Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 102
Filtrar
1.
Adv Sci (Weinh) ; : e2405719, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39164979

RESUMO

The PEGylated ultrasmall iron oxide nanoparticles (PUSIONPs) exhibit longer blood residence time and better biodegradability than conventional gadolinium-based contrast agents (GBCAs), enabling prolonged acquisitions in contrast-enhanced magnetic resonance angiography (CE-MRA) applications. The image quality of CE-MRA is dependent on the contrast agent concentration and the parameters of the pulse sequences. Here, a closed-form mathematical model is demonstrated and validated to automatically optimize the concentration, echo time (TE), repetition time (TR) and flip angle (FA). The pharmacokinetic studies are performed to estimate the dynamic intravascular concentrations within 12 h postinjection, and the adaptive concentration-dependent sequence parameters are determined to achieve optimal signal enhancement during a prolonged measurement window. The presented model is tested on phantom and in vivo rat images acquired from a 3T scanner. Imaging results demonstrate excellent agreement between experimental measurements and theoretical predictions, and the adaptive sequence parameters obtain better signal enhancement than the fixed ones. The low-dose PUSIONPs (0.03 mmol kg-1 and 0.05 mmol kg-1) give a comparable signal intensity to the high-dose one (0.10 mmol kg-1) within 2 h postinjection. The presented mathematical model provides guidance for the optimization of the concentration and sequence parameters in PUSIONPs-enhanced MRA, and has great potential for further clinical translation.

2.
EJNMMI Res ; 14(1): 78, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39210186

RESUMO

BACKGROUND: Parkinson's disease (PD) is a prevalent neurodegenerative disorder worldwide, diagnosed based on classic symptoms like motor dysfunction and cognitive impairments. With the development of various radioactive ligands, positron emission tomography (PET) imaging combined with specific radiolabelling probes has proven to be effective in aiding clinical PD diagnosis. Among these probes, 2ß-Carbomethoxy-3ß-(4-chlorophenyl)-8-(2-[18F]-fluoroethyl) nortropane ([18F]FECNT) has been utilized as a PET tracer to image dopamine transporter (DAT) integrity in striatal presynaptic dopaminergic terminals. However, the presence of brain-penetrant radioactive metabolites produced by [18F]FECNT may impact the accuracy of PET imaging. In previous research, we developed 2ß-Carbomethoxy-3ß-(4-chlorophenyl)-8-(2-[18F]-fluoroethyl-1,1,2,2-d4) nortropane ([18F]FECNT-d4), a deuterated derivative with enhanced stability in plasma and the striatum, along with a slower washout rate. In this study, we further investigated the potential of [18F]FECNT-d4 to detect dopaminergic neuron degeneration in Parkinson's disease. This involved PET imaging in unilaterally-lesioned PD model rats and in vitro autoradiography conducted on postmortem brain sections. RESULTS: PET images revealed reduced specific uptake in the ipsilateral striatum of rats stereotactically injected with 6-hydroxydopamine hydrochloride (6-OHDA). Compared to the sham group, the ratio of standardized uptake value (SUV) in the ipsilateral to contralateral striatum decreased by 13%, 23%, and 63% in the mild, moderate, and severe lesioned groups, respectively. Dopaminergic denervation observed in PET imaging was further supported by behavioral assessments, immunostaining, and monoamine concentration tests. Moreover, the microPET results exhibited positive correlations with these measurements, except for the apomorphine-induced rotational behavior test, which showed a negative correlation. Additionally, [18F]FECNT-d4 uptake was approximately 40% lower in the postmortem striatal sections of a PD patient compared to a healthy subject. Furthermore, estimated human dosimetry (effective dose equivalent: 5.06 E-03 mSv/MBq), extrapolated from rat biodistribution data, remained below the current Food and Drug Administration limit for radiation exposure. CONCLUSION: Our findings demonstrate that [18F]FECNT-d4 accurately estimates levels of dopaminergic neuron degeneration in the 6-OHDA-induced PD rat model and effectively distinguishes between PD patients and healthy individuals. This highly sensitive and safe PET probe holds promising potential for clinical application in the diagnosis and monitoring of Parkinson's disease.

