Bone defect repair is challenging in orthopaedic clinics. For treatment of large bone defects, bone grafting remains the method of choice for the majority of surgeons, as it fills spaces and provides ...support to enhance biological bone repair. As therapeutic agents are desirable for enhancing bone healing, this study was designed to develop such a bioactive composite scaffold (PLGA/TCP/ICT) made of polylactide-co-glycolide (PLGA) and tricalcium phosphate (TCP) as a basic carrier, incorporating a phytomolecule icaritin (ICT), i.e., a novel osteogenic exogenous growth factor. PLGA/TCP/ICT scaffolds were fabricated as PLGA/TCP (control group) and PLGA/TCP in tandem with low/mid/high-dose ICT (LICT/MICT/HICT groups, respectively). To evaluate the in vivo osteogenic and angiogenic potentials of these bioactive scaffolds with slow release of osteogenic ICT, the authors established a 12mm ulnar bone defect model in rabbits. X-ray and high-resolution peripheral quantitative computed tomography results at weeks 2, 4 and 8 post-surgery showed more newly formed bone within bone defects implanted with PLGA/TCP/ICT scaffolds, especially PLGA/TCP/MICT scaffold. Histological results at weeks 4 and 8 also demonstrated more newly mineralized bone in PLGA/TCP/ICT groups, especially in the PLGA/TCP/MICT group, with correspondingly more new vessel ingrowth. These findings may form a good foundation for potential clinical validation of this innovative bioactive scaffold incorporated with the proper amount of osteopromotive phytomolecule ICT as a ready product for clinical applications.
Our understanding of when and how humans adapted to living on the Tibetan Plateau at altitudes above 2000 to 3000 meters has been constrained by a paucity of archaeological data. Here we report data ...sets from the northeastern Tibetan Plateau indicating that the first villages were established only by 5200 calendar years before the present (cal yr B.P.). Using these data, we tested the hypothesis that a novel agropastoral economy facilitated year-round living at higher altitudes since 3600 cal yr B.P. This successful subsistence strategy facilitated the adaptation of farmers-herders to the challenges of global temperature decline during the late Holocene.
SmB6, a well-known Kondo insulator, exhibits a transport anomaly at low temperature. This anomaly is usually attributed to states within the hybridization gap. Recent theoretical work and transport ...measurements suggest that these in-gap states could be ascribed to topological surface states, which would make SmB6 the first realization of topological Kondo insulator. Here by performing angle-resolved photoemission spectroscopy experiments, we directly observe several dispersive states within the hybridization gap of SmB6. These states show negligible kz dependence, which indicates their surface origin. Furthermore, we perform photoemission circular dichroism experiments, which suggest that the in-gap states possess chirality of the orbital angular momentum. These states vanish simultaneously with the hybridization gap at around 150 K. Together, these observations suggest the possible topological origin of the in-gap states.
Summary
Activated calcium‐/calmodulin‐dependent protein kinaseII (CaMKII) is important to promote chondrocytes from proliferative to pre‐hypertrophic state, which probably plays a role in ...osteoarthritis (OA), a widespread degeneration disease with enhanced aberrant chondrocyte differentiation. Our aim was to detect the role of CaMKII, and its relationship with the feedback loop of Indian hedgehog (Ihh) and Parathyroid‐related peptide (PTHrP) in the temporomandibular joints (TMJs) OA. KN93, the competitive inhibitor of CaMKII, was added to the culture medium in vitro and was locally injected to rats TMJs (n = 54, female) every other day for 4 weeks from the beginning of the 5th and 9th week after installing of unilateral anterior crossbite (UAC), termed as 4 wk+4 wk and 8 wk+4 wk, accordingly. The RNA expression of CaMKII α (1.49 ± 0.09), CaMKII β (3.36 ± 0.20), Ihh (1.88 ± 0.06) and PTHrP (1.87 ± 0.12) was all enhanced, especially at 24 dyn/cm2 in vitro (all P < .05), accompanied with downregulated expression of cartilage matrix, but upregulated markers of chondrocytes differentiation (all P < 0.05). Similarity was observed in the 4 wk+4 wk group in vivo. In the 8 wk+4 wk group, UAC upregulated the RNA expression of CaMKII α (1.81 ± 0.24), CaMKII β (1.36 ± 0.07) and Ihh (1.70 ± 0.21), however, down‐regulated PTHrP (0.53 ± 0.04) (all P < .05), in consonance with the protein expression. All these changes were attenuated by KN93 (all P < .05). In conclusion, CaMKII took a role, via Ihh and PTHrP pathways, in promoting biomechanically induced TMJ chondrocytes differentiation, the initiation issue of UAC stimulated osteoarthritic changes in rodent TMJs. Inhibiting CaMKII is helpful to rescue the biomechanically stimulated cartilage degradation and prospective to be a target treatment of OA.
