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To effectively remove heavy metal Hg(II) from water bodies, a novel adsorbent of MgAl-layered double hydroxide (LDH) was designed and functionalized with Schiff base. The characterization results of the adsorbent (MgAl-LDH@SiO2-AG) show that the Schiff base polymer was successfully coated onto the outside surface of MgAl-LDH with hexagonal structure. The theoretical maximum adsorption capacity to Hg(II) is 228.46 mg/g at pH 7 and 298 K. The different pH solutions were investigated from pH 2 to 8, and the optimal capacity of MgAl-LDH@SiO2-AG toward Hg(II) achieves 268.7 mg/g at pH = 7.2, T = 36.8 °C, C0 = 32.1 mg/L and dosage = 0.083 g/L. In reality, the adsorbent not only exhibits efficient removal of Hg(II) in various water bodies, including lake water, river water, effluent from sewage treatment plant, but also has an excellent selectivity in electroplating wastewater containing different heavy metal ions. Low contents of TN and TP in real wastewater have less effect on the removal of Hg(II). Moreover, the prepared adsorbent had a good reusability and stability. The reaction mechanism mainly involves chelation with nitrogen/oxygen-containing groups and the predominant participation of nitrogen atoms in the Schiff base functional group. The removal of Hg(II) relies on the pseudo-second-order kinetics and Langmuir model, and is an endothermic and spontaneous chemical reaction. The present work offers a practical method for preparing highly effective adsorptive materials with the LDH composites and for the treatment of heavy metal Hg(II) from water bodies.
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The construction of covalent organic frameworks (COFs) with unique structures has great significance in exploring the structure-function relationship and extending their potential applications. Fibrous COFs have demonstrated superior performance in specific application scenarios owing to the distinctive three-dimensional (3D) structure. Herein, we report a facile strategy for the fabrication of 3D COF nanofiber by exploiting silver amalgam as a bridging agent to assemble one-dimensional-extended PA-COF modules into a tubular structure. Dimensions of the obtained 3D COF nanofiber were predicted by DFT calculations, and the nanofiber was endowed with the merits of favorable uniformity and high stability. Due to the enhanced exposure of conjugatable binding sites for dye retention offered by the novel 3D architecture, the PA-COF nanofiber exhibits fast adsorption (within 5 min) and superior adsorption capacity to various organic dyes, e.g., 1717 mg g-1 for methylene blue (MB) and 978.3 mg g-1 for methyl orange (MO). Moreover, the PA-COF nanofiber shows excellent reusability in dye adsorption, which makes it a potential medium for removing dye pollutants from wastewater. This work presents an effective strategy to construct COF materials with unique architecture and potential prospects in the fields of separation and wastewater treatment.
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Targeting receptor-interacting protein kinase 1 (RIPK1) has emerged as a promising therapeutic stratagem for neurodegenerative disorders, particularly Alzheimer's disease (AD). A positron emission tomography (PET) probe enabling brain RIPK1 imaging can provide a powerful tool to unveil the neuropathology associated with RIPK1. Herein, the development of a new PET radioligand, [11C]CNY-10 is reported, which may enable brain RIPK1 imaging. [11C]CNY-10 is radiosynthesized with a high radiochemical yield (41.8%) and molar activity (305 GBq/µmol). [11C]CNY-10 is characterized by PET imaging in rodents and a non-human primate, demonstrating good brain penetration, binding specificity, and a suitable clearance kinetic profile. It is performed autoradiography of [11C]CNY-10 in human AD and healthy control postmortem brain tissues, which shows strong radiosignal in AD brains higher than healthy controls. Subsequently, it is conducted further characterization of RIPK1 in AD using [11C]CNY-10-based PET studies in combination with immunohistochemistry leveraging the 5xFAD mouse model. It is found that AD mice revealed RIPK1 brain signal significantly higher than WT control mice and that RIPK1 is closely related to amyloid plaques in the brain. The studies enable further translational studies of [11C]CNY-10 for AD and potentially other RIPK1-related human studies.
