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Chronic compressive spinal cord injury in compressive cervical myelopathy conditions can lead to rapid neurological deterioration in the early phase, followed by partial self-recovery, and ultimately an equilibrium state of neurological dysfunction. Ferroptosis is a crucial pathological process in many neurodegenerative diseases; however, its role in chronic compressive spinal cord injury remains unclear. In this study, we established a chronic compressive spinal cord injury rat model, which displayed its most severe behavioral and electrophysiological dysfunction at 4 weeks and partial recovery at 8 weeks after compression. Bulk RNA sequencing data identified enriched functional pathways, including ferroptosis, presynapse, and postsynaptic membrane activity at both 4 and 8 weeks following chronic compressive spinal cord injury. Transmission electron microscopy and malondialdehyde quantification assay confirmed that ferroptosis activity peaked at 4 weeks and was attenuated at 8 weeks after chronic compression. Ferroptosis activity was negatively correlated with behavioral score. Immunofluorescence, quantitative polymerase chain reaction, and western blotting showed that expression of the anti-ferroptosis molecules, glutathione peroxidase 4 (GPX4) and MAF BZIP transcription factor G (MafG), in neurons was suppressed at 4 weeks and upregulated at 8 weeks following spinal cord compression. There was a positive correlation between the expression of these two molecules, suggesting that they may work together to contribute to functional recovery following chronic compressive spinal cord injury. In conclusion, our study determined the genome-wide expression profile and ferroptosis activity of a consistently compressed spinal cord at different time points. The results showed that anti-ferroptosis genes, specifically GPX4 and MafG, may be involved in spontaneous neurological recovery at 8 weeks of chronic compressive spinal cord injury. These findings contribute to a better understanding of the mechanisms underlying chronic compressive spinal cord injury and may help identify new therapeutic targets for compressive cervical myelopathy., Competing Interests: None

Accumulating studies have demonstrated that hyperbaric oxygen (HBO) treatment alleviates spinal cord injury (SCI). However, the underlying mechanism by which HBO alleviates SCI remains to be elucidated. In this study, we performed genome-wide transcriptional profiling of the spinal cord between SCI mice and mice that received HBO treatment by high-throughput RNA sequencing at 1 week after SCI. We also compared genome-wide transcriptional profiles from SCI mice and sham-operated mice. We found 76 differentially co-expressed genes in sham-operated mice, SCI mice, and HBO-treated SCI mice. Using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, we identified the biological characteristics of these differentially expressed genes from the perspectives of cell component, biological process, and molecular function. We also found enriched functional pathways including ferroptosis, calcium signaling pathway, serotonergic synapse, hypoxia-inducible factor-1 signaling pathway, cholinergic synapse, and neuroactive ligand-receptor interaction. We performed quantitative reverse transcription-polymerase chain reaction and validated that HBO treatment decreased the expression of Hspb1 (heat shock protein beta 1), Hmox1 (heme oxygenase 1), Ftl1 (ferritin light polypeptide 1), Tnc (tenascin C) and Igfbp3 (insulin-like growth factor binding protein 3) and increased the expression of Slc5a7 (solute carrier family 5 choline transporter member 7) after SCI. These results revealed the genome-wide transcriptional profile of the injured spinal cord after HBO treatment. Our findings contribute to a better understanding of the mechanism by which HBO treats SCI and may provide new targets for SCI intervention., Competing Interests: None

