Influence of pressure and dwell time on pressure-assisted sintering of calcium cobaltite

Calcium cobaltite Ca₃Co₄O₉, abbreviated Co349, is a promising thermoelectric material for high-temperature applications in air. Its anisotropic properties can be assigned to polycrystalline parts by texturing. Tape casting and pressure-assisted sintering (PAS) are a possible future way for a cost-effective mass-production of thermoelectric generators. This study examines the influence of pressure and dwell time during PAS at 900°C of tape-cast Co349 on texture and thermoelectric properties. Tape casting aligns lentoid Co349. PAS results in a textured Co349 microstructure with the thermoelectrically favorable ab-direction perpendicular to the pressing direction. By pressure variation during sintering, the microstructure of Co349 can be tailored either toward a maximum figure of merit as required for energy harvesting or toward a maximum power factor as required for energy harvesting. Moderate pressure of 2.5 MPa results in 25% porosity and a textured microstructure with a figure of merit of 0.13 at 700°C, two times higher than the dry-pressed, pressureless-sintered reference. A pressure of 7.5 MPa leads to 94% density and a high power factor of 326 µW/mK² at 800°C, which is 11 times higher than the dry-pressed reference (30 MPa) from the same powder.     

Lamin-Related Congenital Muscular Dystrophy Alters Mechanical Signaling and Skeletal Muscle Growth

Laminopathies are a clinically heterogeneous group of disorders caused by mutations in the LMNA gene, which encodes the nuclear envelope proteins lamins A and C. The most frequent diseases associated with LMNA mutations are characterized by skeletal and cardiac involvement, and include autosomal dominant Emery–Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy type 1B, and LMNA-related congenital muscular dystrophy (LMNA-CMD). Although the exact pathophysiological mechanisms responsible for LMNA-CMD are not yet understood, severe contracture and muscle atrophy suggest that mutations may impair skeletal muscle growth. Using human muscle stem cells (MuSCs) carrying LMNA-CMD mutations, we observe impaired myogenic fusion with disorganized cadherin/β catenin adhesion complexes. We show that skeletal muscle from Lmna-CMD mice is unable to hypertrophy in response to functional overload, due to defective fusion of activated MuSCs, defective protein synthesis and defective remodeling of the neuromuscular junction. Moreover, stretched myotubes and overloaded muscle fibers with LMNA-CMD mutations display aberrant mechanical regulation of the yes-associated protein (YAP). We also observe defects in MuSC activation and YAP signaling in muscle biopsies from LMNA-CMD patients. These phenotypes are not recapitulated in closely related but less severe EDMD models. In conclusion, combining studies in vitro, in vivo, and patient samples, we find that LMNA-CMD mutations interfere with mechanosignaling pathways in skeletal muscle, implicating A-type lamins in the regulation of skeletal muscle growth.     

Cytotoxic Potential of a-Azepano- and 3-Amino-3,4-SeCo-Triterpenoids

Semi-synthetic triterpenoids, holding an amino substituted seven-membered A-ring (azepano-ring), which could be synthesized from triterpenic oximes through a Beckmann type rearrangement followed by a reduction of lactame fragment, are considered to be novel promising agents exhibiting anti-microbial, alpha-glucosidase, and butyrylcholinesterase inhibitory activities. In this study, in an attempt to develop new antitumor candidates, a series of A-ring azepano- and 3-amino-3,4-seco-derivatives of betulin, oleanolic, ursolic, and glycyrrhetinic acids were evaluated for their cytotoxic activity against five human cancer cell lines and non-malignant mouse fibroblasts by means of a colorimetric sulforhodamine assay. Azepanoallobetulinic acid amide derivative 11 was the most cytotoxic compound of this series but showed little selectivity between the different human tumor cell lines. Flow cytometry experiments showed compound 11 to act mainly by apoptosis (44.3%) and late apoptosis (21.4%). The compounds were further screened at the National Cancer Institute towards a panel of 60 cancer cell lines. It was found that compounds 3, 4, 7, 8, 9, 11, 15, 16, 19, and 20 showed growth inhibitory (GI₅₀) against the most sensitive cell lines at submicromolar concentrations (0.20–0.94 μM), and their cytotoxic activity (LC₅₀) was also high (1–6 μM). Derivatives 3, 8, 11, 15, and 16 demonstrated a certain selectivity profile at GI₅₀ level from 5.16 to 9.56 towards K-562, CCRF-CEM, HL-60(TB), and RPMI-8226 (Leukemia), HT29 (Colon cancer), and OVCAR-4 (Ovarian cancer) cell lines. Selectivity indexes of azepanoerythrodiol 3 at TGI level ranged from 5.93 (CNS cancer cell lines SF-539, SNB-19 and SNB-75) to 14.89 for HCT-116 (colon cancer) with SI 9.56 at GI₅₀ level for the leukemia cell line K-562. The present study highlighted the importance of A-azepano-ring in the triterpenic core for the development of novel antitumor agents, and a future aim to increase the selectivity profile will thus lie in the area of modifications of azepano-triterpenic acids at their carboxyl group.     

