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Strategies for controlling the size of metal species using zeolites and their catalytic behavior in industrially relevant processes have attracted widespread attention, but the effect of H2O and CO2 on the catalytic performance of zeolite-based metal catalysts remains obscure. This study investigated the influence of H2O and CO2 on CO oxidation over zeolite-based metal catalysts, along with the precise control of active sites through the regulation of Lewis acidity. It was found that the presence of H2O enhanced CO oxidation and alleviated the inhibitory effect of CO2. Abundant Lewis acid sites of low SiO2/Al2O3 ratios in the Pt/SSZ-13 catalyst facilitate Pt dispersion (61.07%), a high Ptn+/Pt ratio (4.43), and small Pt particles (2.31 nm) formation. In situ DRIFTS revealed that CO2 inhibits CO adsorption and the decomposition of carbon intermediates. Water alters the CO adsorption configuration of Pt0, thereby weakening the Pt–CO bond to promote the CO oxidation reaction. Meanwhile, water dissociated into hydroxyl groups on the surface adsorbs oxygen species, participating in reactions and promoting CO2 production from carbon intermediates. H218O isotope labeling experiments validated the water involvement in the reaction and emphasized the importance of the presence of oxygen species during the water dissociation process. Regulation of Lewis acid sites promotes the Ptn+ species formation, enhancing the CO oxidation activity, while Pt0 species enhance the water-promotion effect. [ABSTRACT FROM AUTHOR]

Matrix effects pose a significant challenge in food analysis for the quantitative analysis of complex food samples. Herein, a novel magnetic covalent organic framework nanocomposite and the copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) click reaction-based stable isotope labeling (SIL) method were presented for highly selective and sensitive detection of steroid hormones in food samples using HPLC-MS/MS. The nanocomposite, Fe3O4@TAPB-COF, with a core–shell structure exhibited high adsorption capacities for steroid hormones. Combined with a SIL method based on the CuAAC click reaction, steroid hormones were accurately quantified in food samples with high sensitivity and selectivity. A pair of SIL agents, N-(2-azidoethyl)aniline (d0-NAEA) and d5-N-(2-azidoethyl)aniline (d5-NAEA), was synthesized to label steroid hormones in the samples and standard solutions, respectively. The labeling reaction is highly specific, and the formation of the derivatives is easily ionized by MS, thus overcoming matrix effects. More surprisingly, the ionization efficiency of steroid hormones increased by a factor of 4 to 56, with matrix effects ranging from 87.3 to 99.3%. Under optimal conditions, this method exhibited a low limit of detection (LOD) ranging from 0.1 to 2.6 μg L−1 and overcame the interference of matrix effects for trace-level steroid hormone analysis in foodstuffs. [ABSTRACT FROM AUTHOR]

Biflorane diterpenoids are unique natural products often seen in marine animals. Recent studies have reported a small number of biflorane synthases. However, the catalytic mechanism and structural basis for biflorane formation remain unclear. To address these issues, we conducted genome mining of terpene synthases from the sea whip coral Paramuricea clavata, resulting in the discovery of a biflorane synthase PcTS1. We performed a series of isotope labeling, crystallography, quantum mechanics/molecular mechanics calculations, and mutagenesis studies toward PcTS1 to investigate the mechanism. Isotopic labeling studies, together with calculations, elucidate a cascade of 1,10-cyclization, 1,3-hydride shift, 1,6-cyclization, 1,2-hydride shift, 2,6-cyclization, cyclopropane ring opening, and deprotonation by the generated pyrophosphate, forming the biflorane scaffold. Crystallography, quantum mechanics/molecular mechanics, and mutagenesis studies confirmed the cascade and produced different terpene scaffolds. Our work demonstrated the mechanism of marine biflorane formation, elucidated the second crystal structure of a coral terpene synthase, and realized the terpene skeleton expansion. [ABSTRACT FROM AUTHOR]

Background: Targeted alpha therapy with Ac-225 showed to be effective in treating metastatic cancers. However, the complex decay chain requires optimized radiolabeling and quality control. This study aims to determine critical parameters and establish optimal labeling and accurate measuring techniques for radiochemical yield and purity with DOTA-TATE as a model molecule. Ac-225 sources were analyzed for metals (ΣFe, Zn, Cu) and quantified by UPLC. Optimization of radiolabeling kinetics for clinical conditions was performed in regards to temperature (20–90 °C), heating time (5–60 min), pH (2.5–10, with/without excess of metal ions), buffers, quenchers, volume (0.1–10 mL) and molar activity (90–540 kBq/nmol). The quality control was investigated using radio-TLC/HPLC by changing gradient to evaluate peak separation, radiolysed peptide and impurity separation. Results: Metal ingrowth was observed in Ac-225 stocks (n = 3), (time of arrival: 17.9, 36.8 and 101.4 nmol per 10 MBq). Optimal radiochemical yields were achieved with > 80 °C (20 min) at pH 8.5 (15 mM TRIS) up to 270 kBq. Labeling at a high pH showed a higher RCY, even in presence of an excess of metals. High stability (RCP > 90%) was achieved after addition of quenchers (cysteine, methionine, ascorbate, histidine, or gentisic acid (35 mM)) up to 24 h. For optimal determination of the radiochemical purity (indirect HPLC) fifty fractions are required. Conclusion: The quality of Ac-225 labeled DOTA-radiopharmaceuticals is highly dependent on the pH and stabilization (buffer/quencher). Within this research it is demonstrated that optimized quality control methods and accurate measurement of the radiolabeling kinetics are crucial to ensure safe implementation for patient treatment. [ABSTRACT FROM AUTHOR]

Bone is one of the most common target organs for distant metastases of solid tumors, which imposes a heavy burden on society. Early diagnosis of bone metastases is of great significance and positron emission tomography (PET) imaging plays an important role in the diagnosis of bone metastases. PET tracers applied for diagnosing bone metastases are constantly being updated, but they all have certain limitations like a relatively low bone/kidney ratio or no capacity to label therapeutic radionuclides. Alendronate, a representative bisphosphonate (BP), has been usually considered the standard clinical treatment for bone related diseases. In this study, alendronate was strategically modified with different linkers in an attempt to improve target/non-target ratios and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was used as the chelator. Finally, three 68Ga-labeled tracers were successfully developed. The results showed that [68Ga]Ga-AABP1/2/3 all exhibited high radiochemical purity, biosafety, and excellent stability. In the biodistribution study of normal BALB/c mice, [68Ga]Ga-AABP3, when modified with phenylalanine and β-alanine as the linker, showed the highest bone/non-bone ratio at 1.5 h. In micro-PET/CT imaging of normal BALB/c mice, [68Ga]Ga-AABP3 showed the highest SUVmax value at the bones (2.24 ± 0.16 at 1.5 h). In micro-PET/CT imaging of the mouse model of bone metastases, compared with [68Ga]Ga-AABP1 and [68Ga]Ga-AABP2, the SUVmax in the foci after injection of [68Ga]Ga-AABP3 was the highest (2.64 ± 0.08 at 0.5 h and 2.67 ± 0.10 at 1.5 h), significantly higher than that of the contralateral normal bone. Besides, [68Ga]Ga-AABP3 showed the highest tumor/non-tumor ratio at 1.5 h. The results suggest that [68Ga]Ga-AABP3 has the potential for diagnosis of bone metastases. Furthermore, AABP3 with the chelator DOTA could also be labeled with 177Lu or 225Ac, providing possibility for further application in radioligand therapy. [ABSTRACT FROM AUTHOR]

