Computational discovery of fast interstitial oxygen conductors.

New highly oxygen-active materials may enhance many energy-related technologies by enabling efficient oxygen-ion transport at lower temperatures, for example, below ~400 °C. Interstitial oxygen conductors have the potential to realize such performance but have received far less attention than vacancy-mediated conductors. Here we combine physically motivated structure and property descriptors, ab initio simulations and experiments to demonstrate an approach to discover new fast interstitial oxygen conductors. Multiple new families were found, which adopt completely different structures from known oxygen conductors. From these families, we synthesized and studied oxygen kinetics in La4Mn5Si4O22+δ, a representative member of the perrierite/chevkinite family. We found that La4Mn5Si4O22+δ has higher oxygen-ion conductivity than the widely used yttria-stabilized ZrO2, and among the highest surface oxygen exchange rates at the intermediate temperature of known materials. The fast oxygen kinetics is the result of simultaneously active interstitial and interstitialcy diffusion pathways. We propose that the essential features for forming an effective interstitial oxygen conductor are the availability of electrons and structural flexibility, enabling a sufficient accessible volume. This work provides a powerful approach for understanding and discovering new interstitial oxygen conductors.

A Calcium-Dependent Protein Kinase Regulates the Defense Response in Citrus sinensis.

Citrus Huanglongbing (HLB), which is caused by 'Candidatus Liberibacter asiaticus' (CLas), is one of the most destructive citrus diseases worldwide, and defense-related Citrus sinensis gene resources remain largely unexplored. Calcium signaling plays an important role in diverse biological processes. In plants, a few calcium-dependent protein kinases (CDPKs/CPKs) have been shown to contribute to defense against pathogenic microbes. The genome of C. sinensis encodes dozens of CPKs. In this study, the role of C. sinensis calcium-dependent protein kinases (CsCPKs) in C. sinensis defense was investigated. Silencing of CsCPK6 compromised the induction of defense-related genes in C. sinensis. Expression of a constitutively active form of CsCPK6 (CsCPK6CA) triggered the activation of defense-related genes in C. sinensis. Complementation of CsCPK6 rescued the defense-related gene induction in an Arabidopsis thaliana cpk4/11 mutant, indicating that CsCPK6 carries CPK activity and is capable of functioning as a CPK in Arabidopsis. Moreover, an effector derived from CLas inhibits defense induced by the expression of CsCPK6CA and autophosphorylation of CsCPK6, which suggests the involvement of CsCPK6 and calcium signaling in defense. These results support a positive role for CsCPK6 in C. sinensis defense against CLas, and the autoinhibitory regulation of CsCPK6 provides a potential genome-editing target for improving C. sinensis defense. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Macrophage mannose receptor CD206 targeting of fluoride-18 labeled mannosylated dextran: A validation study in mice.

PURPOSE: Aluminum fluoride-18-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-conjugated mannosylated dextran derivative (Al[18F]F-NOTA-D10CM) is a new tracer for PET imaging. We report here on in vitro and in vivo validation of the tracer's ability to target the macrophage mannose receptor CD206. METHODS: First, the uptake of intravenously (i.v.) administered Al[18F]F-NOTA-D10CM was compared between wild-type (WT) and CD206-/- knockout (KO) mice. C57BL/6N mice were injected with complete Freund's adjuvant (CFA) in the left hind leg and the uptake of Al[18F]F-NOTA-D10CM after i.v. or intradermal (i.d.) injection was studied at 5 and 14 days after CFA induction of inflammation. Healthy C57BL/6N mice were studied as controls. Mice underwent PET/CT on consecutive days with [18F]FDG, i.v. Al[18F]F-NOTA-D10CM, and i.d. Al[18F]F-NOTA-D10CM. After the last imaging, Al[18F]F-NOTA-D10CM was i.v. injected for an ex vivo biodistribution study and autoradiography of inflamed tissues. Blood plasma samples were analyzed using high-performance liquid chromatography. To evaluate the specificity of Al[18F]F-NOTA-D10CM binding, an in vitro competitive displacement study was performed on inflamed tissue sections using autoradiography. CD206 expression was assessed by immunohistochemical staining. RESULTS: Compared with WT mice, the uptake of Al[18F]F-NOTA-D10CM was significantly lower in several CD206-/- KO mice tissues, including liver (SUV 8.21 ± 2.51 vs. 1.06 ± 0.16, P < 0.001) and bone marrow (SUV 1.63 ± 0.37 vs. 0.22 ± 0.05, P < 0.0001). The uptake of i.v. injected Al[18F]F-NOTA-D10CM was significantly higher in inflamed ankle joint (SUV 0.48 ± 0.13 vs. 0.18 ± 0.05, P < 0.0001) and inflamed foot pad skin (SUV 0.41 ± 0.10 vs. 0.04 ± 0.01, P < 0.0001) than in the corresponding tissues in healthy mice. The i.d.-injected Al[18F]F-NOTA-D10CM revealed differences between CFA-induced lymph node activation and lymph nodes in healthy mice. Ex vivo γ-counting, autoradiography, and immunohistochemistry supported the results, and a decrease of ~ 80% in the binding of Al[18F]F-NOTA-D10CM in the displacement study with excess NOTA-D10CM confirmed that tracer binding was specific. At 60 min after i.v. injection, an average 96.70% of plasma radioactivity was derived from intact Al[18F]F-NOTA-D10CM, indicating good in vivo stability. The uptake of Al[18F]F-NOTA-D10CM into inflamed tissues was positively associated with the area percentage of CD206-positive staining. CONCLUSION: The uptake of mannosylated dextran derivative Al[18F]F-NOTA-D10CM correlated with CD206 expression and the tracer appears promising for inflammation imaging.

