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1.
ChemSusChem ; : e202400512, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38878218

RESUMO

Massive accumulation of postconsumer plastic waste in eco-system has raised growing environmental concerns. Sustainable end-of-life managements of the indispensable plastic are highly demanding and challenging in modern society. To relieve the plastic menace, herein we present a full life cycle sustainable supramolecular bioplastic made from biomass-derived polyelectrolyte (chitosan quaternary ammonium salt, QCS) and natural sodium fatty acid (sodium laurate, SL) through solid-phase molecular self-assembly (SPMSA), by which the QCS-SL complexes, precipitated from mixing the aqueous solutions, self-assemble to form bioplastic film by mildly pressing at room temperature. The QCS-SL bioplastic films display superior hydroplasticity owing to the water-activated molecular rearrangement and electrostatic bond reconstruction, which allows facile self-healing and reprocessing at room temperature to significantly extend the service lifetime of both products and raw materials. With higher water content, the dynamic electrostatic interactions and precipitation-dissolution equilibrium endow the QCS-SL bioplastic films with considerable solubility in water, which is promising to mitigate the plastic accumulation in aquatic environment. Because both QCS and SL are biocompatible and biodegradable, the dissolved QCS-SL films are nontoxic and environmentally friendly. Thus, this novel supramolecular bioplastic is highly sustainable throughout the whole life cycle, which is expected to open a new vista in sustainable plastic materials.

2.
ACS Chem Neurosci ; 15(11): 2112-2120, 2024 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-38776461

RESUMO

Neuroinflammation plays an important role in Alzheimer's disease and primary tauopathies. The aim of the current study was to map [18F]GSK1482160 for imaging of purinergic P2X7R in Alzheimer's disease and primary tauopathy mouse models. Small animal PET was performed using [18F]GSK1482160 in widely used mouse models of Alzheimer's disease (APP/PS1, 5×FAD, and 3×Tg), 4-repeat tauopathy (rTg4510) mice, and age-matched wild-type mice. Increased uptake of [18F]GSK1482160 was observed in the brains of 7-month-old rTg4510 mice compared to wild-type mice and compared to 3-month-old rTg4510 mice. A positive correlation between hippocampal tau [18F]APN-1607 and [18F]GSK1482160 uptake was found in rTg4510 mice. No significant differences in the uptake of [18F]GSK1482160 was observed for APP/PS1 mice, 5×FAD mice, or 3×Tg mice. Immunofluorescence staining further indicated the distribution of P2X7Rs in the brains of 7-month-old rTg4510 mice with accumulation of tau inclusion. These findings provide in vivo imaging evidence for an increased level of P2X7R in the brains of tauopathy mice.


Assuntos
Modelos Animais de Doenças , Camundongos Transgênicos , Tomografia por Emissão de Pósitrons , Receptores Purinérgicos P2X7 , Tauopatias , Animais , Tauopatias/diagnóstico por imagem , Tauopatias/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Camundongos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/diagnóstico por imagem , Radioisótopos de Flúor , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Proteínas tau/metabolismo
3.
ACS Omega ; 9(15): 17423-17431, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38645324

