Porphyromonas gingivalis bacteremia increases the permeability of the blood-brain barrier via the Mfsd2a/Caveolin-1 mediated transcytosis pathway.

Bacteremia induced by periodontal infection is an important factor for periodontitis to threaten general health. P. gingivalis DNA/virulence factors have been found in the brain tissues from patients with Alzheimer's disease (AD). The blood-brain barrier (BBB) is essential for keeping toxic substances from entering brain tissues. However, the effect of P. gingivalis bacteremia on BBB permeability and its underlying mechanism remains unclear. In the present study, rats were injected by tail vein with P. gingivalis three times a week for eight weeks to induce bacteremia. An in vitro BBB model infected with P. gingivalis was also established. We found that the infiltration of Evans blue dye and Albumin protein deposition in the rat brain tissues were increased in the rat brain tissues with P. gingivalis bacteremia and P. gingivalis could pass through the in vitro BBB model. Caveolae were detected after P. gingivalis infection in BMECs both in vivo and in vitro. Caveolin-1 (Cav-1) expression was enhanced after P. gingivalis infection. Downregulation of Cav-1 rescued P. gingivalis-enhanced BMECs permeability. We further found P. gingivalis-gingipain could be colocalized with Cav-1 and the strong hydrogen bonding between Cav-1 and arg-specific-gingipain (RgpA) were detected. Moreover, P. gingivalis significantly inhibited the major facilitator superfamily domain containing 2a (Mfsd2a) expression. Mfsd2a overexpression reversed P. gingivalis-increased BMECs permeability and Cav-1 expression. These results revealed that Mfsd2a/Cav-1 mediated transcytosis is a key pathway governing BBB BMECs permeability induced by P. gingivalis, which may contribute to P. gingivalis/virulence factors entrance and the subsequent neurological impairments.

The Effects of Porphyromonas gingivalis on Inflammatory and Immune Responses and Osteogenesis of Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) are increasingly used in tissue regeneration, not only because of their multilineage differentiation ability, but also because of their immunomodulatory function, which allows them to play a role in the inflammatory milieu, especially in periodontitis. Porphyromonas gingivalis (P. gingivalis) is an important pathogen associated with the progression of periodontitis. Heterogeneous MSC sources show differences in their inflammatory-immune responsiveness and osteogenesis capabilities when exposed to P. gingivalis and its virulence factors. This article reviews the promoted inflammatory and immune responses of periodontal ligament stem cells, which are potential pitfalls in bone regeneration. MSCs from other sources showed contradictory inflammatory and immune reactions in the few studies on this topic. We also summarize the mechanisms involved in the inflammatory, immune responses and osteogenic potential of MSCs exposed to P. gingivalis and its virulence factors to inform an improved utilization of MSCs in regenerative therapies for periodontitis.

Damage Detection in Active Suspension Bridges: An Experimental Investigation.

This paper considers a Hilbert marginal spectrum-based approach to health monitoring of active suspension bridge hangers. The paper proposes to takes advantage of the presence of active cables and use them as an excitation mean of the bridge, while they are used for active damping. The Hilbert⁻Huang transform is used to calculate the Hilbert marginal spectrum and establish a damage index for each hanger of the suspension bridge. The paper aims to investigate the method experimentally, through a series of damage scenarios, on a laboratory suspension bridge mock-up equipped with four active cables; each active cable is made of a displacement actuator collocated with a force sensor. Different locations and levels of damage severity are implemented. For the first time, the investigation demonstrates experimentally the effectiveness of the technique, as well as its limitations, to detect and locate the damage in hangers of a suspension bridge.

An Analytical Approach for Synthesizing Line Actuation Spaces of Parallel Flexure Mechanisms.

In this study, we present an analytical approach for synthesizing line actuation spaces of a parallel flexure mechanism (PFM) that can help designers to arrange linear actuators within the PFM in a correct and optimal way. On the basis of screw theory and upon an assumption of small deformations, an important synthesis criterion stated as "any actuation space of a flexure mechanism is always linearly independent of its constraint space" has been derived and disclosed for the first time. Guided by this criterion, a general synthesis process for the line actuation spaces of PFMs is introduced and demonstrated with several selective examples. The proposed synthesis criterion and process will enable designers to (i) systematically formulate line actuation spaces in the format of screw systems; (ii) likely yield a multiple solution to actuation spaces; and (iii) potentially determine an optimal result from those alternatives for actuator placement.

A Symbolic Formulation for Analytical Compliance Analysis and Synthesis of Flexure Mechanisms.

This paper presents a symbolic formulation for analytical compliance analysis and synthesis of flexure mechanisms with serial, parallel, or hybrid topologies. Our approach is based on the screw theory that characterizes flexure deformations with motion twists and loadings with force wrenches. In this work, we first derive a symbolic formulation of the compliance and stiffness matrices for commonly used flexure elements, flexure joints, and simple chains. Elements of these matrices are all explicit functions of flexure parameters. To analyze a general flexure mechanism, we subdivide it into multiple structural modules, which we identify as serial, parallel, or hybrid chains. We then analyze each module with the known flexure structures in the library. At last, we use a bottom-up approach to obtain the compliance/stiffness matrix for the overall mechanism. This is done by taking appropriate coordinate transformation of twists and wrenches in space. Four practical examples are provided to demonstrate the approach. A numerical example is employed to compare analytical compliance models against a finite element model. The results show that the errors are sufficiently small (2%, compared with finite element (FE) model), if the range of motion is limited to linear deformations. This work provides a systematical approach for compliance analysis and synthesis of general flexure mechanisms. The symbolic formulation enables subsequent design tasks, such as compliance synthesis or sensitivity analysis.