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BACKGROUND: Leading to more and more deaths and disabilities, stroke has become a serious threat to human health. What's more, few effective drugs are available in clinic till now. RESULTS: In this research, we prepared a novel neuroprotective nanoformation (OEA-SPC NPs) via the combination of the nanoparticle drug delivery system with the endogenous N-oleoylethanolamine (OEA). By forming hydrogen bond between OEA and the carrier-soybean phosphatidylcholine (SPC), the form of OEA was turned into amorphus state when loading to the nanoparticles, which greatly improved its bioavailability. Then the following systematic experiments revealed the efficient neuroprotective effect of OEA-SPC NPs in vivo. Compared with the MCAO group, the cerebral infarct volume was reduced by 81.1%, and the edema degree by 78.4% via the oral administration of OEA-SPC NPs. And the neurological deficit scores illustrated that the MCAO rats treated with OEA-SPC NPs exhibited significantly less neurological dysfunction. The Morris water maze test indicated that the spatial learning and memory of cerebral ischemia model rats were almost recovered to the normal level. Besides, the OEA-SPC NPs could inhibit the inflammation of reperfusion to a very slight level. CONCLUSIONS: These results suggest that the OEA-SPC NPs have a great chance to be a potential anti-stroke formation for clinic application and actually bring hope to thousands of stroke patients.
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Agonistas de Receptores de Canabinoides/farmacologia , Endocanabinoides/farmacologia , Etanolaminas/farmacologia , Nanopartículas , Ácidos Oleicos/farmacologia , Fosfatidilcolinas , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Sprague-DawleyRESUMO
When Cr(VI) and Cr(III) coexist, the reasonable assessment of the combined toxicity of chromium in soil and its ecological risk is still not well resolved. In the present study, exogenous mixed concentration combinations were set up to determine the interaction and combined toxicity of Cr(VI) and Cr(III), which were quantified as measured total and resin extractable forms for dose-response experiments with barley root elongation. The concept of toxicity equivalence "α" (the ratio of toxicity intensity coefficient between Cr(VI) and Cr(III), which can be expressed as the relative toxic strength of Cr(VI) to Cr(III)) was proposed for the toxicity assessment of mixed-valence chromium in soil. The results showed that the dose-response relationship was determined more precisely by the extended independent action model (e-IA) than traditional models (e.g., concentration addition model), and the mutual antagonism for resin extractable form (Resin-Cr) was stronger than the measured total form (T-Cr). The values of toxicity equivalence (α) between coexisting Cr(VI) and Cr(III) as Resin-Cr and T-Cr were 0.74 and 160, respectively, which indicated Resin-Cr(III) had relatively stronger toxicity than Resin-Cr(VI), while T-Cr(III) was much less than T-Cr(VI). The α values between Cr(VI) and Cr(III) decreased with their more active forms (decreased to about 0.5% of the original), even as total concentration and activity in solutions, making a dialectical view of the toxicity of both in different forms necessary. Finally, the log-logistic models were developed, enabling mixed-valence Cr toxicity to be assessed from a unilateral perspective using the Cr(III) equivalence concentration (Cr(III)-eq). This work provided innovative ideas for ecological threshold studies for mixed-valence metals in soils.
