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1.
Aging (Albany NY) ; 16(13): 10784-10798, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38990203

RESUMEN

Atherosclerosis (AS) is the main pathological basis of cardiovascular diseases such as coronary heart disease. Black phosphorus quantum dots (BPQDs) are a novel nanomaterial with good optical properties and biocompatibility, which was applied in the treatment of AS in mice, with good results shown in our previous study. In this study, BPQDs were injected into high-fat diet-fed apolipoprotein E knockout mice as a preventive drug for 12 weeks. Simvastatin, a classic preventive drug for AS, was used as a control to verify the preventive effect of BPQDs. The results showed that after preventive treatment with BPQDs, the plaque area in mice was significantly reduced, the vascular elasticity was increased, and serum lipid levels were significantly lower than those in the model group. To explore the mechanism, macrophages were induced to become foam cells using oxidized low-density lipoprotein. We found that BPQDs treatment could increase cell autophagy, thereby regulating intracellular lipid metabolism. Taken together, these data revealed that BPQDs may serve as a functional drug in preventing the development of AS.


Asunto(s)
Aterosclerosis , Dieta Alta en Grasa , Fósforo , Puntos Cuánticos , Animales , Dieta Alta en Grasa/efectos adversos , Aterosclerosis/prevención & control , Ratones , Fósforo/sangre , Ratones Noqueados , Apolipoproteínas E/genética , Masculino , Autofagia/efectos de los fármacos , Ratones Noqueados para ApoE , Metabolismo de los Lípidos/efectos de los fármacos , Modelos Animales de Enfermedad , Placa Aterosclerótica/prevención & control , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/sangre , Simvastatina/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Células Espumosas/efectos de los fármacos , Células Espumosas/metabolismo
2.
Transl Lung Cancer Res ; 13(6): 1383-1395, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38973945

RESUMEN

Background and Objective: A significant number of individuals diagnosed with non-small cell lung cancer (NSCLC) have distant metastases, and the concept of oligometastatic NSCLC has shown promise in achieving a cure. Stereotactic body radiation therapy (SBRT) is currently considered a viable treatment option for a limited number of tumor metastases. It has also been demonstrated that third-generation tyrosine kinase inhibitors (TKIs) are effective in extending the survival of patients with epidermal growth factor receptor (EGFR)-mutated NSCLC. Hence, the combination of SBRT with third-generation TKIs holds the potential to enhance treatment efficacy in patients with oligometastatic EGFR-mutated NSCLC. This review aimed to assess the possibility of combining SBRT with TKIs as an optimum treatment option for patients with oligometastatic EGFR-mutated NSCLC. Methods: We performed a narrative review by searching the PubMed, Web of Science, Elsevier and ClinicalTrials.gov databases for articles published in the English language from January 2009 to February 2024 and by reviewing the bibliographies of key references to identify important literature related to combining SBRT with third-generation TKIs in oligometastatic EGFR-mutated NSCLC. Key Content and Findings: This review aimed to assess the viability of combining SBRT and EGFR-TKIs in oligometastatic EGFR-mutated NSCLC. Current clinical trials suggest that the combined therapies have better progression free survival (PFS) when using SBRT as either concurrent with EGFR-TKIs or consolidated with EGFR-TKIs. Furthermore, research with third-generation EGFR-TKIs and SBRT combinations has demonstrated tolerable toxicity levels without significant additional adverse effects as compared to prior therapies. However, further clinical trials are required to establish its effectiveness. Conclusions: The combined approach of SBRT and TKIs can effectively impede the progression of oligometastatic NSCLC in patients harboring EGFR mutations and, most notably, can prolong progression-free survival rates. However, the feasibility of combining SBRT with third-generation TKIs in clinical trials remains unclear.

