Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 101
Filtrar
1.
Epilepsia Open ; 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38943548

RESUMEN

OBJECTIVE: Subcortical nuclei such as the thalamus and striatum have been shown to be related to seizure modulation and termination, especially in drug-resistant epilepsy. Enhance diffusion-weighted imaging (eDWI) technique and tri-component model have been used in previous studies to calculate apparent diffusion coefficient from ultra high b-values (ADCuh). This study aimed to explore the alterations of ADCuh in the bilateral thalamus and striatum in MRI-negative drug-resistant epilepsy. METHODS: Twenty-nine patients with MRI-negative drug-resistant epilepsy and 18 healthy controls underwent eDWI scan with 15 b-values (0-5000 s/mm2). The eDWI parameters including standard ADC (ADCst), pure water diffusion (D), and ADCuh were calculated from the 15 b-values. Regions-of-interest (ROIs) analyses were conducted in the bilateral thalamus, caudate nucleus, putamen, and globus pallidus. ADCst, D, and ADCuh values were compared between the MRI-negative drug-resistant epilepsy patients and controls using multivariate generalized linear models. Inter-rater reliability was assessed using the intra-class correlation coefficient (ICC) and Bland-Altman (BA) analysis. False discovery rate (FDR) method was applied for multiple comparisons correction. RESULTS: ADCuh values in the bilateral thalamus, caudate nucleus, putamen, and globus pallidus in MRI-negative drug-resistant epilepsy were significantly higher than those in the healthy control subjects (all p < 0.05, FDR corrected). SIGNIFICANCE: The alterations of the ADCuh values in the bilateral thalamus and striatum in MRI-negative drug-resistant epilepsy might reflect abnormal membrane water permeability in MRI-negative drug-resistant epilepsy. ADCuh might be a sensitive measurement for evaluating subcortical nuclei-related brain damage in epilepsy patients. PLAIN LANGUAGE SUMMARY: This study aimed to explore the alterations of apparent diffusion coefficient calculated from ultra high b-values (ADCuh) in the subcortical nuclei such as the bilateral thalamus and striatum in MRI-negative drug-resistant epilepsy. The bilateral thalamus and striatum showed higher ADCuh in epilepsy patients than healthy controls. These findings may add new evidences of subcortical nuclei abnormalities related to water and ion hemostasis in epilepsy patients, which might help to elucidate the underlying epileptic neuropathophysiological mechanisms and facilitate the exploration of therapeutic targets.

2.
Seizure ; 119: 17-27, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38768522

RESUMEN

PURPOSE: To establish and validate a novel nomogram based on clinical characteristics and [18F]FDG PET radiomics for the prediction of postsurgical seizure freedom in patients with temporal lobe epilepsy (TLE). PATIENTS AND METHODS: 234 patients with drug-refractory TLE patients were included with a median follow-up time of 24 months after surgery. The correlation coefficient redundancy analysis and LASSO Cox regression were used to characterize risk factors. The Cox model was conducted to develop a Clinic-PET nomogram to predict the relapse status in the training set (n = 171). The nomogram's performance was estimated through discrimination, calibration, and clinical utility. The prognostic prediction model was validated in the test set (n = 63). RESULTS: Eight radiomics features were selected to assess the radiomics score (radscore) of the operation side (Lat_radscore) and the asymmetric index (AI) of the radiomics score (AI_radscore). AI_radscor, Lat_radscor, secondarily generalized seizures (SGS), and duration between seizure onset and surgery (Durmon) were significant predictors of seizure-free outcomes. The final model had a C-index of 0.68 (95 %CI: 0.59-0.77) for complete freedom from seizures and time-dependent AUROC was 0.65 at 12 months, 0.65 at 36 months, and 0.59 at 60 months in the test set. A web application derived from the primary predictive model was displayed for economic and efficient use. CONCLUSIONS: A PET-based radiomics nomogram is clinically promising for predicting seizure outcomes after temporal lobe epilepsy surgery.


