Aim To explore the altered spontaneous cerebral activity patterns and impaired functional regions in patients with diabetic retinopathy (DR) using resting-state functional magnetic resonance imaging ...(rs-fMRI) based on the amplitude of low-frequency fluctuations (ALFF) algorithm. Materials and methods Twenty-one patients with DR (mean age, 54.9±9.9 years; 11 females) and 17 healthy control subjects (54.8±5.7 years; 9 females) were prospectively studied. The DR patients underwent laboratory tests. All individuals underwent a neuropsychological test. The differences in the ALFF values between the two groups were compared. The relationships between ALFF values and clinical measurements were analysed using a multiple-factor analysis. Results Compared to the controls, the DR group showed significantly increased ALFF values in the bilateral occipital gyrus, right lingual gyrus, and precuneus, and decreased values in the right posterior/anterior cerebellar lobe and the parahippocampal, fusiform, superior temporal, inferior parietal, and angular gyrus. Furthermore, the Montreal Cognitive Assessment (MoCA) scores were negatively correlated with decreased ALFF values in the right occipital lobe of the DR group, while increased ALFF values in the right precuneus and lingual gyrus were found to be positively correlated with glycosylated haemoglobin (HbA1c) levels. Conclusions Patients with DR showed spontaneous cerebral activity abnormalities in many cerebral regions that were associated with cognitive impairments. HbA1c levels altered spontaneous cerebral activity in DR patients.
A rock mechanics test system and the acoustic emission (AE) test system were employed to perform experiments on bedded rock salt samples under uniaxial compression and indirect tension. Based on the ...basic theory of fractal geometry, a column covering method is proposed to analyze the fractal property of the spatial distribution of acoustic emissions during the rock damage and failure process. The experimental results indicate obvious differences in failure features for different parts of a sample due to the structural differences in bedded rock salt. The consistency between the failure state and the AE spatial distribution is confirmed. The relationships of the stress and energy release with the fractal dimension of the AE spatial distribution are established. An increase in the fractal dimension corresponds to a decrease in the stress and an increase in the energy release, which is consistent with the theoretical analysis. When the fractal dimension obtained from uniaxial compression and indirect tensile tests is less than 2.20 and 2.57, respectively, the stresses in the bedded rock salt sample are over 80% of the peak stress. A great amount of accumulated damage occurs, leading to the global failure of the bedded rock salt sample. Therefore, it is possible to forecast the failure state of bedded rock salt by inspecting the variation between the stress or the energy release and the fractal dimension of the AE spatial distribution.
► Column-covering fractal method for AE spatial distribution was proposed. ► AE signals under different loading conditions were monitored for bedded rock salt. ► Fractal properties of bedded rock salt were studied by the fractal method proposed. ► Relationships between fractal dimensions and energy or stress were obtained.
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.
Glycolysis is critical for cancer stem cell reprogramming; however, the underlying regulatory mechanisms remain elusive. Here, we show that pyruvate dehydrogenase kinase 1 (PDK1) is enriched in ...breast cancer stem cells (BCSCs), whereas depletion of PDK1 remarkably diminishes ALDH
subpopulations, decreases stemness-related transcriptional factor expression, and inhibits sphere-formation ability and tumor growth. Conversely, high levels of PDK1 enhance BCSC properties and are correlated with poor overall survival. In mouse xenograft tumor, PDK1 is accumulated in hypoxic regions and activates glycolysis to promote stem-like traits. Moreover, through screening hypoxia-related long non-coding RNAs (lncRNAs) in PDK1-positive tissue, we find that lncRNA H19 is responsible for glycolysis and BCSC maintenance. Furthermore, H19 knockdown decreases PDK1 expression in hypoxia, and ablation of PDK1 counteracts H19-mediated glycolysis and self-renewal ability in vitro and in vivo. Accordingly, H19 and PDK1 expression exhibits strong correlations in primary breast carcinomas. H19 acting as a competitive endogenous RNA sequesters miRNA let-7 to release Hypoxia-inducible factor 1α, leading to an increase in PDK1 expression. Lastly, aspirin markedly attenuates glycolysis and cancer stem-like characteristics by suppressing both H19 and PDK1. Thus, these novel findings demonstrate that the glycolysis gatekeeper PDK1 has a critical role in BCSC reprogramming and provides a potential therapeutic strategy for breast malignancy.