RESUMO

As recurrent and metastatic nasopharyngeal carcinoma (NPC) is the most common cause of death among patients with NPC, there is an urgent clinical need for the development of precision diagnosis to guide personalized treatment. Recent emerging evidence substantiates the increased expression of transferrin receptor 1 (also known as cluster of differentiation 71, CD71) within tumor tissues and the inherent targeting capability of natural heavy-chain ferritin (HFn) toward CD71. This study aimed to synthesize and assess a radiotracer ([64Cu]Cu-NOTA-HFn) designed to target CD71 for positron emission tomography (PET) imaging in an NPC tumor-bearing mouse model. The entire radiolabeling process of [64Cu]Cu-NOTA-HFn was completed within 15 min with high yield (>98.5%) and high molar activity (72.96 ± 21.33 GBq/µmol). The in vitro solubility and stability experiments indicated that [64Cu]Cu-NOTA-HFn had a high water solubility (log P = -2.42 ± 0.52, n = 6) and good stability in phosphate-buffered saline (PBS) for up to 48 h. The cell saturation binding assay indicated that [64Cu]Cu-NOTA-HFn had a nanomolar affinity (Kd = 10.9 ± 6.1 nM) for CD71-overexpressing C666-1 cells. To test the target engagement in vivo, prolonged-time PET imaging was performed at 1, 6, 12, 24, and 36 h postinjection (p.i.) of [64Cu]Cu-NOTA-HFn to C666-1 NPC tumor-bearing mice. The C666-1 tumors could be visualized by [64Cu]Cu-NOTA-HFn and blocked by nonradiolabeled HFn. PET imaging quantitative analysis demonstrated that the uptake of [64Cu]Cu-NOTA-HFn in C666-1 tumors peaked at 6 h p.i. and the best radioactive tumor-to-muscle ratio was 10.53 ± 3.11 (n = 3). Ex vivo biodistribution assay at 6 h p.i. showed that the tumor uptakes were 1.43 ± 0.23%ID/g in the nonblock group and 0.92 ± 0.2%ID/g in the block group (n = 3, p < 0.05). Immunohistochemistry and immunofluorescence staining confirmed positive expression of CD71 and the uptake of HFn in C666-1 tumor tissues. In conclusion, our experiments demonstrated that [64Cu]Cu-NOTA-HFn possesses a very high target engagement for CD71-positive NPC tumors and provided a fundamental basis for further clinical translation.

4.
J Colloid Interface Sci ; 659: 439-448, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38183810

RESUMO

In this study, a Co3O4 catalyst is synthesised using the chitosan-assisted sol-gel method, which simultaneously regulates the grain size, Co valence and surface acidity of the catalyst through a chitosan functional group. The complexation of the free -NH2 complex inhibits particle agglomeration; thus, the average particle size of the catalyst decreases from 82 to 31 nm. Concurrently, Raman spectroscopy, hydrogen temperature-programmed reduction, electron paramagnetic resonance spectroscopy and X-ray photoelectron spectroscopy experiments demonstrate that doping with chitosan N sources effectively modulates Co2+ to promote the formation of oxygen vacancies. In addition, water washing after catalyst preparation can considerably improve the low-temperature (below 250 °C) activity of the catalyst and eliminate the side effects of alkali metal on catalyst activity. Moreover, the presence of Brønsted and Lewis acid sites promotes the adsorption of C8H8. Consequently, CS/Co3O4-W presents the highest catalytic oxidation activity for C8H8 at low temperatures (R250 °C = 8.33 µmol g-1 s-1, WHSV = 120,000 mL hr-1∙g-1). In situ DRIFTS and 18O2 isotope experiments demonstrate that the oxidation of the C8H8 reaction is primarily dominated by the Mars-van Krevelen mechanism. Furthermore, CS/Co3O4-W exhibits superior water resistance (1- and 2- vol% H2O), which has the potential to be implemented in industrial applications.

5.
Eur J Nucl Med Mol Imaging ; 50(12): 3589-3601, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37466648

RESUMO

PURPOSE: Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial spine; however, the quantitative detection of inflammation in AS remains a challenge in clinical settings. We aimed to investigate the feasibility of using a specific P2X7R-targeting 18F-labeled tracer [18F]GSK1482160 for positron emission tomography (PET) imaging and the quantification of AS. METHODS: The radioligand [18F]GSK1482160 was obtained based on nucleophilic aliphatic substitution. Dynamic [18F]GSK1482160 and [18F]FDG micro-PET/CT imaging were performed on AS mice (n = 8) and age-matched controls (n = 8). Tracer kinetics modeling was performed using Logan's graphical arterial input function analysis to quantify the in vivo expression of P2X7R. The post-PET tissues were collected for hematoxylin-eosin (H&E), immunohistochemical (IHC), and immunofluorescence (IF) staining. RESULTS: [18F]GSK1482160 PET/CT imaging revealed that the specific binding in the ankle joint and sacroiliac joint (SIJ) of the AS at 8 weeks group (BPNDankle-AS-8W (non-displaceable binding potential of the ankle) 3.931 ± 0.74; BPND SIJ-AS-8W (BPBD of the SIJ) 4.225 ± 0.84) were significantly higher than the controls at 8 weeks group (BPNDankle-Ctr-8W 0.325 ± 0.15, BPNDSJJ-Ctr-8W 0.319 ± 0.17) respectively, and the AS at 14 weeks group (BPNDankle-AS-14W 12.212 ± 2.25; BPNDSJJ-AS-14W 13.389 ± 3.60) were significantly higher than the controls at 14 weeks group (BPNDankle-Ctr-14W 0.204 ± 0.16, BPNDSJJ-Ctr-14W 0.655 ± 0.35) respectively. The four groups had no significant difference in the [18F]FDG uptake of ankle and SIJ. IHC and IF staining revealed that the overexpression of P2X7R was colocalized with activated macrophages from the ankle synovium and spinal endplate in mice with AS, indicating that quantification of P2X7R may contribute to the understanding of the pathogenesis of inflammation in human AS. CONCLUSION: This study developed a novel P2X7R-targeting PET tracer [18F]GSK1482160 to detect the expression of P2X7R in AS mouse models and provided powerful non-invasive PET imaging and quantification for AS.

