Detection of Novel Biomarkers in Saliva of Rheumatoid Arthritis Model Mice by Proteomics and Pathological Analysis

Rheumatoid arthritis (RA) is an autoimmune disease in which joints are gradually de-stroyed, and early diagnosis and treatment before joint deformation or destruction is im-portant. The detection of novel RA biomarkers in saliva may facilitate the early detection of RA before the onset of disease. In this study, we conducted a comprehensive proteomic analysis of salivary proteins from RA model mice. Proteins were identified by Western blotting and enzyme-linked immunosorbent assay in serum, saliva, and ankle joints from DBA/1JJmsSlc mice, a model of rheumatoid arthritis. Ankle joints and submandibular glands were hematoxylin and eosin stained and immunostained, and the results were compared with those of control mice. Citrullinated α1 antitrypsin (A1AT, 46 kDa) was commonly detected in saliva, serum, and ankle joints of severe RA model mice, and was confirmed by proteome analysis. Western blotting detected a band corresponding to 46 kDa in serum, saliva and ankle joints, and immunostaining of ankle joints with A1AT an-tibody showed a strong positive signal in the synovium. In DBA/1JJmsSlc mice, not only cyclic citrullinated peptide antibodies but also A1AT may be involved in protein citrulli-nation and contribute to the development and severity of RA.

Improving Machining Accuracy for a Robotic Arm with Hybrid Kinematic Chains Based on Deformation Characteristics

The joint deformation has great influence on machining accuracy for a robotic arm. In this paper, the deformation characteristics of the robotic arm with hybrid kinematic chains is investigated in order to improve its machining accuracy. Firstly, the deformation model of the joints has been established based on the Strain energy method and Castigliano theorem according to the robot structure. Secondly, the deformation influence coefficient (DIC) is defined to investigate the deformation influence of main components on the end-effector, and the deformation characteristics are evaluated by the simulation. Finally, a small size robotic arm prototype is established and robotic drilling comparative experiments are conducted. The theoretical and experiment results show that the machining method can be selected according to the DIC, which the force can be applied to the components with better stiffness. On the other hand, the deformation of driving components can also be reduced when the DIC cannot be adjusted to meet the accuracy requirement.

An evolutionarily conserved cis-regulatory element of Nkx3.2 contributes to early jaw joint morphology in zebrafish

The acquisition of movable jaws was a major event during vertebrate evolution. The role of NK3 homeobox 2 (Nkx3.2) transcription factor in patterning the primary jaw joint of gnathostomes (jawed vertebrates) is well known, however knowledge about its regulatory mechanism is lacking. In this study, we report a proximal enhancer element of Nkx3.2 that is deeply conserved in gnathostomes but undetectable in the jawless hagfish. This enhancer is active in the developing jaw joint region of the zebrafish Danio rerio, and was thus designated as jaw joint regulatory sequence 1 (JRS1). We further show that JRS1 enhancer sequences from a range of gnathostome species, including a chondrichthyan and mammals, have the same activity in the jaw joint as the native zebrafish enhancer, indicating a high degree of functional conservation despite the divergence of cartilaginous and bony fish lineages or the transition of the primary jaw joint into the middle ear of mammals. Finally, we show that deletion of JRS1 from the zebrafish genome using CRISPR/Cas9 leads to a transient jaw joint deformation and partial fusion. Emergence of this Nkx3.2 enhancer in early gnathostomes may have contributed to the origin and shaping of the articulating surfaces of vertebrate jaws.

ACTUATION AND MOTION CONTROL OF FLEXIBLE ROBOTS: SMALL DEFORMATION PROBLEM

This paper introduces a new computational approach for the articulated joint/deformation actuation and motion control of robot manipulators with flexible components. Oscillations due to small deformations of relatively stiff robot components can negatively impact the precision and the robot functional operation. Such oscillations, which cannot be ignored, are modeled in this study using the finite element (FE) floating frame of reference (FFR) formulation which employs two coupled sets of coordinates; the reference and elastic coordinates. The inverse dynamics, based on the widely used FFR formulation, leads to driving forces associated with the deformation degrees of freedom. Because of the link flexibility, two approaches can be considered in order to determine the actuation forces required to achieve the desired motion trajectories. These two approaches are the partially-constrained inverse dynamics (PCID) and the fully-constrained inverse dynamics (FCID). The FCID approach, which will be considered in future investigations and allows for motion and shape control, can be used to achieve the desired motion trajectories and suppress undesirable oscillations. The new small-deformation PCID approach introduced in this study, on the other hand, allows for achieving the desired motion trajectories, determining systematically the actuation forces and moments associated with the robot joint and elastic degrees of freedom, and avoiding deteriorations in the vibration characteristics as measured by the differences between the inverse- and forward-dynamics solutions. To this end, a procedure for determining the actuation forces associated with the deformation degrees of freedom is proposed and is exemplified using piezoelectric actuators.

