-We previously reported that specialized and housekeeping genes are differentially regulated via de novo recruitment and pause-release of RNA polymerase II (pol II), respectively, during cardiac hypertrophy. However, the significance of this finding remains to be examined. Therefore, the purpose of this study was to determine the mechanisms that differentially regulate these gene groups and exploit them for therapeutic targeting.
To investigate the effects of boron on growth performance and meat quality, 10-day-old Africa ostrich chicks were randomly divided into 6 groups with 6 replicates in each group. For 80 days, birds in the treatments were fed the same basal diet but given different concentrations of boron-supplemented water. The highest final BW (33.4 ± 0.30 kg), ADFI (376 ± 1.83 g), and ADG (224 ± 1.01 g) appeared in the group receiving 160 mg/L boron (group 4). 160 mg/L boron also decreased drip loss (2.20 ± 0.59), cooking loss (35.3 ± 1.14), and elevated pH value (6.13 ± 0.28) of meat (P < 0.05). Ostrich chicks in the 640 mg/L treatment group (group 6) had the lowest final BW (30.8 ± 1.05 kg) and ADG (208 ± 0.74 g) (P < 0.05). The highest ash (1.35 ± 0.01%) and pH (6.18 ± 0.03) and the lowest protein (20.4 ± 1.74%), drip loss (2.10 ± 0.76%), cooking loss (35.0 ± 0.41%), C18:1 (28.2 ± 0.65%), and C18:3?3 (2.60 ± 0.51%) appeared in group 6 (P < 0.05) as well. Overall, the optimum concentration of 160 mg/L supplemental boron improved ostrich growth performance and meat quality; however, high concentrations of boron decreased both performance and meat quality.
Protein complexes are important for understanding principles of cellular organization and function. High-throughput experimental techniques have produced a large amount of protein-protein interactions (PPIs), making it possible to predict protein complexes from protein-protein interaction networks. On the other hand, the rapidly growing biomedical literature provides a significantly large and readily available source of interaction data, which can be integrated into the protein network for better complex detection performance.
Protein complexes are important for understanding principles of cellular organization and function. High-throughput experimental techniques have produced a large amount of protein interactions, making it possible to predict protein complexes from protein -protein interaction networks. However, most of current methods are unsupervised learning based methods which can't utilize the information of the large amount of available known complexes.
Chemical doping with foreign atoms is an effective approach to significantly enhance the electrochemical performance of the carbon materials. Herein, sulfur-doped three-dimensional (3D) porous reduced graphene oxide (RGO) hollow nanosphere frameworks (S-PGHS) are fabricated by directly annealing graphene oxide (GO)-encapsulated amino-modified SiO2 nanoparticles with dibenzyl disulfide (DBDS), followed by hydrofluoric acid etching. The XPS and Raman spectra confirmed that sulfur atoms were successfully introduced into the PGHS framework via covalent bonds. The as-prepared S-PGHS has been demonstrated to be an efficient metal-free electrocatalyst for oxygen reduction reaction (ORR) with the activity comparable to that of commercial Pt/C (40%) and much better methanol tolerance and durability, and to be a supercapacitor electrode material with a high specific capacitance of 343 F g(-1), good rate capability and excellent cycling stability in aqueous electrolytes. The impressive performance for ORR and supercapacitors is believed to be due to the synergistic effect caused by sulfur-doping enhancing the electrochemical activity and 3D porous hollow nanosphere framework structures facilitating ion diffusion and electronic transfer.
The synthesis of graphene (GR) from graphene oxide (GO) typically involves harmful chemical reducing agents that are undesirable for most practical applications. Here we report a green and facile synthesis method for the synthesis of GR that is soluble in water and organic solvents and that includes the additional benefit of adsorption of heavy metal ions. Acetylacetone, as both a reducing agent and a stabilizer, was used to prepare soluble GR from GO. Transmission electron microscopy and atomic force microscopy provide clear evidence for the formation of few-layer GR. The results from Fourier transform infrared spectroscopy and ultraviolet-visible spectroscopy show that reduction of GO to GR has occurred. Raman spectroscopy and X-ray photoelectron spectroscopy also indicate the removal of oxygen-containing functional groups from GO, resulting in the formation of GR. The results of dispersion experiments show that GR can be highly dispersed in water and N,N-Dimethylformamide. The reaction mechanism for acetylacetone reduction of exfoliated GO was also proposed. This method is a facile and environmentally friendly approach to the synthesis of GR and opens up new possibilities for preparing GR and GR-based nanomaterials for large-scale applications. Of even greater interest is that inductively coupled plasma atomic emission spectroscopy suggests that synthesized GR may be applied in the absorption of Cd(2+) and Co(2+) due to the strong coordination capacity of acetylacetone on the surfaces and edges of GR and the large surface area of GR in aqueous solutions. The maximum adsorptions are 49.28 mg g(-1) for Cd(2+), which is 4.5 times higher than that of carbon nanotubes, and 27.78 mg g(-1) for Co(2+), which is 3.6 times higher than that of titania beans.
Development of a physiologically relevant 3D model system for cancer research and drug development is a current challenge. We have adopted a 3D culture system based on a transglutaminase-crosslinked gelatin gel (Col-Tgel) to mimic the tumor 3D microenvironment. The system has several unique advantages over other alternatives including presenting cell-matrix interaction sites from collagen-derived peptides, geometry-initiated multicellular tumor spheroids, and metabolic gradients in the tumor microenvironment. Also it provides a controllable wide spectrum of gel stiffness for mechanical signals, and technical compatibility with imaging based screening due to its transparent properties. In addition, the Col-Tgel provides a cure-in-situ delivery vehicle for tumor xenograft formation in animals enhancing tumor cell uptake rate. Overall, this distinctive 3D system could offer a platform to more accurately mimic in vivo situations to study tumor formation and progression both in vitro and in vivo.
Abstract Homatula potanini is an endemic and one of ornamental fishes in the upper stream of the Yangtze River and its tributaries. However, wild populations of H. potanini declined sharply due to anthropological activity in the Jinsha River during the past decades. In present study, the complete mitochondrial DNA genome sequence of H. potanini was first determined by DNA sequencing based on the PCR fragments. The complete mitochondrial genome sequence is a circular molecule of 16,569?bp in size. It consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and a control region (D-loop). The gene nucleotide composition of H. potanini is 30.1% A, 26.9% C, 16.7% G, and 26.3% T, with a relatively high A?+?T content (56.4%). The results could provide useful data for studies on genetic structure and rational resource conservation in H. potanini.
This paper presents a frequency-shaping (FS) neural recording architecture and its implementation in a 0.13 ? m CMOS process. Compared with its conventional counterpart, the proposed architecture inherently rejects electrode offset, increases input impedance 5-10 fold, compresses neural data dynamic range (DR) by 4.5-bit, simultaneously records local field potentials (LFPs) and extracellular spikes, and is more suitable for long-term recording experiments. Measured at a 40 kHz sampling clock and ± 0.6 V supply, the recorder consumes 50 ?W/ch, of which 22 ?W per FS amplifier, 24 ? W per buffer, 4 ? W per 11-bit successive approximation register analog-to-digital converter (SAR ADC). The input-referred noise for LFPs and extracellular spikes are 13 ? Vrms and 7 ?Vrms, respectively, which are sufficient to achieve high-fidelity full-spectrum neural data. In addition, the designed recorder has a 3 pF input capacitance and allows " 11+4.5"-bit neural data DR without system saturation, where the extra 4.5-bit owes to the FS technique. Its figure-of-merit (FOM) based on data DR reaches 36.0 fJ/conversion-step.
