Azilsartan inhibits inflammation-triggered bone resorption and osteoclastogenesis in vivo via suppression of TNF-α expression in macrophages

IntroductionHypertension is a major risk factor for cardiovascular disease (CVD) and is associated with increased bone loss due to excessive activity of the local renin-angiotensin system (RAS). Angiotensinogen/Angiotensin (ANG) II/Angiotensin II type 1 receptor (AT1R) axis is considered as the core axis regulating RAS activity. Azilsartan is an FDA-approved selective AT1R antagonist that is used to treat hypertension. This study aimed to determine whether azilsartan affects formation of osteoclast, resorption of bone, and the expression of cytokines linked with osteoclastogenesis during lipopolysaccharide (LPS)-triggered inflammation in vivo.MethodsIn vivo, following a 5-day supracalvarial injection of LPS or tumor necrosis factor-alpha (TNF-α) with or without azilsartan, the proportion of bone resorption and the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells, which are identified as osteoclasts on mice calvariae were counted. The mRNA expression levels of TRAP, cathepsin K, receptor activator of NF-κB ligand (RANKL), and TNF-α were also evaluated. In vitro, the effect of azilsartan (0, 0.01, 0.1, 1, and 10 μM) on RANKL and TNF-α-triggered osteoclastogenesis were investigated. Also, whether azilsartan restrains LPS-triggered TNF-α mRNA and protein expression in macrophages and RANKL expression in osteoblasts were assessed. Furthermore, western blotting for analysis of mitogen-activated protein kinases (MAPKs) signaling was conducted.ResultsAzilsartan-treated calvariae exhibited significantly lower bone resorption and osteoclastogenesis than those treated with LPS alone. In vivo, LPS with azilsartan administration resulted in lower levels of receptor activator of RANKL and TNF-α mRNA expression than LPS administration alone. Nevertheless, azilsartan did not show inhibitory effect on RANKL- and TNF-α-triggered osteoclastogenesis in vitro. Compared to macrophages treated with LPS, TNF-α mRNA and protein levels were lower in macrophages treated by LPS with azilsartan. In contrast, RANKL mRNA and protein expression levels in osteoblasts were the same in cells co-treated with azilsartan and LPS and those exposed to LPS only. Furthermore, azilsartan suppressed LPS-triggered MAPKs signaling pathway in macrophages. After 5-day supracalvarial injection, there is no difference between TNF-α injection group and TNF-α with azilsartan injection group.ConclusionThese findings imply that azilsartan prevents LPS-triggered TNF-α production in macrophages, which in turn prevents LPS-Triggered osteoclast formation and bone resorption in vivo

Temperature-induced low-coordinate Ni single-atom catalyst for boosted CO₂ electroreduction activity

Single-atom catalysts (SACs) exhibit remarkable potential for electrochemical reduction of CO2 to value-added products. However, the commonly pursued methods for preparing SACs are hard to scale up, and sometimes, lack general applicability because of expensive raw materials and complex synthetic procedures. In addition, the fine tuning of coordination environment of SACs remains challenging due to their structural vulnerability. Herein, a simple and universal strategy is developed to fabricate Ni SACs with different nitrogen coordination numbers through one-step pyrolysis of melamine, Ni(NO3 )∙6H2 O, and polyvinylpyrrolidone at different temperatures. Experimental measurements and theoretical calculations reveal that the low-coordinate Ni SACs exhibit outstanding CO2 reduction performance and stability, achieving a Faradic efficiency (FECO ) of 98.5% at -0.76 V with CO current density of 24.6 mA cm-2 , and maintaining FECO of over 91.0% at all applied potential windows from -0.56 to -1.16 V, benefiting from its coordinatively unsaturated structure to afford high catalytic activity and low barrier for the formation of *COOH intermediate. No significant performance degradation is observed over 50 h of continuous operation. Additionally, several other metallic single-atom catalysts are successfully prepared by this synthetic method, demonstrating the universality of this strategy.Nanyang Technological UniversityNational Research Foundation (NRF)This work is supported by the National Natural Science Foundation of China (NSFC) (No. 22105178, 52103237), the Nanyang Technological University, and the National Research Foundation (NRF), Singapore, under its Campus for Research Excellence and Technological Enterprise (CREATE) program through the Carbon Reduction in Chemical Technology (C4T) program

Multifunctional Perovskite Photodetectors: From Molecular-Scale Crystal Structure Design to Micro/Nano-scale Morphology Manipulation

Highlights Multidimensional detection of intensity, wavelength, polarization, and angle of the incidence light significantly accelerates the development of optical information technology and artificial intelligence fields. The first comprehensive overview of the advancement of multifunctional photodetectors for perovskite semiconductors ranging from polarized light detection, spectral detection, and angle-sensing detection to self-powered detection is summarized. The existing problems and perspectives are discussed which can inspire more researchers to rationally design new perovskite materials and micro/nano-structure for high-performance multifunctional photodetectors