Mucic Acid Loaded Polyethylenimine@Gold Nanoparticles for the Treatment of Rheumatoid Arthritis

Rheumatoid arthritis (RA) could be a common autoimmune disease that involves severe Joint deformation. The main off-target medicines unable to cure RA, that permits associate in nursing infection with the unwellness. The nanomaterials-based RA medical aid is a good strategy to enhance the treatment efficaciousness within the inflammatory region. Specifically, metal-based nanomaterials are a wonderful choice for a possible delivery vehicle for inflammatory disease agents, attributable to their novel properties. Herein, we have got developed a small-sized Polyethylenimine (PEI) coated gold nanoparticles (AuNPs) with an average diameter of 80 nm, that area unit used for top loading of carboxylic acid (MA). Various microscopic and qualitative analysis tools like high-resolution transmission microscopy (HR-TEM), Field-emission scanning microscope (FE-SEM), and Fourier-transform infrared (FTIR) spectroscopic analysis studies were accustomed to make sure as-made PEI-AuNPs. The invented PEI-coated AuNPs (PEI-AuNPs) exhibited higher contrast with an extended expanse that's promising to store giant amounts of MA medicine. MA is attributed to deduce the inflammatory response by inhibiting the pro-inflammatory cytokines and averting undesirable ancient drug aspect effects in Collagen-induced inflammatory disease (CIA). Numerous organic chemistry parameters like weight, hind paw volume, protein estimation, anti-serum protein analysis, and microscopic anatomy examination were conducted in Collagen-induced arthritis mice treated at a dose (10 µg) of MA packed PEI-AuNPs. The obtained results showed the MA-PEI-AuNPs were used with success within the treatment of Collagen-induced arthritis, relative to PEI-AuNPs and MA. Therefore, MA loaded PEI-AuNPs as a stimulating candidate in future RA applications.

Candidates for Intra-Articular Administration Therapeutics and Therapies of Osteoarthritis

Osteoarthritis (OA) of the knee is a disease that significantly decreases the quality of life due to joint deformation and pain caused by degeneration of articular cartilage. Since the degeneration of cartilage is irreversible, intervention from an early stage and control throughout life is important for OA treatment. For the treatment of early OA, the development of a disease-modifying osteoarthritis drug (DMOAD) for intra-articular (IA) injection, which is attracting attention as a point-of-care therapy, is desired. In recent years, the molecular mechanisms involved in OA progression have been clarified while new types of drug development methods based on gene sequences have been established. In addition to conventional chemical compounds and protein therapeutics, the development of DMOAD from the new modalities such as gene therapy and oligonucleotide therapeutics is accelerating. In this review, we have summarized the current status and challenges of DMOAD for IA injection, especially for protein therapeutics, gene therapy, and oligonucleotide therapeutics.

Simulating modular rolling guides elastic properties

Due to high performance characteristics of the modular rolling guides, they are widely used in the contemporary CNC machine designs by major manufacturers. The wrong choice of the guide characteristics can result in excessive cost of guides or maintenance, as well as insufficient rigidity of the machine. Various methods of modular rolling guides elastic properties studying and machine tool structure deformation analysis are known. Most of them are analytical solutions in which the cartridge body and the rail are considered non-deformable. The purpose of this study is to develop a hybrid numerical-analytical model based on the FEM and analytical solution. This approach makes it possible to take into account the joint deformation of bodies (cartridge body, rail, etc.) and contact deformation of the balls and raceways of the guides. The study was carried out in SolidWorks Simulation application. The simulation results correlate with the experimental data well. The displacements of the cartridge have lower values than the values obtained using the FEM model. To evaluate the significance of the model nonlinearity and the possibility of its linearization, a series of calculations of the gear hobbing machine structure elements were performed. The hybrid numerical-analytical model created improves the adequacy of the simulation results.