6.
J Appl Physiol (1985) ; 135(2): 251-259, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37318984

RESUMO

Space travel causes rapid weight loss of astronauts, but the underlying reasons are still obscure. Brown adipose tissue (BAT) is a well-known thermogenesis tissue that is innervated by sympathetic nerves, and norepinephrine stimulation can promote the thermogenesis and angiogenesis of BAT. Herein, the structural and physiological changes of BAT as well as serological indicators were investigated in mice under hindlimb unloading (HU) to simulate a weightless environment in space. The results showed that long-term HU could induced the thermogenic activation of BAT by upregulating the mitochondrial uncoupling protein. Further, peptide-conjugated indocyanine green was developed to target the vascular endothelial cells of BAT. Noninvasive fluorescence-photoacoustic imaging presented the neovascularization of BAT on the micron scale in the HU group, accompanying by the increase of vessel density. Downward trend of serum triglyceride and glucose level of mice treated with HU proved the more heat production and energy consumption in BAT compared with the control group. This study suggested that HU may be an effective strategy to curb the occurrence of obesity, whereas fluorescence-photoacoustic dual-modal imaging showed capability of assessing BAT activity.NEW & NOTEWORTHY We found that the mechanism of weight loss of astronauts in space flight may be that hindlimb unloading (HU) promotes the activation of brown adipose tissue (BAT) and the increase of uncoupling protein (UCP1) expression, which accelerates the body's heat production. Meanwhile, the activation of BAT is accompanied by the proliferation of blood vessels. With the help of peptide CPATAERPC conjugated indocyanine green targeting to vascular endothelial cells, fluorescence-photoacoustic imaging has selectively tracked the vascular structure of BAT on the micron scale, which provided noninvasive imaging tools to in situ measure the changes of BAT.


Assuntos
Tecido Adiposo Marrom , Células Endoteliais , Camundongos , Animais , Tecido Adiposo Marrom/metabolismo , Células Endoteliais/metabolismo , Elevação dos Membros Posteriores , Verde de Indocianina , Redução de Peso , Termogênese/fisiologia , Proteína Desacopladora 1/metabolismo , Camundongos Endogâmicos C57BL
7.
ACS Chem Neurosci ; 14(11): 2183-2192, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37134001

RESUMO

In the past decades, translocator protein (TSPO) has been considered as an in vivo biomarker to measure the presence of neuroinflammatory reactions. In this study, expression of TSPO was quantified via [18F]DPA-714 positron emission tomography-magnetic resonance imaging (PET-MRI) to investigate the effects of microglial activation associated with motor behavioral impairments in the 6-hydroxydopamine (6-OHDA)-treated rodent model of Parkinson's disease (PD). [18F]FDG PET-MRI (for non-specific inflammation), [18F]D6-FP-(+)-DTBZ PET-MRI (for damaged dopaminergic (DA) neurons), post-PET immunofluorescence, and Pearson's correlation analyses were also performed. The time course of striatal [18F]DPA-714 binding ratio was elevated in 6-OHDA-treated rats during 1-3 weeks post-treatments, with peak TSPO binding in the 1st week. No difference between the bilateral striatum in [18F]FDG PET imaging were found. Moreover, an obvious correlation between [18F]DPA-714 SUVRR/L and rotation numbers was found (r = 0.434, *p = 0.049). No correlation between [18F]FDG SUVRR/L and rotation behavior was found. [18F]DPA-714 appeared to be a potential PET tracer for imaging the microglia-mediated neuroinflammation in the early stage of PD.


