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1.
Eur J Clin Microbiol Infect Dis ; 43(4): 747-765, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38367094

RESUMO

PURPOSE: High fasting plasma glucose (HFPG) has been identified as a risk factor for drug-resistant tuberculosis incidence and mortality. However, the epidemic characteristics of HFPG-attributable multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) remain unclear. We aimed to analyze the global spatial patterns and temporal trends of HFPG-attributable MDR-TB and XDR-TB from 1990 to 2019. METHODS: Utilizing data from the Global Burden of Disease 2019 project, annual deaths and disability-adjusted life years (DALYs) of HFPG-attributable MDR-TB and XDR-TB were conducted from 1990 to 2019. Joinpoint regression was employed to quantify trends over time. RESULTS: From 1990 to 2019, the deaths and DALYs due to HFPG-attributable MDR-TB and XDR-TB globally showed an overall increasing trend, with a significant increase until 2003 to 2004, followed by a gradual decline or stability thereafter. The low sociodemographic index (SDI) region experienced the most significant increase over the past 30 years. Regionally, Sub-Saharan Africa, Central Asia and Oceania remained the highest burden. Furthermore, there was a sex and age disparity in the burden of HFPG-attributable MDR-TB and XDR-TB, with young males in the 25-34 age group experiencing higher mortality, DALYs burden and a faster increasing trend than females. Interestingly, an increasing trend followed by a stable or decreasing pattern was observed in the ASMR and ASDR of HFPG-attributable MDR-TB and XDR-TB with SDI increasing. CONCLUSION: The burden of HFPG-attributable MDR-TB and XDR-TB rose worldwide from 1990 to 2019. These findings emphasize the importance of routine bi-directional screening and integrated management for drug-resistant TB and diabetes.


Assuntos
Tuberculose Extensivamente Resistente a Medicamentos , Tuberculose Resistente a Múltiplos Medicamentos , Masculino , Feminino , Humanos , Glicemia , Estudos Retrospectivos , Carga Global da Doença , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Jejum
2.
Adv Healthc Mater ; 13(6): e2302687, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37940192

RESUMO

In situ monitoring of bone tissue regeneration progression is critical for the development of bone tissue engineering scaffold. However, engineered scaffolds that can stimulate osteogenic progress and allow for non-invasive monitoring of in vivo bone regeneration simultaneously are rarely reported. Based on a hard-and-soft integration strategy, a multifunctional scaffold composed of 3D printed microfilaments and a hydrogel network containing simvastatin (SV), indocyanine green-loaded superamphiphiles, and aminated ultrasmall superparamagnetic iron oxide nanoparticles (USPIO-NH2 ) is fabricated. Both in vitro and in vivo results demonstrate that the as-prepared scaffold significantly promotes osteogenesis through controlled SV release. The biocomposite scaffold exhibits alkaline phosphatase-responsive near-infrared II fluorescence imaging. Meanwhile, USPIO-NH2 within the co-crosslinked nanocomposite network enables the visualization of scaffold degradation by magnetic resonance imaging. Therefore, the biocomposite scaffold enables or facilitates non-invasive in situ monitoring of neo-bone formation and scaffold degradation processes following osteogenic stimulation, offering a promising strategy to develop theranostic scaffolds for tissue engineering.


Assuntos
Osso e Ossos , Procedimentos de Cirurgia Plástica , Imageamento por Ressonância Magnética , Osteogênese , Fosfatase Alcalina
3.
Quant Imaging Med Surg ; 13(12): 8336-8349, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38106319