Compared with traditional semiconductor quantum dots (QDs) and organic dyes, photoluminescent carbon dots (CDs) are superior because of their high aqueous solubility, robust chemical inertness, facile functionalization, high resistance to photobleaching, low toxicity and good biocompatibility. Herein, a green, large-scale and high-output heterogeneous synthesis of N-doped CDs was developed by reacting calcium citrate and urea under microwave irradiation without the use of any capping agents. The obtained N-doped CDs with a uniform size distribution exhibit good aqueous solubility and yellowish-green fluorescence in the solid and aqueous states. These unique luminescence properties of N-doped CDs inspire new thoughts for applications as fluorescent powders, fluorescent inks, the growth of fluorescent bean sprouts, and fingerprint detection tools.
Online spike detection is an important step to compress neural data and perform real-time neural information decoding. An unsupervised, automatic, yet robust signal processing is strongly desired, thus it can support a wide range of applications. We have developed a novel spike detection algorithm called "exponential component-polynomial component" (EC-PC) spike detection.
Gliomas are hard to treat because of the two barriers involved: the blood-brain barrier and blood-tumor barrier. In this study, a dual-targeting ligand, angiopep-2, and an activatable cell-penetrating peptide (ACP) were functionalized onto nanoparticles for glioma-targeting delivery. The ACP was constructed by conjugating RRRRRRRR (R8) with EEEEEEEE through a matrix metalloproteinase-2 (MMP-2)-sensitive linker. ACP modification effectively enhanced the C6 cellular uptake because of the high expression of MMP-2 on C6 cells. The uptake was inhibited by batimastat, an MMP-2 inhibitor, suggesting that the cell-penetrating property of the ACP was activated by MMP-2. By combining the dual-targeting delivery effect of angiopep-2 and activatable cell-penetrating property of the ACP, the dual-modified nanoparticles (AnACNPs) displayed higher glioma localization than that of single ligand-modified nanoparticles. After loading with docetaxel, a common chemotherapeutic, AnACNPs showed the most favorable antiglioma effect both in vitro and in vivo. In conclusion, a novel drug delivery system was developed for glioma dual targeting and glioma penetrating. The results demonstrated that the system effectively targeted gliomas and provided the most favorable antiglioma effect.
Abstract Lepturichthys fimbriata is an endemic and an important commercial fish which distributes in the upper stream of the Yangtze River. In this study, the complete mitogenome sequence of L. fimbriata has been first sequenced by DNA sequencing based on the PCR fragments. The mitogenome, consisting of 16,567 base pairs (bp), includes 13 protein coding genes, 22 transfer RNAs, 2 ribosomal RNA genes and a non-coding control region (CR). The overall base composition of L. fimbriata is 30.4% A, 28.7% C, 16.5% G, and 24.4% T, with a relatively a slight AT bias of 54.7%. CR of 903?bp length is located between tRNA(Pro) and tRNA(Phe). The complete mitochondrial genome sequence would be useful for further studies on conservation genetics and resource management in L. fimbriata.
Abstract Jinshaia sinensis is an endemic and typical fish which is successfully adaptive to mountain torrents in the upper stream of the Yangtze River and its tributaries. In this study, the complete mitogenome sequence of J. sinensis has been first sequenced by DNA sequencing based on the PCR fragments. The mitogenome, consisting of 16,567 base pairs (bp), had typical vertebrate mitochondrial gene arrangement, including 13 protein coding genes, 22 transfer RNAs, 2 ribosomal RNA genes and a noncoding control region (CR). The overall base composition of J. sinensis is 30.37% A, 28.82% C, 16.59% G, and 24.22% T, with a relatively a slight AT bias of 54.59%. CR of 903?bp length is located between tRNA(Pro) and tRNA(Phe). The complete mitochondrial genome may provide fundamental informative data not only for unravel the population structure and differentiation, but also for further conservation genetics studies on this balitorid species.
Abstract Triplophysa anterodorsalis is an endemic fish in the upper stream of the Yangtze River, Jinsha River and its tributaries. However, wild populations of T. anterodorsalis declined sharply due to cascade hydropower stations constructed successively in the Jinsha River during the past decades. In the present study, the complete mitochondrial DNA genome sequence of T. anterodorsalis was first determined by DNA sequencing based on the PCR fragments. The complete mitochondrial genome sequence of T. anterodorsalis is a circular molecule of 16,567?bp in size. It consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and a control region (D-loop). The gene nucleotide composition of T. anterodorsalis is 27.37% A, 25.68% C, 18.37% G, and 28.57% T, with a relatively a relatively high A?+?T content (55.94%). The results could provide useful data for studies on genetic structure and diversity and rational resource conservation in T. anterodorsalis.
Abstract Schizothorax chongi is an endemic and important polyploidy fish in the upper stream of the Yangtze River. S. chongi represents a typical model species to study historical adaptation and evolution in the Tibetan Plateau. In this study, the complete mitochondrial DNA genome sequence of S. chongi was first determined by DNA sequencing based on the PCR fragments. The complete mitochondrial DNA (mtDNA) genome sequence of S. chongi is a circular molecule of 16,584?bp in length. It consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and a control region (D-loop). The gene nucleotide composition of S. chongi is 29.6% A, 27.1% C, 17.9% G, and 25.4% T, with a high AT content (55.0%). The results could provide useful data for further studies on phylogenetics, conservation genetics and rational resource management for S. chongi.
Graphene nanoscroll (GNS) is a spirally wrapped two-dimensional (2D) graphene sheet (GS) with a 1D tubular structure resembling that of a multiwalled carbon nanotube (MWCNT). GNS provide open structure at both ends and interlayer galleries that can be easily intercalated and adjusted, which show great potential applications in energy storage. Here we demonstrate a novel and simple strategy for the large-scale preparation of GNSs wrapping Fe3O4 nanoparticles (denoted as Fe3O4@GNSs) from graphene oxide (GO) sheets by cold quenching in liquid nitrogen. When a heated aqueous mixed suspension of GO sheets and Fe3O4 nanoparticles is immersed in liquid nitrogen, the in-situ wrapping of Fe3O4 nanoparticles with GNSs is easily realized. The structural conversion is closely correlated with the initial temperature of mixed suspension, the zeta potential of Fe3O4 nanoparticles and the immersion way. Remarkably, such hybrid structure provides the right combination of electrode properties for high-performance lithium-ion batteries. Compared with other wrapping structure, such 1D wrapping structure (GNSs wrapping) effectively limits the volume expansion of Fe3O4 nanoparticles during the cycling process, consequently, a high reversible capacity, good rate capability, and excellent cyclic stability are achieved with the material as anode for lithium storage. The results presented here may pave a way for the large-scale preparation of GNS-based materials in electrochemical energy storage applications.
Dead end 1 (Dnd1), important for maintaining the viability of primordial germ cells, is the first protein containing an RNA recognition motif that has been directly implicated as a heritable cause of spontaneous tumorigenesis. In the present study, c-Jun was identified through yeast two-hybrid screening of a 10.5-day old mouse embryo cDNA library as one of the proteins which interact with dnd1-?. The interaction between Dnd1-? and c-Jun was demonstrated to occur by glutathione S?transferase pull?down and co-immunoprecipitation. Using confocal microscopy, Dnd1-? was found to be specifically expressed in GC-1 spermatogonia cells, mainly in the nuclei. When transfected into GC-1 cells, Dnd1-? and c-Jun were demonstrated to be co-localized principally in the nuclei. Furthermore, in a dual luciferase reporter assay, the transcriptional activity of activator protein 1 was demonstrated to be significantly increased by co-transfection with Dnd1-? and c-Jun plasmids in GC-1 cells. The identification and confirmation of an additional protein interacting with dnd1-? facilitates the investigation of the functions and molecular mechanisms of Dnd1.
