The accumulation of reactive oxygen species has been associated with a loss of seed viability. Therefore, we have investigated the germination ability of a range of seed stocks, including two wheat collections and one barley collection that had been dry‐aged for 5–40 years. Metabolite profiling analysis revealed that the accumulation of glycerol was negatively correlated with the ability to germinate in all seed sets. Furthermore, lipid degradation products such as glycerol phosphates and galactose were accumulated in some seed sets. A quantitative analysis of nonoxidized and oxidized lipids was performed in the wheat seed set that showed the greatest variation in germination. This analysis revealed that the levels of fully acylated and nonoxidized storage lipids like triacylglycerols and structural lipids like phospho‐ and galactolipids were decreasing. Moreover, the abundance of oxidized variants and hydrolysed products such as mono‐/diacylglycerols, lysophospholipids, and fatty acids accumulated as viability decreased. The proportional formation of oxidized and nonoxidized fatty acids provides evidence for an enzymatic hydrolysis of specifically oxidized lipids in dry seeds. The results link reactive oxygen species with lipid oxidation, structural damage, and death in long‐term aged seeds.

Lipid oxidation is a process ubiquitous in life, but the direct and comprehensive analysis of oxidized lipids has been limited by available analytical methods. We applied high resolution liquid chromatography-mass spectrometry (LC-MS) and tandem mass spectrometry (LC-MS/MS) to quantify oxidized lipids (glycerides, fatty acids, phospholipids, lysophospholipids and galactolipids) and implemented a platform-independent high-throughput amenable analysis pipeline for the high confidence annotation and acyl composition analysis of oxidized lipids. Lipid contents of 90 different naturally aged wheat (Triticum aestivum) seed stocks were quantified in an untargeted high-resolution LC-MS experiment, resulting in 18556 quantitative m/z features. In a post hoc LC-MS/MS experiment, high resolution MS/MS spectra (5 mDa accuracy) were recorded for 8957 out of 12080 putatively monoisotopic features of the LC-MS dataset. 353 non-oxidized and 559 oxidized lipids with up to four additional Oxygen atoms were annotated based on the accurate mass recordings (1.5 ppm tolerance) of the LC-MS dataset and filtering procedures. MS/MS spectra available for 828 of these annotations were analyzed by translating experimentally known fragmentation rules of lipids into the fragmentation of oxidized lipids. This led to the identification of 259 non-oxidized and 365 oxidized lipids by both accurate mass and MS/MS spectra and to the determination of acyl compositions for 221 non-oxidized and 295 oxidized lipids. Analysis of fifteen years aged wheat seeds revealed increased lipid oxidation and hydrolysis in seeds stored at ambient vs. cold conditions.

Atherosclerosis, the leading global cause of death, is a chronic inflammatory vascular disease with higher prevalence and earlier onset in men than in women. This study aims to investigate sex differences in the atherogenic endothelial phenotype during early atherosclerosis processes by providing the first comprehensive analysis of hormone-independent responses in human umbilical vein endothelial cells (HUVECs) from opposite-sex twins. HUVECs underwent pro-inflammatory stimulation with TNF-α and supernatant from activated pro-inflammatory THP-1 cells, revealing distinct sex-specific patterns: mRNA expression of focal adhesion proteins talin-I, vinculin, FAK, and α1-actinin increased significantly only in male cells, while paxillin showed elevated mRNA and protein levels in both sexes. Male HUVECs exhibited stronger induction of cell adhesion molecule VCAM-1, pro-inflammatory cytokine IL-1β, and proangiogenic factors Flt-3L, G-CSF, and PDGF-AA, whereas IL-22 secretion was exclusively upregulated in female cells. These sex differences in levels of focal adhesion, adhesion molecules, and cytokine profiles uncover the mechanistic backgrounds of the atherogenic endothelial phenotype, independent of systemic hormones. The findings emphasize cellular sex as a critical biological variable in early atherosclerosis and vascular inflammation.

Lessons from implementing quality control systems in an academic research consortium to improve Good Scientific Practice and reproducibility.

IMPORTANCE: Postoperative delirium (POD) is a multietiological condition and affects 20% of older surgical patients. It is associated with poor clinical outcome and increased mortality. OBJECTIVE: We aimed to develop and validate a risk prediction algorithm for POD based on a multimodal biomarker database exploiting preoperative data (predisposing factors) and procedural factors as well as perioperative molecular changes associated with POD (precipitating factors). DESIGN: BioCog is a prospective cohort study conducted from November 2014 to April 2017. Patients were followed up for seven postoperative days after surgery for POD. Gradient-boosted trees (GBT) with nested cross-validation was used for POD prediction. SETTING: Patients aged ≥65 years were enrolled at the anesthesiologic departments of two tertiary care centers. EXPOSURE: All patients underwent surgery with an expected duration of at least 60min. Clinical, neuropsychological, neuroimaging data and blood were collected and clinically well established as well as non-established biomarkers (e.g., gene expression profiling) were measured pre- and postoperatively. MAIN OUTCOME: POD according to DSM 5 until the seventh postoperative day RESULTS: 184 of 929 (20%) patients experienced POD. A GBT algorithm using both preoperative data, characteristics of the intervention and postoperative changes in laboratory parameters achieved the highest area under the curve (0.83, [0.79; 0.86]) with a Brier score of 0.12 (0.12; 0.13). CONCLUSIONS AND RELEVANCE: Models combining predisposing factors with precipitating factors predict POD best. Non-routine laboratory data provide useful information for POD risk prediction, providing relevant results for future studies on the molecular factors of POD. In addition, possibly relevant molecular mechanisms contributing to the development of POD were identified, mostly indicating a dysregulated postoperative immune response. This study constitutes the basis for future hypothesis-driven analyses or implementation of prediction expert system for clinical practice.

Postoperative cognitive dysfunction (POCD) is a detrimental complication after surgery with a lasting impact on the patients’ daily life. It is most common after postoperative delirium. Dopaminergic dysfunction has been suggested to play a role in delirium, but little knowledge exists regarding its relevance for POCD. We hypothesized that POCD is associated with altered resting-state functional connectivity of the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNc) in functional magnetic resonance imaging (fMRI) before surgery and at postoperative follow-up after three months. Patients ≥65 years old underwent resting-state fMRI and neuropsychological assessment before major elective surgery and at follow-up three months later. POCD was determined as the reliable change index. Connectivity between VTA or SNc and 132 regions were calculated. Principal component analysis (PCA) was used for dimensionality reduction in preoperative connectivity, and components explaining >5% of variance were retained for analysis. To study postoperative changes in patients with POCD, we applied the same transformation to postoperative connectivity, and multi-factor analysis. Regression analyses were used to describe connectivity alterations while adjusting for age, sex, MMSE, surgery and anaesthesia. Of 214 patients, 26 (12%) developed POCD. Among 132 principal components, four components for VTA- and SNc-FC were selected for further analysis. For both VTA and SNc connectivity, one component was significantly associated with POCD. No postoperative alterations of dopaminergic networks were associated with POCD. Altered preoperative functional connectivity of the dopaminergic system predisposes to POCD. Particularly relevant regions are associated with sensory, especially spatial perception and higher cognitive functions. HIGHLIGHTS Dopaminergic dysfunction is a hallmark ofdelirium No evidence for postoperative cognitive dysfunction (POCD) Methods: resting-state functional connectivity of the VTA and SNc Connectivity alterations of the VTA and SNc predispose for POCD Affected areas involed in perception, spatial processing and cognition