3.
Front Immunol ; 15: 1380211, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38898888

RESUMEN

Background: Klebsiella pneumoniae is a common Gram-negative bacterium. Blood infection caused by K. pneumoniae is one of the most common causes of human sepsis, which seriously threatens the life of patients. The immune status of peripheral blood mononuclear cells (PBMCs) based on single-cell RNA sequencing (scRNA-seq) in acute stage and recovery stage of sepsis caused by K. pneumoniae bloodstream infection has not been studied. Methods: A total of 13 subjects were included in this study, 3 healthy controls, 7 patients with K. pneumoniae bloodstream infection in the acute stage (4 patients died), and 3 patients in the recovery stage. Peripheral blood of all patients was collected and PBMCs were isolated for scRNA-seq analysis. We studied the changes of PBMCs components, signaling pathways, differential genes, and cytokines in acute and recovery stages. Results: During K. pneumoniae acute infection we observed a decrease in the proportion of T cells, most probably due to apoptosis and the function of T cell subtypes was disorder. The proportion of monocytes increased in acute stage. Although genes related to their phagocytosis function were upregulated, their antigen presentation capacity-associated genes were downregulated. The expression of IL-1ß, IL-18, IFNGR1 and IFNGR2 genes was also increased in monocytes. The proportion of DCs was depleted during the acute stage and did not recover during sepsis recovery. DCs antigen presentation was weakened during the acute stage but recovered fast during the recovery stage. pDCs response to MCP-1 chemokine was weakened, they recovered it quickly during the recovery stage. B cells showed apoptosis both in the acute stage and recovery stage. Their response to complement was weakened, but their antigen presentation function was enhanced. The proportion of NK cells stable during all disease's stages, and the expression of IFN-γ gene was upregulated. Conclusion: The proportion of PBMCs and their immune functions undergo variations throughout the course of the disease, spanning from the acute stage to recovery. These findings provide new insights into the mechanism of PBMCs immune function during K. pneumoniae bloodstream infection sepsis and recovery and sets the basis for further understanding and treatment.


Asunto(s)
Infecciones por Klebsiella , Klebsiella pneumoniae , Leucocitos Mononucleares , Sepsis , Humanos , Klebsiella pneumoniae/inmunología , Infecciones por Klebsiella/inmunología , Infecciones por Klebsiella/sangre , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Sepsis/inmunología , Sepsis/microbiología , Sepsis/sangre , Sepsis/genética , Anciano , Análisis de la Célula Individual , Citocinas/sangre , Bacteriemia/inmunología , Bacteriemia/microbiología , Bacteriemia/genética , Análisis de Secuencia de ARN , Adulto
4.
RSC Adv ; 14(20): 14374-14391, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38694552

RESUMEN

Burns are a global public health problem, which brings great challenges to public health and the economy. Severe burns often lead to systemic infection, shock, multiple organ failure, and even death. With the increasing demand for the therapeutic effect of burn wounds, traditional dressings have been unable to meet people's needs due to their single function and many side effects. In this context, electrospinning shows a great prospect on the way to open up advanced wound dressings that promote wound repairing and prevent infection. With its large specific surface area, high porosity, and similar to natural extracellular matrix (ECM), electrospun nanofibers can load drugs and accelerate wound healing. It provides a promising solution for the treatment and management of burn wounds. This review article introduces the concept of burn and the types of electrospun nanofibers, then summarizes the polymers used in electrospun nanofiber dressings. Finally, the drugs (plant extracts, small molecule drugs and nanoparticles) loaded with electrospun burn dressings are summarized. Some promising aspects for developing commercial electrospun burn dressings are proposed.

5.
Dev Cell ; 59(13): 1737-1749.e7, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38677285

RESUMEN

Photomorphogenesis is a light-dependent plant growth and development program. As the core regulator of photomorphogenesis, ELONGATED HYPOCOTYL 5 (HY5) is affected by dynamic changes in its transcriptional activity and protein stability; however, little is known about the mediators of these processes. Here, we identified PHOTOREGULATORY PROTEIN KINASE 1 (PPK1), which interacts with and phosphorylates HY5 in Arabidopsis, as one such mediator. The phosphorylation of HY5 by PPK1 is essential to establish high-affinity binding with B-BOX PROTEIN 24 (BBX24) and CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1), which inhibit the transcriptional activity and promote the degradation of HY5, respectively. As such, PPKs regulate not only the binding of HY5 to its target genes under light conditions but also HY5 degradation when plants are transferred from light to dark. Our data identify a PPK-mediated phospho-code on HY5 that integrates the molecular mechanisms underlying the regulation of HY5 to precisely control plant photomorphogenesis.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Regulación de la Expresión Génica de las Plantas , Luz , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/crecimiento & desarrollo , Arabidopsis/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Fosforilación , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Morfogénesis/efectos de la radiación , Proteínas Quinasas/metabolismo , Proteínas Quinasas/genética , Proteínas Represoras
6.
Artículo en Inglés | MEDLINE | ID: mdl-38621199

