Fas signaling was reported to participate in cell apoptosis. However, this pathway has also been shown to promote tumor cell motility, leading to the hypothesis that Fas signaling may induce ...epithelial-mesenchymal transition (EMT) to promote metastasis. The effects of Fas-ligand (FasL) treatment and inhibition of Fas signaling on colorectal and gastric cancer cells were tested using motility assay, immunofluorescence, RT-PCR and immunoblot analyses. Fas signaling downregulated epithelial markers, upregulated mesenchymal markers and promoted motility in gastrointestinal (GI) cancer cells. FasL treatment also increased the expression of EMT transcriptional factors in the nucleus and induced a spindle shape cell morphology in these cells. Knockdown of Snail or Twist expression significantly decreased FasL-induced motility. The ERK1/2 pathway was activated by Fas signaling and is required for FasL-induced EMT and motility. Moreover, oxaliplatin, a chemotherapeutic agent, induced EMT partly through Fas signaling. Evaluation of human GI clinical specimens showed that FasL expression increased whereas E-cadherin expression decreased during GI cancer progression. Both markers were significantly inversely correlated. Tissue samples with a non-EMT phenotype were mainly distributed in patients with early cancer stages, whereas samples with an EMT phenotype were mostly distributed in patients with advanced cancer stages. A non-EMT phenotype significantly correlated with better prognosis. Altogether, these data indicate that Fas signaling may induce EMT to promote tumor motility and metastasis in GI cancer in vivo and in vitro.
Stable chronic functionality of intracortical probes is of utmost importance toward realizing clinical application of brain-machine interfaces. Sustained immune response from the brain tissue to the ...neural probes is one of the major challenges that hinder stable chronic functionality. There is a growing body of evidence in the literature that highly compliant neural probes with sub-cellular dimensions may significantly reduce the foreign-body response, thereby enhancing long term stability of intracortical recordings. Since the prevailing commercial probes are considerably larger than neurons and of high stiffness, new approaches are needed for developing miniature probes with high compliance. In this paper, we present design, fabrication, and
in vitro
evaluation of ultra-miniature (2.7 μm x 10 μm cross section), ultra-compliant (1.4 × 10
-2
μN/μm in the axial direction, and 2.6 × 10
-5
μN/μm and 1.8 × 10
-6
μN/μm in the lateral directions) neural probes and associated probe-encasing biodissolvable delivery needles toward addressing the aforementioned challenges. The high compliance of the probes is obtained by micron-scale cross-section and meandered shape of the parylene-C insulated platinum wiring. Finite-element analysis is performed to compare the strains within the tissue during micromotion when using the ultra-compliant meandered probes with that when using stiff silicon probes. The standard batch microfabrication techniques are used for creating the probes. A dissolvable delivery needle that encases the probe facilitates failure-free insertion and precise placement of the ultra-compliant probes. Upon completion of implantation, the needle gradually dissolves, leaving behind the ultra-compliant neural probe. A spin-casting based micromolding approach is used for the fabrication of the needle. To demonstrate the versatility of the process, needles from different biodissolvable materials, as well as two-dimensional needle arrays with different geometries and dimensions, are fabricated. Further, needles incorporating anti-inflammatory drugs are created to show the co-delivery potential of the needles. An automated insertion device is developed for repeatable and precise implantation of needle-encased probes into brain tissue. Insertion of the needles without mechanical failure, and their subsequent dissolution are demonstrated. It is concluded that ultra-miniature, ultra-compliant probes and associated biodissolvable delivery needles can be successfully fabricated, and the use of the ultra-compliant meandered probes results in drastic reduction in strains imposed in the tissue as compared to stiff probes, thereby showing promise toward chronic applications.
•Established new methods for analyzing depth dependent recordings.•Optimized novel metrics for quantifying evoked MU and LFP recording quality and stability.•Neural recording of resting state ...underestimates the number of neurons available for recording.•Depth of cortical layer IV can fluctuate in the 1stwk after implantation, but stabilizes after 2wks.•There is strong dependence on the biological layers of the cortex on chronic recordings.
