Accessing Azetidines through Magnesium-Mediated Nitrogen Group Transfer from Iminoiodinane to Donor-Acceptor Cyclopropanes.

Herein, we report a Lewis acid-mediated ring expansion of donor-acceptor cyclopropanes (DACs) to substituted azetidines via nucleophilic nitrogen group transfer from readily accessible iminoiodinane. This protocol operates under mild, transition-metal-free conditions, and showcases excellent chemoselectivity, along with broad functional group tolerance. We report for the first time that challenging alkyl donor-acceptor cyclopropanes can undergo ring expansion leading to aliphatic azetidines without relying on external oxidants or precious transition-metal catalysts.

First Biodistribution Study of [68Ga]Ga-NOTA-Insulin Following Intranasal Administration in Adult Vervet Monkeys.

Background: Intranasal insulin (INI) is being explored as a treatment for Alzheimer's disease (AD). Improved memory, functional ability, and cerebrospinal fluid (CSF) AD biomarker profiles have been observed following INI administration. However, the method of intranasal delivery may significantly affect outcomes.

Exploring microtubule dynamics in Alzheimer's disease: Longitudinal assessment using [C]MPC-6827 PET imaging in rodent models of Alzheimer's-related pathology.

Introduction: Microtubule (MT) stability is crucial for proper neuronal function. Understanding MT dysregulation is critical for connecting amyloid beta (Aβ) and tau-based degenerative events and early changes in presymptomatic Alzheimer's disease (AD). Herein we present positron emission tomography (PET) imaging properties of our MT-PET radiotracer, [C]MPC-6827, in multiple established AD mouse models.

Enhancing breast cancer treatment: Comprehensive study of gefitinib-loaded poloxamer 407/TPGS mixed micelles through design, development, in-silico modelling, In-Vitro testing, and Ex-Vivo characterization.

Breast cancer continues to pose a substantial global health challenge, emphasizing the critical need for the advancement of novel therapeutic approaches. Key players in the regulation of apoptosis, a fundamental process in cell death, are the B-cell lymphoma 2 (Bcl-2) family proteins, namely Bcl-2 and Bax. These proteins have garnered attention as highly promising targets for the treatment of breast cancer.

Aziridination via Nitrogen-Atom Transfer to Olefins from Photoexcited Azoxy-Triazenes.

Herein, we report that readily accessible azoxy-triazenes can serve as nitrogen atom sources under visible light excitation for the phthalimido-protected aziridination of alkenes. This approach eliminates the need for external oxidants, precious transition metals, and photocatalysts, marking a departure from conventional methods. The versatility of this transformation extends to the selective aziridination of both activated and unactivated multisubstituted alkenes of varying electronic profiles.

Comparison of brain nicotine accumulation from traditional combustible cigarettes and electronic cigarettes with different formulations.

Rapid brain accumulation is critical for the acute reinforcing effects of nicotine. Although nicotine formulation (free-base vs. protonated or salt) in electronic cigarette (E-cig) liquid affects user satisfaction, its impact on brain nicotine accumulation (BNA) from E-cig use has not been evaluated in comparison with traditional combustible cigarettes (C-cigs) using a within-subjects design.

Dimethyl carbonate synthesis from CO and methanol over CeO: elucidating the surface intermediates and oxygen vacancy-assisted reaction mechanism.

Surface intermediate species and oxygen vacancy-assisted mechanism over CeO catalyst in the direct dimethyl carbonate (DMC) synthesis from carbon dioxide and methanol are suggested by means of transient spectroscopic methodologies in conjunction with multivariate spectral analysis. How the two reactants, CO and methanol, interact with the CeO surface and how they form decisive surface intermediates leading to DMC are unraveled by DFT-based molecular dynamics simulation by precise statistical sampling of various configurations of surface states and intermediates. The atomistic simulations and uncovered stability of different intermediate states perfectly explain the unique DMC formation profile experimentally observed upon transient operations, strongly supporting the proposed oxygen vacancy-assisted reaction mechanism.

Preliminary PET Imaging of Microtubule-Based PET Radioligand [C]MPC-6827 in a Nonhuman Primate Model of Alzheimer's Disease.

The microtubule (MT) instability observed in Alzheimer's disease (AD) is commonly attributed to hyperphosphorylation of the MT-associated protein, tau. PET imaging offers an opportunity to gain critical information about MT changes with the onset and development of AD and related dementia. We developed the first brain-penetrant MT PET ligand, [C]MPC-6827, and evaluated its imaging utility in vervet monkeys.