Asunto(s)
Epilepsia del Lóbulo Temporal , Nomogramas , Tomografía de Emisión de Positrones , Humanos , Epilepsia del Lóbulo Temporal/cirugía , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Masculino , Femenino , Adulto , Adulto Joven , Fluorodesoxiglucosa F18 , Persona de Mediana Edad , Epilepsia Refractaria/cirugía , Epilepsia Refractaria/diagnóstico por imagen , Resultado del Tratamiento , Convulsiones/diagnóstico por imagen , Convulsiones/cirugía , Pronóstico , Estudios de Seguimiento , Adolescente , Estudios Retrospectivos , Radiómica
3.
Brain Pathol ; : e13277, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38779803

RESUMEN

Growing evidence indicates that non-neuronal oligodendrocyte plays an important role in Amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. In patient's brain, the impaired myelin structure is a pathological feature with the observation of TDP-43 in cytoplasm of oligodendrocyte. However, the mechanism underlying the gain of function by TDP-43 in oligodendrocytes, which are vital for the axonal integrity, remains unclear. Recently, we found that the primate-specific cleavage of truncated TDP-43 fragments occurred in cytoplasm of monkey neural cells. This finding opened up the avenue to investigate the myelin integrity affected by pathogenic TDP-43 in oligodendrocytes. In current study, we demonstrated that the truncated TDP-35 in oligodendrocytes specifically, could lead to the dysfunctional demyelination in corpus callosum of monkey. As a consequence of the interaction of myelin regulatory factor with the accumulated TDP-35 in cytoplasm, the downstream myelin-associated genes expression was downregulated at the transcriptional level. Our study aims to investigate the potential effect on myelin structure injury, affected by the truncated TDP-43 in oligodendrocyte, which provided the additional clues on the gain of function during the progressive pathogenesis and symptoms in TDP-43 related diseases.

4.
Chem Sci ; 15(13): 4709-4722, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38550705

RESUMEN

The global population is growing rapidly, which poses a significant challenge to food security. Innovation in agricultural technologies is necessary to achieve sustainable development in agriculture and combat food insecurity. Nanotechnology has emerged as a promising tool in agriculture; compared to conventional agricultural chemicals, demonstrated benefits include increased efficiency of delivery and utilization of both nutrients and pesticides, as well as nanoscale-specific stimulation of stress tolerance pathways. Among the many studied nanomaterials, nano-sulfur has demonstrated superior effects at enhancing plant resilience to pathogens and abiotic stresses, as well as improving plant growth and nutritional quality of edible tissues. A number of published studies have investigated the physiological effects (growth promotion, disease resistance) of single or several sulfur and sulfide compounds on crop species. However, there is no systematic analysis of this literature, including the effects and specific mechanisms of various sulfur forms in agricultural applications. In this review, we will discuss the effects of sulfur (including nano-sulfur) on crop species, the underlying mechanisms of action for their transport and transformation in the soil-plant system, and evaluate their suitability in sustainable agricultural development. Additionally, we discuss the current challenges and knowledge gaps for nanoscale sulfur use in agriculture, and describe future research directions to advance our understanding of the sustainable use of this material at the scale of individual fields.

5.
Talanta ; 272: 125738, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38359717

RESUMEN

The sulfidation is considered as one of the most important environmental transformation processes of silver nanoparticles (AgNPs), which affects their transport, uptake and toxicity. Herein, based on the hollow fiber flow-field flow fractionation coupled with triple quadrupole inductively coupled plasma mass spectrometry (HF5-ICP-QQQ), we developed an efficient approach to accurately characterize the sulfidation process of AgNPs in aquatic solutions. HF5 could efficiently remove interferential ions and separate nanoparticles with different sizes online, and ICP-QQQ could accurately detect S element through monitoring 32S16O+ in mass shift mode. By the proposed method, two kinds of AgNPs, citrate-coated AgNPs and PVP-coated AgNPs, were selected as models to trace their transfer behaviors during the sulfidation. The results showed once AgNPs were exposed to Na2S solution, the overlapping fractograms of 32S16O+ and 107Ag+ were rapidly detected by HF5-ICP-QQQ to indicate the co-presence of Ag and S, and thus confirming the production of Ag2S and AgNPs underwent a rapid sulfidation process. There were substantial differences in the influence of the two coated agents on the stability of the particles under the conditions examined. In the presence of sulfide, PVP-coated AgNPs could maintain initial size distribution with higher stability, while the size distribution of citrate-coated AgNPs changed considerably. The developed HF5-ICP-QQQ method provides a reliable tool to identify and characterize the transformation process of AgNPs in aquatic solution, which contributed to a deeper understanding of the environmental fate and behavior of AgNPs with different coating.

