A Preliminary Study on Silver Isotopic Composition in Polymetallic Ore Deposits in Eastern China

A preliminary survey of silver isotopic composition in four polymetallic ores in eastern China shows a larger variation inδ^(109)Ag from-0.014‰to+0.983‰,which is within the total ranges for the entire respective ore deposit types worldwide.The diversity of silver isotopic compositions in oredeposits reported here and previous studies seemed to preclude simple isotopic links to particular sources,but reflected the silver isotope fractionation in transport-and deposit-related processes instead.Theδ^(109)Ag values in supergene samples from the Qixiashan Pb-Zn-Ag polymetallic deposit are more positive,in consistent with the statistical δ^(109)Ag distribution from-0.4‰to+2.2‰in 36 pieces of supergene ore samples around the World,which reflects the diverse controls on silver isotope fractionation from the first-order thermodynamic effect,reduction-mediated reaction,remobilization of silver with surficial low-temperature weathering processes.The hypogene samples in Dazhuangzi orogenic Au-Ag ore deposit,have δ^(109)Ag values close to 0,which implies that equilibrium partitioning associated with metal sources at the high-temperature does not result in a resolvable difference in silver isotopic compositions.By contrast,the hypogene samples which are dominated by pyrite without visible silver minerals (i.e.,skarn iron ore deposit in Edongnan) have shown the largest variation range of δ^(109)Ag,followed by that from the porphyry copper ore in Zijinshan.It could be concluded that the surface adsorption and/or lattice substitution are important factors to control Ag isotope fractionation in oreforming processes,especially for skarn deposits with only pyrite.The perspective of silver isotope shows great potentials to understand the processes that lead to the concentrations of metals to economic levels and to constrain the physicochemical conditions during ore-mineralization in metallic ore-deposits.

Glutamine mitigates murine burn sepsis by supporting macrophage M2 polarization through repressing the SIRT5-mediated desuccinylation of pyruvate dehydrogenase

Background:Alternative(M2)-activated macrophages drive the anti-inflammatory response against sepsis,a leading cause of death in patients suffering from burn injury.Macrophage M2 polarization is intrinsically linked with dominant oxidative phosphorylation(OXPHOS).Glutamine serves as a major anaplerotic source to fuel OXPHOS,but it remains unknown whether glutamine can modulate metabolic checkpoints in OXPHOS that favour M2 polarization.The study aims to explore whether glutamine essentially supports M2 polarization in IL-4-stimulated murine macrophages by sustaining the activity of PDH and whether glutamine augments macrophage M2 polarization and thus alleviates inflammation and organ injury in a murine burn sepsis model.Methods:To understand how glutamine promotes M2 activation in interleukin(IL-4)-treated murine macrophages,we detected glutamine-dependent M2 polarization and its relationship with the pyruvate dehydrogenase(PDH)complex by RT-PCR,flow cytometry and western blot.To explore how glutamine modulates PDH activity and thus supports M2 polarization,we compared the expression,phosphorylation and succinylation status of PDHA1 and then examined sirtuin SIRT5-dependent desuccinylation of PDHA1 and the effects of SIRT5 overexpression on M2 polarization by RT-PCR,flow cytometry and western blot.To determine whether glutamine or its metabolites affect M2 polarization,macrophages were cocultured with metabolic inhibitors,and then SIRT5 expression and M2 phenotype markers were examined by RT-PCR,flow cytometry and western blot.Finally,to confirm the in vivo effect of glutamine,we established a burn sepsis model by injecting Pseudomonas aeruginosa into burn wounds and observing whether glutamine alleviated proinflammatory injuries by RT-PCR,flow cytometry,western blot,immunofluorescent staining,hematoxylin-eosin staining and enzyme-linked immuno sorbent assay.Results:We showed that consumption of glutamine supported M2 activation in IL-4-treated murine macrophages by upregulating the activity of PDH.Mechanistically,glutamine did not affect the expression or alter the phosphorylation status of PDHA1 but instead downregulated the expression of SIRT5 and repressed SIRT5-dependent desuccinylation on PDHA1,which in turn recovered PDH activity and supported M2 polarization.This effect was implemented by its secondary metaboliteα-ketoglutarate(αKG)rather than glutamine itself.Finally,we demonstrated that glutamine pro-moted macrophage M2 polarization in a murine burn sepsis model,thereby repressing excessive inflammation and alleviating organ injury in model mice.Conclusions:Glutamine mitigates murine burn sepsis by essentially supporting macrophage M2 polarization,with a mechanism involving the repression of the SIRT5-mediated desuccinylation of pyruvate dehydrogenase that replenishes OXPHOS and sustains M2 macrophages.