A review of varietal change in roots,tubers and bananas: consumer preferences and other drivers of adoption and implications for breeding

This review of the literature on varietal change in sub-Saharan Africa looks in detail at adoption of new varieties of bananas in Uganda, cassava in Nigeria, potato in Kenya, sweetpotato in Uganda and yams in Côte d’Ivoire. The review explored three hypotheses about drivers of varietal change. There was a strong confirmation for the hypothesis that insufficient priority given to consumer-preferred traits by breeding programmes contributes to the limited uptake of modern varieties (MVs) and low varietal turnover. Lack of evidence meant the second hypothesis of insufficient attention to understanding and responding to gender differences in consumer preferences for quality and post-harvest traits was unresolved. The evidence on the third hypothesis about the informal seed system contributing to slow uptake of MVs was mixed. In some cases, the informal system has contributed to rapid uptake of MVs, but often it appears to be a barrier with inconsistent varietal naming a major challenge.     

New Biocompatible β-Phosphorylated Linear Nitrones Targeting Mitochondria: Protective Effect in Apoptotic Cells

The mitochondrion, an essential organelle involved in cellular respiration, energy production, and cell death, is the main cellular source of reactive oxygen species (ROS), including superoxide. Mitochondrial diseases resulting from uncontrolled/excess ROS generation are an emerging public health concern and there is current interest in specific mitochondriotropic probes to get information on in-situ ROS production. As such, nitrones vectorized by the triphenylphosphonium (TPP) cation have recently drawn attention despite reported cytotoxicity. Herein, we describe the synthesis of 13 low-toxic derivatives of N-benzylidene-1-diethoxyphosphoryl-1-methylethylamine N-oxide (PPN) alkyl chain-grafted to a pyridinium, triethylammonium or berberinium lipophilic cation. These nitrones showed in-vitro superoxide quenching activity and EPR/spin-trapping efficiency towards biologically relevant free radicals, including superoxide and hydroxyl radicals. Their mitochondrial penetration was confirmed by ³¹P NMR spectroscopy, and their anti-apoptotic properties were assessed in Schwann cells treated with hydrogen peroxide. Two pyridinium-substituted PPNs were identified as potentially better alternatives to TPP nitrones conjugates for studying mitochondrial oxidative damage.     

Cover Feature: Molecular Highway Patrol for Ribosome Collisions (ChemBioChem 20/2023)

During translation, messenger RNAs (mRNAs) are decoded by ribosomes which can stall for various reasons. These include chemical damage, codon composition, starvation, or translation inhibition. Trailing ribosomes can collide with stalled ribosomes, potentially leading to dysfunctional or toxic proteins. Such aberrant proteins can form aggregates and favor diseases, especially neurodegeneration. To prevent this, both eukaryotes and bacteria have evolved different pathways to remove faulty nascent peptides, mRNAs and defective ribosomes from the collided complex. In eukaryotes, ubiquitin ligases play central roles in triggering downstream responses and several complexes have been characterized that split affected ribosomes and facilitate degradation of the various components. As collided ribosomes signal translation stress to affected cells, in eukaryotes additional stress response pathways are triggered when collisions are sensed. These pathways inhibit translation and modulate cell survival and immune responses. Here, we summarize the current state of knowledge about rescue and stress response pathways triggered by ribosome collisions.     

MA‐NOTMP: A Triazacyclononane Trimethylphosphinate Based Bifunctional Chelator for Gallium Radiolabelling of Biomolecules

In the past few years, gallium‐68 has demonstrated significant potential as a radioisotope for positron emission tomography (PET), and the optimization of chelators for gallium coordination is a major goal in the development of radiopharmaceuticals. Methylaminotriazacyclononane trimethylphosphinate (MA‐NOTMP), a new C‐functionalized triazacyclononane derivative with phosphinate pendant arms, presents excellent coordination properties for ⁶⁸Ga (low ligand concentration, labelling at low pH even at room temperature). A “ready‐to‐be‐grafted” bifunctional chelating agent (p‐NCS‐Bz‐MA‐NOTMP) was prepared to allow ⁶⁸Ga labelling of sensitive biological vectors. Conjugation to a bombesin_(7–14) derivative was performed, and preliminary in vitro experiments demonstrated the potential of MA‐NOTMP in the development of radiopharmaceuticals. This new chelator is therefore of major interest for labelling sensitive biomolecules, and further in vivo experiments will soon be performed.     

Assembly and Characterizations of Bifunctional Fluorescent and Magnetic Microneedles With One Decade Length Tunability

This report presents the fabrication of bifunctional magnetic and fluorescent microneedles (µNDs) made of a ternary mixture of magnetic nanoparticles (NPs), quantum dots (QDs), and polyelectrolyte. The assembly relies on the electrostatic complexation of negatively charged NPs with positively charged polymer strands and is controlled by the charge ratio between the nanoparticle building blocks and the polymer mortar. The resulting 1D objects can be actuated using an external magnetic field and can be imaged using fluorescence microscopy, thanks to the fluorescent and superparamagnetic properties inherited from their NP constituents. Using a combination of core and surface characterizations and a state‐of‐the‐art image analysis algorithm, the dependence of the brightness and length on the ternary composition is thoroughly investigated. In particular, statistics on hundreds of µNDs with a range of compositions show that the µNDs have a log‐lormal length distribution and that their mean length can be robustly tuned in the 5–50 µm range to match the relevant length scales of various applications in micromixing, bioassays or biomechanics.