3.
Front Surg ; 11: 1395013, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39022595

RESUMO

Objective: To evaluate the effect of comfort nursing on postoperative nausea and vomiting in patients with idiopathic scoliosis undergoing posterior correction surgery. Methods: 92 patients with idiopathic scoliosis were taken as the subjects and segmented into a control group and an experimental group (n = 46/each group). The former received routine care, while the latter one performed comfortable care. The observation period is 48 h after surgery. Record and compare the incidence, grade, frequency, and pain level of nausea and vomiting in both groups, as well as postoperative physical signs and symptoms, drug use, and postoperative recovery. Investigating the patient's satisfaction with nursing care. The research data is analyzed using SPSS26.0 software. P < 0.05 means statistical significance. Results: Within 48 h after surgery, the number of nausea and vomiting in the control is 24 and the experimental group is 8, with an incidence rate of 52% and 16%. The latter is significantly lower than that in the control. The average number of nausea and vomiting episodes in the control is 2.5, significantly higher than the 0.45 episodes in the experimental set. There is a significant difference in the frequency of nausea and vomiting/temperature and urine volume/scores of nausea, vomiting, dizziness, headache, decreased appetite, and discomfort between the two groups (P < 0.05). Conclusion: Comfortable care has a relieving effect on postoperative nausea and vomiting in patients with idiopathic scoliosis after posterior correction surgery. It can low down the incidence and frequency of nausea and vomiting, and reduce the score of related symptoms. Comfortable care can also help patients recover after surgery, increase dietary intake, and improve nutritional status. Comfortable care has a significant effect on postoperative nausea and vomiting in cases with idiopathic scoliosis undergoing posterior correction surgery, which can improve their postoperative recovery and quality of life.

4.
RSC Adv ; 14(23): 16218-16227, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38769972

RESUMO

In this study, 24 novel ferulic acid derivatives containing 1,3,4-oxadiazole thioether and trifluoromethyl pyrimidine were designed and synthesized. Bioactivity assay showed that some of the target compounds exhibited moderate to good antifungal activity against Botryosphaeria dothidea BD), Phomopsis sp. (PS), Botrytis cinerea (BC), Fusarium spp. (FS), Fusarium graminearum (FG), and Colletotrichum sp. (CS). Especially, compound 6f demonstrated superior antifungal activity against Phomopsis sp., with an EC50 value of 12.64 µg mL-1, outperforming pyrimethanil (35.16 µg mL-1) and hymexazol (27.01 µg mL-1). Meanwhile, compound 6p showed strong antibacterial activity against X. axonopodis pv. citri (XAC) in vitro, with an inhibition ratio of 85.76%, which was higher than thiodiazole copper's 76.59% at 100 µg mL-1. Furthermore, molecular docking simulations elucidated that compound 6f engaged in hydrogen bonding with the succinate dehydrogenase (SDH) enzyme at SER-17, SER-39, ARG-14 and ARG-43 sites, clarifying its mode of action. This study highlights the potential of these novel ferulic acid derivatives as promising agents for controlling fungal and bacterial threats to plant health. To the best of our knowledge, this study represents the first report on the antifungal and antibacterial properties of ferulic acid derivatives containing 1,3,4-oxadiazole thioether and trifluoromethyl pyrimidine skeleton.

5.
IEEE Trans Med Imaging ; 43(9): 3263-3278, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38640054

RESUMO

This paper presents a novel method based on leveraging physics-informed neural networks for magnetic resonance electrical property tomography (MREPT). MREPT is a noninvasive technique that can retrieve the spatial distribution of electrical properties (EPs) of scanned tissues from measured transmit radiofrequency (RF) in magnetic resonance imaging (MRI) systems. The reconstruction of EP values in MREPT is achieved by solving a partial differential equation derived from Maxwell's equations that lacks a direct solution. Most conventional MREPT methods suffer from artifacts caused by the invalidation of the assumption applied for simplification of the problem and numerical errors caused by numerical differentiation. Existing deep learning-based (DL-based) MREPT methods comprise data-driven methods that need to collect massive datasets for training or model-driven methods that are only validated in trivial cases. Hence we proposed a model-driven method that learns mapping from a measured RF, its spatial gradient and Laplacian to EPs using fully connected networks (FCNNs). The spatial gradient of EP can be computed through the automatic differentiation of FCNNs and the chain rule. FCNNs are optimized using the residual of the central physical equation of convection-reaction MREPT as the loss function ( L) . To alleviate the ill condition of the problem, we added multiconstraints, including the similarity constraint between permittivity and conductivity and the l1 norm of spatial gradients of permittivity and conductivity, to the L . We demonstrate the proposed method with a three-dimensional realistic head model, a digital phantom simulation, and a practical phantom experiment at a 9.4T animal MRI system.