Photoinduced Nitroarenes as Versatile Anaerobic Oxidants for Accessing Carbonyl and Imine Derivatives.

Herein, we report a protocol for the anaerobic oxidation of alcohols, amines, aldehydes, and imines promoted by photoexcited nitroarenes. Mechanistic studies support the idea that photoexcited nitroarenes undergo double hydrogen atom transfer (HAT) steps with alcohols and amines to provide the respective ketone and imine products. In the presence of aldehydes and imines, successive HAT and oxygen atom transfer (OAT) events occur to yield carboxylic acids and amides, respectively.

Predictors of Mortality among COVID-19 Patients - A Case Control Study at Tertiary Care Center, Nanded (Maharashtra).

Background: The novel Coronavirus is belonging to the family of SARS & MERS-CoV, the impact of the earlier is more dreadful as demonstrated by the steady increase in morbid cases. The average incubation period of COVID-19 is 1-14 days with a mean of 6 days. Aim - To evaluate predictors of mortality among COVID-19 patients.

First GPR119 PET Imaging Ligand: Synthesis, Radiochemistry, and Preliminary Evaluations.

G-protein-coupled receptor 119 (GPR119) has emerged as a promising target for treating type 2 diabetes mellitus. Activating GPR119 improves glucose homeostasis, while suppressing appetite and weight gain. Measuring GPR119 levels could significantly advance GPR119-based drug development strategies including target engagement, occupancy, and distribution studies.

Binding Parameters of [C]MPC-6827, a Microtubule-Imaging PET Radiopharmaceutical in Rodents.

Impairment and/or destabilization of neuronal microtubules (MTs) resulting from hyper-phosphorylation of the tau proteins is implicated in many pathologies, including Alzheimer's disease (AD), Parkinson's disease and other neurological disorders. Increasing scientific evidence indicates that MT-stabilizing agents protect against the deleterious effects of neurodegeneration in treating AD. To quantify these protective benefits, we developed the first brain-penetrant PET radiopharmaceutical, [C]MPC-6827, for quantification of MTs in rodent and nonhuman primate models of AD.

[F]KS1, a novel ascorbate-based ligand images ROS in tumor models of rodents and nonhuman primates.

Over production of reactive oxygen species (ROS) caused by altered redox regulation of signaling pathways is common in many types of cancers. While PET imaging is recognized as the standard tool for cancer imaging, there are no clinically-approved PET radiotracers for ROS-imaging in cancer diagnosis and treatment. An ascorbate-based radio ligand promises to meet this urgent need.

Validation of a New Graphic Facial Nerve Grading System: FAME Scale.

Background And Objective: Most of the existing qualitative facial nerve grading systems are very subjective while the quantitative grading systems are more complex, require longer data input time and specific software. There is a need for having a scoring system with graphic criteria to improve the subjectivity, reliability and convenience. We aimed to develop and validate such a reliable graphic scale for use in Bell's palsy.

Preliminary mechanistic insights of a brain-penetrant microtubule imaging PET ligand in a tau-knockout mouse model.

Background: Microtubules (MTs) are critical for cell structure, function, and survival. MT instability may contribute to Alzheimer's disease (AD) pathogenesis as evidenced by persistent negative regulation (phosphorylation) of the neuronal microtubule-associated protein tau. Hyperphosphorylated tau, not bound to MTs, forms intraneuronal pathology that correlates with dementia and can be tracked using positron emission tomography (PET) imaging.

Greener and facile synthesis of Cu/ZnO catalysts for CO hydrogenation to methanol by urea hydrolysis of acetates.

Cu/ZnO-based catalysts for methanol synthesis by CO hydrogenation are widely prepared co-precipitation of sodium carbonates and nitrate salts, which eventually produces a large amount of wastewater from the washing step to remove sodium (Na) and/or nitrate (NO ) residues. The step is inevitable since the remaining Na acts as a catalyst poison whereas leftover NO induces metal agglomeration during the calcination. In this study, sodium- and nitrate-free hydroxy-carbonate precursors were prepared urea hydrolysis co-precipitation of acetate salt and compared with the case using nitrate salts.

Fast Pyrolysis Bio-Oil-Based Epoxy as an Adhesive in Oriented Strand Board Production.

