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The transmission of nociceptive and pruriceptive signals in the spinal cord is greatly influenced by descending modulation from brain areas such as the rostral ventromedial medulla (RVM). Within the RVM three classes of neurons have been discovered which are relevant to spinal pain modulation, the On, Off, and Neutral cells. These neurons were discovered due to their functional response to nociceptive stimulation. On cells are excited, Off cells are inhibited, and Neutral cells have no response to noxious stimulation. Since these neurons are identified by functional response characteristics it has been difficult to molecularly identify them. In the present study, we leverage our ability to perform optotagging within the RVM to determine whether RVM On, Off, and Neutral cells are GABAergic. We found that 27.27% of RVM On cells, 47.37% of RVM Off cells, and 42.6% of RVM Neutral cells were GABAergic. These results demonstrate that RVM On, Off, and Neutral cells represent a heterogeneous population of neurons and provide a reliable technique for the molecular identification of these neurons.

Current treatments for neurodegenerative diseases and neural injuries face major challenges, primarily due to the diminished regenerative capacity of neurons in the mammalian CNS as they mature. Here, we investigated the role of Ezh2, a histone methyltransferase, in regulating mammalian axon regeneration. We found that Ezh2 declined in the mouse nervous system during maturation but was upregulated in adult dorsal root ganglion neurons following peripheral nerve injury to facilitate spontaneous axon regeneration. In addition, overexpression of Ezh2 in retinal ganglion cells in the CNS promoted optic nerve regeneration via both histone methylation-dependent and -independent mechanisms. Further investigation revealed that Ezh2 fostered axon regeneration by orchestrating the transcriptional silencing of genes governing synaptic function and those inhibiting axon regeneration, while concurrently activating various factors that support axon regeneration. Notably, we demonstrated that GABA transporter 2, encoded by Slc6a13, acted downstream of Ezh2 to control axon regeneration. Overall, our study underscores the potential of modulating chromatin accessibility as a promising strategy for promoting CNS axon regeneration., Introduction Axon degeneration and neuronal cell death are common consequences of neurodegenerative diseases and neural injuries. Unfortunately, current clinical therapeutics for neural injuries and neurodegenerative diseases still fall short of [...]

Almond oil is a functional vegetable oil obtained from apricot kernel by pressing, extracting and other technologies, which has the effects of anti-oxidation, anti-inflammation, anti-tumor and prevention of cardiovascular diseases. In this review, the extraction process, nutritional composition and health effect of almond oil were summarized, and the future development tendency of almond oil was prospected.

Abstract This study investigated the cognition, information behaviors and preventive behaviors of Taiwanese citizens in the face of the COVID-19 pandemic. An online survey was administered and 610 valid responses were collected. The relationships between demographic variables and optimistic bias, social trust, information credibility, personal protective measures, avoidance of human contact, and immune system strengthening were examined. Results showed that optimistic bias existed, but there was no significant correlation between optimistic bias and personal protective measures. Laypersons had high trust in the government, but also optimistic bias. Gender was the most important predictor; with occupation and region of residence also interacting with different preventive behaviors. People in Taiwan may be overly optimistic in facing the epidemic; relevant information should be properly disclosed to help reduce this bias. Social trust in the government seems to be an important successful factor in the fight against COVID-19 in Taiwan.

Early-stage non-small cell lung cancer (NSCLC) patients are at substantial risk of poor prognosis. We attempted to develop a reliable metabolic gene-set-based signature that can predict prognosis accurately for early-stage patients. Least absolute shrinkage and selection operator method Cox regression models were performed to filter the most useful prognostic genes, and a metabolic gene-set-based signature was constructed. Forty-two metabolism-related genes were finally identified, and with specific risk score formula, patients were classified into high-risk and low-risk groups. Overall survival was significantly different between the two groups in discovery (HR: 5.050, 95% CI: 3.368–7.574, P < 0.001), internal validation series (HR: 6.044, 95% CI: 3.918–9.322, P < 0.001), GSE30219 (HR: 2.059, 95% CI: 1.510–2.808, P < 0.001), and GSE68456 (HR: 2.448, 95% CI: 1.723–3.477, P < 0.001). Survival receiver operating characteristic curve at the 5 years suggested that the metabolic signature (area under the curve [AUC] = 0.805) had better prognostic accuracy than any other clinicopathological factors. Further analysis revealed the distinct differences in immune cell infiltration and tumor purity reflected by an immune and stromal score between high- and low-risk patients. In conclusion, the novel metabolic signature developed in our study shows robust prognostic accuracy in predicting prognosis for early-stage NSCLC patients and may function as a reliable marker for guiding more effective immunotherapy strategies.

Background: The biologics derived from human amniotic membranes (AMs) demonstrate potential pain-inhibitory effects in clinical settings. However, the molecular basis underlying this therapeutic effect remains elusive. HC-HA/PTX3 is a unique water-soluble regenerative matrix that is purified from human AMs. We examined whether HC-HA/PTX3 can modulate the gene networks and transcriptional signatures in the dorsal root ganglia (DRG) neurons transmitting peripheral sensory inputs to the spinal cord. Methods: We conducted bulk RNA-sequencing (RNA-seq) of mouse DRG neurons after treating them with HC-HA/PTX3 (15 µg/mL) for 10 min and 24 h in culture. Differential gene expression analysis was performed using the limma package, and Gene Ontology (GO) and protein–protein interaction (PPI) analyses were conducted to identify the networks of pain-related genes. Western blotting and in vitro calcium imaging were used to examine the protein levels and signaling of pro-opiomelanocortin (POMC) in DRG neurons. Results: Compared to the vehicle-treated group, 24 h treatment with HC-HA/PTX3 induced 2047 differentially expressed genes (DEGs), which were centered on the ATPase activity, receptor–ligand activity, and extracellular matrix pathways. Importantly, PPI analysis revealed that over 50 of these DEGs are closely related to pain and analgesia. Notably, HC-HA/PTX3 increased the expression and signaling pathway of POMC, which may affect opioid analgesia. Conclusions: HC-HA/PTX3 induced profound changes in the gene expression in DRG neurons, centered around various neurochemical mechanisms associated with pain modulation. Our findings suggest that HC-HA/PTX3 may be an important biological active component in human AMs that partly underlies its pain inhibitory effect, presenting a new strategy for pain treatment. [ABSTRACT FROM AUTHOR]

Suction caisson is a new offshore wind power foundation structure developed in recent years. Understanding its penetration characteristics is crucial to the successful application. A field test was conducted in the eastern waters of Rudong, Jiangsu Province, China, to investigate the penetration process of suction caisson. The test results demonstrate that suction caisson can penetrate smoothly to a predetermined elevation of seabed soil under the complex environmental loads, such as natural wind and wave currents. The inclination of the caisson is only 0.018° once the penetration process is complete. The pore water pressure at the outer skirt is primarily influenced by the tide level and drainage conditions of the contact soil layer during penetration, and the peak effective interface pressure at the skirt-soil interface decreases by about 46.7% due to negative pressure inside the skirt. Frictional fatigue effects are found at the skirt-soil interfaces. Meanwhile, the seepage reduction and squeezing induced resistance effects at the skirt-soil interface are the leading causes for the different distributions of effective interface pressure between the inner and outer skirts of the caisson. The findings of this study can guide the future penetration of suction caisson under challenging geological circumstances. [ABSTRACT FROM AUTHOR]