Local functional homogeneity of the human cortex indicates the boundaries between functionally heterogeneous regions and varies remarkably across the cortical mantle. It is unclear whether these variations have the neurobiological and structural basis. We employed structural and resting-state functional magnetic resonance imaging scans from 482 healthy subjects and computed the vertex-wise regional homogeneity of low-frequency fluctuations (2dReHo) and five measures of cortical morphology. We then used these metrics to examine regional variation, morphological association and functional covariance network of 2dReHo. Within the ventral visual stream, increases of 2dReHo reflect reduced complexity of information processing or functional hierarchies. Along the divisions of the prefrontal cortex and posteromedial cortex, the gradients of 2dReHo revealed the hierarchical organization within the two association areas, respectively. Individual differences in 2dReHo are associated with those of cortical morphology, and their whole-brain inter-regional covariation is organized into a functional covariance network, comprising five hierarchically organized modules with hubs of both primary sensory and high-order association areas. These highly reproducible observations suggest that local functional homogeneity has neurobiological relevance that is likely determined by anatomical, developmental and neurocognitive factors and should serve as a neuroimaging marker to investigate the human brain function.
Multi-variate pattern analysis (MVPA) applied to BOLD-fMRI has proven successful at decoding complicated fMRI signal patterns associated with a variety of cognitive processes. One cognitive process, not yet investigated, is the mental representation of "Yes/No" thoughts that precede the actual overt response to a binary "Yes/No" question. In this study, we focus on examining: (1) whether spatial patterns of the hemodynamic response carry sufficient information to allow reliable decoding of "Yes/No" thoughts; and (2) whether decoding of "Yes/No" thoughts is independent of the intention to respond honestly or dishonestly. To achieve this goal, we conducted two separate experiments. Experiment 1, collected on a 3T scanner, examined the whole brain to identify regions that carry sufficient information to permit significantly above-chance prediction of "Yes/No" thoughts at the group level. In Experiment 2, collected on a 7T scanner, we focused on the regions identified in Experiment 1 to examine the capability of achieving high decoding accuracy at the single subject level. A set of regions--namely right superior temporal gyrus, left supra-marginal gyrus, and left middle frontal gyrus--exhibited high decoding power. Decoding accuracy for these regions increased with trial averaging. When 18 trials were averaged, the median accuracies were 82.5%, 77.5%, and 79.5%, respectively. When trials were separated according to deceptive intentions (set via experimental cues), and classifiers were trained on honest trials, but tested on trials where subjects were asked to deceive, the median accuracies of these regions still reached 66%, 75%, and 78.5%. These results provide evidence that concealed "Yes/No" thoughts are encoded in the BOLD signal, retaining some level of independence from the subject's intentions to answer honestly or dishonestly. These findings also suggest the theoretical possibility for more efficient brain-computer interfaces where subjects only need to think their answers to communicate.
The aim of this study was to compare the host tissue integration process and biomechanical behaviour after implantation of porcine small intestine submucosa (PSIS) and porcine acellular dermal matrix (PADM) grafts in a rat abdominal wall defect model during a long-term follow-up of 360 days.
Power line interference may severely corrupt neural recordings at 50/60 Hz and harmonic frequencies. The interference is usually non-stationary and can vary in frequency, amplitude and phase. To retrieve the gamma-band oscillations at the contaminated frequencies, it is desired to remove the interference without compromising the actual neural signals at the interference frequency bands. In this paper, we present a robust and computationally efficient algorithm for removing power line interference from neural recordings.
Yes-associated protein 1 (YAP1) is a candidate oncogene that is involved in tumorigenesis and progression of many malignant tumors. Recently, many studies have revealed that YAP1 is highly expressed in human osteosarcoma. To investigate the role of YAP1 in osteosarcoma tumorigenesis, the expression of YAP1 in the osteosarcoma cell lines (MG-63 and HOS) was knocked down by small hairpin RNA (shRNA), and the cell proliferation and colony formation assay showed that knockdown of YAP1 significantly suppressed the cell proliferation and colony formation of osteosarcoma cells. Subsequently, cell cycle distribution was analyzed by flow cytometry, and the results showed an accumulation of YAP1-knockdown cells in the G0/G1 phase, suggesting that YAP1 knockdown results in the arrest of cell cycle progression. Additionally, the knockdown of YAP1 also inhibited the tumorsphere formation in vitro and the growth of xenograft tumors in vivo. Therefore, these data suggest that YAP1 knockdown inhibits the proliferation of osteosarcoma cells. However, the mechanism of action was unclear. Further investigation showed that in the YAP1-knockdown MG-63 and HOS cells, the level of cylinD1 and c-myc expression, target genes of the Wnt signaling pathway and TOP-Flash reporter activity were all significantly decreased, which indicated that the inhibitory effect of YAP1 knockdown on osteosarcoma might be associated with the Wnt signaling pathway. Taken together, our results demonstrated that YAP1 is an important regulator of osteosarcoma tumorigenesis and knockdown of YAP1 would be a novel therapeutic strategy for osteosarcoma.
Bipolar depression (BD) is a common psychiatric illness characterized by deficits in emotional and cognitive processing. Abnormalities in the subregions of the insula are common findings in neuroanatomical studies of patients with bipolar disorder. However, the specific relationships between morphometric changes in specific insular subregions and the pathogenesis of BD are not clear. In this study, structural magnetic resonance imaging (MRI) was used to investigate gray matter volume abnormalities in the insular subregion in 27 patients with BD and in 27 age and sex-matched controls. Using DARTEL (diffeomorphic anatomical registration through exponentiated lie algebra) for voxel-based morphometry (VBM), we examined changes in regional gray matter volumes of the insula in patients with BD. As compared with healthy controls, the BD patients showed decreased gray matter volumes in the right posterior insula and left ventral anterior insula and increased gray matter volumes in the left dorsal anterior insula. Consistent with the emerging theory of insular interference as a contributor to emotional-cognitive dysregulation, the current findings suggest that the insular cortex may be involved in the neural substrates of BD.
Early-onset schizophrenia (EOS) offers a unique opportunity to study pathophysiological mechanisms and development of schizophrenia. Using 26 drug-naïve, first-episode EOS patients and 25 age- and gender-matched control subjects, we examined intrinsic connectivity network (ICN) deficits underlying EOS. Due to the emerging inconsistency between behavior-based psychiatric disease classification system and the underlying brain dysfunctions, we applied a fully data-driven approach to investigate whether the subjects can be grouped into highly homogeneous communities according to the characteristics of their ICNs. The resultant subject communities and the representative characteristics of ICNs were then associated with the clinical diagnosis and multivariate symptom patterns. A default mode ICN was statistically absent in EOS patients. Another frontotemporal ICN further distinguished EOS patients with predominantly negative symptoms. Connectivity patterns of this second network for the EOS patients with predominantly positive symptom were highly similar to typically developing controls. Our post-hoc functional connectivity modeling confirmed that connectivity strength in this frontotemporal circuit was significantly modulated by relative severity of positive and negative syndromes in EOS. This study presents a novel subtype discovery approach based on brain networks and proposes complex links between brain networks and symptom patterns in EOS.
A simple and effective strategy involving nebulized ethanol assisted infiltration for the general synthesis of 3D structure-based vertically aligned carbon nanotube arrays (VACNTs) uniformly and deeply decorated with various transition-metal oxide (MOs) has been developed. Furthermore, it is demonstrated that the 3D structure-based VACNTs with decorated MnO2 can exhibit superior electrocatalytic oxygen reduction reaction activity, long-term stability, and an excellent resistance to crossover effects compared to the commercial Pt/C catalyst.
The role of the WW domain-containing oxidoreductase (WWOX) gene in multiple types of solid human cancers has been documented extensively. However, the functional role of WWOX in human multiple myeloma has not yet been fully elucidated. The present study aimed to investigate the effects of exogenous WWOX expression on the biological properties of U266 multiple myeloma cells, as well as the possible molecular mechanisms involved. In vitro experiments revealed that exogenous WWOX cDNA transfection resulted in marked growth arrest and the induction of apoptosis in the U266 multiple myeloma cells, accompanied by the activation of the intrinsic apoptotic pathway. Our data provide evidence that WWOX also plays a role as a tumor suppressor gene in multiple myeloma, possibly by suppressing cell proliferation and promoting apoptosis by triggering the intrinsic apoptotic pathway.