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Background: Both HIV and TB are chronic infectious diseases requiring long-term treatment and follow-up, resulting in extensive electronic medical records. With the exponential growth of health and medical big data, effectively extracting and analyzing these data has become the research hotspot. As a fundamental aspect of artificial intelligence, machine learning has been extensively applied in medical research, encompassing diagnosis, treatment, patient monitoring, drug development, and epidemiological investigations. This significantly enhances medical information systems and facilitates the interoperability of medical data. Methods: In our study, we analyzed longitudinal data from the electronic health records of 4540 patients, gathered from the National Clinical Research Center for Infectious Diseases in Shenzhen, China, spanning from 2017 to 2021. Initially, we employed the fine-tuned ChatGLM to structure the electronic medical records. Subsequently, we utilized a multi-layer perceptron to classify each patient and determined the presence of tuberculosis in HIV patients. Using machine learning-based natural language processing, we structured these records to build a specialized database for HIV and TB co-infection. We studied the epidemiological characteristics, focusing on incidence patterns, patient characteristics, and influencing factors, to uncover the transmission characteristics of these diseases in Shenzhen. Additionally, we used Long Short-Term Memory to create a predictive model for TB co-infection among HIV patients, based on their medical records. This model predicted the risk of TB co-infection, providing scientific evidence for clinical decision-making and enabling early detection and precise intervention. Results: Based on the refined ChatGLM model tailored for structured electronic health records, the accuracy of symptom extraction consistently surpassed 0.95 precision. Key symptoms such as diarrhea and normal showed precision rates exceeding 0.90. High scores were also achieved in recall and F1 scores. Among 4540 HIV patients, 758 were diagnosed with concurrent tuberculosis, indicating a 16.7% co-infection rate, while syphilis co-infection affected 25.1%, underscoring the prevalence of concurrent infections among HIV patients. Utilizing electronic health records, a Multilayer Perceptron classifier was developed as a benchmark against Long Short-Term Memory to predict high-risk groups for HIV and tuberculosis co-infections. The Multilayer Perceptron classifier demonstrated predictive ability with AUROC values ranging from 0.616 to 0.682 on the test set, suggesting opportunities for further optimization and generalization despite its accuracy in identifying HIV-TB co-infections. In tuberculosis intelligent diagnosis based on laboratory results, the Long Short-Term Memory showed consistent performance across 5-fold cross-validation, with AUROC values ranging from 0.827 to 0.850, indicating reliability and consistency in tuberculosis prediction. Furthermore, by optimizing classification thresholds, the model achieved an overall accuracy of 81.18% in distinguishing HIV co-infected tuberculosis from simple HIV infection. Conclusion: Combining the Multilayer Perceptron classifier with Long Short-Term Memory represented an advanced approach for effectively extracting electronic health records and utilizing it for disease prediction. This underscored the superior performance of deep learning techniques in managing both structured and unstructured medical data. Models leveraging laboratory time-series data demonstrated notably better performance compared to those relying solely on electronic health records for predicting tuberculosis incidence. This emphasized the benefits of deep learning in handling intricate medical data and provided valuable insights for healthcare providers exploring the use of deep learning in disease prediction and management.
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Background: Myopia is a leading cause of visual impairment in Asia and worldwide. However, accurately predicting the progression of myopia and the high risk of myopia remains a challenge. This study aims to develop a predictive model for the development of myopia. Methods: We first retrospectively gathered 612 530 medical records from five independent cohorts, encompassing 227 543 patients ranging from infants to young adults. Subsequently, we developed a multivariate linear regression algorithm model to predict the progression of myopia and the risk of high myopia. Result: The model to predict the progression of myopia achieved an R2 value of 0.964 vs a mean absolute error (MAE) of 0.119D [95% confidence interval (CI): 0.119, 1.146] in the internal validation set. It demonstrated strong generalizability, maintaining consistent performance across external validation sets: R2 = 0.950 vs MAE = 0.119D (95% CI: 0.119, 1.136) in validation study 1, R2 = 0.950 vs MAE = 0.121D (95% CI: 0.121, 1.144) in validation study 2, and R2 = 0.806 vs MAE = -0.066D (95% CI: -0.066, 0.569) in the Shanghai Children Myopia Study. In the Beijing Children Eye Study, the model achieved an R2 of 0.749 vs a MAE of 0.178D (95% CI: 0.178, 1.557). The model to predict the risk of high myopia achieved an area under the curve (AUC) of 0.99 in the internal validation set and consistently high area under the curve values of 0.99, 0.99, 0.96 and 0.99 in the respective external validation sets. Conclusion: Our study demonstrates accurate prediction of myopia progression and risk of high myopia providing valuable insights for tailoring strategies to personalize and optimize the clinical management of myopia in children.