NO x emissions have consistently posed a key challenge for ammonia-fueled engines. Furthermore, the mechanism of NO x formation is complicated by the co-existence of fuel and thermal NO x in ammonia engines. In this study, the mechanisms behind thermal and fuel NO x formation in ammonia–diesel engines are investigated using isotopic labeling methods. The results indicate that temperature and reaction time jointly influence the formation of both types of NO x. Specifically, higher temperatures and longer reaction times lead to increased thermal NO x formation. However, fuel NO x is primarily affected by oxygen concentration. A turning point in the dominance of fuel and thermal NO x formation was observed with increasing oxygen concentration in marine ammonia–diesel engines. The maximum reaction temperature rose by 310 K when the oxygen concentration increased from 0.14 to 0.20, and the duration above 2400 K was extended by 17° CA. Higher temperatures and prolonged reaction times caused the influence of temperature on thermal NO x to surpass that of oxygen concentration on fuel NO x. When the oxygen concentration exceeded 0.20, thermal NO x constituted a larger proportion than fuel NO x in marine engines. These findings provide a valuable reference for optimizing future NO x emission strategies in ammonia–diesel engines. • Used the isotope labeling method for the research. • Studied the effects of oxygen concentration and temperature on NO x emissions. • Studied oxygen concentration's impact on fuel and thermal NO x in marine engines. • Found that when oxygen exceeds 0.20, thermal NO x dominates in marine engines. • Results offer insights into NO x emission control for ammonia-fueled engines. [ABSTRACT FROM AUTHOR]

Adeno-associated virus (AAV) mediated gene therapy is advancing and needs a noninvasive imaging tool to evaluate its effective targeting, biodistribution and clearance for precise use in humans. In this study, two serotypes of AAVs, AAV9-CMV-fLuc, and a brain targeting variant, AAVBR1-CMV-fLuc, are directly radiolabeled with the positron emission tomography (PET) radioisotope, 89Zr. A radiolabeling synthon, [89Zr]Zr-DFO-Bn-NCS or [89Zr]Zr-DBN, was employed for the direct radiolabeling of AAVs, which enables tracking of AAVs by PET imaging for up to 18 days post-injection. The 89Zr radiolabeled AAVs were administered to BALB/c mice via tail vein and assessed for their biodistribution at various time points up to day 18 post-injection. Imaging of AAVs was followed by ex-vivo biodistribution at day 18, or luciferase imaging at 3rd week or > 30 days post-injection. The two serotypes showed differences in their biodistribution and trafficking in mice as early as 10 min post-injection. The brain targeting serotype, [89Zr]Zr-AAVBR1-CMV-fLuc, showed significantly higher uptake in the brain as compared to [89Zr]Zr-AAV9-CMV-fLuc. The luciferase expression-based infection profile correlated with both PET imaging and ex-vivo biodistribution data. The developed methodology provides a noninvasive approach to image the pharmacokinetics of AAVs in a longitudinal manner and renders a selection of specific AAV serotypes for tissue/organ specific targeting. [ABSTRACT FROM AUTHOR]

Simple Summary: Caffeine contamination in water sources is a growing concern due to its potential impact on food safety and human health. This study focused on understanding how caffeine from water sources accumulates in tea plants, specifically how it moves within the plant and its distribution at the cellular level. Using a hydroponic system, we tracked caffeine labeled with a radioactive isotope 14C. We found that the caffeine mainly accumulated in the roots, with specific distribution patterns observed within the cells. The study also discovered that different varieties of tea plants metabolite caffeine differently. In one variety, the caffeine remained mostly unchanged, while in another variety, caffeine was converted into xanthine. Caffeine contamination in water sources raises concerns about its transfer to agricultural products and potential risks to human health through the food chain. Despite these concerns, limited research has focused on the accumulation and distribution of exogenous caffeine in tea plants. This study explored the uptake, translocation, targeted accumulation, subcellular distribution, and preliminary metabolism of 14C-labeled caffeine in a hydroponic tea seedling system. After 192 h of cultivation, more than 83.8% of the caffeine had been removed from the nutrient solution. Within the plants, 14C-caffeine and its metabolites predominantly accumulated in the roots. Subcellular analysis indicates that in root cells, 14C was mainly distributed in the soluble fraction, cell walls, and plastids, while in shoot cells, it was concentrated in the soluble fraction and cell walls. Metabolic profiling reveals distinct varietal differences: in Longjing 43 tea seedlings, 14C was predominantly present as the caffeine parent compound, whereas in Jiaming No. 1 tea seedlings, 14C was found both as the parent compound and as its metabolite, xanthine. This study revealed differences in the uptake, translocation, and metabolism of exogenous caffeine among different tea plant varieties, providing broader insights into the impact of caffeine pollution on agricultural ecosystems. [ABSTRACT FROM AUTHOR]

Citrinin (CIT) is a nephrotoxic mycotoxin commonly found in a broad range of foods, including cereals, spices, nuts, or Monascus fermentation products. Analyses have shown that CIT is present in processed foods in significantly lower concentrations than in unprocessed materials. Modified forms of CIT arising during food processing may provide an explanation for the discrepancy. This study deals with the thermal stability of CIT and the formation of reaction products of CIT with carbohydrates, followed by toxicological evaluations using cell culture models. HPLC-HRMS degradation curves of CIT heated in different matrix model systems were recorded, and the formation of decarboxycitrinin (DCIT), the main degradation product, was quantified. Additionally, chemical structures of reaction products of CIT with carbohydrates were tentatively identified using MS/MS spectra and stable isotope labelling. Subsequently, the degradation of CIT during biscuit baking was studied, and carbohydrate-bound forms of CIT were detected after enzymatic starch digestion. The formation of DCIT could explain the majority of CIT degradation, but, depending on the process, covalent binding to carbohydrates can also be highly relevant. Cytotoxicity of DCIT in IHKE-cells was found to be lower compared to CIT, while the toxicity as well as the intestinal metabolism of carbohydrate-bound CIT was not evaluated. [ABSTRACT FROM AUTHOR]

Background: Cancer-associated fibroblasts (CAFs) are key contributors to the tumorigenic process, with fibroblast activation protein (FAP) overexpressed on CAFs in numerous epithelial carcinomas. FAP represents a promising target for tumor imaging and therapy. We aimed to develop a novel [18F]AlF-H3RESCA-FAPI radiotracer with a high labeling yield at room temperature for positron emission tomography (PET) imaging of FAP-expressing tumors. Methods: The H3RESCA-FAPI chelator was synthesized and radiolabeled with [18F]AlF. Its radiotracer binding affinity to FAP was assessed using surface plasmon resonance (SPR). Its in vitro stability, plasma clearance, and biodistribution were evaluated. PET imaging was performed in U87MG tumor-bearing mice, with a blocking study to assess tracer specificity. Results: The [18F]AlF-H3RESCA-FAPI radiotracer demonstrated a high binding affinity to FAP (KD < 10.09 pM) and favorable radiochemical yields (92.4 ± 2.4%) with >95% radiochemical purity. In vitro and in vivo studies showed good stability and rapid clearance from non-target tissues. PET imaging revealed specific tumor uptake, which was significantly reduced by co-injection with unlabeled DOTA-FAPI-04. Conclusions: [18F]AlF-H3RESCA-FAPI is a promising radiotracer for PET imaging of FAP-expressing tumors. Further optimization of its pharmacokinetics could make it a potential candidate for clinical translation. [ABSTRACT FROM AUTHOR]