An active targeting delivery system helps increase intracellular drug delivery, which is promising for the treatment of glioblastoma. Interleukin 13 (IL-13) peptide which was derived from IL-13 protein could specially bind with IL-13R?2, a receptor highly expressed on glioblastoma cells but not on normal brain cells, suggesting IL-13 peptide is an optional ligand for glioblastoma targeted therapy. In this contribution, IL-13 peptide was functionalized to nanoparticles (ILNP) to form a glioblastoma targeted drug delivery system where docetaxel was used as a model drug. The cellular uptake and intracellular delivery of ILNP indicated that IL-13 peptide facilitated cellular uptake of nanoparticles and Golgi apparatus was involved in the sorting and trafficking of ILNP rather than NP in U87 cells. Transmission electron microscopy observation revealed that ILNP mainly distributed into endosomes, cytoplasm and Golgi apparatus. In vitro apoptosis assay indicated docetaxel-loaded ILNP could induce polymerization of microtubules and produce the highest early and late apoptosis of U87 cells. Growth inhibition results of tumor spheroids demonstrated ILNP displayed the best growth inhibition of tumor spheroids. In vivo imaging suggested that ILNP accumulated significantly more in the glioma site than NP while more NP was distributed in liver, lung and spleen than ILNP. Transmission electron microscopy further demonstrated ILNP could distribute into different organelles of cells in glioma site. Thus, docetaxel loaded ILNP could induce the most apoptosis of glioma cells which was demonstrated by TUNEL. In conclusion, we presented a glioblastoma-targeting drug delivery system ILNP, which could increase the intracellular delivery of nanoparticles as well as precisely target to glioblastoma cells, and significantly increase the anti-proliferation and anti-spheroid growth effect.
The purpose of the present study is to determine if visfatin is involved in inflammation or apoptosis induced by LPS in rat. Forty Wistar rats were divided into four groups: saline group, LPS group, visfatin group and Visfatin?+?LPS co-stimulated group. Spleen samples from each group of rats were collected for study. The spleen structure was examined by histological imaging. Apoptosis was evaluated with TUNEL reaction. Caspase-3 was detected with immunohistochemistry and western blot. The apoptosis-related genes were detected by qPCR and inflammatory cytokines were tested by ELISA. Our main findings were as follows. (1) Macrophages were markedly increased in the visfatin group compared with the saline group. This finding was confirmed when spleen samples were examined with western blot using CD68 antibody. (2) Visfatin promoted the expression of CD68 and caspase-3 in rat spleen, whereas visfatin could inhibit the expression of CD68 and activated caspase-3 in spleen of LPS-induced acute inflammation. (3) Visfatin had a pro-apoptotic effect on normal rat spleen, whereas it exerted an anti-apoptotic effect during LPS-induced lymphocytes apoptosis in rat spleen. Moreover, the effect of visfatin on cell apoptosis was mediated by the mitochondrial pathway. (4) Visfatin could modulate both the anti-inflammatory cytokines and pro-inflammatory cytokines in rat spleen, such as IL-10, IL-4, IL-6, TNF-? and IL-1?. Taken together, we demonstrate that visfatin could participate in the inflammatory process in rat spleen by modulating the macrophages and inflammatory cytokines. Also, visfatin plays a dual role in the apoptosis in rat spleen, which is mediated by the mitochondrial pathway.
Aim: Nanoparticles are easier to pass through cell membranes, and they are considered to be the ideal biocompatible and mechanically stable platforms for supporting stem cell growth and differentiation. The aim of this study is to determine the effects of carbon nanotubes (CNTs), graphene oxide (GO) and graphene (GR) on the dopamine neural differentiation of mouse embryonic stem cells (ESCs). Materials & methods: GO was prepared according to a modified Hummers method. GR was synthesized by reduction of GO via l-ascorbic acid as a reductant in an aqueous solution at room temperature. CNTs were fabricated by chemical vapor deposition method. ESCs were differentiated by a stromal cell-derived inducing activity (SDIA) method after 10 days coculture with PA6 cells. The dopamine neural differentiation of the ESCs-GFP was examined by immunocytochemistry and real-time PCR. Results: We found that only GO could effectively promote dopamine neuron differentiation after induction of SDIA and further enhance dopamine neuron-related gene expression compared with cells treated with no nanoparticle control, and the other two nanoparticles (CNTs and GR). Conclusion: These findings suggest that GO is a promising nanomaterial-based technical platform to effectively enhance dopamine neural differentiation of ESCs, which can be potentially applied for cell transplantation therapy. Original submitted 22 April 2013; Revised submitted 13 October 2013.
Cells respond to various chemical signals as well as environmental aspects of the extracellular matrix (ECM) that may alter cellular structures and functions. Hence, better understanding of the mechanical stimuli of the matrix is essential for creating an adjuvant material that mimics the physiological environment to support cell growth and differentiation, and control the release of the growth factor. In this study, we utilized the property of transglutaminase cross-linked gelatin (TG-Gel), where modification of the mechanical properties of TG-Gel can be easily achieved by tuning the concentration of gelatin. Modifying one or more of the material parameters will result in changes of the cellular responses, including different phenotype-specific gene expressions and functional differentiations. In this study, stiffer TG-Gels itself facilitated focal contact formation and osteogenic differentiation while soft TG-Gel promoted cell proliferation. We also evaluated the interactions between a stimulating factor (i.e. BMP-2) and matrix rigidity on osteogenesis both in vitro and in vivo. The results presented in this study suggest that the interactions of chemical and physical factors in ECM scaffolds may work synergistically to enhance bone regeneration.
Parkinson's disease (PD) drug therapy remains a challenge. Dual modulation of dopamine and 5-HT receptors has emerged as a promising approach in anti-PD drug development. Taking advantage of the newly discovered aporphine analogue(s), (6aR)-11-amino-N-propyl-noraporphine (SOMCL-171), which exhibited dual D2/5-HT1A receptor agonistic activity, we studied the effects of the compound on levodopa-induced dyskinesia (LID) in a PD animal model. The results demonstrated that SOMCL-171 elicited a potent anti-PD effect in a 6-OHDA-lesioned rat model. Chronic use of SOMCL-171 reduced LID without compromising the antiparkinsonian efficacy. Furthermore, we found that the antidyskinesia effect of SOMCL-171 is associated with its 5-HT1A agonistic activity and the up-regulation of the striatal 5-HT1A receptor. The present data indicated that chronic SOMCL-171 alone produced potent antiparkinsonian effects with weak dyskinesia, compared with that of levodopa. In addition, chronic SOMCL-171 application attenuated the development of levodopa-induced LID at no expense to the antiparkinsonian efficacy. Taken together, our data suggested that dual modulation of D2/5-HT1A receptors may provide a novel approach for drug development in PD and LID.
Dirofilaria immitis (heartworm) infections affect domestic dogs, cats, and various wild mammals with increasing incidence in temperate and tropical areas. More sensitive antibody detection methodologies are required to diagnose asymptomatic dirofilariasis with low worm burdens. Applying current transcriptomic technologies would be useful to discover potential diagnostic markers for D. immitis infection. A filarial homologue of the mammalian translationally controlled tumor protein (TCTP) was initially identified by screening the assembled transcriptome of D. immitis (DiTCTP). A BLAST analysis suggested that the DiTCTP gene shared the highest similarity with TCTP from Loa loa at protein level (97%). A histidine-tagged recombinant DiTCTP protein (rDiTCTP) of 40 kDa expressed in Escherichia coli BL21 (DE3) showed immunoreactivity with serum from a dog experimentally infected with heartworms. Localization studies illustrated the ubiquitous presence of rDiTCTP protein in the lateral hypodermal chords, dorsal hypodermal chord, muscle, intestine, and uterus in female adult worms. Further studies on D. immitis-derived TCTP are warranted to assess whether this filarial protein could be used for a diagnostic purpose.
