WTAP-mediated m6A modification modulates bone marrow mesenchymal stem cells differentiation potential and osteoporosis

Abstract An imbalance in the differentiation potential of bone marrow mesenchymal stem cells (BMSCs) is an important pathogenic mechanism underlying osteoporosis (OP). N6-methyladenosine (m6A) is the most common post-transcriptional modification in eukaryotic cells. The role of the Wilms’ tumor 1-associated protein (WTAP), a member of the m6A functional protein family, in regulating BMSCs differentiation remains unknown. We used patient-derived and mouse model-derived samples, qRT-PCR, western blot assays, ALP activity assay, ALP, and Alizarin Red staining to determine the changes in mRNA and protein levels of genes and proteins associated with BMSCs differentiation. Histological analysis and micro-CT were used to evaluate developmental changes in the bone. The results determined that WTAP promoted osteogenic differentiation and inhibited adipogenic differentiation of BMSCs. We used co-immunoprecipitation (co-IP), RNA immunoprecipitation (RIP), methylated RNA immunoprecipitation (MeRIP), RNA pulldown, and dual-luciferase assay to explore the direct mechanism. Mechanistically, the expression of WTAP increased during osteogenic differentiation and significantly promoted pri-miR-181a and pri-miR-181c methylation, which was recognized by YTHDC1, and increased the maturation to miR-181a and miR-181c. MiR-181a and miR-181c inhibited the mRNA expression of SFRP1, promoting the osteogenic differentiation of BMSCs. Our results demonstrated that the WTAP/YTHDC1/miR-181a and miR-181c/SFRP1 axis regulated the differentiation fate of BMSCs, suggesting that it might be a potential therapeutic target for osteoporosis

Novel Nonconjugated Polymer as Cathode Buffer Layer for Efficient Organic Solar Cells

A novel nonconjugated polymer named poly­(2-acrylamido-2-methyl-1-propanesulfonic acid sodium salt) (PAMPS-Na) was designed and synthesized. The PAMPS-Na has good solubility in polar solvents, such as water, methanol, and ethanol, which can be used as the cathode buffer layer in organic solar cells (OSCs) through solution processing without damaging the underlying active layer. Moreover, it was found that PAMPS-Na can significantly decrease the Al work function when it was modified with Al. To reveal its universal application in organic photovoltaic devices, a variety of photovoltaic donor materials, including two medium-band gap polymers, a wide-band gap polymer, and a small molecule donor were employed to fabricate OSCs. Compared with OSCs with Ca/Al electrode, the devices based on PAMPS-Na/Al exhibited higher photovoltaic performance, mainly because of the increased short-circuit current. Additionally, OSCs with PAMPS-Na/Al displayed better ambient stability than devices with Ca/Al. It is also interesting to find that the performance of the devices can tolerate a wide change of PAMPS-Na’s thickness, enabling the potential for large-scale fabrication of OSCs. The results suggest that PAMPS-Na is a promising candidate as the cathode buffer layer to improve the efficiency and stability of OSCs

Tunnel vision optimization method for VR flood scenes based on Gaussian blur

The visualization of flood disasters in virtual reality (VR) scenes is useful for the representation and sharing of disaster knowledge and can effectively improve users’ cognitive efficiency in comprehending disaster information. However, the existing VR methods of visualizing flood disaster scenes have some shortcomings, such as low rendering efficiency and poor user experience. In this paper, a tunnel vision optimization method for VR flood scenes based on Gaussian blur is proposed. The key techniques are studied, such as region of interest (ROI) calculation and tunnel vision optimization considering the characteristics of the human visual system. A prototype system has been developed and used to carry out an experimental case analysis. The experimental results show that the number of triangles drawn in a flood VR scene is reduced by approximately 30%–40% using this method and that the average frame rate is stable at approximately 90 frames per second (fps), significantly improving the efficiency of scene rendering and reducing motion sickness

“Matryoshka Doll”-Like CeO₂ Microspheres with Hierarchical Structure To Achieve Significantly Enhanced Microwave Absorption Performance

Recently, it is still a great challenge to develop a new type of absorber that possesses special advantages of low cost, ultrawide bandwidth, and strong absorption intensity. Herein, the unique “Matryoshka doll”-like CeO₂ microspheres with tunable interspaces were successfully synthesized by a facile and template-free method. The as-synthesized hierarchical yolk–shell CeO₂ microspheres were constructed by a layer of outer shell and multiple inner cores. The interspace gap of the microspheres can be simply adjusted only by altering the solvothermal reaction time. Simultaneously, Ostwald ripening, Kirkendall effect, and self-etching process contribute a synergetic growth mechanism responsible for this amazing hierarchical architecture. Importantly, the “Matryoshka doll”-like CeO₂ microspheres exhibited significantly strong microwave absorption in the frequency range of 2–18 GHz, with a reflection loss of −71.3 dB at 14.5 GHz and an effective absorption bandwidth of 5.4 GHz (<−10 dB), which is superior to the multicomponent absorbers. Such an outstanding microwave absorption performance stems from the unique hierarchical yolk–shell structure and the designable interspaces, leading to the multiple scattering, interfacial polarization, and plasma dielectric oscillation from the abundant interfaces and curved surfaces, which can be illustrated by the related results from electron holography and electron energy loss spectroscopy. To the best of our knowledge, the “Matryoshka doll”-like CeO₂ microspheres with a facile synthesis process, low cost, and excellent microwave absorption performance are believed to be an optimal candidate of single-component absorbers and helpful in the study of absorption mechanism