RESUMEN

Recently, the combination of the piezoelectric effect in the photocatalytic process, referred to as piezo-photocatalysis, has gained considerable attention as a promising approach for enhancing the degradation of organic pollutants. In this investigation, we studied the piezo-photocatalysis by fabricating arrays of barium strontium titanate (Ba0.7Sr0.3TiO3) nanorods (BST NRs) on a glass substrate as recoverable catalysts. We found that the degradation rate constant k of the rhodamine B solution achieved 0.0447 min-1 using poled BST NRs in the piezo-photocatalytic process, indicating a 2-fold increase in efficiency compared to the photocatalytic process (0.00183 min-1) utilizing the same material. This is mainly ascribed to the generation of the piezopotential in the poled BST NRs under ultrasonic vibration. Moreover, the BST NR array demonstrated a hydrogen (H2) production rate of 411.5 µmol g-1 h-1. In the photoelectrochemical process, the photocurrent density of poled BST NRs achieved 1.97 mA cm-2 at an applied potential of 1.23 V (ERHE (reversible hydrogen electrode)) under ultrasonic vibrations, representing a 1.7-fold increase compared with the poled BST NRs without ultrasonic vibrations. The measurement results from the liquid chromatograph mass spectrometer (LC-MS) demonstrated the formulation of a degradation pathway for rhodamine B molecules. Moreover, ab initio molecular dynamics (AIMD) simulation results demonstrate the dominance of hydroxyl radicals (•OH) rather than superoxide radicals (•O2-) in the degradation process. This study not only benefits the understanding of the principle of the piezo-photocatalytic process but also provides a new perspective for improving the catalytic efficiency for organic pollutants degradation.

7.
Ecotoxicol Environ Saf ; 275: 116249, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38522286

RESUMEN

The microplastic pollution in freshwater system is gradually becoming more severe, which has led to increasing attention on the distribution and potential harmful effects of microplastics. Moreover, microplastics may have an impact on river ecology and pose risks to ecosystems. Therefore, it is important to reveal this process. This study aimed to explore correlations between microplastics and free-living microorganisms in an urban drinking water source of Xiangjiang River by using multivariate statistical analysis. The results indicated that the abundance of microplastics (size 50 µm to 5 mm) in surface water and sediments ranged from 0.72 to 18.6 (mean ± SD: 7.32 ± 2.36) items L-1 and 26.3-302 (150 ± 75.6) items kg-1 dry weight (dw), respectively, suggesting potential microplastic pollution despite the protected status as a drinking water source. Higher microplastic abundances were observed in urban areas and the downstream of wastewater plants, with mostly granular shape, transparent and black color as well as 50-100 µm in size. The multivariate statistical analysis presented that the abundance of microplastics is not significantly correlated with water indicators, due to the complexity of the abundance data. The water indicators showed an obvious correlation with microplastics in colors of transparent and black, and smaller sizes of 50-100 µm. This is also true for microplastics and microorganisms in water and sediment. Proteobacteria was the main prokaryote in water and sediments, being positively correlated with 50-100 µm microplastics; while Chloroplastida was the dominated eukaryotes, presenting a weak correlation with smaller-size microplastics. Overall, when considering the properties of microplastics such as shape, color and size, the potential correlations with water indicators and microorganisms were more evident than abundance. This study provides new insights into the multivariate statistical analysis, explaining the potential correlations among microplastic properties, microorganisms and environmental factors in a river system.


