A highly efficient deep red-emitting Mn4+-powered oxyfluoride nanophosphor developed for plant growth and optical thermometric applications.

This research mainly highlighted an intense deep red-emitting and Mn4+-powered oxyfluoride nanophosphor, Mg14Ge4.99O16F8:0.01Mn4+ (MGOF:Mn), which was synthesized via adopting a scalable synthesis route for commercial temperature sensing and artificial plant growth applications. The electron microscopic analysis confirmed the formation of nanosized particles without any defined shape or size distribution. The obtained nanophosphor exhibited sharp emission peaks at 659 nm and 631 nm under UV (317 nm) and blue excitation (417 nm) owing to Mn4+:2Eg → 4A2g and Mn4+:2T1g → 4A2g transitions, respectively. The emission spectrum is situated in the deep red region of the CIE color diagram where the red color purity approached 100% under both the excitations. The absorption efficiency and the internal and external quantum efficiencies of this red-emitting system were calculated to be 53%, ∼77%, and ∼41%, respectively, under blue excitation of 417 nm, which indicated its potential for indoor plant cultivation. A prototype red LED was fabricated by pasting the red-emitting MGOF:Mn4+ nanophosphor powder on a 410 nm blue LED chip. The resulting electroluminescence spectrum overlapped with those of the important organic pigments of normal plants. Importantly, the thermometric properties of the nanophosphor were evaluated in detail for FIR and lifetime-based thermometry applications. The examined nanophosphor showed an extreme absolute sensitivity of 0.00326 K-1 at 373 K with excellent reproducibility and temperature resolution. Because of the small particle size and high luminescence efficiency, the nanophosphor could be implemented in various nano-devices where non-contact optical thermometry is necessary for high performance.

Viscous fingering instabilities in spontaneously formed blisters of MoS2 multilayers.

The viscous fingering in the Hele-Shaw cell can be suppressed by replacing the upper-bounding rigid plate with an elastic membrane. Recently, graphene multilayers while polymer-curing-induced blistering showed the dynamical evolution of viscous fingering patterns on a viscoelastic substrate due to their thickness-dependent elasticity. Under certain conditions, the elastic solid-based instability couples with the viscoelastic substrate-based instability. The mechanisms underlying such a coupling in the blisters of 2D materials and the dynamical evolution of the viscous fingering patterns underneath the blisters are yet to be addressed. Herein, we investigate the viscous fingering instabilities in spontaneously formed blisters of MoS2 multilayers, and provide thorough analytical and experimental insights for the elucidation of the dynamical evolution of the viscous fingering patterns and the coupled instabilities in the blisters. We also estimate the interfacial adhesion energy of the MoS2 flakes over a (poly)vinyl alcohol (PVA) substrate and the confinement pressure inside the MoS2 blisters using a conventional blister-test model. It is observed that the presence of instability gives rise to anomalies in the modeling of the blister test. The adhesion mechanical insights would be beneficial for fundamental research as well as practical applications of 2D material blisters in flexible optoelectronics.

Positron Emission Tomography Imaging of Cell Trafficking: A Method of Cell Radiolabeling.

Stem cell and chimeric antigen receptor (CAR) T-cell therapies are emerging as promising therapeutics for organ regeneration and as immunotherapy for various cancers. Despite significant progress having been made in these areas, there is still more to be learned to better understand the pharmacokinetics and pharmacodynamics of the administered therapeutic cells in the living system. For noninvasive, in vivo tracking of cells with positron emission tomography (PET), a novel [89Zr]Zr-p-isothiocyanatobenzyl-desferrioxamine ([89Zr]Zr-DBN)-mediated cell radiolabeling method has been developed utilizing 89Zr (t1/2 78.4 h). The present protocol describes a [89Zr]Zr-DBN-mediated, ready-to-use, radiolabeling synthon for direct radiolabeling of variety of cells, including mesenchymal stem cells, lineage-guided cardiopoietic stem cells, liver regenerating hepatocytes, white blood cells, melanoma cells, and dendritic cells. The developed methodology enables noninvasive PET imaging of cell trafficking for up to 7 days post-administration without affecting the nature or the function of the radiolabeled cells. Additionally, this protocol describes a stepwise method for the radiosynthesis of [89Zr]Zr-DBN, biocompatible formulation of [89Zr]Zr-DBN, preparation of cells for radiolabeling, and finally the radiolabeling of cells with [89Zr]Zr-DBN, including all the intricate details needed for the successful radiolabeling of cells.

