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.

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.

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.

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.

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+.

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.

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.

Imaging of Myocardial αvß3 Integrin Expression for Evaluation of Myocardial Injury After Acute Myocardial Infarction.

[68Ga]Ga-NODAGA-Arg-Gly-Asp (RGD) is a PET tracer targeting αvß3 integrin, which is upregulated during angiogenesis soon after acute myocardial infarction (AMI). We prospectively evaluated determinants of myocardial uptake of [68Ga]Ga-NODAGA-RGD and its associations with left ventricular (LV) function in patients after AMI. Methods: Myocardial blood flow and [68Ga]Ga-NODAGA-RGD uptake (60 min after injection) were evaluated by PET in 31 patients 7.7 ± 3.8 d after primary percutaneous coronary intervention for ST-elevation AMI. Transthoracic echocardiography of LV function was performed on the day of PET and at the 6-mo follow-up. Results: PET images showed increased uptake of [68Ga]Ga-NODAGA-RGD in the ischemic area at risk (AAR), predominantly in injured myocardial segments. The SUV in the segment with the highest uptake (SUVmax) in the ischemic AAR was higher than the SUVmean of the remote myocardium (0.73 ± 0.16 vs. 0.51 ± 0.11, P < 0.001). Multivariable predictors of [68Ga]Ga-NODAGA-RGD uptake in the AAR included high peak N-terminal pro-B-type natriuretic peptide (P < 0.001), low LV ejection fraction, low global longitudinal strain (P = 0.01), and low longitudinal strain in the AAR (P = 0.01). [68Ga]Ga-NODAGA-RGD uptake corrected for myocardial blood flow and perfusable tissue fraction in the AAR predicted improvement in global longitudinal strain at follow-up (P = 0.002), independent of peak troponin, N-terminal pro-B-type natriuretic peptide, and LV ejection fraction. Conclusion: [68Ga]Ga-NODAGA-RGD uptake shows increased αvß3 integrin expression in the ischemic AAR early after AMI that is associated with regional and global systolic dysfunction, as well as increased LV filling pressure. Increased [68Ga]Ga-NODAGA-RGD uptake predicts improvement of global LV function 6 mo after AMI.

Enhancing Thermoelectric Performance in P-Type Sb2Te3-Based Compounds Through Nb─Ag Co-Doping with Donor-Like Effect.

P-type Sb2Te3 has been recognized as a potential thermoelectric material for applications in low-medium temperature ranges. However, its inherent high carrier concentration and lattice thermal conductivity led to a relatively low ZT value, particularly around room temperature. This study addresses these limitations by leveraging high-energy ball milling and rapid hot-pressing techniques to substantially enhance the Seebeck coefficient and power factor of Sb2Te3, yielding a remarkable ZT value of 0.55 at 323 K due to the donor-like effect. Furthermore, the incorporation of Nb─Ag co-doping increases hole concentration, effectively suppressing intrinsic excitations ≈548 K while maintaining the favorable power factor. Simultaneously, the lattice thermal conductivity can be significantly reduced upon doping. As a result, the ZT values of Sb2Te3-based materials attain an impressive range of 0.5-0.6 at 323 K, representing an almost 100% improvement compared to previous research endeavors. Finally, the ZT value of Sb1.97Nb0.03Ag0.005Te3 escalates to 0.92 at 548 K with a record average ZT value (ZTavg) of 0.75 within the temperature range of 323-573 K. These achievements hold promising implications for advancing the viability of V-VI commercialized materials for low-medium temperature application.

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.

Tetrazine Glycoconjugate for Pretargeted Positron Emission Tomography Imaging of trans-Cyclooctene-Functionalized Molecular Spherical Nucleic Acids.

Pretargeted concept in positron emission tomography (PET) together with bioorthogonal chemistry is an elegant solution to study processes with slow pharmacokinetics by utilizing radiotracers labeled with short-lived radionuclides. Namely, radiotracers based on tetrazine ligation with trans-cyclooctene (TCO) via the inverse electron demand Diels-Alder (IEDDA) reaction have become a state-of-the-art for the pretargeted PET imaging. For radiolabeling of tetrazine scaffolds, indirect radiofluorination methods are often preferred, as tetrazines are vulnerable to harsh conditions typically necessary for the direct radiofluorination. 18F-Fluoroglycosylation is an indirect radiofluorination method, which allows the introduction of a widely accessible glucose analog 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) to aminooxy-functionalized precursors via oxime formation. Here, we report the biological evaluation of [18F]FDG-Tz as a tracer for pretargeted PET imaging of TCO-functionalized molecular spherical nucleic acids (MSNA) against human epidermal growth factor receptor 2 (HER2) mRNA. The oxime ether formation between [18F]FDG and tetrazine oxyamine resulted in [18F]FDG-Tz with high radiochemical purity (>99%) and moderate yields (6.5 ± 3.6%, n = 5). Biological evaluation of [18F]FDG-Tz in healthy mice indicated favorable pharmacokinetics with quick blood clearance, urinary excretion as the main elimination route, and the absence of GLUT1 transportation. The successful pretargeted experiments with TCO-functionalized MSNA revealed higher tumor uptake compared to preclicked MSNA in HER2-expressing human breast cancer xenograft-bearing mice.