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Enfermedad de Alzheimer , Encéfalo , Tomografía de Emisión de Positrones , Proteína Serina-Treonina Quinasas de Interacción con Receptores , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/diagnóstico por imagen , Animales , Tomografía de Emisión de Positrones/métodos , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Ratones , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Humanos , Modelos Animales de Enfermedad , Radiofármacos/metabolismo , Radiofármacos/farmacocinética , Masculino , Ratas , Femenino , Autorradiografía/métodos , Radioisótopos de Carbono/metabolismoRESUMEN
Sigma-1 receptor (σ1R) is an intracellular protein implicated in a spectrum of neurodegenerative conditions, notably Alzheimer's disease (AD). Positron emission tomography (PET) imaging of brain σ1R could provide a powerful tool for better understanding the underlying pathomechanism of σ1R in AD. In this study, we successfully developed a 18F-labeled σ1R radiotracer [18F]CNY-05 via an innovative ruthenium (Ru)-mediated 18F-deoxyfluorination method. [18F]CNY-05 exhibited preferable brain uptake, high specific binding, and slightly reversible pharmacokinetics within the PET scanning time window. PET imaging of [18F]CNY-05 in nonhuman primates (NHP) indicated brain permeability, metabolic stability, and safety. Moreover, autoradiography and PET studies of [18F]CNY-05 in the AD mouse model found a significantly decreased brain uptake compared to that in wild-type mice. Collectively, we have provided a novel 18F-radiolabeled σ1R PET probe, which enables visualizing brain σ1R in health and neurological diseases.
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Enfermedad de Alzheimer , Encéfalo , Radioisótopos de Flúor , Tomografía de Emisión de Positrones , Radiofármacos , Receptores sigma , Receptor Sigma-1 , Receptores sigma/metabolismo , Animales , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Radioisótopos de Flúor/química , Tomografía de Emisión de Positrones/métodos , Ratones , Radiofármacos/química , Radiofármacos/farmacocinética , Radiofármacos/síntesis química , Masculino , Imagen Molecular/métodos , Halogenación , Distribución Tisular , HumanosRESUMEN
A novel strategy in which palladium(II)-catalyzed tandem cyclization is used to obtain N-heterocyclic architectures containing a seven-membered ring has been developed and used to synthesize a series of derivatives. The reaction uses an eco-friendly mixed solvent (water : EtOH = 2 : 1) instead of DMSO and maintains a high yield (91%). Its potential application value and reaction mechanism have also been explored.
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Introduction: Sirtuins (SIRTs) comprise a group of histone deacetylase enzymes crucial for regulating metabolic pathways and contributing significantly to various disease mechanisms. Sirtuin 1 (SIRT1), among the seven known mammalian homologs, is extensively investigated and understood, playing a key role in neurodegenerative disorders and cancer. This study focuses on potential as a therapeutic target for conditions such as Parkinson's disease (PD), Huntington's disease (HD), and Alzheimer's disease (AD). Methods: Utilizing positron emission tomography (PET) as a noninvasive molecular imaging modality, we aimed to expedite the validation of a promising sirtuin 1 inhibitor for clinical trials. However, the absence of a validated sirtuin 1 PET radiotracer impedes clinical translation. We present the development of [11C]1, and 11C-labeled benzoxazine-based derivative, as a lead imaging probe. The radiosynthesis of [11C]1 resulted in a radiochemical yield of 31 ± 4%. Results: Baseline studies demonstrated that [11C]1 exhibited excellent blood-brain barrier (BBB) penetration capability, with uniform accumulation throughout various brain regions. Self-blocking studies revealed that introducing an unlabeled compound 1, effectively blocking sirtuin 1, led to a substantial reduction in whole-brain uptake, emphasizing the in vivo specificity of [11C]1 for sirtuin 1. Discussion: The development of [11C]1 provides a valuable tool for noninvasive imaging investigations in rodent models with aberrant sirtuin 1 expression. This novel radiotracer holds promise for advancing our understanding of sirtuin 1's role in disease mechanisms and may facilitate the validation of sirtuin 1 inhibitors in clinical trials.