As the most common malignant brain tumors, glioblastoma multiforme (GBM) was characterized by angiogenesis and tumor cells proliferation. Dual targeting to neovasculature and GBM cells could deliver cargoes to these two kinds of cells, leading to a combination treatment. In this study, polymeric nanoparticles were functionalized with RGD and interleukin-13 peptide (IRNPs) to construct a neovasculature and tumor cell dual targeting delivery system in which RGD could target ?v?3 on neovasculature and interleukin-13 peptide could target IL13R?2 on GBM cells. In vitro, interleukin-13 peptide and RGD could enhance the uptake by corresponding cells (C6 and human umbilical vein endothelial cells). Due to the expression of both receptors on C6 cells, RGD also could enhance the uptake by C6 cells. Through receptor labeling, it clearly showed that ?v?3 could mediate the internalization of RGD modified nanoparticles and IL13R?2 could mediate the internalization of interleukin-13 peptide modified nanoparticles. The ligand functionalization also resulted in a modification on endocytosis pathways, which changed the main endocytosis pathways from macropinocytosis for unmodified nanoparticles to clathrin-mediated endocytosis for IRNPs. IRNPs also displayed the strongest penetration ability according to tumor spheroid analysis. In vivo, IRNPs could effectively deliver cargoes to GBM with higher intensity than monomodified nanoparticles. After CD31-staining, it demonstrated IRNPs could target both neovasculature and GBM cells. In conclusion, IRNPs showed promising ability in dual targeting both neovasculature and GBM cells.
Multi-layered hollow LiYF4:Eu(3+) micro-octahedrons, with about 400 nm of single-layer thickness and 300 nm of interlayer space, have been synthesized via a facile hydrothermal route in the presence of surfactant ethylenediamine tetraacetic acid (EDTA). The mechanisms of the morphology evolution of the LiYF4:Eu micro-octahedrons are investigated in detail. Time-dependent experiments indicate that the growth of the micro-octahedrons undergoes four different stages including the aggregation growth of the primary YF3 particle, the transformation of the substance from the orthorhombic-phase YF3 to the tetragonal-phase LiYF4 by the Kirkendall effect with the inward diffusion of quasi-steady state LiF species, adsorption and in situ crystallization, and local Ostwald ripening. The Ostwald ripening process is terminated by the organic adsorption of interlaminar leading to a hollow structure with multilevel interiors. The LiYF4:Eu micro-octahedrons are annealed under the designed temperatures, which leads to the collapse of octahedral structures indicating the role of EDTA on building the octahedron. The spectral measurements show that the calcination approach has a stronger effect on the luminescence tuning of the LiYF4:Eu micro-octahedrons due to the modification of the crystal phase, structure and size. The present study is of great importance in the preparation of rare-earth ion doped LiYF4 hollow materials as well as in applications as building blocks for functional devices.
Calanus sinicus Brodsky (Copepoda, Crustacea) is a dominant zooplanktonic species widely distributed in the margin seas of the Northwest Pacific Ocean. In this study, we utilized an RNA-Seq-based approach to develop molecular resources for C. sinicus. Adult samples were sequenced using the Illumina HiSeq 2000 platform. The sequencing data generated 69,751 contigs from 58.9 million filtered reads. The assembled contigs had an average length of 928.8?bp. Gene annotation allowed the identification of 43,417 unigene hits against the NCBI database. Gene ontology (GO) and KEGG pathway mapping analysis revealed various functional genes related to diverse biological functions and processes. Transcripts potentially involved in stress response and lipid metabolism were identified among these genes. Furthermore, 4,871 microsatellites and 110,137 single nucleotide polymorphisms (SNPs) were identified in the C. sinicus transcriptome sequences. SNP validation by the melting temperature (T m )-shift method suggested that 16 primer pairs amplified target products and showed biallelic polymorphism among 30 individuals. The present work demonstrates the power of Illumina-based RNA-Seq for the rapid development of molecular resources in nonmodel species. The validated SNP set from our study is currently being utilized in an ongoing ecological analysis to support a future study of C. sinicus population genetics.
To evaluate the internalization and subcellular fate of AS1411 aptamer (for glioma targeting) and TGN peptide (for blood-brain barrier targeting)-modified nanoparticles (AsTNPs), which was important for optimizing targeted delivery systems and realizing the potential toxicity to cells.
Numerous studies have shown cerebellar involvement in item-specific association, a form of explicit learning. However, very few have demonstrated cerebellar participation in automation of non-motor cognitive tasks. Applying fMRI to a repeated verb-generation task, we sought to distinguish cerebellar involvement in learning of item-specific noun-verb association and automation of verb generation skill. The same set of nouns was repeated in six verb-generation blocks so that subjects practiced generating verbs for the nouns. The practice was followed by a novel block with a different set of nouns. The cerebellar vermis (IV/V) and the right cerebellar lobule VI showed decreased activation following practice; activation in the right cerebellar Crus I was significantly lower in the novel challenge than in the initial verb-generation task. Furthermore, activation in this region during well-practiced blocks strongly correlated with improvement of behavioral performance in both the well-practiced and the novel blocks, suggesting its role in the learning of general mental skills not specific to the practiced noun-verb pairs. Therefore, the cerebellum processes both explicit verbal associative learning and automation of cognitive tasks. Different cerebellar regions predominate in this processing: lobule VI during the acquisition of item-specific association, and Crus I during automation of verb-generation skills through practice.
The present study aimed to determine the mechanism by which low?intensity intermittent negative pressure affects the differentiation and proliferation of human mesenchymal stem cells (MSCs). Alkaline phosphatase (ALP) activity, type I collagen and vascular endothelial growth factor (VEGF) were detected to analyze differentiation. MTT and flow cytometry were employed to measure proliferation and apoptosis. Western blot analysis was used to examine endoplasmic reticulum (ER) stress?associated factors. This study was divided into two groups, including a normal group (without any treatment) and vacuum group (treated with a vacuum). There was a significant decrease in the proliferation of cells in the vacuum group. The number of cells in S phase was reduced significantly, while the rate of apoptosis and the activity of ALP were markedly increased under vacuum conditions. Expression of collagen type I and VEGF was significantly increased, and the ratio of osteoprotegrin to osteoprotegrin ligand was decreased significantly in the vacuum group. ER stress?associated proteins, p?PRKR?like ER kinase, inositol?requiring enzyme 1 and cleaved activating transcription factor 6, as well as the downstream factors, were activated when treated with negative pressure. In conclusion, treatment with low?intensity and intermittent negative pressure may inhibit the proliferation of MSCs and trigger ER stress?associated cellular apoptosis, further enhancing osteogenesis activity and inducing differentiation to osteoblasts.
Photoelectrode of nanocables (NCs) structure of ZnO nanowires (NWs) coated with Al-doped ZnO (AZO) shells was investigated for CdS quantum dots sensitized solar cells (QDSSCs). ZnO NWs serve as the frame for the preparation of AZO shells, in which electron transport more rapidly due to the more higher electron mobility of AZO (n-ZnO) than that of i-ZnO. AZO shells were assembled onto the surface of ZnO NWs via a spin-coating method. Optical band-gap of the ZnO/AZO films varies from 3.19 eV for pure ZnO to 3.25 eV for AZO (15%) depending on the Al-doping concentration. The PL intensity of AZO/ZnO, V(oc), J(sc) and ? of the cells first increased and then decreased with the increase in the Al-doping (from 0% to 20%) and post-annealed temperature. Remarkably, the value of V(oc) can achieve above 0.8 V after Al-doping. The dark current and absorption spectrum provided direct evidence of the increase in J(sc) and V(oc), respectively. Moreover, we discussed the effect of Al-doping on optical band-gap of the samples and the transfer of electron.
