Wei Qiao

Abstract Despite the widespread observations on the osteogenic effects of magnesium ion (Mg 2+ ), the diverse roles of Mg 2+ during bone healing have not been systematically dissected. Here, we reveal a previously unknown, biphasic mode of action of Mg 2+ in bone repair. During the early inflammation phase, Mg 2+ contributes to an upregulated expression of transient receptor potential cation channel member 7 (TRPM7), and a TRPM7-dependent influx of Mg 2+ in the monocyte-macrophage lineage, resulting in the cleavage and nuclear accumulation of TRPM7-cleaved kinase fragments (M7CKs). This then triggers the phosphorylation of Histone H3 at serine 10, in a TRPM7-dependent manner at the promoters of inflammatory cytokines, leading to the formation of a pro-osteogenic immune microenvironment. In the later remodeling phase, however, the continued exposure of Mg 2+ not only lead to the over-activation of NF-κB signaling in macrophages and increased number of osteoclastic-like cells but also decelerates bone maturation through the suppression of hydroxyapatite precipitation. Thus, the negative effects of Mg 2+ on osteogenesis can override the initial pro-osteogenic benefits of Mg 2+ . Taken together, this study establishes a paradigm shift in the understanding of the diverse and multifaceted roles of Mg 2+ in bone healing.

Abstract Understanding cell–biomaterial interactions is critical for the control of cell fate for tissue engineering and regenerative medicine. Here, cerium oxide nanoparticles (CeONPs) are applied at different Ce 4+ /Ce 3+ ratios (i.e., 0.46, 1.23, and 3.23) to titanium substrate surfaces by magnetron sputtering and vacuum annealing. Evaluation of the cytotoxicity of the modified surface to cultured rat bone marrow mesenchymal stem cells (BMSCs) reveals that the cytocompatibility and cell proliferation are proportional to the increases in Ce 4+ /Ce 3+ ratio on titanium surface. The bone formation capability induced by these surface modified titanium alloys is evaluated by implanting various CeONP samples into the intramedullary cavity of rat femur for 8 weeks. New bone formation adjacent to the implant shows a close relationship to the surface Ce 4+ /Ce 3+ ratio; higher Ce 4+ /Ce 3+ ratio achieves better osseointegration. The mechanism of this in vivo outcome is explored by culturing rat BMSCs and RAW264.7 murine macrophages on CeONP samples for different durations. The improvement in osteogenic differentiation capability of BMSCs is directly proportional to the increased Ce 4+ /Ce 3+ ratio on the titanium surface. Increases in the Ce 4+ /Ce 3+ ratio also elevate the polarization of the M2 phenotype of RAW264.7 murine macrophages, particularly with respect to the healing‐associated M2 percentage and anti‐inflammatory cytokine secretion. The manipulation of valence states of CeONPs appears to provide an effective modulation of the osteogenic capability of stem cells and the M2 polarization of macrophages, resulting in favorable outcomes of new bone formation and osseointegration.

Abstract Rational regulation of active hydrogen (*H) behavior is crucial for advancing electrocatalytic nitrate reduction reaction (NO 3 RR) to ammonia (NH 3 ), yet in‐depth understanding of the *H generation, transfer, and utilization remains ambiguous, and explorations for *H dynamic optimization are urgently needed. Herein we engineer a Ni 3 N nanosheet array intimately decorated with Cu nanoclusters (NF/Ni 3 N−Cu) for remarkably boosted NO 3 RR. From comprehensive experimental and theoretical investigations, the Ni 3 N moieties favors water dissociation to generate *H, and then *H can rapidly transfer to the Cu via unique reverse hydrogen spillover mediating interfacial Ni−N−Cu bridge bond, thus increasing *H coverage on the Cu site for subsequent deoxygenation/hydrogenation. More impressively, such intriguing reverse hydrogen spillover effect can be further strengthened via elegant engineering of the Ni 3 N/Cu heterointerface with more intimate contact. Consequently, the NF/Ni 3 N−Cu with Cu nanoclusters intimate anchoring presents record NH 3 yield rate of 1.19 mmol h −1 cm −2 and Faradaic efficiency of 98.7 % at −0.3 V vs. RHE, being on par with the state‐of‐the‐art ones. Additionally, with NF/Ni 3 N−Cu as the cathode, a high‐performing Zn−NO 3 − battery can be assembled. This contribution illuminates a novel pathway to optimize *H behavior via distinct reverse hydrogen spillover for promoted NO 3 RR and other hydrogenation reactions.

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. ] However, little is known about outcomes of patients after failure of front-line venetoclax-based regimens. We found that patients failing front-line VEN+HMA have high-risk biology, dismal overall survival (OS) despite salvage therapy, and new putative mechanisms of resistance. This knowledge may help guide physicians' expectations, inform discussion with patients, and design clinical trials in patients after venetoclax failure.