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Benzoxazinas , Radioisótopos de Carbono , Sirtuina 1 , Animales , Sirtuina 1/metabolismo , Benzoxazinas/metabolismo , Tomografía de Emisión de Positrones/métodos , Neuroimagen/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Mamíferos/metabolismoRESUMEN
Purpose: Orexin receptors (OXRs) play a crucial role in modulating various physiological and neuropsychiatric functions within the central nervous system (CNS). Despite their significance, the precise role of OXRs in the brain remains elusive. Positron emission tomography (PET) imaging is instrumental in unraveling CNS functions, and the development of specific PET tracers for OXRs is a current research focus. Methods: The study investigated MDK-5220, an OX2R-selective agonist with promising binding properties (EC50 on OX2R: 0.023 µM, Ki on hOX2R: 0.14 µM). Synthesized and characterized as an OX2R PET probe, [11C]MDK-5220 was evaluated for its potential as a tracer. Biodistribution studies in mice were conducted to assess OX2R binding selectivity, with particular attention to its interaction with P-glycoprotein (P-gp) on the blood-brain barrier. Results: [11C]MDK-5220 exhibited promising attributes as an OX2R PET probe, demonstrating robust OX2R binding selectivity in biodistribution studies. However, an observed interaction with P-gp impacted its brain uptake. Despite this limitation, [11C]MDK-5220 presents itself as a potential candidate for further development. Discussion: The study provides insights into the functionality of the OX system and the potential of [11C]MDK-5220 as an OX2R PET probe. The observed interaction with P-gp highlights a consideration for future modifications to enhance brain uptake. The findings pave the way for innovative tracer development and propel ongoing research on OX systems, contributing to a deeper understanding of their role in the CNS. Conclusion: [11C]MDK-5220 emerges as a promising OX2R PET probe, despite challenges related to P-gp interaction. This study lays the foundation for further exploration and development of PET probes targeting OXRs, opening avenues for advancing our understanding of OX system functionality within the brain.
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Radioisótopos de Carbono , Neuroimagen , Tomografía de Emisión de Positrones , Ratones , Animales , Orexinas , Distribución Tisular , Tomografía de Emisión de Positrones/métodos , Receptores de Orexina/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismoRESUMEN
A one-pot synthesis afforded a magnetic, crosslinked polymer adsorbent (m-P6) with a variety of functional groups to realize simultaneous adsorption of Cd2+, Pb2+, Hg2+, and As3+. The material was characterized by TEM-EDS, XRD, FT-IR, VSM, and XPS. Kinetic and isothermal analyses suggested mainly chemisorption processes of heavy metal ions that form multiple layers on heterogeneous surfaces. Theoretical adsorption capacities calculated by a pseudo-2nd-order kinetic model and the Sips isothermal model were 282.88 mg/g for Cd2+, 326.18 mg/g for Pb2+, 117.85 mg/g for Hg2+, and 320.29 mg/g for As3+. m-P6 not only can efficiently adsorb divalent heavy metals (Cd2+, Pb2+, Hg2+), but also demonstrate a process of adsorption-driven catalytic oxidation by single-electron transfer (SET) from As3+ to As5+. In application, in addition to adsorption in water, m-P6 is capable of minimizing matrix interference, and extracting trace heavy metals in a complex environment (cereal) through easy operations for improving the detection accuracy, as well as it is potential for application in detection of trace heavy metals in foodstuffs. m-P6 can be readily regenerated and efficiently recycled for 5 cycles using eluent E12 and dilute acid.
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The NOD-like receptor (NLR) family pyrin-domain-containing 3 (NLRP3) inflammasome, an essential component of the innate immune system, has been emerging as a viable drug target and a potential biomarker for human diseases. In our efforts to develop novel small molecule NLRP3 inhibitors, a 1-(5-chloro-2-methoxybenzyl)-4-phenyl-1H-1,2,3-triazole scaffold was designed via a rational approach based on our previous leads. Structure-activity relationship studies and biophysical studies identified a new lead compound 8 as a potent (IC50: 0.55 ± 0.16 µM), selective, and direct NLRP3 inhibitor. Positron emission tomography (PET) imaging studies of [11C]8 demonstrated its rapid and high brain uptake as well as fast washout in mice and rhesus macaque. Notably, plasma kinetic analysis of this radiotracer from the PET/magnetic resonance imaging studies in rhesus macaque suggested radiometabolic stability. Collectively, our data not only encourage further studies of this lead compound but also warrant further optimization to generate additional novel NLRP3 inhibitors and suitable central nervous system PET radioligands with translational promise.