6.
Plant Physiol Biochem ; 207: 108428, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38364633

RESUMEN

Manganese (Mn) is one of the essential elements for plant growth and is involved in the process of photosynthesis and seed germination. Herein, we applied two Mn-based nanoparticles, MnO2 and Mn3O4, to the soil to investigate their effects on radish growth, antioxidant system, and nutrients. The radish plant height after treatment with 10 mg/kg of MnO2 and Mn3O4 NPs were increased, compare to the control. In radish's shoot, MnO2 NPs at high concentrations (100 mg/kg) increased MDA activity by 58 % compared to the control group, while exposure to Mn3O4 NPs at the same concentration decreased MDA activity by 14 %. The nutrient content of radishes, such as soluble sugar and vitamin C, was improved. Moreover, single particle inductively coupled plasma mass spectrometry (SP ICP-MS) was used to understand the patterns of migration of Mn-based NPs in radish and subsequent impact on nutrients. We found that Mn-based NPs accumulated mainly in the roots of radish. Interestingly, the accumulation characteristics of MnO2 NPs and Mn3O4 NPs were different. MnO2 NPs accumulated more in radish leaves than in fruits, while the accumulation of Mn3O4 NPs gradually decreased from roots to leaves. Finally, we determined the mineral element content of the leaves, fruits, and roots of radish, and found that the uptake of main metallic mineral elements (e.g. Cu, Fe, Mg, Zn, Na, K) was inhibited by the application of Mn-based NPs. These findings underscore the importance of considering species and multifaceted impacts of Mn-based NPs as nanofertilizers for their wide application in agriculture.


Asunto(s)
Nanopartículas , Raphanus , Raphanus/química , Manganeso/farmacología , Compuestos de Manganeso/farmacología , Óxidos/farmacología , Minerales/farmacología
7.
Jpn J Radiol ; 42(3): 261-267, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37812304

RESUMEN

OBJECTIVE: Diagnosis of cochlear malformation on temporal bone CT images is often difficult. Our aim was to assess the utility of deep learning analysis in diagnosing cochlear malformation on temporal bone CT images. METHODS: A total of 654 images from 165 temporal bone CTs were divided into the training set (n = 534) and the testing set (n = 120). A target region that includes the area of the cochlear was extracted to create a diagnostic model. 4 models were used: ResNet10, ResNet50, SE-ResNet50, and DenseNet121. The testing data set was subsequently analyzed using these models and by 4 doctors. RESULTS: The areas under the curve was 0.91, 0.94, 0.93, and 0.73 in ResNet10, ResNet50, SE-ResNet50, and DenseNet121. The accuracy of ResNet10, ResNet50, and SE-ResNet50 is better than chief physician. CONCLUSIONS: Deep learning technique implied a promising prospect for clinical application of artificial intelligence in the diagnosis of cochlear malformation based on CT images.


Asunto(s)
Aprendizaje Profundo , Humanos , Inteligencia Artificial , Cóclea/diagnóstico por imagen , Cóclea/anomalías , Hueso Temporal/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos
8.
Eco Environ Health ; 2(2): 61-73, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38075291

RESUMEN

The wide application of nanomaterials and plastic products generates a substantial number of nanoparticulate pollutants in the environment. Nanoparticulate pollutants are quite different from their bulk counterparts because of their unique physicochemical properties, which may pose a threat to environmental organisms and human beings. To accurately predict the environmental risks of nanoparticulate pollutants, great efforts have been devoted to developing reliable methods to define their occurrence and track their fate and transformation in the environment. Herein, we summarized representative studies on the preconcentration, separation, formation, and transformation of nanoparticulate pollutants in environmental samples. Finally, some perspectives on future research directions are proposed.

9.
J Agric Food Chem ; 71(51): 20405-20418, 2023 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-38032362

RESUMEN

Global warming has posed significant pressure on agricultural productivity. The resulting abiotic stresses from high temperatures and drought have become serious threats to plants and subsequent global food security. Applying nanomaterials in agriculture can balance the plant's oxidant level and can also regulate phytohormone levels and thus maintain normal plant growth under heat and drought stresses. Nanomaterials can activate and regulate specific stress-related genes, which in turn increase the activity of heat shock protein and aquaporin to enable plants' resistance against abiotic stresses. This review aims to provide a current understanding of nanotechnology-enhanced plant tolerance to heat and drought stress. Molecular mechanisms are explored to see how nanomaterials can alleviate abiotic stresses on plants. In comparison with organic molecules, nanomaterials offer the advantages of targeted transportation and slow release. These advantages help the nanomaterials in mitigating drought and heat stress in plants.