RESUMO

Background: Rhabdomyolysis (RM)-induced acute kidney injury (AKI) is a common renal disease with low survival rate and inadequate prognosis. In this study, we investigate the feasibility of chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) for assessing the progression of RM-induced AKI in a mouse model. Methods: AKI was induced in C57BL/6J mice via intramuscular injection of 7.5 mL/kg glycerol (n=30). Subsequently, serum creatinine (SCr), blood urea nitrogen (BUN), and hematoxylin-eosin (HE) and Masson staining, were performed. Longitudinal CEST-MRI was conducted on days 1, 3, 7, 15, and 30 after AKI induction using a 7.0-T MRI system. CEST-MRI quantification parameters including magnetization transfer ratio (MTR), MTR asymmetric analysis (MTRasym), apparent amide proton transfer (APT*), and apparent relayed nuclear Overhauser effect (rNOE*) were used to investigate the feasibility of detecting RM-induced renal damage. Results: Significant increases of SCr and BUN demonstrated established AKI. The HE staining revealed various degrees of tubular damage, and Masson staining indicted an increase in the degree of fibrosis in the injured kidneys. Among CEST parameters, the cortical MTR presented a significant difference, and it also showed the best diagnostic performance for AKI [area under the receiver operating characteristic curve (AUC) =0.915] and moderate negative correlations with SCr and BUN. On the first day of renal damage, MTR was significantly reduced in cortex (22.7%±0.04%, P=0.013), outer stripe of outer medulla (24.7%±1.6%, P<0.001), and inner stripe of outer medulla (27.0%±1.5%, P<0.001) compared to the control group. Longitudinally, MTR increased steadily with AKI progression. Conclusions: The MTR obtained from CEST-MRI is sensitive to the pathological changes in RM-induced AKI, indicating its potential clinical utility for the assessment of kidney diseases.

4.
Artigo em Inglês | MEDLINE | ID: mdl-37823234

RESUMO

BACKGROUND: The chronic rhinosinusitis patient-reported outcome (CRS-PRO) is a recently published disease-specific questionnaire designed for CRS patients, with fewer entries and ease of completion. This study aimed to translate the CRS-PRO questionnaire into Chinese and assess its reliability, validity, and responsiveness to provide Chinese patients with a more concise and efficient subjective assessment instrument. METHODS: The Chinese version of the CRS-PRO was created through forward-backward translations and cultural adaptation. Here, 168 CRS patients (118 patients CRS with nasal polyps [CRSwNP] and 50 patients with CRS without nasal polyps [CRSsNP]) and 43 healthy individuals were enrolled. All participants completed the CRS-PRO, 22-item Sinonasal Outcome Test (SNOT-22), and EuroQol five dimensions questionnaire (EQ-5D) questionnaires preoperatively as well as 3 and 6 months after surgery. RESULTS: The Chinese version of the CRS-PRO demonstrated good internal consistency, with a Cronbach's α of 0.813. It also exhibited a higher criterion validity (r = 0.65, p < 0.05) than the SNOT-22. A moderate association was found between the CRS-PRO and objective indicators such as the Lund-Mackay and endoscopic scores. Furthermore, the CRS-PRO, like the SNOT-22, could clearly distinguish CRS patients from healthy subjects (p < 0.01), as well as between the CRSwNP and CRSsNP subtypes (p < 0.01). Additionally, changes in the CRS-PRO exhibited a larger effect size compared to changes in the SNOT-22 (Cohen's d = 1.05 and 0.93 vs. 0.71 and 0.90 for 3 and 6 months, respectively, all p < 0.01). CONCLUSIONS: The Chinese version of the CRS-PRO is a concise, reliable, and responsive instrument that can be utilized as a novel subjective evaluation tool for future clinical practice.

5.
ACS Chem Neurosci ; 14(21): 3959-3971, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37830541

RESUMO

The microtubule-associated protein tau (MAPT) has a critical role in the development and preservation of the nervous system. However, tau's dysfunction and accumulation in the human brain can lead to several neurodegenerative diseases, such as Alzheimer's disease, Down's syndrome, and frontotemporal dementia. The microtubule binding (MTB) domain plays a significant, important role in determining the tau's pathophysiology, as the core of paired helical filaments PHF6* (275VQIINK280) and PHF6 (306VQIVYK311) of R2 and R3 repeat units, respectively, are formed in this region, which promotes tau aggregation. Post-translational modifications, and in particular lysine acetylation at K280 of PHF6* and K311 of PHF6, have been previously established to promote tau misfolding and aggregation. However, the exact aggregation mechanism is not known. In this study, we established an atomic-level nucleation-extension mechanism of the separated aggregation of acetylated PHF6* and PHF6 hexapeptides, respectively, of tau. We show that the acetylation of the lysine residues promotes the formation of ß-sheet enriched high-ordered oligomers. The Markov state model analysis of ac-PHF6* and ac-PHF6 aggregation revealed the formation of an antiparallel dimer nucleus which could be extended from both sides in a parallel manner to form mixed-oriented and high-ordered oligomers. Our study describes the detailed mechanism for acetylation-driven tau aggregation, which provides valuable insights into the effect of post-translation modification in altering the pathophysiology of tau hexapeptides.


