Search

Notum, which belongs to the α/β hydrolase family, is a deacylated extracellular protein that regulates the Wnt signaling pathway. Studies have found that Notum participates in the progression of colorectal cancer and hepatocellular carcinoma, but its role in oral squamous cell carcinoma (OSCC) is currently unclear. This study aimed to explore the role of Notum in regulating OSCC and further reveal the underlying mechanisms. Various approaches including bioinformatics analysis, enzyme-linked immunosorbent assay and immunohistochemical staining were used to detect the expression of Notum in OSCC cells and tissues. Cell counting kit-8 assay, clone formation assay, wound healing assay, transwell assay and in-gel zymography assay were explored to evaluate the regulation of Notum in OSCC proliferation and migration. Hoechst 33342/PI assay, cell immunofluorescence, flow cytometry and in vivo tumorigenesis experiment were applied for OSCC apoptosis. Real-time quantitative polymerase chain reaction analysis was performed for mRNA level while western blotting was conducted to detect protein expression. The results showed that Notum was highly expressed in OSCC tissues and cells, and Notum promoted the proliferation and migration of OSCC cells while it inhibited their apoptosis. Furthermore, signaling pathway analysis showed that Notum led to potential pro-survival of OSCC through crosstalk between sonic hedgehog (Shh) and Wnt/β-catenin signaling via phosphorylation of glycogen synthase kinase-3 beta. These results will help to elucidate the mechanism and also provide new ideas for targeted treatment of OSCC. [ABSTRACT FROM AUTHOR]

Abstract: We in-detail investigated the profile evolution processes of highly ordered alumina under the cyclic treatment of mild anodizing of aluminum foils in oxalic acid followed by etching in phosphoric acid. With the cyclic times increasing, the profiles of nanopores were gradually evolved into the parabola-like, trumpet-like and conical shape. Although the inserted etching itself nearly had no impact on the growth rate of the nanopores due to the rapid recovering of thinned barrier layer at the initial stage of next anodizing, overmuch etching could bring apparent side effects such as wall-breaking, thinning and taper-removing from the top down. The anodizing and etching kinetics and their synergetic effects in modulating different aspect ratios and open sizes of conical pores were studied systematically. These findings are helpful to tailor high-quality anodic alumina taper-pores with tunable profiles. [Copyright &y& Elsevier]

• The polypeptide OP 3-4 promoted bone regeneration of mandibular defect. • OP 3-4 improved osteogenic differentiation of bone marrow mesenchymal stem cells. • OP 3-4 promoted osteogenic differentiation by AKT/GSK3β/β-catenin pathway. The aims of this study were to explore: (ⅰ) the effect of the polypeptide OP 3-4 on bone regeneration in vivo ; (ⅱ) the effect of OP 3-4 on osteogenic differentiation of bone marrow mesenchymal stem cells in vitro ; and (ⅲ) the potential mechanism of OP 3-4 in promoting osteogenic differentiation of bone marrow mesenchymal stem cells. 30 Wistar rats (8-week, male) were randomly divided into Control group (n = 5), Hydrogel group (n = 5), and Hydrogel loaded OP 3-4 group (n = 5). Hematoxylin and eosin staining was used to evaluate the level of bone regeneration in mandibular defect. Immunohistochemistry staining was used to evaluate the expression of alkaline phosphatase, runt-related transcription factor 2, and type Ⅰ collagen. Flow cytometry was applied to identify the phenotype of bone marrow mesenchymal stem cells. Furthermore, LY294002, the inhibitor of protein kinase B, was applied to verify the role of OP 3-4 in promoting osteogenic differentiation via protein kinase B/glycogen synthase kinase 3β/β-catenin pathway through western blot. OP 3-4 promoted bone regeneration of rat mandibular defect. The expression of osteogenic differentiation related markers were increased after adding OP 3-4 to bone marrow mesenchymal stem cells. OP 3-4 promoted osteogenic differentiation of bone marrow mesenchymal stem cells via protein kinase B/glycogen synthase kinase 3β/β-catenin pathway. OP 3-4 could promote bone regeneration of mandibular defect and improve osteogenic differentiation through protein kinase B/glycogen synthase kinase 3β/β-catenin pathway. [ABSTRACT FROM AUTHOR]

• Notum expression increased in gingival tissues. • Notum expression increased in periodontal ligament. • Notum inhibited human periodontal ligament stem cell (hPDLSC) osteogenesis. • Notum regulated hPDLSC osteogenesis through Wnt/beta-catentin signaling. The aims of this study were to explore: (ⅰ) the effect of Notum on periodontitis in vivo ; (ⅱ) the effect of Notum on the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) in vitro ; and (ⅲ) the potential mechanism of Notum in inhibiting the osteogenic differentiation of hPDLSCs. C57BL/6J mice were randomly assigned into two groups: control group (n = 4) and periodontitis group (n = 4). Immunohistochemical staining was used to evaluate the expression of Notum. In in vitro experiments, Western blot, qRT- PCR and ELISA were used to examine the expression of Notum in a lipopolysaccharide-induced inflammation model. Alkaline phosphatase staining was used to evaluate alkaline phosphatase activity. Western blot and qRT - PCR were used to measure the expression of osteogenic-related markers after adding human recombinant Notum and Notum inhibitor ABC99. In addition, LiCl, an agonist of the Wnt/Beta-catenin signaling pathway, was added to explore using Western blot whether Notum was involved in regulating the osteogenic differentiation of human periodontal ligament stem cells through the Wnt/Beta-catenin signaling pathway. Notum was highly expressed in periodontal tissues of mice and lipopolysaccharide-induced inflammation cell model. The protein and messenger ribonucleic acid levels of hPDLSCs osteogenic markers were reduced after adding human recombinant Notum. However, the inhibitory effect of Notum on the osteogenic differentiation of hPDLSCs could be significantly reversed by adding LiCl. These results demonstrated that Notum inhibited the osteogenic differentiation of hPDLSCs probably via the Wnt/Beta-catenin the downstream signaling pathway. [ABSTRACT FROM AUTHOR]