Asunto(s)
Agua Potable , Contaminantes Químicos del Agua , Microplásticos/toxicidad , Plásticos , Calidad del Agua , Ecosistema , Monitoreo del Ambiente/métodos , Contaminantes Químicos del Agua/análisis , Sedimentos Geológicos
8.
PLoS One ; 19(3): e0289820, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38498570

RESUMEN

Inflammatory bowel disease (IBD) and atherosclerosis (AS) are both common chronic inflammatory diseases with similar pathophysiological mechanisms. Some studies have shown that IBD patients are at increased risk for early atherosclerosis, myocardial infarction and venous thrombosis. Here we set up a hybrid mouse model associated with atherosclerosis and acute colitis in order to investigate the interplay of the two diseases. We fed ApoE-/- mice with high fat diet to establish atherosclerosis model, and used animal ultrasound machine to detect the artery of mice noninvasively. Then a new hybrid model of atherosclerosis and acute colitis was prepared by drinking water for 7 days. At the end of the experiment, the hybrid model mice showed typically pathological and intuitionistic changes of atherosclerosis and acute colitis. We found the shortened colon length, high histopathological scores of the colon with mucosal erosion and necrosis, hyperlipidemia, a plaque-covered mouse aorta and plaque with foam cells and lipid deposition in the hybrid model group, which proved that the hybrid model was successfully established. At the same time, ultrasonic detection showed that the end-diastolic blood flow velocity and the relative dilation value were decreased, while systolic time / diastolic time, the wall thickness, systolic diameters as well as diastolic diameters were gradually increased, and statistical significance appeared as early as 8 weeks. We clearly described the process of establishing a hybrid model of atherosclerosis and acute colitis, which might provide a repeatable platform for the interaction mechanism exploring and drug screening of atherosclerosis and inflammatory bowel disease in preclinical study.


Asunto(s)
Aterosclerosis , Colitis , Enfermedades Inflamatorias del Intestino , Placa Aterosclerótica , Humanos , Ratones , Animales , Ratones Noqueados , Ratones Noqueados para ApoE , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/genética , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/complicaciones , Dieta Alta en Grasa/efectos adversos , Apolipoproteínas E/genética , Colitis/complicaciones , Enfermedades Inflamatorias del Intestino/complicaciones , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad
9.
Sci Rep ; 14(1): 5620, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38453971

RESUMEN

In this paper, the tribological characteristics of an oil-soluble magnetic fluid additive under mixed lubrication are studied by experiments and numerical simulation. [bmim][FeCl4] is dissolved in CF10W-40 lubricating oil as a magnetic liquid additive, and its friction coefficient is tested by a point contact friction tester at different temperatures, rotational speeds and magnetic field intensities. The transition condition of lubrication state is obtained through analyzing the Stribeck curves based on the experiments, and the strength model of boundary film is established accordingly. A mixed lubrication model is established by substituting the boundary film strength model and the surface roughness model into the hydrodynamic lubrication model based on Reynolds equation. The results show that the magnetic solution as an additive can obviously reduce friction and wear, and the effect is more obvious under the condition of magnetic field. The boundary film strength model can accurately reflect the transition characteristics of lubrication state in the presence of boundary film, and the mixed lubrication model based on boundary film strength model can more precisely reflect the tribological characteristics of friction pairs, so this study provides a new theoretical method for the related research on the influence of boundary film on lubrication characteristics.

10.
Environ Geochem Health ; 46(3): 94, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38374291

RESUMEN

The mining and utilization of coal resources has not only promoted rapid economic development but also poses a potential threat to the ecological environment. The purpose of this study is to clarify the effects both of mining and land use types on the spatial distribution and particular sources of heavy metals in soil, using inverse distance weighted (IDW) and the Positive Matrix Factorization (PMF) model. A total of 99 topsoil and profile soil samples across different land use types and mining conditions were collected. The contamination of soil with Cd, Pb, and Hg in the research area was most severe, with the coefficient of variation (CV) of Hg being the largest, while also being heavily influenced by human activities. Severely polluted regions were mainly distributed in the center of the coal mining area, as well as near the highway. The contents of heavy metals for various land use patterns were ranked as follows: forestland > farmland > bare land > grassland > building land. Hg, Cd, Pb, Cr, and Zn had showed migration in the 0-60 cm depth range, and the enrichment factors (EFs) of Cd, Pb, Hg, and As in the soil profile were the most significant. The PMF demonstrated that the contributions of industrial activities and atmospheric deposition, transportation and mining activities, agricultural activities, and natural sources accounted for 31.25%, 28.13%, 22.24%, and 18.38%, respectively. The migration and deposition of atmospheric particulate matter from coal mining, transportation, and coal combustion under winds triggered heavy metal contamination in semi-arid areas of northern China. This phenomenon has important implications for the prevention and reduction of heavy metal pollution through various effective measures in coal-mining cities in northern China.