Radiometals in Imaging and Therapy: Highlighting Two Decades of Research.

The present article highlights the important progress made in the last two decades in the fields of molecular imaging and radionuclide therapy. Advancements in radiometal-based positron emission tomography, single photon emission computerized tomography, and radionuclide therapy are illustrated in terms of their production routes and ease of radiolabeling. Applications in clinical diagnostic and radionuclide therapy are considered, including human studies under clinical trials; their current stages of clinical translations and findings are summarized. Because the metalloid astatine is used for imaging and radionuclide therapy, it is included in this review. In regard to radionuclide therapy, both beta-minus (ß-) and alpha (α)-emitting radionuclides are discussed by highlighting their production routes, targeted radiopharmaceuticals, and current clinical translation stage.

PET and SPECT Imaging of ALS: An Educational Review.

Amyotrophic lateral sclerosis (ALS) is a disease leading to progressive motor degeneration and ultimately death. It is a complex disease that can take a significantly long time to be diagnosed, as other similar pathological conditions must be ruled out for a definite diagnosis of ALS. Noninvasive imaging of ALS has shed light on disease pathology and altered biochemistry in the ALS brain. Other than magnetic resonance imaging (MRI), two types of functional imaging, positron emission tomography (PET) and single photon emission computed tomography (SPECT), have provided valuable data about what happens in the brain of ALS patients compared to healthy controls. PET imaging has revealed a specific pattern of brain metabolism through [18F]FDG, while other radiotracers have uncovered neuroinflammation, changes in neuronal density, and protein aggregation. SPECT imaging has shown a general decrease in regional cerebral blood flow (rCBF) in ALS patients. This educational review summarizes the current state of ALS imaging with various PET and SPECT radiopharmaceuticals to better understand the pathophysiology of ALS.

A Review of Theranostics: Perspectives on Emerging Approaches and Clinical Advancements.

Theranostics is the combination of two approaches-diagnostics and therapeutics-applied for decades in cancer imaging using radiopharmaceuticals or paired radiopharmaceuticals to image and selectively treat various cancers. The clinical use of theranostics has increased in recent years, with U.S. Food and Drug Administration (FDA) approval of lutetium 177 (177Lu) tetraazacyclododecane tetraacetic acid octreotate (DOTATATE) and 177Lu-prostate-specific membrane antigen vector-based radionuclide therapies. The field of theranostics has imminent potential for emerging clinical applications. This article reviews critical areas of active clinical advancement in theranostics, including forthcoming clinical trials advancing FDA-approved and emerging radiopharmaceuticals, approaches to dosimetry calculations, imaging of different radionuclide therapies, expanded indications for currently used theranostic agents to treat a broader array of cancers, and emerging ideas in the field. Keywords: Molecular Imaging, Molecular Imaging-Cancer, Molecular Imaging-Clinical Translation, Molecular Imaging-Target Development, PET/CT, SPECT/CT, Radionuclide Therapy, Dosimetry, Oncology, Radiobiology © RSNA, 2023.

Morpho-nutritional status of micronutrient efficient wheat (Triticum aestivum L.) genotypes under changing environments.