Magnesium alloys have shown potential as biodegradable metallic materials for orthopedic applications due to their degradability, resemblance to cortical bone and biocompatible degradation/corrosion ...products. However, the fast corrosion rate and the potential toxicity of their alloying element limit the clinical application of Mg alloys. From the viewpoint of both metallurgy and biocompatibility, strontium (Sr) was selected to prepare hot rolled Mg–Sr binary alloys (with a Sr content ranging from 1 to 4wt.%) in the present study. The optimal Sr content was screened with respect to the mechanical and corrosion properties of Mg–Sr binary alloys and the feasibility of the use of Mg–Sr alloys as orthopedic biodegradable metals was investigated by in vitro cell experiments and intramedullary implantation tests. The mechanical properties and corrosion rates of Mg–Sr alloys were dose dependent with respect to the added Sr content. The as-rolled Mg–2Sr alloy exhibited the highest strength and slowest corrosion rate, suggesting that the optimal Sr content was 2wt.%. The as-rolled Mg–2Sr alloy showed Grade I cytotoxicity and induced higher alkaline phosphatase activity than the other alloys. During the 4weeks implantation period we saw gradual degradation of the as-rolled Mg–2Sr alloy within a bone tunnel. Micro-computer tomography and histological analysis showed an enhanced mineral density and thicker cortical bone around the experimental implants. Higher levels of Sr were observed in newly formed peri-implant bone compared with the control. In summary, this study shows that the optimal content of added Sr is 2wt.% for binary Mg–Sr alloys in the rolled state and that the as-rolled Mg–2Sr alloy in vivo produces an acceptable host response.
The effect of controlled thermal annealing on charge transport and photogeneration in bulk‐heterojunction solar cells made from blend films of regioregular poly(3‐hexylthiophene) (P3HT) and ...methanofullerene (PCBM) has been studied. With respect to the charge transport, it is demonstrated that the electron mobility dominates the transport of the cell, varying from 10–8 m2 V–1 s–1 in as‐cast devices to ≈3 × 10–7 m2 V–1 s–1 after thermal annealing. The hole mobility in the P3HT phase of the blend is dramatically affected by thermal annealing. It increases by more than three orders of magnitude, to reach a value of up to ≈ 2 × 10–8 m2 V–1 s–1 after the annealing process, as a result of an improved crystallinity of the film. Moreover, upon annealing the absorption spectrum of P3HT:PCBM blends undergo a strong red‐shift, improving the spectral overlap with solar emission, which results in an increase of more than 60 % in the rate of charge‐carrier generation. Subsequently, the experimental electron and hole mobilities are used to study the photocurrent generation in P3HT:PCBM devices as a function of annealing temperature. The results indicate that the most important factor leading to a strong enhancement of the efficiency, compared with non‐annealed devices, is the increase of the hole mobility in the P3HT phase of the blend. Furthermore, numerical simulations indicate that under short‐circuit conditions the dissociation efficiency of bound electron–hole pairs at the donor/acceptor interface is close to 90 %, which explains the large quantum efficiencies measured in P3HT:PCBM blends.
The effect of controlled thermal annealing on charge transport and photogeneration in bulk‐heterojunction solar cells made from blend films of poly(3‐hexylthiophene) (P3HT) and methanofullerene is investigated. The hole mobility in the P3HT phase of the blend is dramatically affected by annealing (see Figure). An increase in this hole mobility is the most important factor leading to a strong enhancement of the efficiency.
Polymethacrylimide (PMI) foams own the highest specific stiffness and strength of all foams. In situ x-ray micro computed tomography (CT) is used to map three-dimensional (3D) microstructures of this ...representative closed-cell foam under quasi-static compression. The strain fields obtained via digital volume correlation reveal divergent types (discrete or spreading) of deformation banding for the PMI foam with different densities (52 or 75 kgm−3). Significant cell collapse occurs in the deformation bands, leading to ∼40% reduction of the mean cell size, and alignment of cell orientations. Microstructure-based finite element analysis confirms that elastic buckling of cell walls dominates cell collapse, and the buckling strength of walls depends highly on their thicknesses and inclination angles. An edge segmentation technique is then used to quantify the morphology and buckling strength index of cell walls. The spatial distribution of the weakest 3% cell walls correlates well with the modes of deformation banding. Based on elastic buckling of cell walls, new analytical models are developed to predict the strength–density scaling law and stress–strain curves of the PMI foam, which agree well with the experimental results.