Asunto(s)
Minas de Carbón , Mercurio , Metales Pesados , Contaminantes del Suelo , Humanos , Suelo , Cadmio/análisis , Plomo/análisis , Contaminantes del Suelo/análisis , Monitoreo del Ambiente , Metales Pesados/análisis , China , Mercurio/análisis , Carbón Mineral/análisis , Medición de Riesgo
11.
Sci Total Environ ; 919: 170217, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38307274

RESUMEN

In recent, soil microplastic pollution arising from organic fertilizers has been of a great increasing concern. In response to this concern, this review presents a comprehensive analysis of the occurrence and evolution of microplastics in organic fertilizers, their ingress into the soil, and the subsequent impacts. Organic fertilizers are primarily derived from solid organic waste generated by anthropocentric activities including urban (daily-life, municipal wastes and sludge), agricultural (manure, straw), and industrial (like food industrial waste etc.) processes. In order to produce organic fertilizer, the organic solid wastes are generally treated by aerobic composting or anaerobic digestion. Currently, microplastics have been widely detected in the raw materials and products of organic fertilizer. During the process of converting organic solid waste materials into fertilizer, intense oxidation, hydrolysis, and microbial actions significantly alter the physical, chemical, and surface biofilm properties of the plastics. After the organic fertilizer application, the abundances of microplastics significantly increased in the soil. Additionally, the degradation of these microplastics often promotes the adsorption of organic pollutants and affects their retention time in the soil. These microplastics, covered by biofilms, also significantly alter soil ecology due to the unique properties of the biofilm. Furthermore, the biofilms also play a role in the degradation of microplastics in the soil environment. This review offers a new perspective on the soil environmental processes involving microplastics from organic fertilizer sources and highlights the challenges associated with further research on organic fertilizers and microplastics.

12.
Environ Pollut ; 344: 123302, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38190875

RESUMEN

Pyrethroid insecticides are the most commonly used household insecticides and pose substantial risks to marine aquatic organisms. many studies have detected pyrethroid insecticides in the waters and estuaries of the western United States, but their distributions within western Pacific estuaries have not been reported. Accordingly, we used high-throughput organic analyses combined with high volume solid-phase extraction to comprehensively assess 13 pyrethroid insecticides in East China Sea estuaries and the Huangpu River. The results demonstrated the presence of various ∑13pyrethroid insecticides in East China Sea estuaries (mean and median values of 8.45 ± 5.57 and 7.78 ng L-1, respectively), among which cypermethrin was the primary contaminant. The concentrations of ∑12pyrethroid insecticide detected in the surface waters at the Huangpu River (mean 6.7 ng L-1, outlet 16.4 ng L-1) were higher than those in the Shanghai estuary (4.7 ng L-1), suggesting that runoff from inland areas is a notable source of insecticides. Wetlands reduced the amount of runoff containing pyrethroid insecticides that reached the ocean. Several factors influenced pesticide distributions in East China Sea estuaries, and higher proportions were derived from agricultural sources than from urban sources, with a higher proportion of agricultural sources than urban sources, influenced by anthropogenic use in the region. Permethrin and cypermethrin were the main compounds contributing to the high ecological risk in the estuaries. Consequently, to prevent risks to marine aquatic life, policymakers should aim to reduce insecticide contaminants derived from urban and agricultural sources.


