Enhanced Skull Bone Regeneration by Sustained Release of BMP-2 in Interpenetrating Composite Hydrogels.

Direct administration of bone morphogenetic protein-2 (BMP-2) for bone regeneration could cause various clinical side effects such as osteoclast activation, inflammation, adipogenesis, and bone cyst formation. In this study, thiolated gelatin/poly(ethylene glycol) diacrylate (PEGDA) interpenetrating (IPN) composite hydrogels were developed for guided skull bone regeneration. To promote bone regeneration, either polycation-based coacervates (Coa) or gelatin microparticles (GMPs) were incorporated within IPN gels as BMP-2 carriers. Both BMP-2 loaded Coa and BMP-2 loaded GMPs showed significantly enhanced in vitro alkaline phosphate (ALP) activity of human mesenchymal stem cells (hMSCs) than non-BMP-2 treated control. Moreover, BMP-2 loaded GMPs group exhibited statistically increased ALP activity compared to both bolus BMP-2 administration and BMP-2 loaded Coa group, indicating that our carriers could protect and maintain biological activity of cargo BMP-2. Sustained release kinetics of BMP-2 from IPN composite hydrogels could be controlled by different formulations. For in vivo bone regeneration, various IPN gel formulations (i.e., (1) control, (2) only hydrogel, (3) hydrogel with bolus BMP-2, (4) hydrogel with BMP-2-loaded Coa, and (5) hydrogel with BMP-2-loaded GMPs) were bilaterally implanted into 5 mm-sized rat calvarial defects. After 4 weeks, micro-CT and histological analysis were performed to evaluate new bone formation. Significantly higher scores for bony bridging and union were observed in BMP-2-loaded Coa and BMP-2-loaded GMP groups as compared to other formulations. In addition, rats treated with BMP-2-loaded GMPs showed a significantly higher ratio of bone volume/total volume and lower trabecular separation scores than others. Finally, rats treated with either Coa or GMP groups exhibited a significant increase in bone formation area, as assessed via histomorphometric analysis. Taken together, it could be concluded that Coa and GMPs were effective carriers to maintain the bioactivity of cargo BMP-2 during its sustained release. Consequently, our IPN composite hydrogel system that combines such BMP-2 carriers could effectively promote skull bone regeneration.

Recombinant measles virus encoding the spike protein of SARS-CoV-2 efficiently induces Th1 responses and neutralizing antibodies that block SARS-CoV-2 variants.

Owing to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, the development of effective and safe vaccines has become a priority. The measles virus (MeV) vaccine is an attractive vaccine platform as it has been administered to children for more than 40 years in over 100 countries. In this study, we developed a recombinant MeV expressing the full-length SARS-CoV-2 spike protein (rMeV-S) and tested its efficacy using mouse and hamster models. In hCD46Tg mice, two-dose rMeV-S vaccination induced higher Th1 secretion and humoral responses than one-dose vaccination. Interestingly, neutralizing antibodies induced by one-dose and two-dose rMeV-S immunization effectively blocked the entry of the α, ß, γ, and δ variants of SARS-CoV-2. Furthermore, two-dose rMeV-S immunization provided complete protection against SARS-CoV-2 in the hamster model. These results suggest the potential of rMeV-S as a vaccine candidate for targeting SARS-CoV-2 and its variants.

The effects of antecedent dry days on the nitrogen removal in layered soil infiltration systems for storm run-off control.

The effects of antecedent dry days (ADD) on nitrogen removal efficiency were investigated in soil infiltration systems, with three distinguishable layers: mulch layer (ML), coarse soil layer (CSL) and fine soil layer (FSL). Two sets of lab-scale columns with loamy CSL (C1) and sandy CSL (C2) were dosed with synthetic run-off, carrying chemical oxygen demand of 100 mg L(-1) and total nitrogen of 13 mg L(-1). The intermittent dosing cycle was stepwise adjusted for 5, 10 and 20 days. The influent ammonium and organic nitrogen were adsorbed to the entire depth in C1, while dominantly to the FSL in C2. In both columns, the effluent ammonium concentration increased while the organic nitrogen concentration decreased, as ADD increased from 5 to 20 days. The effluent of C1 always showed nitrate concentration exceeding influent, caused by nitrification, by increasing amounts as ADD increased. However, the wash-out of nitrate in C1 was not distinct in terms of mass since the effluent flow rate was only 25% of the influent. In contrast, efficient reduction (>95%) of nitrate loading was observed in C2 under ADD of 5 and 10 days, because of insignificant nitrification in the CSL and denitrification in the FSL. However, for the ADD of 20 days, a significant nitrate wash-out appeared in C2 as well, possibly because of the re-aeration by the decreasing water content in the FSL. Consequently, the total nitrogen load escaping with the effluent was always smaller in C2, supporting the effectiveness of sandy CSL over loamy FSL for nitrogen removal under various ADDs.

The regulatory impact of RNA-binding proteins on microRNA targeting.

Argonaute is the primary mediator of metazoan miRNA targeting (MT). Among the currently identified >1,500 human RNA-binding proteins (RBPs), there are only a handful of RBPs known to enhance MT and several others reported to suppress MT, leaving the global impact of RBPs on MT elusive. In this study, we have systematically analyzed transcriptome-wide binding sites for 150 human RBPs and evaluated the quantitative effect of individual RBPs on MT efficacy. In contrast to previous studies, we show that most RBPs significantly affect MT and that all of those MT-regulating RBPs function as MT enhancers rather than suppressors, by making the local secondary structure of the target site accessible to Argonaute. Our findings illuminate the unappreciated regulatory impact of human RBPs on MT, and as these RBPs may play key roles in the gene regulatory network governed by metazoan miRNAs, MT should be understood in the context of co-regulating RBPs.

Recent Strategies in Fabrication of Gradient Hydrogels for Tissue Engineering Applications.

Hydrogels are widely used as scaffold in tissue engineering field because of their ability to mimic the cellular microenvironment. However, mimicking a completely natural cellular environment is complicated due to the differences in various physical and chemical properties of cellular environments. Recently, gradient hydrogels provide excellent heterogeneous environment to mimic the different cellular microenvironments. To create hydrogels with an anisotropic distribution, gradient hydrogels have been widely developed by adopting several gradient generation techniques. Herein, the various gradient hydrogel fabrication techniques, including dual syringe pump systems, microfluidic device, photolithography, diffusion, and bio-printing are summarized. As the effects of gradient 3D hydrogels with stems have been reviewed elsewhere, this review focuses principally on gradient hydrogel fabrication for multi-model tissue regeneration. This review provides new insights into the key points for fabrication of gradient hydrogels for multi-model tissue regeneration.

Membrane fouling control using a rotary disk in a submerged anaerobic membrane sponge bioreactor.

Despite significant research efforts over the last few decades, membrane fouling in anaerobic membrane bioreactors (AnMBRs) remains an unsolved problem that increases the overall operational costs and obstructs the industrial applications. Herein, we developed a method for effectively controlling the membrane fouling in a sponge-submerged AnMBRs using an anaerobic rotary disk MBR (ARMBR). The disk rotation led the effective collision between the sponge and membrane surface; thus successfully enhanced the membrane permeability in the ARMBR. The effect of the disk rotational speed and sponge volume fraction on the membrane permeability and the relationship between the water flow direction and membrane permeability were investigated. The long-term feasibility was tested over 100days of synthetic wastewater treatment. As a result, stable and economical performance was observed without membrane replacement and washing. The proposed integrated rotary disk-supporting media appears to be a feasible and even beneficial option in the AnMBR technology.