• A coordinated restoration model is proposed for power-gas-transportation distribution systems. • Repair crews and energy hubs are simultaneously optimized to enhance post-disaster resilience. • Spatial interdependency between power-gas systems and transportation systems is considered to ensure the feasibility of the obtained restoration decisions. • Modified Boolean logic equations are proposed to represent the spatial interdependency. Recently, extreme events have caused widespread blackouts over energy systems. In addition, the increasing interactions between power distribution networks and natural gas networks bring new challenges to the fast recovery of energy systems. Mobile emergency resources, such as repair crews (RCs), play an essential role in the restoration. However, power distribution networks and gas networks have geographical correlations with transportation systems in urban areas, therefore, there exists spatial interdependency between infrastructural systems. This property results in the dependency between RCs' routings and road states in transportation systems. To this end, this paper proposes a sequential restoration model for power-gas-transportation distribution networks. The post-disaster restoration model contains the dispatch of both RCs and fixed resources. The spatial interdependency is modeled by modified Boolean logic equations to obtain feasible recovery schedules in practice. Convex relaxations and linearization methodologies are utilized to transform the proposed model into a mixed-integer second-order cone programming (MISOCP) model. Simulations are carried out on 33–14–20 and 136–20–39 bus coupled systems. Numerical results indicate that the proposed restoration strategy could increase the post-disaster resilience index by 19.5 % in 33-bus power system, 8.7 % in 136-bus power system, 25.6 % in 14-node gas system, and 27.2 % in 20-node gas system, respectively. [ABSTRACT FROM AUTHOR]

Eldecalcitol (ED-71) is a new type of vitamin D analog, and vitamin D has been reported to have therapeutic effects in infectious disease, autoimmune disease, and cancer. However, the anti-cancer effect of ED-71 remains unclear. The objective of this study was to explore the anti-cancer effect of ED-71 in human osteosarcoma cells and to identify the related mechanism. The CCK8 assay results showed that ED-71 inhibited MG-63 cell viability in dose and time dependent manners. Cloning and Transwell invasion assays showed that ED-71 inhibited clonal and invasion ability of MG-63 cells. Flow cytometry results showed ED-71 the G2/M cycle arrest rate, apoptosis, and intracellular ROS. Western blot was used to detect cleaved-caspase-3, Bax, Bcl-2, LC3-II/LC3-I, and P62 levels and the mTOR pathway. The increase of LC3-II and P62 indicated that ED-71 induced the formation of autophagosomes and inhibited autophagy flux. Furthermore, ED-71-induced apoptosis was weakened after adding 3-methyladenine and ED-71-induced early autophagy was weakened by caspase-3 inhibitor (Z -VAD-FMK), which indicated the two processes active each other in the presence of ED-71. Furthermore, N-acetylcysteine (NAC) pretreatment reversed the ED-71-treatment outcomes, including increased apoptosis and autophagy and inhibition of the PI3K/Akt/mTOR pathway. In conclusion, our results reveal that ED-71 induced G2/M arrest, apoptosis and autophagy in MG-63 cells by accumulating ROS to suppress the PI3K/Akt/mTOR signaling pathway • ED-71 induced early autophagy and apoptosis in MG-63 cells. • Autophagy induced by ED-71 lead to cell death rather than survival by inducing apoptosis. • Autophagy and apoptosis induced by ED-71 promoted each other. • Autophagy and apoptosis induced by ED-71 were regulated by accumulating ROS to suppress the PI3K/Akt/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Aldol condensation between furfural (FA) and MIBK is used to synthesize branched bio-jet-fuel precursors. It remains difficult to design hybrid solid bases to efficiently promote this reaction, because only strong basic sites can activate MIBK. Different basic species were immobilized into zirconia/carbon hybrid supports by thermal decomposition of GO/UiO materials loaded with corresponding alkane (earth) nitrides. Only Cs immobilized zirconia/carbon (CsZC) could efficiently promote this reaction, while counterparts with Li, Mg and Ca species showed little activity over condensation between MIBK and FA. Optimized CsZC showed excellent FA conversion and selectivity towards desired products (88.6% in yields of FMIBK in 6 h at 130 °C). Two indirect proofs were provided to check the influence of basic strength on the catalytic performance, and only Cs samples had enough strong basic sites to accelerate the reaction. After modified with octyl groups, hydrophobic CsZC were reused for 4th cycle while retaining most of its original activity. Functionalization with organosilanes increased the hydrophobicity of the surface, which had dramatical promotion on activity, selectivity, and stability. It was the first time to run recycling experiments for this reaction, to afford the demands for chemical sustainability. Cs immobilized zirconia/carbon hybrid solid bases (CsZC) were synthesized by thermal decomposition of CsNO 3 loaded GO/zirconium MOFs. CsZC could efficiently catalyze aldol condensation of furfural and MIBK to produce bio-jet-fuel precursors, and catalytic stability was greatly promoted by hydrophobic modification of CsZC with octyl groups. Unlabelled Image [ABSTRACT FROM AUTHOR]