In vivo neural recordings are often corrupted by different artifacts, especially in a less-constrained recording environment. Due to limited understanding of the artifacts appeared in the in vivo neural data, it is more challenging to identify artifacts from neural signal components compared with other applications. The objective of this work is to analyze artifact characteristics and to develop an algorithm for automatic artifact detection and removal without distorting the signals of interest.
Recycling is a simple and efficient strategy for improving the peak resolution. In this work, a novel multi-channel recycling counter-current chromatography (CCC) was successfully established and three representative three-channel recycling CCC systems including 1R, 2R, and 3R CCC recycling on one, two, and three channel columns were developed for four typical tanshinones fractions. The results demonstrated that all recycling CCC separations were efficient for the isolation of targeted tanshinones. 1R CCC not only provided the single recycling separation, but also offered two parallel recycling separation or repeated preparation for multiple targets. 2R CCC provided the increased peak resolution and less risk of overlapping. 3R CCC offered versatile elution and recycling modes for multiple targets. Compared to 1R and 2R CCC, 3R CCC was easier to separate the more complex natural products with more targets in the complex natural extracts. In summary, the developed multi-channel recycling CCC systems including 1R, 2R, and 3R CCC were successful and efficient for resolving the complex natural tanshinones. To the best of our knowledge, this is the first document to report the multi-channel recycling CCC methods for the separation of tanshinones. They may be used as new multi-dimensional recycling CCC for targeted and non-targeted isolation of natural products. It may be widely used for current natural drug development and metabolome analysis.
The surface wettability is one of the most important factors to control the morphology of nanoparticle arrangement on the solid substrates. The various morphologies of FePt nanoparticles were fabricated on different substrates with different wetting surfaces by the Langmuir-Blodgett (LB) technology at large scale. A highly ordered structure and a dense arrangement of FePt nanoparticle monolayer were obtained on different substrates with contact angle up to 66°. The air pockets could be presented between the nanoparticles and solid substrate by theoretical analysis, because FePt nanoparticles had hydrophobic surface. A net structure of FePt nanoparticles on solid substrates could be also obtained by controlling about 45° contact angles of their surfaces. This method potentially opens up a new approach to controlling assembly of nanoparticle monolayer on solid substrates by change of the wettability on the surfaces of solid substrate and provides a promising thin film which may exhibit the excellent ultra high density magnetic recording properties.
The objective of this study was the development of a dual-modality imaging device, namely (111)In-core-cross-linked polymeric micelle (CCPM)-octreotide, for neuroendocrine tumor detection, using near-infrared fluoroscopy (NIRF) and single photon emission computed tomography (SPECT). The tumor targeting ability of the (111)In-labeled CCPM-octreotide was evaluated in a tumor mouse model. SPECT/CT, NIRF and gamma imaging results showed high tumor uptake of (111)In-labeled CCPM-octreotide. In contrast, there was a much lower signal in the same mouse model injected with (111)In-labeled CCPM. The high accumulation of (111)In-labeled CCPM-octreotide in U87 tumor was reduced after co-injection with an excess amount of CCPM-octreotide. These results suggested CCPM-octreotide's potential applications in tumor diagnosis, drug delivery and molecular imaging.
Silicone rubber (SR) is a common soft tissue filler material used in plastic surgery. However, it presents a poor surface for cellular adhesion and suffers from poor biocompatibility. In contrast, hydroxyapatite (HA), a prominent component of animal bone and teeth, can promote improved cell compatibility, but HA is an unsuitable filler material because of the brittleness in mechanism. In this study, using a simple and economical method, two sizes of HA was applied to coat on SR to counteract the poor biocompatibility of SR. Surface and mechanical properties of SR and HA/SRs confirmed that coating with HA changes the surface topology and material properties. Analysis of cell proliferation and adhesion as well as measurement of the expression levels of adhesion related molecules indicated that HA-coated SR significantly increased cell compatibility. Furthermore, mass spectrometry proved that the biocompatibility improvement may be related to elongation factor 1-beta (EF1?)/?-actin adjusted cytoskeletal rearrangement.
Medical device implants are drawing increasing amounts of interest from modern medical practitioners. However, this attention is not evenly spread across all such devices; most of these implantable devices can cause adverse reactions such as inflammation, fibrosis, thrombosis, and infection. In this work, the biocompatibility of silicone rubber (SR) was improved through carbon (C) ion implantation. Scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) results confirmed that these newly generated carbon-implanted silicone rubbers (C-SRs) had large, irregular peaks and deep valleys on their surfaces. The water contact angle of the SR surface decreased significantly after C ion implantation. C ion implantation also changed the surface charge distribution, silicone oxygen rate, and chemical-element distribution of SR to favor cell attachment. The dermal fibroblasts cultured on the surface C-SR grew faster and showed more typical fibroblastic shapes. The expression levels of major adhesion proteins, including talin-1, zyxin, and vinculin, were significantly higher in dermal fibroblasts cultured on C-SR coated plates than in dermal fibroblasts cultured on SR. Those same dermal fibroblasts on C-SRs showed more pronounced adhesion and migration abilities. Osteopontin (OPN), a critical extracellular matrix (ECM) protein, was up-regulated and secreted from dermal fibroblasts cultured on C-SR. Matrix metalloproteinase-9 (MMP-9) activity was also increased. These cells were highly mobile and were able to adhere to surfaces, but these abilities were inhibited by the monoclonal antibody against OPN, or by shRNA-mediated MMP-9 knockdown. Together, these results suggest that C ion implantation significantly improves SR biocompatibility, and that OPN is important to promote cell adhesion to the C-SR surface.
Whether Tai Chi Chuan (TCC) can influence the intrinsic functional architecture of the human brain remains unclear. To examine TCC-associated changes in functional connectomes, resting-state functional magnetic resonance images were acquired from 40 older individuals including 22 experienced TCC practitioners (experts) and 18 demographically matched TCC-naïve healthy controls, and their local functional homogeneities across the cortical mantle were compared. Compared to the controls, the TCC experts had significantly greater and more experience-dependent functional homogeneity in the right post-central gyrus (PosCG) and less functional homogeneity in the left anterior cingulate cortex (ACC) and the right dorsal lateral prefrontal cortex. Increased functional homogeneity in the PosCG was correlated with TCC experience. Intriguingly, decreases in functional homogeneity (improved functional specialization) in the left ACC and increases in functional homogeneity (improved functional integration) in the right PosCG both predicted performance gains on attention network behavior tests. These findings provide evidence for the functional plasticity of the brain's intrinsic architecture toward optimizing locally functional organization, with great implications for understanding the effects of TCC on cognition, behavior and health in aging population.
A simple and sensitive gap-electrical biosensor based on self-catalytic growth of unmodified gold nanoparticles (AuNPs) as conductive bridges has been developed for amplifying DNA hybridization events. In this strategy, the signal amplification degree of such conductive bridges is closely related to the variation of the glucose oxidase (GOx)-like catalytic activity of AuNPs upon interaction with single- and double-stranded DNA (ssDNA and dsDNA), respectively. In the presence of target DNA, the obtained dsDNA product cannot adsorb onto the surface of AuNPs due to electrostatic interaction, which makes the unmodified AuNPs exhibit excellent GOx-like catalytic activity. Such catalytic activity can enlarge the diameters of AuNPs in the glucose and HAuCl4 solution and result in a connection between most of the AuNPs and a conductive gold film formation with a dramatically increased conductance. For the control sample, the catalytic activity sites of AuNPs are fully blocked by ssDNA due to the noncovalent interaction between nucleotide bases and AuNPs. Thus, the growth of the assembled AuNPs will not happen and the conductance between microelectrodes will be not changed. Under the optimal experimental conditions, the developed strategy exhibited a sensitive response to target DNA with a high signal-to-noise ratio. Moreover, this strategy was also demonstrated to provide excellent differentiation ability for single-nucleotide polymorphism. Such performances indicated the great potential of this label-free electrical strategy for clinical diagnostics and genetic analysis under real biological sample separation.