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The reuse of reclaimed water (RW) for river ecological restoration in global water-shortage regions has inevitably brought some potential risks for groundwater. However, little is known about the effects of reclaimed water on the hydrochemical evolution of groundwater especially under long-term infiltration conditions. Herein, 11-years monitoring data (2007-2018) of reclaimed water and groundwater were adopted to analyze the characteristics and genesis of groundwater hydrochemical evolution under long-term infiltration of reclaimed water from Jian River to Chaobai River in Beijing. The results showed that the hydrochemical components in groundwater totally performed a significant increase in Na+, Cl-, and K+and decrease in Ca2+, Mg2+, and HCO3- concentration after long-term infiltration of reclaimed water. Meanwhile, a significant hydrochemical evolution difference between the groundwater of Jian River and Chaobai River was observed. In Jian River, the hydrochemical type in groundwater shifted gradually from HCO3-Ca·Mg to the type of HCO3·Cl-Na·Ca approaching reclaimed water. In contrast, the hydrochemical evolution in the Chaobai River shows an obvious opposite trend from HCO3-Ca·Mg to HCO3·Cl-Na·Mg and finally deviating reclaimed water type of Cl·HCO3·SO4-Na. PHREEQC simulation indicated that the differences in hydrochemical evolution were mediated synergically by sediment thickness and geochemical processes (e.g. mixing and sulfate reduction). In such mediators, thinner sediment and strong mixing in the Jian River were confirmed to be the genesis of groundwater hydrochemical evolution progressively approaching reclaimed water. Different from the Jian River, multiple regression analyses revealed that the genesis of groundwater hydrochemical evolution in the Chaobai River was divided into two stages according to the increase of sediment thickness. Reclaimed water quality and infiltration amount are the leading proposed cause in the initial stage (2007-2008) due to thinner sediment formation, contributing 53.5% and 29.8% within the 95% confidence interval, respectively. Subsequently, the rise in sediment thickness is proved to play a crucial role in groundwater hydrochemical evolution trend away from reclaimed water (2009-2018), with a contribution of 41.6% within the 95% confidence interval. It is mainly attributed to the reduced reclaimed water infiltration rate and favorable sulfate reduction conditions. These findings advance our understanding on groundwater hydrochemical evolution under long-term infiltration of reclaimed water and also guide future prediction of evolution trends.
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Água Subterrânea , Poluentes Químicos da Água , Rios , Pequim , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , Água Subterrânea/análise , Qualidade da Água , Sulfatos , ChinaRESUMO
Electrochemical decomposition of lipopolysaccharide (LPS) was firstly investigated over titania nanotubes (TNTs) arrays electrode. The TNTs layer of this electrode consisted of numerous tubular structures which arranged tightly, and the average diameter of each nanotube is 100⯱â¯5â¯nm. The degradation of LPS and polysaccharides followed pseudo-first-order kinetics. The optimal LPS removal ratio was nearly 80 %. The endotoxin toxicity of LPS steadily decreased during the electrolysis process. The acute toxicity of the intermediates increased suddenly at the beginning of electrochemical degradation process (< 5â¯min), then maintained high inhibition ratio (> 95 %) for about 150â¯min, and decreased significantly (< 10 %) after electrolysis for 240â¯min. After 20â¯min of electrolysis, LPS with molecular weight of 116,854â¯Da was transformed into small molecular compounds with molecular weights of 59,312 - 12,209â¯Da. Possible degradation and detoxification mechanisms of LPS including electric-field-force-driving accumulation, adsorption and direct electron transfer on TNTs arrays electrode, and â¢OH oxidation were proposed. This study underscores that electrochemical technique can be applied to eliminate and decrease the toxicity of LPS from contaminated water.
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Lipopolissacarídeos/química , Nanotubos/química , Titânio/química , Aliivibrio fischeri/efeitos dos fármacos , Aliivibrio fischeri/metabolismo , Técnicas Eletroquímicas , Eletrodos , Lipopolissacarídeos/toxicidade , Medições LuminescentesRESUMO
The degrading genes of hydrophobic organic compounds (HOCs) serve as indicators of in situ HOC degradation potential, and the existing forms and bioavailability of HOCs might influence the distribution of HOC-degrading genes in natural waters. However, little research has been conducted to study the relationship between them. In the present study, nahAc and nidA genes, which act as biomarkers for naphthalene- and pyrene-degrading bacteria, were selected as model genotypes to investigate the response of polycyclic aromatic hydrocarbon (PAH)-degrading genes to PAH bioavailability in the overlying water, suspended sediment (SPS), and deposited sediment of the Yangtze River. The freely dissolved concentration, typically used to reflect HOC bioavailability, and total dissolved, as well as sorbed concentrations of PAHs were determined. Phylogenetic analysis showed that all the PAH-ring hydroxylating dioxygenase gene sequences of Gram-negative bacteria (PAH-RHD[GN]) were closely related to nahAc, nagAc, nidA, and uncultured PAH-RHD genes. The PAH-RHD[GN] gene diversity as well as nahAc and nidA gene copy numbers decreased in the following order: deposited sediment>SPS>overlying water. The nahAc and nidA gene abundance was not significantly correlated with environmental parameters but was significantly correlated with the bioavailable existing forms of naphthalene and pyrene in the three phases. The nahAc gene copy numbers in the overlying water and deposited sediment were positively correlated with freely dissolved naphthalene concentrations in the overlying and pore water phases, respectively, and so were nidA gene copy numbers. This study suggests that the distribution and abundance of HOC-degrading bacterial population depend on the HOC bioavailability in aquatic environments.