The International Myeloma Working Group recently fully incorporated 18 F-FDG PET into multiple myeloma (MM) diagnosis and response evaluation. Moreover, a few studies demonstrated the prognostic value of several biomarkers extracted from this imaging at baseline. Before these 18 F-FDG PET biomarkers could be fully endorsed as risk classifiers by the hematologist community, further characterization of underlying molecular aspects was necessary. Methods: Reported prognostic biomarkers ( 18 F-FDG avidity, SUV max , number of focal lesions, presence of paramedullary disease [PMD] or extramedullary disease) were extracted from 18 F-FDG PET imaging at baseline in a group of 139 patients from CASSIOPET, a companion study of the CASSIOPEIA cohort (ClinicalTrials.gov identifier NCT02541383). Transcriptomic analyses using RNA sequencing were realized on sorted bone marrow plasma cells from the same patients. An association with a high-risk gene expression signature (IFM15), molecular classification, progression-free survival, a stringent clinical response, and minimal residual disease negativity were explored. Results: 18 F-FDG PET results were positive in 79.4% of patients; 14% and 11% of them had PMD and extramedullary disease, respectively. Negative 18 F-FDG PET results were associated with lower levels of expression of hexokinase 2 ( HK2 ) (fold change, 2.1; adjusted P = 0.04) and showed enrichment for a subgroup of patients with a low level of bone disease. Positive 18 F-FDG PET results displayed 2 distinct signatures: either high levels of expression of proliferation genes or high levels of expression of GLUT5 and lymphocyte antigens. PMD and IFM15 were independently associated with a lower level of progression-free survival, and the presence of both biomarkers defined a group of "double-positive" patients at very high risk of progression. PMD and IFM15 were related neither to minimal residual disease assessment nor to a stringent clinical response. Conclusion: Our study confirmed and extended the association between imaging biomarkers and transcriptomic programs in MM. The combined prognostic value of PMD and a high-risk IFM15 signature may help define MM patients with a very high risk of progression., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: The mechanism of winter survival for perennials involves multiple levels of gene regulation, especially cold resistance. Agropyron mongolicum is one important perennial grass species, but there is little information regarding its overwintering mechanism. We performed a comprehensive transcriptomics study to evaluate global gene expression profiles regarding the winter survival of Agropyron mongolicum. A genome-wide gene expression analysis involving four different periods was identified. Twenty-eight coexpression modules with distinct patterns were performed for transcriptome profiling. Furthermore, differentially expressed genes (DEGs) and their functional characterization were defined using a genome database such as NT, NR, COG, and KEGG., Result: A total of 79.6% of the unigenes were characterized to be involved in 136 metabolic pathways. In addition, the expression level of ABA receptor genes, regulation of transcription factors, and a coexpression network analysis were conducted using transcriptome data. We found that ABA receptors regulated downstream gene expression by activating bZIP and NAC transcription factors to improve cold resistance and winter survival., Conclusion: This study provides comprehensive transcriptome data for the characterization of overwintering-related gene expression profiles in A. mongolicum. Genomics resources can help provide a better understanding of the overwintering mechanism for perennial gramineae species. By analyzing genome-wide expression patterns for the four key stages of tiller bud development, the functional characteristics of the DEGs were identified that participated in various metabolic pathways and have been shown to be strongly associated with cold tolerance. These results can be further exploited to determine the mechanism of overwintering in perennial gramineae species.

For pyruvate-producing strains, intracellular reduced nicotinamide adenine dinucleotide (NADH) accumulation is the main reason for the glycolysis inhibition. Comparing with glucose, using sodium gluconate as carbon source brought a decrease in NADH production and an increase in pyruvate production in engineered strain YP211. In order to explore the metabolic advantages of gluconate, genome-wide transcriptome analysis was employed to compare the metabolic differences between the two carbon sources. The results showed that the transcription of the genes gntU, gntK, and gntT responsible for transport and phosphorylation of gluconate, and genes edd and eda belonging to the Entner-Doudoroff (ED) pathway, was significantly enhanced. This suggested that the shortest route for the synthesis of pyruvate from gluconate was activated, and the synthesis of NADH was halved. Besides, the transcription of genes glpABCDTKF related to the glycerol metabolism was significantly enhanced, which might be because glycerol metabolism pathways were activated in the absence of glucose. These results provided valuable information for the further design of metabolic pathways in the construction of pyruvate-producing strains., Significance and Impact of the Study: Comparing with glucose, using sodium gluconate as carbon source brought a decrease in nicotinamide adenine dinucleotide and an increase in pyruvate production in engineered strain YP211. From the genome-wide transcriptome analysis, the Entner-Doudoroff pathway was activated strongly in gluconate metabolism, which innovatively provided a shorter and more effective pathway for pyruvate production., (© 2017 The Society for Applied Microbiology.)