidade Infantil/etiologia , Instituições Acadêmicas
11.
Langmuir ; 36(33): 9756-9769, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32787125

RESUMO

The adsorption behavior of CO2, CH4, and CO2/CH4 mixtures in four different mature kerogens in the absence/presence of water was studied using grand canonical Monte Carlo and classical molecular dynamics methods. The results exhibit that the adsorption isotherms of single-component CO2 or CH4 in kerogen present similar trends and show type I Langmuir adsorption behavior according to the IUPAC classification; the total adsorbed amount of both gases follows the order of type II-A < type II-B < type II-C < type II-D kerogen under the same conditions. The changing behavior of isosteric heat decreases first and then increases, which can explain the heterogeneous characteristic of the kerogen pore surface. The Coulombic and van der Waals interactions between CO2 and kerogens play an important role on adsorption, while for CH4 adsorption, the electrostatic effect is very small, even negligible. The N-, S-, and O-containing groups in kerogen have more remarkable influence on adsorption of CO2 than CH4 because of their strong adsorption energy, therefore notably improving the selectivity of CO2 over CH4 and following the order of type II-A > type II-B > type II-C > type II-D, which is beneficial to carbon capture and storage. Both pressure and temperature have an obvious impact on gas molecule diffusion, and low pressure and high temperature correspond to a large diffusion coefficient. In addition, preabsorbed water has a negative effect on the adsorption of CO2/CH4, and for the same amount of water molecules, the effect follows the order of type II-A > type II-B > type II-C > type II-D kerogens. The binding energy of water-kerogen is stronger than that of pure CH4 or CO2-kerogen. The selectivity of CO2 over CH4 on kerogen increases with an increasing water content.

12.
BMC Ophthalmol ; 20(1): 439, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33160315

RESUMO

BACKGROUND: The Prevalence of myopia is increasing in China. This study aimed to explore the distribution of spherical equivalent (SE) and its association with age, body mass index (BMI), gender in a non-myopic Chinese children population aged 6 to 12 years. METHODS: A total of 6362 students were recruited for ophthalmological investigation. Demographic and myopia related behavioral information was collected. SE value was measured by the Topcon RM-8900 or KR-800autorefractors. Potential independent risk factors were determined with Odds Ratio (OR) and 95% Confidence Interval (CI) by logistic regression analysis. We further constructed the nomogram model to predict future onset of myopia. RESULTS: Among the study population, 3900 (61.3%) were non-myopic. The prevalence of myopia is 38.0% for boys and 39.5% for girls. The average SE values were 0.50 ± 0.70 D for boys and 0.60 ± 0.80 D for girls. The mean SE values decreased with age, and the value of height and BMI took on a stable trend. Threshold values for myopia varied across age groups and gender. Paternal myopia (OR: 1.22, 95%CI: 1.01-1.48), near-work activities on weekends (2.56, 1.17-5.61), and outdoor activities (0.68, 0.54-0.86) were associated with potential myopic in students. CONCLUSION: A series of age-gender based SE threshold values were established to predict myopia in Chinese children aged 6 to 12 years. High risk factors for myopia included paternal myopia, near-work activities on weekends, and outdoor activities. Countermeasures are encouraged to reverse the increasing trend of myopia in children.


Assuntos
Miopia , Criança , China/epidemiologia , Feminino , Humanos , Masculino , Miopia/epidemiologia , Prevalência , Refração Ocular , Estudantes , Testes Visuais
13.
Mol Carcinog ; 57(10): 1358-1370, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30295962

RESUMO

Hepatocellular Carcinoma (HCC) is a malignant tumor with high rate of relapse and metastasis. Ethanol is a well-known risk factor for HCC; it promotes the progression and aggressiveness of HCC. However, the underlying mechanism remains unclear. In clinic studies, we showed that alcohol consumption is positively correlated with TNM stage and vessel invasion; HCC patients with chronic drinking history had faster progression rate and poorer prognosis compared to non-drinkers. In experimental models, ethanol exposure enhanced the metastasis, and invasion of HCC cells. Ethanol exposure increased cancer stem cells (CSC) population and enhanced stemness of HCC cells in vitro and in vivo. Mechanically, we found that ethanol exposure induced epithelial to mesenchymal transition (EMT) through activating Wnt/ß-catenin signaling pathway in HCC cells. We further demonstrated that ß-catenin siRNA or salinomycin (an inhibitor of Wnt/ß-catenin pathway) partially rescued ethanol-induced EMT. In conclusion, this study suggested that ethanol exposure promotes the metastasis and stemness of HCC cells by inducing EMT.


