No abstract

Protease nexin-1 (PN-1), an inhibitor of serine proteases, contributes to tissue homeostasis and influences the behavior of some tumor cells. The internalization of PN-1 protease complexes is considered to be mediated by the low-density lipoprotein receptor related protein 1 (LRP1). In this study, both wild-type and LRP1-/- mouse embryonic fibroblasts (MEF) were shown to internalize PN-1. Receptor associated protein (RAP) interfered with PN-1 uptake only in wild-type MEF cells, indicating that another receptor mediates PN-1 uptake in the absence of LRP1. In LRP1-/- MEF cells, inhibitor sensitivity and kinetic values (t(1/2) at 45 min) of PN-1 uptake showed a similarity to syndecan-1-mediated endocytosis. In these cells, PN-1 uptake was increased by overexpression of full-length syndecan-1 and decreased by RNA interference targeting this proteoglycan. Most important, in contrast to PKA activation known to be triggered by LRP1-mediated internalization, our study shows that syndecan-1-mediated internalization of PN-1 stimulated the Ras-ERK signaling pathway.

The world‐class Huize Pb‐Zn deposits of Yunnan province, in southwestern China, located in the center of the Sichuan‐Yunnan‐Guizhou Pb‐Zn polymetallic metallogenic province, has Pb+Zn reserves of more than 5 million tons at Pb+Zn grade of higher than 25% and contains abundant associated metals, such as Ag, Ge, Cd, and Ga. The deposits are hosted in the Lower Carboniferous carbonate strata and the Permian Emeishan basalts which distributed in the northern and southwestern parts of the orefield. Calcite is the only gangue mineral in the primary ores of the deposits and can be classified into three types, namely lumpy, patch and vein calcites in accordance with their occurrence. There is not intercalated contact between calcite and ore minerals and among the three types of calcite, indicating that they are the same ore‐forming age with different stages and its forming sequence is from lumpy to patch to vein calcites. This paper presents the rare earth element (REE) and C‐O isotopic compositions of calcites in the Huize Pb‐Zn deposits. From lumpy to patch to vein calcites, REE contents decrease as LREE/HREE ratios increase. The chondrite‐normalized REE patterns of the three types of calcites are characterized by LREE‐rich shaped, in which the lumpy calcite shows (La)N < (Ce)N < (Pr)N≈ (Nd)N with Eu/Eu* < 1, the patch calcite has (La)N < (Ce)N < (Pr)N≈ (Nd)N with Eu/Eu* > 1, and the vein calcite displays (La)N > (Ce)N > (Pr)N > (Nd)N with Eu/Eu* > 1. The REE geochemistry of the three types of calcite is different from those of the strata of various age and Permian Emeishan basalt exposed in the orefield. The δ13CPDB and δ18OSMOW values of the three types of calcites vary from −3.5‰ to −2.1‰ and 16.7‰ to 18.6‰, respectively, falling within a small field between primary mantle and marine carbonate in the δ13CPDB vs δ18OSMOW diagram. Various lines of evidence demonstrate that the three types of calcites in the deposits are produced from the same source with different stages. The ore‐forming fluids of the deposits resulted from crustal‐mantle mixing processes, in which the mantle‐derived fluid components might be formed from degassing of mantle or/and magmatism of the Permian Emeishan basalts, and the crustal fluid was mainly provided by carbonate strata in the orefield. The ore‐forming fluids in the deposits were homogenized before mineralization, and the ore‐forming environment varied from relatively reducing to oxidizing.