Stem cell matrix and cartilage regeneration

Cartilage defects caused by injuries of the knee affect about 900,000 Americans annually, resulting in more than 200,000 surgical procedures. Cartilage repair remains a major challenge due to its limited healing capacity. Current cell-based therapy using autologous chondrocyte implantation has been developed for decades and promising results have been observed in clinic. However, the shortage of autologous chondrocytes and their uncertain long-term effectiveness have led researchers to find alternative solutions. Stem cells from various tissues have been shown to be potential sources of chondrocytes. Among them, synovium-derived stem cells (SDSCs) have been suggested as tissue-specific stem cells for chondrogenesis. However, a major obstacle challenging the cartilage tissue engineering is cell senescence, which is due mainly to extensive ex vivo passaging and elderly donors. A reconstructed ex vivo microenvironment that can maintain or enhance stemness is urgently needed for facilitating large-scale tissue engineering. To facilitate ex vivo expansion, the conventional methods for stem cell expansion were extensively investigated. We first compared the influence of low- and high-seeding density on human SDSC stemness during ex vivo expansion. Low-density seeding expansion yielded SDSCs with enhanced proliferative and multi-differentiation capacities compared to high-density seeding though it is not highly efficient. Downregulation of ERK1/2 and JNK and upregulation of p38 might be attributed to the retained stemness under low-density expansion. We next compared the impact of hypoxia, fibroblast growth factor-2 (FGF-2) supplementation and a novel approach of SDSC-deposited decellularized extracellular matrix (DECM) on SDSC stemness. DECM expansion enhanced greater SDSC proliferation while retaining stem cell characteristics, compared to FGF-2 supplementation alone. The combination of hypoxia, FGF-2 and DECM contributed to the highest cell number in SDSC expansion, indicating their synergistic effects. Although the chondrogenic index was comparable between DECM expansion and FGF-2 supplementation, which were much higher than expansion on plastic flask alone, the observations that FGF-2 induced hypertrophic marker genes suggested the superiority of DECM in enhancing SDSC self-renewal while retaining stemness. Other potential cell sources for depositing DECM were also evaluated. We found that, besides SDSCs, adipose- or urine-derived stem cells and dermal fibroblasts could also deposit the DECM, which could enhance SDSC self-renewal and chondrogenic potential without concomitantly enhancing adipogenic and osteogenic potentials. These findings suggest that, given an optimal DECM substrate, the chondrogenic potential within the tissue-specific SDSC could be substantially enhanced. We further characterized human fetal synovial fibroblasts as fetal SDSCs as they possessed the multi-lineage differentiation capacities and mesenchymal stem cell surface marker expression. Fetal SDSC-derived DECM expansion not only increased cell number and enhanced chondrogenic potential, it also lowered SDSC senescence marker expression while enhancing MSC marker expression compared to expansion on plastic flasks alone. As cell senescence is a limiting factor for tissue regeneration, we then investigated whether the DECM derived from fetal SDSCs referred to as a young stem cell microenvironment could be used for rejuvenating adult SDSC. We found that fetal SDSC-derived DECM (FE) was superior to adult SDSC-deposited DECM (AE) in promoting SDSC proliferation and chondrogenic potential. Further investigation revealed that unique proteins in FE might be responsible for the rejuvenation effect and advantageous proteins in AE might contribute to differentiation more than proliferation. Compared to AE, the lower elasticity of FE yielded expanded SDSCs with lower elasticity, which could be responsible for the enhancement of chondrogenic differentiation. MAPK and noncanonical Wnt signals were also actively involved in DECM-mediated SDSC rejuvenation. The young and healthy microenvironment provided by fetal SDSCs could serve as a fountain of youth for adult SDSC rejuvenation. Finally, we tested whether the DECM expansion system would also be beneficial to the chondrocyte-like nucleus pulposus cell (NPC) rejuvenation from human herniated discs and whether fetal DECM is superior to adult DECM. Although both SDSC and NPC deposited DECMs (SECM and NECM) significantly enhanced NPC proliferation, only NECM expanded NPCs manifested the increased redifferentiation capacities after chondrogenic induction. NECM is better than SECM in functioning as an expansion system in vitro by promoting NPC proliferation and redifferentiation. In conclusion, we have demonstrated that the DECM deposited by human primary cells or stem cells serves as an ex vivo expansion system for maintaining self-renewal and differentiation potential, which could greatly benefit the future generation of cell-based therapy for cartilage and intervertebral disc regeneration

Treating Heavy Oil Wastewater for Beneficial Use by Integrated Technology of Bio-Oxidation and RO

