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Objective To ascertain the biomechanical effects of a degenerated L4 -L5 segment on the lower lumbar spine through a comprehensive simulation of disc degeneration. Methods A three-dimensional nonlinear finite element model of a normal L3 -S1 lumbar spine was constructed and validated. This normal model was then modified such that three degenerated models with different degrees of degeneration (mild, moderate, or severe) at the L4 -L5 level were constructed. While experiencing a follower compressive load (500 N), hybrid moment loads were applied to all models to determine range of motion (ROM), intradiscal pressure (IDP), maximum von Mises stress in the annulus, maximum shear stress in the annulus, and facet joint force. Results As the degree of disc degeneration increased, the ROM of the L4 -L5 degenerated segment declined dramatically in all postures (flexion: 5.79°-1.91°; extension: 5.53°-2.62°; right lateral bending: 4.47°-1.46°; left lateral bending: 4.86°-1.61°; right axial rotation: 2.69°-0.74°; left axial rotation: 2.69°-0.74°), while the ROM in adjacent segments increased (1.88°-8.19°). The largest percent decrease in motion of the L4 -L5 segment due to disc degeneration was in right axial rotation (75%), left axial rotation (69%), flexion (67%), right lateral bending (67%), left lateral bending right (67%), and extension (53%). The change in the trend of the IDP was the same as that of the ROM. Specifically, the IDP decreased (flexion: 0.592-0.09 MPa; extension: 0.678-0.334 MPa; right lateral bending: 0.498-0.205 MPa; left lateral bending: 0.523-0.272 MPa; right axial rotation: 0.535-0.246 MPa; left axial rotation: 0.53-0.266 MPa) in the L4 -L5 segment, while the IDP in adjacent segments increased (0.511-0.789 MPa). The maximum von Mises stress and maximum shear stress of the annulus in whole lumbar spine segments increased (L4 -L5 segment: 0.413-2.626 MPa and 0.412-2.783 MPa, respectively; adjacent segment of L4 -L5 : 0.356-1.493 MPa and 0.359-1.718 MPa, respectively) as degeneration of the disc progressively increased. There was no apparent regularity in facet joint force in the degenerated segment as the degree of disc degeneration increased. Nevertheless, facet joint forces in adjacent healthy segments increased as the degree of disc degeneration increased (extension: 49.7-295.3 N; lateral bending: 3.5-171.2 N; axial rotation: 140.2-258.8 N). Conclusion Degenerated discs caused changes in the motion and loading pattern of the degenerated segments and adjacent normal segments. The abnormal load and motion in the degenerated models risked accelerating degeneration in the adjacent normal segments. In addition, accurate simulation of degenerated facet joints is essential for predicting changes in facet joint loads following disc degeneration.

Background and purpose Anxiety disorder is a common mental health disorder. However, there are few safe and fast-acting anxiolytic drugs available that can treat anxiety disorder. We previously demonstrated that the interaction of neuronal NOS (nNOS) with its carboxy-terminal PDZ ligand (CAPON) is involved in regulating anxiety-related behaviours. Here, we further investigated the anxiolytic effects of nNOS-CAPON disruptors in chronic stress-induced anxiety in animals. Experimental approach Mice were intravenously treated with nNOS-CAPON disruptors, ZLc-002 or Tat-CAPON12C, at the last week of chronic mild stress (CMS) exposure. We also infused corticosterone (CORT) into the hippocampus of mice to model anxiety behaviours and also delivered ZLc-002 or Tat-CAPON12C on the last week of chronic CORT treatment via pre-implanted cannula. Anxiety-related behaviours were examined using elevated plus maze, open field, novelty-suppressed feeding and light-dark (LD) tests. The level of nNOS-CAPON interaction was determined by co-immunoprecipitation (CO-IP) and proximity ligation assay (PLA). The neural mechanisms underlying the behavioural effects of nNOS-CAPON uncoupling in anxiety animal models were assessed by western blot, immunofluorescence and Golgi-Cox staining. Key results ZLc-002 and Tat-CAPON12C reversed CMS- or CORT-induced anxiety-related behaviours. ZLc-002 and Tat-CAPON12C increased synaptogenesis along with improved dendritic remodelling in CMS mice or CORT-treated cultured neurons. Meanwhile, blocking nNOS-CAPON interaction significantly activated the cAMP response element-binding protein (CREB)-brain-derived neurotrophic factor (BDNF) pathway, which is associated with synaptic plasticity. Conclusion and implications Collectively, these results provide evidence for the anxiolytic effects of nNOS-CAPON uncouplers and their underlying mechanisms in anxiety disorders.