Assuntos
Doença de Alzheimer , Simulação de Dinâmica Molecular , Humanos , Lisina/metabolismo , Proteínas tau/metabolismo , Peptídeos/metabolismo , Doença de Alzheimer/metabolismo , Emaranhados Neurofibrilares/metabolismo , Proteínas Repressoras/metabolismo
6.
BMJ Open ; 13(9): e074134, 2023 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-37770275

RESUMO

OBJECTIVE: This study aimed to analyse the burden and temporal trends of tuberculosis (TB) incidence and mortality globally, as well as the association between mortality-to-incidence ratio (MIR) and Socio-Demographic Index (SDI). DESIGN: A retrospective analysis of TB data from 1990 to 2019 was conducted using the Global Burden of Disease Study database. RESULTS: Between 1990 and 2019, there was a declining trend in the global incidence and mortality of TB. High SDI regions experienced a higher declining rate than in low SDI regions during the same period. Nearly half of the new patients occurred in South Asia. In addition, there is a sex-age imbalance in the overall burden of TB, with young males having higher incidence and mortality than females. In terms of the three subtypes of TB, drug-sensitive (DS)-TB accounted for more than 90% of the incidents and deaths and experienced a decline over the past 30 years. However, drug-resistant TB (multidrug-resistant (MDR)-TB and extensively drug-resistant (XDR)-TB) showed an overall increasing trend in age-standardised incidence rates and age-standardised mortality rates, with an inflection point after the year 2000. At the regional level, South Asia and Eastern Europe remained a high burden of drug-resistant TB incidence and mortality. Interestingly, a negative correlation was found between the MIR and SDI for TB, including DS-TB, MDR-TB and XDR-TB. Notably, central sub-Saharan Africa had the highest MIR, which indicated a higher-than-expected burden given its level of sociodemographic development. CONCLUSION: This study provides comprehensive insights into the global burden and temporal trends of TB incidence and mortality, as well as the relationship between MIR and SDI. These findings contribute to our understanding of TB epidemiology and can inform public health strategies for prevention and management.


Assuntos
Infecções por HIV , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Masculino , Feminino , Humanos , Carga Global da Doença , Estudos Retrospectivos , Tuberculose/epidemiologia , Incidência , Saúde Global , Infecções por HIV/epidemiologia
7.
Environ Sci Pollut Res Int ; 30(42): 96019-96039, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37561292

RESUMO

As the issue of global climate change caused by carbon emissions is of great concern, China has proposed achieving its achieve carbon peak goal by 2030. Building carbon emissions account for approximately 50% of China's total carbon emissions. It is crucial to study the time and values of building carbon peaks. In this paper, based on a system dynamics model, logarithmic mean Divisia index model and Monte Carlo simulation, we predict the building carbon peak in China. The following conclusions are obtained: 1) in the baseline scenario, China's building carbon emissions will peak at 5,427 million tons in 2027. In the high-speed development scenario, China's building carbon emissions will peak at 6,298 million tons in 2032. In the coordinated development scenario, the green development scenario, the low-carbon development scenario, and the low-speed development scenario, the peak occurs in 2030 at 5,972 million tons, 5,991 million tons, 5,657 million tons, and 6,329 million tons, respectively. 2) According to the comprehensive simulation, China's building carbon emissions will reach the peak in 2030, with an 80% probability of reaching 5,729-6,171 million tons.