In India, where cereal-based meals make up the majority of the daily diet, bread wheat (Triticum aestivum L.) is a key grain crop. Micronutrient deficiencies are a result of the lack of a diverse food culture in the nation. Genotypes of bread wheat that have been biofortified might be introduced to address this. It is anticipated that more information on the genotype x year interaction of these nutrients in grain will help us better understand the size of this interaction and perhaps even identify more stable genotypes for this attribute. Year revealed divergent responses to grain iron and zinc. Compared to zinc, iron showed lowest variation across year. Maximum temperature was the major determinant for the four traits. Iron is also significant correlation with zinc. Among the total fifty-two genotype, HP-06, HP-22, HP-24, HP-25, HP-33, HP-44, and HP-45 were found superior for zinc and iron content. These genotypes with high levels of zinc and iron can be used in a hybridization programme to further crop improvement. Wide-scale cultivation of the chosen genotype with high zinc and iron content in the agro-climatic conditions of Jammu will work with the region's current cropping systems.

Isotopic composition of serum zinc and copper in healthy children and children with autism spectrum disorder in North America.

To better understand zinc and copper regulation and their involvement in various biochemical pathways as it relates to autism spectrum disorder (ASD), isotopic composition of serum zinc and copper were evaluated in both healthy children and children with ASD in North America. No significant difference in isotopic composition of serum zinc or copper with respect to healthy controls and ASD children were identified. However, the isotopic composition of serum copper in boys was found to be enriched in 65Cu in comparison to previously published healthy adult copper isotopic composition. Furthermore, in both boys and girls, the average isotopic composition of serum zinc is heavier than previously published healthy adult isotopic zinc composition. There was also a negative association between total zinc concentrations in serum and the zinc isotopic composition of serum in boys. Finally, children with heavier isotopic composition of copper also showed a high degree of variability in their zinc isotopic composition. While numerous studies have measured the isotopic composition of serum zinc and copper in adults, this is one of the first studies which measured the isotopic composition of serum copper and zinc in children, specifically those diagnosed with ASD. The results of this study showed that age and gender specific normal ranges of isotopic composition must be established to effectively use isotopic composition analysis in studying various diseases including ASD.

The role of selenoproteins in neurodevelopment and neurological function: Implications in autism spectrum disorder.

Selenium and selenoproteins play a role in many biological functions, particularly in brain development and function. This review outlines the role of each class of selenoprotein in human brain function. Most selenoproteins play a large antioxidant role within the brain. Autism spectrum disorder (ASD) has been shown to correlate with increased oxidative stress, and the presumption of selenoproteins as key players in ASD etiology are discussed. Further, current literature surrounding selenium in ASD and selenium supplementation studies are reviewed. Finally, perspectives are given for future directions of selenoprotein research in ASD.

Hoop compression driven instabilities in spontaneously formed multilayer graphene blisters over a polymeric substrate.

The blistering of elastic membranes is prone to elastic-solid as well as substrate-based mechanical instabilities. The solid-based instabilities have been well-explored in the mechanically indented blisters of elastic membranes over the rigid/solid substrates, but an integrated study illustrating the underlying mechanism for the onset of solid as well as substrate-based instabilities in the spontaneous blistering of a 2D material is still lacking in the literature. In this article, an extensive experimental as well as analytical analysis of the spontaneous blister-formation in the multilayer graphene (MLG) flakes over a polymeric substrate is reported, which elucidates the involved mechanism and the governing parameters behind the development of elastic-solid as well as viscoelastic-substrate based instabilities. Herein, a 'blister-collapse model' is proposed, which infers that the suppression of the hoop compression, resulting from the phase-transition of the confined matter, plays a crucial role in the development of the instabilities. The ratio of blister-height to flake-thickness is a direct consequence of the taper-angle of the MLG blister and the thickness-dependent elasticity of the upper-bounding MLG flake, which shows a significant impact on the growth-dynamics of the viscous fingering pattern (viscoelastic-substrate based instability) under the MLG blister.

Governing the crystallographic sites for tuning Eu2+ emission in an apatite oxyfluoride host to be applied for superior white light emitting diodes.