Intracortical electrode arrays that can record extracellular action potentials from small, targeted groups of neurons are critical for basic neuroscience research and emerging clinical applications. In general, these electrode devices suffer from reliability and variability issues, which have led to comparative studies of existing and emerging electrode designs to optimize performance. Comparisons of different chronic recording devices have been limited to single-unit (SU) activity and employed a bulk averaging approach treating brain architecture as homogeneous with respect to electrode distribution.
In this study, we optimize the methods and parameters to quantify evoked multi-unit (MU) and local field potential (LFP) recordings in eight mice visual cortices.
These findings quantify the large recording differences stemming from anatomical differences in depth and the layer dependent relative changes to SU and MU recording performance over 6-months. For example, performance metrics in Layer V and stratum pyramidale were initially higher than Layer II/III, but decrease more rapidly. On the other hand, Layer II/III maintained recording metrics longer. In addition, chronic changes at the level of layer IV are evaluated using visually evoked current source density.
The use of MU and LFP activity for evaluation and tracking biological depth provides a more comprehensive characterization of the electrophysiological performance landscape of microelectrodes.
A more extensive spatial and temporal insight into the chronic electrophysiological performance over time will help uncover the biological and mechanical failure mechanisms of the neural electrodes and direct future research toward the elucidation of design optimization for specific applications.
•A coupled crystal-plasticity and phase-field model is developed for tungsten.•Four typical fracture processes, namely brittle, semi-brittle, micro-ductile and ductile fracture, are well ...captured.•Underlying mechanism is revealed for the formation of different fracture surface morphologies.•Competition mechanisms between screw dislocation motion and crack propagation are analyzed.•Non-Schmid effect significantly affects tungsten fracture behaviors at low and medium temperatures.
The brittle-ductile transition (BDT) of tungsten depends heavily on temperature-dependent dislocation mobility. To well understand the underlying mechanism of tungsten fracture behavior, the dislocation activities need to be well described, but the related model remains limited. In this work, a coupled crystal-plasticity and phase-field model (CP-PFM) is developed based on a unified thermodynamic framework, which considers the thermal activated kink-pair mechanism of screw dislocation motion, the evolution of dislocation density, and the coupling effects between the plasticity and the crack propagation. The developed model can well predict the experimental results and is used to study the BDT process of tungsten. Four typical fracture processes are disclosed depending on the temperature, including the brittle fracture, semi-brittle fracture, micro-ductile fracture and ductile fracture. They exhibit different micro-cleavage crack features, induced by the competition between the shielding effect of the plastic zone and the crack propagation near the crack tip zone. In addition, the fracture process of tungsten is found to be significantly influenced by non-Schmid effect in the low and medium temperature regimes.
Corundum-structured α-Ga2O3 thin films have been employed to deposit on m-plane (300) α-Al2O3 substrates under different temperature, oxygen pressure, pulse laser energy and frequency by laser ...molecular beam epitaxy method. (300)-oriented α-Ga2O3 epitaxial thin film can be obtained under the appropriate growth parameters. The prepared α-Ga2O3 thin film shows a band gap of 5.15eV which is larger than that of β-Ga2O3, exhibiting an excellent solar-blind ultraviolet (UV) characteristic. The α-Ga2O3 thin film exhibits obvious photoresponse under 254nm UV light irradiation, and it increases in photocurrent with both the increase of optical input power and applied bias. However, it is not sensitive to 365nm light. The results suggest that α-Ga2O3 thin film is a promising candidate for use in solar-blind photodetectors.
•High-quality (300)-oriented corundum-structured α-Ga2O3 epitaxial thin films have been fabricated by LMBE on m-plane α-Al2O3 substrates .•The α-Ga2O3 epitaxial thin film with a band gap of 5.15eV exhibits a promising use in solar-blind photodetectors.