Assuntos
Dióxido de Carbono , Carbono , Carbono/análise , Dióxido de Carbono/análise , China , Mudança Climática , Desenvolvimento Econômico
8.
BMC Bioinformatics ; 24(1): 264, 2023 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-37355560

RESUMO

A nonhomogeneous dynamic Bayesian network model, which combines the dynamic Bayesian network and the multi-change point process, solves the limitations of the dynamic Bayesian network in modeling non-stationary gene expression data to a certain extent. However, certain problems persist, such as the low network reconstruction accuracy and poor model convergence. Therefore, we propose an MD-birth move based on the Manhattan distance of the data points to increase the rationality of the multi-change point process. The underlying concept of the MD-birth move is that the direction of movement of the change point is assumed to have a larger Manhattan distance between the variance and the mean of its left and right data points. Considering the data instability characteristics, we propose a Markov chain Monte Carlo sampling method based on node-dependent particle filtering in addition to the multi-change point process. The candidate parent nodes to be sampled, which are close to the real state, are pushed to the high probability area through the particle filter, and the candidate parent node set to be sampled that is far from the real state is pushed to the low probability area and then sampled. In terms of reconstructing the gene regulatory network, the model proposed in this paper (FC-DBN) has better network reconstruction accuracy and model convergence speed than other corresponding models on the Saccharomyces cerevisiae data and RAF data.


Assuntos
Algoritmos , Redes Reguladoras de Genes , Teorema de Bayes , Cadeias de Markov , Saccharomyces cerevisiae/genética , Método de Monte Carlo
9.
Huan Jing Ke Xue ; 44(2): 807-815, 2023 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-36775604

RESUMO

Polycyclic aromatic hydrocarbons (PAHs), as a highly toxic persistent organic pollutant, are commonly found in soil and water environments. In recent years, the pollution of PAHs in groundwater has attracted wide attention from scientists. To study the pollution characteristics and sources of polycyclic aromatic hydrocarbon in groundwater of the coking site, 16 PAHs priorly controlled by the US EPA were analyzed and discussed. In this study, we identified the contamination characteristics of PAHs in groundwater, analyzed the pollution sources of PAHs, and evaluated the ecological risk of PAHs in the coking site by combining statistical techniques, the positive matrix factorization (PMF) model, and risk quotient (RQ) methods. The results indicated that the total detection rate of PAHs in groundwater of the coking plant was 46.7%. The concentrations of PAHs in groundwater of the coking plant ranged from below the detection limit to 444.9 µg·L-1, with the average value of 1.88 µg·L-1. The concentration of PAHs in the groundwater of different production workshops was significantly different. The most polluted workshop was in the tar-refining area, and the concentration of 16 PAHs was 444.9 µg·L-1. Based on the PMF model, we identified the two primary contamination sources of PAHs in groundwater of the coking plant:① oil combustion and ② coal and biomass combustion and oil leakage. The contribution ratios of the two sources to PAHs of groundwater were 38.6% and 61.4%, respectively. The results of the ecological risk assessment indicated that Σ16PAHs in groundwater of the coking plant had high ecological risk, and the ecological risk of single PAHs in 53.4% of the groundwater sampling site was at a high ecological risk level. In conclusion, it is urgent to carry out the treatment and restoration of the groundwater environment in the coking plant site.


Assuntos
Coque , Água Subterrânea , Hidrocarbonetos Policíclicos Aromáticos , Coque/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Monitoramento Ambiental/métodos , Medição de Risco , China
10.
PLoS One ; 18(1): e0277965, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36689409

RESUMO

We examine whether equity incentive can encourage exploratory innovation from the perspective of dynamic innovation decision-making process. Using the data of equity incentives in China's listed companies from 2006 to 2017, we construct exploratory intensity of innovation strategy and analyze the impact of equity incentive on corporation exploratory innovation strategy from both the cross-sectional and time-series perspectives. We find a positive relationship between the vesting period and explorative innovation strategy in the cross-sectional dimension. However, the time-series analyses show that the innovation strategy becomes less explorative and more exploitative after the third period during equity incentive. The effect of vesting period is stronger in smaller firms and during the non-financial crisis period. Further analysis reveals that followed by the changes in innovation strategy, the growth rates of innovation output and firm performance also decline.