Asunto(s)
Insecticidas , Piretrinas , Contaminantes Químicos del Agua , Insecticidas/análisis , Estuarios , Contaminantes Químicos del Agua/análisis , Sedimentos Geológicos , China , Piretrinas/análisis , Ríos , Organismos Acuáticos , Medición de Riesgo , Monitoreo del Ambiente
14.
Sci Total Environ ; 912: 169406, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38114037

RESUMEN

Top soil moisture (SM) is an important medium connecting the exchange of matter and energy between the ground and the atmosphere. Previous studies of the relationship between SM and environmental factors, especially aerodynamics, have lacked analysis of the variability in the timing of effects. In this study, we analyzed how environmental factors affect SM, as well as soil moisture memory, by observing precipitation, radiation, and wind speed during the 2019 to 2021 growing seasons in grazing prohibited and grazed areas of a semiarid grassland. The results show that there is a clear threshold (7 mm) for the effect of precipitation on SM, that changes in SM across time scales were influenced by preceding precipitation and net radiation in addition to lagging vegetation greening characteristics (NDVI) and wind speed, and that the role of albedo was related to grazing management. The inhibitory effect of albedo on SM and the depletion of SM by NDVI were more pronounced in comparison to other meteorological factors. Wind speed, precipitation, and radiation directly or indirectly influenced SM duration, and these relationships varied with grazing management and annual variation. These results help to clarify the influence of environmental factors on SM, and provide insight for minimizing the degradation of grassland ecosystems in the process of climate change.


Asunto(s)
Ecosistema , Suelo , Pradera , Conceptos Meteorológicos , Atmósfera
15.
Front Aging Neurosci ; 15: 1194986, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37860122

RESUMEN

Objective: To determine the extent to which the regional brain volumes associated with slow gait speed can inform subsequent cognitive decline in older adults from the Rush Memory and Aging Project. Approach: We utilized deformation-based morphometry (DBM) in a whole-brain exploratory approach to identify the regional brain volumes associated with gait speed assessed over a short distance during an in-home assessment. We created deformation scores to summarize the gait-associated regions and entered the scores into a series of longitudinal mixed effects models to determine the extent to which deformation predicted change in cognition over time, controlling for associations between gait and cognition. Results: In 438 older adults (81 ± 7; 76% female), DBM revealed that slower gait speed was associated with smaller volumes across frontal white matter, temporal grey matter, and subcortical areas and larger volumes in the ventricles during the same testing cycle. When a subset was followed over multiple (5 ± 2) years, slower gait speed was also associated with annual declines in global cognition, executive functioning, and memory abilities. Several of the gait-related brain structures were associated with these declines in cognition; however, larger ventricles and smaller medial temporal lobe volumes proved most robust and attenuated the association between slow gait and cognitive decline. Conclusion: Regional brain volumes in the ventricles and temporal lobe associated with both slow gait speed and faster cognitive decline have potential to improve risk stratification for cognitive decline in older adults.

16.
J Transl Med ; 21(1): 762, 2023 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-37891586

RESUMEN

BACKGROUND: Early availability of pathogen identification in urinary tract infections (UTIs) has critical importance in disease management. Metagenomic next-generation sequencing (mNGS) has the potential to transform how acute and serious infections are diagnosed by offering unbiased and culture-free pathogen detection. However, clinical experience with application of the mNGS test is relatively limited. METHODS: We therefore established a MinION-based mNGS pathogens diagnostic platform and evaluated its potential for clinical implementation in UTIs with clinical samples. 213 urine samples from patients with suspected UTIs were included and subjected to mNGS testing using the MinION platform. mNGS results were compared to the gold standard of clinical culture and composite standard of combining clinical testing, confirmatory qPCR testing, and clinical adjudication by doctors. RESULTS: The mNGS exhibited a sensitivity of 81.4% and a specificity of 92.3%, along with a positive predictive value of 96.6%, a negative predictive value of 64.9%, and an overall accuracy of 84.4%, all of which were determined based on the gold standard of routine culture results. When assessed against the composite standard, the sensitivity and specificity both increased to 89.9% and 100%, respectively, while the accuracy rose to 92.4%. Notably, the positive predictive value and negative predictive value also saw improvements, reaching 100% and 76.8%, respectively. Moreover, this diagnostic platform successfully identified dsDNA viruses. Among the 65 culture-negative samples, the viral detection rate reached 33.8% (22/65) and was subsequently validated through qPCR. Furthermore, the automatic bioinformatics pipeline we developed enabled one-click analysis from data to results, leading to a significant reduction in diagnosis time. CONCLUSION: These results demonstrate that the pathogen detection performance of mNGS is sufficient for diagnostic testing in clinical settings. As the method is generally unbiased, it can improve diagnostic testing of UTIs and other microbial infections.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Infecciones Urinarias , Humanos , Infecciones Urinarias/diagnóstico , Análisis por Conglomerados , Biología Computacional , Metagenómica , Sensibilidad y Especificidad
17.
J Alzheimers Dis ; 95(4): 1585-1595, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37718813

