Regulation of the Catabolic Cascade in Osteoarthritis by the Zinc-ZIP8-MTF1 Axis

SummaryOsteoarthritis (OA), primarily characterized by cartilage degeneration, is caused by an imbalance between anabolic and catabolic factors. Here, we investigated the role of zinc (Zn2+) homeostasis, Zn2+ transporters, and Zn2+-dependent transcription factors in OA pathogenesis. Among Zn2+ transporters, the Zn2+ importer ZIP8 was specifically upregulated in OA cartilage of humans and mice, resulting in increased levels of intracellular Zn2+ in chondrocytes. ZIP8-mediated Zn2+ influx upregulated the expression of matrix-degrading enzymes (MMP3, MMP9, MMP12, MMP13, and ADAMTS5) in chondrocytes. Ectopic expression of ZIP8 in mouse cartilage tissue caused OA cartilage destruction, whereas Zip8 knockout suppressed surgically induced OA pathogenesis, with concomitant modulation of Zn2+ influx and matrix-degrading enzymes. Furthermore, MTF1 was identified as an essential transcription factor in mediating Zn2+/ZIP8-induced catabolic factor expression, and genetic modulation of Mtf1 in mice altered OA pathogenesis. We propose that the zinc-ZIP8-MTF1 axis is an essential catabolic regulator of OA pathogenesis

Improvements to the APBS biomolecular solvation software suite

The Adaptive Poisson-Boltzmann Solver (APBS) software was developed to solve the equations of continuum electrostatics for large biomolecular assemblages that has provided impact in the study of a broad range of chemical, biological, and biomedical applications. APBS addresses three key technology challenges for understanding solvation and electrostatics in biomedical applications: accurate and efficient models for biomolecular solvation and electrostatics, robust and scalable software for applying those theories to biomolecular systems, and mechanisms for sharing and analyzing biomolecular electrostatics data in the scientific community. To address new research applications and advancing computational capabilities, we have continually updated APBS and its suite of accompanying software since its release in 2001. In this manuscript, we discuss the models and capabilities that have recently been implemented within the APBS software package including: a Poisson-Boltzmann analytical and a semi-analytical solver, an optimized boundary element solver, a geometry-based geometric flow solvation model, a graph theory based algorithm for determining p$K_a$ values, and an improved web-based visualization tool for viewing electrostatics

Secured delivery of basic fibroblast growth factor using human serum albumin-based protein nanoparticles for enhanced wound healing and regeneration

Background Basic fibroblast growth factor (bFGF) is one of the critical components accelerating angiogenesis and tissue regeneration by promoting the migration of dermal fibroblasts and endothelial cells associated with matrix formation and remodeling in wound healing process. However, clinical applications of bFGF are substantially limited by its unstable nature due to rapid decomposition under physiological microenvironment. Results In this study, we present the bFGF-loaded human serum albumin nanoparticles (HSA-bFGF NPs) as a means of enhanced stability and sustained release platform during tissue regeneration. Spherical shape of the HSA-bFGF NPs with uniform size distribution (polydispersity index???<???0.2) is obtained via a simple desolvation and crosslinking process. The HSA-bFGF NPs securely load and release the intact soluble bFGF proteins, thereby significantly enhancing the proliferation and migration activity of human dermal fibroblasts. Myofibroblast-related genes and proteins were also significantly down-regulated, indicating decrease in risk of scar formation. Furthermore, wound healing is accelerated while achieving a highly organized extracellular matrix and enhanced angiogenesis in vivo. Conclusion Consequently, the HSA-bFGF NPs are suggested not only as a delivery vehicle but also as a protein stabilizer for effective wound healing and tissue regeneration

Impact of Molecular Weight on Molecular Doping Efficiency of Conjugated Polymers and Resulting Thermoelectric Performances

The effect of molecular weight of a series of conjugated polymers (CPs) on the doping efficiency, electrical conductivity, and related thermoelectric properties of doped CPs is studied. Low (L), medium (M), and high (H) molecular weight batches of PDFD-T polymers, based on difluorobenzothia-diazole and dithienosilole moieties, are synthesized and denoted as PDFD-T(L), PDFD-T(M), and PDFD-T(H), respectively. Furthermore, to compare the effects of different donor moieties, donor units of PDFD-T(L) are structurally modified from thiophene to thienothiophene (TT) and dithienothiophene (DTT), denoted as PDFD-TT(L) and PDFD-DTT(L), respectively. After doping the CPs with FeCl3, d-PDFD-T(H) exhibits an electrical conductivity of 402.9 S cm(-1), which is significantly higher than those of d-PDFD-T(L), d-PDFD-T(M), d-PDFD-TT(L), and d-PDFD-DTT(L). The highest power factor of 101.1 mu W m(-1) K-2 is achieved through organic thermoelectric devices fabricated using PDFD-T(H). Through various characterizations, it is demonstrated that CPs with a high molecular weight tend to have a high carrier mobility while maintaining their original crystallinity and good charge trans- port pathways even after doping. Therefore, it is suggested that optimizing the molecular weight of CPs is an essential strategy for maximal power generation from their doped CP films.11Nsciescopu

Molecular beam epitaxy of large-area SnSe2 with monolayer thickness fluctuation

The interest in layered materials is largely based on the expectation that they will be beneficial for a variety of applications, from low-power-consuming, wearable electronics to energy harvesting. However, the properties of layered materials are highly dependent on thickness, and the difficulty of controlling thickness over a large area has been a bottleneck for commercial applications. Here, we report layer-by-layer growth of SnSe2, a layered semiconducting material, via van der Waals epitaxy. The films were fabricated on insulating mica substrates with substrate temperatures in the range of 210 degrees C-370 degrees C. The surface consists of a mixture of Nand (N +/- 1) layers, showing that the thickness of the film can be defined with monolayer accuracy (+/- 0.6 nm). High-resolution transmission electron microscopy reveals a polycrystalline film with a grain size of similar to 100 nm and clear Moire patterns from overlapped grains with similar thickness. We also report field effect mobility values of 3.7 cm(2) V-1 s(-1) and 6.7 cm(2) V-1 s(-1) for 11 and 22 nm thick SnSe2, respectively. SnSe2 films with customizable thickness can provide valuable platforms for industry and academic researchers to fully exploit the potential of layered materials.clos

Improvements to the APBS biomolecular solvation software suite.

The Adaptive Poisson-Boltzmann Solver (APBS) software was developed to solve the equations of continuum electrostatics for large biomolecular assemblages that have provided impact in the study of a broad range of chemical, biological, and biomedical applications. APBS addresses the three key technology challenges for understanding solvation and electrostatics in biomedical applications: accurate and efficient models for biomolecular solvation and electrostatics, robust and scalable software for applying those theories to biomolecular systems, and mechanisms for sharing and analyzing biomolecular electrostatics data in the scientific community. To address new research applications and advancing computational capabilities, we have continually updated APBS and its suite of accompanying software since its release in 2001. In this article, we discuss the models and capabilities that have recently been implemented within the APBS software package including a Poisson-Boltzmann analytical and a semi-analytical solver, an optimized boundary element solver, a geometry-based geometric flow solvation model, a graph theory-based algorithm for determining pKa values, and an improved web-based visualization tool for viewing electrostatics