Glutathione (GSH) is a brain marker for oxidative stress and has previously been associated with cerebral amyloid deposition and memory decline. However, to date, no study has examined the links among GSH, sex, age, amyloid, and Apolipoprotein E (APOE) genotype in a large non-clinical cohort of older adults. We performed APOE genotyping, magnetic resonance spectroscopy (MRS) as well as simultaneous positron emission tomography with the radiotracer Flutemetamol (Amyloid-PET), in a group of older adults. The final analysis set comprised 140 healthy older adults (mean age: 64.7 years) and 49 participants with mild cognitive impairment (mean age: 71.4 years). We recorded metabolites in the posterior cingulate cortex (PCC) by a GSH-edited MEGAPRESS sequence. Structural equation modeling revealed that higher GSH levels were associated with female sex, but neither APOE- epsilon 4 carrier status nor age showed significant associations with GSH. Conversely, older age and the presence of an APOE4 allele, but not sex, are linked to higher global amyloid load. Our results suggest that the PCC shows sex-specific GSH alterations in older adults.

The ability of parasitic wasps to manipulate a host\'s metabolism is under active investigation. Components of venom play a major role in this process. In the present work, we studied the effect of the venom of the ectoparasitic wasp Habrobracon hebetor on the metabolism of the greater wax moth host (Galleria mellonella). We identified and quantified 45 metabolites in the lymph (cell-free hemolymph) of wax moth larvae on the second day after H. hebetor venom injection, using NMR spectroscopy and liquid chromatography coupled with mass spectrometry. These metabolites included 22 amino acids, nine products of lipid metabolism (sugars, amines and alcohols) and four metabolic intermediates related to nitrogenous bases, nucleotides and nucleosides. An analysis of the larvae metabolome suggested that the venom causes suppression of the tricarboxylic acid cycle, an increase in the number of free amino acids in the lymph, an increase in the concentration of trehalose in the lymph simultaneously with a decrease in the amount of glucose, and destructive processes in the fat body tissue. Thus, this parasitoid venom not only immobilizes the prey but also modulates its metabolism, thereby providing optimal conditions for the development of larvae.

UNASSIGNED: Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) is a standard technique for diagnosing myocardial infarction (MI), which, however, poses risks due to gadolinium contrast usage. Techniques enabling MI assessment based on contrast-free CMR are desirable to overcome the limitations associated with contrast enhancement.
UNASSIGNED: We introduce a novel deep generative learning method, termed cine-generated enhancement (CGE), which transforms standard contrast-free cine CMR into LGE-equivalent images for MI assessment. CGE features with multislice spatiotemporal feature extractor, enhancement contrast modulation, and sophisticated loss function. Data from 430 patients with acute MI from 3 centers were collected. After image quality control, 1525 pairs (289 patients) of center I were used for training, and 293 slices (52 patients) of the same center were reserved for internal testing. The 40 patients (401 slices) of the other 2 centers were used for external testing. The CGE robustness was further tested in 20 normal subjects in a public cine CMR data set. CGE images were compared with LGE for image quality assessment and MI quantification regarding scar size and transmurality.
UNASSIGNED: The CGE method produced images of superior quality to LGE in both internal and external data sets. There was a significant (P<0.001) correlation between CGE and LGE measurements of scar size (Pearson correlation, 0.79/0.80; intraclass correlation coefficient, 0.79/0.77) and transmurality (Pearson correlation, 0.76/0.64; intraclass correlation coefficient, 0.76/0.63) in internal/external data set. Considering all data sets, CGE demonstrated high sensitivity (91.27%) and specificity (95.83%) in detecting scars. Realistic enhancement images were obtained for the normal subjects in the public data set without false positive subjects.
UNASSIGNED: CGE achieved superior image quality to LGE and accurate scar delineation in patients with acute MI of both internal and external data sets. CGE can significantly simplify the CMR examination, reducing scan times and risks associated with gadolinium-based contrasts, which are crucial for acute patients.