Assuntos
Carcinoma Hepatocelular/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Etanol/farmacologia , Neoplasias Hepáticas/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Consumo de Bebidas Alcoólicas , Animais , Anti-Infecciosos Locais/farmacologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Feminino , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Nus , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Experimentais/genética , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Transplante Heterólogo
14.
Plant Biotechnol J ; 14(2): 638-48, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26096084

RESUMO

Analyses of genome variations with high-throughput assays have improved our understanding of genetic basis of crop domestication and identified the selected genome regions, but little is known about that of modern breeding, which has limited the usefulness of massive elite cultivars in further breeding. Here we deploy pedigree-based analysis of an elite rice, Huanghuazhan, to exploit key genome regions during its breeding. The cultivars in the pedigree were resequenced with 7.6× depth on average, and 2.1 million high-quality single nucleotide polymorphisms (SNPs) were obtained. Tracing the derivation of genome blocks with pedigree and information on SNPs revealed the chromosomal recombination during breeding, which showed that 26.22% of Huanghuazhan genome are strictly conserved key regions. These major effect regions were further supported by a QTL mapping of 260 recombinant inbred lines derived from the cross of Huanghuazhan and a very dissimilar cultivar, Shuanggui 36, and by the genome profile of eight cultivars and 36 elite lines derived from Huanghuazhan. Hitting these regions with the cloned genes revealed they include numbers of key genes, which were then applied to demonstrate how Huanghuazhan were bred after 30 years of effort and to dissect the deficiency of artificial selection. We concluded the regions are helpful to the further breeding based on this pedigree and performing breeding by design. Our study provides genetic dissection of modern rice breeding and sheds new light on how to perform genomewide breeding by design.


Assuntos
Genoma de Planta , Oryza/genética , Linhagem , Melhoramento Vegetal/métodos , Cromossomos de Plantas/genética , Sequência Conservada , Fluxo Gênico , Genes de Plantas , Polimorfismo de Nucleotídeo Único/genética , Característica Quantitativa Herdável , Análise de Sequência de DNA
15.
J Neurosci ; 34(40): 13535-48, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-25274829

RESUMO

Stroke is a major public health concern. The lack of effective therapies heightens the need for new therapeutic targets. Mammalian brain has the ability to rewire itself to restore lost functionalities. Promoting regenerative repair, including neurogenesis and dendritic remodeling, may offer a new therapeutic strategy for the treatment of stroke. Here, we report that interaction of neuronal nitric oxide synthase (nNOS) with the protein postsynaptic density-95 (PSD-95) negatively controls regenerative repair after stroke in rats. Dissociating nNOS-PSD-95 coupling in neurons promotes neuronal differentiation of neural stem cells (NSCs), facilitates the migration of newborn cells into the injured area, and enhances neurite growth of newborn neurons and dendritic spine formation of mature neurons in the ischemic brain of rats. More importantly, blocking nNOS-PSD-95 binding during the recovery stage improves stroke outcome via the promotion of regenerative repair in rats. Histone deacetylase 2 in NSCs may mediate the role of nNOS-PSD-95 association. Thus, nNOS-PSD-95 can serve as a target for regenerative repair after stroke.


Assuntos
Infarto da Artéria Cerebral Média/cirurgia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Células-Tronco Neurais/transplante , Óxido Nítrico Sintase Tipo I/metabolismo , Regeneração/fisiologia , Animais , Encéfalo/patologia , Encéfalo/ultraestrutura , Diferenciação Celular/fisiologia , Células Cultivadas , Córtex Cerebral/citologia , Técnicas de Cocultura , Modelos Animais de Doenças , Proteína 4 Homóloga a Disks-Large , Embrião de Mamíferos , Glucose/deficiência , Histona Desacetilase 2/genética , Histona Desacetilase 2/metabolismo , Hipóxia/fisiopatologia , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Células-Tronco Neurais/fisiologia , Neurogênese/fisiologia , Neurônios/metabolismo , Neurônios/patologia , Neurônios/ultraestrutura , Óxido Nítrico Sintase Tipo I/genética , Ratos , Ratos Sprague-Dawley
16.
J Phys Chem A ; 119(40): 10204-11, 2015 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-26377371