Assuntos
Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Redes Neurais de Computação , Imagens de Fantasmas , Tomografia , Imageamento por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodos , Tomografia/métodos , Animais , Algoritmos
6.
Mol Divers ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687400

RESUMO

In this paper, a series of novel 1,2,4-trizaole-substituted 1,3,4-oxadiazole derivatives with a dual thioether moiety were constructed. The synthetic compounds were characterized by 1H NMR, 13C NMR, HRMS, and single crystal diffraction. The antimicrobial activities of title compounds against fungi (Pyricutaria oryzae Cav., Phomopsis sp., Botryosphaeria dothidea, cucumber Botrytis cinerea, tobacco Botrytis cinerea, blueberry Botrytis cinerea) and bacteria (Xanthomonas oryzae pv. oryzicola, Xoc; Xanthomonas axonopodis pv. citri, Xac) revealed these compounds possessed excellent antibacterial activity through mycelial growth rate method and turbidity method, respectively. Among them, compounds 7a, 7d, 7g, 7k, 7l, and 7n had the antibacterial inhibition rate of 90.68, 97.86, 93.61, 97.70, 97.26, and 92.34%, respectively. The EC50 values of 7a, 7d, 7g, 7k, 7l, and 7n were 58.31, 48.76, 58.50, 40.11, 38.15, and 46.99 µg/mL, separately, superior to that of positive control pesticide thiodiazole copper (104.26 µg/mL). The molecular docking simulation of compound 7l and glutathione s-transferase also confirmed its good activity. The in vivo bioassay toward Xac infected citrus leaves was also performed to evaluate the potential of compounds as efficient antibacterial reagent. Further study of antibacterial mechanism was also carried out, including extracellular polysaccharide production, permeability of bacterial membrane, and scanning electron microscope observations. The excellent antibacterial activities of these compounds provided a strong support for its application for preventing and control plant diseases.

7.
Asia Pac J Clin Nutr ; 33(1): 47-55, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38494687

RESUMO

BACKGROUND AND OBJECTIVES: To assess the vitamin D nutritional status (VDN) of pregnant women in early pregnancy and investigate the effects of periconceptional supplementation with multiple micronutrients (MMs) on this status. METHODS AND STUDY DESIGN: Data were taken from the Pregnancy Health Care System and Hospital Information System in 2018 in Beijing. Vitamin D nutritional status in early pregnancy was evaluated among 4,978 pregnant women, and 4,540 women who took folic acid only (FA) or multiple mi-cronutrients supplements (MM) during the periconceptional period, were include to estimate the associations between periconceptional supplementation with MM and prevalence of vitamin D deficiency or insufficiency with logistic regression model. RESULTS: The mean early-pregnancy vitamin D concentration was 18.6 (±7.5) ng/mL, and the rates of deficiency and insufficiency were 31.6% and 60.5%, respectively. Compared to the FA group, the adjusted odds ratio (aOR, 95%confidence interval, CI) for insufficiency or deficiency of the MM group were 0.25(0.18-0.34), and the aOR (95%CI) for deficiency of the MM group were 0.17 (0.12-0.23). Women who took MMs for a longer period of time, at higher frequencies, and with higher compliance scores had lower rates of deficiency and insufficiency. In winter, spring, and autumn, taking MMs could reduce deficiency by about 70%; in summer, there was little effect. CONCLUSIONS: Among women in Beijing, serum concentrations of vitamin D in early pregnancy are relatively low, and the rates of deficiency and insufficiency are high. Taking MMs during the periconceptional period could improve this situation.


Assuntos
Estado Nutricional , Vitamina D , Gravidez , Feminino , Humanos , Vitaminas , Ácido Fólico , Suplementos Nutricionais
8.
Prostaglandins Other Lipid Mediat ; 172: 106832, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38460759

