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An N-heterocyclic stannylene :Sn(NONAd) (NONAd = [O(SiMe2NAd)2]2−, Ad = 1-adamantyl), reacts rapidly with 2,4,6-tricyclohexylphenyl azide (TCHP)N3, affording a stannaimine, (NONAd)Sn＝N(TCHP). Solutions of (NONAd)Sn＝N(TCHP) react immediately with carbon dioxide (CO2) to give a [2+2]-cycloaddition product, which, upon heating, subsequently engages in a metathesis process to give [Sn(NONAd)(μ-O)]2 and the bulky isocyanate, (TCHP)NCO. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI) quantification of intramuscular fat accumulation is a responsive biomarker in neuromuscular diseases. Despite emergence of automated methods, manual muscle segmentation remains an essential foundation. We aimed to develop a training programme for new observers to demonstrate competence in lower limb muscle segmentation and establish reliability benchmarks for future human observers and machine learning segmentation packages. Methods: The learning phase of the training programme comprised a training manual, direct instruction, and eight lower limb MRI scans with reference standard large and small regions of interest (ROIs). The assessment phase used test–retest scans from two patients and two healthy controls. Interscan and interobserver reliability metrics were calculated to identify underperforming outliers and to determine competency benchmarks. Results: Three experienced observers undertook the assessment phase, whilst eight new observers completed the full training programme. Two of the new observers were identified as underperforming outliers, relating to variation in size or consistency of segmentations; six had interscan and interobserver reliability equivalent to those of experienced observers. The calculated benchmark for the Sørensen-Dice similarity coefficient between observers was greater than 0.87 and 0.92 for individual thigh and calf muscles, respectively. Interscan and interobserver reliability were significantly higher for large than small ROIs (all p < 0.001). Conclusions: We developed, implemented, and analysed the first formal training programme for manual lower limb muscle segmentation. Large ROI showed superior reliability to small ROI for fat fraction assessment. Relevance statement: Observers competent in lower limb muscle segmentation are critical to application of quantitative muscle MRI biomarkers in neuromuscular diseases. This study has established competency benchmarks for future human observers or automated segmentation methods. Key points: • Observers competent in muscle segmentation are critical for quantitative muscle MRI biomarkers. • A training programme for muscle segmentation was undertaken by eight new observers. • We established competency benchmarks for future human observers or automated segmentation methods. [ABSTRACT FROM AUTHOR]

Simple Summary: Estimating the risk of postoperative complications is important for shared decision-making with the patient. This also helps multidisciplinary teams to plan preoperative management and postoperative care and predict duration of recovery. In this retrospective pilot study, we aim to evaluate the accuracy and reliability of the P-POSSUM and ACS-NSQIP surgical risk calculators in predicting postoperative complications in gynaecological–oncological (GO) robotic surgery (RS). We were able to demonstrate that the ACS-NSQIP risk tool showed 90% accuracy in prediction of five major complications and mortality. Purpose: In this retrospective pilot study, we aim to evaluate the accuracy and reliability of the P-POSSUM and ACS-NSQIP surgical risk calculators in predicting postoperative complications in gynaecological–oncological (GO) robotic surgery (RS). Methods: Retrospective data collection undertaken through a dedicated GO database and patient notes at a tertiary referral cancer centre. Following data lock with the actual post-op event/complication, the risk calculators were used to measure predictive scores for each patient. Baseline analysis of 153 patients, based on statistician advice, was undertaken to evaluate P-POSSUM and ACS-NSQIP validity and relevance in GO patients undergoing RS performed. Results: P-POSSUM reports on mortality and morbidity only; ACS-NSQIP reports some individual complications as well. ACS-NSQIP risk prediction was most accurate for venous thromboembolism (VTE) (area under the curve (AUC)-0.793) and pneumonia (AUC-0.657) and it showed 90% accuracy in prediction of five major complications (Brier score 0.01). Morbidity was much better predicted by ACS-NSQIP than by P-POSSUM (AUC-0.608 vs. AUC-0.551) with the same result in mortality prediction (Brier score 0.0000). Moreover, a statistically significant overestimation of morbidity has been shown by the P-POSSUM calculator (p = 0.018). Conclusions: Despite the limitations of this pilot study, the ACS-NSQIP risk calculator appears to be a better predictor of major complications and mortality, making it suitable for use by GO surgeons as an informed consent tool. Larger data collection and analyses are ongoing to validate this further. [ABSTRACT FROM AUTHOR]

