Reversible enzyme-catalysed NAD/NADH electrochemistry.

Formate dehydrogenase (FdsDABG) from is a Mo-containing enzyme capable of catalysing both formate oxidation to CO and the reverse CO reduction to formate by utilising NAD or NADH, respectively. This enzyme is part of the NADH dehydrogenase superfamily. Its subcomplex, FdsBG, lacking the formate oxidizing/CO-reducing Mo-cofactor, but harbouring an FMN as well as [2Fe-2S] and [4Fe-4S] clusters, reversibly interconverts the NAD/NADH redox pair.

Characterisation of the Self-Sufficient Cytochrome P450 CYP116B234 From Rhodococcus globerulus and Its Suggested Native Role in 2-Hydroxyphenylacetic Acid Metabolism.

Cytochromes P450 (P450s) are exceptional biocatalysts that enable the selective oxidation of unactivated C-H bonds using molecular oxygen. Typically, auxiliary redox partner proteins deliver electrons from NAD(P)H to the P450, enabling oxygen activation. However, associating native redox partners with P450s can be challenging, particularly when they are genomically separated.

Lu-DOTATATE in Combination with PARP Inhibitor Olaparib Is Feasible in Patients with Somatostatin-Positive Tumors: Results from the LuPARP Phase I Trial.

This phase I trial aimed to assess the feasibility and toxicity of combining the poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib with Lu-DOTATATE in patients with somatostatin receptor-positive tumors, with the goal of enhancing treatment efficacy through the inhibition of tumor cell DNA repair mechanisms. Eighteen patients were enrolled, mostly with pancreatic or small intestinal neuroendocrine tumors or atypical lung carcinoids. Patients received a standard dose of Lu-DOTATATE (7,400 MBq) for up to 4 cycles, combined with escalating doses of olaparib (50-300 mg twice a day [BID]).

Electrostatically tuning radical addition and atom abstraction reactions with distonic radical ions.

Although electrostatic catalysis can enhance the kinetics and selectivity of reactions to produce greener synthetic processes, the highly directional nature of electrostatic interactions has limited widespread application. In this study, the influence of oriented electric fields (OEF) on radical addition and atom abstraction reactions are systematically explored with ion-trap mass spectrometry using structurally diverse distonic radical ions that maintain spatially separated charge and radical moieties. When installed on rigid molecular scaffolds, charged functional groups lock the magnitude and orientation of the internal electric field with respect to the radical site, creating an OEF which tunes the reactivity across the set of gas-phase carbon-centred radical reactions.

Diel vertical migration rates of the dinoflagellate species in a lower Chesapeake Bay tributary.

is a mixotrophic dinoflagellate harmful algal bloom (HAB) species that blooms annually in the lower Chesapeake Bay. undertakes a diel vertical migration (DVM) which may give it a competitive advantage over purely phototrophic organisms who cannot access deeper nutrient pools and allow it to form large toxic blooms. Laboratory-based estimates of DVM rates suggest that it is one of the fastest known dinoflagellate swimmers and understanding this behavior is likely important for modeling and predicting blooms.

Goondolinones A and B: Terpenyl-quinolin-4(1)-ones from an Australian Volcanic Crater Soil-Derived sp., with Selective Activity against (Heartworm).

A chemical investigation of the Australian pasture soil-derived sp. S4S-00245B09, supported by chemical, bioactivity and cultivation profiling, yielded a new class of terpenyl-quinolin-4(1)-ones, goondolinones A and B ( and ), featuring an unprecedented fused seven-membered ether. Structures were assigned to and on the basis of detailed spectroscopic analysis, including X-ray analysis of , and biosynthetic considerations.

Hyperstable alkenes: are they remarkably unreactive?

In 1981, Maier and Schleyer first identified a select number of cage bicyclic olefins (alkenes) as "hyperstable", and predicted them to be "remarkably unreactive", based solely on theoretical methods. Since that time only three systems meeting the criteria of a hyperstable alkene have been reported in the literature. A one-pot, telescoped synthesis, of four hyperstable alkenes is reported herein, which has uncovered unexpected reactivity towards oxidation.

Targeting lysosomes by design: novel -acridine thiosemicarbazones that enable direct detection of intracellular drug localization and overcome P-glycoprotein (Pgp)-mediated resistance.

