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Dysfunctional gene expression in nociceptive pathways plays a critical role in the development and maintenance of neuropathic pain. Super enhancers (SEs), composed of a large cluster of transcriptional enhancers, are emerging as new players in the regulation of gene expression. However, whether SEs participate in nociceptive responses remains unknown. Here, we report a spinal-specific SE (SS-SE) that regulates chronic constriction injury (CCI)-induced neuropathic pain by driving Ntmt1 and Prrx2 transcription in dorsal horn neurons. Peripheral nerve injury significantly enhanced the activity of SS-SE and increased the expression of NTMT1 and PRRX2 in the dorsal horn of male mice in a bromodomain-containing protein 4 (BRD4)-dependent manner. Both intrathecal administration of a pharmacological BRD4 inhibitor JQ1 and CRISPR-Cas9-mediated SE deletion abolished the increased NTMT1 and PRRX2 in CCI mice and attenuated their nociceptive hypersensitivities. Furthermore, knocking down Ntmt1 or Prrx2 with siRNA suppressed the injury-induced elevation of phosphorylated extracellular-signal-regulated kinase (p-ERK) and glial fibrillary acidic protein (GFAP) expression in the dorsal horn and alleviated neuropathic pain behaviors. Mimicking the increase in spinal Ntmt1 or Prrx2 in naive mice increased p-ERK and GFAP expression and led to the genesis of neuropathic pain-like behavior. These results redefine our understanding of the regulation of pain-related genes and demonstrate that BRD4-driven increases in SS-SE activity is responsible for the genesis of neuropathic pain through the governance of NTMT1 and PRRX2 expression in dorsal horn neurons. Our findings highlight the therapeutic potential of BRD4 inhibitors for the treatment of neuropathic pain. [ABSTRACT FROM AUTHOR]

Mytilus coruscus is a dominant shellfish in the Yangtze estuary and its adjacent sea area. Food deprivation often occurs during their growth due to fluctuations in algal abundance caused by seasonal freshwater flushing and high-density aquaculture mode. To investigate the coping strategies of M. coruscus to starvation stress, electron microscopy and differential proteomic analysis were performed on the critical feeding organ gill of the mussels after 9 days of starvation. The electron microscopy results showed that the cilia of the mussel gills were dissolved, and the gaps between gill filaments widened under starvation. Differential proteomic analysis revealed that phagocytosis-related proteins such as ATPeV1E, ATPeV1C, LAMP1_2 and CTSL were significantly upregulated, and the phagocytosis pathway was significantly enriched (p < 0.05). In addition, the corin content in gill and myeloperoxidase level as well as the number of dead cells in blood were both significantly increased (p < 0.05). What's more, proteomic data suggested that immune maintenance, cellular transport and metabolism related pathways were significantly enriched, which illustrated an immune and metabolism responses under starvation. This study reveals for the first time that phagocytosis functions as an essential strategy for M. coruscus to cope with starvation, which provides new scientific knowledge and a theoretical basis for understanding the adaptation mechanisms of mussel to starvation and for rational optimization of mussel culture patterns. [ABSTRACT FROM AUTHOR]

Lode gold deposits, which are currently the world’s major gold supply, have been shown to be generated mostly by phase separation of metamorphic fluids and/or interaction between these fluids and wall rocks. Here we use garnet oxygen isotopes by secondary ion mass spectrometry to document the crucial role of magmatic hydrothermal fluids and their mixing with meteoric water in the formation of the world-class Dongping gold deposit in the North China Craton. Garnet grains from quartz veins of various paragenetic stages and the mineralized alteration envelope at Dongping have dynamic δ18O variations of 3.8 to 211.0‰, with large intragrain fluctuations up to 5.3‰. These values correspond to calculated δ18O values of 6.1 to 29.1‰for the hydrothermal fluids from which the garnet formed. The isotope data, notably the cyclic alternation in δ18O within individual garnet grains, are best interpreted to reflect multiple pulses of magmatically derived fluids and subsequent mixing of each pulse with variable amounts of meteoric water. The results presented here allow us to quantify the significant interplay between magmatic hydrothermal fluids and meteoric water that spanned the entire mineralization history and triggered gold deposition of a lode gold deposit. This study highlights the potential use of in situ oxygen isotope analysis of garnet in tracing the origin and evolution of hydrothermal fluids in the Earth’s crust that may have formed other giant ore deposits. [ABSTRACT FROM AUTHOR]

A 68-year-old man presented with a three-week history of rapidly progressive dementia, gait ataxia and myoclonus. Subsequent electroencephalography showed periodic sharp wave complexes, and cerebrospinal fluid assay revealed the presence of a 14-3-3 protein. A probable diagnosis of sporadic Creutzfeldt-Jakob disease was made, which was further supported by magnetic resonance (MR) imaging of the brain showing asymmetric signal abnormality in the cerebral cortices and basal ganglia. The aetiology, clinical features, diagnostic criteria, various MR imaging patterns and radiologic differential diagnosis of sporadic Creutzfeldt-Jakob disease are discussed in this article. [ABSTRACT FROM AUTHOR]

Background: Salidroside (SDS) is the main effective ingredient of Rhodiola rosea L with a variety of pharmacologic properties. We aim to investigate the effects of SDS on ventilation induced lung injury (VILI) and explore the possible underlying molecular mechanism. Methods: Lung injury was induced in male ICR mice via mechanical ventilation (30 ml/kg) for 4h. The mice were divided in four groups:(1) Control group; (2) Ventilation group; (3) SDS group; (4) Ventilation with SDS group. SDS (50 mg/kg) was injected intraperitoneally 1h before operation. Mouse lung vascular endothelial cells (MLVECs) were subjected to cyclic stretch for 4h. Results: It was found that SDS attenuated VILI as shown in HE staining, cell count and protein content levels in BAL fluid, W/D and Evans blue dye leakage into the lung tissue. SDS treatment inhibited the activation of NLRP3 inflammasome and subsequent caspase-1 cleavage as well as interleukin (IL)-1β secretion both in vivo and in vitro. Moreover, SDS administration up-regulated SIRT1 expression. Importantly, knockdown of SIRT1 reversed the inhibitory effect of SDS on NLRP3 inflammasome activation. Conclusions: Taken together, these findings indicate that SDS may confer protection against ventilation induced lung injury via SIRT1-dependent inhibition of NLRP3 inflammasome activation. [ABSTRACT FROM AUTHOR]

Purpose To determine the distribution of peripheral refraction, including astigmatism, in 7- and 14-year-old Chinese children. Methods 2134 7-year-old and 1780 14-year-old children were measured with cycloplegic central and horizontal peripheral refraction (15° and 30° at temporal and nasal visual fields). Results 7- and 14-year-old children included 9 and 594, respectively, with moderate and high myopia (⩽-3.0 D), 259 and 831 with low myopia (-2.99 to -0.5 D), 1207 and 305 with emmetropia (-0.49 to +1.0 D), and 659 and 50 with hyperopia (>1.0 D), respectively. Myopic children had relative peripheral hyperopia while hyperopic and emmetropic children had relative peripheral myopia, with greater changes in relative peripheral refraction occurring in the nasal than the temporal visual field. The older group had the greater relative peripheral hyperopia and higher peripheral J180. Both age groups showed positive slopes of J45 across the visual field, with greater slopes in the older group. Conclusions Myopic children in mainland China have relative peripheral hyperopia while hyperopic and emmetropic children have relative peripheral myopia. Significant differences exist between 7- and 14-year-old children, with the latter showing more relative peripheral hyperopia, greater rate of change in J45 across the visual field, and higher peripheral J180. [ABSTRACT FROM AUTHOR]