In Vitro Biological Activity and Primary Structure of Polysaccharide Extracted from Flower of Panax Ginseng C.A. Meyer.

This study investigates how three different extraction methods impact the biological activity and structure characteristics of polysaccharides from the flower of Panax ginseng C.A. Meyer. The three polysaccharides were named AHEP, DWEP and ANEP that extracted by acid solvent (HCL 0.01 mol/L), distilled water and alkali solvent (NaOH 0.01 mol/L) respectively. The results showed that the yield of ANEP was highest compared to the others, as well as the capacity of antioxidant, cholate-binding and inhibition to α-glucosidase were better than AHEP and DWEP (P<0.05). Moreover, the activity retention rate in vitro with simulated digestion demonstrated that ANEP were superior to AHEP and DWEP. The large components, nominated ANEP-1 and ANEP-2, were eluted from the ANEP by DEAE-52-cellulose. UV-Vis and FT-IR analysis demonstrated that ANEP-1 and ANEP-2 had typical characteristic absorption of proteoglycan, but SEM results showed that the surface shapes of ANEP-1 and ANEP-2 were quite different. It can be concluded that ANEP has great potential as an effective strategy for obtaining polysaccharides from ginseng flower.

Vascular adhesion protein-1-targeted PET imaging in autoimmune myocarditis.

BACKGROUND: Vascular adhesion protein-1 (VAP-1) is an adhesion molecule and primary amine oxidase, and Gallium-68-labeled 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetra-acetic acid conjugated sialic acid-binding immunoglobulin-like lectin 9 motif containing peptide ([68Ga]Ga-DOTA-Siglec-9) is a positron emission tomography (PET) tracer targeting VAP-1. We evaluated the feasibility of PET imaging with [68Ga]Ga-DOTA-Siglec-9 for the detection of myocardial lesions in rats with autoimmune myocarditis. METHODS: Rats (n = 9) were immunized twice with porcine cardiac myosin in complete Freund's adjuvant. Control rats (n = 6) were injected with Freund's adjuvant alone. On day 21, in vivo PET/computed tomography (CT) imaging with [68Ga]Ga-DOTA-Siglec-9 was performed, followed by ex vivo autoradiography, histology, and immunohistochemistry of tissue sections. In addition, myocardial samples from three patients with cardiac sarcoidosis were studied. RESULTS: [68Ga]Ga-DOTA-Siglec-9 PET/CT images of immunized rats showed higher uptake in myocardial lesions than in myocardium outside lesions (SUVmean, 0.5 ± 0.1 vs 0.3 ± 0.1; P = .003) or control rats (SUVmean, 0.2 ± 0.03; P < .0001), which was confirmed by ex vivo autoradiography of tissue sections. Immunohistochemistry showed VAP-1-positive staining in lesions of rats with myocarditis and in patients with cardiac sarcoidosis. CONCLUSION: VAP-1-targeted [68Ga]Ga-DOTA-Siglec-9 PET is a potential novel technique for the detection of myocardial lesions.

A complete MAP kinase cascade controls hyphopodium formation and virulence of Verticillium dahliae.

Phytopathogens develop specialized infection-related structures to penetrate plant cells during infection. Different from phytopathogens that form appressoria or haustoria, the soil-borne root-infecting fungal pathogen Verticillium dahliae forms hyphopodia during infection, which further differentiate into penetration pegs to promote infection. The molecular mechanisms underlying the regulation of hyphopodium formation in V. dahliae remain poorly characterized. Mitogen-activated protein kinases (MAPKs) are highly conserved cytoplasmic kinases that regulate diverse biological processes in eukaryotes. Here we found that deletion of VdKss1, out of the five MAPKs encoded by V. dahliae, significantly impaired V. dahliae hyphopodium formation, in vitro penetration, and pathogenicity in cotton plants. Constitutive activation of MAPK kinase (MAPKK) VdSte7 and MAPK kinase kinase (MAPKKK) VdSte11 specifically activate VdKss1. Deletion of VdSte7 or VdSte11 resulted in a phenotype similar to that of the mutant with VdKss1 deletion. Thus, this study demonstrates that VdSte11-VdSte7-VdKss1 is a core MAPK cascade that regulates hyphopodium formation and pathogenicity in V. dahliae. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-023-00102-y.