Single white light-emitting phosphors for near-UV-converted white light-emitting diodes (WLEDs) are the best alternatives to tricolour phosphor blends and blue light converted yellow-emitting garnets. Nevertheless, achieving white light with elevated colour rendering (CRI) from a single-phase phosphor activated with a lone activator ion is a major challenge. This study aimed at the generation of white light from a single-phase composition activated only with europium. The study started with structural evaluations of Eu3+-activated Ca4La6Si6O24F2 phosphors using X-ray diffraction (XRD) and Eu3+ photoluminescence to elucidate the local environment of rare-earth ions and the symmetric nature of the lattice sites. Ca4La6Si6O24F2 crystallized in the hexagonal P63/m space group. The predominant 5D0-7F2 electric dipole transition at 614 nm, and the non-splitting as well as the zero-shifting behaviour of 5D0-7F0 at 578 nm, suggested that the rare-earth ionic substitutions preferably took place at the larger asymmetric sites. Introducing Sr2+ ions in Ca4La6Si6O24F2:Eu3+/Eu2+ that is synthesized under a reducing atmosphere suppressed Eu3+ emission. From the optimized Ca1.98Sr1.98La6Si6O24F2:0.04Eu2+, a sequence of M2+-codoped (M = Mg/Ba) Ca1.98Sr1.98La6Si6O24F2:0.04Eu2+ phosphors were further developed. The substitutions of Mg2+ and Ba2+ altered the crystal field by changing the lattice parameters. The Mg2+ -doped samples showed a blue-shift from 520 nm (Mg2+ = 0) to 471 nm (Mg2+ = 1.0), whereas the Ba2+-doped compositions showed a red-shift from 520 nm (Ba2+ = 0) to 536 nm (Ba2+ = 1.2). The change of symmetry owing to the Mg2+/Ba2+ substitution could have led to the centroid shift, which was responsible for the blue- or red-shift of the emission spectra. The XRD of Ca1.38Sr1.38La6Si6O24F2:0.04Eu2+,1.2Ba2+ indicated a Ba2+-induced lattice site expansion. Keeping this in view, the Eu2+ ions concentrations were further enhanced from 0.04 to 0.3, and the resultant photoluminescence was further enhanced and red-shifted. The optimized sample showed better intensity compared with the commercial Y3Al5O12:Ce3+ and exhibited decent photoluminescence above 70% at 150 °C as compared with that at room temperature. Finally, several prototype WLEDs were fabricated using the single phosphor Ca1.365Sr1.365La6Si6O24F2:0.07Eu2+,1.2Ba2+ with near-UV and violet-LED chips. The outcomes indicated the promising nature of this single-composition phosphor for indoor lighting.

A Comprehensive Review on Liver Targeting: Emphasis on Nanotechnology- based Molecular Targets and Receptors Mediated Approaches.

BACKGROUND: The pathogenesis of hepatic diseases involves several cells, which complicates the delivery of pharmaceutical agents. Many severe liver diseases affecting the worldwide population cannot be effectively treated. Major hindrances or challenges are natural physiological barriers and non-specific targeting of drugs administered, leading to inefficient treatment. Hence, there is an earnest need to look for novel therapeutic strategies to overcome these hindrances. A kind of literature has reported that drug safety and efficacy are incredibly raised when a drug is incorporated inside or attached to a polymeric material of either hydrophilic or lipophilic nature. This has driven the dynamic investigation for developing novel biodegradable materials, drug delivery carriers, target-specific drug delivery systems, and many other novel approaches. OBJECTIVE: Present review is devoted to summarizing receptor-based liver cell targeting using different modified novel synthetic drug delivery carriers. It also highlights recent progress in drug targeting to diseased liver mediated by various receptors, including asialoglycoprotein, mannose and galactose receptor, Fc receptor, low-density lipoprotein, glycyrrhetinic, and bile acid receptor. The essential consideration is given to treating liver cancer targeting using nanoparticulate systems, proteins, viral and non-viral vectors, homing peptides and gene delivery. CONCLUSION: Receptors based targeting approach is one such approach that was explored by researchers to develop novel formulations which can ensure site-specific drug delivery. Several receptors are on the surfaces of liver cells, which are highly overexpressed in various disease conditions. They all are helpful for the treatment of liver cancer.