Reported here is the induced helical aggregation of an achiral cationic perylene-3,4-dicarboximide (1) that contains a phenylboronic acid group, together with UMP that bears a cis-diol moiety able to interact with boronic acid and an imide group known to coordinate with Hg2+. In selected solvents, 1 exists in monomer form, even in the presence of either UMP or Hg2+. Helical aggregation only takes place if 1 is mixed with both UMP and Hg2+, which is shown to result from the formation of a building block consisting of five components in the form 1–U–Hg2+–U–1. Strong exciton-coupled circular dichroism signals were observed in the absorption window of the achiral dye chromophore, demonstrating the transfer of the chirality of UMP to the supramolecular aggregates of P-helicity. Synergism was shown to occur upon aggregation of the 1–U–Hg2+–U–1 building block, as substantially enhanced affinity and binding selectivity were observed for UMP and Hg2+, despite the otherwise weak and less selective interactions of 1–UMP and UMP–Hg2+. In support of this synergism, the g-factor of the aggregates was found to be 1.4×10−2, which represents a high value. We thus show a strategy of in situ construction of a building block from multiple components, among which the interactions can be weak and less selective. Therefore, the design and syntheses of the constituent components are substantially simplified, yet diverse functions can be expected from their supramolecular aggregates.

Background The proximal lateral lower leg flap is a flap suited for the reconstruction of small and thin defects. The purpose of this study was to map the position and consistency of the perforator vessels and to review its reliability and technical considerations clinically. Methods The location, number, and size of perforator vessels in the proximal third of the lateral lower leg were investigated in 20 fresh frozen cadaveric lower limbs. This was analyzed together with 22 clinical cases. Results Cadaveric dissection showed that there were 1–2 perforators in the proximal third of the lateral lower leg and these perforator vessels were found to be 63% septocutaneous and 37% musculocutaneous. The source vessel of the perforators was variable. Clinically the recipient site consisted of the head and neck in 8 cases, the foot and ankle region in 13 cases, and 1 case in the hand. The mean thickness of this flap was 5.8 ± 0.8 mm. Vascular pedicle length ranged from 5 to 8.5 cm. The mean diameter of flap artery was 1.3 ± 0.3 mm. One flap failure was seen due to arterial thrombosis. The overall flap survival rate was 95%. Conclusions The proximal lateral lower leg flap has the advantages of being thin and pliable, quick to harvest with no major arteries sacrificed. There is minimal donor site morbidity and primary closure of the donor site is possible in the majority of cases. © 2014 Wiley Periodicals, Inc. Microsurgery 35:115–122, 2015.

A series of polyimides (PIs) with various side-chain structures were prepared via copolymerization of pyromellitic dianhydride, 3,3′-dimethyl-4,4′-methylenediamine and three functional diamines: 4-(4-octyloxybenzoyloxy)biphenyl-3′,5′-diaminobenzoate (C8-BPDA), 4-octyloxybiphenyl-3′,5′-diaminobenzoate (C8-PDA) and 4-(4-butoxybenzoyloxy)biphenyl-3′,5′-diaminobenzoate (C4-BPDA). PIs derived from C8-BPDA and C4-BPDA exhibited excellent rubbing resistance in comparison with PI from C8-PDA and the pretilt angle could be controlled over 89° after rubbing. Thermogravimetric analysis showed that the thermal degradation of PIs under nitrogen atmosphere occurred above 320 °C, and PI derived from C8-BPDA showed the best thermal stability. Wide-angle X-ray diffraction patterns indicated an amorphous morphology of the PIs, and the PIs also had outstanding solubility in polar aprotic solvents. The resultant PI films were light colored and maintained high transparency in the visible light region. By increasing the rigidity of side-chains, the rubbing resistance and the thermal stability of PIs could be promoted at the same time. © 2012 Society of Chemical Industry

