Shan-Shan Pan

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of proinflammatory innate immune reactions, and it is an essential mediator of death in sepsis. However, the ligand for TREM-1 has not been fully identified. Previous research identified a natural ligand of TREM-1 distributed on platelets that contributed to the development of sepsis. However, the exact signal for TREM-1 recognization remains to be identified. Here, we identified actin as a TREM-1-interacting protein on platelets and found that recombinant actin could interact with recombinant TREM-1 extracellular domain directly. Furthermore, actin co-localized with TREM-1 on the surface of activated Mouse macrophage RAW264.7 cells interacting with platelets. Additionally, recombinant actin could enhance the inflammatory response of macrophages from wt mice but not from trem1-/- mice, and the enhancement could be inhibited by LP17 (a TREM-1 inhibitor) in a dose-dependent manner. Importantly, extracellular actin showed co-localization with TREM-1 in lung tissue sections from septic mice, which suggested that TREM-1 recognized actin during activation in sepsis. Therefore, the present study identified actin as a new ligand for TREM-1 signaling, and it also provided a link between both essential regulators of death in sepsis.

Abstract Human health has been seriously endangered by arsenic pollution in drinking water. In this paper, iron hydroxide nanopetalines were synthesized through a precipitation method using KBH 4 and their performance and mechanism of As(V) and As(III) removal were investigated. The prepared material was characterized by SEM–EDX, XRD, BET, zeta potential and FTIR analyses. Batch experiments indicated that the iron hydroxide nanopetalines exhibited more excellent performance for As(V) and As(III) removal than ferrihydrite. The adsorption processes were very fast in the first stage, followed a relatively slower adsorption rate and reached equilibria after 24 h, and the reaction could be fitted best by the pseudo-second order model, followed by the Elovich model. The adsorption isotherm data followed to the Freundlich model, and the maximal adsorption capacities of As(V) and As(III) calculated by the Langmuir model were 217.76 and 91.74 mg/g at pH 4.0, respectively, whereas these values were 187.84 and 147.06 mg/g at pH 8.0, respectively. Thermodynamic studies indicated that the adsorption process was endothermic and spontaneous. The removal efficiencies of As(V) and As(III) were significantly affected by the solution pH and presence of PO 4 3– and citrate. The reusability experiments showed that more than 67% of the removal efficiency of As(V) could be easily recovered after four cycles. The SEM and XRD analyses indicated that the surface morphology and crystal structure before and after arsenic removal were stable. Based on the analyses of FTIR, XRD and XPS, the predominant adsorption mechanism was the formation of inner-sphere surface complexes by the surface hydroxyl exchange reactions of Fe–OH groups with arsenic species. This research provides a new strategy for the development of arsenic immobilization materials and the results confirm that iron hydroxide nanopetalines could be considered as a promising material for removing arsenic from As-contaminated water for their highly efficient performance and stability.

BACKGROUND: Late exercise preconditioning (LEP) is confirmed to have a protective effect on acute cardiovascular stress. However, the mechanisms by which mitophagy participates in exercise preconditioning (EP)-induced cardioprotection remain unclear. LEP may involve mitophagy mediated by the receptors PARK2 gene-encoded E3 ubiquitin ligase (Parkin) and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (Bnip3) to scavenge damaged mitochondria. METHODS: Our EP protocol involved four 10-minute periods of running, separated by 10-minute recovery intervals, plus a period of exhaustive running at 24 hours after EP. We assessed this late protective effect by injection of the autophagy inhibitor wortmannin, transmission electron microscopy, laser scanning confocal microscopy, and other molecular biotechnology methods; we simultaneously detected related markers, analyzed the specific relationships between mitophagy proteins, and assessed mitochondrial translocation. RESULTS: Exhaustive exercise (EE) causes serious injuries to cardiomyofibrils, inducing hypoxia-ischemia and changing the ultrastructure. EE fails to clear excessively generated mitochondria to link with LC3 accumulation. After EP, increased autophagy levels at 30 minutes were converted to mitophagy within 24 hours. We found that LEP significantly suppressed EE-induced injuries, which we confirmed by observing decreased levels of the mitochondria-localized proteins COX4/1 and TOM20. LEP to exhaustion caused mitochondrial degradation by increasing the efficiency of LC3-outer mitochondrial membrane translocation in a Parkin-mediated manner, in which activated protein kinase and TOM70 may play both key roles. However, we did not observe mitophagy to be associated with Bnip3 mediation in LEP-induced cardioprotection. However, Bnip3 may play a role in inducing mitochondrial LC3-II increases. Wortmannin had no effect on LC3 translocation; instead, it influenced LC3-I to convert to LC3-II. Thus, suppressing mitophagy led to the attenuation of EP-induced cardioprotection.