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 momentum spectrum and number density of created bosons for two types of arbitrarily polarized electric fields are calculated and compared with those of created fermions, employing the equal-time ...Feshbach-Villars-Heisenberg-Wigner formalism, which confirms that for a uniform and time-varying electric field it is completely equivalent to the quantum Vlasov equation in scalar QED. For an elliptically polarized field, it is found that the number density of created bosons is the square root of the number density of spin-up electrons times that of spin-down ones for a circularly polarized multicycle field. Moreover, the degree of spin polarization roughly grows as the Keldysh adiabaticity parameter increases for arbitrarily polarized multicycle fields. For a field constituted of two circularly polarized fields with a time delay, it is shown that momentum vortices also exist in boson pair creation and are induced only by the orbital angular momentum of particles. However, the vortices can reproduce the quantum statistic effect due to the effect of spin of particles. These results further deepen the understanding of some significant signatures in pair production.
The momentum signatures of created pairs in the multiphoton regime in strong fields are investigated and obvious vortex patterns that are constituted of the quasi-Archimedian spirals are found when ...considering two opposite-handedness circularly polarized fields. Distinguished from the familiar Ramsey interference fringes with the concentric rings under two identical-handedness fields, however, the finding vortices are associated to the interference between the pair production amplitudes of these two opposite-handedness fields. Moreover, the sensitive dependence of vortex patterns on the relative carrier envelope phase, the time delay, and the handedness between two fields imply also a new way to detect the applied laser field characteristics.
Abstract Some types of peripheral neuropathic pain are associated with damage to myelin rather than to axons of primary sensory neurons. It is extremely important to develop selective demyelination ...animal models for understanding neuropathic pain caused by demyelination. We induced a rapid-onset and reversible demyelination of peripheral A-fibers and neuropathic pain behaviors in adult rats by a single injection of cobra venom into the sciatic nerve. The relation between A-fiber demyelination and the abnormal pain behaviors was investigated using this model. Microfilament recordings revealed that cobra venom selectively blocked A-fibers, but not C-fibers. Selective blockade of A-fibers may result from A-fiber demyelination at the site of venom injection as demonstrated by microscope examination. The axons of the demyelinated A-fibers appeared to be otherwise normal. Neuropathic pain behaviors appeared almost immediately after venom injection and lasted about 3 weeks. Electrophysiological studies indicated that venom injection induced loss of conduction in A-fibers, increased sensitivity of C-polymodal nociceptors to innocuous stimuli, and triggered spontaneous activity from both peripheral and central terminals of C-fiber nociceptors. Neurogenic inflammatory responses were also observed in the affected skin via Evan's Blue extravasation experiments. Both antidromic C-fiber spontaneous activity and neurogenic inflammation were substantially decreased by continuous A-fiber threshold electric stimuli applied proximally to the venom injection site. The data suggest that normal activity of peripheral A-fibers may produce inhibitory modulation of C-fiber polymodal nociceptors. Removal of inhibition to C-fiber polymodal nociceptors following demyelination of A-fibers may result in pain and neurogenic inflammation in the affected receptive field.
Extensive research has shown that fluid flow through rock fractures is greatly influenced by surface roughness. For a single rock fracture, the roughness of the upper and bottom surfaces is the same ...in the initial condition and then its deformation occurs with normal stress and shear stress imposed on the natural rock. Previous researchers have paid considerable attention to describing the roughness of the single fracture and its effects on fluid flow. However, few studies have explained the fluid flow with shear displacement and the direction of the fluid flow velocity field. In this work, a more detailed 2D numerical model was developed using a laser scanner system with a spacing grid of 0.1 mm. To investigate the influence of shear displacement accurately, the COMSOL multiphase codes were applied. By applying the Navier–Stokes equations, the results of the procedure for shear displacement simulation illustrate the distribution of the absolute velocity and pressure drop under the constant pressure gradient. The velocities predicted at the vertical profiles of the inlet were similar to the parabolic velocity curve defined by the cubic laws. The mean mechanical aperture was usually larger than the hydraulic aperture from the measured flow rates, and a devised empirical equation was proposed to describe the relationship between the mechanical aperture and the hydraulic aperture values. The recirculation zones observed in directional fluid flow during shear explain the anisotropy of roughness of a single fracture, and the phenomenon argues the applicability of local cubic laws which overestimate the total fluid flow rate.
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