Background: The rapid rise in cancer incidence significantly augments efforts to improve cancer treatments. A multimodal approach in the nanobrachytherapy of solid tumors is one of the promising methods under investigation. This study presents a novel biocompatible lignin-based nanomaterial, loaded with cytostatic agent SN-38 and radionuclide 131I, for simultaneous radiation and chemotherapy of solid tumors by a nanobrachytherapy approach. Method: Nanoparticles of ~100 nm in size, composed of lignin alone or loaded with 10% (m/m) of SN-38 (SN-38@lignin), were synthesized using a bottom-up approach and characterized. Subsequent radiolabeling of the nanoparticles by 131I produced 131I-lignin and 131I-SN-38@lignin. Their antitumor efficiency was tested against luciferase-expressing 4T1 mouse breast cancer xenografts of ~100 mm3 size on Balb/c mice. Results: An intratumoral injection of 1.85 MBq of 131I-lignin was retained within the tumor and achieved a moderate twofold decrease in tumor size compared to the control group. Injecting SN-38@lignin containing 25 µg of SN-38 decreased tumor size 3.5-fold. The therapy using the same doses of 131I-SN-38@lignin produced the most potent antitumor effect, with tumors being 6-fold smaller and having extensive intratumoral necrosis, all of it without signs of systemic toxicity. Conclusions: These results support the intratumoral delivery of lignin-based nanomaterial carrying radioisotopes and camptothecins for effective multimodal anticancer therapy. [ABSTRACT FROM AUTHOR]

Dual-labeled compounds that combine radiolabeling and fluorescence labeling represent a significant advancement in precision oncology. Their clinical implementation enhances patient care and outcomes by leveraging the high sensitivity of radioimaging for tumor detection and taking advantage of fluorescence-based optical visualization for surgical guidance. Non-invasive radioimaging facilitates immediate identification of both primary tumors and metastases, while fluorescence imaging assists in decision-making during surgery by offering a spatial distinction between malignant and non-malignant tissue. These advancements hold promise for enhancing patient outcomes and personalization of cancer treatment. The development of dual-labeled molecular probes targeting various cancer biomarkers is crucial in addressing the heterogeneity inherent in cancer pathology and recent studies had already demonstrated the impact of dual-labeled compounds in surgical decision-making (NCT03699332, NCT03407781). This review focuses on the development and application of small dual-labeled peptides in the imaging and treatment of various cancer types. It summarizes the biomarkers targeted to date, tracing their development from initial discovery to the latest advancements in peptidomimetics. Through comprehensive analysis of recent preclinical and clinical studies, the review demonstrates the potential of these dual-labeled peptides to improve tumor detection, localization, and resection. Additionally, it highlights the evolving landscape of dual-modality imaging, emphasizing its critical role in advancing personalized and effective cancer therapy. This synthesis of current research underscores the promise of dual-labeled peptides in enhancing diagnostic accuracy and therapeutic outcomes in oncology. [ABSTRACT FROM AUTHOR]

2-Amino-3-(4-hydroxyphenyl)-1-hydroxypropyl-1,1-bisphosphonic acid (TyrBP), a nitrogenated bisphosphonate (NBP), has been synthesized in a one-pot two-step process involving the phosphonation of L-tyrosine with phosphorus reagents (PCl3 and H3PO3) followed by hydrolysis. TyrBP was characterized using IR, NMR, and mass spectroscopy, and underwent a 99mTc-radiolabeling study to produce a potential bone imaging agent using sodium borohydride as a reducing agent for 99mTc eluted from the 99Mo/99mTc generator. Optimization of the radiolabeling conditions was performed to achieve a high radiochemical yield. [ABSTRACT FROM AUTHOR]

This study explored the use of ultrasound as an alternative to the traditional boiling water bath method for producing [99mTc]Tc-MAG3, a radiopharmaceutical. The researchers compared the efficiency, stability, and biological distribution of the radiotracer prepared by both methods. Ultrasound irradiation proved to be an effective and efficient method for producing [99mTc]Tc-MAG3, offering a greener and potentially more clinically viable approach. [ABSTRACT FROM AUTHOR]

Background: Through its central role in neurotransmission, the vesicular acetylcholine transporter (VAChT) is an increasingly valuable target for positron emission tomography (PET). VAChT ligands have been mostly derived from the vesamicol structure, but with limitations in available labelling methods and selectivity for VAChT against σ receptors being a common pitfall of such compounds, the development of selective VAChT tracers remains a challenge. Modern labelling techniques, in this case the [11C]MeLi cross-coupling methodology, expands labelling opportunities, allowing to explore novel vesamicol-based structures as potential PET-tracers. Results: A series of vesamicol derivatives was synthesized and their binding towards VAChT, σ1 and σ2 receptors assessed. Of all compound tested, (-)-2-methylspirobenzovesamicol ((-)-4) was the most promising with a 16 ± 4 nM affinity towards VAChT, a 29-fold weaker affinity for σ1 receptors and negligible binding (> 1 μM) towards σ2 receptors. The radiolabelling was performed from the corresponding bromide using a [11C]MeLi cross-coupling protocol, yielding 2-[11C]methylspirobenzovesamicol in 32–37% RCY. New in vitro binding data is also made available for (-)-FEOBV with human-sourced σ1 receptors, revealing a 300-fold stronger affinity for VAChT compared to σ receptors. Conclusion: (-)-2-methylspirobenzovesamicol was identified as a potent and selective VAChT ligand, with moderate to low affinity for σ receptors, and its racemate was radiolabeled in good radiochemical yields with Carbon-11. At this stage, [11C]-methyl-2-methylspirobenzovesamicol appears a promising 11C-PET tracer for VAChT imaging. [ABSTRACT FROM AUTHOR]

Cystic echinococcosis is a parasitic disease caused by the development of the larval form (hydatid cyst) of Echinococcus granulosus sensu lato (s.l) in humans and herbivores. In this study, antigen 5 (Ag 5), recognized as the major and most immunogenic fraction of E. granulosus (s.l), was partially purified using ammonium sulfate precipitation at 70 % saturation and characterized by physicochemical and immunological methods. Analysis of the supernatant resulting from the precipitation showed typical mobility for antigen 5. The antigen produced a single precipitation arc when tested against a pool of sera from patients and rabbits immunized with this antigen. A band of approximately 66 kDa was observed through SDS-PAGE under denaturing conditions. Radiolabeling of the antigen with iodine-125 (I125) achieved a yield of 63 % with a radiochemical purity of 92.6 %. In evaluating antigenic integrity, a tolerable non-specific binding of 16 % was observed, alongside satisfactory specific binding of 60 % when tested with rabbit anti-fraction 5 serum. These preliminary results are promising and will be further refined to determine optimal conditions for preparing a high-quality tracer, which could be valuable in the diagnosis of hydatid disease. [ABSTRACT FROM AUTHOR]

