A novel risk score model based on fourteen chromatin regulators-based genes for predicting overall survival of patients with lower-grade gliomas.

Background: Low grade gliomas(LGGs) present vexatious management issues for neurosurgeons. Chromatin regulators (CRs) are emerging as a focus of tumor research due to their pivotal role in tumorigenesis and progression. Hence, the goal of the current work was to unveil the function and value of CRs in patients with LGGs. Methods: RNA-Sequencing and corresponding clinical data were extracted from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) database. A single-cell RNA-seq dataset was sourced from the Gene Expression Omnibus (GEO) database. Altogether 870 CRs were retrieved from the published articles in top academic journals. The least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression analysis were applied to construct the prognostic risk model. Patients were then assigned into high- and low-risk groups based on the median risk score. The Kaplan-Meier (K-M) survival curve and receiver operating characteristic curve (ROC) were performed to assess the prognostic value. Sequentially, functional enrichment, tumor immune microenvironment, tumor mutation burden, drug prediction, single cell analysis and so on were analyzed to further explore the value of CR-based signature. Finally, the expression of signature genes were validated by immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR). Results: We successfully constructed and validated a 14 CRs-based model for predicting the prognosis of patients with LGGs. Moreover, we also found 14 CRs-based model was an independent prognostic factor. Functional analysis revealed that the differentially expressed genes were mainly enriched in tumor and immune related pathways. Subsequently, our research uncovered that LGGs patients with higher risk scores exhibited a higher TMB and were less likely to be responsive to immunotherapy. Meanwhile, the results of drug analysis offered several potential drug candidates. Furthermore, tSNE plots highlighting the magnitude of expression of the genes of interest in the cells from the scRNA-seq assay. Ultimately, transcription expression of six representative signature genes at the mRNA level was consistent with their protein expression changes. Conclusion: Our findings provided a reliable biomarker for predicting the prognosis, which is expected to offer new insight into LGGs management and would hopefully become a promising target for future research.

The real identity and sensory overlap mechanism of special vestibular afferent neurons that sense both rotation and linear force.

AIMS: Although the vestibular system has been widely investigated over the past 50 years, there is still an unsolved mystery. Some special vestibular afferent (SVA) neurons responding to both rotation and linear force were found through neurophysiological techniques, however, the sensory overlap mechanism of SVA neurons is still unclear, which may be closely related to vestibular-related diseases. MATERIALS AND METHODS: To address the above-mentioned problem, a cupula buoyancy theory was established in the present study, where SVA neurons were considered semicircular canal afferent (SCCA) neurons. Then labyrinth anatomy and neural response dynamics of vestibular afferent neurons in chinchilla were investigated through vestibular labyrinth reconstruction and single unit recording technique, respectively. KEY FINDINGS: We analyzed the deflections of cupulae under multiple conditions with the help of Amira Software and predicted the neural response law of SCCA neurons to linear force based on the cupula buoyancy theory. Data analysis confirmed that the basic response characteristic of SVA neurons had no significant difference to those of SCCA neurons, but were significantly different from those of otolith afferent neurons. Further, the actual responses of SVA neurons to linear force are completely consistent with our predictions. These results strongly suggest that SVA neurons actually are SCCA neurons, and the cupula buoyancy theory is the key to the sensory overlap mechanism of SCCA neurons. SIGNIFICANCE: Our study revealed the real identity of SVA neurons and provided a reasonable mechanism for sensory overlap of rotation and linear force, which improved our understanding about the vestibular system.

The head fixation based on skull cap: An improved protocol used in single unit recording in the vestibular system.

Single unit recording has an important application in neuroscience, especially in the vestibular system such as visual stabilization, posture maintenance, spatial orientation and cognition. However, single unit recording conducted in living animals is a demanding technique and non-ideal mechanical stability between the recording location of nerve tissues and the tip of microelectrode always results in failure to obtain successful recordings in the vestibular system. In order to improve the mechanical stability during single unit recording, we constructed a novel head fixation method based on skull cap. This article describes in detail how to construct this novel head fixation. Following the step-by-step procedure mentioned in this article will provide a high-quality mechanical stability for single unit recording in the vestibular system, allowing us to successfully record the nonlinear neural dynamic response over a big magnitude motion stimulation. This improvement of head fixation contributes to the in-depth understanding of the vestibular system.

The expression of bradykinin and its receptors in spinal cord ischemia-reperfusion injury rat model.

OBJECTIVE: To investigate the expression and time-dependent manner of bradykinin (BK) as well as its receptors (Bradykinin receptors 1 and 2, B1R and B2R) in spinal cord ischemia-reperfusion injury (SCII) in rat model. METHODS: Sprague-Dawley (SD) rats were subjected to 1 h of infra-renal abdominal aorta occlusion and reperfused for 3 h to 5 d to induce SCII. The concentration of BK in serum was detected by enzyme linked immunosorbent assay (ELISA). In situ expression of BK receptors was evaluated by immunochemistry and their mRNA level was evaluated by Real time quantitative-PCR (RTq-PCR). RESULTS: The concentration of BK in serum was increased right after following SCII. Both of the BK receptors were detected and up-regulated in 24 h and 48 h after injury. The levels of B1R and B2R mRNA were up-regulated after SCII, and the B1R mRNA dropped to basal level after 6 h, but B2R mRNA dropped to lower level right after injury, peaked at 3 h, then remained a lower level from 6 h till 5 day. CONCLUSION: This study provides the evidence of the expression of BK and its receptors in SCII in rat model, and suggests that BK and its receptors may have some physiological or pathological significance in SCII.