Asunto(s)
Sequías , Regulación de la Expresión Génica de las Plantas , Plantas/genética , Respuesta al Choque Térmico , Estrés Fisiológico/genética
10.
J Hazard Mater ; 458: 132050, 2023 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-37459760

RESUMEN

In this study, based on the assessment of soil heavy metals (HMs) pollution using relevant indices, a comprehensive approach combined network environ analysis (NEA), human health risk assessment (HHRA) method and positive definite matrix factor (PMF) model to quantify the risks among ecological communities in a special environment around mining area in northwest Yunnan, calculated the risk to human health caused by HMs in soil, and analyzed the pollution sources of HMs. The integrated risks for soil microorganisms, vegetations, herbivores, and carnivores were 2.336, 0.876, 0.114, and 0.082, respectively, indicating that soil microorganisms were the largest risk receptors. The total hazard indexes (HIT) for males, females, and children were 0.542, 0.591, and 1.970, respectively, revealing a relatively high and non-negligible non-carcinogenic risks (NCR) for children. The total cancer risks (TCR) for both females and children exceeded 1.00E-04, indicating that soil HMs posed carcinogenic risks (CR) to them. Comparatively, Pb was the high-risk metal, accounting for 53.76%, 57.90%, and 68.09% of HIT in males, females, and children, respectively. PMF analysis yielded five sources of pollution, F1 (industry), F2 (agriculture), F3 (domesticity), F4 (nature), and F5 (traffic).


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Niño , Humanos , Suelo , China , Monitoreo del Ambiente , Contaminantes del Suelo/análisis , Medición de Riesgo , Metales Pesados/análisis , Carcinógenos
11.
Sci Adv ; 9(27): eadg2252, 2023 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-37418525

RESUMEN

The blood circulation is considered the only way for the orally administered nanoparticles to enter the central nervous systems (CNS), whereas non-blood route-mediated nanoparticle translocation between organs is poorly understood. Here, we show that peripheral nerve fibers act as direct conduits for silver nanomaterials (Ag NMs) translocation from the gut to the CNS in both mice and rhesus monkeys. After oral gavage, Ag NMs are significantly enriched in the brain and spinal cord of mice with particle state however do not efficiently enter the blood. Using truncal vagotomy and selective posterior rhizotomy, we unravel that the vagus and spinal nerves mediate the transneuronal translocation of Ag NMs from the gut to the brain and spinal cord, respectively. Single-cell mass cytometry analysis revealed that enterocytes and enteric nerve cells take up significant levels of Ag NMs for subsequent transfer to the connected peripheral nerves. Our findings demonstrate nanoparticle transfer along a previously undocumented gut-CNS axis mediated by peripheral nerves.


Asunto(s)
Nanoestructuras , Plata , Animales , Ratones , Sistema Nervioso Central , Médula Espinal , Nervios Periféricos
12.
Environ Sci Technol ; 57(19): 7547-7558, 2023 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-37134233

RESUMEN

Nickel (Ni) is a trace element beneficial for plant growth and development and could improve crop yield by stimulating urea decomposition and nitrogen-fixing enzyme activity. A full life cycle study was conducted to compare the long-term effects of soil-applied NiO nanoparticles (n-NiO), NiO bulk (b-NiO), and NiSO4 at 10-200 mg kg-1 on plant growth and nutritional content of soybean. n-NiO at 50 mg kg-1 significantly promoted the seed yield by 39%. Only 50 mg kg-1 n-NiO promoted total fatty acid content and starch content by 28 and 19%, respectively. The increased yield and nutrition could be attributed to the regulatory effects of n-NiO, including photosynthesis, mineral homeostasis, phytohormone, and nitrogen metabolism. Furthermore, n-NiO maintained a Ni2+ supply for more extended periods than NiSO4, reducing potential phytotoxicity concerns. Single-particle inductively coupled plasma mass spectrometry (sp-ICP-MS) for the first time confirmed that the majority of the Ni in seeds is in ionic form, with only 28-34% as n-NiO. These findings deepen our understanding of the potential of nanoscale and non-nanoscale Ni to accumulate and translocate in soybean, as well as the long-term fate of these materials in agricultural soils as a strategy for nanoenabled agriculture.