Background: The immunopeptidome is constantly monitored by T cells to detect foreign or aberrant HLA peptides. It is highly dynamic and reflects the current cellular state, enabling the immune system to recognize abnormal cellular conditions, such as those present in cancer cells. To precisely determine how changes in cellular processes, such as those induced by drug treatment, affect the immunopeptidome, quantitative immunopeptidomics approaches are essential. Methods: To meet this need, we developed a pulsed SILAC-based method for quantitative immunopeptidomics. Metabolic labeling with lysine, arginine, and leucine enabled isotopic labeling of nearly all HLA peptides across all allotypes (> 90% on average). We established a data analysis workflow that integrates the de novo sequencing-based tool Peptide-PRISM for comprehensive HLA peptide identification with MaxQuant for accurate quantification. Results: We employed this strategy to explore the modulation of the immunopeptidome upon MAPK pathway inhibition (MAPKi) and to investigate alterations associated with early cellular responses to inhibitor treatment and acquired resistance to MAPKi. Our analyses demonstrated significant changes in the immunopeptidome early during MAPKi treatment and in the resistant state. Moreover, we identified putative tumor-specific cryptic HLA peptides linked to these processes that might represent exploitable targets for cancer immunotherapy. Conclusions: We have developed a new mass spectrometric approach that allowed us to investigate the effects of common MAPK inhibitors on the immunopeptidome of melanoma cells. This finally led to the discovery of new potential targets for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Plant cell walls are made of a complex network of interacting polymers that play a critical role in plant development and responses to environmental changes. Thus, improving plant biomass and fitness requires the elucidation of the structural organization of plant cell walls in their native environment. The 13C-based multi-dimensional solid-state nuclear magnetic resonance (ssNMR) has been instrumental in revealing the structural information of plant cell walls through 2D and 3D correlation spectral analyses. However, the requirement of enriching plants with 13C limits the applicability of this method. To our knowledge, there is only a very limited set of methods currently available that achieve high levels of 13C-labeling of plant materials using 13CO2, and most of them require large amounts of 13CO2 in larger growth chambers. Results: In this study, a simplified protocol for 13C-labeling of plant materials is introduced that allows ca 60% labeling of the cell walls, as quantified by comparison with commercially labeled samples. This level of 13C-enrichment is sufficient for all conventional 2D and 3D correlation ssNMR experiments for detailed analysis of plant cell wall structure. The protocol is based on a convenient and easy setup to supply both 13C-labeled glucose and 13CO2 using a vacuum-desiccator. The protocol does not require large amounts of 13CO2. Conclusion: This study shows that our 13C-labeling of plant materials can make the accessibility to ssNMR technique easy and affordable. The derived high-resolution 2D and 3D correlation spectra are used to extract structural information of plant cell walls. This helps to better understand the influence of polysaccharide-polysaccharide interaction on plant performance and allows for a more precise parametrization of plant cell wall models. [ABSTRACT FROM AUTHOR]

Due to their intriguing emission profile, Terbium-161 (161Tb) radiopharmaceuticals seem to bring significant advancement in theranostic applications to cancer treatment. The combination of 161Tb with nanoscale brachytherapy as an approach for cancer treatment is particularly advantageous and promising. Herein, we propose the application of a hybrid nanosystem comprising gold decorated (Au@TADOTAGA) iron oxide nanoflowers as a form of injectable nanobrachytherapy for the local treatment of breast cancer. More specifically, Au@TADOTAGA and NFAu@TADOTAGA NPs were efficiently radiolabeled with 161Tb, and their in vitro stability was assessed up to 21 d post-radiolabeling. Furthermore, their cytotoxic profile against 4T1 breast cancer cells was evaluated, and their ex vivo biodistribution characteristics were revealed after intratumoral injection in the same animal model. The enhanced retention at the tumor site urged us to evaluate the therapeutic effect of the [161Tb]Tb-NFAu@TADOTAGA nanosystem after intratumoral administration to 4T1-tumor-bearing mice, over a period of 24 days. Three different therapeutic protocols were performed in order to identify which therapeutic approach would offer the optimum results and identify the proposed nanosystem as a promising nanoscale brachytherapy agent. [ABSTRACT FROM AUTHOR]

Despite considerable experimental effort, the physiological mechanisms governing temperate tree species' water and carbon dynamics before the onset of the growing period remain poorly understood. We applied 2H‐enriched water during winter dormancy to the soil of four potted European tree species. After 8 weeks of chilling, hydrogen isotopes in stem, twig and bud water were measured six times during 2 consecutive weeks of forcing conditions (Experiment 1). Additionally, we pulse‐labelled above‐ground plant tissues using 2H‐enriched water vapour and 13C‐enriched CO2 7 days after exposure to forcing conditions to trace atmospheric water and carbon uptake (Experiment 2). Experiment 1 revealed soil water incorporation into the above‐ground organs of all species during the chilling phase and significant species‐specific differences in water allocation during the forcing conditions, which we attributed to differences in structural traits. Experiment 2 illustrated water vapour incorporation into all above‐ground tissue of all species. However, the incorporation of carbon was found for evergreen saplings only. Our results suggest that temperate trees take up and reallocate soil water and absorb atmospheric water to maintain sufficient above‐ground tissue hydration during winter. Therefore, our findings provide new insights into the water allocation dynamics of temperate trees during early spring. Summary statement: Our stable isotope labelling study demonstrates that tree saplings take up soil and atmospheric water to hydrate above‐ground tissues before budburst. However, no carbon uptake was found for the investigated deciduous species during this period. [ABSTRACT FROM AUTHOR]

A novel Radioimmunoassay (RIA) method was developed for measuring C-reactive protein (CRP) in human serum. The development of CRP-RIA includes CRP radiolabelling with Na125I using the Chloramine -T method to prepare 125I-CRP tracer and purify it using Sephadex G-25 Column. Polyclonal anti-CRP was coupled with magnetizable cellulose particles with an average particle size of < 2 µm. Two types of assays were developed: (1) An assay with an extended standard range (0–6400 ng/mL), which can measure CRP levels up to 160,000 ng/mL, and (2) A sensitive assay (0–200 ng/mL), which can measure the CRP level in human serum as low as 3 ng/mL. The developed assay procedures were validated after studying standard assay parameters such as sensitivity, assay variations, linearity of dilution, etc. This assay is user-friendly, with only three pipetting steps and a convenient incubation time of 1 h at room temperature. The developed CRP-RIA method covers the entire physiological and clinical useful range for routine estimation of CRP in human serum. [ABSTRACT FROM AUTHOR]

In this study, we have labeled methacetin with carbon-11 [11C] as a PET imaging radiotracer. The radiolabeling was carried out by reacting acetaminophen with [11C]methyl iodide in the presence of a base using [11C]methyl iodide. [11C]methacetin was synthesized via methylation at 70 °C for 5 min with a radiochemical purity of 99.3 ± 0.4 % and radiochemical yield was 34.6 ± 4.7 %. The tissue distribution showed higher uptake in blood pool at 5 min followed by increased uptake in lungs, liver and spleen. [ABSTRACT FROM AUTHOR]

Objective(s): Liver malignancies are among the most prevalent causes of cancerrelated deaths worldwide. Intra-arterial administration of particulates labeled with beta-emitting radionuclides is one of the non-surgical promising modalities for the treatment of liver cancer. Methods: In this work, the radiation absorbed dose of 166Ho-hydroxyapatite (166Ho-HA) radiopharmaceutical was estimated for adult men based on biodistribution data in normal Wistar rats. The MIRD dose calculation method and the Sparks and Aydogan methodology were applied. Results: The results show that more than 84% of the absorbed dose is localized in liver tissue (7.35 mGy MBq-1). Also, radiation absorbed doses of 166Ho-HA for red bone marrow, osteogenic cells, and spleen tissues were estimated to be about 0.18, 0.38, and 0.24 mGy MBq-1, respectively. The maximum administrated activity was obtained at 87.5 MBq kg-1 of body weight with an effective dose of 0.39 mSv MBq-1. The maximum tolerable dose (MTD) for liver tissue was 6.13 GBq (165.56 mCi). Conclusion: This study indicated that 166Ho-HA can provide an impressive dose for liver cancer malignancies with an insignificant dose to healthy tissues. [ABSTRACT FROM AUTHOR]