Ultrafast and sensitive room temperature NH3 gas sensors based on chemically reduced graphene oxide (rGO) are demonstrated in this work. rGO, which was prepared via the reduction of graphene oxide by pyrrole, exhibited excellent responsive sensitivity and selectivity to ammonia (NH3) gas. The high sensing performance of these rGO sensors with resistance change as high as 2.4% and response time as fast as 1.4 s was realized when the concentration of NH3 gas was as low as 1 ppb. Furthermore, the rGO sensors could rapidly recover to their initial states with IR illumination. The devices also showed excellent repeatability and selectivity to NH3. These rGO sensors, with low cost, low power, and easy fabrication, as well as scalable properties, showed great potential for ultrasensitive detection of NH3 gas in a wide variety of fields.
The plasmonic optical properties of nanostructures including a dimer, a linear chain, a T-shaped nanostructure, and a 2D array consisting of Ag nanocubes have been investigated using the discrete dipole approximation method. The simulation results indicate that both the interparticle gap and polarization have an important impact on far-field and near-field characteristics. With decreasing interparticle distance for four nanostructures, the plasmon resonance peak is monotonically red-shifted and the electric intensity enhancement factor increases rapidly due to increased interparticle coupling interaction. Moreover, we also find that a T-shaped nanostructure has the largest electric intensity enhancement factor compared with other three nanostructures due to the coupling interaction at the intersection. This coupling is caused by the radiative interference between subradiant and superradiant resulting in Fano resonance. These results show how nanostructure arrangement design, gap adjustment, and polarization control can be used to achieve high field enhancements.
Highly uniform hole spacing micro brushes were fabricated based on aligned carbon nanotube (CNT) arrays synthesized by chemical vapor deposition method with the assistance of anodic aluminum oxide (AAO) template. Different micro brushes from CNT arrays were constructed on silicon, glass, and polyimide substrates, respectively. The micro brushes had highly uniform hole spacing originating from the regularly periodic pore structure of AAO template. The CNT arrays, serving as bristles, were firmly grafted on the substrates. The brushes can easily clean particles with scale of micrometer on the surface of silicon wafer and from the narrow spaces between the electrodes in a series of cleaning experiments. The results show the potential application of the CNT micro brushes as a cleaning tool in microelectronics manufacture field.
In this paper we propose an algorithm for distributed optimization in mobile nodes. Compared with many published works, an important consideration here is that the nodes do not know the cost function beforehand. Instead of decision-making based on linear combination of the neighbor estimates, the proposed algorithm relies on information-rich nodes that are iteratively identified. To quickly find these nodes, the algorithm adopts a larger step size during the initial iterations. The proposed algorithm can be used in many different applications, such as distributed odor source localization and mobile robots. Comparative simulation results are presented to support the proposed algorithm.
Experiment analysis on in-vivo data sequences suggests a wide system dynamic range (DR) is required to simultaneously record local field potentials (LFPs), extra-cellular spikes, and artifacts/interferences. In this paper, we present a 13 µW 87 dB DR ?? modulator for full-spectrum neural recording. To achieve a wide DR and low power consumption, a fully-differential topology is used with multi-bit (MB) quantization scheme and switched-opamp (SO) technique. By adopting a novel fully-clocked scheme, a power-efficient current-mirror SO is developed with 50% power saving, which doubles the figure-of-merit (FOM) over its counterpart. A new static power-less multi-bit quantizer with 96% power and 69% area reduction is also introduced. Besides, instead of metal-insulator-metal (MIM) capacitor, three high-density MOS capacitor (MOSCAP) structures are employed to reduce circuit area. Measurement results show a peak signal-to-noise and distortion ratio (SNDR) of 85 dB with 10 kHz bandwidth at 1.0 V supply, corresponding to an FOM of 45 fJ/conv.-step. which is implemented in a 0.18 µm CMOS.
This paper models signals and noise for extracellular neural recording. Although recorded data approximately follow Gaussian distribution, there are slight deviations that are critical for signal detection: a statistical examination of neural data in Hilbert space shows that noise forms an exponential term while signals form a polynomial term. These two terms can be used to estimate a spiking probability map that indicates spike presence. Both synthesized data and animal data are used for the detection performance evaluation and comparison against other popular detectors. Experimental results suggest that the predicted spiking probability map is consistent with the benchmark and work robustly with different recording preparations.
In extracellular neural recording experiments, spike detection is an important step for information decoding of neuronal activities. An ASIC implementation of detection algorithms can provide substantial data-rate reduction and facilitate wireless operations. In this paper, we present a 16-channel neural spike detection ASIC. The chip takes raw data as inputs, and outputs three data streams simultaneously: field potentials down sampled at 1.25 KHz, band-pass filtered neural data, and spiking probability maps sampled at 40 KHz. The functionality and the performance of the chip have been verified in both in-vivo and benchtop experiments. Fabricated in a 0.13 µm CMOS process, the chip has a peak power dissipation of 85 µW per channel and achieves a data-rate reduction of 98.44%.
The exposure of skin keratinocytes to Ultraviolet (UV) irradiation leads to Akt phosphorylation at Ser-473, which is important for the carcinogenic effects of excessive sun exposure. The present study investigated the underlying mechanism of Akt Ser-473 phosphorylation by UVB radiation.
Glioblastoma multiforme (GBM), one of the most common primary malignant brain tumors, was characterized by angiogenesis and tumor cells proliferation. Antiangiogenesis and antitumor combination treatment gained much attention because of the potency in dual inhibition of both the tumor proliferation and the tumor invasion. In this study, a neovasculature and tumor cell dual targeting delivery system was developed through modification of nanoparticles with interleukin-13 peptide and RGD (IRNPs), in which interleukin-13 peptide was targeting GBM cells and RGD was targeting neovasculature. To evaluate the potency in GBM treatment, docetaxel was loaded into IRNPs. In vitro, interleukin-13 peptide and RGD could enhance the corresponding cells (C6 and human umbilical vein endothelial cells) uptake and cytotoxicity. In combination, IRNPs showed high uptake in both cells and increased the cytotoxicity on both cells. In vivo, IRNPs could effectively deliver cargoes to GBM with higher intensity than mono-modified nanoparticles. Correspondingly, docetaxel-IRNPs displayed best anti-tumor effect with a median survival time of 35 days, which was significantly longer than that of mono-modified and unmodified nanoparticles. Importantly, treatment with docetaxel-IRNPs could avoid the accumulation of HIF1? in GBM site, which was crucial for the tumor invasion. After the treatment, there was no obvious change in normal organs of mice.
To test the hypothesis that the astrocytic chemokine (C-C motif) ligand 2 (CCL2) plays an important role in nocifensive behaviors after experimental tooth movement (ETM), the expression and cellular localization of CCL2 and astrocyte activation in the medullary dorsal horn (MDH) were determined by immunohistochemistry in rats. The dose-dependent effects of intrathecal C-C chemokine receptor type 2 (CCR2) antagonists on these changes in nocifensive behaviors were evaluated. Exogenous CCL2 was added to medullary dorsal horn slices to evaluate its contributory role in the induction of extracellular signal-regulated kinase (ERK) activation ex vivo. We found a significant increase in the expression of CCL2 and glial fibrillary acidic protein (GFAP), corresponding well to the nocifensive behaviors after ETM. In addition, application of recombinant CCL2 led to ERK activation, which could be attenuated effectively by pretreatment with CCL2-neutralizing antibody ex vivo. The magnitude of the nocifensive behavior could be reduced by medullary CCR2 antagonists in a dose-dependent manner. Therefore, the astrocytic CCL2 is actively involved in the development and maintenance of tooth-movement pain and thus may be a potential target for analgesics in orthodontic nocifensive responses control.
