Photoinduced formation of a platina-α-lactone - a carbon dioxide complex of platinum. Insights from femtosecond mid-infrared spectroscopy.

The binding of carbon dioxide to a transition metal is a complex phenomenon that involves a major redistribution of electron density between the metal center and the triatomic ligand. The chemical reduction of the ligand reveals itself unambiguously by an angular distortion of the CO-molecule as a result of the occupation of an anti-bonding π-orbital and a shift of its antisymmetric stretching vibration, ν, to lower wavenumbers. Here, we generate a carbon dioxide complex of the heavier group-10 metal, platinum, by ultrafast electronic excitation and cleavage of CO from the photolabile oxalate precursor, oxaliplatin, and monitored the ensuing primary dynamics with ultrafast mid-infrared spectroscopy.

Rationalizing Predictions of Isoform-Selective Phosphoinositide 3-Kinase Inhibitors Using MolAnchor Analysis.

Explaining the predictions of machine learning models is of critical importance for integrating predictive modeling in drug discovery projects. We have generated a test system for predicting isoform selectivity of phosphoinositide 3-kinase (PI3K) inhibitors and systematically analyzed correct predictions of selective inhibitors using a new methodology termed MolAnchor, which is based on the "anchors" concept from explainable artificial intelligence. The approach is designed to generate chemically intuitive explanations of compound predictions.

Phytochemical Profile, Acute and Subacute Toxicity of Spray-Dried Hydroethanolic Extract from Punica granatum Leaves.

This study aimed to provide a comprehensive understanding of the acute and subacute safety and phytochemical profile of pomegranate leaves, aligning with the growing interest in sustainable, plant-based therapeutics. The phytochemical composition, the acute and subacute toxicity of a spray-dried hydroethanolic extract from pomegranate leaves (SDE) were investigated using experimental animal models. Utilizing UV-visible spectrophotometry and liquid chromatography-mass spectrometry (LC-MS), a diverse array of tannins and flavonoids, totaling 38 compounds, was identified.

A "phosphorus derivative" of aziridines: on the importance of ring strain energy and three heteropolar bonds in azaphosphiridines.

Compared to aziridines, azaphosphiridines, which formally result from the replacement of a carbon atom by phosphorus, have been much less studied. In this work, accurate values for one of the most prominent properties, the ring strain energy (RSE), have been theoretically examined for a wide range of azaphosphiridine derivatives. Strongly related aspects of interest for developing the use of azaphosphiridines in heteroatom and polymer chemistry are ring opening reactions and polymerisations, the latter facilitated by their significantly high RSE.

The earliest large carpenter bee () and its adhering pollen (Araliaceae, Theaceae).

The association of pollinators with their host plants is a critical element of ecosystem functioning and one that is usually determined indirectly in the fossil record from specific morphological traits of flowers or putative pollinating animals. The exceptionally fine preservation at Messel, Germany, offers an excellent source of data on pollen from fossil flowers as well as preserved adhering to insects as direct evidence of their association with specific floral lineages. Here, we report on pollen recovered from the body and legs of a large carpenter bee (Apidae: Xylocopinae: Xylocopini) from the Eocene of Messel.

EEFSEC deficiency: A selenopathy with early-onset neurodegeneration.

Inborn errors of selenoprotein expression arise from deleterious variants in genes encoding selenoproteins or selenoprotein biosynthetic factors, some of which are associated with neurodegenerative disorders. This study shows that bi-allelic selenocysteine tRNA-specific eukaryotic elongation factor (EEFSEC) variants cause selenoprotein deficiency, leading to progressive neurodegeneration. EEFSEC deficiency, an autosomal recessive disorder, manifests with global developmental delay, progressive spasticity, ataxia, and seizures.

The biarylitides: understanding the structure and biosynthesis of a fascinating class of Cytochrome P450 modified RiPP natural products.

The biarylitides are a recently discovered class of RiPP natural products that are fascinating both from the small size of the core peptides as well as the diversity of peptide crosslinking exhibited by the cytochrome P450 enzymes found in these systems. In this review, we address the discovery and biosynthetic diversity of these systems and discuss the methods and challenges of analysing the structures of these constrained cyclic peptides. We also discuss the structures of the P450 enzymes involved in these pathways and address the potential for alternate catalytic outcomes and activities as seen most recently with the inclusion of biarylitide related enzymes within rufomycin biosynthesis.

