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Excessive alarmins S100A8/A9 escalate the inflammation and even exacerbate immune-driven thrombosis and multi-organ damage. However, the regulatory mechanisms of S100A8/A9 expression in infectious diseases remain unclear. In this study, high-dimensional transcriptomic data analyses revealed a high proportion of CD14+FCN1hi macrophages within the pulmonary niche post-severe SARS-CoV-2 infection. By constructing the S100-coexpression gene list and supervised module scoring, we found that CD14+FCN1hi macrophages presented the highest scores of alarmin S100, and possibly served as the trigger and amplifier of inflammation in severe COVID-19. These CD14+FCN1hi cells lacked the positive regulatory activity of transcription factor PPARγ, and lost their differentiation ability towards mature macrophages. Ex vivo experiments further validated that the epithelial cells with high ORF-3a expression promoted the expression and secretion of S100A8/A9 through ANXA1/SAA1-FPR1 signaling. S100A8/A9 heterodimers, as well as the co-localization of S100A8/A9 with microtubules, were both diminished by the FPR1 inhibitor. Phospho-kinase protein array indicated that STAT3 promoted transcription, and PLC-γ and ERK1/2 pathways were involved in the hetero-dimerization and unconventional secretion of S100A8/A9. Our study highlights the pivotal role of FPR1 signaling in the excessive production of S100A8/A9 and provides a promising target for the prevention and control of severe COVID-19 and post-acute COVID-19 sequelae. CD14+FCN1hi macrophages highly express S100A8/S100A9, which is initiated by FPR1 signaling in severe COVID-19. An FPR1 inhibitor prevents the transcription, hetero-dimerization, and secretion of S100A8/A9 through STAT3/PLC-γ/ERK1/2 pathways. [ABSTRACT FROM AUTHOR]

Carbon-supported platinum-nickel alloy catalysts have become one of the main choices of proton exchange membrane fuel cells (PEMFCs) due to the high catalytic activity toward oxygen reduction reaction (ORR). In this work, carbon aerogel supported platinum-nickel solid solution alloy catalysts (Pt3Ni/CA) with small particles (~ 3.5 nm) and uniform distribution were prepared via a simple one-step rapid reduction method during which no structure guide or stabilizer is added. In rotating disk electrode (RDE), the mass activity (MA, 0.25 A mgPt−1) and specific activity (SA, 4.69 A m−2) of the optimized Pt3Ni/CA catalysts for ORR are nearly 3.8 times and 6.5 times that of the state-of-the-art commercial carbon-supported platinum catalysts (Pt/C, 0.07 A mgPt−1 and 0.72 A m−2), respectively. After the accelerated durability test (ADT), the as-prepared Pt3Ni/CA catalysts still keep a satisfactory MA and SA which are more than 3.4 and 8.9 times as high as that of Pt/C. The Koutecký-Levich (K-L) equation shows that the electrochemical reaction conforms to be a 4e− process. [ABSTRACT FROM AUTHOR]

Fine-grained 01420 Al-Li alloy sheets were produced by thermo-mechanical processing based on the mechanism of particle stimulated nucleation of recrystallization. The thermo-mechanically processed sheets were observed to contain layers of different microstructures along the thickness. The precipitate behavior of the second phase particles and their effects on the distribution of dislocations and layered recrystallized grain structure were analyzed by optical microscopy(OM), scanning electron microscopy(SEM), transmission electron microscopy(TEM) and X-ray diffractometry(XRD). The formation mechanism of the gradient particles was discussed. The results show that after aging, a gradient distribution of large particles along the thickness is observed, the particles in the surface layer(SL) are distributed homogeneously, whereas those in the center layer(CL) are mainly distributed parallel to the rolling direction, and the volume fraction of the particles in the SL is higher than that in the CL. Subsequent rolling in the presence of layer-distributed particles results in a corresponding homogeneous distribution of highly strained regions in the SL and a banded distribution of them in CL, which is the main reason for the formation of layered grain structure along the thickness in the sheets. [ABSTRACT FROM AUTHOR]