Isotopic pulse-labelling of photosynthate allows tracing of carbon (C) from tree canopies to below-ground biota and calculations of its turnover in roots and recipient soil microorganisms. A high concentration of label is desirable but is difficult to achieve in field studies of intact ecosystem patches with trees. Moreover, root systems of trees overlap considerably in most forests, which requires a large labelled area to minimize the impact of C allocated below-ground by un-labelled trees. We describe a method which combines a high level of labelling at ambient concentrations of CO2, [CO2], with undisturbed root systems and a model to account for root C and root-derived C from un-labelled trees. We raised 5-m-tall chambers, each covering 50 m2 of ground (volume 250 m3) in a young boreal Pinus sylvestris L. forest with up to 5 m tall trees. Rather than a conventional single release of 13CO2, we used five consecutive releases, each followed by a draw-down period, thus avoiding high [CO2]. Hence, we elevated successively the 13CO2 from 1.1 to 23 atom% after the first release to 61 atom% after the fifth, while maintaining [CO2] below 500 p.p.m. during 4–4.5 h of labelling. The average abundance of 13CO2 was as high as 42 atom%. We used the central 10 m2 of the 50 m2 area for sampling of roots and other soil biota. We modelled the dilution of labelled C across the plots by un-labelled C from roots of trees outside the area. In the central 10 m2 area, ~85% of roots and root-associated biota received C from labelled trees. In summary, we elevated the labelling of roots and associated soil biota four-fold compared with previous studies and described the commonly overlooked impact of roots from un-labelled trees outside the labelled area. [ABSTRACT FROM AUTHOR]

Human heat shock protein 90 (Hsp90) is one of the most important chaperones that play a role in the late stages of protein folding. Errors in the process of the chaperone cycle can lead to diseases such as cancer and neurodegenerative diseases. Therefore, the activity of Hsp90 must be carefully regulated. One of the possibilities is allosteric regulation by its natural allosteric modulators—nucleotides, co-chaperones and client proteins—and synthetic small-molecule allosteric modulators, such as those targeting the middle domain or the C-terminal domain (CTD) of Hsp90. Since no experimentally determined structure of a small-molecule allosteric modulator bound to the CTD of human Hsp90 has yet been obtained, the challenge for a structure-based design of allosteric modulators remains. Solution nuclear magnetic resonance (NMR) spectroscopy could be utilized to overcome these problems. The main aim of this review article is to discuss how solution NMR techniques, especially protein-based, and the advanced isotope labeling of proteins have been used to investigate the allosteric regulation of the cytosolic isoforms of human Hsp90 with allosteric modulators. This article provides the basis for planning future NMR experiments, with the aim of gaining insights into allosteric sites and the mechanisms of allosteric regulation. [ABSTRACT FROM AUTHOR]

The accumulation of Cd by rice poses significant health risks. Foliar fertilization with Zn can reduce grain Cd contents in rice grown in Cd-contaminated soils. However, atmospheric deposition on leaves is another vector of Cd contamination, and it remains unclear how Zn application affects the allocation of such Cd. We conducted an experiment where the flag leaves of rice plants were treated with solutions with various Zn concentrations and a constant Cd concentration. The 111Cd stable isotope was used to trace the flux of foliar-applied Cd. Higher levels of foliar-applied Zn enhanced Cd efflux and grain allocation. This is attributed to limited sequestration of foliar-applied Cd in the leaf cell symplasm and increased Cd desorption from leaf cell walls when a high Zn2+ concentration occurs in the apoplast. Nonionic Zn oxide nanoparticles mitigated these effects. Additionally, the expressions of OsLCT1 and OsZIP7 in flag leaves and OsHMA2 and OsZIP7 in the uppermost nodes were upregulated under high-Zn2+ treatment, which may facilitate Cd phloem loading and grain allocation. Caution is advised in using foliar Zn in areas with high atmospheric Cd due to potential grain-contamination risks. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] Neoantigens exclusively presented by human leukocyte antigens (HLAs) on cancer cell surfaces are newly discovered and highly cancer-specific biomarkers for cancer diagnosis. The current available method for detecting neoantigens is predominantly based on Mass spectrometry with inevitable limitations of high cost, complexity and isotope labels. In this work, we describe the development of an innovative catalytic electrochemical biosensor for ultrasensitive detection of neoantigen in cell lysates. Such biosensor design involves the synthesis of new and highly catalytic CoFe-prussian blue analogue/ZIF-67 yolk-shell nanocube-decorated MBene nanosheets (CoFe-PBA/ZIF-67/MBene) and the derivatization of electrochemically inert neoantigen to electroactive molecule. The as synthesized CoFe-PBA/ZIF-67/MBene nanocomposite exhibits large specific surface area, excellent conductivity and abundant active sites for electrochemical oxidation of the derivatized neoantigens for the yield of considerably amplified currents for sensitive detection of target neoantigen with low to 0.047 nM detection limit. The biosensor can also be applied for monitoring low levels of HLA-presented neoantigen complexes in cell lysates, offering new insights into methodological advancements in neoantigen analyses for cancer research. [ABSTRACT FROM AUTHOR]

Oxidative cleavage of aromatic C(sp2)−O bond is important to the conversion of biomass and plastic wastes into value‐added chemicals. Here we put forward the oxidative cleavage of para‐C−O bonds in phenolic compounds in use of oxoammonium salts as oxidant and water as the oxygen source. The mechanism is that oxoammonium cation activates water to form hydroxy‐oxoammonium adduct and thus realizes the ipso‐substitution of 4‐alkoxyphenol, which is proved by substituent effect, isotope labelling experiments, and kinetic analysis. Furthermore, this protocol is successfully applied into the depolymerization of both lignin model compounds with α‐O‐5 and 4‐O‐5 linkages and polyphenylene oxide (PPO). [ABSTRACT FROM AUTHOR]

The synthesis and evaluation of the newest generation of our DFO2 chelator family—DFO2K—is described. DFO2K was designed with a simple synthetic route to access different bifunctional derivatives, with each derivative having similar metal ion coordination spheres and high denticity (up to 12 coordinate) to ensure stable coordination of zirconium-89. The high denticity could potentially enhance stability with other large oxophilic radiometals. Zirconium-89 is the most popular radionuclide to pair with large macromolecules such as antibodies (immunoPET) for positron emission tomography applications. Although clinically successful, the stability of the "gold standard" chelator desferrioxamine B (DFO) can be improved as significant bone uptake is observed in animal models, despite no obvious stability issues in humans. Following the synthesis of DFO2K we assessed its radiolabeling efficiency with zirconium-89 and compared with DFO, which revealed rapid and nearly identical radiolabeling kinetics to DFO. The resultant [89Zr]Zr–DFO2K complex showed improved stability over [89Zr]Zr–DFO in different in vitro stability assays such as hydroxyapatite and 1000-fold molar excess EDTA challenges. Furthermore, biodistribution studies of the non-bifunctional chelators in healthy mice showed that [89Zr]Zr–DFO2K had a similar distribution profile and clearance to [89Zr]Zr–DFO. The bifunctional derivative p-SCN–Ph–DFO2K was conjugated to a non-specific human IgG antibody and evaluated after 2 weeks circulating in healthy female CD1 mice. Mice administered [89Zr]Zr–DFO2K–IgG showed substantially lower bone uptake in PET-CT images than [89Zr]Zr–DFO–IgG, with PET ROI data and ex vivo biodistribution revealing a statistically significantly lower bone uptake for DFO2K. Overall, owing to its high denticity, ease of synthesis, improved solubility over DFO2 and DFO2p, and stable chelation of zirconium-89, DFO2K appears to be an improved alternative chelator to DFO for zirconium-89 chelation. [ABSTRACT FROM AUTHOR]