RESUMEN

BACKGROUND: Latinos are at higher risk of developing mild cognitive impairment (MCI) and Alzheimer's disease than non-Latino Whites. Acculturation factors may influence this risk, yet there are few studies that have examined associations of acculturation, particularly in the context of socioenvironmental and familial factors, and brain health in older Latinos. OBJECTIVE: To examine potential associations between acculturation in context and brain health in older Latinos. METHODS: Using three previously established composites of acculturation-in-context, (acculturation-related: nativity status, language preference, acculturation scores; contextually-related socioenvironmental: perceived discrimination, loneliness/social isolation, social network size; and familism), and diffusion-tensor imaging (DTI), associations with white matter structural integrity were examined in 92 Latino adults without dementia participating in one of three epidemiological studies of aging. Linear regression models were used to test associations with DTI-derived metrics (fractional anisotropy, FA; trace) as separate outcomes and acculturation composite scores as individual predictors, while adjusting for age, sex, education, scanner, and white matter hyperintensities (voxelwise and total volumes normalized by intracranial volume). RESULTS: Higher scores on the socioenvironmental composite were associated with lower FA in two clusters of left-hemisphere connections. Cluster 1 was dominated by both short association pathways connecting frontal regions and projection pathways connecting frontal regions with the thalamus. Cluster 2 was dominated by long association pathways connecting parietal, frontal, and temporal regions. CONCLUSIONS: This study of older Latino adults demonstrated an association between reduced brain white matter integrity and contextually related socioenvironmental experiences known to increase risk of MCI and Alzheimer's disease.


Asunto(s)
Enfermedad de Alzheimer , Imagen de Difusión Tensora , Humanos , Anciano , Imagen de Difusión Tensora/métodos , Aculturación , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/psicología , Procesamiento de Imagen Asistido por Computador/métodos , Encéfalo/diagnóstico por imagen , Anisotropía , Hispánicos o Latinos
18.
Pharmaceutics ; 15(9)2023 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-37765283

RESUMEN

Smart drug delivery, through which the drug molecules are delivered according to the requests of human biological rhythms or by maximizing drug therapeutic effects, is highly desired in pharmaceutics. Many biomacromolecules have been exploited for this application in the past few decades, both in industry and laboratories. Biphasic release, with an intentional pulsatile release and a following extended release stage, represents a typical smart drug delivery approach, which aims to provide fast therapeutic action and a long time period of effective blood drug concentration to the patients. In this study, based on the use of a well-known biomacromolecule, i.e., cellulose acetate (CA), as the drug (acetaminophen, ATP)-based sustained release carrier, a modified coaxial electrospraying process was developed to fabricate a new kind of core-shell nanoparticle. The nanoparticles were able to furnish a pulsatile release of ATP due to the shell polyvinylpyrrolidone (PVP). The time cost for a release of 30% was 0.32 h, whereas the core-shell particles were able to provide a 30.84-h sustained release of the 90% loaded ATP. The scanning electron microscope and transmission electron microscope results verified in terms of their round surface morphologies and the obvious core-shell double-chamber structures. ATP presented in both the core and shell sections in an amorphous state owing to its fine compatibility with CA and PVP. The controlled release mechanisms of ATP were suggested. The disclosed biomacromolecule-based process-structure-performance relationship can shed light on how to develop new sorts of advanced nano drug delivery systems.