Deep learning-based patient stratification for prognostic enrichment of clinical dementia trials.

Dementia probably due to Alzheimer's disease is a progressive condition that manifests in cognitive decline and impairs patients' daily life. Affected patients show great heterogeneity in their symptomatic progression, which hampers the identification of efficacious treatments in clinical trials. Using artificial intelligence approaches to enable clinical enrichment trials serves a promising avenue to identify treatments.

Metastasis Detection Using True and Artificial T1-Weighted Postcontrast Images in Brain MRI.

Objectives: Small lesions are the limiting factor for reducing gadolinium-based contrast agents in brain magnetic resonance imaging (MRI). The purpose of this study was to compare the sensitivity and precision in metastasis detection on true contrast-enhanced T1-weighted (T1w) images and artificial images synthesized by a deep learning method using low-dose images.

Materials And Methods: In this prospective, multicenter study (5 centers, 12 scanners), 917 participants underwent brain MRI between October 2021 and March 2023 including T1w low-dose (0.

Influence of Data Curation and Confidence Levels on Compound Predictions Using Machine Learning Models.

While data curation principles and practices are a major topic in data science, they are often not explicitly considered in machine learning (ML) applications in chemistry. We have been interested in evaluating the potential effects of data curation on the performance of molecular ML models. Therefore, a sequential curation scheme was developed for compounds and activity data, and different ML classification models were generated at increasing data confidence levels and evaluated.

Identification of cell type-specific cell-penetrating peptides through in vivo phage display leveraged by next generation sequencing.

Vascular anomalies (VA) refer to abnormal blood or lymphatic vessel architecture, most often as a result of dysregulated growth. Venous malformations (VM), a subgroup of VAs, are triggered by activating mutations in the Angiopoietin/TIE2-PI3K/AKT/mTOR signaling pathway with TIE2 L914F (gene name TEK) being one of the most frequent mutations in patients with VMs. Although systemic targeting of the overactivated pathway is possible, it would be a therapeutic advantage to restrict treatment to only the affected lesions.

Linear and Two-Dimensional Infrared Spectroscopy of the Multifunctional Vibrational Probe, 3-(4-Azidophenyl) Propiolonitrile. Deperturbing a Fermi Triad by Isotopic Substitution.

Infrared probes are chemical moieties whose vibrational modes are used to obtain spectroscopic information about structural dynamics of complex systems; in particular, of biomacromolecules. Here, we explore the vibrational spectroscopy and dynamics of a reagent, 3-(4-azidophenyl)propiolonitrile (AzPPN), for selectively tagging thiols in protein environments with a multifunctional infrared probe containing both, an azide and a nitrile chromophore. The linear infrared spectrum of AzPPN is heavily perturbed in the antisymmetric azide stretching region as a result of accidental Fermi resonances.

Strong coupling between WS monolayer excitons and a hybrid plasmon polariton at room temperature.

Light-matter interactions between plasmonic and excitonic modes have attracted considerable interest in recent years. A major challenge in achieving strong coupling is the identification of suitable metallic nanostructures that combine tight field confinement with sufficiently low losses. Here, we report on a room-temperature study on the interaction of tungsten disulfide (WS) monolayer excitons with a hybrid plasmon polariton (HPP) mode supported by nanogroove grating structures milled into single-crystalline silver flakes.

Pain chronification risk assessment: advanced phenotyping and scoring for prediction and treatments tailored to individualized patient profile.

Unlabelled: Acute pain is a physiologic, protective life-important warning neurological signal indicating multi-level tissue modulations caused by a broad spectrum of health adverse events such as stress overload, mechanical trauma, ischemia-reperfusion, sterile and infection-triggered inflammation, single- and multi-organ damage, acute and chronic wounds, tissue remodeling and degeneration, amongst others. On the other hand, pain chronification results in a pathologic transformation from the protective pain signaling into persistent debilitative medical condition with severe consequences including but not restricted to phenotype-specific behavioral patterns, reduced quality of life, and cognitive and mood disorders. Who is predisposed to an increased vs.

Homozygous variant in translocase of outer mitochondrial membrane 7 leads to metabolic reprogramming and microcephalic osteodysplastic dwarfism with moyamoya disease.