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Poluentes Ambientais/análise , Genes Bacterianos/genética , Sedimentos Geológicos/química , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/análise , Rios/química , Biodegradação Ambiental , Disponibilidade Biológica , Biomarcadores/metabolismo , China , Dioxigenases/genética , Poluentes Ambientais/metabolismo , Variação Genética , Filogenia , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , PirenosRESUMO
Displacement chromatography was successfully used to separate a binary isomer mixture, epirubicin and doxorubicin, on Kromasil KR100-10 C18 250x4.6 mm I.D. (10 microm) column. Displacement parameters such as the types and the concentrations of displacer, the composition and the flow rate of the mobile phase were critically examined in this study. The displacer employed was 30 mg/ml benzethonium chloride. Loading of feed at lower initial organic level of mobile phase coupled with displacement at higher organic level was found to give efficient separation. A 30-mg amount of binary isomer mixture was separated on an analytical column. The purification of epirubicin from the closely related impurities present in raw product solution by displacement chromatography was also investigated. The purity of epirubicin required was greater than 99% with a recovery of 60%. The results have indicated that this process made good use of the high feed load, low solvent costs, and high resolution characteristics of displacement chromatography and offered the chromatographic engineer a powerful tool for the preparative purification of therapeutic compounds.
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Cromatografia Líquida/métodos , Doxorrubicina/isolamento & purificação , Epirubicina/isolamento & purificação , IsomerismoRESUMO
Hydrophilic interaction chromatography has been applied for the separation of epirubicin and its analogues using high-purity silica column with aqueous-organic mobile phase. Parameters affecting the chromatographic behavior of the solutes such as organic modifier, buffer pH, ionic strength and sample size, have been investigated. Of utmost importance for successful separation of these analogues is the choice of organic modifier, since it impacts both the solvent selectivity and the ionization of silica silanols as well as buffer solution, and consequently the retention behavior of solutes. Acetonitrile was shown to offer superior separation of these analogues to methanol, isopropanol or tetrahydrofuran. Results of the effects of organic modifier, buffer pH and ion strength indicate that the retention mechanism is a mixed-mode of adsorption and ion exchange. In addition, an irreversible adsorption of these compounds was found on silica in the weakly acidic or neutral mobile phases, and the effect of various factors on irreversible adsorption was also preliminarily discussed. More significantly, these basic compounds have exhibited peaks with a slanted front and a sharp tail, a typical overloading peak profile belonging to the behavior of competitive anti-Langmuir isotherm by increasing the sample size at the experimental conditions.
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Antibióticos Antineoplásicos/isolamento & purificação , Cromatografia Líquida de Alta Pressão/métodos , Epirubicina/isolamento & purificação , Adsorção , Soluções Tampão , Concentração de Íons de Hidrogênio , Concentração OsmolarRESUMO
Displacement chromatography was successfully used to separate, at the preparative scale, a binary isomer mixture of epirubicin and doxorubicin, which are anthracycline antitumor antibiotics, on an analytical column (Kromasil KR100-10C18 column, 250 mm x 4.6 mm i.d., 10 microm). Displacement parameters such as the type and the concentration of displacer, the composition and the flow-rate of mobile phase were investigated. The displacer employed was 30 g/L benzethonium chloride. The flow-rate was 0.2 mL/min. Loading of feed at lower initial organic level of mobile phase coupled with displacement at higher organic level was found to give efficient separation. The binary isomer mixture of 30 mg was separated on the analytical column. The results have indicated that displacement mode had high efficiency, greatly reduced solvent consumption in the process of purification, and offered the possibility of both high resolution and high loading. It has also demonstrated again that high performance displacement chromatography is one of the effective methods for the purification of therapeutic compounds in industrial processes.