Assuntos
Motivação , Organizações , Estudos Transversais , Tomada de Decisões
11.
Cancer Med ; 12(3): 3532-3542, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36000818

RESUMO

BACKGROUND: This study examined the acceptance and willingness to pay (WTP) of rural residents toward packaging cancer screening (PCS) to provide a reference basis for promoting the screening sustainable development. METHODS: A face-to-face questionnaire survey was conducted among rural residents aged 40-69. The combination of double-bounded dichotomous choices and open-ended questions in the Contingent Valuation Method was used to guide participants' WTP. Logistic regression was used to explore the influencing factors of participants' screening acceptance, and Tobit model was used to analyze the associated factors of WTP. RESULTS: Of the 959 respondents, 89.36% were willing to accept PCS, but 10.64% stated unwillingness for the dominant reason that they did not attend clinics until symptom onset. Willingness to accept screening was significantly associated with region (Dongchangfu, OR = 0.251, 95%CI: 0.113~0.557; Linqu, OR = 0.150, 95%CI: 0.069~0.325), age with 60-69 (OR = 0.321, 95%CI: 0.126~0.816), annual income with 10,000-30,000 (OR = 1.632, 95%CI: 1.003~2.656) and having cancer-screening experience (OR = 0.581, 95%CI: 0.371~0.909). And 57.66% of participants were willing to pay part of the screening cost among those willing to accept PCS. The residents' average WTP was ¥622, accounting for 20.73% of the total cost (¥3000). Willingness to pay for PCS was positively correlated with male gender, self-employed occupation, residence in Feicheng (than Linqu), higher income, and having cancer-screening experience. CONCLUSIONS: Most rural residents were willing to accept free PCS, more than half of them were willing to pay part of the ¥3000 total cost, but their WTP-values were low. It is necessary to carry out PCS publicity activities to improve public awareness and participation in precancerous screening. Additionally, for expanding the coverage and sustainability of screening, the appropriate proportion of rural residents to pay for screening costs should be controlled at about 20%, and governments, insurance and other sources are encouraged to actively participate to cover the remaining costs.


Assuntos
Detecção Precoce de Câncer , Neoplasias , Aceitação pelo Paciente de Cuidados de Saúde , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Detecção Precoce de Câncer/economia , População do Leste Asiático , Neoplasias/diagnóstico , População Rural , Inquéritos e Questionários , Gastos em Saúde
12.
ACS Omega ; 7(35): 30954-30966, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36092573

RESUMO

Waste tire pyrolysis has received increasing attention as a promising technology recently due to the shortage of fossil resources and the severity of environmental impact. In this study, the process of waste tire pyrolysis and upgrading to obtain high-value products was simulated by Aspen Plus. Also, based on life cycle assessment, the indexes of energy, environmental, economic, and comprehensive performance were proposed to evaluate different high-value pathways. Results demonstrate that the integrated system of waste tire pyrolysis, pyrolytic oil (TPO) refining, and pyrolytic carbon black (CBp) modification has higher energy efficiency than the independent system of TPO refining, with an improvement rate of 2.6%. Meanwhile, the resource-environmental performance of the integrated system is better. However, combined with the economic benefit, the independent system is more comprehensively beneficial, with the index of comprehensive performance (BEECR) of 0.94, which increases by 3.3% compared with the integrated system. Furthermore, the comparisons of different improved high-value paths based on the independent system as the benchmark indicate that the pathway of promoting sulfur conversion during pyrolysis to reduce the sulfur content in TPO can increase the BEECR from 0.94 to 1.064, with the growth of 13.2%. Also, the physical modification of CBp to reduce the production cost and environmental impact has better performance of BEECR, increasing by 20.2%. The final sensitivity analyses show that the combined improved high-value case established by the abovementioned two paths can achieve a favorable benefit in a wide range of crude oil and waste tire prices and the environmental tax.

