Parathyroid hormone (PTH) and its related peptide (PTH-related peptide 1–34) are two of the Food and Drug Administration-approved bone-promoting drugs for age-related osteoporosis. Treatment with PTH stimulates bone formation. However, the molecular mechanisms of PTH-mediated osteoblast differentiation and cell proliferation are still not completely understood. In this study, we showed that PTH induced endoplasmic reticulum (ER) stress in osteoblasts through the PKR-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2α (EIF2α)-activating transcription factor 4 (ATF4)-signaling pathway. After separately blocking PERK-EIF2α-ATF4 signaling with two different inhibitors [AMG’44 and integrated stress response inhibitor (ISRIB)] or specific small interfering RNA for PERK and ATF4, the following targets were all downregulated: expression of osteoblast differentiation markers [runt-related transcription factor 2 (Runx2), alkaline phosphatase (Alp), type I collagen (Col1a1), and osteocalcin (Ocn)], cell proliferation markers (CyclinE, CyclinD, and CDC2), amino acid import (Glyt1), and metabolism-related genes (Asns). Additionally, Alp-positive staining cells, Alp activity, matrix mineralization, Ocn secretion, and cell proliferation indexes were inhibited. Interestingly, we found that salubrinal enhanced PTH-induced osteoblast differentiation and proliferation by maintenance of phosphorylation of EIF2α. Furthermore, we observed that PTH increased the association between heat shock protein 90 (HSP90) and PERK and maintained PERK protein stabilization in the early stages of PTH-induced ER stress. Treatment of MC3T3-E1 cells with geldanamycin, an HSP90 inhibitor, decreased PERK protein expression and inhibited osteoblast differentiation and cell proliferation upon PTH treatment. Taken together, our data demonstrate that PTH regulates osteoblast differentiation and cell proliferation, partly by activating the HSP90-dependent PERK-EIF2α-ATF4 signaling pathway.
The electrochemical carbon dioxide (CO2) reduction provides a means to upgrade CO2 into value‐added chemicals. When powered by renewable electricity, CO2 electroreduction holds the promise of chemical manufacturing with carbon neutrality. A commercially relevant CO2 electroreduction process should be highly selective and productive toward desired products, energetically efficient for power conversion, and stable for long‐term operation. To achieve these goals, designing gas‐diffusion catalytic electrodes and prototyping reactors built upon in‐depth understandings of the reaction mechanisms are of paramount importance. In this review, the fundamentals of gas‐diffusion electrodes are briefly presented. Then, the most recent advances in developing high‐performance CO2 reduction using gas‐diffusion electrodes are overviewed. Reactor engineering aiming at enhancing productivity, energy efficiency, CO2 single‐pass utilization, and operating lifetime is further discussed. Challenges in developing CO2 electroreduction systems are included. The prospects for advancing CO2 electroreduction toward practical applications are also narrated.
The sustainable production of methane (CH 4 ) via the electrochemical conversion of carbon dioxide (CO 2 ) is an appealing approach to simultaneously mitigating carbon emissions and achieving energy storage in chemical bonds. Copper (Cu) is a unique material to produce hydrocarbons and oxygenates. However, selective methane generation on Cu remains a great challenge due to the preferential *CO dimerization pathway toward multi-carbon (C 2+ ) products at neighboring catalytic sites. Herein, a conjugated copper phthalocyanine polymer (CuPPc) is designed by a facile solid-state method for highly selective CO 2 -to-CH 4 conversion. The spatially isolated CuN 4 sites in CuPPc favor the *CO protonation to generate the key *CHO intermediate, thus significantly promoting the formation of CH 4 . As a result, the CuPPc catalyst exhibits a high CH 4 Faradaic efficiency of 55% and a partial current density of 18 mA cm −2 at −1.25 V versus the reversible hydrogen electrode. It also stably operates for 12 h. This study may offer a new solution to regulating the chemical environment of the active sites for the development of highly efficient copper-based catalysts for electrochemical CO 2 reduction.
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