Characterization of the wheat leaf metabolome during grain filling and under varied N-supply

Progress in improving crop growth is an absolute goal despite the influence multifactorial components have on crop yield and quality. An Avalon × Cadenza doubled-haploid wheat mapping population was used to study the leaf metabolome of field grown wheat at weekly intervals during the time in which the canopy contributes to grain filling, i.e.,from anthesis to 5 weeks post-anthesis. Wheat was grown under four different nitrogen supplies reaching from residual soil N to a luxury over-fertilization (0, 100, 200, and 350 kg N ha−1). Four lines from a segregating doubled haploid population derived of a cross of the wheat elite cvs. Avalon and Cadenza were chosen as they showed pairwise differences in either N utilization efficiency (NUtE) or senescence timing. 108 annotated metabolites of primary metabolism and ions were determined. The analysis did not provide genotype specific markers because of a remarkable stability of the metabolome between lines. We speculate that the reason for failing to identify genotypic markers might be due to insufficient genetic diversity of the wheat parents and/or the known tendency of plants to keep metabolome homeostasis even under adverse conditions through multiple adaptations and rescue mechanism. The data, however, provided a consistent catalogue of metabolites and their respective responses to environmental and developmental factors and may bode well for future systems biology approaches, and support plant breeding and crop improvement

Metformin Treatment is Associated with Mortality in Patients with Type 2 Diabetes and Chronic Heart Failure in the Intensive Care Unit: A Retrospective Cohort Study

Objective: Patients receiving intensive care often have diabetes mellitus (DM) together with chronic heart failure (CHF). In these patients, the use of metformin in intensive care is controversial. This study was aimed at assessing the mortality rates of patients with DM and CHF treated with metformin. Methods: The Medical Information Mart for Intensive Care database was used to identify patients with type 2 diabetes mellitus (T2DM) and CHF. A 90-day mortality comparison was conducted between patients who were and were not administered metformin. Propensity score matching analysis and multivariable Cox proportional hazard regression were used to ensure the robustness of our results. Results: A total of 2153 patients (180 receiving metformin and 1973 not receiving metformin) with T2DM and CHF were included in the study. The 90-day mortality rates were 30.5% (601/1971) and 5.5% (10/182) in the non-metformin and metformin groups, respectively. In the propensity score matching analyses, metformin use was associated with a 71% lower 90-day mortality (hazard ratio, 0.29; 95% confidence interval, 0.14–0.59; P < 0.001). The results were insensitive to change when sensitivity analyses were performed. Conclusion: Metformin treatment may decrease the mortality risk in critically ill patients with T2DM and CHF in the intensive care unit

Preoperative inflammatory markers predict postoperative clinical outcomes in patients undergoing heart valve surgery: A large-sample retrospective study

IntroductionPreoperative inflammation affects the postoperative outcomes of patients undergoing heart valve surgery. This study aimed to explore the role and predictive effects of preoperative inflammation on the primary outcomes after valvular cardiac surgery.MethodsThis retrospective study utilized a medical recording system to screen 5075 patients who underwent heart valve surgery. Data on the C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and neutrophil-to-lymphocyte ratio (NLR) before heart valve surgery were collected from the hospital’s medical system. Postoperative hepatic insufficiency, acute kidney injury, heart failure, and myocardial damage were assessed using blood indicators. Patients with and without prolonged mechanical ventilation, extended intensive care unit stays, prolonged hospital stays, and death within 30 days after surgery (considered the primary outcome in this study) were compared. Group comparisons, receiver operating characteristic (ROC) curve analyses, and logistic analyses were performed to determine the associations between preoperative inflammation and outcomes after heart valve surgery.ResultsA total of 3249 patients were included in the analysis. Significant differences in CRP level, ESR, and NLR were found between patients with and without postoperative adverse outcomes. ROC analysis showed that CRP levels &gt;5 mg/L effectively predicted postoperative heart failure, and NLR &gt;3.5 had a good predictive effect on all-cause mortality within 30 days after surgery. Patients with CRP levels &gt;5 mg/L had a higher incidence of postoperative heart failure than other patients (20.7% vs. 12.6%, P&lt;0.001), with a relative risk of 1.447 (95% confidence interval: 1.155–1.814). Patients with NLR &gt;3.5 had a higher incidence of death within 30 days after surgery (5.3% vs. 1.2%, P&lt;0.001), with a relative risk of 3.236 (95% confidence interval: 1.773–5.906).ConclusionPreoperative inflammation can affect postoperative outcomes in patients undergoing heart valve surgery. CRP level &gt;5 mg/L and NLR &gt;3.5 can effectively predict postoperative heart failure and death within 30 days after surgery, respectively

Change in perioperative neutrophil-lymphocyte ratio as a potential predictive biomarker for chronic postsurgical pain and quality of life: an ambispective observational cohort study