RESUMO

Density functional theory has been used to probe the mechanism of gas-phase methanol decomposition by bare Fe(+) and ligated Fe(C(2)H(4))(+) in both quartet and sextet states. For the Fe(+)/methanol system, Fe(+) could directly attach to the O and methyl-H atoms of methanol, respectively, forming two encounter isomers. The methanol reaction with Fe(+) prefers initial C-O bond activation to yield methyl with slight endothermicity, whereas CH(4) elimination is hindered by the strong endothermicity and high-energy barrier of hydroxyl-H shift. For the Fe(C(2)H(4))(+)/methanol system, the major product of H(2)O is formed through six elementary steps: encounter complexation, C-O bond activation, C-C coupling, ß-H shift, hydride H shift, and nonreactive dissociation. Both ligand exchange and initial C-O bond activation mechanisms could account for ethylene elimination with the ion products Fe(CH(3)OH)(+) and (CH(3))Fe(OH)(+), respectively. With the assistance of a π-type C(2)H(4) ligand, the metal center in the Fe(C(2)H(4))(+)/CH(3)OH system avoids formation of unfavorable multi-σ-type bonding and thus greatly enhances the reactivity compared to that of bare Fe(+).


Assuntos
Etilenos/química , Ferro/química , Metanol/química , Teoria Quântica , Ligantes , Modelos Moleculares , Termodinâmica
17.
Comput Biol Med ; 169: 107900, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38199213

RESUMO

Drug-drug interactions (DDIs) play a central role in drug research, as the simultaneous administration of multiple drugs can have harmful or beneficial effects. Harmful interactions lead to adverse reactions, some of which can be life-threatening, while beneficial interactions can promote efficacy. Therefore, it is crucial for physicians, patients, and the research community to identify potential DDIs. Although many AI-based techniques have been proposed for predicting DDIs, most existing computational models primarily focus on integrating multiple data sources or combining popular embedding methods. Researchers often overlook the valuable information within the molecular structure of drugs or only consider the structural information of drugs, neglecting the relationship or topological information between drugs and other biological objects. In this study, we propose MSKG-DDI - a two-component framework that incorporates the Drug Chemical Structure Graph-based component and the Drug Knowledge Graph-based component to capture multimodal characteristics of drugs. Subsequently, a multimodal fusion neural layer is utilized to explore the complementarity between multimodal representations of drugs. Extensive experiments were conducted using two real-world datasets, and the results demonstrate that MSKG-DDI outperforms other state-of-the-art models in binary-class, multi-class, and multi-label prediction tasks under both transductive and inductive settings. Furthermore, the ablation analysis further confirms the practical usefulness of MSKG-DDI.


Assuntos
Redes Neurais de Computação , Reconhecimento Automatizado de Padrão , Humanos , Interações Medicamentosas
18.
J Hazard Mater ; 480: 135842, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39316917

RESUMO

Air pollution is associated with vision loss in children, but the relationship with vision trajectories has not been explored. The study was conducted as a prospective cohort in 16 districts of Shanghai from 2021 to 2023, involving 5612 children with complete survey data. Each child underwent 3-4 eye tests, including unaided visual acuity and computerized refraction. Children's air pollutant exposure levels (PM2.5, PM10, O3, SO2, NO2, and CO) were assessed using school addresses and examination dates. Latent class mixture modeling was used to identify the trajectories of changes in vision-related measurements in children. Multinomial logistic regression and Cox proportional hazards regression were used to examine the association of air pollutant exposure and visual trajectories, as well as visual impairment outcomes. The study identified three trajectory categories for children's unaided visual acuity, spherical equivalent, and four trajectory categories for axial length. Increased levels of PM2.5, PM10, O3, and SO2 exposure are associated with an increased risk of categorizing vision-related measurements into the "poor" category trajectory in children. Increased exposure to PM2.5, O3, and NO2 was associated with an increased risk of visual impairment outcomes in children with normal vision at baseline, and the effect was more significant in female and older children.