13.
Sci Total Environ ; 851(Pt 1): 158146, 2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-35987231

RESUMO

The interactive effects of ocean acidification (OA) and copper (Cu) ions on the mussel Mytilus galloprovincialis are not well understood. The underlying mechanisms also remain obscure. In this study, individuals of M. galloprovincialis were exposed for 28 days to 25 µg/L and 50 µg/L Cu ions at two pH levels (ambient level - pH 8.1; acidified level - pH 7.6). The mussels were then monitored for 56 days to determine their recovery ability. Physiological parameters (clearance rate and respiration rate), oxidative stress and neurotoxicity biomarkers (activities of superoxide dismutase, lipid peroxidation, catalase, and acetylcholinesterase), as well as the recovery ability of these parameters, were investigated in two typical tissues (i.e., gills and digestive glands). Results showed that (1) OA affected the bioconcentration of Cu in the gills and digestive glands of the mussels; (2) both OA and Cu can lead to physiological disturbance, oxidative stress, cellular damage, energy metabolism disturbance, and neurotoxicity on M. galloprovincialis; (3) gill is more sensitive to OA and Cu than digestive gland; (4) Most of the biochemical and physiological alternations caused by Cu and OA exposures in M. galloprovincialis can be repaired by the recovery experiments; (5) integrated biomarker response (IBR) analysis demonstrated that both OA and Cu ions exposure caused survival stresses to the mussels, with the highest effect shown in the co-exposure treatment. This study highlights the necessity to include OA along with pollutants in future studies to better elucidate the risks of ecological perturbations. The work also sheds light on the recovery of marine animals after short-term environmental stresses when the natural environment has recovered.


Assuntos
Mytilus , Poluentes Químicos da Água , Acetilcolinesterase/metabolismo , Animais , Biomarcadores/metabolismo , Catalase/metabolismo , Cobre/análise , Concentração de Íons de Hidrogênio , Íons/metabolismo , Estresse Oxidativo , Água do Mar , Superóxido Dismutase/metabolismo , Poluentes Químicos da Água/análise
14.
Ann Allergy Asthma Immunol ; 129(6): 720-730.e8, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36002091

RESUMO

BACKGROUND: High body mass index (BMI) plays a key role in the progression of asthma and asthma related to high BMI resulted in a high burden of disease globally. OBJECTIVE: To explore the geographic and temporal trends in the global burden of asthma associated with high BMI from 1990 to 2019. METHODS: This is a retrospective analysis with data based on the Global Burden of Disease Study 2019 database. Deaths, disability-adjusted life-years (DALYs), age-standardized mortality rate (ASMR), and age-standardized DALY rate (ASDR) were estimated according to sex, age, and sociodemographic index levels. The estimated annual percentage change was used to evaluate the variation trends of ASMR and ASDR from 1990 to 2019. RESULTS: In 2019, the number of global asthma deaths and DALYs related to high BMI increased by 69.69% and 63.91%, respectively, compared with 1990, among which more deaths and DALYs occurred in women. The corresponding ASMR and ASDR exhibited a slightly decreasing tendency globally. South Asia accounted for the highest number of deaths and DALYs, with India ranking first worldwide in 2019. The number of deaths and DALYs were mainly seen in individuals 60 to 79 years old and 55 to 69 years old, respectively, from 1990 to 2019. The heaviest burden existed in the low-middle sociodemographic index region. CONCLUSION: The global asthma burden associated with obesity increased in absolute value but the standardized burden decreased slightly. Large variations existed in the high BMI-related asthma burdens among sexes, ages, and regions.


Assuntos
Asma , Carga Global da Doença , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Índice de Massa Corporal , Anos de Vida Ajustados por Qualidade de Vida , Estudos Retrospectivos , Saúde Global , Asma/epidemiologia
15.
Int J Mol Sci ; 23(5)2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35269542

RESUMO

The formation of neurofibrillary tangles (NFT) with ß-sheet-rich structure caused by abnormal aggregation of misfolded microtubule-associated protein Tau is a hallmark of tauopathies, including Alzheimer's Disease. It has been reported that acetylation, especially K174 located in the proline-rich region, can largely promote Tau aggregation. So far, the mechanism of the abnormal acetylation of Tau that affects its misfolding and aggregation is still unclear. Therefore, revealing the effect of acetylation on Tau aggregation could help elucidate the pathogenic mechanism of tauopathies. In this study, molecular dynamics simulation combined with multiple computational analytical methods were performed to reveal the effect of K174 acetylation on the spontaneous aggregation of Tau peptide 171IPAKTPPAPK180, and the dimerization mechanism as an early stage of the spontaneous aggregation was further specifically analyzed by Markov state model (MSM) analysis. The results showed that both the actual acetylation and the mutation mimicking the acetylated state at K174 induced the aggregation of the studied Tau fragment; however, the effect of actual acetylation on the aggregation was more pronounced. In addition, acetylated K174 plays a major contributing role in forming and stabilizing the antiparallel ß-sheet dimer by forming several hydrogen bonds and side chain van der Waals interactions with residues I171, P172, A173 and T175 of the corresponding chain. In brief, this study uncovered the underlying mechanism of Tau peptide aggregation in response to the lysine K174 acetylation, which can deepen our understanding on the pathogenesis of tauopathies.


Assuntos
Lisina/química , Mutação , Proteínas tau/química , Proteínas tau/genética , Acetilação , Humanos , Ligação de Hidrogênio , Cadeias de Markov , Modelos Moleculares , Simulação de Dinâmica Molecular , Agregados Proteicos , Conformação Proteica , Dobramento de Proteína
16.
Comput Intell Neurosci ; 2022: 3785685, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35126489

RESUMO

A data-driven intelligent analysis method is proposed in this paper to explore and identify the enterprise's technological innovation influencing factors. Questionnaire surveys or expert interviews are usually adopted by the traditional evaluation methods for indicators of technological innovation selection. However, it inevitably involves human factors and experts' subjective judgments, which may affect the result of enterprises evaluation. The research presents an improved text clustering method based on a semantic concept model to explore and analyze the key influencing factors of enterprise's technological innovation. The study collects textual data from 400 enterprises in Beijing and smart analyzes the critical influencing factors of enterprise's technological innovation by using the proposed method. The influencing factors can be divided into seven categories. In addition, compared with the traditional K-means clustering method, the proposed method has a good effect. We proposed a methodology to conduct an intelligent analysis for enterprise's technological innovation under the data-driven. It can provide more objective and auxiliary suggestions for the evaluation of the enterprise's technology innovation.


Assuntos
Big Data , Invenções , Pequim , Humanos , Modelos Teóricos
17.
Nutr Metab (Lond) ; 19(1): 8, 2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35135573

RESUMO

INTRODUCTION: Obesity has becoming a global health issue. Fetus exposed to adversity in the uterine are susceptible to unhealth stimulus in adulthood. Prenatal inflammation is related to poor neonatal outcomes like neurodevelopmental impairments and respiratory complications. Recent studies suggested prenatal lipopolysaccharide (LPS) exposure could result in metabolic disorders. Thus, we hypothesized that offspring exposed to prenatal inflammation could develop into metabolic disorder. METHODS: The pregnant C57BL/6J mice were intraperitoneally injected with 50 µg/kg LPS or saline only once at GD15. The male offspring were weighted weekly until sacrificed. Indirect calorimetry and body composition were both performed at 9 and 18 weeks old. At 20 weeks old, mice were fasted overnight before collecting blood samples and liver for metabolomics analysis and RNA sequencing, respectively. Differentially expressed genes were further verified by RT-qPCR and western blotting. RESULTS: Prenatal inflammation resulted in obesity with increased fat percentage and decreased energy expenditure in middle-age male offspring. Abnormal lipid accumulation, changes of gene expression profile and upregulation of multi-component mechanistic target of rapamycin complex 1 (mTOR)/Peroxisome proliferator-activated receptor-γ pathway was observed in liver, accompanied with decreased bile acids level, unsaturated fatty acids androgens and prostaglandins in serum. Indirect calorimetry showed increased respiratory exchange rate and deceased spontaneous activity at 9 weeks in LPS group. Impaired energy expenditure was also observed at 18 weeks in LPS group. CONCLUSION: Prenatal LPS exposure led to obesity and abnormal lipid metabolism through impaired energy expenditure.

