3D multiscale characterization of the human placenta: Bridging anatomy and histology by X-ray phase-contrast tomography.

The human placenta exhibits a complex three-dimensional (3D) structure with a interpenetrating vascular tree and large internal interfacial area. In a unique and yet insufficiently explored way, this parenchymal structure enables its multiple functions as a respiratory, renal, and gastrointestinal multiorgan. The histopathological states are highly correlated with complications and health issues of mother, and fetus or newborn.

A transdisciplinary, comparative analysis reveals key risks from Arctic permafrost thaw.

Permafrost thaw poses diverse risks to Arctic environments and livelihoods. Understanding the effects of permafrost thaw is vital for informed policymaking and adaptation efforts. Here, we present the consolidated findings of a risk analysis spanning four study regions: Longyearbyen (Svalbard, Norway), the Avannaata municipality (Greenland), the Beaufort Sea region and the Mackenzie River Delta (Canada) and the Bulunskiy District of the Sakha Republic (Russia).

Prodrugs and their activation mechanisms for brain drug delivery.

Prodrugs are masked drugs that first become pharmacologically active after undergoing a structural change . They are designed to improve physicochemical/biopharmaceutical drug properties and increase site specificity. The prodrug approach is important when developing brain-targeting drugs due to the presence of the brain barriers that seriously limit the brain entry of highly polar, multifunctional drug entities.

Insights into Homogeneous Bulk Boron Doping at the Tetrahedral Site of NCM811 Cathode Materials: Structure Stabilization by Inductive Effect on TM-O-B Bonds.

Rechargeable lithium-ion batteries (LIBs) are critical for enabling sustainable energy storage. The capacity of cathode materials is a major limiting factor in the LIB performance, and doping has emerged as an effective strategy for enhancing the electrochemical properties of nickel-rich layered oxides such as NCM811. In this study, boron is homogeneously incorporated into the tetrahedral site of NCM811 through co-precipitation, leading to an inductive effect on transition metal (TM)-O-B bonds that delayed structural collapse and reduced oxygen release.

Design, Synthesis, and Screening of an RNA Optimized Fluorinated Fragment Library.

Fragment-based screening is an efficient method for early-stage drug discovery. In this study, we aimed to create a fragment library optimized for producing high hit rates against RNA targets. RNA has historically been an underexplored target, but recent research suggests potential for optimizing small molecule libraries for RNA binding.

Examining the moderation of the relationship between socio-economic status and consumption intentions by food information labels.

Front-of-package-labelling needs to portray health and/or sustainability information effectively to all consumers in a way that is both effective and equitable. There is mixed evidence for the effectiveness of such labels based on socioeconomic status (SES). Framing health consequences in an intuitive manner could help to reduce disparities in label comprehension across SES.

PTV Margins in MR-guided and Beam-gated SBRT of Liver Metastases: GTV Dose Escalation Can Reduce the Required PTV.

Aims: Determining appropriate PTV margins for SBRT of liver metastases is a non-trivial task, especially with motion management included. The widely used analytical van Herk margin recipe (van Herk et al., 2000) could break down due to (i) a low number of fractions, (ii) non-Gaussian errors, or (iii) non-homogenous dose distributions.

Increased fish abundance, biodiversity, and body size near a North Sea oil and gas platform.

In the North Sea, offshore oil and gas (O&G) platforms must be totally removed through decommissioning at the end of their productive life. However, the role of O&G platforms in marine ecosystems, especially for fish assemblages, is not well enough defined yet. Here, we document the association between an O&G platform in the North Sea and the fish assemblages along a distance gradient of 1-600 m from the platform.

Establishment of a 3D-Printed Tissue-on-a-Chip Model for Live Imaging of Bacterial Infections.

Despite advances in healthcare, bacterial pathogens remain a severe global health threat, exacerbated by rising antibiotic resistance. Lower respiratory tract infections, with their high death toll, are of particular concern. Accurately replicating host-pathogen interactions in laboratory models is crucial for understanding these diseases and evaluating new therapies.

Interferon-α promotes HLA-B-restricted presentation of conventional and alternative antigens in human pancreatic β-cells.

Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but the effect of IFN-α on the antigen repertoire of HLA Class I (HLA-I) in pancreatic β-cells is unknown. Here we characterize the HLA-I antigen presentation in resting and IFN-α-exposed β-cells and find that IFN-α increases HLA-I expression and expands peptide repertoire to those derived from alternative mRNA splicing, protein cis-splicing and post-translational modifications. While the resting β-cell immunopeptidome is dominated by HLA-A-restricted peptides, IFN-α largely favors HLA-B and only marginally upregulates HLA-A, translating into increased HLA-B-restricted peptide presentation and activation of HLA-B-restricted CD8 T cells.

Multivariate Approaches Boosting Lithium-Mediated Ammonia Electrosynthesis in Different Electrolytes.

Ammonia electrosynthesis through the lithium-mediated approach has recently reached promising results towards high activity and selectivity in aprotic media, reaching high Faradaic efficiency (FE) values and NH3 production rates. To fasten the comprehension and optimization of the complex lithium-mediated nitrogen reduction system, for the first time a multivariate approach is proposed as a powerful tool to reduce the number of experiments in comparison with the classical one-factor-at-a-time approach. Doehlert design and surface response methodology are employed to optimize the electrolyte composition for a batch autoclaved cell.

Development of a yeast-based sensor platform for evaluation of ligands recognized by the human Free Fatty Acid 2 Receptor.

Yeast-based sensors have shown great applicability for deorphanization of G protein-coupled receptors (GPCRs) and screening of ligands targeting these. A GPCR of great interest is free fatty acid 2 receptor (FFA2R), for which short-chain fatty acids such as propionate and acetate are agonists. FFA2R regulates a wide array of downstream receptor signaling pathways in both adipose tissue and immune cells and has been recognized as a promising therapeutic target, having been implicated in several metabolic and inflammatory diseases.

Analysis of enzyme kinetics of fungal methionine synthases in an optimized colorimetric microscale assay for measuring cobalamin-independent methionine synthase activity.

Aspergillus spp. and Rhizopus spp., used in solid-state plant food fermentations, encode cobalamin-independent methionine synthase activity (MetE, EC 2.

amVAE: Age-aware multimorbidity clustering using variational autoencoders.

Multimorbidity, the co-occurrence of multiple chronic conditions within the same individual, is increasing globally. This is a challenge for the single patients, as these individuals are subject to a heavy disease and treatment burden, yet evidence on the epidemiology and consequences of multimorbidity remains underexplored. Historically, studies aiming to understand multimorbidity patterns predominantly utilized cross-sectional data, neglecting the essential temporal dynamics which shape multimorbidity progression.

No Bacterial Biomass Detected in Tissue From Patients With Ovarian Cancer and Serous Tubal Intraepithelial Carcinomas Using 16S rDNA Sequencing.

The ovarian oncobiome is subject to increasing scientific focus, but a potential link between bacterial dysbiosis and ovarian carcinogenesis remains controversial. Our primary aim was to characterize the bacterial microbiota in epithelial ovarian cancer samples. Secondarily, we aimed to compare results from the bacterial microbiota in formalin-fixed, paraffin-embedded ovarian tissue samples from 194 patients with epithelial ovarian cancer, fallopian tube tissue samples from 16 patients with serous tubal intraepithelial carcinomas and in benign fallopian tube tissue samples from 25 patients.

The mechanism of amyloid fibril growth from Φ-value analysis.

Amyloid fibrils are highly stable misfolded protein assemblies that play an important role in several neurodegenerative and systemic diseases. Although structural information of the amyloid state is now abundant, mechanistic details about the misfolding process remain elusive. Inspired by the Φ-value analysis of protein folding, we combined experiments and molecular simulations to resolve amino-acid contacts and determine the structure of the transition-state ensemble-the rate-limiting step-for fibril elongation of PI3K-SH3 amyloid fibrils.

Clinical validation of explainable AI for fetal growth scans through multi-level, cross-institutional prospective end-user evaluation.

