A comparative study of mesoporous glass/silk and non-mesoporous glass/silk scaffolds: Physiochemistry and in vivo osteogenesis

Mesoporous bioactive glass (MBG) is a new class of biomaterials with a well-ordered nanochannel structure, whose in vitro bioactivity is far superior than that of non-mesoporous bioactive glass (BG); the material's in vivo osteogenic properties are, however, yet to be assessed. Porous silk scaffolds have been used for bone tissue engineering, but this material's osteoconductivity is far from optimal. The aims of this study were to incorporate MBG into silk scaffolds in order to improve their osteoconductivity and then to compare the effect of MBG and BG on the in vivo osteogenesis of silk scaffolds. MBG/silk and BG/silk scaffolds with a highly porous structure were prepared by a freeze-drying method. The mechanical strength, in vitro apatite mineralization, silicon ion release and pH stability of the composite scaffolds were assessed. The scaffolds were implanted into calvarial defects in SCID mice and the degree of in vivo osteogenesis was evaluated by microcomputed tomography (μCT), hematoxylin and eosin (H&E) and immunohistochemistry (type I collagen) analyses. The results showed that MBG/silk scaffolds have better physiochemical properties (mechanical strength, in vitro apatite mineralization, Si ion release and pH stability) compared to BG/silk scaffolds. MBG and BG both improved the in vivo osteogenesis of silk scaffolds. μCT and H&E analyses showed that MBG/silk scaffolds induced a slightly higher rate of new bone formation in the defects than did BG/silk scaffolds and immunohistochemical analysis showed greater synthesis of type I collagen in MBG/silk scaffolds compared to BG/silk scaffolds

CaSiO3 microstructure modulating the in vitro and in vivo bioactivity of poly(lactide-co-glycolide) microspheres

Poly (lactide-co-glycolide) (PLGA) microspheres have been used for regenerative medicine due to their ability for drug delivery and generally good biocompatibility, but they lack adequate bioactivity for bone repair application. CaSiO3 (CS) has been proposed as a new class of material suitable for bone tissue repair due to its excellent bioactivity. In this study, we set out to incorporate CS into PLGA microspheres to investigate how the phase structure (amorphous and crystal) of CS influences the in vitro and in vivo bioactivity of the composite microspheres, with a view to the application for bone regeneration. X-ray diffraction (XRD), N2 adsorption-desorption analysis and scanning electron microscopy (SEM) were used to analyze the phase structure, surface area/pore volume, and microstructure of amorphous CS (aCS) and crystal CS (cCS), as well as their composite microspheres. The in vitro bioactivity of aCS and cCS – PLGA microspheres was evaluated by investigating their apatite-mineralization ability in simulated body fluids (SBF) and the viability of human bone mesenchymal stem cells (BMSCs). The in vivo bioactivity was investigated by measuring their de novo bone-formation ability. The results showed that the incorporation of both aCS and cCS enhanced the in vitro and in vivo bioactivity of PLGA microspheres. cCS/PLGA microspheres improved better in vitro BMSC viability and de novo bone-formation ability in vivo, compared to aCS/PLGA microspheres. Our study indicates that controlling the phase structure of CS is a promising method to modulate the bioactivity of polymer microsphere system for potential bone tissue regeneration

Poliovirus intrahost evolution is required to overcome tissue-specific innate immune responses.

RNA viruses, such as poliovirus, have a great evolutionary capacity, allowing them to quickly adapt and overcome challenges encountered during infection. Here we show that poliovirus infection in immune-competent mice requires adaptation to tissue-specific innate immune microenvironments. The ability of the virus to establish robust infection and virulence correlates with its evolutionary capacity. We further identify a region in the multi-functional poliovirus protein 2B as a hotspot for the accumulation of minor alleles that facilitate a more effective suppression of the interferon response. We propose that population genetic dynamics enables poliovirus spread between tissues through optimization of the genetic composition of low frequency variants, which together cooperate to circumvent tissue-specific challenges. Thus, intrahost virus evolution determines pathogenesis, allowing a dynamic regulation of viral functions required to overcome barriers to infection.RNA viruses, such as polioviruses, have a great evolutionary capacity and can adapt quickly during infection. Here, the authors show that poliovirus infection in mice requires adaptation to innate immune microenvironments encountered in different tissues

Determining the Balance Between Drug Efficacy and Safety by the Network and Biological System Profile of Its Therapeutic Target

One of the most challenging puzzles in drug discovery is the identification and characterization of candidate drug of well-balanced profile between efficacy and safety. So far, extensive efforts have been made to evaluate this balance by estimating the quantitative structure–therapeutic relationship and exploring target profile of adverse drug reaction. Particularly, the therapeutic index (TI) has emerged as a key indicator illustrating this delicate balance, and a clinically successful agent requires a sufficient TI suitable for it corresponding indication. However, the TI information are largely unknown for most drugs, and the mechanism underlying the drugs with narrow TI (NTI drugs) is still elusive. In this study, the collective effects of human protein–protein interaction (PPI) network and biological system profile on the drugs' efficacy–safety balance were systematically evaluated. First, a comprehensive literature review of the FDA approved drugs confirmed their NTI status. Second, a popular feature selection algorithm based on artificial intelligence (AI) was adopted to identify key factors differencing the target mechanism between NTI and non-NTI drugs. Finally, this work revealed that the targets of NTI drugs were highly centralized and connected in human PPI network, and the number of similarity proteins and affiliated signaling pathways of the corresponding targets was much higher than those of non-NTI drugs. These findings together with the newly discovered features or feature groups clarified the key factors indicating drug's narrow TI, and could thus provide a novel direction for determining the delicate drug efficacy-safety balance

Ionic-to-electronic current amplification in hybrid perovskite solar cells: ionically gated transistor-interface circuit model explains hysteresis and impedance of mixed conducting devices

Mobile ions in hybrid perovskite semiconductors introduce a new degree of freedom to electronic devices suggesting applications beyond photovoltaics. An intuitive device model describing the interplay between ionic and electronic charge transfer is needed to unlock the full potential of the technology. We describe the perovskite-contact interfaces as transistors which couple ionic charge redistribution to energetic barriers controlling electronic injection and recombination. This reveals an amplification factor between the out of phase electronic current and the ionic current. Our findings suggest a strategy to design thin film electronic components with large, tuneable, capacitor-like and inductor-like characteristics. The resulting simple equivalent circuit model, which we verified with time-dependent drift-diffusion simulations of measured impedance spectra, allows a general description and interpretation of perovskite solar cell behaviour