A bioinspired configurable cochlea based on memristors.

Cochleas are the basis for biology to process and recognize speech information, emulating which with electronic devices helps us construct high-efficient intelligent voice systems. Memristor provides novel physics for performing neuromorphic engineering beyond complementary metal-oxide-semiconductor technology. This work presents an artificial cochlea based on the shallen-key filter model configured with memristors, in which one filter emulates one channel. We first fabricate a memristor with the TiN/HfOx/TaOx/TiN structure to implement such a cochlea and demonstrate the non-volatile multilevel states through electrical operations. Then, we build the shallen-key filter circuit and experimentally demonstrate the frequency-selection function of cochlea's five channels, whose central frequency is determined by the memristor's resistance. To further demonstrate the feasibility of the cochlea for system applications, we use it to extract the speech signal features and then combine it with a convolutional neural network to recognize the Free Spoken Digit Dataset. The recognition accuracy reaches 92% with 64 channels, compatible with the traditional 64 Fourier transform transformation points of mel-frequency cepstral coefficients method with 95% recognition accuracy. This work provides a novel strategy for building cochleas, which has a great potential to conduct configurable, high-parallel, and high-efficient auditory systems for neuromorphic robots.

Low energy consumption fiber-type memristor array with integrated sensing-memory.

The increasing growth of electronic information science and technology has triggered the renaissance of the artificial sensory nervous system (SNS), which can emulate the response of organisms towards external stimuli with high efficiency. In traditional SNS, the sensor units and the memory units are separated, and therefore difficult to miniaturize and integrate. Here, we have incorporated the sensor unit and the memory unit into one system, taking advantage of the unique properties of the ion-gel system. Meanwhile, the weaving-type memory array presents paramount advantages of integration and miniaturization and conformal lamination to curved surfaces. It is worth noting that the electrical double layer (EDL) within the ion gel endow the device with a low operation voltage (<1 V) to achieve low energy consumption. Finally, according to the relationship of pressure stimuli and electrical behavior, the integrated responsiveness-storage external stimuli ability is achieved. Our work offers a new platform for designing cutting edge SNS.

A Heterogeneously Integrated Spiking Neuron Array for Multimode-Fused Perception and Object Classification.

Multimode-fused sensing in the somatosensory system helps people obtain comprehensive object properties and make accurate judgments. However, building such multisensory systems with conventional metal-oxide-semiconductor technology presents serious device integration and circuit complexity challenges. Here, a multimode-fused spiking neuron (MFSN) with a compact structure to achieve human-like multisensory perception is reported. The MFSN heterogeneously integrates a pressure sensor to process pressure and a NbOx -based memristor to sense temperature. Using this MFSN, multisensory analog information can be fused into one spike train, showing excellent data compression and conversion capabilities. Moreover, both pressure and temperature information are distinguished from fused spikes by decoupling the output frequencies and amplitudes, supporting multimodal tactile perception. Then, a 3 × 3 MFSN array is fabricated, and the fused frequency patterns are fed into a spiking neural network for enhanced tactile pattern recognition. Finally, a larger MFSN array is simulated for classifying objects with different shapes, temperatures, and weights, validating the feasibility of the MFSNs for practical applications. The proof-of-concept MFSNs enable the building of multimodal sensory systems and contribute to the development of highly intelligent robotics.

Implementing in-situ self-organizing maps with memristor crossbar arrays for data mining and optimization.

A self-organizing map (SOM) is a powerful unsupervised learning neural network for analyzing high-dimensional data in various applications. However, hardware implementation of SOM is challenging because of the complexity in calculating the similarities and determining neighborhoods. We experimentally demonstrated a memristor-based SOM based on Ta/TaOx/Pt 1T1R chips for the first time, which has advantages in computing speed, throughput, and energy efficiency compared with the CMOS digital counterpart, by utilizing the topological structure of the array and physical laws for computing without complicated circuits. We employed additional rows in the crossbar arrays and identified the best matching units by directly calculating the similarities between the input vectors and the weight matrix in the hardware. Using the memristor-based SOM, we demonstrated data clustering, image processing and solved the traveling salesman problem with much-improved energy efficiency and computing throughput. The physical implementation of SOM in memristor crossbar arrays extends the capability of memristor-based neuromorphic computing systems in machine learning and artificial intelligence.