We aimed to develop and evaluate Explainable Artificial Intelligence (XAI) for fetal ultrasound using actionable concepts as feedback to end-users, using a prospective cross-center, multi-level approach. We developed, implemented, and tested a deep-learning model for fetal growth scans using both retrospective and prospective data. We used a modified Progressive Concept Bottleneck Model with pre-established clinical concepts as explanations (feedback on image optimization and presence of anatomical landmarks) as well as segmentations (outlining anatomical landmarks).

Formic acid dehydrogenation catalysed by a novel amino-di(N-heterocyclic carbene) based Ru-CNC pincer complex.

A new Ru(II) complex featuring a novel amino-di(N-heterocyclic carbene) CNC pincer ligand, CNC-RuCl(CO) (Ru-1), has been developed and characterised in depth. Ru-1 forms an efficient and durable catalytic formic acid dehydrogenation system in combination with the ionic liquid 1-ethyl-3-methylimidazolium diethylphosphate (EMIM PO(OEt)).

Formation of acrylamide in commercially available plant-based meat alternatives during domestic cooking.

The formation and occurrence of acrylamide in carbohydrate-rich foods has been extensively studied over the course of the past few decades. However, the emergence of plant-based meat alternatives presents a new challenge in this field. The aim of this study was to evaluate the levels of acrylamide in commercially available plant-based meat alternatives before and after heat treatment.

Electrochemical Ammonia Synthesis: The Energy Efficiency Challenge.

We discuss the challenges associated with achieving high energy efficiency in electrochemical ammonia synthesis at near-ambient conditions. The current Li-mediated process has a theoretical maximum energy efficiency of ∼28%, since Li deposition gives rise to a very large effective overpotential. As a starting point toward finding electrocatalysts with lower effective overpotentials, we show that one reason why Li and alkaline earth metals work as N reduction electrocatalysts at ambient conditions is that the thermal elemental processes, N dissociation and NH desorption, are both facile at room temperature for these metals.

De novo designed proteins neutralize lethal snake venom toxins.

Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage and inhibition of nicotinic acetylcholine receptors, resulting in life-threatening neurotoxicity. At present, the only available treatments for snakebites consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs.

Improving the accuracy of temperature measurement on TEM samples using plasmon energy expansion thermometry (PEET): Addressing sample thickness effects.

Advances in analytical scanning transmission electron microscopy (STEM) and in microelectronic mechanical systems (MEMS) based microheaters have enabled in-situ materials' characterization at the nanometer scale at elevated temperature. In addition to resolving the structural information at elevated temperatures, detailed knowledge of the local temperature distribution inside the sample is essential to reveal thermally induced phenomena and processes. Here, we investigate the accuracy of plasmon energy expansion thermometry (PEET) as a method to map the local temperature in a tungsten (W) lamella in a range between room temperature and 700 °C.

Complete genome sequences of two actinomycetes containing abyssomicin-like gene clusters: DSM 45791 and sp. NL15-2K.

Here, we report the resequencing, assembly, and annotation of two actinomycete genomes containing abyssomicin gene clusters. DSM 45791 with a circular chromosome of 11,681,598 bp and 4 circular plasmids (14,175-207,548 bp) and sp. NL15-2K with a 12,368,159 bp linear genome and circular plasmid (11,584 bp).

Pangenome mining of the Streptomyces genus redefines species' biosynthetic potential.

Background: Streptomyces is a highly diverse genus known for the production of secondary or specialized metabolites with a wide range of applications in the medical and agricultural industries. Several thousand complete or nearly complete Streptomyces genome sequences are now available, affording the opportunity to deeply investigate the biosynthetic potential within these organisms and to advance natural product discovery initiatives.

Results: We perform pangenome analysis on 2371 Streptomyces genomes, including approximately 1200 complete assemblies.

Multiplex genome editing eliminates lactate production without impacting growth rate in mammalian cells.

The Warburg effect, which describes the fermentation of glucose to lactate even in the presence of oxygen, is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production in cells for bioprocessing have failed as lactate dehydrogenase is essential for cell growth. Here, we effectively eliminate lactate production in Chinese hamster ovary and in the human embryonic kidney cell line HEK293 by simultaneous knockout of lactate dehydrogenases and pyruvate dehydrogenase kinases, thereby removing a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA.