Pullulan Polysaccharide as an Eco-Friendly Depressant for Flotation Separation of Chalcopyrite and Molybdenite.

It is difficult to separate molybdenite and chalcopyrite by froth flotation due to the good floatability of the two minerals. In this paper, the separation of copper-molybdenum sulfide minerals was realized by using pullulan polysaccharide (PU) as the depressant. The flotation test results showed that the copper concentrate grade increased from 16.24 to 29.86%, and the copper concentrate recovery reached 83.55% under low alkali conditions. The selective separation mechanism of the two minerals by PU was revealed through contact angle measurements, ζ-potential measurements, Fourier transform infrared (FTIR) spectroscopy analyses, and X-ray photoelectron spectroscopy (XPS) analyses. The ζ-potential and contact angle results showed that PU is more easily adsorbed on molybdenite to strengthen the hydrophilicity of molybdenite. The FTIR and XPS results showed that PU is adsorbed on molybdenite by physical interactions, and hydrophobic interactions and hydrogen bonding play a major role.

Density Functional Theory and XPS Studies of the Adsorption of Cyanide on Chalcopyrite Surfaces.

In this work, both the density functional theory (DFT) calculation and X-ray photoelectron spectroscopy (XPS) were conducted to investigate the depression mechanisms of cyanide on the flotation performance of chalcopyrite. The density functional theory calculation results showed that cyanide could be adsorbed on a chalcopyrite (112) surface spontaneously, which preferably occurred on the surface Fe-Fe hollow site. Both C and N atoms of cyanide could bond with Fe atoms of the chalcopyrite (112) surface, while the interaction of Fe-C bond was more intense, where the Fe 3d orbital donated electrons to the hybrid sp orbital of a C atom forming a back-donating bond. XPS analysis indicated that the chemical interaction between cyanide and surface Fe atoms occurred, resulting in the generation of a hydrophilic iron-cyanide complex on the chalcopyrite surface, which deteriorated the flotation performance of chalcopyrite.

Bacterial outer membrane vesicles induce disseminated intravascular coagulation through the caspase-11-gasdermin D pathway.

BACKGROUND: Disseminated intravascular coagulation (DIC), a severe complication of sepsis, promotes multiple organ dysfunctions and lethality. Bacterial infection is the most common cause of sepsis. We previously show an important role of bacteria-released outer membrane vesicles (OMVs) in bacterial infection-induced DIC. In the light of recent advance that activation of caspase-11 and its enzymatic substrate gasdermin D (GSDMD) is able to trigger coagulation, we postulate that OMVs might induce DIC through the caspase-11-GSDMD pathway. METHODS: Caspase-11- or GSDMD-deficient mice and their wild-type (WT) controls were injected with purified Escherichia coli-derived OMVs. Blood samples were then collected. The development of DIC was assessed in terms of the occurrence of coagulopathy, the organ injuries and the lethality. Peritoneal macrophages derived from WT, Caspase-11- or GSDMD-deficient mice were stimulated with OMVs. Then the cell surface tissue factor (TF) activity and thrombin generation were assessed. RESULTS: Genetic deletion of Caspase-11 or GSDMD or pharmacological inhibition of caspase-11 markedly attenuated OMVs-induced coagulopathy, multiple organ injuries and mortality. Caspase-11- or GSDMD-deficient macrophages exhibited markedly reduced TF activity after OMVs stimulation. CONCLUSION: OMVs induce DIC through the caspase-11-GSDMD pathway. These findings might open a new avenue to prevent or treat bacterial infection-induced DIC.

The role of type 1 interferons in coagulation induced by gram-negative bacteria.

Bacterial infection not only stimulates innate immune responses but also activates coagulation cascades. Overactivation of the coagulation system in bacterial sepsis leads to disseminated intravascular coagulation (DIC), a life-threatening condition. However, the mechanisms by which bacterial infection activates the coagulation cascade are not fully understood. Here we show that type 1 interferons (IFNs), a widely expressed family of cytokines that orchestrate innate antiviral and antibacterial immunity, mediate bacterial infection-induced DIC by amplifying the release of high-mobility group box 1 (HMGB1) into the bloodstream. Inhibition of the expression of type 1 IFNs and disruption of their receptor IFN-α/ßR or downstream effector (eg, HMGB1) uniformly decreased gram-negative bacteria-induced DIC. Mechanistically, extracellular HMGB1 markedly increased the procoagulant activity of tissue factor by promoting the externalization of phosphatidylserine to the outer cell surface, where phosphatidylserine assembles a complex of cofactor-proteases of the coagulation cascades. These findings not only provide novel insights into the link between innate immune responses and coagulation, but they also open a new avenue for developing novel therapeutic strategies to prevent DIC in sepsis.

Ethyl pyruvate confers protection against endotoxemia and sepsis by inhibiting caspase-11-dependent cell pyroptosis.

Ethyl pyruvate exertsa special protectiveeffecton endotoxin-induced endotoxemia and experimental sepsis, but the underlying mechanism remains elusive. Werecently demonstrated that ethyl pyruvate inhibited caspase-11-mediated macrophage pyroptotic cell death. GasderminDis akeymolecule incaspase-11 mediated non-canonical inflammasome-inducedpyroptosis. We proved that ethyl pyruvate significantly decreased caspase-11 and gasdermin D-mediated pyroptosis induced by cytoplasmic lipopolysaccharide (LPS) and bacterial outer membrane vesicles (OMVs). Ethyl pyruvate treatment offered effective protection against lethal endotoxemia and reduced the release of IL-1α and IL-1ß. Similarresults were observed in the mousececal ligation and puncture (CLP)peritonitissepsismodel. These findings identified ethyl pyruvate as an inhibitor against LPS-mediated activation of cytoplasmic caspase-11 and gasdermin D. This mechanism is believed to contribute tothe further explanation of theprotectiveactionof ethyl pyruvate in experimental sepsis and endotoxemia and the potential application of ethyl pyruvate for rescuing sepsis.

Bacterial Endotoxin Activates the Coagulation Cascade through Gasdermin D-Dependent Phosphatidylserine Exposure.

Excessive activation of the coagulation system leads to life-threatening disseminated intravascular coagulation (DIC). Here, we examined the mechanisms underlying the activation of coagulation by lipopolysaccharide (LPS), the major cell-wall component of Gram-negative bacteria. We found that caspase-11, a cytosolic LPS receptor, activated the coagulation cascade. Caspase-11 enhanced the activation of tissue factor (TF), an initiator of coagulation, through triggering the formation of gasdermin D (GSDMD) pores and subsequent phosphatidylserine exposure, in a manner independent of cell death. GSDMD pores mediated calcium influx, which induced phosphatidylserine exposure through transmembrane protein 16F, a calcium-dependent phospholipid scramblase. Deletion of Casp11, ablation of Gsdmd, or neutralization of phosphatidylserine or TF prevented LPS-induced DIC. In septic patients, plasma concentrations of interleukin (IL)-1α and IL-1ß, biomarkers of GSDMD activation, correlated with phosphatidylserine exposure in peripheral leukocytes and DIC scores. Our findings mechanistically link immune recognition of LPS to coagulation, with implications for the treatment of DIC.

Bacteria-released outer membrane vesicles promote disseminated intravascular coagulation.

INTRODUCTION: Sepsis is frequently complicated by disseminated intravascular coagulation (DIC), which promotes multiple organ dysfunctions and significantly increase the mortality of patients with sepsis. How bacteria cause DIC is not fully understood. Outer membrane vesicles (OMVs) are membrane-enclosed microvesicles released by variety of bacteria. The aim of this study is to determine whether OMVs contribute to the pathogenesis of DIC during bacterial infection. METHODS: Wild-type (WT) or Toll-like receptor 4 (TLR4) knock-out mice were intraperitoneally injected with purified Escherichia coli (E.coli) derived OMVs, or with either wild type E.coli or E.coli with genetic deletion of ypjA, which is critical for OMV's production. Blood samples, liver and lung tissues were collected. The development of DIC was assessed in terms of the occurrence of coagulopathy, the thrombi deposition in livers and lungs, the multiple organ injuries, and the lethality. RESULTS: Genetic deletion of ypjA significantly attenuated E.coli-induced coagulopathy, intravascular thrombi deposition, multiple organ injuries and mortality, whereas injection of purified E.coli-derived OMVs resulted in the development of DIC in a TLR4-dependent manner. CONCLUSIONS: OMVs importantly contribute to the pathogenesis of DIC during Gram-negative bacterial infection. These findings might open a new avenue to prevent infection-associated coagulopathy by targeting OMVs production.

Trimethylamine N-oxide promotes tissue factor expression and activity in vascular endothelial cells: A new link between trimethylamine N-oxide and atherosclerotic thrombosis.

Trimethylamine-N-oxide (TMAO), one of the products in choline metabolite, is recently reported to be associated with cardiovascular diseases (CVD) that mainly attribute to atherothrombosis. However, the mechanisms how TMAO functions in the pathogenesis of CVD and atherothrombosis remain elusive. Tissue factor (TF) has been implicated in the thrombogenicity of atherosclerotic plaques. In the present study, we demonstrated that TMAO promoted TF (but not TF pathway inhibitor) expression via activation of NF-κB signaling pathway in primary human coronary artery endothelial cells (HCAECs). TMAO strongly increased TF activity and thrombin production. Further, a small dose of TMAO significantly increased TF expression and nuclear translocation of NF-κB with the synergistic action of low-dose of pro-atherosclerotic factors, such as TNF-α and HMGB1. Importantly, plasma TMAO level was positively correlated with TF activity in patients with ST-elevation myocardial infarction (STEMI). Altogether, our data revealed that TMAO promoted thrombosis through increasing TF expression and activity. The understanding of the new link between TMAO and atherothrombosis may facilitate therapeutic strategy in the prevention and treatment of atherothrombosis.