Background: Impaired mitochondrial protein import machinery leads to phenotypically heterogeneous diseases. Here, we report a recurrent homozygous missense variant in the gene that encodes the translocase of outer mitochondrial membrane 7 (TOMM7) in nine patients with microcephaly, short stature, facial dysmorphia, atrophic macular scarring, and moyamoya disease from seven unrelated families.

Methods: To prove the causality of the TOMM7 variant, mitochondrial morphology, proteomics, and respiration were investigated in CRISPR/Cas9-edited iPSCs-derived endothelial cells.

Structural Insights into the Iodothyronine Deiodinase 2 Catalytic Core and Deiodinase Catalysis and Dimerization.

Iodothyronine deiodinases (Dio) are selenocysteine-containing membrane enzymes that activate and inactivate the thyroid hormones (TH) through reductive iodide eliminations. The three deiodinase isoforms are homodimers sharing highly conserved amino acid sequences, but they differ in their regioselectivities for the deiodination reaction and regulatory features. We have now solved a crystal structure of the mouse deiodinase 2 (Dio2) catalytic domain.

YeeE-like bacterial SoxT proteins mediate sulfur import for oxidation and signal transduction.

Many sulfur-oxidizing prokaryotes oxidize sulfur compounds through a combination of initial extracytoplasmic and downstream cytoplasmic reactions. Facultative sulfur oxidizers adjust transcription to sulfur availability. While sulfur-oxidizing enzymes and transcriptional repressors have been extensively studied, sulfur import into the cytoplasm and how regulators sense external sulfur are poorly understood.

PRDX6 contributes to selenocysteine metabolism and ferroptosis resistance.

Selenocysteine (Sec) metabolism is crucial for cellular function and ferroptosis prevention and begins with the uptake of the Sec carrier, selenoprotein P (SELENOP). Following uptake, Sec released from SELENOP is metabolized via selenocysteine lyase (SCLY), producing selenide, a substrate for selenophosphate synthetase 2 (SEPHS2), which provides the essential selenium donor, selenophosphate (HSePO), for the biosynthesis of the Sec-tRNA. Here, we discovered an alternative pathway in Sec metabolism mediated by peroxiredoxin 6 (PRDX6), independent of SCLY.

Protocol to calculate and compare exact Shapley values for different kernels in support vector machine models using binary features.

The Shapley value formalism from cooperative game theory was adapted to explain predictions of machine learning models. Here, we present a protocol to calculate and compare exact Shapley values for support vector machine models with commonly used kernels and binary input features. We describe steps for installing software, preparing data, and calculating Shapley values with customizable Python scripts.

Upregulation vs. loss of function of NTRK2 in 44 affected individuals leads to two distinct neurodevelopmental disorders.

Introduction: Heterozygous pathogenic variants in NTRK2 (HGNC: 8032) have been associated with global developmental delay. However, only scattered cases have been described in small or general studies. The aim of our work was to consolidate our understanding of NTRK2-related disorders and to delineate the clinical presentation METHODS: We report extended cohort of 44 affected individuals, of whom 19 are from the literature and 25 were previously unreported.

Type I Interferon Drives a Cellular State Inert to TCR-Stimulation and Could Impede Effective T-Cell Differentiation in Cancer.

Background: Head and neck squamous cell carcinoma (HNSCC) is linked to human papillomavirus (HPV) infection. HPV-positive and HPV-negative HNSCC exhibit distinct molecular and clinical characteristics. Although checkpoint inhibitors have shown efficiency in recurrent/metastatic HNSCC, response variability persists regardless of HPV status.

Silylium-Ion-Promoted (3 + 2) Annulation of Allenylsilanes with Internal Alkynes Involving a Pentadienyl-to-Allyl Cation Electrocyclization.

A (3 + 2) annulation of allenyl- and, after rapid isomerization, propargylsilanes with internal 1-aryl-1-alkynes to form 4-methylenecyclopentenes is reported. The reaction is initiated by a silylium ion, and the catalytic cycle is subsequently maintained by the self-regeneration of the silylium-ion promoter. Unlike the well-established Danheiser annulation, where the allenylsilane serves as a , the present transformation engages the allenylsilane as a .