Zika and dengue virus nonstructural protein 5 antagonism of STAT2, a critical interferon signaling transcription factor, to suppress the host interferon response is required for viremia and pathogenesis in a vertebrate host. This affects viral species tropism, as mouse STAT2 resistance renders only immunocompromised or humanized STAT2 mice infectable. Here, we explore how STAT2 evolution impacts antagonism. By measuring the susceptibility of 38 diverse STAT2 proteins, we demonstrate that resistance arose numerous times in mammalian evolution. In four species, resistance requires distinct sets of multiple amino acid changes that often individually disrupt STAT2 signaling. This reflects an evolutionary ridge where progressive resistance is balanced by the need to maintain STAT2 function. Furthermore, resistance may come with a fitness cost, as resistance that arose early in lemur evolution was subsequently lost in some lemur lineages. These findings underscore that while it is possible to evolve resistance to antagonism, complex evolutionary trajectories are required to avoid detrimental host fitness consequences. Zika and Dengue virus non-structural protein 5 can antagonise STAT2 modulating the host response and this interaction is involved in determining tropism. Here the authors show mammals independently evolved resistance to flavivirus NS5 multiple times, involving complex genetic changes in STAT2 which balance viral defence whilst maintaining STAT2's critical functions. [ABSTRACT FROM AUTHOR]

Reduction of the magnesium(II) diamide [Mg(TripNON)] (TripNON = 4,5-bis(2,4,6-triisopropylanilido)-2,7-diethyl-9,9-dimethyl-xanthene) with 5% w/w K/KI leads to a good yield of a dianionic dimagnesium(I) species, as its potassium salt, [{K(TripNON)Mg}2]. An X-ray crystallographic analysis shows the molecule to contain a very long Mg–Mg bond (3.137(2) Å). The formation of [{K(TripNON)Mg}2] contrasts with a previously reported reduction of a magnesium(II) complex incorporating a bulkier diamide ligand, which instead afforded a magnesium–dinitrogen complex. In the current study, [{K(TripNON)Mg}2] has been shown to be a viable reagent for the reductive activation of CO, H2 and N2O. [ABSTRACT FROM AUTHOR]

A simple sequential addition protocol for the reductive coupling of ketones and aldehydes by a potassium aluminyl grants access to unsymmetrical pinacolate derivatives. Isolation of an aluminium ketyl complex presents evidence for the accessibility of radical species. Product release from the aluminium centre was achieved using an iodosilane, forming the disilylated 1,2‐diol and a neutral aluminium iodide, thereby demonstrating the steps required to generate a closed synthetic cycle for pinacol (cross) coupling at an aluminyl anion. [ABSTRACT FROM AUTHOR]

Extant salamanders are used as modern analogs of early digit-bearing tetrapods due to general similarities in morphology and ecology, but the study species have been primarily terrestrial and relatively smaller when the earliest digit-bearing tetrapods were aquatic and an order of magnitude larger. Thus, we created a 3D computational model of underwater walking in extant Japanese giant salamanders (Andrias japonicus) using 3D photogrammetry and open-access graphics software (Blender) to broaden the range of testable hypotheses about the incipient stages of terrestrial locomotion. Our 3D model and software protocol represent the initial stages of an open-access pipeline that could serve as a "one-stop-shop" for studying locomotor function, from creating 3D models to analyzing the mechanics of locomotor gaits. While other pipelines generally require multiple software programs to accomplish the different steps in creating and analyzing computational models of locomotion, our protocol is built entirely within Blender and fully customizable with its Python scripting so users can devote more time to creating and analyzing models instead of navigating the learning curves of several software programs. The main value of our approach is that key kinematic variables (e.g. speed, stride length, and elbow flexion) can be easily altered on the 3D model, allowing scientists to test hypotheses about locomotor function and conduct manipulative experiments (e.g. lengthening bones) that are difficult to perform in vivo. The accurate 3D meshes (and animations) generated through photogrammetry also provide exciting opportunities to expand the abundance and diversity of 3D digital animals available for researchers, educators, artists, conservation biologists, etc. to maximize societal impacts., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

A bulky, unsymmetrical β-diketiminate ligand, [HC{MeCN(Dip)}{MeCN(TCHP)}] - ( Dip/TCHP Nacnac; Dip = 2,6-diisopropylphenyl, TCHP = 2,4,6-tricyclohexylphenyl), has been utilised in the preparation of a series of magnesium alkyl and calcium, strontium and barium amide complexes. Reaction of these with PhSiH 3 afforded the first complete series of β-diketiminato heavier group 2 metal hydride complexes, [{( Dip/TCHP Nacnac)M(μ-H)} 2 ] (M = Mg, Ca, Sr or Ba). The unsymmetrical nature of the β-diketiminate ligand seemingly promotes stabilising interactions of ligand Dip groups with the metal centres in the Ca, Sr and Ba hydride complexes.