Asunto(s)
Nanopartículas , Níquel , Níquel/química , Glycine max , Nitrógeno , Suelo
13.
Proc Natl Acad Sci U S A ; 120(20): e2218739120, 2023 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-37155879

RESUMEN

Carbon-based nanomaterials (CNMs) have recently been found in humans raising a great concern over their adverse roles in the hosts. However, our knowledge of the in vivo behavior and fate of CNMs, especially their biological processes elicited by the gut microbiota, remains poor. Here, we uncovered the integration of CNMs (single-walled carbon nanotubes and graphene oxide) into the endogenous carbon flow through degradation and fermentation, mediated by the gut microbiota of mice using isotope tracing and gene sequencing. As a newly available carbon source for the gut microbiota, microbial fermentation leads to the incorporation of inorganic carbon from the CNMs into organic butyrate through the pyruvate pathway. Furthermore, the butyrate-producing bacteria are identified to show a preference for the CNMs as their favorable source, and excessive butyrate derived from microbial CNMs fermentation further impacts on the function (proliferation and differentiation) of intestinal stem cells in mouse and intestinal organoid models. Collectively, our results unlock the unknown fermentation processes of CNMs in the gut of hosts and underscore an urgent need for assessing the transformation of CNMs and their health risk via the gut-centric physiological and anatomical pathways.


Asunto(s)
Microbioma Gastrointestinal , Nanoestructuras , Nanotubos de Carbono , Humanos , Animales , Ratones , Microbioma Gastrointestinal/fisiología , Nanotubos de Carbono/efectos adversos , Fermentación , Butiratos/metabolismo
14.
Quant Imaging Med Surg ; 13(4): 2038-2052, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37064372

RESUMEN

Background: Cynomolgus monkeys are widely used in studies related to osteoporosis, and there is no evidence of age-related changes in volumetric bone mineral density (vBMD) measured using quantitative computed tomography (QCT) in nonhuman primates. This study aimed to describe changes in the characteristics of lumbar vBMD with age, to analyze the relationship between lumbar vBMD and body composition, and to investigate the precision of QCT measurements in healthy female cynomolgus monkeys. Methods: Age-related changes in lumbar vBMD were described using cubic regression models, and the accumulated bone loss rates (ABLR) of the lumbar spine were calculated. Spearman rank correlation and ridge regression analysis were used to investigate the relationship of the average lumbar vBMD and body components. Thirty animals were selected to analyze the short-term in vivo precision of the QCT measurements. The precision was expressed as the root-mean-square coefficient of variation (RMS-CV%) or root-mean-square standard deviation (RMS-SD). Results: A total of 72 healthy female cynomolgus monkeys, aged 1-25 years, were included in this study. The average lumbar vBMD of female cynomolgus monkeys increased with age until the age of 10 years, around which it reached peak bone mass, with a relatively marked decline after the age of 13 years. The ABLRs of female cynomolgus monkeys in the premenopausal (13-19 years) and postmenopausal age groups (20-25 years) were -4.9% and -21.2%, respectively. Ridge regression analysis showed that age and subcutaneous adipose tissue (SAT) contributed positively to the average lumbar vBMD in animals aged ≤10 years, whereas in animals aged >10 years, age contributed negatively to lumbar vBMD. The RMS-CV% (RMS-SD) of the lumbar vBMD measured using QCT ranged from 0.47% to 1.60% (1.91-6.31 mg/cm3). Conclusions: Age-related changes in lumbar vBMD measured using QCT in healthy female monkeys showed similar trends to those in humans. Age and SAT may affect the lumbar vBMD in female cynomolgus monkeys. QCT revealed good precision in measuring the lumbar vBMD in female cynomolgus monkeys.

15.
Cell Discov ; 9(1): 27, 2023 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-36878905

RESUMEN

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that affects social interaction and behavior. Mutations in the gene encoding chromodomain helicase DNA-binding protein 8 (CHD8) lead to autism symptoms and macrocephaly by a haploinsufficiency mechanism. However, studies of small animal models showed inconsistent findings about the mechanisms for CHD8 deficiency-mediated autism symptoms and macrocephaly. Using the nonhuman primate as a model system, we found that CRISPR/Cas9-mediated CHD8 mutations in the embryos of cynomolgus monkeys led to increased gliogenesis to cause macrocephaly in cynomolgus monkeys. Disrupting CHD8 in the fetal monkey brain prior to gliogenesis increased the number of glial cells in newborn monkeys. Moreover, knocking down CHD8 via CRISPR/Cas9 in organotypic monkey brain slices from newborn monkeys also enhanced the proliferation of glial cells. Our findings suggest that gliogenesis is critical for brain size in primates and that abnormal gliogenesis may contribute to ASD.