Assuntos
Microglia , Doença de Parkinson , Animais , Ratos , Proteínas de Transporte/metabolismo , Modelos Animais de Doenças , Radioisótopos de Flúor/metabolismo , Fluordesoxiglucose F18/metabolismo , Imageamento por Ressonância Magnética , Microglia/metabolismo , Oxidopamina/toxicidade , Doença de Parkinson/metabolismo , Tomografia por Emissão de Pósitrons/métodos
8.
Appl Spectrosc ; 77(6): 652-665, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37218159

RESUMO

Amorphous simvastatin (amorphous SIM) and Form I of SIM were prepared separately from SIM acetone (AC)/ethyl acetate (ETAC)/ethanol (ET) solutions by simply controlling the solvent evaporation rate, and the kinetic formation of amorphous SIM from SIM AC/ETAC/ET solutions was explained using mid-frequency Raman difference spectra analysis. The mid-frequency Raman difference spectra analysis results indicate that the amorphous phase has close connections with solutions and might be the bridge, playing an important role in the intermediate phase, between solutions and their outcome polymorphs.


Assuntos
Sinvastatina , Sinvastatina/química , Cristalização , Difração de Raios X
9.
Diagn Interv Radiol ; 29(3): 548-554, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-37154799

RESUMO

PURPOSE: To investigate the feasibility and usefulness of 2-deoxy-2-(18F)-fluoro-D-glucose positron emission tomography/computed tomography [(18F)-FDG PET/CT] as a novel examination in the surveillance of abnormal myocardial energy metabolism and cardiac dysfunction after cardiopulmonary resuscitation (CPR). METHODS: Thirteen male Sprague-Dawley rats were randomly divided into a sham group (n = 4), CPR group (n = 4), and trimetazidine (TMZ) + CPR group (n = 5). The expression levels of the myocardial injury marker cardiac troponin I (CTNI) in serum were tested at 6 hours after CPR or TMZ + CPR. The ejection fraction and fraction shortening were evaluated by echocardiography. (18F)-FDG PET/CT was used to measure the FDG uptake and the standardized uptake value (SUV) after CPR or TMZ + CPR for 6 hours. The intermediary carbohydrate metabolites of glycolysis including phosphoenolpyruvate, 3-phospho-D-glycerate, and the lactate/pyruvate ratio were detected through the multiple reaction monitoring approach. Simultaneously, the authors also tested the expression levels of the total adenosine triphosphate (ATP) and the key intermediate products of glucose ovidation as alpha ketoglutarate, citrate, and succinate in the myocardium. RESULTS: The authors found that the aerobic oxidation of glucose was reduced, and the anaerobic glycolysis was significantly enhanced in the myocardium in the early stage of CPR. Meanwhile, the myocardial injury marker CTNI was upregulated considerably (P = 0.014, P = 0.021), and the left ventricular function of the animal heart also markedly deteriorated with the downregulation of ATP after CPR. In contrast, myocardial injury and cardiac function were greatly improved with the increase of ATP in the CPR + TMZ group. In addition, aerobic glucose oxidation metabolites were significantly increased (P < 0.05) and anaerobic glycolysis metabolites were significantly decreased (P < 0.05) after CPR in the myocardium. Surprisingly, (18F)-FDG PET/CT could track the above changes by detecting the FDG uptake value and the SUV. CONCLUSION: Glucose metabolism is an essential factor for myocardial self-repair after CPR. (18F) FDG PET/CT, as a non-invasive technology, can monitor myocardial energy metabolism and cardiac function by tracking changes in glucose metabolism after CPR.