RESUMO

Atherosclerosis (AS) represents a prevalent initiating factor for cardiovascular events. Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) is an oncofetal RNA-binding protein that participates in cardiovascular diseases. This work aimed to elaborate the effects of IGF2BP3 on AS and the probable mechanism by using an oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) model. Results indicated that IGF2BP3 expression was declined in the blood of AS patients and ox-LDL-induced HUVECs. IGF2BP3 elevation alleviated ox-LDL-provoked viability loss, apoptosis, oxidative DNA damage and endothelial dysfunction in HUVECs. Moreover, IGF2BP3 bound SESN1 and stabilized SESN1 mRNA. Furthermore, SESN1 interference reversed the impacts of IGF2BP3 overexpression on the apoptosis, oxidative DNA damage and endothelial dysfunction of ox-LDL-challenged HUVECs. Additionally, the activation of Nrf2 signaling mediated by IGF2BP3 up-regulation in ox-LDL-treated HUVECs was blocked by SESN1 absence. Collectively, SESN1 stabilized by IGF2BP3 might protect against AS by activating Nrf2 signaling.


Assuntos
Células Endoteliais da Veia Umbilical Humana , Lipoproteínas LDL , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , RNA Mensageiro , Proteínas de Ligação a RNA , Transdução de Sinais , Humanos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Lipoproteínas LDL/farmacologia , Lipoproteínas LDL/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Apoptose/efeitos dos fármacos , Aterosclerose/metabolismo , Aterosclerose/genética , Aterosclerose/patologia , Estabilidade de RNA/efeitos dos fármacos , Dano ao DNA , Sestrinas
9.
Bioorg Med Chem Lett ; 102: 129678, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38408514

RESUMO

The dopamine transporter (DAT) is closely related to a variety of neurological disorders including Parkinson's disease (PD) and other neurodegenerative diseases. In vivo imaging of DAT with radio-labelled tracers has become a powerful technique in related disorders. The radioiodine-labelled tropane derivative [123I]FP-CIT ([123I]1a) is widely used in clinical single photon emission computed tomography (SPECT) imaging as a DAT imaging agent. To develop more metabolically stable DAT radioligands for accurate imaging, this work compared two novel deuterated tropane derivatives ([131I]1c-d) with non-deuterated tropane derivatives ([131I]1a-b). [131I]1a-d were obtained in high radiochemical purity (RCP) above 99 % with molar activities of 7.0-10.0 GBq/µmol. The [131I]1a and [131I]1c exhibited relatively higher affinity to DAT (Ki: 2.0-3.12 nM) than [131I]1b and [131I]1d. Biodistribution results showed that [131I]1c consistently exhibited a higher ratio of the target to non-target (striatum/cerebellum) than [131I]1a. Furthermore, metabolism studies indicated that the in vivo metabolic stability of [131I]1c was superior to that of [131I]1a. Ex vivo autoradiography showed that [131I]1c selectively localized on DAT-rich striatal regions and the specific signal could be blocked by DAT inhibitor. These results indicated that [131I]1c might be a potential probe for DAT SPECT imaging in the brain.


Assuntos
Proteínas da Membrana Plasmática de Transporte de Dopamina , Radioisótopos do Iodo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Radioisótopos do Iodo/metabolismo , Distribuição Tecidual , Tropanos , Tomografia Computadorizada de Emissão de Fóton Único/métodos
11.
Metallomics ; 16(2)2024 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-38285613

RESUMO

The essential metal manganese (Mn) induces neuromotor disease at elevated levels. The manganese efflux transporter SLC30A10 regulates brain Mn levels. Homozygous loss-of-function mutations in SLC30A10 induce hereditary Mn neurotoxicity in humans. Our prior characterization of Slc30a10 knockout mice recapitulated the high brain Mn levels and neuromotor deficits reported in humans. But, mechanisms of Mn-induced motor deficits due to SLC30A10 mutations or elevated Mn exposure are unclear. To gain insights into this issue, we characterized changes in gene expression in the basal ganglia, the main brain region targeted by Mn, of Slc30a10 knockout mice using unbiased transcriptomics. Compared with littermates, >1000 genes were upregulated or downregulated in the basal ganglia sub-regions (i.e. caudate putamen, globus pallidus, and substantia nigra) of the knockouts. Pathway analyses revealed notable changes in genes regulating synaptic transmission and neurotransmitter function in the knockouts that may contribute to the motor phenotype. Expression changes in the knockouts were essentially normalized by a reduced Mn chow, establishing that changes were Mn dependent. Upstream regulator analyses identified hypoxia-inducible factor (HIF) signaling, which we recently characterized to be a primary cellular response to elevated Mn, as a critical mediator of the transcriptomic changes in the basal ganglia of the knockout mice. HIF activation was also evident in the liver of the knockout mice. These results: (i) enhance understanding of the pathobiology of Mn-induced motor disease; (ii) identify specific target genes/pathways for future mechanistic analyses; and (iii) independently corroborate the importance of the HIF pathway in Mn homeostasis and toxicity.


