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Measurement of phospholipid lateral diffusion at high pressure by in situ magic-angle spinning NMR spectroscopy

The development of experimental methodologies that enable investigations of biochemistry at high pressure promises to yield significant advances in our understanding of life on Earth and its origins. Here, we introduce a method for studying lipid membranes at thermodynamic conditions relevant for life at deep sea hydrothermal vents. Using in situ high pressure magic-angle spinning solid state nuclear magnetic resonance spectroscopy (NMR), we measure changes in the fluidity of model microbial membranes at pressures up to 28 MPa. We find that the fluid-phase lateral diffusion of phospholipids at high pressure is significantly affected by the stoichiometric ratio of lipids in the membrane. Our results were facilitated by an accessible pressurization strategy that we have developed to enable routine preparation of solid state NMR rotors to pressures of 30 MPa or greater.

Blood pressure elevations post-lenvatinib treatment in hepatocellular carcinoma: a potential marker for better prognosis

Lenvatinib is a tyrosine kinase inhibitor that effectively inhibits vascular endothelial growth factor signaling and is used for treating hepatocellular carcinoma. However, angiogenesis inhibitors often cause hypertension. Although lenvatinib-induced hypertension has been proposed as a potential surrogate marker for better prognosis, studies on blood pressure elevations and outcomes following lenvatinib initiation are limited. This study included 67 patients who underwent lenvatinib therapy at the Department of Gastroenterology, Kagoshima University Hospital, between May 2018 and December 2023. The median age of the cohort was 71 years, and 82.1% of the patients were male. The median blood pressure at admission was 128/73 mmHg, which significantly increased to 136/76 mmHg the day after lenvatinib administration. Grade 3 hypertension (≥160/100 mmHg) occurred in 37.3% of patients during hospitalization. The median increase in systolic blood pressure from admission to its peak during hospitalization was 26 mmHg. Patients who experienced an increase in blood pressure of ≥26 mmHg were classified into the blood pressure elevation group, which showed a significantly lower mortality rate than that of the blood pressure non-elevation group (35.3% vs. 81.8%, log-rank p = 0.007), even after adjusting for age, sex, disease stage, performance status, and liver reserve function. This study demonstrated that patients who experienced earlier blood pressure elevation after lenvatinib administration had lower overall mortality rates. These findings suggest that blood pressure elevations after lenvatinib initiation may serve as valuable prognostic indicators in patients with cancer undergoing lenvatinib therapy.

Tuning a magnetic energy scale with pressure and field in UTe2

When a fragile ordered state is suppressed to zero temperature, a quantum phase transition occurs, which is often marked by the appearance of unconventional superconductivity. While the quantum critical point can be hidden, the influence of the quantum criticality extends to fairly high temperatures, manifesting non-Fermi liquid behavior in a wide range of the field-temperature-pressure phase space. Here, we report the tuning of a magnetic energy scale in the heavy-fermion superconductor UTe2, previously identified with a peak in the c-axis electrical transport temperature dependence, using applied hydrostatic pressures and a-axis-oriented magnetic fields as complementary (and opposing) tuning parameters: the characteristic peak in c-axis resistivity decreases in temperature with applied pressure before vanishing near the critical pressure of 15 kbar (1.5 GPa), while the application of field shifts the peak to a higher temperature and broadens it under all studied pressures. At the critical pressure, the transport behavior deviates from Fermi liquid behavior, exhibiting a nearly linear temperature dependence of resistivity with an enhanced pre-factor. Our results shed light on the microscopic origin of the c-axis resistivity peak and provide a clear picture of magnetic energy scale evolution relevant to quantum criticality in UTe2.

Using high pressure to investigate the stability of a high entropy wurtzite structured (MnFeCuAgZnCd)S

High entropy metal chalcogenides are an emergent class of materials that have shown exceptional promise in applications such as energy storage, catalysis, and thermoelectric energy conversion. However, the stability of these materials to factors other than temperature are as yet unknown. Here we set out to assess the stability of the high entropy metal sulfide (MnFeCuAgZnCd)S with high pressure (up to 9 GPa), compared to an enthalpically stabilised Ag3CuS2, and a quasi-stable (MnFeZnCd)S. Compression and pressure-annealing of (MnFeCuAgZnCd)S showed diffusion-controlled time and pressure dependent exsolution of jalpaite (Ag3CuS2) from the bulk. Bulk materials characterisation found minor phase impurities and possible elemental localisations in (MnFeCuAgZnCd)S prior to pressure-annealing. To gain deeper understanding of the material pre- and post-pressure annealing at the nanoscale an advanced technique was used which combined machine learning, unsupervised clustering analysis of STEM-EDX mapping with scanning precession electron diffraction (SPED), which revealed a chemically distinct post-pressure annealed jalpaite exsolved from (MnFeCuAgZnCd)S.

Chromosomal aberrations and early mortality in a non-mammalian vertebrate: example from pressure-induced triploid Atlantic salmon

In commercial aquaculture, the production of triploid fish is currently the most practical approach to prevent maturation and farm-to-wild introgression following escapes. However, triploids often exhibit poor welfare, and the underlying mechanisms remain unclear. Inheritance issues associated with sub-optimal hydrostatic pressure treatments used to induce triploidy, or the genetic background of parental fish, have been speculated to contribute. We tested this by quantifying the frequency and type of chromosomal aberrations in Atlantic salmon subjected to a gradient of sub-optimal pressure treatments (Experiment 1) and from multiple mothers (Experiment 2). From these experiments, we genotyped a subsample of ~900 eyed eggs and all ~3300 surviving parr across ~20 microsatellites. In contrast to the low frequency of chromosomal aberrations in the diploid (no hydrostatic pressure) and triploid (full 9500 PSI treatment) controls, eyed eggs subjected to sub-optimal pressure treatments (6500–8500 PSI) had a higher incidence of chromosomal aberrations such as aneuploidy and uniparental disomy, corresponding to lower triploidization success and higher egg mortality rates. We also observed maternal effects on triploidization success and incidence of chromosomal aberrations, with certain half-sibling families exhibiting more aberrations than others. Chromosomal aberrations were rare among surviving parr, suggesting a purge of maladapted individuals during early development. This study demonstrates that sub-optimal hydrostatic pressure treatments and maternal effects not only influence the success of triploidization treatments, but may also affect the incidence of chromosomal aberrations and early mortality. The results have important implications for aquaculture breeding programs and their efforts to prevent farm-to-wild introgression.

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