IntroductionAccurate and accessible predictors of chronic postsurgical pain (CPSP) to identify high-risk postsurgical patients are prerequisite for preventive and interventional strategies. We investigated the incidence and risk factors of CPSP after abdominal surgery, with a focus on plasma immunological markers.Materials and methodsThis was a retrospective analysis of patients who underwent abdominal surgery under general anesthesia at a tertiary center between January 2021 and January 2022. The preoperative demographics, laboratory test data, and surgical factors of the participants were collected from the electronic medical record system. Postoperative pain intensity and living conditions at 1 year after discharge from the hospital were assessed via a phone survey. Univariate and multivariate analyses were used to explore independent risk factors associated with CPSP.ResultsA total of 968 patients were included, and 13.53% (n = 131 of 968) of patients reported CPSP 1 year after surgery. Patients with older age, open surgery, higher American Association of Anesthesiologists classification, patient-controlled intravenous analgesia application, longer surgery duration, higher postoperative absolute neutrophil count, and neutrophil-lymphocyte ratio (NLR), lower postoperative absolute lymphocyte count, and higher white blood cell count, were more likely to suffer from CPSP. A changed ratio of NLR (postoperative to preoperative) ≥ 5 significantly correlated with CPSP, moderate to severe pain, maximum numeric rating score since discharge from the hospital, and affected quality of life.DiscussionThe changed ratio of NLR could be used for the early identification of patients at risk for CPSP and affect the quality of life to alert the clinician to undertake further assessment

The Roles of Post-translational Modifications in the Context of Protein Interaction Networks

<div><p>Among other effects, post-translational modifications (PTMs) have been shown to exert their function via the modulation of protein-protein interactions. For twelve different main PTM-types and associated subtypes and across 9 diverse species, we investigated whether particular PTM-types are associated with proteins with specific and possibly “strategic” placements in the network of all protein interactions by determining informative network-theoretic properties. Proteins undergoing a PTM were observed to engage in more interactions and positioned in more central locations than non-PTM proteins. Among the twelve considered PTM-types, phosphorylated proteins were identified most consistently as being situated in central network locations and with the broadest interaction spectrum to proteins carrying other PTM-types, while glycosylated proteins are preferentially located at the network periphery. For the human interactome, proteins undergoing sumoylation or proteolytic cleavage were found with the most characteristic network properties. PTM-type-specific protein interaction network (PIN) properties can be rationalized with regard to the function of the respective PTM-carrying proteins. For example, glycosylation sites were found enriched in proteins with plasma membrane localizations and transporter or receptor activity, which generally have fewer interacting partners. The involvement in disease processes of human proteins undergoing PTMs was also found associated with characteristic PIN properties. By integrating global protein interaction networks and specific PTMs, our study offers a novel approach to unraveling the role of PTMs in cellular processes.</p></div

Heatmap of significant A) biological process and B) GO-Component terms across all studied PTM-types.

<p>The top five GO-terms were included that were found significantly enriched for each PTM-type. Each element in the heat map (Euclidean distance hierarchical clustering, average linkage) represents the grey-scale-encoded <i>p</i>-value, in which a particular combination of PTM-type and GO-term was found significantly enriched. The combined whole UniProtKB-GOA for all the selected species was used as the background set, Fisher’s exact test with FDR correction was used for the enrichment analysis, and the <i>p</i>-value (FDR) threshold indicating significance was set to 0.01.</p

Association of PTM-type and PIN-property specific protein sets with known human disease proteins.

<p>Protein sets were sorted in descending order of the respective PIN-property and the top/bottom 25% tested for overlap with human disease genes reported in OMIM (<a href="http://www.ncbi.nlm.nih.gov/omim" target="_blank">http://www.ncbi.nlm.nih.gov/omim</a>) based on a Fisher’s exact test with FDR-correction with respective counts of proteins binned according to binary decisions top/bottom 25% property and disease association yes/no forming the 2×2 contingency table. <i>p</i>-values highlighted red indicate significant overlap of the top-25% set of proteins for a particular network property with human disease proteins, while blue values signify larger than expected overlaps of the bottom-25% protein sets with proteins annotated to be involved in disease processes at p-value thresholds of <i>p</i>-value 0.05, 0.01 (if underlined), respectively. Black font color indicates no significant overlap of neither the top nor the bottom 25% set.</p><p>Association of PTM-type and PIN-property specific protein sets with known human disease proteins.</p

Degree, clustering coefficient, closeness centrality analysis for proteins with different PTM-types in each considered species and associated high-confidence STRING and IntAct PIN.

<p>The species are ordered according to their phylogenetic relationships as shown on the left. For every PTM-type, the log-2 of fold difference value for the degree/clustering coefficient/closeness centrality value relative to the respective value associated with proteins not carrying this particular PTM-type are given for PINs based on STRING and IntAct, respectively. Color scale indicates increased (red) or decreased (blue) values in the PTM-set relative to the non-PTM-set with symmetric color intervals (i.e. full color saturation based on the maximal absolute increase or decrease fold difference observed across all values in the table.) Bold-font (underlined) fold-changes indicate significant fold-changes at <i>p</i><0.05 (<i>p</i><0.01) by Mann-Whitney test with FDR correction, the values in red or blue text represent significantly higher or lower network properties, which are inconsistent with the background color based on mean (not median) values. PTM-types “carboxylation”, “proteolytic cleavage”, “hydroxylation”, and “disulfide bond” are not included in this analysis as associated numbers were available for <i>Homo sapiens</i> only.</p

Examples of human PTM-carrying proteins with characteristic PIN-properties and their known disease involvement.

<p>Examples of human PTM-carrying proteins with characteristic PIN-properties and their known disease involvement.</p