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•In situ tomography and strain mapping in PMI foams under compression.•Initial density affects structural disorder and deformation banding.•Meso-FEM confirms elastic buckling of cell walls induces cell collapse.•New buckling-based density-scaling law and constitutive models derived.
The adult nucleus pulposus (NP) and articular cartilage are similar in terms of their histocytological components and biomechanical functionalities, requiring a deep understanding of NP-specific ...markers to better evaluate stem-cell-based NP regeneration. Here, we seek to distinguish NP cells from articular chondrocytes (ACs), focusing on differences in their embryonic formation and evolutionary origin. Embryonically, NP cells are conservatively derived from the axial notochord, whereas ACs originate in a diversified manner from paraxial mesoderm and neural crest cells. Evolutionarily, although the origins of vertebrate NP and AC cells can be traced to similar structures within protostomia-like bilaterian ancestors, the distant phylogenetic relationship between the two groups of animals and the differences in the bodily origins of the tissues suggest that the tissues may in fact have undergone parallel evolution within the protostomia and deuterostomia. The numbers of supposedly NP-specific markers are increasing gradually as microarray studies proceed, but no final consensus has been attained on the specificity and physiology of “exclusive” NP markers because of innate variations among species; intrinsic expression of genes that destabilize the circadian clock; and cooperation by, and crosstalk among, different genes in terms of physiology-related phenotypes. We highlight the embryonic and evolutionary boundaries between NP and AC cells, to aid in recognition of the challenges associated with evaluation of the role played by nucleopulpogenic differentiation during stem-cell-based intervertebral disc regeneration.
Abstract The solar type J radio burst is a variant of type III bursts, which are a probe for understanding solar energetic electrons and local electron density. This study investigates a type J burst ...event on 2017 September 9. We have combined the data from the extreme-ultraviolet (EUV) imaging and the EUV Imaging Spectrometer (EIS) to analyze the event. Within 4 minutes several type J bursts with similar morphology occur. Two of them, with clear fundamental and second harmonic bands, are studied in detail. We find a delay of 2 ± 0.5 s between their different harmonic bands. During type J bursts, only one coronal loop brightens significantly at its northern footpoint, in correlation with the continuous injection of erupting jets into the loop. The EUV intensity of the brightening footpoint is correlated with the radio flux at 245 and 410 MHz, with correlation coefficients of 0.2 and 0.4, respectively. These observations suggest that the type J bursts should originate from this coronal loop. By analyzing the electron number density distribution along the coronal loop diagnosed from the EIS data and the time evolution of the plasma frequency calculated from the type J burst, we determine that the velocities of the energetic electrons exciting the two type Js are 0.10 ± 0.02 c and 0.12 ± 0.02 c . Our results confirm previous studies on type J bursts.
As an active constituent of the beetle Mylabris used in traditional Chinese medicine, cantharidin is a potent and selective inhibitor of protein phosphatase 2A (PP2A) that plays a crucial role in ...cell cycle progression, apoptosis, and cell fate. The role and possible mechanisms exerted by cantharidin in cell growth and metastasis of breast cancer were investigated in this study. Cantharidin was found to inhibit cell viability and clonogenic potential in a time- and dose-dependent manner. Cell cycle analysis revealed that cell percentage in G2/M phase decreased, whereas cells in S and G1 phases progressively accumulated with the increasing doses of cantharidin treatment. In a xenograft model of breast cancer, cantharidin inhibited tumor growth in a dose-dependent manner. Moreover, high doses of cantharidin treatment inhibited cell migration in wound and healing assay and downregulated protein levels of major matrix metalloproteinases (MMP)-2 and MMP-9. MDA-MB-231 cell migration and invasion were dose-dependently inhibited by cantharidin treatment. Interestingly, the members of the mitogen-activated protein kinase (MAPK) signaling family were less phosphorylated as the cantharidin dose increased. Cantharidin was hypothesized to exert its anticancer effect through the MAPK signaling pathway. The data of this study also highlighted the possibility of using PP2A as a therapeutic target for breast cancer treatment.
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