The aim of our study was to construct macroporous calcium phosphate bone cements (CPCs) with enhanced osteogenic potential. For this purpose, 300 mM sodium dodecyl sulfate (SDS) as an air-entraining agent was added to the liquid phase and 1, 5, and 10% simvastatin (SIM) was homogenized with the solid phase. The physical and mechanical characteristics of the test samples were investigated. Biological properties of the new CPCs were examined after intramuscular and endosteal implantation in rabbits. The introduction of SDS produced interconnected macropores and did not significantly affect initial setting time, transformation of solid phase to hydroxyapatite, and biocompatibility of CPCs. Large amounts (10 wt %) of SIM could decrease the compressive strength and induce severe muscular necrosis and inflammatory reaction. Small amounts (1 wt %) of SIM were compatible with the CPCs did not affect the physico-chemical properties or biocompatibility and were sufficient to enhance the osteogenic potential of macroporous CPCs. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A:2991–3000, 2012.

The Notch signaling pathway plays critical roles in human cancers, including osteosarcoma, suggesting that the discovery of specific agents targeting Notch would be extremely valuable for osteosarcoma. Curcumin, a naturally occurring phenolic compound found in curcuma longa, has been shown to inhibit proliferation and induce apoptosis of osteosarcoma cells in vitro and tumor growth in xenotransplant or orthotransplant models. However, the precise molecular mechanisms by which curcumin exerts its antitumor activity remain unclear. Here we used multiple molecular approaches, such as the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, the invasion assay, gene transfection, real-time RT-PCR, western blot and gelatin zymography, to investigate whether the downregulation of Notch-1 contributes to curcumin-induced inhibition of proliferation and invasion in osteosarcoma cells. The results showed that curcumin caused marked inhibition of osteosarcoma cell growth and G2/M phase cell cycle arrest. This was associated with concomitant attenuation of Notch-1 and downregulation of its downstream genes, such as matrix metalloproteinases, resulting in the inhibition of osteosarcoma cell invasion through Matrigel. We also found that specific downregulation of Notch-1 via small-interfering RNA prior to curcumin treatment resulted in enhanced inhibition of cell growth and invasion. These results suggest that antitumor activity of curcumin is mediated through a novel mechanism involving inactivation of the Notch-1 signaling pathway. Our data provide the first evidence that the downregulation of Notch-1 by curcumin may be an effective approach for the treatment of osteosarcoma.

The organic multiferroic effect receives increasing attention in organic electronics. Recently, the renaissance of organic multiferroics has yielded in a deep understanding of organic magnetism and magnetoelectric coupling. Here, through fabricating polythiophene nanowire/CH3NH3PbBr3 multiferroic heterojunction, the origin of organic magnetism, optically controlled magnetization, and magnetoelectric coupling with optical approach is studied. Specifically, the optical approach utilizes double beam 355 and 607 nm excitations to separately operate the CH3NH3PbBr3 and polythiophene nanowire layers. This double-beam-light approach allows to elucidate the effects of photogenerated charges on organic magnetism and magnetoelectric coupling effect. It is found that magnetization and magnetoelectric coupling of polythiophene nanowire/CH3NH3PbBr3 heterojunction can be effectively tuned through the photoexcitation of CH3NH3PbBr3, rather than photoexcitation of polythiophene nanowire phase, which has been further confirmed by electron spin resonance. Furthermore, the dominated factors are discussed to reveal room-temperature magnetization in organics. This work provides a strategy for optically controlled organic magnetism and magnetoelectric effect in charge transfer heterojunction.

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