16.
Materials (Basel) ; 16(5)2023 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-36902901

RESUMEN

High-performance bolts made of carbon/carbon (C/C) composites are necessary for connecting thermally-insulating structural components of aerospace vehicles. To enhance the mechanical properties of the C/C bolt, a new silicon infiltration-modified C/C (C/C-SiC) bolt was developed via vapor silicon infiltration. The effects of silicon infiltration on microstructure and mechanical properties were systematically studied. Findings reveal that dense and uniform SiC-Si coating has been formed after silicon infiltration of the C/C bolt, strongly bonding with the C matrix. Under tensile stress, the C/C-SiC bolt undergoes a tensile failure of studs, while the C/C bolt is subject to the pull-out failure of threads. The breaking strength of the former (55.16 MPa) is 26.83% higher than the failure strength of the latter (43.49 MPa). Under double-sided shear stress, both the crushing of threads and the shear failure of studs occur within two bolts. As a result, the shear strength of the former (54.73 MPa) exceeds that of the latter (43.88 MPa) by 24.73%. According to CT and SEM analysis, matrix fracture, fiber debonding, and fiber bridging are the main failure modes. Therefore, a mixed coating formed by silicon infiltration can effectively transfer loads from coating to carbon matrix and carbon fiber, thereby enhancing the load-bearing capacity of C/C bolts.

17.
Pharmacol Res ; 189: 106681, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36746361

RESUMEN

OBJECTIVES: Translocator protein 18 kDa (TSPO) positron emission tomography (PET) can be harnessed for the non-invasive detection of macrophage-driven inflammation. [18F]LW223, a newly reported TSPO PET tracer which was insensitive to rs6971 polymorphism, showed favorable performance characteristics in a recent imaging study involving a rat myocardial infarction model. To enable quantitative neuroimaging with [18F]LW223, we conducted kinetic analysis in the non-human primate (NHP) brain. Further, we sought to assess the utility of [18F]LW223-based TSPO imaging in a first-in-human study. METHODS: Radiosynthesis of [18F]LW223 was accomplished on an automated module, whereas molar activities, stability in formulation, lipophilicity and unbound free fraction (fu) of the probe were measured. Brain penetration and target specificity of [18F]LW223 in NHPs were corroborated by PET-MR imaging under baseline and pre-blocking conditions using the validated TSPO inhibitor, (R)-PK11195, at doses ranging from 5 to 10 mg/kg. Kinetic modeling was performed using one-tissue compartment model (1TCM), two-tissue compartment model (2TCM) and Logan graphical analyses, using dynamic PET data acquisition, arterial blood collection and metabolic stability testing. Clinical PET scans were performed in two healthy volunteers (HVs). Regional brain standard uptake value ratio (SUVr) was assessed for different time intervals. RESULTS: [18F]LW223 was synthesized in non-decay corrected radiochemical yields (n.d.c. RCYs) of 33.3 ± 6.5% with molar activities ranging from 1.8 ± 0.7 Ci/µmol (n = 11). [18F]LW223 was stable in formulation for up to 4 h and LogD7.4 of 2.31 ± 0.13 (n = 6) and fu of 5.80 ± 1.42% (n = 6) were determined. [18F]LW223 exhibited good brain penetration in NHPs, with a peak SUV value of ca. 1.79 in the whole brain. Pre-treatment with (R)-PK11195 substantially accelerated the washout and attenuated the area under the time-activity curve, indicating in vivo specificity of [18F]LW223 towards TSPO. Kinetic modeling demonstrated that 2TCM was the most suitable model for [18F]LW223-based neuroimaging. Global transfer rate constants (K1) and total volumes of distribution (VT) were found to be 0.10 ± 0.01 mL/cm3/min and 2.30 ± 0.17 mL/cm3, respectively. Dynamic PET data analyses across distinct time windows revealed that the VT values were relatively stable after 60 min post-injection. In a preliminary clinical study with two healthy volunteers, [18F]LW223 exhibited good brain uptake and considerable tracer retention across all analyzed brain regions. Of note, an excellent correlation between SUVr with VT was obtained when assessing the time interval from 20 to 40 min post tracer injection (SUVr(20-40 min), R2 = 0.94, p < 0.0001), suggesting this time window may be suitable to estimate specific binding to TSPO in human brain. CONCLUSION: Our findings indicate that [18F]LW223 is suitable for quantitative TSPO-targeted PET imaging in higher species. Employing state-of-the-art kinetic modeling, we found that [18F]LW223 was effective in mapping TSPO throughout the NHP brain, with best model fits obtained from 2TCM and Logan graphical analyses. Overall, our results indicate that [18F]LW223 exhibits favorable tracer performance characteristics in higher species, and this novel imaging tool may hold promise to provide effective neuroinflammation imaging in patients with neurological disease.