Two-Dimensional Graphitic Carbon Nitride for Improving the Performance of Organic Solar Cells.

Organic solar cells (OSCs) have attracted lots of attention owing to their low cost, lightweight, and flexibility properties. Nowadays, the performance of OSCs is continuously improving with the development of active layer materials. However, the traditional hole transport layer (HTL) material Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) presents insufficient conductivity and rapid degradation, which decreases the efficiency and stability of OSCs. To conquer the challenge, the two-dimensional (2D) graphitic carbon nitride (g-C3N4) nanomaterials incorporated into the PEDOT:PSS as hybrid HTL are reported. The addition of g-C3N4 into PEDOT:PSS enables the thickness of the HTL to decrease for enhancing the transmittance of the film and increase the conductivity of PEDOT:PSS. Thus, the device exhibts improved charge transport and suppressed carrier recombination, leading to the increase in short-circuit current density and power conversion efficiency of the devices. This work demonstrates that the incorporation of 2D g-C3N4 into PEDOT:PSS for D18:Y6 and PM6:L8-BO-based OSCs can significantly improve the device efficiency to 17.48% and 18.47% with the enhancement of 7.04% and 8.46%, respectively.

Atomic Local Ordering and Alloying Effects on the Mg3(Sb1-xBix)2 Thermoelectric Material.

Mg3(Sb1-xBix)2 alloy has been extensively studied in the last 5 years due to its exceptional thermoelectric (TE) performance. The absence of accurate force field for inorganic alloy compounds presents great challenges for computational studies. Here, we explore the atomic microstructure, thermal, and elastic properties of the Mg3(Sb1-xBix)2 alloy at different solution concentrations through atomic simulations with a highly accurate machine learning interatomic potential (ML-IAP). We find atomic local ordering in the optimized structure with the Bi-Bi pair inclined to join adjacent layers and Sb-Sb pair preferring to stay within the same layer. The thermal conductivity changes with the solution concentrations can be correctly predicted through ML-IAP-based molecular dynamics simulations. Spectral thermal conductance analysis shows that the continuous movement of low-frequency peak to high frequency is responsible for the reduction of the thermal conductivity upon alloying. Elastic calculations reveal that similar to the thermal conductivity, solid solution alloying can reduce the overall elastic properties at both Mg3Sb2 and Mg3Bi2 ends, while anisotropic behavior is clearly observed with linear interpolation relationship upon alloying along the interlayer direction and nonlinearity along the intralayer direction. Although the atomic local ordering shows little effects on the properties of the Mg3(Sb1-xBix)2 alloy with only two alloying elements, it possesses potential important impacts on multiprincipal element inorganic TE alloys. This work provides a recipe for computational studies on the TE alloy systems and thus can accelerate the discovery and optimization of TE materials with high TE performance.

Clinical Characteristics and Economic Burden of Asthma in China: A Multicenter Retrospective Study.

Asthma is a common chronic airway inflammation that produces a healthcare burden on the economy. We aim to obtain a better understanding of the clinical status and disease burden of patients with asthma in China. A retrospective study was carried out based on the computerized medical records in the Jinan Health Medical Big Data Platform between 2011 and 2019 (available data from 38 hospitals). The asthma severity of each patient was assessed retrospectively and categorized as mild, moderate, or severe according to Global Initiative for Asthma 2020 (GINA 2020). The results revealed that the majority (75.0%) of patients suffered from mild asthma. Patients treated with inhaled corticosteroids (ICS)/long-acting beta-agonists (LABA) at emergency department visits had lower frequencies of exacerbations compared with non-ICS/LABA-treated patients. The incidence rates for 1, 2, 3, and 4 exacerbation of the patients treated with ICS/LABA are lower than those treated without ICS/LABA (14.49 vs. 15.01%, 11.94% vs. 19.12%, 6.51% vs.12.92% and 4.10% vs. 9.35%). The difference got a statistical significance Chronic obstructive pulmonary disease (COPD) and gastroesophageal reflux disease (GERD), two comorbidities related to asthma, were risk factors for asthma exacerbation. Finally, patients who suffered from exacerbations produced a heavier economic burden compared to the patients who never suffered exacerbations (mean costs are ï¿¥3,339.67 vs. ï¿¥968.45 separately).  These results provide a reference for clinicians and patients to obtain a better treatment and therapy strategy management for people living with asthma.