Assuntos
Proteínas de Transporte de Cátions , Manganês , Humanos , Animais , Camundongos , Manganês/metabolismo , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Transmissão Sináptica/genética , Camundongos Knockout , Hipóxia
12.
ACS Omega ; 9(1): 1424-1435, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38222640

RESUMO

In recent years, the severity of plant diseases caused by plant pathogenic fungi and viruses has been on the rise. However, there is a limited availability of pesticide chemicals in the market for effectively controlling both fungal and viral infections. To solve this problem, a series of novel pyrimidine derivatives containing a 1,3,4-oxadiazole thioether fragment were synthesized. Among them, compound 6s exhibited remarkable in vivo protection activity against tobacco mosaic virus, demonstrating the superior 50% effective concentration (EC50) value of 0.42 µM, outperforming ningnanmycin (0.60 µM). Meanwhile, compound 6s exhibited remarkable antifungal activity against Botrytis cinerea Pers. in postharvest blueberry in vitro, with an EC50 value of 0.011 µM, surpassing the inhibition rate of Pyrimethanil (0.262 µM). Additionally, compound 6s also demonstrated remarkable curative and protection activities against blueberry fruit gray mold in vivo, with control efficiencies of 54.2 and 60.4% at 200 µg/mL concentration, respectively, which were comparable to those of Pyrimethanil (49.3 and 63.9%, respectively). Scanning electron microscopy showed that the compound 6s-treated hyphae of B. cinerea Pers. in postharvest blueberry became abnormally collapsed and shriveled. Furthermore, the molecular docking simulation demonstrated that compound 6s formed hydrogen bonds with SER-17, ARG-43, and SER-39 of succinate dehydrogenase (SDH), providing a possible explanation for the mechanism of action between the target compounds and SDH. This study represents the first report on the antiviral and antifungal activities of novel pyrimidine derivatives containing a 1,3,4-oxadiazole thioether fragment.

13.
J Org Chem ; 88(17): 12658-12667, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37595016

RESUMO

A photocatalytic synthesis of difluoromethylated selenides from selenosulfonates is described here. Bench-stable difluoromethyl phosphonium salt [Ph3PCF2H]Br reacts smoothly with selenosulfonates to give a series of functionalized difluoromethylated selenides in moderate to good yields via a radical process. This protocol is free of a stoichiometric base and reductant, has tolerance of functional groups, and has successful late-stage modification of bioactive molecules, which provides facile access to molecules of pharmaceutical relevance.

14.
Aging (Albany NY) ; 15(11): 5052-5065, 2023 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-37294547

RESUMO

BACKGROUND: Atherosclerosis (AS) is a disease characterized by the disorder of lipid metabolism and the formation of atherosclerotic plaques in the arterial wall, leading to arterial stenosis. Sestrins 1 (SESN1) plays an important regulatory role in AS, but the specific regulatory mechanism is still unclear. METHODS: ApoE-/- mouse models of AS were constructed. After overexpressing SESN1, oil red O staining was used to detect the degree of aortic plaque. HE staining detected the endothelial damage of the surrounding tissues. ELISA was used to detect the levels of vascular inflammation and oxidative stress. The iron metabolism in vascular tissues was detected by immunofluorescence. The expressions of SESN1 and ferroptosis-related proteins were detected by western blot. In the oxidized low-density lipoprotein (ox-LDL)-induced injury model in human umbilical vein endothelial cells (HUVECs), CCK8, ELISA, immunofluorescence and western blot were respectively used to detect cell viability, inflammatory response, oxidative stress and ferroptosis. The regulatory mechanism of SESN1 on endothelial ferroptosis in AS was further explored following the addition of P21 inhibitor UC2288. RESULTS: Overexpression of SESN1 could inhibit the extent of the plaque and reduce the endothelial injury of plaque tissues in AS mice. In both mouse and cell models of AS, SESN1 overexpression inhibited inflammatory response, oxidative stress response, and endothelial ferroptosis. The inhibitory effect of SESN1 on endothelial ferroptosis might be achieved through activation of P21. CONCLUSION: SESN1 overexpression plays an inhibitory role in vascular endothelial ferroptosis through the activation of P21 in AS.