Assuntos
Reanimação Cardiopulmonar , Cardiopatias , Ratos , Masculino , Animais , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Glucose/metabolismo , Fluordesoxiglucose F18 , Ratos Sprague-Dawley , Miocárdio/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Cardiopatias/metabolismo , Metabolismo Energético , Trifosfato de Adenosina/metabolismo , Compostos Radiofarmacêuticos/metabolismo
11.
Small ; 19(30): e2300688, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37029578

RESUMO

The creation of anisotropic nanostructures with precise size control is desirable for new properties and functions, but it is challenging for ionic self-assembly (ISA) because of the non-directional electrostatic interactions. Herein, the formation of size-controllable tetragonal nanoprisms is reported via crystallization-directed ionic self-assembly (CDISA) through evaporating a micellar solution on solid substrates. First, ISA is designed with a crystalline polyethylene oxide (PEO) containing cationic polymer poly(2-(2-guanidinoethoxy)ethyl methacrylate)-b-poly(ethyleneoxide)-b-poly(2-(2-guanidinoethoxy)-ethylmethacrylate) (PGn -PEO230 -PGn ) and an anionic 5,10,15,20-Tetrakis(4-sulfonatophenyl) porphyrin (TPPS) to form micelles in aqueous solution. The PG segments binds excessive TPPS with amplenet chargeto form hydrophilic corona, while the PEO segments are unprecedentedly dehydrated and tightly packed into cores. Upon naturally drying the micellar solution on a silicon wafer, PEO crystallizationdirects the micelles to aggregate into square nanoplates, which are further connected to nanoprisms. Length and width of the nanoprisms can be facilely tuned by varying the initial concentration. In this hierarchical process, the aqueous self-assembly is prerequisite and the water evaporation rate is crucial for the formation of nanostructures, which provides multiple factors for morphology regulating. Such precise size-control strategy is highly expected to provide a new vision for the design of advanced materials with size controllable anisotropic nanostructures.

12.
Adv Mater ; 35(8): e2207688, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36373548

RESUMO

Supramolecular materials with room-temperature healability and recyclability are highly desired because they can extend materials lifetimes and reduce resources consumption. Most approaches toward healing and recycling rely on the dynamically reversible supramolecular interactions, such as hydrogen, ionic and coordinate bonds, which are hygroscopic and vulnerable to water. The general water-induced plasticization facilitates the healing and reprocessing process but cause a troubling problem of random self-adhesion. To address this issue, here it is reported that by modifying the hygroscopic surfaces with hydrophobic alkyl chains of dodecyltrimethoxysilane (DTMS), supramolecular plastic films based on commercial raw materials of sodium alginate (SA) and cetyltrimethylammonium bromide (CTAB) display extraordinary damage-specific healability. Owing to the hydrophobic surfaces, random self-adhesion is eliminated even under humid environment. When damage occurs, the fresh surfaces with ionic groups and hydroxyl groups expose exclusively at the damaged site. Thus, damage-specific healing can be readily facilitated by water-induced plasticization. Moreover, the films display excellent room-temperature recyclability. After multiple times of reprocessing and re-modifying with DTMS, the rejuvenated films exhibit fatigueless mechanical properties. It is anticipated that this approach to damage-specific healing and room-temperature recycling based on surface hydrophobization can be applied to design various of supramolecular plastic polysaccharides materials for building sustainable societies.

13.
Front Neurosci ; 16: 959174, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389243

RESUMO

Stress in life is ubiquitous and unavoidable. Prolonged exposure to severe stress can lead to physical intolerance and impair cognitive function. Non-human primates are considered to be the best animal model for studying cognitive function, especially memory and attention. The finger maze test, with the advantages of short training time and lower cost, is recommended to evaluate learning and memory in non-human primates. In this study, we modified the finger maze test method to evaluate the cognitive function of single-housed cynomolgus monkeys. The flexibility and attention of cynomolgus monkeys were assessed by performing the complex task test and the stranger intrusion interference test, respectively, which increased the difficulty of obtaining rewards, and the ability of long-term memory was also evaluated by the memory test. Furthermore, the changes in cognitive function of the cynomolgus monkeys were tested by using the finger maze test after audio-visual stimulation, and the changes in the cortisol levels during stimulation were also analyzed. We found that, after completing the learning test, there was no significant decrease in their success rate when monkeys processed multitasks at the same time. In the stranger intrusion interference test, all subjects were distracted, but the accuracy did not decrease. The monkeys completed the memory tests in the 1st and 2nd months after the learning tests, with a high success rate. However, the success rate decreased significantly at the end of the 4th month. During audio-visual stimulation, the plasma cortisol level significantly increased in the first 2 months and was maintained at a high level thereafter. One month after audio-visual stimulation, the accuracy of the memory test was significantly reduced, and the total time of distraction was significantly prolonged. In conclusion, chronic audio-visual stimulation can increase blood cortisol levels and impair cognitive function. The modified finger maze test can evaluate many aspects of cognitive function and assess the changes in the cognitive function of adult cynomolgus monkeys under stress.