19.
Int J Biol Macromol ; 278(Pt 2): 134783, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39153673

RESUMO

Glucagon-like peptide-1 (GLP-1) as a multifunctional hormone is secreted mainly from enteroendocrine L-cells, and enhancing its endogenous secretion has potential benefits of regulating glucose homeostasis and controlling body weight gain. In the present study, a novel polysaccharide (h-DHP) with high ability to enhance plasma GLP-1 level in mice was isolated from Dendrobium huoshanense protocorm-like bodies under the guidance of activity evaluation. Structural identification showed that h-DHP was an acidic polysaccharide with the molecular weight of 1.38 × 105 Da, and was composed of galactose, glucose, arabinose and glucuronic acid at a molar ratio of 15.7: 11.2: 4.5: 1.0 with a backbone consisting of →5)-α-L-Araf-(1→, →3)-α-D-Galp-(1→, →6)-α-D-Galp-(1→, →3,6)-α-D-Galp-(1→, →6)-ß-D-Glcp-(1→ and →4,6)-ß-D-Glcp-(1→ along with branches consisting of α-L-Araf-(1→, α-D-Galp-(1→, α-D-GlcAp-(1→, ß-D-Glcp-(1→ and →4)-ß-D-Glcp-(1→. Animal experiments with different administration routes demonstrated that h-DHP-enhanced plasma GLP-1 level was attributed to h-DHP-promoted GLP-1 secretion in the enteroendocrine L-cells, which was supported by h-DHP-enhanced extracellular GLP-1 level in STC-1 cells. Inhibition of adenylate cyclase and phospholipase C indicated that cAMP and cAMP-triggered intracellular Ca2+ increase participated in h-DHP-promoted GLP-1 secretion. These results suggested that h-DHP has the potential of enhancing endogenous GLP-1 level through h-DHP-promoted and cAMP-mediated GLP-1 secretion from enteroendocrine cells.


Assuntos
Dendrobium , Peptídeo 1 Semelhante ao Glucagon , Polissacarídeos , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/sangue , Dendrobium/química , Animais , Polissacarídeos/farmacologia , Polissacarídeos/química , Camundongos , Masculino , Peso Molecular , Células Enteroendócrinas/metabolismo , Células Enteroendócrinas/efeitos dos fármacos , AMP Cíclico/metabolismo
20.
J Ethnopharmacol ; 332: 118363, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-38763373

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum, a renowned tonic traditional Chinese medicine, is widely recognized for the exceptional activity in soothing nerves and nourishing the brain. It has been extensively employed to alleviate various neurological disorders, notably Parkinson's disease (PD). AIM OF THE STUDY: To appraise the antiparkinsonian effect of GAA, the main bioactive constituent of G. lucidum, and clarify the molecular mechanism through the perspective of ferritinophagy-mediated dopaminergic neuron ferroptosis. MATERIALS AND METHODS: PD mouse and cell models were established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+), respectively. Cell viability, behavioral tests and immunofluorescence analysis were performed to evaluate the neurotoxicity, motor dysfunction and dopaminergic loss, respectively. Biochemical assay kits were used to determine the levels of iron, lipid reactive oxygen species (ROS), malondialdehyde (MDA), total ROS and glutathione (GSH). Western blot and immunofluorescence were applied to detect the expressions of nuclear receptor co-activator 4 (NCOA4), ferritin heavy chain 1 (FTH1), p62 and LC3B. Additionally, NCOA4-overexpressing plasmid vector was constructed to verify the inhibitory effect of GAA on the neurotoxicity and ferroptosis-related parameters in PD models. RESULTS: GAA significantly mitigated MPP+/MPTP-induced neurotoxicity, motor dysfunction and dopaminergic neuron loss (p<0.01 or p<0.05). In contrast to MPP+/MPTP treatment, GAA treatment decreased the levels of iron, MDA, lipid and total ROS, while increasing the GSH level. GAA also reduced the levels of NCOA4 and LC3B, and enhanced the expressions of FTH1 and p62 in PD models (p<0.01 or p<0.05). However, the protective effect of GAA against the neurotoxicity, NCOA4-mediated ferritinophagy and ferroptosis in PD model was abolished by the overexpression of NCOA4 (p<0.01). CONCLUSION: GAA exerted a protective effect on PD, and this effect was achieved by suppressing dopaminergic neuron ferroptosis through the inhibition of NCOA4-mediated ferritinophagy.


Assuntos
Neurônios Dopaminérgicos , Ferritinas , Ferroptose , Camundongos Endogâmicos C57BL , Coativadores de Receptor Nuclear , Animais , Ferroptose/efeitos dos fármacos , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Coativadores de Receptor Nuclear/metabolismo , Camundongos , Masculino , Ferritinas/metabolismo , Fármacos Neuroprotetores/farmacologia , Autofagia/efeitos dos fármacos , Antiparkinsonianos/farmacologia , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/induzido quimicamente , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Modelos Animais de Doenças
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