(D-Ala²)GIP Inhibits Inflammatory Bone Resorption by Suppressing TNF-α and RANKL Expression and Directly Impeding Osteoclast Formation

Glucose-insulinotropic polypeptide (GIP) is an incretin hormone that induces insulin secretion and decreases blood glucose levels. In addition, it has been reported to suppress osteoclast formation. Native GIP is rapidly degraded by dipeptidyl peptidase-4 (DPP-4). (D-Ala2)GIP is a newly developed GIP analog that demonstrates enhanced resistance to DPP-4. This study aimed to evaluate the influence of (D-Ala2)GIP on osteoclast formation and bone resorption during lipopolysaccharide (LPS)-induced inflammation in vivo and in vitro. In vivo, mice received supracalvarial injections of LPS with or without (D-Ala2)GIP for 5 days. Osteoclast formation and bone resorption were evaluated, and TNF-α and RANKL expression were measured. In vitro, the influence of (D-Ala2)GIP on RANKL- and TNF-α-induced osteoclastogenesis, LPS-triggered TNF-α expression in macrophages, and RANKL expression in osteoblasts were examined. Compared to the LPS-only group, calvariae co-administered LPS and (D-Ala2)GIP led to less osteoclast formation, lower bone resorption, and decreased TNF-α and RANKL expression. (D-Ala2)GIP inhibited osteoclastogenesis induced by RANKL and TNF-α and downregulated TNF-α expression in macrophages and RANKL expression in osteoblasts in vitro. Furthermore, (D-Ala2)GIP suppressed the MAPK signaling pathway. The results suggest that (D-Ala2)GIP dampened LPS-triggered osteoclast formation and bone resorption in vivo by reducing TNF-α and RANKL expression and directly inhibiting osteoclastogenesis

Template synthesis of nitrogen-doped carbon nanocages–encapsulated carbon nanobubbles as catalyst for activation of peroxymonosulfate

Nitrogen-doped carbon nanocages–encapsulated carbon nanobubbles (CBs@NCCs) were feasibly fabricated by the in situ thermal conversion of Co–Fe Prussian blue analogues (Co–Fe PBAs) coated with polydopamine (PDA) shells. Interestingly, PBA cores can act as a self-sacrificing template and decompose during high-temperature treatment. PDA shells play a crucial role in stabilizing the steric architecture, supplementing nitrogen-doping of CBs@NCCs under high-temperature treatments. When compared with carbon nanobubbles (CBs) without the protection of carbon nanocages, CBs@NCCs possess higher specific surface area and pore volume. The contributions of a unique configuration and proper nitrogen modification are significant for improving the peroxymonosulfate (PMS) activation performance of CBs@NCCs, which is expected to be a promising alternative to other conventional carbocatalysts and metal oxides. Moreover, the applicability of the as-synthesized carbocatalysts was systematically investigated by adjusting several operating parameters, and some ubiquitous anions and natural organic matters (NOMs) were also taken into account in methylene blue (MB) degradation. The radical evolution and PMS activation mechanism are investigated by radical quenching and electron paramagnetic resonance (EPR) tests, which revealed that sulfate radicals (SO4˙−) and singlet oxygen (1O2) are simultaneously responsible for the overall MB removal in a CBs@NCCs-800/PMS system. This study may provide a broader perspective for upgrading the catalytic efficiency of various green heterogeneous carbocatalysts

Fabrication of Thorny Au Nanostructures on Polyaniline Surfaces for Sensitive Surface-Enhanced Raman Spectroscopy

Here we demonstrate, for the first time, the fabrication of Au nanostructures on polyaniline (PANI) membrane surfaces for surface enhanced Raman spectroscopy (SERS) applications, through a direct chemical reduction by PANI. Introduction of acids into the HAuCl₄ solution leads to homogeneous Au structures on the PANI surfaces, which show only sub-ppm detection levels toward the target analyte, 4-mercaptobenzoic acid (4-MBA), because of limited surface area and lack of surface roughness. Thorny Au nanostructures can be obtained through controlled reaction conditions and the addition of a capping agent poly (vinyl pyrrolidone) (PVP) in the HAuCl₄ solution and the temperature kept at 80 °C in an oven. Those thorny Au nanostructures, with higher surface areas and unique geometric feature, show a SERS detection sensitivity of 1 × 10^–9 M (sub-ppb level) toward two different analyte molecules, 4-MBA and Rhodamine B, demonstrating their generality for SERS applications. These highly sensitive SERS-active substrates offer novel robust structures for trace detection of chemical and biological analytes