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Osteolytic bone lesion is a major cause of lower quality of life and poor prognosis in patients with multiple myeloma (MM), but molecular pathogenesis of the osteolytic process in MM remains elusive. Fms-like tyrosine kinase 3 ligand (FLT3L) was reported to be elevated in bone marrow (BM) and blood of patients with advanced MM who often show osteolysis. Here, we investigated a functional link of FLT3L to osteolytic process in MM. We recruited 86, 306, and 52 patients with MM, acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL), respectively. FLT3L levels of patients with hematologic malignancies were measured in BM-derived plasma and found to be significantly higher in MM than in AML or ALL, which rarely show osteolysis. FLT3L levels were further elevated in MM patients with bone lesion compared with patients without bone lesion. In vitro cell-based assays showed that the administration of FLT3L to HEK293T, HeLa, and U2OS cells led to an increase in the DKK1 transcript level through STAT3 phosphorylation at tyrosine 705. WNT reporter assay showed that FLT3L treatment reduced WNT signaling and nuclear translocation of β-catenin. These results collectively show that the FLT3L-STAT3-DKK1 pathway inhibits WNT signaling-mediated bone formation in MM, which can cause osteolytic bone lesion. Finally, transcriptomic profiles revealed that FLT3L and DKK1 were predominantly elevated in the hyperdiploidy subtype of MM. Taken together, FLT3L can serve as a promising biomarker for predicting osteolytic bone lesion and also a potential therapeutic target to prohibit the progression of the osteolytic process in MM with hyperdiploidy.

Cations in an electrolyte modulate microenvironments near the catalyst surface and affect product distribution from an electrochemical CO 2 reduction reaction, and thus, their interaction with intermediate states has been tried to be probed. Herein, we directly observed the cation effect on *CO intermediates on the Cu(OH) 2 -derived catalyst in real time through operando surface-enhanced Raman spectroscopy at high overpotentials (-1.0 V RHE ). Atop *CO peaks are composed of low-frequency binding *CO (*CO LFB ) and high-frequency binding *CO (*CO HFB ) because of their adsorption sites. These two *CO intermediates are found to have different sensitivities to the cation-induced field, and each *CO is proposed to be suitably stabilized for efficient C-C coupling. The proportions between *CO HFB and *CO LFB are dependent on the type of alkali cations, and the increases in the *CO HFB ratio have a high correlation with selective C 2 H 4 production under K + and Cs + , indicating that *CO HFB is the dominant and fast active species. In addition, as the hydrated cation size decreases, *CO LFB is more sensitively red-shifted than *CO HFB , which promotes C-C coupling and suppresses C 1 products. Through time-resolved operando measurements, dynamic changes between the two *CO species are observed, showing the rapid initial adsorption of *CO HFB and subsequently reaching a steady ratio between *CO LFB and *CO HFB .