Complement receptor 4 mediates the clearance of extracellular tau fibrils by microglia.

Tauopathies exhibit a characteristic accumulation of misfolded tau aggregates in the brain. Tau pathology shows disease-specific spatiotemporal propagation through intercellular transmission, which is closely correlated with the progression of clinical manifestations. Therefore, identifying molecular mechanisms that prevent tau propagation is critical for developing therapeutic strategies for tauopathies. The various innate immune receptors, such as complement receptor 3 (CR3) and complement receptor 4 (CR4), have been reported to play a critical role in the clearance of various extracellular toxic molecules by microglia. However, their role in tau clearance has not been studied yet. In the present study, we investigated the role of CR3 and CR4 in regulating extracellular tau clearance. We found that CR4 selectively binds to tau fibrils but not to tau monomers, whereas CR3 does not bind to either of them. Inhibiting CR4, but not CR3, significantly reduces the uptake of tau fibrils by BV2 cells and primary microglia. By contrast, inhibiting CR4 has no effect on the uptake of tau monomers by BV2 cells. Furthermore, inhibiting CR4 suppresses the clearance of extracellular tau fibrils, leading to more seed-competent tau fibrils remaining in the extracellular space relative to control samples. We also provide evidence that the expression of CR4 is upregulated in the brains of human Alzheimer's disease patients and the PS19 mouse model of tauopathy. Taken together, our data strongly support that CR4 is a previously undescribed receptor for the clearance of tau fibrils in microglia and may represent a novel therapeutic target for tauopathy.

3D Printing of dynamic tissue scaffold by combining self-healing hydrogel and self-healing ferrogel.

Hydrogels have been widely utilized in tissue engineering applications as functional and biological synthetic extracellular matrices (ECMs) can be created with gels. However, typical hydrogels cannot be exploited in 3D printing, especially in extrusion printing, unless post-cross-linking after printing is provided. Additionally, dynamic tissue scaffolds that can mimic ECM environments in the body have been demonstrated to be useful in tissue engineering. Here, we hypothesized that a 3D-printed dynamic tissue scaffold could be fabricated by combining self-healing hydrogel and self-healing ferrogel without post-cross-linking, which could be useful for the regulation of cell phenotype under magnetic stimulation. Hydrogels were formed from oxidized sodium hyaluronate and glycol chitosan, and adipic acid dihydrazide was additionally utilized for self-healing behavior of the gel. Superparamagnetic iron oxide nanoparticles (SPIONs) were also used to prepare a magnetically responsive hydrogel system (i.e., ferrogel). Physicochemical properties, cytotoxicity, and printability of the self-healing hydrogel/ferrogel system fabricated by a 3D printing process, were investigated. Dimensional changes in a tissue scaffold were achieved by the application of a magnetic field. Interestingly, chondrogenic differentiation of ATDC5 cells cultured within the dynamic tissue scaffold was enhanced by applying a magnetic field in vitro. This approach may be useful for fabricating dynamic tissue scaffolds by a 3D printing method for tissue engineering applications.

3D printing of self-healing ferrogel prepared from glycol chitosan, oxidized hyaluronate, and iron oxide nanoparticles.

Hydrogel systems that show self-healing ability after mechanical damage are receiving increasing attention. However, self-healing hydrogels suitable for biomedical applications are limited owing to complex preparation methods. Furthermore, few studies have demonstrated the self-healing property of ferrogels. In this study, we demonstrated that glycol chitosan (GC) and oxidized hyaluronate (OHA) can be used to form a self-healing ferrogel in the presence of superparamagnetic iron oxide nanoparticles (SPIONs) without additional chemical cross-linkers. The overall characteristics of GC/OHA/SPION ferrogel varied based on the GC/OHA ratio, SPION content, and total polymer concentration. Interestingly, GC/OHA/SPION ferrogel was used to fabricate 3D-printed constructs of various shapes via an extrusion printing method. These constructs were responsive to the magnetic field, suggesting their potential application in 4D printing. This approach to developing self-healing ferrogels with biocompatible polysaccharides may prove useful in designing and fabricating drug delivery systems and tissue engineering scaffolds, via 3D printing.

Origin of macroscopic adhesion in organic light-emitting diodes analyzed at different length scales.

Organic light-emitting diodes (OLEDs) have been widely studied because of their various advantages. OLEDs are multi-layered structures consisting of organic and inorganic materials arranged in a heterojunction; the nature of adhesion at their heterogeneous interfaces has a significant effect on their properties. In this study, the origin of macroscopic adhesion was explored in OLEDs using a combination of microscopy techniques applied at different length scales. The different techniques allowed the identification of layers exposed by a peel test, which aided direct characterization of their macroscopic adhesion. Further, the contribution of each exposed layer to macroscopic adhesion could be determined through an analysis of photographic images. Finally, analysis of the local roughness and adhesion confirmed that the interface between an anode and emission layer could play a predominant role in determining the nature of macroscopic adhesion in OLEDs. These results may provide guidelines for exploring the origin of macroscopic adhesion properties through a combination of various microscopy techniques.

A 12-week rehabilitation program improves body composition, pain sensation, and internal/external torques of baseball pitchers with shoulder impingement symptom.

The aim of this study was to investigate the effects of a 12-week rehabilitation program on body composition, shoulder pain, and isokinetic internal/external torques of pitchers with impingement syndrome. A total of 30 pitchers were divided into 2 groups: experimental group (EG, n = 16) and control group (CG, n= 14). The rehabilitation program consisted of physical therapy, warm-up, work-out, and cool-down. As results, body weight and fat mass of EG were decreased whereas muscle mass of EG was significantly increased after the experiment. The pain degrees in resting, normal daily activity, and strenuous activity on the numeric pain rating scale were significantly decreased in the EG. The internal and external peak torques (PTs) of uninvolved and involved sides of EG were increased in EG after 12 weeks. Such results provide a deficit ratio of both sides in EG close to normal values. The ratios of internal/external PTs in EG were also close to the reference values. The internal and external total works of both sides in EG were similar to the values of PT. The fatigue indices of internal and external rotators of both sides in EG were decreased. As a conclusion, a 12-week rehabilitation program reduced the shoulder pain, improved the body composition and enhanced the isokinetic shoulder internal/external rotators in EG with impingement symptoms. Also the study suggested that the rehabilitation program evened out the ratio between internal and external rotators and lowered the fatigue level after the experiment.