Assuntos
Aterosclerose , Ferroptose , Placa Aterosclerótica , Humanos , Animais , Camundongos , Sestrinas/metabolismo , Aterosclerose/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Placa Aterosclerótica/metabolismo , Estresse Oxidativo , Apoptose
15.
Nucl Med Biol ; 118-119: 108334, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37028197

RESUMO

INTRODUCTION: The dopamine transporter (DAT) is vitally correlated with Parkinson's disease (PD) and other neurodegenerative diseases. Non-invasive imaging of DAT contributes to early diagnosis and monitoring of related diseases. Recently, we reported a deuterated [18F]fluoroethyl tropane analogue [18F]FECNT-d4 as a potential DAT PET imaging agent. The objective of this work was to extend the investigation by comparing four deuterated [18F]fluoroethyl tropane derivatives ([18F]2a-d) to develop metabolically stable DAT radioligands. METHODS: Four fluoroethyl substituted phenyl-tropane compounds 1a-d and deuterated compounds 2a-d were synthesized and their IC50 values to DAT were evaluated. The [18F]fluoroethyl ligands [18F]1a-d and [18F]2a-d were obtained from corresponding labeling precursors by one-step radio-labeling reactions and investigated in terms of lipophilicity and in vitro binding affinity studies. [18F]1d and [18F]2d were then selected for further evaluations by in vivo metabolism study, biodistribution, ex vivo autoradiography, and microPET imaging studies. RESULTS: [18F]1a-d and [18F]2a-d were obtained in radiochemical yield of 11-32 % with molar activities of 28-54 GBq/µmol. The 1d and 2d exhibited relatively high affinity to DAT (IC50: 1.9-2.1 nM). Ex vivo autoradiography and microPET studies showed that [18F]2d selectively localized on DAT-rich striatal regions and the specific signal could be blocked by DAT inhibitor. Biodistribution results showed that [18F]2d consistently exhibited a higher ratio of the target to non-target (striatum/cerebellum) than [18F]1d. Furthermore, metabolism study indicated that the in vivo metabolic stability of [18F]2d was superior to that of [18F]1d. CONCLUSION: Our findings suggested that the deuterated compound [18F]2d might be a potential probe for DAT PET imaging in the brain.


Assuntos
Proteínas da Membrana Plasmática de Transporte de Dopamina , Tropanos , Encéfalo/metabolismo , Diagnóstico por Imagem , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Ligantes , Distribuição Tecidual , Tropanos/química , Tropanos/farmacologia , Masculino , Animais , Ratos , Ratos Sprague-Dawley
17.
Birth Defects Res ; 115(5): 545-554, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36595654

RESUMO

BACKGROUND: This study aimed to explore the relationship between maternal periconceptional supplementation with folic acid only (FAO) or with multiple micronutrients containing folic acid (MMFA) and non-syndromic cleft lip/palate in offspring. METHOD: The data came from a prenatal health care system and a birth defects surveillance system in Beijing, China, from 2013 to 2018. Information on maternal FAO/MMFA supplementation was collected by questionnaire in the first trimester, and data on cleft lip/palate were collected at delivery or termination of pregnancy. Inverse probability weighting (IPW) by the propensity score to adjust for the confounders and Poisson regression model was used to estimate risk ratios (RRs) and their 95% confidence intervals (CIs). RESULTS: A total of 63,969 participants were included in the study. Compared to the no-supplementation group, the adjusted RR for the supplementation group was 0.51 (95% CI: 0.40, 0.64). And the adjusted RRs for FAO and MMFA compared to the no-supplementation group were 0.56 (95% CI: 0.40, 0.76) and 0.48 (95% CI: 0.35, 0.65), respectively. Compared to supplement FAO and MMFA with less than 8 days out of 10 days, the adjusted RRs for FAO and MMFA with 8 or more days out of 10 days were 1.17 (95% CI: 0.78, 1.75), and 2.05 (95% CI: 1.37, 3.31), respectively. CONCLUSION: Maternal supplementation with micronutrients, either FAO or MMFA, during the periconceptional period can reduce the risk for non-syndromic cleft lip/palate in offspring. However, women should be more cautious with MMFA supplementation.