Asunto(s)
Encéfalo , Tomografía de Emisión de Positrones , Animales , Humanos , Encéfalo/metabolismo , Proteínas Portadoras/metabolismo , Cinética , Tomografía de Emisión de Positrones/métodos , Primates/metabolismo , Radiofármacos , Receptores de GABA/metabolismo , Receptores de GABA-A/metabolismo
18.
Comput Biol Med ; 155: 106663, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36803796

RESUMEN

Deep learning networks have achieved remarkable progress in various tasks of medical imaging. Most of the recent success in computer vision highly depend on large amounts of carefully annotated data, whereas labelling is arduous, time-consuming and in need of expertise. In this paper, a semi-supervised learning method, Semi-XctNet, is proposed for volumetric images reconstruction from a single X-ray image. In our framework, the effect of regularization on pixel-level prediction is enhanced by introducing a transformation consistent strategy into the model. Furthermore, a multi-stage training strategy is designed to ameliorate the generalization performance of the teacher network. An assistant module is also introduced to improve the pixel quality of pseudo-labels, thereby further improving the reconstruction accuracy of the semi-supervised model. The semi-supervised method proposed in this paper has been extensively validated on the LIDC-IDRI lung cancer detection public data set. Quantitative results show that SSIM (structural similarity measurement) and PSNR (peak signal noise ratio) are 0.8384 and 28.7344 respectively. Compared with the state-of-the-arts, Semi-XctNet exhibits excellent reconstruction performance, thus demonstrating the effectiveness of our method on the task of volumetric images reconstruction network from a single X-ray image.


Asunto(s)
Neoplasias Pulmonares , Humanos , Aprendizaje Automático Supervisado , Tórax , Procesamiento de Imagen Asistido por Computador
19.
Biometrics ; 79(2): 587-591, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36448885

RESUMEN

Ye, Ertefaie, Flory, Hennessy, and Small (YEFHS) proposed a new method, instrumented difference-in-differences, for dealing with unmeasured confounding. In this note, I connect and compare assumptions and identifications in instrumental variable (IV) and difference-in-differences (DID) methods with those in YEFHS, derive new identification results, and discuss different choices when extending such results to adjust for covariates.

20.
J Environ Sci (China) ; 126: 494-505, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36503776

RESUMEN

Single particle-inductively coupled plasma mass spectrometry (SP-ICP-MS) is a powerful tool for size-characterization of metal-containing nanoparticles (MCNs) at environmentally relevant concentrations, however, coexisting dissolved metal ions greatly interfere with the accuracy of particle size analysis. The purpose of this study is to develop an online technique that couples hollow fiber ultrafiltration (HFUF) with SP-ICP-MS to improve the accuracy and size detection limit of MCNs by removing metal ions from suspensions of MCNs. Through systematic optimization of conditions including the type and concentration of surfactant and complexing agent, carrier pH, and ion cleaning time, HFUF completely removes metal ions but retains the MCNs in suspension. The optimal conditions include using a mixture of 0.05 vol.% FL-70 and 0.5 mmol/L Na2S2O3 (pH = 8.0) as the carrier and 4 min as the ion cleaning time. At these conditions, HFUF-SP-ICP-MS accurately determines the sizes of MCNs, and the results agree with the size distribution determined by transmission electron microscopy, even when metal ions also are present in the sample. In addition, reducing the ionic background through HFUF also lowers the particle size detection limit with SP-ICP-MS (e.g., from 28.3 to 14.2 nm for gold nanoparticles). This size-based ion-removal principle provided by HFUF is suitable for both cations (e.g., Ag+) and anions (e.g., AuCl4-) and thus has good versatility compared to ion exchange purification and promising prospects for the removal of salts and macromolecules before single particle analysis.


Asunto(s)
Nanopartículas del Metal , Oro , Iones , Análisis Espectral , Ultrafiltración
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...