Switching the Chemoselectivity in the Preparation of [18F]FNA-N-CooP, a Free Thiol-Containing Peptide for Targeted Positron Emission Tomography Imaging of Fatty Acid Binding Protein 3.

Fatty acid binding protein 3 (FABP3) is expressed both in tumor cells and in the tumor vasculature, making it a potential target for medical imaging and therapy. In this study, we aimed to radiolabel a CooP peptide with a free amino and thiol group, and evaluate the radiolabeled product [18F]FNA-N-CooP for imaging FABP3 expression in breast cancer brain metastases by positron emission tomography. [18F]FNA-N-CooP was prepared by highly chemoselective N-acylation and characterized using different chemical approaches. We validated its binding to the target using in vitro tissue section autoradiography and performed stability tests in vitro and in vivo. [18F]FNA-N-CooP was successfully synthesized in 16.8% decay-corrected radiochemical yield with high radiochemical purity (98.5%). It exhibited heterogeneous binding on brain metastasis tissue sections from a patient with breast cancer, with foci of radioactivity binding corresponding to FABP3 positivity. Furthermore, the tracer binding was reduced by 55% in the presence of nonradioactive FNA-N-CooP a blocker, indicating specific tracer binding and that FABP3 is a viable target for [18F]FNA-N-CooP. Favorably, the tracer did not bind to necrotic tumor tissue. However, [18F]FNA-N-CooP displayed limited stability both in vitro in mouse plasma or human serum and in vivo in mouse, therefore further studies are needed to improve the stability [18F]FNA-N-CooP to be used for in vivo applications.

Cs+ Promoting the Diffusion of K+ and Inhibiting the Generation of Newberyite in Struvite-K Cements: Experiments and Molecular Dynamics Simulation Calculations.

Struvite-K cements, also called magnesium potassium phosphate cements (MKPCs), are applicable for particular applications, especially the immobilization of radioactive Cs+ in the nuclear industry. This work focuses on how Cs+ affects the hydration mechanism of struvite-K cements because newberyite and brucite in the hydration products are deemed to be risky products that result in cracking. Experiments and molecular dynamics simulations showed that Cs+ promoted the diffusion of K+ to the surface of MgO, which greatly facilitates the formation of more K-struvite crystals, inhibiting the formation of newberyite and brucite. A total of 0.02 M Cs+ resulted in a 40.44%, 13.93%, 60.81%, and 32.18% reduction in the amount of newberyite and brucite, and the Cs immobilization rates were 99.07%, 99.84%, 99.87%, and 99.83% when the ratios of Mg/P were 1, 3, 5, and 7, respectively. This provides new evidence of stability for struvite-K cements on radioactive Cs+ immobilization. Surprisingly, another new crystal, [CsPO3·H2O]4, was found to be a dominating Cs-containing phase in Cs-immobilizing struvite-K cements, in addition to Cs-struvite.

Effect of K+ Diffusion on Hydration of Magnesium Potassium Phosphate Cement with Different Mg/P Ratios: Experiments and Molecular Dynamics Simulation Calculations.

Magnesium potassium phosphate cement (MKPC) is formed on the basis of acid-base reaction between dead burnt MgO and KH2PO4 in aqueous solution with K-struvite as the main cementitious phase. Due to the unique characteristics of these cements, they are suitable for special applications, especially the immobilization of radioactive metal cations and road repair projects at low temperature. However, there are few articles about the hydration mechanism of MKPC. In this study, the types, proportions and formation mechanism of MKPC crystalline phases under different magnesium to phosphorus (Mg/P) ratios were studied by means of AAS, ICP-OES, SEM, EDS and XRD refinement methods. Corresponding MD simulation works were used to explain the hydration mechanism. This study highlights the fact that crystalline phases distribution of MKPC could be adjusted and controlled by different Mg/P ratios for the design of the MKPC, and the key factor is the kinetic of K+.