Innovative -acridine thiosemicarbazones (NATs) were designed along with their iron(iii), copper(ii), and zinc(ii) complexes. Lysosomal targeting was promoted by specifically incorporating the lysosomotropic Pgp substrate, acridine, into the thiosemicarbazone scaffold to maintain the tridentate N, N, S-donor system. The acridine moiety enables a significant advance in thiosemicarbazone design, since: (1) it enables tracking of the drugs by confocal microscopy using its inherent fluorescence; (2) it is lysosomotropic enabling lysosomal targeting; and (3) as acridine is a P-glycoprotein (Pgp) substrate, it facilitates lysosomal targeting, resulting in the drug overcoming Pgp-mediated resistance.

Dosimetric implications of kidney anatomical volume changes in Lu-DOTATATE therapy.

Introduction: This study aims to evaluate the use of CT-based whole kidney parenchyma (WKP) segmentation in Lu-DOTATATE dosimetry. Specifically, it investigates whether WKP volumes change during treatment and evaluates the accuracy of applying a single delineated WKP volume for dosimetry. Furthermore, it aims to determine the cause of WKP volume changes-whether caused by radiation or amino acid infusion-by comparing them with spleen volume changes as a marker for radiation-induced alterations.

Ten-year follow-up cohort of the everolimus versus azathioprine multinational prospective study focusing on intravascular ultrasound findings.

Background: Long-term clinical outcomes of early intravascular ultrasound (IVUS) findings in a prospective cohort of heart transplantation (HTx) patients have not been evaluated.

Methods: This study included patients from 20 centers across Europe and North and South America among the original cohort of the RAD B253 study. Among these patients, 91 had paired IVUS images at baseline and 1-year post-transplant: everolimus 1.

Comparison of the tolerability of Tb- and Lu-labeled somatostatin analogues in the preclinical setting.

Purpose: [Lu]Lu-DOTATATE is an established somatostatin receptor (SSTR) agonist for the treatment of metastasized neuroendocrine neoplasms, while the SSTR antagonist [Lu]Lu-DOTA-LM3 has only scarcely been employed in clinics. Impressive preclinical data obtained with [Tb]Tb-DOTA-LM3 in tumor-bearing mice indicated the potential of terbium-161 as an alternative to lutetium-177. The aim of the present study was to compare the tolerability of Tb- and Lu-based DOTA-LM3 and DOTATATE in immunocompetent mice.

Optimizing neurointerventional procedures: an algorithm for embolization coil detection and automated collimation to enable dose reduction.

Purpose: Monitoring radiation dose and time parameters during radiological interventions is crucial, especially in neurointerventional procedures, such as aneurysm treatment with embolization coils. The algorithm presented detects the presence of these embolization coils in medical images. It establishes a bounding box as a reference for automated collimation, with the primary objective being to enhance the efficiency and safety of neurointerventional procedures by actively optimizing image quality while minimizing patient dose.

Isosteric Replacement of Sulfur to Selenium in a Thiosemicarbazone: Promotion of Zn(II) Complex Dissociation and Transmetalation to Augment Anticancer Efficacy.

We implemented isosteric replacement of sulfur to selenium in a novel thiosemicarbazone (PPTP4c4mT) to create a selenosemicarbazone (PPTP4c4mSe) that demonstrates potentiated anticancer efficacy and selectivity. Their design specifically incorporated cyclohexyl and styryl moieties to sterically inhibit the approach of their Fe(III) complexes to the oxy-myoglobin heme plane. Importantly, in contrast to the Fe(III) complexes of the clinically trialed thiosemicarbazones Triapine, COTI-2, and DpC, the Fe(III) complexes of PPTP4c4mT and PPTP4c4mSe did not induce detrimental oxy-myoglobin oxidation.

Influence of anatomical structure on antiscatter grid performance in 2D: application to x-ray angiography and a prototype 29:1 ratio grid.

The use of uniform phantoms to assess the influence of x-ray scatter and antiscatter grids on x-ray angiography and fluoroscopy image quality disregards the influence of spatially variable x-ray attenuation of patients. The purpose of this work was to measure scatter to primary ratio (SPR) and antiscatter grid SNR improvement factor () using experimental conditions which better mimic patient imaging conditions.Three adult-sized anthropomorphic phantoms were used.

Miniaturized Cultivation Profiling (MATRIX)-Facilitated Discovery of Noonazines A-C and Noonaphilone A from an Australian Marine-Derived Fungus, CMB-M0339.

Subjecting the Australian marine-derived fungus CMB-M0339 to cultivation profiling using an innovative miniaturized 24-well plate format (MATRIX) enabled access to new examples of the rare class of 2,6-diketopiperazines, noonazines A-C (-), along with the known analogue coelomycin (), as well as a new azaphilone, noonaphilone A (). Structures were assigned to - on the basis of a detailed spectroscopic analysis, and in the case of -, an X-ray crystallographic analysis. Plausible biosynthetic pathways are proposed for -, involving oxidative Schiff base coupling/dimerization of a putative Phe precursor.

Nitrogen uptake rates and phytoplankton composition across contrasting North Atlantic Ocean coastal regimes north and south of Cape Hatteras.

Understanding nitrogen (N) uptake rates respect to nutrient availability and the biogeography of phytoplankton communities is crucial for untangling the complexities of marine ecosystems and the physical, biological, and chemical forces shaping them. In the summer of 2016, we conducted measurements of bulk microbial uptake rates for six N-labeled substrates: nitrate, nitrite, ammonium, urea, cyanate, and dissolve free amino acids across distinct marine provinces, including the continental shelf of the Mid-and South Atlantic Bights (MAB and SAB), the Slope Sea, and the Gulf Stream, marking the first instance of simultaneously measuring six different N uptake rates in this dynamic region. Total measured N uptake rates were lowest in the Gulf Stream followed by the SAB.

Goondansamycins A-H: Benzenoid Ansamycins from an Australian Volcanic Crater Soil-Derived sp. S4S-00069B08.

A chemical investigation of Australian soil-derived bacteria sp. S4S-00069B08 yielded eight new benzenoid ansamycins, goondansamycins A-H. Goondansamycins feature rare 1,4-benzoxazin-3-one or -diamino--benzoquinone moieties and can exist as both aglycones or 9--α-glycosides of either d-rhodinose or d-amicetose.

Relationship Between Absorbed Dose and Response in Neuroendocrine Tumors Treated with [Lu]Lu-DOTATATE.

Peptide receptor radionuclide therapy presents the possibility of tracing and quantifying the uptake of the drug in the body and performing dosimetry, potentially allowing individualization of treatment schemes. However, the details of how neuroendocrine tumors (NETs) respond to different absorbed doses are insufficiently known. Here, we investigated the relationship between tumor-absorbed dose and tumor response in a cohort of patients with NETs treated with [Lu]Lu-DOTATATE.

X-ray absorption and emission spectroscopy of NS Cu(II)/(III) complexes.

This study investigates the influence of ligand charge on transition energies in a series of CuNS complexes based on dithiocarbazate Schiff base ligands using Cu K-edge X-ray absorption spectroscopy (XAS) and Kβ valence-to-core (VtC) X-ray emission spectroscopy (XES). By comparing the formally Cu(II) complexes [CuII(HL1)] (HL1 = dimethyl pentane-2,4-diylidenebis[carbonodithiohydrazonate]) and [CuII(HL2)] (HL2 = dibenzyl pentane-2,4-diylidenebis[carbonodithiohydrazonate]) and the formally Cu(III) complex [CuIII(L2)], distinct changes in transition energies are observed, primarily attributed to the metal oxidation state. Density functional theory (DFT) calculations demonstrate how an increased negative charge on the deprotonated L2 ligand stabilizes the Cu(III) center through enhanced charge donation, modulating the core transition energies.

Macrocyclic Copper(II) Complexes as Catalysts for Electrochemically Mediated Atom Transfer.

Copper-catalyzed electrochemical atom transfer radical addition (ATRA) is a new method for the creation of new C-C bonds under mild conditions. In this work, we have explored the reactivity of an analogous series of N macrocyclic Cu complexes as ATRA precatalysts, which are primed by reduction to their monovalent oxidation state. These complexes were fully characterized structurally, spectroscopically, and electrochemically.