The objectives of this study were to utilize bio-oil-based epoxy resin in oriented strand board (OSB) production and investigate the effect of bio-oil substitution in epoxy resin as an adhesive for OSB production. Bio-oil was produced by the fast pyrolysis (FP) process using southern yellow pine ( spp.).

Initial Evaluations of the Microtubule-Based PET Radiotracer, [C]MPC-6827 in a Rodent Model of Cocaine Abuse.

Purpose: Microtubules (MTs) are structural units made of α and β tubulin subunits in the cytoskeleton responsible for axonal transport, information processing, and signaling mechanisms-critical for healthy brain function. Chronic cocaine exposure affects the function, organization, and stability of MTs in the brain, thereby impairing overall neurochemical and cognitive processes. At present, we have no reliable, non-invasive methods to image MTs for cocaine use disorder (CUD).

Arthroscopic Excision of Localized Nodular Tenosynovitis of Carpometacarpal Joint of Thumb: A Case Report and Review of Literature.

Giant cell tumors of tendon sheath are classified according to their clinical presentation as localized or diffuse, and they may occur at intra-articular or extra-articular locations. Although magnetic resonance imaging is mandatory and sufficient for diagnosis in many cases, histological examination is needed to confirm the diagnosis. Complete surgical resection is the mainstay of treatment.

Effect of ethanol and cocaine on [C]MPC-6827 uptake in SH-SY5Y cells.

Microtubules (MTs) are structural units in the cytoskeleton. In brain cells they are responsible for axonal transport, information processing, and signaling mechanisms. Proper function of these processes is critical for healthy brain functions.

Radical Rearrangement of Aryl/Alkylidene Malononitriles Aza Michael Addition/Decynoformylation/Addition Sequence: An Access to α-Aminonitriles and α-Aminoamides.

An efficient, safe, and environmentally friendly tertiary butyl hydrogen peroxide (TBHP)-mediated rearrangement of aryl/alkylidene malononitrile with anilines has been developed with generation of HCN as the cyanide source for the synthesis of substituted α-aminonitriles and α-aminoamide. A diverse set of α-aminonitriles and α-aminoamides was efficiently synthesized in good to excellent yields. This method features a broad substrate scope and good functional group tolerance, and the -generated HCN bypasses the use of an external cyanide source.

Iodine-Mediated Oxidative Rearrangement of α,β-Unsaturated Diaryl Ketones: A Facile Access to 1,2-Diaryl Diketones.

A metal-free oxidative rearrangement was explored for the synthesis of 1,2-diaryl diketones by utilizing α,β-unsaturated diaryl ketones and I/TBHP in good to high yields. The reaction proceeds via oxidative aryl migration, followed by C-C bond cleavage. A simple and high-yielding protocol was developed for the synthesis of a wide range of 1,2-diaryl diketones, which are the backbone for a variety of medicinally important molecules.

A Novel Technique for the Surgical Management of Chronic Lateral Epicondylitis.

Lateral epicondylitis is the most common condition affecting the elbow and is self-limiting in most cases. However, when conservative treatment fails, surgery is required for resistant cases. In this study, we describe a novel technique for the management of chronic lateral epicondylitis.

Decisive Role of Perimeter Sites in Silica-Supported Ag Nanoparticles in Selective Hydrogenation of CO to Methyl Formate in the Presence of Methanol.

Methyl formate synthesis by hydrogenation of carbon dioxide in the presence of methanol offers a promising path to valorize carbon dioxide. In this work, silica-supported silver nanoparticles are shown to be a significantly more active catalyst for the continuous methyl formate synthesis than the known gold and copper counterparts, and the origin of the unique reactivity of Ag is clarified. Transient in situ and operando vibrational spectroscopy and DFT calculations shed light on the reactive intermediates and reaction mechanisms: a key feature is the rapid formation of surface chemical species in equilibrium with adsorbed carbon dioxide.

Metal-free hypervalent iodine/TEMPO mediated oxidation of amines and mechanistic insight into the reaction pathways.

A highly efficient metal free approach for the oxidation of primary and secondary amines to their corresponding aldehydes and ketones using PhI(OAc) in combination with a catalytic amount of TEMPO as an oxidizing agent is described. This protocol is rapid and provides diverse products under milder reaction conditions in excellent yields. In addition, the mechanistic study is well demonstrated by spectroscopic methods.