Microbes exist at and colonize mucosal surfaces striking a balance with the host immune system, so that these microbes can thrive on host tissues without causing pathology. Because of this, mucosal barrier-colonizing bacteria can be leveraged to act as long-term delivery vehicles for naturally derived therapeutics. Here, we use a mouse model of corneal wound healing to show that the eye-colonizing bacterium, Corynebacterium mastitidis (C. mast) can be engineered to produce and secrete bioactive murine anti-inflammatory interleukin (mIL)-10. Specifically, we used transposon mutagenesis to identify a native C. mast-specific secretion signal that was used to direct C. mast to secrete mIL-10. Mini-transposons were generated to deliver secretion capable mIL-10 to the bacterial genome. After screening, two isolates were identified that can: 1) colonize the eye, 2) produce and secrete mIL-10, and 3) enhance wound healing in an IL-10-dependent manner. This proof of concept illustrates that eye-colonizing bacteria can be engineered to deliver therapeutics to the ocular surface for the alleviation of ocular surface disease(s).

In this contribution, we present "Birch-type", and other reductions of simple arenes by the potassium salt of an anionic magnesium dinitrogen complex, [{K( TCHP NON)Mg} 2 (μ-N 2 )] ( TCHP NON=4,5-bis(2,4,6-tricyclohexylanilido)-2,7-diethyl-9,9-dimethyl-xanthene), which acts as a masked dimagnesium(I) diradical in these reactions. This reagent is non-hazardous, easy-to-handle, and in some cases provides access to 1,4-cyclohexadiene reduction products under relatively mild reaction conditions. This system works effectively to reduce benzene, naphthalene and anthracene through magnesium-bound "Birch-type" reduction intermediates. Cyclohexadiene products can be subsequently released from the magnesium centres by protonolysis with methanol. In contrast, the reduction of substituted arenes is less selective and involves competing reaction pathways. For toluene and 1,3,5-triphenylbenzene, the structural authentication of "Birch-type" reduction intermediates is conclusive, although the formation of corresponding 1,4-cyclohexadiene derivatives was low yielding. Reduction of anisole did not yield an isolable "Birch-type" intermediate, but instead gave a C-O activation product. Treating triphenylphosphine with [{K( TCHP NON)Mg} 2 (μ-N 2 )] resulted in the extrusion of both biphenyl and dinitrogen to afford a magnesium(II) phosphanide [{K( TCHP NON)Mg(μ-PPh 2 )} 2 ]. Reduction of fluorobenzene proceeded via C-F activation of the arene, and isolation of the magnesium(II) fluoride [{K( TCHP NON)Mg(μ-F)} 2 ]. Finally, the two-electron reduction of 1,3,5,7-cyclooctatetraene (COT) with [{K( TCHP NON)Mg} 2 (μ-N 2 )] yielded a complex, [{K( TCHP NON)Mg} 2 (μ-COT)], incorporating the aromatic dianion (COT 2- )., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

The bulky β-diketiminate ligand frameworks [BDI DCHP ] - and [BDI Dipp/Ar ] - (BDI=[HC{C(Me) 2 N-Dipp/Ar} 2 ] - (Dipp=2,6-diisopropylphenyl (Dipp); Ar=2,6-dicyclohexylphyenyl (DCHP) or 2,4,6-tricyclohexylphyenyl (TCHP)) have been developed for the kinetic stabilisation of the first europium (II) hydride complexes, [(BDI DCHP )Eu(μ-H)] 2 , [(BDI Dipp/DCHP )Eu(μ-H)] 2 and [(BDI Dipp/TCHP )Eu(μ-H)] 2 , respectively. These complexes represent the first step beyond the current lanthanide(II) hydrides that are all based on ytterbium. Tuning the steric profile of β-diketiminate ligands from a symmetrical to unsymmetrical disposition, enhanced solubility and stability in the solution-state. This provides the first opportunity to study the structure and bonding of these novel Eu(II) hydride complexes crystallographically, spectroscopically and computationally, with their preliminary reactivity investigated., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Reduction of the magnesium(II) diamide [Mg( Trip NON)] ( Trip NON = 4,5-bis(2,4,6-triisopropylanilido)-2,7-diethyl-9,9-dimethyl-xanthene) with 5% w/w K/KI leads to a good yield of a dianionic dimagnesium(I) species, as its potassium salt, [{K( Trip NON)Mg} 2 ]. An X-ray crystallographic analysis shows the molecule to contain a very long Mg-Mg bond (3.137(2) Å). The formation of [{K( Trip NON)Mg} 2 ] contrasts with a previously reported reduction of a magnesium(II) complex incorporating a bulkier diamide ligand, which instead afforded a magnesium-dinitrogen complex. In the current study, [{K( Trip NON)Mg} 2 ] has been shown to be a viable reagent for the reductive activation of CO, H 2 and N 2 O.