Evaluation of different 89Zr-labeled synthons for direct labeling and tracking of white blood cells and stem cells in healthy athymic mice.

Cell based therapies are evolving as an effective new approach to treat various diseases. To understand the safety, efficacy, and mechanism of action of cell-based therapies, it is imperative to follow their biodistribution noninvasively. Positron-emission-tomography (PET)-based non-invasive imaging of cell trafficking offers such a potential. Herein, we evaluated and compared three different ready-to-use direct cell radiolabeling synthons, [89Zr]Zr-DFO-Bn-NCS, [89Zr]Zr-Hy3ADA5-NCS, and [89Zr]Zr-Hy3ADA5-SA for PET imaging-based trafficking of white blood cells (WBCs) and stem cells (SCs) up to 7 days in athymic nude mice. We compared the degree of 89Zr complexation and percentage of cell radiolabeling efficiencies with each. All three synthons, [89Zr]Zr-DFO-Bn-NCS, [89Zr]Zr-Hy3ADA5-NCS, and [89Zr]Zr-Hy3ADA5-SA, were successfully prepared, and used for radiolabeling of WBCs and SCs. The highest cell radiolabeling yield was found for [89Zr]Zr-DFO-Bn-NCS, followed by [89Zr]Zr-Hy3ADA5-NCS, and [89Zr]Zr-Hy3ADA5-SA. In terms of biodistribution, WBCs radiolabeled with [89Zr]Zr-DFO-Bn-NCS or [89Zr]Zr-Hy3ADA5-NCS, were primarily accumulated in liver and spleen, whereas SCs radiolabeled with [89Zr]Zr-DFO-Bn-NCS or [89Zr]Zr-Hy3ADA5-NCS were found in lung, liver and spleen. A high bone uptake was observed for both WBCs and SCs radiolabeled with [89Zr]Zr-Hy3ADA5-SA, suggesting in-vivo instability of [89Zr]Zr-Hy3ADA5-SA synthon. This study offers an appropriate selection of ready-to-use radiolabeling synthons for noninvasive trafficking of WBCs, SCs and other cell-based therapies.

Design, Synthesis, and Preliminary Evaluation of [68Ga]Ga-NOTA-Insulin as a PET Probe in an Alzheimer's Disease Mouse Model.

Aberrant insulin signaling has been considered one of the risk factors for the development of Alzheimer's disease (AD) and has drawn considerable attention from the research community to further study its role in AD pathophysiology. Herein, we describe the development of an insulin-based novel positron emission tomography (PET) probe, [68Ga]Ga-NOTA-insulin, to noninvasively study the role of insulin in AD. The developed PET probe [68Ga]Ga-NOTA-insulin showed a significantly higher uptake (0.396 ± 0.055 SUV) in the AD mouse brain compared to the normal (0.140 ± 0.027 SUV) mouse brain at 5 min post injection and also showed a similar trend at 10, 15, and 20 min post injection. In addition, [68Ga]Ga-NOTA-insulin was found to have a differential uptake in various brain regions at 30 min post injection. Among the brain regions, the cortex, thalamus, brain stem, and cerebellum showed a significantly higher standard uptake value (SUV) of [68Ga]Ga-NOTA-insulin in AD mice as compared to normal mice. The inhibition of the insulin receptor (IR) with an insulin receptor antagonist peptide (S961) in normal mice showed a similar brain uptake profile of [68Ga]Ga-NOTA-insulin as it was observed in the AD case, suggesting nonfunctional IR in AD and the presence of an alternative insulin uptake route in the absence of a functional IR. The Gjedde-Patlak graphical analysis was also performed to predict the input rate of [68Ga]Ga-NOTA-insulin into the brain using MicroPET imaging data and supported the in vivo results. The [68Ga]Ga-NOTA-insulin PET probe was successfully synthesized and evaluated in a mouse model of AD in comparison with [18F]AV1451 and [11C]PIB to noninvasively study the role of insulin in AD pathophysiology.

Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography.

T cells genetically engineered to express chimeric antigen receptors (CAR) have shown unprecedented results in pivotal clinical trials for patients with B cell malignancies or multiple myeloma (MM). However, numerous obstacles limit the efficacy and prohibit the widespread use of CAR T cell therapies due to poor trafficking and infiltration into tumor sites as well as lack of persistence in vivo. Moreover, life-threatening toxicities, such as cytokine release syndrome or neurotoxicity, are major concerns. Efficient and sensitive imaging and tracking of CAR T cells enables the evaluation of T cell trafficking, expansion, and in vivo characterization and allows the development of strategies to overcome the current limitations of CAR T cell therapy. This paper describes the methodology for incorporating the sodium iodide symporter (NIS) in CAR T cells and for CAR T cell imaging using [18F]tetrafluoroborate-positron emission tomography ([18F]TFB-PET) in preclinical models. The methods described in this protocol can be applied to other CAR constructs and target genes in addition to the ones used for this study.

Polymer curing assisted formation of optically visible sub-micron blisters of multilayer graphene for local strain engineering.

The local or global straining techniques are used to modulate the electronic, vibrational and optical properties of the two-dimensional (2D) materials. However, manipulating the physical properties of a 2D material under a local strain is comparatively more challenging. In this work, we demonstrate an easy and efficient polymer curing assisted technique for the formation of optically visible multilayer graphene (MLG) blisters of different shapes and sizes. The detailed spectroscopic and morphological analyses have been employed for exploring the dynamics of the confined matter inside the sub-micron blisters, which confirms that the confined matter inside the blister is liquid (water). From further analyses, we find the nonlinear elastic plate model as an acceptable model under certain limits for the mechanical analyses of the MLG blisters over the (poly)vinyl alcohol (PVA) polymer film to estimate the MLG-substrate interfacial adhesion energy and confinement pressure inside the blisters. The findings open new pathways for exploiting the technique for the formation of sub-micron blisters of the 2D materials for local strain-engineering applications, as well as the temperature-controlled release of the confined matter.

A new solid target design for the production of 89Zr and radiosynthesis of high molar activity [89Zr]Zr-DBN.

Due to the advent of various biologics like antibodies, proteins, cells, viruses, and extracellular vesicles as biomarkers for disease diagnosis, progression, and as therapeutics, there exists a need to have a simple and ready to use radiolabeling synthon to enable noninvasive imaging trafficking studies. Previously, we reported [89Zr]zirconium-p-isothiocyanatobenzyl-desferrioxamine ([89Zr]Zr-DBN) as a synthon for the radiolabeling of biologics to allow PET imaging of cell trafficking. In this study, we focused on improving the molar activity (Am) of [89Zr]Zr-DBN, by enhancing 89Zr production on a low-energy cyclotron and developing a new reverse phase HPLC method to purify [89Zr]Zr-DBN. To enhance 89Zr production, a new solid target was designed, and production yield was optimized by varying, thickness of yttrium foil, beam current, irradiation duration and proton beam energy. After optimization, 4.78±0.33 GBq (129.3±8.9 mCi) of 89Zr was produced at 40 µA for 180 min (3 h) proton irradiation decay corrected to the end of bombardment with a saturation yield of 4.56±0.31 MBq/µA. Additionally, after reverse phase HPLC purification the molar activity of [89Zr]Zr-DBN was found to be in 165-316 GBq/µmol range. The high molar activity of [89Zr]Zr-DBN also allowed radiolabeling of low concentration of proteins in relatively higher yield. The stability of [89Zr]Zr-DBN was measured over time with and without the presence of ascorbic acid. The newly designed solid target assembly and HPLC method of [89Zr]Zr-DBN purification can be adopted in the routine production of 89Zr and [89Zr]Zr-DBN, respectively.

Corrigendum: Evaluation of Zn, Cu, and Se Levels in the North American Autism Spectrum Disorder Population.

[This corrects the article DOI: 10.3389/fnmol.2021.665686.].