18.
Sci Total Environ ; 824: 153780, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35176363

RESUMO

To accurately predict the fitness of marine ectotherms under the climate change scenarios, interactive effects from multiple environmental stressors should be considered, such as ocean acidification (OA), ocean warming (OW) and diurnal temperature cycling (DTC). In this work, we evaluated and compared the antioxidant capacity and metabolism homeostasis of two sea urchins, viz. the temperate species Strongylocentrotus intermedius and the tropical species Tripneustes gratilla, in response to oceanic conditions under a climate change scenario. The two species were treated separately/jointly by acidic (pH 7.6), thermal (ambient temperature + 3 °C), and temperature fluctuating (5 °C fluctuations daily) seawater for 28 days. The activities of antioxidant enzymes (catalase and superoxide dismutase) and the cellular energy allocation in the urchins' gonads were assessed subsequently. Results showed that exposure to OA, OW, and DTC all induced antioxidant responses associated with metabolism imbalance in both S. intermedius and T. gratilla. The physiological adjustments and energy strategies towards exposure of OA, OW, and DTC are species specific, perhaps owing to the different thermal acclimation of species from two latitudes. Moreover, decrease of cellular energy allocation were detected in both species under combined OA, OW, and DTC conditions, indicating unsustainable bioenergetic states. The decrease of cellular energy allocation is weaker in T. gratilla than in S. intermedius, implying higher acclimation capacity to maintain the energy homeostasis in tropical urchins. These results suggest that climate change might affect the population replenishment of the two sea urchins species, especially for the temperate species.


Assuntos
Strongylocentrotus , Animais , Antioxidantes/farmacologia , Mudança Climática , Homeostase , Concentração de Íons de Hidrogênio , Ouriços-do-Mar/fisiologia , Água do Mar , Temperatura
19.
Sci Total Environ ; 818: 151818, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-34813802

RESUMO

Hypoxia, largely triggered by anthropogenic activities and global climate change, exerts widespread and expanding stress on marine ecosystems. As an emerging contaminant, the influence of nanoplastics on marine organisms has also attracted attention in recent years. However, the impact of hypoxia on the risk assessments of nanoplastics is rarely considered. This study investigated the toxicity of PS-NPs (0, 0.5, and 5 mg/L) to the coastal mussels Mytilus galloprovincialis under different patterns of hypoxia (normoxia, constant hypoxia, and fluctuating hypoxia). The results showed that constant hypoxia might reduce the accumulation of PS-NPs in mussels by decreasing the standard metabolic rate. The impairment of PS-NPs on mussel immunity was also exacerbated by constant hypoxia. Fluctuating hypoxia did not affect the accumulation of PS-NPs, but aggravated the oxidative damage caused by PS-NPs. These findings emphasize the importance of environmental factors and their temporal variability in plastic risk assessment.


Assuntos
Mytilus , Poluentes Químicos da Água , Animais , Mudança Climática , Ecossistema , Hipóxia , Microplásticos/toxicidade , Mytilus/metabolismo , Plásticos/metabolismo , Plásticos/toxicidade , Poliestirenos/toxicidade , Medição de Risco , Poluentes Químicos da Água/análise
20.
Environ Monit Assess ; 193(10): 655, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34532779

RESUMO

Heavy metals' pollution of agricultural soil is an environmental problem of widespread concern, especially in China, but, how to accurately identify their sources is still a great challenge. Here, we implemented a high-density sampling strategy (2194 samples collected) and combined correlation analysis (CA), principal component analysis (PCA), positive matrix factorization (PMF) modeling, and geostatistical analyses to identify and quantify the source contributions of heavy metals in agricultural soil in a key commodity grain base of China. The results showed that the excess risk rate of Cd was the highest (4.3%), and contributing to 42.7% of the total potential ecological risk in the region. Hence, Cd is the most important ecological risk factor. Heavy metals in the region mainly originated from oil extraction and smelting (7.5%), parent materials and traffic emissions (59.2%), coal-related industrial activities (11.6%), and agricultural sources (21.7%). Cd was mainly derived from oil extraction and smelting (90.1%). As (73.6%), Cr (90.3%), and Pb (67.1%) were closely associated with parent materials and traffic emissions. Hg (87.7%) was mainly originated from coal-related industrial sources. In addition, As (25.6%) and Pb (24.3%) were also from agricultural sources (such as fertilizer, pesticides, and manure). This study confirms that the combination of these methods can accurately identify the sources of heavy metals in agricultural soil. These findings can assist governmental agencies in implementing targeted control strategies to prevent the spread of heavy metals.


Assuntos
Metais Pesados , Poluentes do Solo , China , Monitoramento Ambiental , Metais Pesados/análise , Análise de Componente Principal , Medição de Risco , Solo , Poluentes do Solo/análise
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