UNASSIGNED: Evidence from animal and human studies suggests glutamatergic dysfunction in posttraumatic stress disorder (PTSD). The purpose of this study was to investigate glutamate abnormalities in the dorsolateral prefrontal cortex (DLFPC) of individuals with PTSD using 7T MRS, which has better spectral resolution and signal-to-noise ratio than lower field strengths, thus allowing for better spectral quality and higher sensitivity. We hypothesized that individuals with PTSD would have lower glutamate levels compared to trauma-exposed individuals without PTSD and individuals without trauma exposure. Additionally, we explored potential alterations in other neurometabolites and the relationship between glutamate and psychiatric symptoms.
UNASSIGNED: Individuals with PTSD (n = 27), trauma-exposed individuals without PTSD (n = 27), and individuals without trauma exposure (n = 26) underwent 7T MRS to measure glutamate and other neurometabolites in the left DLPFC. The severities of PTSD, depression, anxiety, and dissociation symptoms were assessed.
UNASSIGNED: We found that glutamate was lower in the PTSD and trauma-exposed groups compared to the group without trauma exposure. Furthermore, N-acetylaspartate (NAA) was lower and lactate was higher in the PTSD group compared to the group without trauma exposure. Glutamate was negatively correlated with depression symptom severity in the PTSD group. Glutamate was not correlated with PTSD symptom severity.
UNASSIGNED: In this first 7T MRS study of PTSD, we observed altered concentrations of glutamate, NAA, and lactate. Our findings provide evidence for multiple possible pathological processes in individuals with PTSD. High-field MRS offers insight into the neurometabolic alterations associated with PTSD and is a powerful tool to probe trauma- and stress-related neurotransmission and metabolism in vivo.

We report bio-structural, bio-chemical and bio-physical evidence demonstrating how small molecules can bind to both wild-type and mutant IDH1, but only inhibit the enzymatic activity of the mutant isoform. Enabled through x-ray crystallography, we characterized a series of small molecule inhibitors that bound to mutant IDH1 differently than the marketed inhibitor Ivosidenib, for which we have determined the x-ray crystal structure. Across the industry several mutant IDH1 inhibitor chemotypes bind to this allosteric IDH1 pocket and selectively inhibit the mutant enzyme. Detailed characterization by a variety of biophysical techniques and NMR studies led us to propose how compounds binding in the allosteric IDH1 R132H pocket inhibit the production of 2-Hydroxy glutarate.

BACKGROUND: In soccer, most studies evaluate metabolic profile changes in male athletes, often using data from a single match. Given the current landscape of women\'s soccer and the effects of biological sex on the physiological response and adaptation to exercise, more studies targeting female athletes and analyzing pre- and post-game moments throughout the season are necessary.
OBJECTIVE: To describe the metabolomics profile of female soccer athletes from an elite team in Brazil. The study observed the separation of groups in three pre- and post-game moments and identified the discriminating metabolites.
METHODS: The study included 14 female soccer athletes. Urine samples were collected and analyzed using Nuclear Magnetic Resonance in pre-game and immediate post-game moments over three national championship games. The metabolomics data were then used to generate OPLS-DA and VIP plots.
RESULTS: Forty-three metabolites were identified in the samples. OPLS-DA analyses demonstrated a progressive separation between pre-post conditions, as supported by an increasing Q2 value (0.534, 0.625, and 0.899 for games 1, 2 and 3, respectively) and the first component value (20.2% and 19.1% in games 1 and 2 vs. 29.9% in game 3). Eight out of the fifteen most discriminating metabolites appeared consistently across the three games: glycine, formate, citrate, 3-hydroxyvalerate, glycolic acid, trimethylamine, urea, and dimethylglycine.
CONCLUSIONS: The main difference between the three games was the increasing separation between groups throughout the championship. Since the higher VIP-scores metabolites are linked to energy and protein metabolism, this separation may be attributed several factors, one being the accumulation of fatigue.

Emulsions stabilized via Pickering particles are becoming more and more popular due to their high stability and biocompatibility. Hence, developing new ways to produce effective Pickering particles is essential. In this work, we present a crystal engineering approach to obtain precise control over particle properties such as size, shape, and crystal structure, which may affect wettability and surface chemistry. A highly reproducible synthesis method via anti-solvent crystallization was developed to produce sub-micron sized curcumin crystals of the metastable form III, to be used as Pickering stabilizers. The produced crystals presented a clear hydrophobic nature, which was demonstrated by their preference to stabilize water-in-oil (W/O) emulsions. A comprehensive experimental and computational characterization of curcumin crystals was performed to rationalize their hydrophobic nature. Analytical techniques including Raman spectroscopy, powder X-ray diffraction (PXRD), Solid-State Nuclear Magnetic Resonance (SSNMR), scanning electron microscopy (SEM), Differential Scanning Calorimetry (DSC), confocal fluorescence microscopy and contact angle measurements were used to characterize curcumin particles in terms of shape, size and interfacial activity. The attachment energy model was instead applied to study relevant surface features of curcumin crystals, such as topology and facet-specific surface chemistry. This work contributes to the understanding of the effect of crystal properties on the mechanism of Pickering stabilization, and paves the way for the formulation of innovative products in fields ranging from pharmaceuticals to food science.

Prolyl-hydroxylation is an oxygen-dependent posttranslational modification (PTM) that is known to regulate fibril formation of collagenous proteins and modulate cellular expression of hypoxia-inducible factor (HIF) α subunits. However, our understanding of this important but relatively rare PTM has remained incomplete due to the lack of biophysical methodologies that can directly measure multiple prolyl-hydroxylation events within intrinsically disordered proteins. Here, we describe a real-time 13C-direct detection NMR-based assay for studying the hydroxylation of two evolutionarily conserved prolines (P402 and P564) simultaneously in the intrinsically disordered oxygen-dependent degradation domain of hypoxic-inducible factor 1α by exploiting the \"proton-less\" nature of prolines. We show unambiguously that P564 is rapidly hydroxylated in a time-resolved manner while P402 hydroxylation lags significantly behind that of P564. The differential hydroxylation rate was negligibly influenced by the binding affinity to prolyl-hydroxylase enzyme, but rather by the surrounding amino acid composition, particularly the conserved tyrosine residue at the +1 position to P564. These findings support the unanticipated notion that the evolutionarily conserved P402 seemingly has a minimal impact in normal oxygen-sensing pathway.

Paired-pulse transcranial magnetic stimulation is a valuable tool for investigating inhibitory mechanisms in motor cortex. We recently demonstrated its use in measuring cortical inhibition in visual cortex, using an approach in which participants trace the size of phosphenes elicited by stimulation to occipital cortex. Here, we investigate age-related differences in primary visual cortical inhibition and the relationship between primary visual cortical inhibition and local GABA+ in the same region, estimated using magnetic resonance spectroscopy. GABA+ was estimated in 28 young (18 to 28 years) and 47 older adults (65 to 84 years); a subset (19 young, 18 older) also completed a paired-pulse transcranial magnetic stimulation session, which assessed visual cortical inhibition. The paired-pulse transcranial magnetic stimulation measure of inhibition was significantly lower in older adults. Uncorrected GABA+ in primary visual cortex was also significantly lower in older adults, while measures of GABA+ that were corrected for the tissue composition of the magnetic resonance spectroscopy voxel were unchanged with age. Furthermore, paired-pulse transcranial magnetic stimulation-measured inhibition and magnetic resonance spectroscopy-measured tissue-corrected GABA+ were significantly positively correlated. These findings are consistent with an age-related decline in cortical inhibition in visual cortex and suggest paired-pulse transcranial magnetic stimulation effects in visual cortex are driven by GABAergic mechanisms, as has been demonstrated in motor cortex.

BACKGROUND: Cystathionine accumulates selectively in 1p/19q-codeleted gliomas, and can serve as a possible noninvasive biomarker. This study aims to optimize the echo time (TE) of point-resolved spectroscopy (PRESS) for cystathionine detection in gliomas, and evaluate the diagnostic accuracy of PRESS for 1p/19q-codeletion identification.
METHODS: The TE of PRESS was optimized with numerical and phantom analysis to better resolve cystathionine from the overlapping aspartate multiplets. The optimized and 97 ms TE PRESS were then applied to 84 prospectively enrolled patients suspected of glioma or glioma recurrence to examine the influence of aspartate on cystathionine quantification by fitting the spectra with and without aspartate. The diagnostic performance of PRESS for 1p/19q-codeleted gliomas were assessed.
RESULTS: The TE of PRESS was optimized as (TE1, TE2) = (17 ms, 28 ms). The spectral pattern of cystathionine and aspartate were consistent between calculation and phantom. The mean concentrations of cystathionine in vivo fitting without aspartate were significantly higher than those fitting with full basis-set for 97 ms TE PRESS (1.97 ± 2.01 mM vs. 1.55 ± 1.95 mM, p < 0.01), but not significantly different for 45 ms method (0.801 ± 1.217 mM and 0.796 ± 1.217 mM, p = 0.494). The cystathionine concentrations of 45 ms approach was better correlated with those of edited MRS than 97 ms counterparts (r = 0.68 vs. 0.49, both p < 0.01). The sensitivity and specificity for discriminating 1p/19q-codeleted gliomas were 66.7% and 73.7% for 45 ms method, and 44.4% and 52.5% for 97 ms method, respectively.
CONCLUSIONS: The 45 ms TE PRESS yields more precise cystathionine estimates than the 97 ms method, and is anticipated to facilitate noninvasive diagnosis of 1p/19q-codeleted gliomas, and treatment response monitoring in those patients. Medium diagnostic performance of PRESS for 1p/19q-codeleted gliomas were observed, and warrants further investigations.