14.
ACS Chem Neurosci ; 13(23): 3464-3476, 2022 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-36441909

RESUMO

The P2X7 receptor (P2X7R) is a key neuroinflammation target in a variety of neurodegenerative diseases. Improved radiosynthesis was developed according to the previously reported P2X7R antagonist GSK1482160. Biodistribution, radiometabolite, and dynamic positron emission tomography/computed tomography-magnetic resonance imaging (PET/CT-MRI) of the lipopolysaccharide (LPS) rat model and the transgenic mouse model of Alzheimer's disease (AD) revealed a stable, low uptake of [18F]4A in the brain of healthy rats but a higher standardized uptake value ratio (SUVR) in LPS-treated rats (1.316 ± 0.062, n = 3) than in sham (1.093 ± 0.029, n = 3). There were higher area under curves (AUCs) in the neocortex (25.12 ± 1.11 vs 18.94 ± 1.47), hippocampus (22.50 ± 3.41 vs 15.90 ± 1.59), and basal ganglia (22.26 ± 0.81 vs 15.32 ± 1.76) of AD mice (n = 3) than the controls (n = 3) (p < 0.05). Furthermore, 50 min dynamic PET in healthy nonhuman primates (NHPs) indicated [18F]4A could penetrate the blood-brain barrier (BBB). In conclusion, [18F]4A from this study is a potent P2X7R PET tracer that warrants further neuroinflammation quantification in human studies.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptores Purinérgicos P2X7 , Animais , Camundongos , Ratos , Distribuição Tecidual
15.
Int J Med Sci ; 19(10): 1539-1547, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36185330

RESUMO

Purpose: To early identify abnormal lesions by applying the 18F-FDG PET dynamic modeling approach for discharged patients recovering from COVID-19. Methods: Seven discharged COVID-19 patients (COVID-19 group), twelve healthy volunteers (control group 1), and eight cancer patients with normal pulmonary function (control group 2) were prospectively enrolled. Control group 1 completed static 18F-FDG PET/CT only; COVID-19 group and control group 2 completed 60-min dynamic 18F-FDG PET/CT. Among COVID-19 group and control group 2, the uptake of FDG on the last frame (at 55-60 min) of dynamic scans was used for static analysis. Prior to performing scans, COVID-19 patients provided negative real-time Reverse Transcription-Polymerase Chain Reaction (rRT-PCR) of SARS-CoV-2, normal lung functions test, and normal laboratory test. Organ-to-liver standard uptake ratio (OLR, i.e. SUVmax evaluated organ/ SUVmax liver) from conventional static data and Patlak analysis based on the dynamic modeling to calculate the 18F-FDG net uptake rate constant (Ki) were performed. Results: Compared to the control groups, COVID-19 patients at two to three months after discharge still maintained significantly higher Ki values in multiple organs (including lung, bone marrow, lymph nodes, myocardium and liver), although results for regular OLR measurements were normal for all discharged COVID-19 patients. Taking the image of lung as an example, the differences of SUVmax images between COVID-19 group and control group were hard to distinguish. In contrast, a high 18F-FDG signal of the lung among the COVID-19 group was observed for Ki images. Conclusion: The Ki from 18F-FDG PET/CT dynamic imaging quantification might contribute to identifying residual lesions for COVID-19 survivors. Trial registration: The trial is registered with ClinicalTrials.gov, number NCT04519255 (IRB-approved number, K52-1).


