Self-Assembling Peptide RADA16 Nanofiber Scaffold Hydrogel-Wrapped Concentrated Growth Factors in Osteogenesis of MC3T3.

Concentrated growth factors (CGFs) are widely used in surgery with bone grafting, but the release of growth factors from CGFs is rapid. RADA16, a self-assembling peptide, can form a scaffold that is similar to the extracellular matrix. Based on the properties of RADA16 and CGF, we hypothesized that the RADA16 nanofiber scaffold hydrogel could enhance the function of CGFs and that the RADA16 nanofiber scaffold hydrogel-wrapped CGFs (RADA16-CGFs) would perform a good osteoinductive function. This study aimed to investigate the osteoinductive function of RADA16-CGFs. Scanning electron microscopy, rheometry, and ELISA were performed, and MC3T3-E1 cells were used to test cell adhesion, cytotoxicity, and mineralization after administration with RADA16-CGFs. We found that RADA16 endowed with the sustained release of growth factors from CGFs, which can help maximize the function of CGFs in osteoinduction. The application of the atoxic RADA16 nanofiber scaffold hydrogel with CGFs can be a new therapeutic strategy for the treatment of alveolar bone loss and other problems that require bone regeneration.

Control of multilayer biological networks and applied to target identification of complex diseases.

BACKGROUND: Networks have been widely used to model the structures of various biological systems. The ultimate aim of research on biological networks is to steer biological system structures to desired states by manipulating signals. Despite great advances in the linear control of single-layer networks, it has been observed that many complex biological systems have a multilayer networked structure and extremely complicated nonlinear processes. RESULT: In this study, we propose a general framework for controlling nonlinear dynamical systems with multilayer networked structures by formulating the problem as a minimum union optimization problem. In particular, we offer a novel approach for identifying the minimal driver nodes that can steer a multilayered nonlinear dynamical system toward any desired dynamical attractor. Three disease-related biology multilayer networks are used to demonstrate the effectiveness of our approaches. Moreover, in the set of minimum driver nodes identified by the algorithm we proposed, we confirmed that some nodes can act as drug targets in the biological experiments. Other nodes have not been reported as drug targets; however, they are also involved in important biological processes from existing literature. CONCLUSIONS: The proposed method could be a promising tool for determining higher drug target enrichment or more meaningful steering nodes for studying complex diseases.

Lipidic cubic phase serial millisecond crystallography using synchrotron radiation.

Lipidic cubic phases (LCPs) have emerged as successful matrixes for the crystallization of membrane proteins. Moreover, the viscous LCP also provides a highly effective delivery medium for serial femtosecond crystallography (SFX) at X-ray free-electron lasers (XFELs). Here, the adaptation of this technology to perform serial millisecond crystallography (SMX) at more widely available synchrotron microfocus beamlines is described. Compared with conventional microcrystallography, LCP-SMX eliminates the need for difficult handling of individual crystals and allows for data collection at room temperature. The technology is demonstrated by solving a structure of the light-driven proton-pump bacteriorhodopsin (bR) at a resolution of 2.4 Å. The room-temperature structure of bR is very similar to previous cryogenic structures but shows small yet distinct differences in the retinal ligand and proton-transfer pathway.

Natively inhibited Trypanosoma brucei cathepsin B structure determined by using an X-ray laser.

The Trypanosoma brucei cysteine protease cathepsin B (TbCatB), which is involved in host protein degradation, is a promising target to develop new treatments against sleeping sickness, a fatal disease caused by this protozoan parasite. The structure of the mature, active form of TbCatB has so far not provided sufficient information for the design of a safe and specific drug against T. brucei. By combining two recent innovations, in vivo crystallization and serial femtosecond crystallography, we obtained the room-temperature 2.1 angstrom resolution structure of the fully glycosylated precursor complex of TbCatB. The structure reveals the mechanism of native TbCatB inhibition and demonstrates that new biomolecular information can be obtained by the "diffraction-before-destruction" approach of x-ray free-electron lasers from hundreds of thousands of individual microcrystals.