Assembling phenyl-modified colloidal silica on graphene oxide towards ethanol redispersible graphene oxide powder.

Recently, ethanol has shown promising potential in the large-scale reduction of graphene oxide (GO) into graphene. However, dispersion of GO powder in ethanol is a challenge due to its poor affinity, which hinders permeation and intercalation of ethanol between GO molecule layers. In this paper, phenyl-modified colloidal silica nanospheres (PSNS) were synthesized by phenyl-tri-ethoxy-silane (PTES) and tetra-ethyl ortho-silicate (TEOS) using a sol-gel method. PSNS was then assembled onto a GO surface to form a PSNS@GO structure by possible non-covalent π-π stacking interactions between the phenyl groups and GO molecules. The surface morphology, chemical composition, and dispersion stability were analyzed by scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetry, Raman spectroscopy, X-ray diffractometry, nuclear magnetic resonance, and particle sedimentation test. The results showed that the as-assembled PSNS@GO suspension had excellent dispersion stability with an optimal PSNS concentration of 5 vol% PTES. With the optimized PSNS@GO, ethanol can permeate between the GO layers and intercalate along with PSNS particles via formation of hydrogen bonds between assembled PSNS on GO and ethanol, achieving a stable dispersion of GO in ethanol. The optimized PSNS@GO powder remained redispersible after drying and milling according to this interaction mechanism which is favorable for large scale reduction processes. Higher PTES concentration may result in agglomeration of PSNS and formation of wrapping structures of PSNS@GO after drying and worsen its dispersion capability.

High folate receptor expression in gliomas can be detected in vivo using folate-based positron emission tomography with high tumor-to-brain uptake ratio divulging potential future targeting possibilities.

Introduction: Non-invasive imaging techniques such as positron emission tomography (PET) are extremely important for cancer detection and characterization especially for difficult to biopsy or extremely delicate organs such as the brain. The folate analogue 1,4,7-triazacylononane-1,4,7-triacetic acid-conjugated folate radiolabeled with aluminum fluoride-18 ([18F]FOL) has been previously shown to accumulate preferentially in tumor cells with an overexpression of folate receptors (FRs) and here was investigated for its ability to detect orthotopic gliomas in a rat model. In addition, we studied the expression of FRs in human glioblastoma samples to investigate if an analogous relationship may exist. Methods: Nine BDIX rats were injected with BT4C rat glioma cells into the right hemisphere of the brain. Animals were imaged with gadolinium-enhanced magnetic resonance imaging at on days prior to PET/computed tomography (CT) imaging. Animals were divided into two groups, and were PET/CT imaged with either [18F]FOL or 2-deoxy-2-18F-fluoro-D-glucose ([18F]FDG) on 19 and 32-days post glioma grafting. Two subjects were also PET/CT imaged with [18F]FOL on day 16. Biodistribution was studied and brains were cryosectioned for autoradiography, immunofluorescence, and histological studies. Patient-derived paraffin-embedded glioblastomas were sectioned and stained with similar methods. Results: PET imaging showed an increase of [18F]FOL tumor-to-brain uptake ratio (TBR) over the study duration from day 16/19 (3.3 ± 0.9) increasing to 5.7 ± 1.0 by day 32. [18F]FDG PET-imaged rats had a consistent TBR of 1.6 ± 0.1 throughout the study. Ex vivo autoradiography results revealed an exceptionally high TBR of 116.1 ± 26.9 for [18F]FOL while the [18F]FDG values were significantly lower giving 2.9 ± 0.6 (P<0.0001). Immunostaining demonstrated an increased presence of FR-α in the BT4C gliomas versus the contralateral brain tissue, while FR-ß was present only on glioma periphery. Human sections assayed showed similar FRs expression characteristics. Conclusion: This study shows upregulation of FR-α inside glioma regions in both human and animal tissue, providing a biochemical basis for the observed increased [18F]FOL uptake in animal PET images. These results suggest that FRs targeting imaging and therapeutic compounds may possess clinically relevant translational abilities for the detection and treatment of gliomas.