Assuntos
COVID-19 , Fluordesoxiglucose F18 , COVID-19/diagnóstico por imagem , Humanos , Alta do Paciente , Projetos Piloto , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , SARS-CoV-2
16.
Mol Pharm ; 19(11): 4264-4274, 2022 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-36067000

RESUMO

Tracking the pathogen of coronavirus disease 2019 (COVID-19) in live subjects may help estimate the spatiotemporal distribution of SARS-CoV-2 infection in vivo. This study developed a positron emission tomography (PET) tracer of the S2 subunit of spike (S) protein for imaging SARS-CoV-2. A pan-coronavirus inhibitor, EK1 peptide, was synthesized and radiolabeled with copper-64 after being conjugated with 1,4,7-triazacyclononane-1,4,7-triyl-triacetic acid (NOTA). The in vitro stability tests indicated that [64Cu]Cu-NOTA-EK1 was stable up to 24 h both in saline and in human serum. The binding assay showed that [64Cu]Cu-NOTA-EK1 has a nanomolar affinity (Ki = 3.94 ± 0.51 nM) with the S-protein of SARS-CoV-2. The cell uptake evaluation used HEK293T/S+ and HEK293T/S- cell lines that showed that the tracer has a high affinity with the S-protein on the cellular level. For the in vivo study, we tested [64Cu]Cu-NOTA-EK1 in HEK293T/S+ cell xenograft-bearing mice (n = 3) and pseudovirus of SARS-CoV-2-infected HEK293T/ACE2 cell bearing mice (n = 3). The best radioactive xenograft-to-muscle ratio (X/Nxenograft 8.04 ± 0.99, X/Npseudovirus 6.47 ± 0.71) was most evident 4 h postinjection. Finally, PET imaging in the surrogate mouse model of beta-coronavirus, mouse hepatic virus-A59 infection in C57BL/6 J mice showed significantly enhanced accumulation in the liver than in the uninfected mice (1.626 ± 0.136 vs 0.871 ± 0.086 %ID/g, n = 3, P < 0.05) at 4 h postinjection. In conclusion, our experimental results demonstrate that [64Cu]Cu-NOTA-EK1 is a potential molecular imaging probe for tracking SARS-CoV-2 in extrapulmonary infections in living subjects.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Humanos , Camundongos , Células HEK293 , COVID-19/diagnóstico por imagem , Camundongos Endogâmicos C57BL , Radioisótopos de Cobre/química , Tomografia por Emissão de Pósitrons/métodos , Sondas Moleculares , Linhagem Celular Tumoral
17.
Bioorg Med Chem ; 73: 116996, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36126443

RESUMO

The purinergic P2X7 receptor (P2X7R), an ATP gated ion channel, is an important therapeutic target for various inflammatory immune and neurodegenerative diseases. A novel P2X7R targeting radiotracer GSK1482160 was radiosynthesized by hetero-aryl bromides precursor 10 with [18F]Et4NF, 20-30 % radiochemical yield, > 68 GBq/µmol specific activity, >98 % radiochemical purity. Evaluation in healthy male Sprague-Dawley rats revealed that [18F]GSK1482160 ([18F]11) was stably retained 87.81 %, 72.45 %, and 56.32 % in brain, blood and liver respectively 60-min post-injection. Ex-vivo biodistribution of [18F]11 proved that it was able to target the P2X7R in vivo and there was no defluorination in the major organs. PET/MRI imaging and autoradiography revealed that [18F]11 was able to penetrate the blood-brain barrier (BBB) and to be a promising P2X7R PET radioligand for clinical translation.


Assuntos
Brometos , Receptores Purinérgicos P2X7 , Trifosfato de Adenosina , Animais , Encéfalo/diagnóstico por imagem , Radioisótopos de Flúor , Masculino , Tomografia por Emissão de Pósitrons/métodos , Ácido Pirrolidonocarboxílico , Compostos Radiofarmacêuticos , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
18.
Polymers (Basel) ; 14(18)2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36145909