Hyaluronic Acid Modified Curcumin-Loaded Chitosan Nanoparticles Inhibit Chondrocyte Apoptosis to Attenuate Osteoarthritis via Upregulation of Activator Protein 1 and RUNX Family Transcription Factor 2.

Hyaluronic acid (HA) and curcumin (CUR) have been previously utilized for osteoarthritis (OA) treatment. CUR-loaded chitosan nanoparticles (CUR@CS NPs) and HA CUR@CS NPs were synthesized in our research to ascertain the synergistic impacts of HA and CUR-loaded NPs on OA treatment. CUR@CS NPs and HA CUR@CS NPs were synthesized with evaluation of their particle size, potential, PDI, encapsulation efficiency, drug loading and surface coating as well as HA binding rate. The in vitro CUR release curve and stability of HA-CUR@CS NPs were measured. Chondrocytes were isolated from the cartilages of OA patients, followed by cell uptake assay. The chondrocyte viability and apoptosis were determined. Subsequently, the knee OA model was established, followed by H&E, Safranin O/Fast green staining and micro-CT. HA CUR@CS NPs improved CUR stability and bioavailability. CUR@CS NPs and HA-CUR@CS NPs were successfully characterized and could further be internalized by chondrocytes. CUR@CS NPs promoted tBHP-induced chondrocyte viability and inhibited chondrocyte apoptosis. HA-CUR@CS NPs upregulated the AP-1 and RUNX2 transcription levels to activate Hedgehog pathway, which subsequently blocked the Notch pathway. Mechanically, HA-CUR@CS NPs sustained release and long-lasting effect and long-term retention in the joint cavity and downregulated the expression of several pro-inflammatory cytokines in vivo. HA-CUR@CS NPs exhibited superior effects in the preceding experiments than CUR@CS NPs. Altogether, HA-CUR@CS NPs may restrict inflammation and chondrocyte apoptosis in OA through upregulation of AP-1 and RUNX2.

Self-powered bifunctional sensor based on tribotronic planar graphene transistors.

With the development of material science, micro-nano-fabrication and microelectronics, the higher level requirements are posed on the electronic skins (E-skin). The lower energy consumption and multiple functions are the imperative requirements to spurred scientists and mechanists to make joint efforts to meet. To achieve lower energy consumption, a promising energy-harvesting style of triboelectric nanogenerators (TENG) is incorporated into the field effect transistors (FETs) to play the important role for sensor. For bifunctional sensor, to harness the difficult for reflecting the magnitude of frequency, we resorted to synaptic transistors to achieve more intelligentization. Furthermore, with regards to the configuration of FET, we continued previous work: using the electrolyte gate dielectrics of FET-ion gel as the electrification layer to achieve high efficient, compact and extensively adoption for mechanosensation. The working principle of the GFET was based on the coupling effects of the FET and the TENG. This newly emerged self-powered sensor would offer a new platform for lower power consumption sensor for human-machine interface and intelligent robot.

Hybrid memristor-CMOS neurons for in-situ learning in fully hardware memristive spiking neural networks.

Spiking neural network, inspired by the human brain, consisting of spiking neurons and plastic synapses, is a promising solution for highly efficient data processing in neuromorphic computing. Recently, memristor-based neurons and synapses are becoming intriguing candidates to build spiking neural networks in hardware, owing to the close resemblance between their device dynamics and the biological counterparts. However, the functionalities of memristor-based neurons are currently very limited, and a hardware demonstration of fully memristor-based spiking neural networks supporting in-situ learning is very challenging. Here, a hybrid spiking neuron combining a memristor with simple digital circuits is designed and implemented in hardware to enhance neuron functions. The hybrid neuron with memristive dynamics not only realizes the basic leaky integrate-and-fire neuron function but also enables the in-situ tuning of the connected synaptic weights. Finally, a fully hardware spiking neural network with the hybrid neurons and memristive synapses is experimentally demonstrated for the first time, and in-situ Hebbian learning is achieved with this network. This work opens up a way towards the implementation of spiking neurons, supporting in-situ learning for future neuromorphic computing systems.

SF2523 inhibits human chondrosarcoma cell growth in vitro and in vivo.

Developing novel therapeutic agents against chondrosarcoma is important. SF2523 is a PI3K-Akt-mTOR and bromodomain-containing protein 4 (BRD4) dual inhibitor. Its activity in human chondrosarcoma cells is tested. Our results show that SF2523 potently inhibited survival, proliferation and migration, and induced apoptosis activation in SW1353 cells and primary human chondrosarcoma cells. The dual inhibitor was yet non-cytotoxic to the primary human osteoblasts and OB-6 osteoblastic cells. SF2523 blocked Akt-mTOR activation and downregulated BRD4-regulated genes (Bcl-2 and c-Myc) in chondrosarcoma cells. It was more efficient in killing chondrosarcoma cells than other established PI3K-Akt-mTOR and BRD4 inhibitors, including JQ1, perifosine and OSI-027. In vivo, intraperitoneal injection of SF2523 (30 mg/kg) potently inhibited subcutaneous SW1353 xenograft tumor growth in severe combined immunodeficient mice. Akt-mTOR inhibition as well as Bcl-2 and c-Myc downregulation were detected in SF2523-treated SW1353 tumor tissues. In conclusion, targeting PI3K-Akt-mTOR and BRD4 by SF2523 potently inhibited chondrosarcoma cell growth in vitro and in vivo.

Photocatalytic Reduction of Graphene Oxide-TiO2 Nanocomposites for Improving Resistive-Switching Memory Behaviors.

Graphene oxide (GO)-based resistive-switching (RS) memories offer the promise of low-temperature solution-processability and high mechanical flexibility, making them ideally suited for future flexible electronic devices. The RS of GO can be recognized as electric-field-induced connection/disconnection of nanoscale reduced graphene oxide (RGO) conducting filaments (CFs). Instead of operating an electrical FORMING process, which generally results in high randomness of RGO CFs due to current overshoot, a TiO2 -assisted photocatalytic reduction method is used to generate RGO-domains locally through controlling the UV irradiation time and TiO2 concentration. The elimination of the FORMING process successfully suppresses the RGO overgrowth and improved RS memory characteristics are achieved in graphene oxide-TiO2 (Go-TiO2 ) nanocomposites, including reduced SET voltage, improved switching variability, and increased switching speed. Furthermore, the room-temperature process of this method is compatible with flexible plastic substrates and the memory cells exhibit excellent flexibility. Experimental results evidence that the combined advantages of reducing the oxygen-migration barrier and enhancing the local-electric-field with RGO-manipulation are responsible for the improved RS behaviors. These results offer valuable insight into the role of RGO-domains in GO memory devices, and also, this mild photoreduction method can be extended to the development of carbon-based flexible electronics.

Rapamycin causes growth arrest and inhibition of invasion in human chondrosarcoma cells.

