Background: N6-methyladenosine (m6A) is the most prevalent post-transcriptional modification of eukaryotic mRNA. It has been reported that there is a stimulus-dependent regulation of m6A in the mammalian central nervous system in response to sensory experience, learning, and injury. The mRNA m6A methylation pattern in rat cortex after traumatic brain injury (TBI) has not been investigated. Results: In this study, we conducted a genome-wide profiling of mRNA m6A methylation in rat cortex via methylated RNA immunoprecipitation sequencing (MeRIP-Seq). After TBI, the expressions of METTL14 and FTO were significantly down-regulated in rat cerebral cortex. Using MeRIP-Seq, we identified a total of 2165 significantly changed peaks, of which 1062 were significantly up-regulated and 1103 peaks were significantly down-regulated. These m6A peaks were located across 1850 genes. The analysis of both m6A peaks and mRNA expression revealed that there were 175 mRNA significantly altered methylation and expression levels after TBI. Moreover, it was found that functional FTO is necessary to repair neurological damage caused by TBI but has no effect on the spatial learning and memory abilities of TBI rats by using FTO inhibitor FB23–2. Conclusion: This study explored the m6A methylation pattern of mRNA after TBI in rat cortex and identified FTO as possible intervention targets in the epigenetic modification of TBI.

Traumatic brain injury (TBI) is a primary cause of disability and death across the world. Previously, RNA analysis was widely used to study the pathophysiological mechanisms underlying TBI; however, the relatively low correlation between the transcriptome and proteome revealed that RNA transcription abundance does not reliably predict protein abundance, which led to the emergence of proteomic research. In this study, an iTRAQ proteomics approach was applied to detect protein alterations after TBI on a large scale. A total of 3937 proteins were identified, and 146 proteins were significantly changed after TBI. Moreover, 23 upregulated proteins were verified by parallel reaction monitoring (PRM), and fold changes in 16 proteins were consistent with iTRAQ outcomes. Transthyretin (Ttr) upregulation has been demonstrated at the transcriptional level, and this study further confirmed this at the protein level. After treatment with thyroxine (T4), which is transported by Ttr, the effects of T4 on neuronal histopathology and behavioral performance were determined in vivo (TBI + T4 group). Brain edema was alleviated, and the integrity of the blood brain barrier (BBB) improved. Escape latency in the Morris water maze (MWM) declined significantly compared with the group without T4 treatment. Modified neurological severity scores (mNSS) of the TBI + T4 group decreased from day 1 to day 7 post-TBI compared with the TBI + saline group. These results indicate that T4 treatment has potential to alleviate pathologic and behavioral abnormalities post-TBI. Protein alterations after T4 treatment were also detected by iTRAQ proteomics. Upregulation of proteins like Lgals3, Gfap and Apoe after TBI were reversed by T4 treatment. GO enrichment showed T4 mainly affected intermediate filament organization, cholesterol transportation and axonal regeneration. In summary, iTRAQ proteomics provides information about the impact of TBI on protein alterations and yields insight into underlying mechanisms and pathways involved in TBI and T4 treatment. Finally, Ttr and other proteins identified by iTRAQ may become potential novel treatment targets post-TBI.

Traumatic brain injury (TBI) poses a major global health challenge, leading to serious repercussions for those affected and imposing considerable financial strains on families and healthcare systems. RNA methylation, especially 5-methylcytosine (m⁵C), plays a crucial role as an epigenetic modification in regulating RNA at the level of post-transcriptional regulation. However, the impact of TBI on the m⁵C methylation profile of long non-coding RNAs (lncRNAs) remains unexplored. In the present study, we conducted a thorough transcriptome-wide examination of m⁵C methylation in lncRNAs in a rat TBI model utilizing MeRIP-Seq. Our results revealed significant differences in the amount and distribution of m⁵C methylation in lncRNAs between TBI and control groups, indicating profound changes in m⁵C methylation following TBI. Bioinformatic analyses linked these specifically methylated transcripts to pathways involved in immune response, neural repair, and lipid metabolism, providing insight into possible mechanisms underlying TBI pathology. These findings offer novel perspectives on the post-transcriptional modifications in lncRNA m⁵C methylation following TBI, which may contribute to understanding the disease mechanisms and developing targeted therapeutic strategies.

Background: The coronavirus disease 2019 (COVID-19) has affected approximately 2 million individuals worldwide; however, data regarding fatal cases have been limited. Objective: To report the clinical features of 162 fatal cases of COVID-19 from 5 hospitals in Wuhan between December 30, 2019 and March 12, 2020. Methods: The demographic data, signs and symptoms, clinical course, comorbidities, laboratory findings, computed tomographic (CT) scans, treatments, and complications of the patients with fatal cases were retrieved from electronic medical records. Results: The median patient age was 69.5 (interquartile range: 63.0–77.25) years, and 80% of the patients were over 61 years. A total of 112 (69.1%) patients were men. Hypertension (45.1%) was the most common comorbidity, while 59 (36.4%) patients had no comorbidity. At admission, 131 (81.9%) patients had severe or critical COVID-19, whereas 39 (18.1%) patients with hypertension or chronic lung disease had moderate COVID-19. In total, 126 (77.8%) patients received antiviral treatment, while 132(81.5%) patients received glucocorticoid treatment. A total of 116 (71.6%) patients were admitted to the intensive care unit (ICU), and 137 (85.1%) patients received mechanical ventilation. Most patients received mechanical ventilation before ICU admission. Approximately 93.2% of the patients developed respiratory failure or acute respiratory distress syndrome. There were no significant differences in the inhospital survival time among the hospitals (P=0.14). Conclusion: Young patients with moderate COVID-19 without comorbidity at admission could also develop fatal outcomes. The in-hospital survival time of the fatal cases was similar among the hospitals of different levels in Wuhan.