Id2 promotes the invasive growth of MCF-7 and SKOV-3 cells by a novel mechanism independent of dimerization to basic helix-loop-helix factors

<p>Abstract</p> <p>Background</p> <p>Inhibitor of differentiation 2 (<it>Id2</it>) is a critical factor for cell proliferation and differentiation in normal vertebrate development. Most of the biological function of Id2 has been ascribed to its helix-loop-helix motif. Overexpression of Id2 is frequently observed in various human tumors, but its role for invasion potential in tumor cells is dispute. We aimed to reveal the role of Id2 in invasion potential in poorly invasive and estrogen receptor α (ERα)-positive MCF-7 and SKOV-3 cancer cells.</p> <p>Methods</p> <p>MCF-7 and SKOV-3 cells were stably transfected with the wild-type, degradation-resistant full-length or helix-loop-helix (HLH)-deleted Id2, respectively. Protein levels of Id2 and its mutants and E-cadherin were determined by western blot analysis and mRNA levels of Id2 and its mutants were determined by RT-PCR. The effects of Id2 and its mutants on cell proliferation were determined by [³H]-thymidine incorporation assay and the 3- [4, 5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) dye method. The <it>in vitro </it>invasion potential of cells was evaluated by Transwell assay. Cell motility was assessed by scratch wound assay. The promoter activity of <it>E-cadherin </it>was determined by cotransfection and luciferase assays.</p> <p>Results</p> <p>Ectopic transfection of the wild-type Id2 markedly increased the protein and mRNA expression of <it>Id2 </it>in MCF-7 and SKOV-3 cells; the protein level but not mRNA level was further increased by transfection with the degradation-resistant Id2 form. The ectopic expression of Id2 or its mutants did not alter proliferation of either MCF-7 or SKOV-3 cells. Transfection of the wild-type Id2 significantly induced the invasion potential and migratory capacity of cells, which was further augmented by transfection with the degradation-resistant full-length or HLH-deleted Id2. E-cadherin protein expression and transactivation of the proximal E-cadherin promoter were markedly suppressed by the degradation-resistant full-length or HLH-deleted Id2 but not wild-type Id2. Ectopic expression of E-cadherin in MCF-7 and SKOV-3 cells only partially blunted the invasion potential induced by the degradation-resistant HLH-deleted Id2.</p> <p>Conclusion</p> <p>Overexpression of Id2 in ERα-positive epithelial tumor cells indeed increases the cells' invasive potential through a novel mechanism independent of dimerization to basic helix-loop-helix factors. E-cadherin contributes only in part to Id2-induced cell invasion when Id2 is accumulated to a higher level in some specific cell types.</p

Optimal wholesale price and technological innovation under dual credit policy on carbon emission reduction in a supply chain

The adoption of new energy vehicles (NEVs) can effectively reduce vehicle exhaust emissions and achieve carbon peaking and carbon neutrality goals in the transportation sector. To facilitate the development of NEVs, the Chinese government issued the dual credit policy (DCP). However, whether the DCP can promote the technological innovation of NEVs and effectively reduce carbon emissions in the transportation sector remains to be studied. This study constructed the decision-making model of NEVs under the DCP and obtained the optimal strategy to study the impact of the DCP on carbon emissions. Furthermore, we constructed a bargaining game model based on an alliance strategy to demonstrate the coordination of the NEV supply chain. The results showed that implementing the DCP can effectively reduce carbon emissions in the transportation field. The higher the technological innovation credit coefficient or credit price, the more significant the DCP’s incentive effect on reducing carbon emissions. Decentralized decision-making weakens the DCP’s incentive effect on reducing carbon emissions. The bargaining game based on alliance negotiation can enable independent companies to achieve carbon emission reduction when making centralized decisions so that the DCP’s incentive effect on reducing carbon emissions is optimized. The alliance between manufacturers is not to increase profits but to enhance their product advantages. However, suppliers can gain higher profits by participating in the alliance, which provides a theoretical reference for the alliance’s cooperation in decision-making

Effect of implant placement depth on the peri-implant bone defect configurations in ligature-induced peri-implantitis : an experimental study in dogs

The subcrestal placement of implant platform has been considered a key factor in the preservation of crestal bone, but the influence of implant placement depth on bone remodeling combined with peri-implantitis is not fully understood. The aim of this study was to assess the effect of the crestal or subcrestal placement of implants on peri-implant bone defects of ligature-induced peri-implantitis in dogs. Eight weeks after tooth extraction in six beagle dogs, two different types of implants (A: OsseoSpeed?, Astra, Mölndal, Sweden; B: Integra-CP?, Bicon, Boston, USA) were placed at either crestal or subcrestal (-1.5 mm) positions on one side of the mandible. Ligature-induced peri-implantitis was initiated four weeks after the installation of the healing abutment connections. After 12 weeks, tissue biopsies were processed for histological analyses. Supra-alveolar bone loss combined with a shallow infrabony defect was observed in crestal level implants while deep and wide infrabony defects were present in subcrestal level groups. Subcrestal groups showed significantly greater ridge loss, depths and widths of infrabony defects when compared to crestal groups (P<0.001). Within the limitations of the animal study, it can be stated that the implants at subcrestal position displayed greater infra-osseous defect than implants at crestal position under an experimental ligature-induced peri-implantitis

Electric-field Control of Magnetism with Emergent Topological Hall Effect in SrRuO3 through Proton Evolution

Ionic substitution forms an essential pathway to manipulate the carrier density and crystalline symmetry of materials via ion-lattice-electron coupling, leading to a rich spectrum of electronic states in strongly correlated systems. Using the ferromagnetic metal SrRuO3 as a model system, we demonstrate an efficient and reversible control of both carrier density and crystalline symmetry through the ionic liquid gating induced protonation. The insertion of protons electron-dopes SrRuO3, leading to an exotic ferromagnetic to paramagnetic phase transition along with the increase of proton concentration. Intriguingly, we observe an emergent topological Hall effect at the boundary of the phase transition as the consequence of the newly-established Dzyaloshinskii-Moriya interaction owing to the breaking of inversion symmetry in protonated SrRuO3 with the proton compositional film-depth gradient. We envision that electric-field controlled protonation opens a novel strategy to design material functionalities

Obstacle Avoidance of Semi-Trailers Based on Nonlinear Model Predictive Control

Obstacle avoidance is a core part of the autonomous driving of off-road vehicles, such as semi-trailers. Due to the long length of semi-trailers, the traditional obstacle avoidance controller based on the circumcircle model can ensure that there is no collision between the semi-trailer and the obstacle, but it also greatly reduces the passable area. To solve this problem, we propose a new obstacle avoidance model. In this model, the distance between the obstacle and the middle line of semi-trailers is used as the indicator of obstacle avoidance. Based on this model, we design a new obstacle avoidance controller for semi-trailers. The simulation results show that the proposed controller can ensure that no collision occurs between the semi-trailer and the obstacle. The minimum distance between the obstacle center and the semi-trailer body trajectory is greater than the sum of the obstacle radius and the safety margin. Compared with the traditional obstacle avoidance controller based on the circumcircle model, the proposed controller greatly reduces the error between the semi-trailer and the reference path during obstacle avoidance. Document type: Articl