The coordination chemistry of an amine-rich CpN3 ligand has been explored with cobalt. We demonstrate that in the presence of NaCo(CO)4, the cationic precursor [CpN3]+ yields the complex CpN3CoI(CO)2. While 2e− oxidation generates new CoIII complexes such as [CpN3Co(NCMe)3]2+ and CpN3CoI2(CO), subsequent ligand loss is facile, generating free [CpN3]+ or the protonated dication [CpN3H]2+. We have structurally characterized both these ligand release products via single crystal X-ray diffraction and obtained thermochemical C–H bond strengths via experiment and density functional theory (DFT). Upon reversible 1e− reduction, the radical cation [CpN3H]˙+ has a weak C–H BDFE of 52 kcal mol−1 in acetonitrile. Mechanistic analysis shows that [CpN3H]˙+ undergoes radical–radical disproportionation in the absence of exogenous H-atom acceptors, which is supported by deuterium isotope labelling experiments. Structural comparison of these organic molecules shows a high degree of iminium-like electron delocalization over the C–N bonds connected to the central five-membered ring. [ABSTRACT FROM AUTHOR]

Here we present an effective nickel‐catalyzed carbonylative cross‐coupling for direct access to alkyl aryl ketones from readily accessible redox‐activated tetrachlorophthalimide esters and aryl boronic acids. The methodology, which is run employing only 2.5 equivalents of CO and simple Ni(II) salts as the metal source, exhibits a broad substrate scope under mild conditions. Furthermore, this carbonylation chemistry provides an easy switch between isotopologues for stable (13CO) and radioactive (14CO) isotope labeling, allowing its adaptation to the late‐stage isotope labeling of pharmaceutically relevant compounds. Based on DFT calculations as well as experimental evidence, a catalytic cycle is proposed involving a carbon‐centered radical formed via nickel(I)‐induced outer‐sphere decarboxylative fragmentation of the redox‐active ester. [ABSTRACT FROM AUTHOR]

19F nuclei serve as versatile sensors for detecting protein interactions and dynamics in biomolecular NMR spectroscopy. Although various methods have been developed to incorporate fluorine-containing aromatic residues into proteins using E. coli or cell-free expression techniques, similar approaches for protein production in mammalian cell lines remain limited. Here, we present a cost-effective synthetic route to obtain selectively deuterated, carbon-13 labeled fluorotryptophan and demonstrate its use in introducing 19F–13C spin pairs into carbonic anhydrase 2 and superoxide dismutase, following an expression protocol utilizing HEK cells. [ABSTRACT FROM AUTHOR]

Several approaches have been utilised to deliver therapeutic nanoparticles inside the brain but rendered by certain limitation such as active efflux, non-stability, toxicity of the nanocarrier, transport, physicochemical properties and many more. In this context use of biocompatible nano carriers is currently investigated. We herein present the hypothesis that the nucleoside-lipid based conjugates (nucleolipids) which are biocompatible in nature and have molecular recognition can be tuned for improved permeation across blood–brain barrier (BBB). In this work, a di-C15-palmitoyl-ketal nucleolipid nanoparticle bearing an acyclic chelator has been formulated, radiolabeled with 99mTc and evaluated for in vivo fate using SPECT imaging. The mean particle size of particles was 113 nm and found to be nontoxic as depticted through haemolytic assay (2.33% erythrocyte destruction) and 75 ± 0.3% HEK(Human Embryonic Kidney) cells survived at 72 h as depicted in SRB (Sulforhodamine B) toxicity assay. The encapsulation efficiency (68 ± 2.75%) and drug loading capacity (22 ± 1.8%.) was calculated for nanoparticles using Methotrexate as model anti-cancer drug. The mathematical models indicate fickian release with a release constant KH = 20.70. With 98 ± 0.75% radiolabelling efficiency and established in vitro stability, nanoparticles showed brain uptake in normal mice as 0.91 times in comparison to BBB compromised mice (1.6% ± 0.03 ID/g)indicating higher brain uptake with rapid clearance as depicted through blood kinetics. Graphical absract: [ABSTRACT FROM AUTHOR]

Background: The NOTI chelating scaffold can readily be derivatized for bioconjugation without impacting its metal complexation/radiolabeling properties making it an attractive building block for the development of multimeric/-valent radiopharmaceuticals. The objective of the study was to further explore the potential of the NOTI chelating platform by preparing and characterizing homotrimeric PSMA radioconjugates in order to identify a suitable candidate for clinical translation. Results: Altogether, three PSMA conjugates based on the NOTI-TVA scaffold with different spacer entities between the chelating unit and the Glu-CO-Lys PSMA binding motif were readily prepared by solid phase-peptide chemistry. Cell experiments allowed the identification of the homotrimeric conjugate 9 comprising NaI-Amc spacer with high PSMA binding affinity (IC50 = 5.9 nM) and high PSMA-specific internalization (17.8 ± 2.5%) compared to the clinically used radiotracer [68Ga]Ga-PSMA-11 with a IC50 of 18.5 nM and 5.2 ± 0.2% cell internalization, respectively. All 68Ga-labeled trimeric conjugates showed high metabolic stability in vitro with [68Ga]Ga-9 exhibiting high binding to human serum proteins (> 95%). Small-animal PET imaging revealed a specific tumor uptake of 16.0 ± 1.3% IA g−1 and a kidney uptake of 67.8 ± 8.4% IA g−1 for [68Ga]Ga-9. Clinical PET imaging allowed identification of all lesions detected by [68Ga]Ga-PSMA-11 together with a prolonged blood circulation as well as a significantly lower kidney and higher liver uptake of [68Ga]Ga-9 compared to [68Ga]Ga-PSMA-11. Conclusions: Trimerization of the Glu-CO-Lys binding motif for conjugate 9 resulted in a ~ threefold higher binding affinity and cellular uptake as well as in an altered biodistribution profile compared to the control [68Ga]Ga-PSMA-11 due to its intrinsic high binding to serum proteins. To fully elucidate its biodistribution, future studies in combination with long-lived radionuclides, such as 64Cu, are warranted. Its prolonged biological half-life and favorable tumor-to-kidney ratio make this homotrimeric conjugate also a potential candidate for future radiotherapeutic applications in combination with therapeutic radionuclides such as 67Cu. [ABSTRACT FROM AUTHOR]

