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The involvement of inwardly rectifying potassium channel 4.1 (Kir4.1) in neuropathic pain has been established. However, there is limited understanding of the downstream mechanism through which Kir4.1 contributes to orofacial neuropathic pain. The objective of this study was to examine the regulation of Kir4.1 on the expression of pannexin 3 (Panx3) in the trigeminal ganglion (TG) and the underlying mechanism in the context of orofacial neuropathic pain caused by chronic constriction injury of the infraorbital nerve (CCI‐ION). The study observed a significant increase in Panx3 expression in the TG of mice with CCI‐ION. Inhibition of Panx3 in the TG of CCI‐ION mice resulted in alleviation of orofacial mechanical allodynia. Furthermore, conditional knockdown (CKD) of Kir4.1 in the TG of both male and female mice led to mechanical allodynia and upregulation of Panx3 expression. Conversely, overexpression of Kir4.1 decreased Panx3 levels in the TG and relieved mechanical allodynia in CCI‐ION mice. In addition, silencing Kir4.1 in satellite glial cells (SGCs) decreased Panx3 expression and increased the phosphorylation of P38 MAPK. Moreover, silencing Kir4.1 in SGCs increased the levels of reactive oxygen species (ROS). The elevated phosphorylation of P38 MAPK resulting from Kir4.1 silencing was inhibited by using a superoxide scavenger known as the tempol. Silencing Panx3 in the TG in vivo attenuated the mechanical allodynia caused by Kir4.1 CKD. In conclusion, these findings suggest that the reduction of Kir4.1 promotes the expression of Panx3 by activating the ROS‐P38 MAPK signalling pathway, thus contributing to the development of orofacial neuropathic pain. [ABSTRACT FROM AUTHOR]

Extensive investigations have been conducted regarding the potential correlation between blood type and the immune system, as well as cancer risk in the Southern Chinese population. However, the prognostic value of the blood group and its genetic determinants in the context of immune checkpoint inhibitor (ICI) treatment remains unclear. Therefore, the associations between the ABO blood group and its single nucleotide polymorphisms (SNPs) were examined in relation to ICI treatment outcomes in 370 eligible patients with cancer. This approach allowed us to derive the blood group from the SNPs responsible for blood group determination. In the discovery cohort (N = 168), antigen A carriers (blood types A and AB) exhibited an extended progression‐free survival (PFS; hazard ratio (HR) = 0.58, 95% confidence interval (CI) = 0.34–0.98). The association results from the SNP‐derived blood were consistent with those from the measured blood group. In the validation cohort (N = 202), Cox regression analysis revealed that the antigen A carriers (rs507666 AA+GA genotype carriers) experienced significantly extended PFS compared with the non‐antigen A carriers (HR = 0.61, 95% CI = 0.40–0.93). Therefore, a longer PFS was observed in antigen A carriers (P value = 0.003, HR = 0.60, 95% CI = 0.44–0.84). Furthermore, haplotype 2 carriers (rs507666 GA and rs659104 GG) demonstrated both extended PFS and improved overall survival. Notably, the presence of antigen A was not associated with the occurrence of overall immune‐related adverse events (irAEs) or organ‐specific toxicity. In summary, our findings revealed that antigen A carriers did not experience a higher incidence of irAEs while exhibiting better immunotherapy efficacy. [ABSTRACT FROM AUTHOR]

With more than 11,000 t of gold resources, the Central Asian orogenic belt is the most significant gold deposit belt in the world. The majority of the orogenic belt's gold resources are found in a layer of carbon‐rich black shale. However, there is disagreement regarding the origin and metallogenic process of such a significant quantity of gold. The Haoyaoerhudong gold deposit is located where the northern margin of the North China Craton and the southern margin of the Central Asian orogenic belt converge. It is the most significant black shale gold deposit in the northern margin of North China Craton gold province. The pyrite that typically develops in the Haoyaoerhudong gold deposit has been categorized into five varieties through comprehensive field investigation and mineralogical research, which correspond to five metallogenic stages: Stage 1, sedimentary diagenesis; Stage 2, tectonic deformation; Stage 3, hydrothermal; Stage 4, hydrothermal transformation; Stage 5, late metallogenic. For pyrite in the previous four metallogenic stages, in situ LA‐ICP‐MS trace element analysis and pyrite sulfide isotope analyses were performed. The results suggest that: The average Au contents in the pyrite of sedimentary diagenesis stage is 0.098 ppm; the average Au contents in the pyrite of the tectonic deformation stage and hydrothermal stage, is below the detection limit mostly; the average Au contents in the pyrite of hydrothermal transformation stage is 0.12 ppm. The results indicate that only 22.4% more gold is present in hydrothermal transformation stage than in sedimentary diagenetic stage overall. It may be inferred that the gold enrichment of Haoyaoerhudong gold deposit mostly took place during the sedimentary diagenetic stage; subsequent brittle‐ductile shear and hydrothermal fluid activity did not result in a further enrichment of gold. The sulfur isotope test results of various metallogenic stages in the deposit can be analyzed, and they are generally consistent. The δ34S values range from +10.15% to +16.47%, with an average value of +13.02%. It suggests that there might be a single source of sulfur. According to extensive analysis, the Haoyaoerhudong gold deposit formed a relatively low‐grade ore body during the sedimentary diagenesis stage, and the subsequent tectonic deformation stage and hydrothermal stage provided physical conditions for further activation of gold metal but did not bring corresponding material sources for mineralization. [ABSTRACT FROM AUTHOR]