Analysis of sleep apnea research with a special focus on the use of positron emission tomography as a study tool.

The quality of sleep plays a significant role in determining human well-being, and studying sleep and sleep disorders using various methods can aid in the prevention and treatment of diseases. Positron emission tomography (PET) is a noninvasive and highly sensitive medical imaging technique that has been widely adopted in the clinic. This review article provides data on research activity related to sleep and sleep apnea and discusses the use of PET in investigating sleep apnea and other sleep disorders. We conducted a statistical analysis of the number of original research articles published on sleep and sleep apnea between 1965 and 2021 and found that there has been a dramatic increase in publications since 1990. The distribution of contributing countries and regions has also undergone significant changes. Although there is an extensive body of literature on sleep research (256,399 original research articles during 1965-2021), PET has only been used in 54 of these published studies, indicating a largely untapped area of research. Nonetheless, PET is a useful tool for identifying connections between sleep disorders and pathological changes in various diseases, including neurological, metabolic, and cardiovascular disorders, as well as cancer. To facilitate the broader use of PET in sleep apnea research, further studies are needed in both clinical and preclinical settings.

Preparation and Characterization of Graphite-SiO2 Composites for Thermal Storage Cement-Based Materials.

Thermal storage cement-based materials, formed by integrating phase change materials into cementitious materials, exhibit significant potential as energy storage materials. However, poor thermal conductivity severely limits the development and application of these materials. In this study, an amorphous SiO2 shell is encapsulated on a graphite surface to create a novel thermally modified admixture (C@SiO2). This material exhibits excellent thermal conductivity, and the surface-encapsulated amorphous SiO2 enhances its bond with cement. Further, C@SiO2 was added to the thermal storage cement-based materials at different volume ratios. The effects of C@SiO2 were evaluated by measuring the fluidity, thermal conductivity, phase change properties, temperature change, and compressive strength of various thermal storage cement-based materials. The results indicate that the newly designed thermal storage cement-based material with 10 vol% C@SiO2 increases the thermal conductivity coefficient by 63.6% and the latent heat of phase transition by 11.2% compared to common thermal storage cement-based materials. Moreover, C@SiO2 does not significantly impact the fluidity and compressive strength of the thermal storage cement-based material. This study suggests that C@SiO2 is a promising additive for enhancing thermal conductivity in thermal storage cement-based materials. The newly designed thermal storage cement-based material with 10 vol% C@SiO2 is a promising candidate for energy storage applications.

Mannose receptor independent uptake of transmembrane glycocluster immunostimulant TADM by macrophages.

Triacedimannose (TADM) is a synthetic trivalent acetylated glycocluster comprising ß-1,2-linked mannobioses that in humans induces TNF in vitro and in vivo. The purpose of this study was to analyze whether uptake of acetylated glycoclusters of such ß-1,2-linked mannobioses by human macrophages is dependent on the mannose receptor (CD206) or if it is mediated by transmembrane activation. In mannose receptor blocking assays, monocyte-derived polarized macrophages were incubated with carbohydrate test-compounds and their binding to the mannose receptor was demonstrated as inhibition of FITC-Dextran binding. For 1H NMR spectroscopy, macrophages were incubated with TADM. The cells were collected at 6 and 24 h of incubation, centrifuged and washed twice with PBS. We found dose-dependent blocking of the mannose receptor in macrophage carbohydrate constructs containing free hydroxyl groups, but not by the trivalent acetylated glycocluster molecules. NMR spectroscopic analyses demonstrated that TADM was found in washed cellular pellets after 6-h co-culture, while after 24-h co-culture TADM was no more detectable, suggesting cleavage of the acetyl groups in vitro. The Type 1 immune response enhancing effects of TADM and other, stereochemically and structurally similar, trivalent acetylated glycoclusters may be due to transmembrane uptake of macrophages independent of the mannose receptor.

Radiosynthesis, structural identification and in vitro tissue binding study of [18F]FNA-S-ACooP, a novel radiopeptide for targeted PET imaging of fatty acid binding protein 3.