Isotopic labeling is an attractive modality that has been widely used in many aspects of chemistry, the life sciences, and medical research; especially deuterated drugs and radioactive molecules have been used in the diagnosis and treatment of cancer and neurodegenerative diseases. The widespread application and rapid development of isotopically labeled molecules has led to an increased demand for new isotopic labeling chemical methods to synthesize highly specific molecules bearing defined nuclides. Multicomponent reactions (MCRs) are modular build-up approaches for the rapid generation of complex molecules often containing biologically relevant scaffold structures. There is great potential to use MCRs to construct isotopically labeled molecules because assembly speed and reaction diversity are key advantages of MCR. In this review, we provide an overview of the recent literature on this topic that can provide insight into the application of MCRs in the field of isotopic labeling. [ABSTRACT FROM AUTHOR]

Pretargeted imaging is an emerging technique to study the in vivo biodistribution of nanomedicines. Currently, the tetrazine ligation is considered the most promising bioorthogonal reaction for pretargeting. Recently, Zheng et al. described an ultrafast late-stage radiolabeling of tetrazines based on sulfur18 F-fluoride exchange click chemistry ([18 F]SuFEx). However, bispyridyl and H-tetrazines—the most promising structures for in vivo pretargeted applications—cannot be labeled using the proposed reaction conditions as they lead to decomposition of the tetrazine core. Here, we report improved conditions, exploiting basic preconditioning conditions for the quaternary methyl ammonium (QMA) cartridge and the use of low basic anions that allow18 F-labeling of bispyridyl and H-tetrazines using SuFEx. This strategy resulted in fast and efficient radiolabeling of highly reactive tetrazines with radiochemical conversions of up to 85% and radiochemical purity above 95%. This opens up the possibility to use SuFEx to18 F-label tetrazines, which are suitable for in vivo pretargeted imaging. [ABSTRACT FROM AUTHOR]

A key challenge in oligosaccharide synthesis is the stereoselective installation of glycosidic bonds. Each glycosidic linkage has one of two possible stereo‐chemical geometries, α/β or 1,2‐cis/trans. An established approach to install 1,2‐trans glycosidic bonds is neighboring group participation (NGP), mediated by a 2‐O‐acyl group. Extension of this intramolecular stabilization to nucleophilic groups located at more remote positions has also been suggested, but remains poorly understood. Previously, we employed infrared ion spectroscopy to characterize the molecular ions of monoacetylated sugar donors and showed how the strength of the stabilizing effect depends on the position of the participating ester group on the glycosyl donor ring as well as on its relative stereochemistry. In this work, we investigated glycosyl donors carrying two acyl groups. Using isotope labelling and isomer population analysis we were able to resolving spectra of isomeric mixtures and establish the relative contribution of individual species. We conclude that 3,4‐diacetyl mannosyl donors exclusively form a dioxanium ion as a result of C‐3 acyl stabilization. In contrast, the glucosyl and galactosyl cations form mixtures of C‐3 and C‐4 acyl participation products. Hence, the combination of isotope labeling and population analysis allows for the study of increasingly complex glycosyl cations. [ABSTRACT FROM AUTHOR]

Increased atmospheric nitrogen (N) deposition significantly disturbs ecosystem N cycle. Although foliar interception and uptake of N deposition can provide an important alternative N supply to forest ecosystems, the mechanisms regulating foliar N uptake from wet deposition are not fully understood. Here, we selected 19 woody species with a wide range of plant traits from different functional groups and conducted a 15N isotope labelling experiment through brushing 15NH4+ and 15NO3− solution on canopy leaves. Our findings demonstrate that leaves can directly absorb N from wet deposition within a few hours. The average leaf 15N recoveries were 10% and 28% under 15NH4+ and 15NO3− treatments across species, respectively, while twig N recoveries were only 1%–7% of leaf N recoveries. Differences in foliar N uptake efficiency among species were closely associated with leaf traits but were little influenced by meteorological conditions or soil nutrient status. Specifically, plants with higher leaf N concentration, larger specific leaf area and lower wax concentration exhibited higher leaf N recovery. Our results indicated that tree canopies could directly absorb N from atmospheric deposition. We highlight the critical role of leaf traits in determining canopy foliar N uptake, which may consequently influence plant competition under elevated N deposition. Summary Statement: We conducted a 15N‐labelling experiment on canopy leaves of 19 woody species with diverse traits. We found that species with acquisitive traits had higher foliar nitrogen (N) uptake than conservative species, providing insights into the necessity of accounting foliar uptake into ecosystem N budget. [ABSTRACT FROM AUTHOR]

Background: Bromodomain and extra-terminal (BET) proteins are critical regulators of gene transcription, as they recognize acetylated lysine residues. The BD1 bromodomain of BRD4, a member of the BET family, has emerged as a promising therapeutic target for various diseases. This study aimed to develop and evaluate a novel C-11 labeled PET radiotracer, [11C]YL10, for imaging the BD1 bromodomain of BRD4 in vivo. Methods: [11C]YL10 was synthesized and evaluated for its ability to bind to the BD1 bromodomain selectively. PET imaging studies were conducted in mice to assess brain penetration, pharmacokinetics, and selectivity. In vitro autoradiography and blocking experiments were performed to confirm the tracer's specificity for the BD1 domain. Results: [11C]YL10 demonstrated good brain penetration, high selectivity for the BD1 bromodomain, and favorable pharmacokinetics in initial PET imaging studies. In vitro autoradiography and blocking experiments confirmed the specific binding of [11C]YL10 to the BD1 domain of BRD4, further validating its potential as a targeted radiotracer. Conclusions: The development of [11C]YL10 provides a new tool for studying BRD4 bromodomains using PET imaging technology. This radiotracer offers potential advancement in the diagnosis and research of neurodegenerative diseases and related disorders involving BRD4 dysregulation. [ABSTRACT FROM AUTHOR]

Carum carvi-derived quantum dots (CcQDs) were prepared using thermal pyrolyzing. The surface functionalization of CcQDs were achieved via L-cysteine ligand. Labeled CcQDs with technetium-99m were prepared using a simple direct radiolabeling method. Radio chromatographic techniques were used to analyze radiochemical yield. Quality control results indicated that QDs could be efficiently labeled with 99mTc-radionuclide (> 98% radiochemical yield). The in vivo biodistribution parameters were studied in tumorized BALB/c mouse. The amount of uptake in xenograft models of mice colon carcinoma was 1.27 ± 0.15% ID/g after 1 h. 99mTc-labeled T-Cysteine-CcQDs, could be included as a radiotracer for imaging colon carcinoma tumors. [ABSTRACT FROM AUTHOR]

This study investigates the synthesis and radiolabeling of zeolitic imidazolate frameworks (ZIF-8) with the radioisotope technetium-99 m (99mTc) using a solvothermal method in methanol. The methanolic medium facilitated the formation of nanoparticles with favorable characteristics, including a smaller particle size (198 ± 9.8 nm) and a low polydispersity index (PDI = 0.219 ± 0.011). Radiolabeling efficiency (RE%) and radiochemical purity (RCP%) were optimized by employing SnCl2 as a reducing agent, resulting in an RE% of 95.2 ± 1.9% and an RCP% of 96.1 ± 1.7% in triplicate (n = 3) at 65 °C. The nanoparticles exhibited high serum stability, retaining 99.05% of RCP% after 24 h, and demonstrated hemocompatibility, with hemolysis rates below 5% across all tested concentrations. In vitro biocompatibility assessments using NIH-3T3 cells indicated cell viability above 70% at concentrations up to 40 μg/mL. Biodistribution studies in rabbits (n = 6) revealed predominant accumulation in the bladder, with radiotracer uptake in the bladder being 6.3, 7.2, and 36.2 times higher than in the liver, kidneys, and heart (p < 0.0001), respectively, suggesting renal clearance. These results underscore the potential of 99mTc-(ZIF-8) nanoparticles for biomedical applications, particularly in targeted imaging and drug delivery. Future research will focus on improving targeting specificity and enhancing therapeutic efficacy in disease models. [ABSTRACT FROM AUTHOR]