19.
Environ Geochem Health ; 45(11): 8787-8802, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37749354

RESUMEN

The use of hexachlorocyclohexanes (HCHs) in pesticides has been prohibited for decades in China. Since then, there have been urbanization and transformation of the functional areas of many sites, which were formerly involved in the HCH industry. However, it is possible that, unless properly managed, these sites may still contain HCH residues in the soil and thus pose a threat to the surrounding environment and the quality of groundwater. This study aimed to characterize soil residues in a typical site that was historically involved in HCH production in southern China, by analyzing the α-HCH, ß-HCH, and γ-HCH contents of the soil. The results suggested that HCHs persist in the environment and can have long-term effects. It was found that α-HCH and ß-HCH were present in many samples in concentrations that were comparable or higher than those specified by China's Class 1 screening values. The distribution of residues was significantly correlated with the historical HCH production activities in the areas. The characteristic ratios of α-HCH/γ-HCH and ß-HCH/(α + γ)-HCH at different soil depths were 1.4-3.7 and 0.21-1.04, respectively, which indicated the presence of significant localized residues of HCHs. The presence of HCHs in the soil suggested a downward migration, with concentrations rapidly decreasing in the upper layer soil (0-5 m), but a gradual increase in the deeper soil (5-14 m). HCHs were detected at depths exceeding 24 m, indicating heavy penetration. The proportions of γ-HCH and ß-HCH changed with increasing soil depth, which was related to their relatively volatile and stable molecular structures, respectively. The results strongly suggested that there is widespread contamination of both soil and groundwater by HCHs even after decades. The likelihood of residual HCHs in the soil should therefore be taken into full consideration during urban planning to limit risks to human and environmental health.


Asunto(s)
Agua Subterránea , Hidrocarburos Clorados , Plaguicidas , Contaminantes del Suelo , Humanos , Hexaclorociclohexano/análisis , Suelo/química , Monitoreo del Ambiente , Plaguicidas/análisis , Hidrocarburos Clorados/análisis , Contaminantes del Suelo/análisis , China
20.
N Engl J Med ; 389(7): 602-611, 2023 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-37466280

RESUMEN

BACKGROUND: Findings from observational studies suggest that dietary patterns may offer protective benefits against cognitive decline, but data from clinical trials are limited. The Mediterranean-DASH Intervention for Neurodegenerative Delay, known as the MIND diet, is a hybrid of the Mediterranean diet and the DASH (Dietary Approaches to Stop Hypertension) diet, with modifications to include foods that have been putatively associated with a decreased risk of dementia. METHODS: We performed a two-site, randomized, controlled trial involving older adults without cognitive impairment but with a family history of dementia, a body-mass index (the weight in kilograms divided by the square of the height in meters) greater than 25, and a suboptimal diet, as determined by means of a 14-item questionnaire, to test the cognitive effects of the MIND diet with mild caloric restriction as compared with a control diet with mild caloric restriction. We assigned the participants in a 1:1 ratio to follow the intervention or the control diet for 3 years. All the participants received counseling regarding adherence to their assigned diet plus support to promote weight loss. The primary end point was the change from baseline in a global cognition score and four cognitive domain scores, all of which were derived from a 12-test battery. The raw scores from each test were converted to z scores, which were averaged across all tests to create the global cognition score and across component tests to create the four domain scores; higher scores indicate better cognitive performance. The secondary outcome was the change from baseline in magnetic resonance imaging (MRI)-derived measures of brain characteristics in a nonrandom sample of participants. RESULTS: A total of 1929 persons underwent screening, and 604 were enrolled; 301 were assigned to the MIND-diet group and 303 to the control-diet group. The trial was completed by 93.4% of the participants. From baseline to year 3, improvements in global cognition scores were observed in both groups, with increases of 0.205 standardized units in the MIND-diet group and 0.170 standardized units in the control-diet group (mean difference, 0.035 standardized units; 95% confidence interval, -0.022 to 0.092; P = 0.23). Changes in white-matter hyperintensities, hippocampal volumes, and total gray- and white-matter volumes on MRI were similar in the two groups. CONCLUSIONS: Among cognitively unimpaired participants with a family history of dementia, changes in cognition and brain MRI outcomes from baseline to year 3 did not differ significantly between those who followed the MIND diet and those who followed the control diet with mild caloric restriction. (Funded by the National Institute on Aging; ClinicalTrials.gov number, NCT02817074.).


Asunto(s)
Disfunción Cognitiva , Demencia , Dieta Mediterránea , Anciano , Anciano de 80 o más Años , Humanos , Encéfalo/diagnóstico por imagen , Cognición , Disfunción Cognitiva/prevención & control , Demencia/prevención & control , Dieta Hiposódica , Restricción Calórica
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