PURPOSE: Chondrosarcoma is a highly malignant tumor that is characterized by a potent capacity to invade locally and cause distant metastasis and notable for its lack of response to conventional chemotherapy or radiotherapy. Rapamycin, the inhibitor of mammalian target of rapamycin (mTOR), is a valuable drug with diverse clinical applications and regulates many cellular processes. However, the effects of rapamycin on cell growth and invasion of human chondrosarcoma cells are not well known. METHODS: We determined the effect of rapamycin on cell proliferation, cell cycle arrest and invasion by using MTS, flow cytometry and invasion assays in two human chondrosarcoma cell lines, SW1353 and JJ012. Cell cycle regulatory and invasion-related genes' expression analysis was performed by quantitative RT-PCR (qRT-PCR). We also evaluated the effect of rapamycin on tumor growth by using mice xenograph models. RESULTS: Rapamycin significantly inhibited the cell proliferation, induced cell cycle arrest and decreased the invasion ability of human chondrosarcoma cells. Meanwhile, rapamycin modulated the cell cycle regulatory and invasion-related genes' expression. Furthermore, the tumor growth of mice xenograph models with human chondrosarcoma cells was significantly inhibited by rapamycin. CONCLUSIONS: These results provided further insight into the role of rapamycin in chondrosarcoma. Therefore, rapamycin targeted therapy may be a potential treatment strategy for chondrosarcoma.

Gefitinib causes growth arrest and inhibition of metastasis in human chondrosarcoma cells.

PURPOSE: Chondrosarcomas are primary malignant cartilage-forming tumors of bone which are not responsive either to chemotherapy or radiation treatment and display potent capacity to invade locally and cause distant metastasis. Epidermal growth factor receptor (EGFR) pathway plays an important role in the development and progression of many cancers. However, the effect of EGFR inhibitor gefitinib on cell growth and metastasis in human chondrosarcoma cells is largely unknown. METHODS: Features of the protein expression of EGFR in 3 human chondrosarcoma cell lines JJ2012, SW1353 and OUMS27 were analyzed. The inhibitory effects of EGFR inhibitor gefitinib on cell proliferation, cell cycle and metastasis were assessed by using MTS, flow cytometry and migration assays, respectively. The expression of metastasis-related proteins was evaluated by western blotting. RESULTS: All the three human chondrosarcoma cell lines expressed EGFR protein. Gefitinib significantly inhibited the growth, induced cell cycle arrest and decreased the migra- tion ability of human chondrosarcoma cells. In addition, gefitinib also reduced the expression of metastasis-related proteins, basic fibroblast growth factor (bFGF), matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9). CONCLUSIONS: The discovery that gefitinib inhibited the proliferation and reduced the metastatic capacity of chondrosarcoma cells may help increase the understanding of the mechanism underlying human chondrosarcoma growth and metastasis. Thus, gefitinib may represent a promising agent for controlling chondrosarcoma proliferation and metastasis.

Histone deacetylase inhibitors repress chondrosarcoma cell proliferation.

PURPOSE: Due to the high resistance to conventional therapy, there is still no convincingly effective treatment for chondrosarcoma. As a promising new treatment strategy, histone deacetylase inhibitors (HDACIs) have been reported to induce cell arrest, apoptosis and differentiation in some kinds of malignancies, but how HDACi exert their effects on chondrosarcoma is not well understood yet. METHODS: We investigated the effects of HDACIs trichostatin A (TSA) and sodium valproate (VPA) on chondrosarcoma cells in vitro and in vivo. The cell proliferation and cell cycle were examined in two chondrosarcoma cell lines, SW1353 and JJ012, by MTS and flow cytometry assays, respectively. The in vivo effects of HDACIs were investigated by assessing the chondrosarcoma growth in a mouse xenograft model. RESULTS: Our results showed that TSA and VPA significantly repressed the proliferation of chondrosarcoma cells in a concentration-dependent manner. Flow cytometry indicated that TSA arrested the cell cycle in G2/M phase and VPA arrested the cell cycle in G1 phase. The tumor growth was markedly suppressed in mice treated with TSA and VPA. CONCLUSIONS: HDACIs significantly repress the proliferation of chondrosarcoma cells in vitro and in vivo. Our findings imply that HDACIs may provide a novel therapeutic target for the treatment of chondrosarcoma.