AbstractHydrolytic and oxidative damage to pyrimidine nucleobases in DNA represents a significant source of mutations in the human genome. To better understand how these lesions are incorporated and repaired in human cells, it is desirable to have ready access to isotopically enriched nucleosides for use in isotope tracing and mass spectrometry-based quantification experiments. Here we report on improved syntheses of deoxyuridine, deoxycytidine, 5-hydroxydeoxyuridine, and 5-hydroxydeoxycytidine nucleosides labeled with 13C and 15N. Deoxyuridine was synthesized from uracil in a direct glycosylation reaction with excellent stereoselectivity without the need to reduce a ribonucleoside intermediate. Deoxyuridine was further converted to deoxycytidine using mild O4 activation conditions with high efficiency. Finally, we document the synthetic details of preparative oxidation of deoxyuridine and deoxycytidine to their 5-hydroxy counterparts. Overall, our protocols avoid hazardous reagents and tedious conditions found in previous methods. [ABSTRACT FROM AUTHOR]

The significance of small molecule metabolites as biomarkers for disease diagnosis and prognosis is growing increasingly evident, necessitating the development of highly sensitive qualitative and quantitative methods. Herein, multi‐chemoselective probes are synthesized and applied for profiling metabolites, including carboxyl, phosphate, hydroxyl, amino, thiol, and carbonyl compounds. This approach seamlessly integrates magnetic solid‐phase materials, orthogonal cleavage sites, isotopic tags, and selective coupling sites, minimizes matrix interference, and enhances quantitative accuracy. Meanwhile, a homemade program, High‐Resolution Isotope‐Assisted Identification and Quantitative (HRIAIQuant) is developed to process the data, which adeptly filters through 33,874 ion pairs present in human serum, leading to the identification of 701 known metabolites and a remarkable 1,062 potential novel ones. This method is successfully applied to analyze metabolites in multiple brain regions of SAMP8 and SAMR1 models, offering a novel tool for Alzheimer's disease research. [ABSTRACT FROM AUTHOR]

The cytochrome P450 homolog, TxtE, efficiently catalyzes the direct and regioselective aromatic nitration of the indolyl moiety of L‐tryptophan to 4‐nitro‐L‐tryptophan, using nitric oxide (NO) and dioxygen (O2) as co‐substrates. Pathways for such direct and selective nitration of heteroaromatic motifs present platforms for engineering new nitration biocatalysts for pharmacologically beneficial targets, among a medley of other pivotal industrial applications. Precise mechanistic details concerning this pathway are only weakly understood, albeit a heme iron(III)‐peroxynitrite active species has been postulated. To shed light on this unique reaction landscape, we investigated the indole nitration pathway of a series of biomimetic ferric heme superoxide mimics, [(Por)FeIII(O2−⋅)], in the presence of NO. Therein, our model systems gave rise to three distinct nitroindole products, including 4‐nitroindole, the product analogous to that obtained with TxtE. Moreover, 15N and 18O isotope labeling studies, along with meticulously designed control experiments lend credence to a heme peroxynitrite active nitrating agent, drawing close similarities to the tryptophan nitration mechanism of TxtE. All organic and inorganic reaction components have been fully characterized using spectroscopic methods. Theoretical investigation into several mechanistic possibilities deem a unique indolyl radical based reaction pathway as the most energetically favorable, products of which, are in excellent agreement with experimental findings. [ABSTRACT FROM AUTHOR]

DOTA‐functionalized bisphosphonates can be useful tools for PET imaging of bone metastases when radiolabeled with 68Ga. Moreover, the versatility of DOTA allows the complexation of radiometals with therapeutic applications (e.g., 177Lu), positioning these bisphosphonates as attractive theranostic agents. Among these molecules, BPAMD is a compound whose radiolabeling with 68Ga has already been described, but only through manual methods. Thus, a fully automated protocol for 68Ga radiolabeling of BPAMD on the GAIA® ± LUNA® synthesis module was designed, and a thorough study of the radiolabeling conditions was undertaken. [68Ga]Ga‐BPAMD was produced in good radiochemical purity (> 93%) and high radiochemical yield (> 91%) using 0.3 M HEPES buffer. The nature of the reaction vessel showed no significant effect on the radiolabeling outcome. Similarly, addition of an antiradiolysis compound to the reaction medium did not significantly improve the already excellent stability of [68Ga]Ga‐BPAMD over time. The radiolabeled product obtained by automated synthesis was evaluated in vivo in healthy mice and confirmed high accumulation in the joints and along the backbone. [ABSTRACT FROM AUTHOR]

The deep migration of soil nitrogen (N) poses a significant risk of N leaching, contributing to non-point-source pollution. This study examines the influence of microbial networks on the deep migration of chemical fertilizer N under varying irrigation management and multiple N fertilizer sources. A soil column experiment with eight treatments was conducted, utilizing 15N isotope labeling and metagenomic sequencing technology. The findings revealed that reduced irrigation significantly curbs the deep migration of chemical fertilizer N, and straw returning also mitigates this migration under conventional irrigation. Microbial network complexity and stability were markedly higher under reduced irrigation compared to conventional practices. Notably, network node count, average degree, and modularity exhibited significant negative correlations with the deep migration of chemical fertilizer N. The network topology indices, including node count, average clustering coefficient, average degree, modularity, and edge count, were found to be relatively more important for the deep migration of chemical fertilizer N. In conclusion, microbial networks play an important role in reducing the deep migration of chemical fertilizer N. [ABSTRACT FROM AUTHOR]

Side chain isotope labelling is a powerful tool to study protein structure and interactions by NMR spectroscopy. 1H,13C labelling of side-chain methyl groups in a deuterated background allows studying large molecules, while side-chain aromatic groups are highly sensitive to the interaction with ligands, drugs, and other proteins. In E. coli, side chain labelling is performed by substituting amino acids with isotope-labelled precursors. However, proteins that can only be produced in mammalian cells require expensive isotope-labelled amino acids. Here we provide a simple and cost-effective method to label side chains in mammalian cells, which exploits the reversible reaction catalyzed by endogenous transaminases to convert isotope-labelled α-ketoacid precursors. We show by in-cell and in-lysate NMR spectroscopy that replacing an amino acid in the medium with its cognate precursor is sufficient to achieve selective labelling without scrambling, and how this approach allows monitoring conformational changes such as those arising from ligand binding. [ABSTRACT FROM AUTHOR]

An efficient oxidation of stilbenes to α‐diketones co‐catalyzed by bismuth nitrate and iodine is reported. The utilization of molecular oxygen as a terminal oxidant and water as the reaction solvent provides a low‐cost and environmentally friendly approach to preparing the α‐diketone derivatives from readily available stilbenes. Isotope labeling experiments suggest that the two oxygen atoms of the α‐ diketone products mainly originate from water. The method displays high functional group tolerance and we have demonstrated a concise route for preparing trifenagrel and HIV‐1 integrase inhibitors from 1,2‐diphenylethene. [ABSTRACT FROM AUTHOR]