Oral pathogen aggravates atherosclerosis by inducing smooth muscle cell apoptosis and repressing macrophage efferocytosis

Periodontitis imparting the increased risk of atherosclerotic cardiovascular diseases is partially due to the immune subversion of the oral pathogen,particularly the Porphyromonas gingivalis(P.gingivalis),by inducing apoptosis.However,it remains obscure whether accumulated apoptotic cells in P.gingivalis-accelerated plaque formation are associated with impaired macrophage clearance.

Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells promote alveolar bone regeneration by regulating macrophage polarization

Alveolar bone regeneration has been strongly linked to macrophage polarization.M1 macrophages aggravate alveolar bone loss,whereas M2 macrophages reverse this process.Berberine(BBR),a natural alkaloid isolated and refined from Chinese medicinal plants,has shown therapeutic effects in treating metabolic disorders.In this study,we first discovered that culture supernatant(CS)collected from BBR-treated human bone marrow mesenchymal stem cells(HBMSCs)ameliorated periodontal alveolar bone loss.CS from the BBR-treated HBMSCs contained bioactive materials that suppressed the M1 polarization and induced the M2 polarization of macrophages in vivo and in vitro.To clarify the underlying mechanism,the bioactive materials were applied to different animal models.We discovered macrophage colony-stimulating factor(M-CSF),which regulates macrophage polarization and promotes bone formation,a key macromolecule in the CS.Injection of pure M-CSF attenuated experimental periodontal alveolar bone loss in rats.Colony-stimulating factor 1 receptor(CSF1R)inhibitor or anti-human M-CSF(M-CSF neutralizing antibody,Nab)abolished the therapeutic effects of the CS of BBR-treated HBMSCs.Moreover,AKT phosphorylation in macrophages was activated by the CS,and the AKT activator reversed the negative effect of the CSF1R inhibitor or Nab.These results suggest that the CS of BBR-treated HBMSCs modulates macrophage polarization via the M-CSF/AKT axis.Further studies also showed that CS of BBR-treated HBMSCs accelerated bone formation and M2 polarization in rat teeth extraction sockets.Overall,our findings established an essential role of BBR-treated HBMSCs CS and this might be the first report to show that the products of BBR-treated HBMSCs have active effects on alveolar bone regeneration.

Ultimate dielectric scaling of 2D transistors via van der Waals metal integration

The two-dimensional transition metal dichalcogenides(TMDs)have attracted intense interest as an atomically thin semiconductor channel for the continued transistor scaling.However,with a dangling bond free surface,it has been a key challenge to reliably integrate high-quality gate dielectrics on TMDs.In particular,the atomic layer deposition of dielectrics on TMDs typically features highly non-uniform nucleation and produces a highly rough or porous dielectric film with rich pinholes that are prone to further damage during the gate integration process.Herein we report a van der Waals(vdW)integration route towards highly reliable gate metal integration on porous dielectrics.The physical lamination process employed by the vdW integration avoids the direct deposition of metal electrodes into porous dielectrics to ensure reliable gate integration and produce low gate leakage devices.The electrical measurements demonstrate the vdW integrated MoS_(2) top gate devices exhibit substantially reduced gate leakage current that is about 3-5 orders of magnitude smaller than that with deposited metal electrodes.Furthermore,we show the vdW integration process can be used to create high performance top-gated MoS_(2) transistors with ultrathin Al_(2)O_(3) dielectrics down to 1 nm,representing the ultimate dielectric scaling for TMDs transistors.This study demonstrates that vdW integration can enable highly reliable gate integration on relatively low quality dielectrics on TMDs,and opens an interesting pathway to high-performance top-gate transistors using dangling bond free two-dimensional(2D)semiconductors.