RESUMO

With the aim of developing green coatings, styrene-acrylic emulsion has been widely used in architectural coatings due to its excellent environmental protection and energy conservation. Nevertheless, the lack of water and oxygen resistance of water-based styrofoam coatings has promoted various nanomaterials being studied for modification. To improve the performance of waterborne styrofoam coating, we introduced the graphene nanopowder and expected to enable it with the function of electromagnetic interference (EMI) shielding to reduce the damage of electromagnetic radiation. In this paper, the problem of poor interface compatibility between graphene and polymer resin was successfully addressed by in situ polymerization. In the process of pre-polymerization of styrene-acrylic emulsion monomer, graphene-modified styrene-acrylic emulsion was obtained by introducing graphene aqueous dispersion. The results showed that the styrene-acrylic emulsion with 4 wt% aqueous graphene dispersions exhibited the best dispersion stability, improved water and oxygen resistance, and the conductivity reached 1.89 × 10-2 S/cm. Then, the graphene-modified coating for building was prepared by using graphene-modified styrofoam emulsion. All the performance indexes of the coating are in line with the industry standards, and it still showed benign EMI shielding effect even when the graphene content was low. It is demonstrated that in situ polymerization technology and the application of graphene in resin coatings modification will promote the development of green coatings.

19.
J Phys Chem B ; 126(33): 6345-6353, 2022 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-35971652

RESUMO

Molecular self-assembled materials have attracted considerable interest in recent years. As part of the efforts to overcome the shortcoming that the solution-based methods were hardly applicable in preparing bulk macroscopic molecular self-assemblies, Yan [ CCS Chem. 2020, 2, 98-106] developed a strategy of solid-phase molecular self-assembly (SPMSA) that allows scaling up the generation of massive supramolecular films. It is highly desired to understand the physical insight into the SPMSA at a molecular level. Here, in combination with the experimental study, we report molecular dynamics (MD) simulations on the SPMSA of the surfactant sodium dodecyl sulfate (SDS) using a coarse-grained method with the Martini force field model. The MD simulations clearly manifest that a small amount of water is required to endow the SDS molecules with sufficient mobility to self-assemble, and the smaller size of the preassembled SDS particles favors their further fusion into mesophases by reducing the total surface Gibbs free energy, while the smaller interparticle distance decreases the time for the particle fusion. The simulation results agree well with the conditions required in the experiment, confirming that SMPSA is a free-energy-favored process leading to bulk self-assembled materials.


Assuntos
Simulação de Dinâmica Molecular , Água , Entropia , Dodecilsulfato de Sódio , Tensoativos
20.
Mol Imaging ; 2022: 8081299, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35903246

RESUMO

It has been a big challenge to distinguish synchronous multiple primary lung cancer (sMPLC) from primary lung cancer with intrapulmonary metastases (IPM). We aimed to assess the clinical application of dynamic 18F-FDG PET/CT in patients with multiple lung cancer nodules. We enrolled patients with multiple pulmonary nodules who had undergone dynamic 18F-FDG PET/CT and divided them into sMPLC and IPM groups based on comprehensive features. The SUVmax, fitted K i value based on dynamic scanning, and corresponding maximum diameter (D max) from the two largest tumors were determined in each patient. We determined the absolute between-tumor difference of SUVmax/D max and K i /D max (ΔSUVmax/D max; ΔK i /D max) and assessed the between-group differences. Further, the diagnostic accuracy was evaluated by ROC analysis and the correlation between ΔSUVmax/D max and ΔK i /Dmax from all groups was determined. There was no significant difference for ΔSUVmax/D max between the IPM and sMPLC groups, while the IPM group had a significantly higher ΔK i /Dmax than the sMPLC group. The AUC of ΔK i /D max for differentiating sMPLC from IPM was 0.80 (cut-off value of K i = 0.0059, sensitivity 79%, specificity 75%, p < 0.001). There was a good correlation (Pearson r = 0.91, 95% CI: 0.79-0.96, p < 0.0001) between ΔSUVmax/D max and ΔK i /D max in the IPM group but not in the sMPLC group (Pearson r = 0.45, p > 0.05). Dynamic 18F-FDG PET/CT could be a useful tool for distinguishing sMPLC from IPM. K i calculation based on Patlak graphic analysis could be more sensitive than SUVmax in discriminating IPM from sMPLC in patients with multiple lung cancer nodules.


Assuntos
Neoplasias Pulmonares , Neoplasias Primárias Múltiplas , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos Retrospectivos
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