BACKGROUND: Fatty acid binding protein 3 (FABP3) is a target with clinical relevance and the peptide ligand ACooP has been identified for FABP3 targeting. ACooP is a linear decapeptide containing a free amino and thiol group, which provides opportunities for conjugation. This work is to develop methods for radiolabeling of ACooP with fluorine-18 (18F) for positron emission tomography (PET) applications, and evaluate the binding of the radiolabeled ACooP in human tumor tissue sections with high FABP3 expression. RESULTS: The prosthetic compound 6-[18F]fluoronicotinic acid 4-nitrophenyl ester was conveniently prepared with an on-resin 18F-fluorination in 29.9% radiochemical yield and 96.6% radiochemical purity. Interestingly, 6-[18F]fluoronicotinic acid 4-nitrophenyl ester conjugated to ACooP exclusively by S-acylation instead of the expected N-acylation, and the chemical identity of the product [18F]FNA-S-ACooP was confirmed. In the in vitro binding experiments, [18F]FNA-S-ACooP exhibited heterogeneous and high focal binding in malignant tissue sections, where we also observed abundant FABP3 positivity by immunofluorescence staining. Blocking study further confirmed the [18F]FNA-S-ACooP binding specificity. CONCLUSIONS: FABP3 targeted ACooP peptide was successfully radiolabeled by S-acylation using 6-[18F]fluoronicotinic acid 4-nitrophenyl ester as the prosthetic compound. The tissue binding and blocking studies together with anti-FABP3 immunostaining confirmed [18F]FNA-S-ACooP binding specificity. Further preclinical studies of [18F]FNA-S-ACooP are warranted.

Detection of Intestinal Inflammation by Vascular Adhesion Protein-1-Targeted [68Ga]Ga-DOTA-Siglec-9 Positron Emission Tomography in Murine Models of Inflammatory Bowel Disease.

PURPOSE: Inflammatory bowel disease (IBD) can be imaged with positron emission tomography (PET), but existing PET radiopharmaceuticals have limited diagnostic accuracy. Vascular adhesion protein-1 (VAP-1) is an endothelial cell surface molecule that controls leukocyte extravasation into sites of inflammation. However, the role of inflammation-induced VAP-1 expression in IBD is still unclear. Therefore, this study investigated the utility of VAP-1-targeted [68Ga]Ga-DOTA-Siglec-9 positron emission tomography/computed tomography (PET/CT) for assessing inflammation in two mouse models of IBD. PROCEDURES: Studies were performed using K8-/- mice that develop a chronic colitis-phenotype and C57Bl/6NCrl mice with acute intestinal inflammation chemically-induced using 2.5% dextran sodium sulfate (DSS) in drinking water. In both diseased and control mice, uptake of the VAP-1-targeting peptide [68Ga]Ga-DOTA-Siglec-9 was assessed in intestinal regions of interest using in vivo PET/CT, after which ex vivo gamma counting, digital autoradiography, and histopathological analyses were performed. Immunofluorescence staining was performed to determine VAP-1-expression in the intestine, including in samples from patients with ulcerative colitis. RESULTS: Intestinal inflammation could be visualized by [68Ga]Ga-DOTA-Siglec-9 PET/CT in two murine models of IBD. In both models, the in vivo PET/CT and ex vivo studies of [68Ga]Ga-DOTA-Siglec-9 uptake were significantly higher than in control mice. The in vivo uptake was increased on average 1.4-fold in the DSS model and 2.0-fold in the K8-/- model. Immunofluorescence staining revealed strong expression of VAP-1 in the inflamed intestines of both mice and patients. CONCLUSIONS: This study suggests that the VAP-1-targeting [68Ga]Ga-DOTA-Siglec-9 PET tracer is a promising tool for non-invasive imaging of intestinal inflammation. Future studies in patients with IBD and evaluation of the potential value of [68Ga]Ga-DOTA-Siglec-9 in diagnosis and monitoring of the disease are warranted.

Highlight selection of radiochemistry and radiopharmacy developments by editorial board.

BACKGROUND: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. MAIN BODY: This selection of highlights provides commentary on 24 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first-in-human application of novel radiopharmaceuticals. CONCLUSION: Trends in radiochemistry and radiopharmacy are highlighted. Hot topics cover the entire scope of EJNMMI Radiopharmacy and Chemistry, demonstrating the progress in the research field in many aspects.

Learning properties of ordered and disordered materials from multi-fidelity data.

Predicting the properties of a material from the arrangement of its atoms is a fundamental goal in materials science. While machine learning has emerged in recent years as a new paradigm to provide rapid predictions of materials properties, their practical utility is limited by the scarcity of high-fidelity data. Here, we develop multi-fidelity graph networks as a universal approach to achieve accurate predictions of materials properties with small data sizes. As a proof of concept, we show that the inclusion of low-fidelity Perdew-Burke-Ernzerhof band gaps greatly enhances the resolution of latent structural features in materials graphs, leading to a 22-45% decrease in the mean absolute errors of experimental band gap predictions. We further demonstrate that learned elemental embeddings in materials graph networks provide a natural approach to model disorder in materials, addressing a fundamental gap in the computational prediction of materials properties.