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Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Ratones , Animales , Humanos , Macaca mulatta , Cinética , Tomografía de Emisión de PositronesRESUMEN
Optical three-dimensional (3D) molecular imaging is highly desirable for providing precise distribution of the target-of-interest in disease models. However, such 3D imaging is still far from wide applications in biomedical research; 3D brain optical molecular imaging, in particular, has rarely been reported. In this report, we designed chemiluminescence probes with high quantum yields, relatively long emission wavelengths, and high signal-to-noise ratios to fulfill the requirements for 3D brain imaging in vivo. With assistance from density-function theory (DFT) computation, we designed ADLumin-Xs by locking up the rotation of the double bond via fusing the furan ring to the phenyl ring. Our results showed that ADLumin-5 had a high quantum yield of chemiluminescence and could bind to amyloid beta (Aß). Remarkably, ADLumin-5's radiance intensity in brain areas could reach 4 × 107 photon/s/cm2/sr, which is probably 100-fold higher than most chemiluminescence probes for in vivo imaging. Because of its strong emission, we demonstrated that ADLumin-5 could be used for in vivo 3D brain imaging in transgenic mouse models of Alzheimer's disease.
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Enfermedad de Alzheimer , Ratones , Animales , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Luminiscencia , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Ratones Transgénicos , Neuroimagen/métodos , Placa Amiloide/metabolismo , Modelos Animales de EnfermedadRESUMEN
Effective control over the crystallization of metal-organic framework (MOF) films is of great importance not only for the performance study and optimization in related applications but also for the fundamental understanding of the involved reticular chemistry. Featuring many technological advantages, electrochemical synthesis has been extensively reported for many MOF materials but is still challenged by the production of dense oriented films with a large-range tuning of thickness. Here, we report a ligand-oxidation-based anodic strategy capable of synthesizing oriented films of two-dimensional (2D) and three-dimensional (3D) conductive M-catecholate MOFs (2D Cu3(HHTP)2, 2D Zn3(HHTP)2, 2D Co3(HHTP)2, 3D YbHHTP, and 2D Cu2TBA) with tunable thicknesses up to tens of micrometers on commonly used electrodes. This anodic strategy relies on the oxidation of redox-active catechol ligands and follows a stepwise electrochemical-chemical reaction mechanism to achieve effective control over crystallizing M-catecholate MOFs into films oriented in the [001] direction. Benefiting from the electrically conductive nature, Cu3(HHTP)2 films could be thickened at a steady rate (17.4 nm·min-1) from â¼90 nm to 10.7 µm via a growth mechanism differing from those adopted in previous electrochemical synthesis of dense MOF films with limited thickness due to the self-inhibition effect. This anodic synthesis could be further combined with a templating strategy to fabricate not only films with well-defined 2D features in sizes from micrometers to millimeters but also high aspect ratio mesostructures, such as nanorods, of Cu3(HHTP)2.
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BACKGROUND: Prostate cancer (PCa) is the most common malignancy diagnosed in men. Immune checkpoint blockade (ICB) alone showed disappointing results in PCa. It is partly due to the formation of immunosuppressive tumor microenvironment (TME) could not be reversed effectively by ICB alone. METHODS: We used PCa cell lines to evaluate the combined effects of CN133 and anti-PD-1 in the subcutaneous and osseous PCa mice models, as well as the underlying mechanisms. RESULTS: We found that CN133 could reduce the infiltration of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), and CN133 combination with anti-PD-1 could augment antitumor effects in the subcutaneous PCa of allograft models. However, anti-PD-1 combination with CN133 failed to elicit an anti-tumor response to the bone metastatic PCa mice. Mechanistically, CN133 could inhibit the infiltration of PMN-MDSCs in the TME of soft tissues by downregulation gene expression of PMN-MDSC recruitment but not change the gene expression involved in PMN-MDSC activation in the CN133 and anti-PD-1 co-treatment group relative to the anti-PD-1 alone in the bone metastatic mice model. CONCLUSIONS: Taken together, our work firstly demonstrated that combination of CN133 with anti-PD-1 therapy may increase the therapeutic efficacy to PCa by reactivation of the positive immune microenvironment in the TME of soft tissue PCa.
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Células Supresoras de Origen Mieloide , Neoplasias de la Próstata , Humanos , Masculino , Animales , Ratones , Inhibidores de Histona Desacetilasas/metabolismo , Inhibidores de Histona Desacetilasas/farmacología , Células Supresoras de Origen Mieloide/metabolismo , Microambiente Tumoral , Línea Celular Tumoral , Inmunoterapia , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genéticaRESUMEN
This paper investigates the correlation between the degree and severity of CT inflammatory infiltration in the retroperitoneal space of acute pancreatitis (AP). A total of 113 patients were included based on diagnostic criteria. The general data of the patients and the relationship between the computed tomography severity index (CTSI) and pleural effusion (PE), involvement, degree of inflammatory infiltration of retroperitoneal space (RPS), number of peripancreatic effusion sites, and degree of pancreatic necrosis on contrast-enhanced CT at different times were studied. The results showed that the mean age of onset in females was later than that in males; 62 cases involved RPS to varying degrees, with a positive rate of 54.9% (62/113), and the total involvement rates of only the anterior pararenal space (APS); both APS and perirenal space (PS); and APS, PS, and posterior pararenal space (PPS) were 46.9% (53/113), 53.1% (60/113), and 17.7% (20/113), respectively. The degree of inflammatory infiltration in the RPS worsened with the increase in CTSI score; the incidence of PE was higher in the group greater than 48 hours than in the group less than 48 hours; necrosis >50% grade was predominant (43.2%) 5 to 6 days after onset, with a higher detection rate than other time periods (P < 0.05). Thus, when the PPS was involved, the patient's condition can be treated as severe acute pancreatitis (SAP); the higher the degree of inflammatory infiltration in the retroperitoneum, the higher the severity of AP. Enhanced CT examination 5 to 6 days after onset in patients with AP revealed the greatest extent of pancreatic necrosis.
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Pancreatitis Aguda Necrotizante , Masculino , Femenino , Humanos , Pancreatitis Aguda Necrotizante/diagnóstico por imagen , Espacio Retroperitoneal/diagnóstico por imagen , Enfermedad Aguda , Tomografía Computarizada por Rayos X , ComputadoresRESUMEN
Monitoring of uric acid (UA) levels in biological samples is of great significance for human health, while the development of a simple and effective method for the precise determination of UA content is still challenging. In the present study, a two-dimensional (2D) imine-linked crystalline pyridine-based covalent organic framework (TpBpy COF) was synthesized using 2,4,6-triformylphloroglucinol (Tp) and [2,2'-bipyridine]-5,5'-diamine (Bpy) as precursors via Schiff-base condensation reactions and was characterized with scanning electron microscopy (SEM), Energy dispersive X-ray spectroscopy (EDS), Powder X-ray diffraction (PXRD), Fourier transform infrared (FT-IR) spectroscopy, and Brunauer-Emmett-Teller (BET) assays. The as-synthesized TpBpy COF exhibited excellent visible light-induced oxidase-like activity, ascribed to the generation of superoxide radicals (O2â¢-) by photo-generated electron transfer. TpBpy COF could efficiently oxidase the colorless substrate 3,3',5,5'-tetramethylbenzydine (TMB) into blue oxidized TMB (oxTMB) under visible light irradiation. Based on the color fade of the TpBpy COF + TMB system by UA, a colorimetric procedure was developed for UA determination with a detection limit of 1.7 µmol L-1. Moreover, a smartphone-based sensing platform was also constructed for instrument-free and on-site detection of UA with a sensitive detection limit of 3.1 µmol L-1. The developed sensing system was adopted for UA determination in human urine and serum samples with satisfactory recoveries (96.6-107.8%), suggesting the potential practical application of the TpBpy COF-based sensor for UA detection in biological samples.
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Estructuras Metalorgánicas , Oxidorreductasas , Humanos , Ácido Úrico/orina , Estructuras Metalorgánicas/química , Colorimetría/métodos , Teléfono Inteligente , Espectroscopía Infrarroja por Transformada de Fourier , Sistemas de Atención de Punto , LuzRESUMEN
Scar-free wound healing is a challenging process due to the excessive deposition of extracellular matrix and collagen. To overcome this issue, hydrogels with superior biochemical and mechanical properties have been used in combination with medicinal compounds as wound dressings. In this study, a novel composite hydrogel consisting of double-crosslinked photocurable hyaluronic acid methacrylate (HAMA) and Laponite (Lap) loaded with bioactive bone morphogenetic protein 4 (BMP4) was developed and thoroughly characterized for its properties such as degradation, morphology, porosity, compression, skin adhesion and load release. The effect of the HAMA/Lap/BMP4 hydrogel was evaluated through both in vitro and in vivo experiments. In the in vivo rabbit ear-scar model, the HAMA/Lap/BMP4 hydrogel dressing was found to reduce scar-related expressions of α-SAM and decrease the ratio of collagen Ι/III in wounded tissue. Additionally, histopathological examination indicated that the HAMA/Lap/BMP4 hydrogel-treated groups exhibited enhanced wound repair and increased levels of collagen maintenance compared to other standard groups, ultimately leading to scarless wound healing. Therefore, this sustained-release photocurable HAMA/Lap/BMP4 hydrogel offers a therapeutic approach for scar-free wound healing.
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This study proposes an eluent-free isolation strategy for the direct isolation of thrombin from whole blood via tandem temperature/pH dual-responsive polyether sulfone monolith and photoreversible DNA nanoswitch-functionalized metal-organic framework (MOF) aerogel. Temperature/pH dual-responsive microgel immobilized on polyether sulfone monolith was adopted to remove the matrix complexity of blood sample via size/charge screening effect. Photoreversible DNA nanoswitches, comprising thrombin aptamer, aptamer complementary ssDNA (cDNA) and the azobenzene-modified ssDNA (control DNA), were functionalized on MOF aerogel to offer efficient capturing of thrombin under irradiation of ultraviolet light (365 nm), driven by electrostatic and hydrogen bond interactions. The release of captured thrombin was easily achieved by changing the complementary behaviors of DNA strands via blue light (450 nm) irradiation. Thrombin with purity higher than 95 % can be directly obtained from whole blood using this tandem isolation procedure. Fibrin production and substrate chromogenic tests showed that the released thrombin possessed high biological activity. The photoreversible thrombin capturing-release strategy is merited with eluent-free, avoiding the loss of activity of thrombin in chemical circumstances and undesired dilution, providing a robust guarantee for subsequent application.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , Estructuras Metalorgánicas , Trombina , Polímeros , ADN/química , Sulfonas , Aptámeros de Nucleótidos/química , Estructuras Metalorgánicas/químicaRESUMEN
Flow cytometry is among the most powerful tools for single-cell analysis, while the high cost and mechanical complexity of the commercial instrumentation limit the applications in personalized single-cell analysis. For this issue, we hereby construct an open and low-cost flow cytometer. It is highly compact to integrate the functions of (1) single cell aligning by a lab-made modularized 3D hydrodynamic focusing device, and (2) fluorescence detection of the single cells by a confocal laser-induced fluorescence (LIF) detector. The ceiling cost of the entire hardware for the LIF detection unit and 3D focusing device is $ 3200 and $ 400 respectively. A sheath flow velocity of 150 µL/min produces a focused sample stream of 17.6 µm × 14.6 µm at sample flow of 2 µL/min, based on the LIF response frequency and the laser beam spot diameter. The assay performance of the flow cytometer was evaluated by characterizing fluorescent microparticles and acridine orange (AO) stained HepG2 cells, producing throughputs of 40.5/s and 6.2/s respectively. Favorable assay precision and accuracy were demonstrated by the agreement of frequency histogram with imaging analysis, and good Gaussian-like distributions of fluorescent microparticles and AO-stained HepG2 cells. Practically, the flow cytometer was successfully applied for the evaluation of ROS generation in single HepG2 cells.
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Colorantes , Hidrodinámica , Citometría de Flujo/métodos , Naranja de Acridina , Rayos LáserRESUMEN
Carbon dots (CDs) have been extensively employed in biomolecule imaging. However, the imaging of biological enzymes with CDs has not been reported, which greatly limits their application in biological imaging. Herein, for the first time, a new type of fluorescent CDs is elaborately designed to realize the direct mapping of alkaline phosphatase (ALP) in cells. The obtained phosphorus and nitrogen co-doped CDs (P, N-CDs) generate specific structures including xanthene oxide and phosphate ester, thereby enabling P, N-CDs to be exclusively cleaved by ALP without auxiliary media. The fluorescence intensity of P, N-CDs can be specifically turned on in the presence of ALP, making them powerful probes for sensitive sensing of ALP activity with a detection limit of 1.27 U·L-1. Meanwhile, P, N-CDs possessing electron deficiency structure fulfill sensitive responding to polarity variations. The excellent photo-bleaching resistance and biocompatibility of the P, N-CDs are taken for directly mapping the intracellular endogenous ALP via turned-on fluorescence imaging, as well as real-time monitoring the polarity fluctuation in cells through ratiometric fluorescence imaging. The present work offers a new way to design and synthesize functional CDs for direct imaging of intracellular enzymes.
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Fosfatasa Alcalina , Puntos Cuánticos , Puntos Cuánticos/química , Carbono/química , Colorantes Fluorescentes/química , Fosfatos , Ésteres , Nitrógeno/químicaRESUMEN
Accrued evidence has indicated that epigenetic mechanisms altered by alcohol have been implicated in the progression and development of alcoholic liver disease (ALD). SIRT1 plays an important role in ALD progression and has emerged as a promising therapeutic target for treating ALD. The purpose of this study is to investigate the efficacy of [11C]WL-1 for quantitative imaging of SIRT1 in mouse models of early-stage ALD. Positron emission tomography/computerized tomography (PET/CT) imaging was carried out 60 min following the injection of [11C]WL-1 in mouse models of early-stage ALD and normal control mice. The time-activity curves for ALD mouse livers showed remarkably decreased total uptake of [11C]WL-1 relative to that for control mouse livers. Moreover, compared with the normal control mice, decreased uptake in the cortex, hippocampus, and cerebellum was also observed in early-stage ALD mice, while the uptake of [11C]WL-1 in amygdala showed no significant changes. Western blot analysis confirmed that the protein levels of SIRT1 in the brains of early-stage ALD mice were decreased significantly when compared to the normal control mouse brains. Collectively, PET imaging with [11C]WL-1 would facilitate future clinical studies, aiming to demonstrate the roles of SIRT1 in ALD.
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Hepatopatías Alcohólicas , Sirtuina 1 , Animales , Ratones , Sirtuina 1/metabolismo , Tomografía Computarizada por Tomografía de Emisión de Positrones , Hepatopatías Alcohólicas/diagnóstico por imagen , Hepatopatías Alcohólicas/metabolismo , Etanol/metabolismo , Hígado/diagnóstico por imagen , Hígado/metabolismoRESUMEN
BACKGROUND: We study the adverse events (AEs) of bamlanivimab (BAM), bamlanivimab/etesevimab (BAM/ETE) to alert risk factors during coronavirus disease 2019 (COVID-19) treatment and provide references for drug safety. RESEARCH DESIGN AND METHODS: Extract AEs from the COVID-19 Emergency Use Authorization (EUA) FDA Adverse Event Reporting System (FAERS) Public Dashboard. Disproportionality analysis was performed to discover the potential risks of BAM and BAM/ETE. RESULTS: With COVID-19 drugs as the research background, the number of BAM/ETE signals is about half that of BAM, and 80% of signals overlap with BAM. Signals such as atrial fibrillation, tachycardia, and confusional state are present in BAM but not in BAM/ETE. With BAM and BAM/ETE as the research background, potential safety signals of BAM/ETE such as acute respiratory failure, hypersensitivity, and infusion-related reaction require long-term observation, especially acute respiratory failure which is not in the label. CONCLUSIONS: The AEs report on this study confirm most of the label information of BAM and BAM/ETE. BAM/ETE is relatively safe, while the risk signals such as acute respiratory failure and infusion-related reaction require to be monitored.