Graphene, whose absorbance is approximately independent of wavelength, allows broadband light-matter interactions with ultrafast responses. The interband optical absorption of graphene can be ...saturated readily under strong excitation, thereby enabling scientists to exploit the photonic properties of graphene to realize ultrafast lasers. The evanescent field interaction scheme of the propagating light with graphene covered on a D-shaped fibre or microfibre has been employed extensively because of the nonblocking configuration. Obviously, most of the fibre surface is unused in these techniques. Here, we exploit a graphene-clad microfibre (GCM) saturable absorber in a mode-locked fibre laser for the generation of ultrafast pulses. The proposed all-surface technique can guarantee a higher efficiency of light-graphene interactions than the aforementioned techniques. Our GCM-based saturable absorber can generate ultrafast optical pulses within 1.5 μm. This saturable absorber is compatible with current fibre lasers and has many merits such as low saturation intensities, ultrafast recovery times, and wide wavelength ranges. The proposed saturable absorber will pave the way for graphene-based wideband photonics.
•Silastic sealants limit cell infiltration into the craniotomy and improve image clarity.•Low concentration hydrogel sealants failed to prevent cell infiltration.•High concentration hydrogels ...displaced brain tissue and disrupted probe performance.•CX3CR1+ giant cells were identified on windows and probes.•BBB dye leakage was greatest in the craniotomy on the outside of the dura matter.
Two-photon microscopy has enabled the visualization of dynamic tissue changes to injury and disease in vivo. While this technique has provided powerful new information, in vivo two-photon chronic imaging around tethered cortical implants, such as microelectrodes or neural probes, present unique challenges.
A number of strategies are described to prepare a cranial window to longitudinally observe the impact of neural probes on brain tissue and vasculature for up to 3 months.
It was found that silastic sealants limit cell infiltration into the craniotomy, thereby limiting light scattering and preserving window clarity over time. In contrast, low concentration hydrogel sealants failed to prevent cell infiltration and their use at high concentration displaced brain tissue and disrupted probe performance.
The use of silastic sealants allows for a suitable imaging window for long term chronic experiments and revealed new insights regarding the dynamic leukocyte response around implants and the nature of chronic BBB leakage in the sub-dural space.
The presented method provides a valuable tool for evaluating the chronic inflammatory response and the performance of emerging implantable neural technologies.
The dorsal root ganglion is an attractive target for implanting neural electrode arrays that restore sensory function or provide therapy via stimulation. However, penetrating microelectrodes designed ...for these applications are small and deliver low currents. For long-term performance of microstimulation devices, novel coating materials are needed in part to decrease impedance values at the electrode-tissue interface and to increase charge storage capacity.
Conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and multi-wall carbon nanotubes (CNTs) were coated on the electrode surface and doped with the anti-inflammatory drug, dexamethasone. Electrode characteristics and the tissue reaction around neural electrodes as a result of stimulation, coating and drug release were characterized. Hematoxylin and eosin staining along with antibodies recognizing Iba1 (microglia/macrophages), NF200 (neuronal axons), NeuN (neurons), vimentin (fibroblasts), caspase-3 (cell death) and L1 (neural cell adhesion molecule) were used. Quantitative image analyses were performed using MATLAB.
Our results indicate that coated microelectrodes have lower in vitro and in vivo impedance values. Significantly less neuronal death/damage was observed with coated electrodes as compared to non-coated controls. The inflammatory response with the PEDOT/CNT-coated electrodes was also reduced.
This study is the first to report on the utility of these coatings in stimulation applications. Our results indicate PEDOT/CNT coatings may be valuable additions to implantable electrodes used as therapeutic modalities.
In this paper, the double-pulse laser-induced breakdown spectroscopy (DP-LIBS) technique was used to analyze the heavy metal samples collected in the atmosphere using an air sampler. The enhancement ...characteristics of the plasma spectra were studied by using different laser wavelength combinations with 1064, 532, and 355 nm Nd:YAG lasers. The plasma spectrum of the sample was greatly enhanced when the combined laser wavelengths were 355 and 1064 nm. On this basis, the optimal inter-pulse delay time is obtained to get the maximum plasma spectrum. The relationship of the signal to background ratio, electron temperature, and electron density of the plasma spectrum with inter-pulse delay and acquisition delay is also discussed. Finally, the optimal pulse delay and acquisition time were obtained. DP-LIBS technology can effectively improve the detection effect of heavy metals in the atmosphere, which is a very promising tool in the field of environmental monitoring.
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