Assuntos
Fenda Labial , Fissura Palatina , Anormalidades da Boca , Gravidez , Humanos , Feminino , Fenda Labial/epidemiologia , Fissura Palatina/epidemiologia , Fatores de Risco , Ácido Fólico , Micronutrientes
18.
IEEE Trans Cybern ; 53(4): 2558-2571, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34851846

RESUMO

Block compressive sensing (CS) is a well-known signal acquisition and reconstruction paradigm with widespread application prospects in science, engineering, and cybernetic systems. However, state-of-the-art block-based image CS (BCS) methods generally suffer from two issues. The sparsifying domain and the sensing matrices widely used for image acquisition are not data driven and, thus, both the features of the image and the relationships among subblock images are ignored. Moreover, it requires to address a high-dimensional optimization problem with extensive computational complexity for image reconstruction. In this article, we provide a deep learning (DL) strategy for BCS, called AutoBCS, which automatically takes the prior knowledge of images into account in the acquisition step and establishes a reconstruction model for performing fast image reconstruction. More precisely, we present a learning-based sensing matrix to accomplish image acquisition, thereby capturing and preserving more image characteristics than those captured by the existing methods. In addition, we build a noniterative reconstruction network, which provides an end-to-end BCS reconstruction framework to maximize image reconstruction efficiency. Furthermore, we investigate comprehensive comparison studies with both traditional BCS approaches and newly developed DL methods. Compared with these approaches, our proposed AutoBCS can not only provide superior performance in terms of image quality metrics (SSIM and PSNR) and visual perception but also automatically benefit reconstruction speed.

19.
Rev Sci Instrum ; 93(11): 114711, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36461547

RESUMO

In this study, the authors report the design and fabrication of a small mixed-integrated balun for magnetic resonance imaging (MRI). The device was designed by using the positive anti-symmetric coupling method, which applies the lump surface-mount technology capacitors as well as mirror-symmetric coupling strips that were etched on the top and bottom layers of a printed circuit board. The capacitors reduced the length of the coupling strips and compensated for imbalances in the phase and gain due to errors in the fabrication process. The structure and equivalent even-odd circuit model of the device was modeled and examined using commercial software to optimize the design parameters. Following this, the device was fabricated and its performance was assessed through measurements using a network analyzer. The results showed that imbalances in the gain and phase were lower than 0.1 dB and 1°, respectively, and the insertion loss and the input voltage standing-wave ratio (VSWR) were lower than 0.4 dB and -25 dB, respectively. More importantly, the device was small, with dimensions of 50 × 60 × 1.5 mm. This makes it suitable for MRI applications involving highly integrated miniaturized systems. The proposed device was integrated into a 3.0 T radio-frequency power amplifier (RFPA) and reduced the dimensions of its power modules by 20% compared with the traditional balun. Finally, the RFPA module was used in an 3.0T MRI system for imaging experiments, and the results showed that the balun can help obtain high-quality scanning images.


Assuntos
Amplificadores Eletrônicos , Imageamento por Ressonância Magnética , Software
20.
Forensic Sci Int ; 341: 111501, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36274344

RESUMO

Identifying new psychoactive substances (NPSs) and their metabolites is essential for regulating such substances for purposes of law enforcement and forensics. NPSs can be regulated on the basis of their chemical structures before they become a critical threat to society. Further, NPS metabolites can be targeted for analysis in urine, blood, and hair. This case study reports an incident in which 10 bags with approximately 15 g of crystalline material were seized from suspects by law enforcement officers and sent to the laboratory for confirmation. Gas chromatography-mass spectrometry, liquid chromatography-high-resolution mass spectrometry, and nuclear magnetic resonance (NMR) were employed to analyze these materials. The analyses revealed that the materials were a new ketamine analog, 2-fluorodeschloro-N-ethyl-ketamine (2-FDCNEK). Single-crystal X-ray diffraction (SXRD) analysis was also employed to confirm this result. In addition, metabolites of 2-FDCNEK were investigated using a fungal model and a urine sample from an abuser. The results suggest that 2-FDCNEK and 2-fluorodeschoro-norketamine are optimal metabolites for biological samples. This report presents the mass fragmentation, NMR analysis, and SXRD data of 2-FDCNEK. In addition, it provides suggestions regarding metabolites of 2-FDCNEK for law enforcement and forensic purposes, thereby facilitating the detection of this new ketamine analog.


Assuntos
Ketamina , Ketamina/análise , Cromatografia Líquida , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Massas , Cabelo/química , Detecção do Abuso de Substâncias/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA