A potential role of human esophageal cancer-related gene-4 in cardiovascular homeostasis.

Human esophageal cancer related gene-4 (ECRG-4) encodes a 148-aminoacid pre-pro-peptide that can be processed tissue-dependently into multiple small peptides possessing multiple functions distinct from, similar to, or opposite to the tumor suppressor function of the full-length Ecrg4. Ecrg-4 is covalently bound to the cell surface through its signal peptide, colocalized with the innate immunity complex (TLR4-CD14-MD2), and functions as a 'sentinel' molecule in the maintenance of epithelium and leukocyte homeostasis, meaning that the presence of Ecrg-4 on the cell surface signals the maintained homeostasis, whereas the loss of Ecrg-4 due to tissue injury activates pro-inflammatory and tissue proliferative responses, and the level of Ecrg-4 gradually returns to its pre-injury level upon wound healing. Interestingly, Ecrg-4 is also highly expressed in the heart and its conduction system, endothelial cells, and vascular smooth muscle cells. Accumulating evidence has shown that Ecrg-4 is involved in cardiac rate/rhythm control, the development of atrial fibrillation, doxorubicin-induced cardiotoxicity, the ischemic response of the heart and hypoxic response in the carotid body, the pathogenesis of atherosclerosis, and likely the endemic incidence of idiopathic dilated cardiomyopathy. These preliminary discoveries suggest that Ecrg-4 may function as a 'sentinel' molecule in cardiovascular system as well. Here, we briefly review the basic characteristics of ECRG-4 as a tumor suppressor gene and its regulatory functions on inflammation and apoptosis; summarize the discoveries about its distribution in cardiovascular system and involvement in the development of CVDs, and discuss its potential as a novel therapeutic target for the maintenance of cardiovascular system homeostasis.

Human-specific CHRFAM7A primes macrophages for a heightened pro-inflammatory response at the earlier stage of inflammation.

α7-Nicotinic acetylcholine receptor (α7-nAChR) is the key effector molecule of the cholinergic anti-inflammatory pathway. Evolution has evolved a uniquely human α7-nAChR encoded by CHRFAM7A. It has been demonstrated that CHRFAM7A dominant negatively regulates the functions of α7-nAChR. However, its role in inflammation remains to be fully characterized. CHRFAM7A transgenic (Tg) mice were phenotypically normal and their peritoneal macrophages exhibited decreased ligand-binding capability and, importantly, an activated gene expression profile of pro-inflammatory cytokines. Surprisingly, when challenged with sepsis, the Tg mice showed no survival disadvantage relative to their wild-type (Wt) counterparts. Further analysis showed that the complete blood count and serum levels of pro-inflammatory cytokines were comparable at resting state, but the degrees of leukocyte mobilization and the increase of pro-inflammatory cytokines were significantly higher in Tg than Wt mice at the early stage of sepsis. In vitro, peritoneal macrophages of the Tg mice exhibited an exaggerated response to lipopolysaccharides (LPSs), especially at the earlier time points and at lower dosages of LPS. Remarkably, monocytes from CHRFAM7A-carrier showed similar dynamic changes of the pro-inflammatory cytokines to that observed in the Tg mice upon LPS challenge. Our results suggest that CHRFAM7A increases the mobilization of leukocytes and primes macrophages that confer an enhanced immune response at the early stage of inflammation, which may lead to prompt pathogen clearance, an evolutionary advantage in less severe inflammatory conditions.

An improved risk zoning method of bed-separation water inrush in underground coal mines: a case study in Ningxia, China.

Bed-separation water inrush (BSWI) is a new type of coal mine disaster that has caused serious damage. The shortcomings of previous studies on this topic are as follows: 1) most studies focused on the BSWI mechanism, evolution, and control methods, and there is a lack of research on BSWI risk assessment methods and 2) previous risk assessment studies ignored the factors of the water yield property. First, based on the proposed BSWI engineering geological model, three first-order factors are proposed: 1) separation space between layers, 2) water production characteristics, and 3) water resistance effect. Then, eight secondary factors are determined: 1) production thickness (MT), 2) hard rock thickness (HRT), 3) improved lithology index (ILCI), 4) core recovery (CR), 5) aquifer depth (AD), 6) drilling fluid consumption (DFC), 7) protective layer thickness (PLT), and 8) self-healing potential index (SPI). Subsequently, the corresponding weights are calculated, and the multifactor superposition method is used to draw the BSWI risk map. The area is divided into three risk grades: low, medium, and high. The results are validated by observations of BSWI accidents and bed-separation water exploration and discharge boreholes in the study area. The proposed method can be used to effectively prevent BSWI disasters in other coal mines with similar geological conditions.

Zoning for eco-geological environment before mining in Yushenfu mining area, northern Shaanxi, China.

Zoning for the eco-geological environment (EGE) aims to protect and improve the regional ecological environment. It is the basis for evaluating the ecological characteristics of a mining area prior to mining activities and has the purpose of implementing water-preserved mining according to zoning type. In this study, four EGE types were proposed following field investigation in the Yushenfu mining area: oasis type with phreatic water and bottomland in desert (OTPWBD), oasis type with surface water and valley river (OTSWVR), loess gully type with surface runoff (LGTSR), and regional deep groundwater enrichment type (RDGET). Nine EGE evaluation indices were selected: rainfall, evaporation capacity, Luohe formation thickness, surface elevation, Sara Wusu aquifer water abundance, surface lithology, topography, slope, and normalized difference vegetation index (NDVI). Remote sensing technology and geographic information systems were first used to generate the evaluation index thematic maps. Then, the weight of each evaluation index was determined based on an analytic hierarchy process (AHP). Third, the index weight was used to form an improved weighted fuzzy C s clustering algorithm, and EGE zones were assigned using the MATLAB computing platform. For comparison, the AHP was also adopted for EGE zoning and a map of zoning differences was obtained. Finally, EGE field surveys of typical mines were carried out, which verified that EGE zoning using fuzzy clustering was accurate and reasonable.