Multi-dimensional chromatography offers the increased resolution and peak capacity by coupling of multiple columns with the same or different separation mechanisms. In this work, a novel multi-channel multi-dimensional counter-current chromatography (CCC) has been successfully constructed and used for several two-dimensional (2D) and three-dimensional (3D) CCC separations including 2D A×B/A×C, A×B-C and A-B×C, and 3D A×B×C systems. These 2D and 3D CCC systems were further applied to separate the bioactive tanshinones from the extract of Tanshen (or Danshen, Salvia miltiorrhiza Bunge), a famous Traditional Chinese Medicine (TCM). As a result, the developed 2D and 3D CCC methods were successful and efficient for resolving the tanshinones from complex extracts. Compared to the 1D multiple columns CCC separation, the 2D and 3D CCC decrease analysis time, reduce solvent consumption and increase sample throughput significantly. It may be widely used for current drug development, metabolomic analysis and natural product isolation.
ZnO with graphene oxide (GO-ZnO) & reduced graphene oxide (rGO-ZnO) buffer layers were fabricated. Photoluminescence (PL) properties of GO-ZnO and rGO-ZnO compositions induced by oxygen vacancies defects were investigated using photoluminescence spectroscopy. The results showed that blue emission is quenched while yellow-orange emissions from GO-ZnO and rGO-ZnO compositions are significantly increased as compared to that of ZnO films. In stark contrast to enhanced yellow-orange emissions, PL spectra show three sharp, discrete emissions that characterize the dominant optical active defect, which is the oxygen vacancies and extended oxygen vacancies. Our results highlight the ability of GO & rGO buffer layers to modulate defect concentrations in ZnO and contribute to understanding the optical properties of deep-level defects, which is significant for development of long-wavelength photoelectric devices related with graphene materials.
A dual targeting delivery system was developed to completely conquer the two barriers that glioma treatment faces: the blood-brain barrier (BBB) and the brain-glioma barrier. Recently, a system comprising AS1411 aptamer (for glioma targeting) and TGN peptide (for BBB targeting) modified nanoparticles (AsTNPs) was developed, which can effectively target brain glioma and improve the survival of glioma-bearing mice. However, the in vitro models currently used are far too different from the in vivo tumor microenvironment that the glioma targeting delivery system actually faces. In this study, the pharmacology mechanisms of AsTNPs were explored in several models that imitated the tumor microenvironment. AsTNPs can be selectively taken up by endothelial and glioma cells, effectively penetrating the BBB and brain-glioma barriers to reach glioma cells and display their anti-glioma effect. The cell monolayers, tumor spheroids and coculture systems were more suitable in vitro models for the pharmacology evaluation of targeted drug delivery systems.
Tumor-targeted delivery systems are useful in enhancing drug delivery and increasing anti-tumor effects. Cell-penetrating peptides have been widely used for this purpose but have been hampered by the poor selectivity between neoplastic and non-neoplastic cells. As a peptide derived from interleukin-13, interleukin-13 peptide (IL-13p) is specifically targeted to IL13R?2, a tumor-restricted receptor. More interestingly, IL-13p possesses cell-penetrating properties that can specifically enhance the uptake by tumor cells compared with endothelial cells. Thus, we anchored IL-13p onto nanoparticles (ILNPs) for glioma-targeting delivery. The uptake of ILNPs by U87 cells was higher than that of unmodified nanoparticles (NPs). However, there was no significant difference in the uptake by human umbilical vein endothelial cells. In addition, free IL-13p could also enhance the uptake of both NPs and ILNPs by U87 cells. Anchoring with IL-13p could enhance the penetration of particles into the core of spheroids. In vivo, the fluorescence intensity of ILNPs in tumors was 2.96-fold higher than that of NPs. The modification with IL-13p also significantly improved the speed and rate of penetration from vessels to tumor cells. The enhanced tumor localization of ILNPs was mostly attributable to the elevated tumor cell internalization of ILNPs, whereas most NPs were colocalized with microvessels or macrophages. Correspondingly, docetaxel-loaded NPs effectively suppressed the growth of subcutaneous U87 tumors. The average tumor volume of the ILNP group was only 31.4% that of the control, which was significantly smaller than that of the docetaxel and NP groups. In conclusion, the modification of IL-13p selectively enhanced tumor cell uptake, improved the penetration effect of NPs and improved the glioma localization ability, which led to a better tumor-suppression effect.
We demonstrate a facile one-pot approach for the synthesis of reduced graphene oxide (rGO)-cuprous sulfide quantum dot (Cu?S QD) hybrids, wherein the reduction of GO and the growth of Cu?S QDs on graphene occur simultaneously. The as-synthesized rGO-Cu?S QD hybrids exhibit an excellent photoelectric response and efficient electron transfer from the Cu?S QDs to the rGO sheets.
Retinal prostheses have restored light perception to people worldwide who have poor or no vision as a consequence of retinal degeneration. To advance the quality of visual stimulation for retinal implant recipients, a higher number of stimulation channels is expected in the next generation retinal prostheses, which poses a great challenge to system design and verification. This paper presents a system verification platform dedicated to the development of retinal prostheses. The system includes primary processing, dual-band power and data telemetry, a high-density stimulator array, and two methods for output verification. End-to-end system validation and individual functional block characterization can be achieved with this platform through visual inspection and software analysis. Custom-built software running on the computers also provides a good way for testing new features before they are realized by the ICs. Real-time visual feedbacks through the video displays make it easy to monitor and debug the system. The characterization of the wireless telemetry and the demonstration of the visual display are reported in this paper using a 256-channel retinal prosthetic IC as an example.
The default network of the human brain has drawn much attention due to its relevance to various brain disorders, cognition, and behavior. However, its functional components and boundaries have not been precisely defined. There is no consensus as to whether the precuneus, a hub in the functional connectome, acts as part of the default network. This discrepancy is more critical for brain development and aging studies: it is not clear whether age has a stronger impact on the default network or precuneus, or both. We used Generalized Ranking and Averaging Independent Component Analysis by Reproducibility (gRAICAR) to investigate the lifespan trajectories of intrinsic functional networks. By estimating individual-specific spatial components and aligning them across subjects, gRAICAR measures the spatial variation of component maps across a population without constraining the same components to appear in every subject. In a cross-lifespan fMRI dataset (N=126, 7-85years old), we observed stronger age dependence in the spatial pattern of a precuneus-dorsal posterior cingulate cortex network compared to the default network, despite the fact that the two networks exhibit considerable spatial overlap and temporal correlation. These results remained even when analyses were restricted to a subpopulation with very similar head motion across age. Our analyses further showed that the two networks tend to merge with increasing age. Post-hoc analyses of functional connectivity confirmed the distinguishable cross-lifespan trajectories between the two networks. Based on these observations, we proposed a dynamic model of cross-lifespan functional segregation and integration between the two networks, suggesting that the precuneus network may have a different functional role than the default network, which declines with age. These findings have implications for understanding the functional roles of the default network, gaining insight into its dynamics throughout life, and guiding interpretation of alterations in brain disorders.
This study aimed to explore the assessment value of virtual touch quantization (VTQ) for the clinicopathological typing of renal fibrosis. The quantitative detection of 76 patients with nephropathy was performed using acoustic radiation force impulse imaging (ARFI). The extent of the renal fibrosis in each patient was confirmed using ultrasound-guided biopsy pathology. The VTQ values were compared with the degree of renal fibrosis in order to analyze the correlation between them. Patients were divided pathologically into four groups, as follows: non-fibrosis (n=14), mild fibrosis (n=40), moderate fibrosis (n=21) and severe fibrosis (n=1). Compared with the non-fibrosis group, the VTQ values of the mild and moderate fibrosis groups were significantly increased (P<0.01); however, there was no significant difference between the VTQ values of the mild and moderate fibrosis groups (P>0.05). According to the receiver operating characteristic (ROC) curve, a VTQ value of renal parenchyma of >1.67 m/sec was determined to be an indicator of renal fibrosis, with a sensitivity of 86.3% and a specificity of 83.3%. VTQ technology may be significant in the assessment of the extent of renal fibrosis.
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