Dispase rapidly and effectively purifies Schwann cells from newborn mice and adult rats.

In the present study, Schwann cells were isolated from the sciatic nerve of neonatal mice and purified using dispase and collagenase. Results showed that after the first round of purification with dispase, most of the Schwann cells appeared round in shape and floated in culture solution after 15 minutes. In addition, cell yield and cell purity were higher when compared to the collagenase group. After the second round of purification, the final cell yield for the dispase group was higher than that for the collagenase group, but no significant difference was found in cell purity. Moreover, similar results in cell quantity and purity were observed in adult Sprague-Dawley rats. These findings indicate that purification with dispase can result in the rapid isolation of Schwann cells with a high yield and purity.

RNAi-mediated knockdown of cyclooxygenase2 inhibits the growth, invasion and migration of SaOS2 human osteosarcoma cells: a case control study.

BACKGROUND: Cyclooxygenase2 (COX-2), one isoform of cyclooxygenase proinflammatory enzymes, is responsible for tumor development, invasion and metastasis. Due to its role and frequent overexpression in a variety of human malignancies, including osteosarcoma, COX-2 has received considerable attention. However, the function of COX-2 in the pathogenesis of cancer is not well understood. We examined the role of COX-2 in osteosarcoma. METHODS: We employed lentivirus mediated-RNA interference technology to knockdown endogenous gene COX-2 expression in human osteosarcoma cells (SaOS2) and analyzed the phenotypical changes. The effect of COX-2 treatment on the proliferation, cell cycle, invasion and migration of the SaOS2 cells were assessed using the MTT, flow cytometry, invasion and migration assays, respectively. COX-2, vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) mRNA and protein expression were detected by RT-PCR and western blotting. RESULTS: Our results indicate that a decrease of COX-2 expression in human osteosarcoma cells significantly inhibited the growth, decreased the invasion and migration ability of SaOS2 cells. In addition, it also reduced VEGF, EGF and bFGF mRNA and protein expression. CONCLUSIONS: The COX-2 signaling pathway may provide a novel therapeutic target for the treatment of human osteosarcoma.

[Biological characteristics of human umbilical cord-derived mesenchymal stem cells and their differentiation into chondrogenic and osteogenic cells].

OBJECTIVE: To investigate the isolation and expansion of mesenchymal stem cells (MSCS) from human umbilical cord Wharton's jelly and their biological identities, and explore the possibility of inducing human umbilical cord-derived MSCS to differentiate into chondrogenic and osteogenic cells. METHODS: The hUCMSCs were isolated form human umbilical cord by tissue adherence and digested with collagenase NB4, dispase II and hyaluronidase. The morphology, proliferation and immunophenotype of the 3rd passage cells were analyzed, and then the chondrogenic and osteogenic differentiation was tested and evaluated by specific staining methods.cells were induced to chondrogenic and osteogenic differentiation in vitro. RESULTS: The isolation of hUCMSCs by digestion with collagenase NB4, dispase II and hyaluronidase was efficient. After seeded for 24 hours, the adherent cells showed spindle shape and fibroblast cell-like shape and the size of hUCMSCs was homogeneous. Flow cytometry analysis revealed that the hUCMSCs were positive for CD44, CD105, CD90, CD73, but were negative for CD45, CD34, CD14, CD19 and HLA-DR. These cells could be induced to differentiate into chondrogenic and osteogenic cells under proper inducing conditions. The hUCMSCs retained the appearance and phenotype even after being expanded more than 40 passages in vitro. CONCLUSIONS: The human MSCs could be isolated from human umbilical cord Wharton's jelly, and it was easy to propagate these MSCs. An in vitro method for isolation and purification of hUCMSCs from human umbilical cord has been established. The cultured cells were composed of only undifferentiated cells and their biological properties were stable. The hUCMSCs are expected to be a new type of stem cells of tissue engineering.