Organic Solar Cells Based on WO2.72 Nanowire Anode Buffer Layer with Enhanced Power Conversion Efficiency and Ambient Stability

Tungsten oxide as an alternative to conventional acidic PEDOT:PSS has attracted much attention in organic solar cells (OSCs). However, the vacuum-processed WO₃ layer and high-temperature sol–gel hydrolyzed WO_X are incompatible with large-scale manufacturing of OSCs. Here, we report for the first time that a specific tungsten oxide WO_2.72 (W₁₈O₄₉) nanowire can function well as the anode buffer layer. The nw-WO_2.72 film exhibits a high optical transparency. The power conversion efficiency (PCE) of OSCs based on three typical polymer active layers PTB7:PC₇₁BM, PTB7-Th:PC₇₁BM, and PDBT-T1:PC₇₁BM with nw-WO_2.72 layer were improved significantly from 7.27 to 8.23%, from 8.44 to 9.30%, and from 8.45 to 9.09%, respectively compared to devices with PEDOT:PSS. Moreover, the photovoltaic performance of OSCs based on small molecule <i>p</i>-DTS­(FBTTh₂)₂:PC₇₁BM active layer was also enhanced with the incorporation of nw-WO_2.72. The enhanced performance is mainly attributed to the improved short-circuit current density (<i>J</i>_sc), which benefits from the oxygen vacancies and the surface apophyses for better charge extraction. Furthermore, OSCs based on nw-WO_2.72 show obviously improved ambient stability compared to devices with PEDOT:PSS layer. The results suggest that nw-WO_2.72 is a promising candidate for the anode buffer layer materials in organic solar cells

Arginine methylation of PPP1CA by CARM1 regulates glucose metabolism and affects osteogenic differentiation and osteoclastic differentiation

Abstract Background The imbalance between osteoblasts and osteoclasts may lead to osteoporosis. Osteoblasts and osteoclasts have different energy requirements, with aerobic glycolysis being the prominent metabolic feature of osteoblasts, while osteoclast differentiation and fusion are driven by oxidative phosphorylation. Methods By polymerase chain reaction as well as Western blotting, we assayed coactivator‐associated arginine methyltransferase 1 (CARM1) expression in bone tissue, the mouse precranial osteoblast cell line MC3T3‐E1 and the mouse monocyte macrophage leukaemia cell line RAW264.7, and expression of related genes during osteogenic differentiation and osteoclast differentiation. Using gene overexpression (lentivirus) and loss‐of‐function approach (CRISPR/Cas9‐mediated knockout) in vitro, we examined whether CARM1 regulates osteogenic differentiation and osteoblast differentiation by metabolic regulation. Transcriptomic assays and metabolomic assays were used to find the mechanism of action of CARM1. Furthermore, in vitro methylation assays were applied to clarify the arginine methylation site of PPP1CA by CARM1. Results We discovered that CARM1 reprogrammed glucose metabolism in osteoblasts and osteoclasts from oxidative phosphorylation to aerobic glycolysis, thereby promoting osteogenic differentiation and inhibiting osteoclastic differentiation. In vivo experiments revealed that CARM1 significantly decreased bone loss in osteoporosis model mice. Mechanistically, CARM1 methylated R23 of PPP1CA, affected the dephosphorylation of AKT‐T450 and AMPK‐T172, and increased the activities of phosphofructokinase‐1 and pructose‐2,6‐biphosphatase3, causing an up‐regulation of glycolytic flux. At the same time, as a transcriptional coactivator, CARM1 regulated the expression of pyruvate dehydrogenase kinase 3, which resulted in the inhibition of pyruvate dehydrogenase activity and inhibition of the tricarboxylic acid cycle, leading to a subsequent decrease in the flux of oxidative phosphorylation. Conclusions These findings reveal for the first time the mechanism by which CARM1 affects both osteogenesis and osteoclast differentiation through metabolic regulation, which may represent a new feasible treatment strategy for osteoporosis

Cortistatin prevents glucocorticoid-associated osteonecrosis of the femoral head via the GHSR1a/Akt pathway

Abstract Long-term use of glucocorticoids (GCs) is known to be a predominant cause of osteonecrosis of the femoral head (ONFH). Moreover, GCs can mediate apoptosis of various cell types by exaggerating oxidative stress. We have previously found that Cortistatin (CST) antagonizes oxidative stress and improves cell apoptosis in several conditions. In this study, we detected that the CST expression levels were diminished in patients with ONFH compared with femoral neck fracture (FNF). In addition, a GC-induced rat ONFH model was established, which impaired bone quality in the femoral head. Then, administration of CST attenuated these ONFH phenotypes. Furthermore, osteoblast and endothelial cells were cultured and stimulated with dexamethasone (Dex) in the presence or absence of recombinant CST. As a result, Dex induced impaired anabolic metabolism of osteoblasts and suppressed tube formation in endothelial cells, while additional treatment with CST reversed this damage to the cells. Moreover, blocking GHSR1a, a well-accepted receptor of CST, or blocking the AKT signaling pathway largely abolished the protective function of CST in Dex-induced disorder of the cells. Taken together, we indicate that CST has the capability to prevent GC-induced apoptosis and metabolic disorder of osteoblasts in the pathogenesis of ONFH via the GHSR1a/AKT signaling pathway