Heavy oil exploitation wastewater is characterized by its high concentration of emulsified oil, high salinity, high temperature and complex chemical components. This paper discuss a successful pilot-scale demonstration application of a unique technology integrating heat exchanger, gas floatation, biological contact oxygen, filtration, ultra-filtration, reverse osmosis at Chenzhuang oilfield. The scale of the process was about 360 m3/d, and the performance of the treatment process, the effectiveness of the technology for removal of oil and for controlling RO membranes fouling, and the economic effect are also discussed. Operation results show that the biological contact oxidation--ultra filtration process can reduce the oil contents to less than 0.5 mg/L and TDS to less than 3. The conductivity of RO effluent is below 456 μS·cm-1, the treated water can meet the required standard for steam-injected boiler, and it can also be used to prepare polymer solution for viscosity keeping.Key words: Heavy oil wastewater; Biological contact oxygen; RO; Steam boiler; Polymer solutio

Chondrogenic priming of human fetal synovium-derived stem cells in an adult stem cell matrix microenvironment

Cartilage defects are a challenge to treat clinically due to the avascular nature of cartilage. Low immunogenicity and extensive proliferation and multidifferentiation potential make fetal stem cells a promising source for regenerative medicine. In this study, we aimed to determine whether fetal synovium-derived stem cells (FSDSCs) exhibited replicative senescence and whether expansion on decellularized extracellular matrix (dECM) deposited by adult SDSCs (AECM) promoted FSDSCs\u27 chondrogenic potential. FSDSCs from passage 2 and 9 were compared for chondrogenic potential, using Alcian blue staining for sulfated glycosaminoglycans(GAGs), biochemical analysis for DNA and GAG amounts, and real-time PCR for chondrogenic genes including ACAN and COL2A1. Passage 3 FSDSCs were expanded for one passage on plastic flasks (PL), AECM, or dECM deposited by fetal SDSCs (FECM). During expansion, cell proliferation was evaluated using flow cytometry for proliferation index, stem cell surface markers, and resistance to hydrogen peroxide. During chondrogenic induction, expanded FSDSCs were evaluated for tri-lineage differentiation capacity. We found that cell expansion enhanced FSDSCs\u27 chondrogenic potential at least up to passage 9. Expansion on dECMs promoted FSDSCs\u27 proliferative and survival capacity and adipogenic differentiation but not osteogenic capacity. AECM-primed FSDSCs exhibited an enhanced chondrogenic potential

Chondrogenic priming of human fetal synovium-derived stem cells in an adult stem cell matrix microenvironment

Cartilage defects are a challenge to treat clinically due to the avascular nature of cartilage. Low immunogenicity and extensive proliferation and multidifferentiation potential make fetal stem cells a promising source for regenerative medicine. In this study, we aimed to determine whether fetal synovium-derived stem cells (FSDSCs) exhibited replicative senescence and whether expansion on decellularized extracellular matrix (dECM) deposited by adult SDSCs (AECM) promoted FSDSCs\u27 chondrogenic potential. FSDSCs from passage 2 and 9 were compared for chondrogenic potential, using Alcian blue staining for sulfated glycosaminoglycans(GAGs), biochemical analysis for DNA and GAG amounts, and real-time PCR for chondrogenic genes including ACAN and COL2A1. Passage 3 FSDSCs were expanded for one passage on plastic flasks (PL), AECM, or dECM deposited by fetal SDSCs (FECM). During expansion, cell proliferation was evaluated using flow cytometry for proliferation index, stem cell surface markers, and resistance to hydrogen peroxide. During chondrogenic induction, expanded FSDSCs were evaluated for tri-lineage differentiation capacity. We found that cell expansion enhanced FSDSCs\u27 chondrogenic potential at least up to passage 9. Expansion on dECMs promoted FSDSCs\u27 proliferative and survival capacity and adipogenic differentiation but not osteogenic capacity. AECM-primed FSDSCs exhibited an enhanced chondrogenic potential

Graphene oxide-Au nano particle coated quartz crystal microbalance biosensor for the real time analysis of carcinoembryonic antigen

A label-free quartz crystal microbalance (QCM) biosensor was developed for the selective and real-time estimation of carcinoembryonic antigen (CEA) through the present study. Graphene oxide-Au nanoparticles (GO-AuNPs) was in situ synthesised on the surface of the QCM electrode and the antibody of CEA (monoclonal anti-CEA from mouse) was covalently immobilized on this layer as the bioreceptor for CEA. Mercaptoacetic acid–EDC–NHS reaction mechanism was used for anti-CEA immobilization. The effect of oxygen plasma treatment of the QCM electrode surface before bioreceptor preparation on the performance of the biosensor was tested and was found promising. CEA solutions with various concentrations were analysed using the bioreceptors to estimate the sensitivity and detection limit of the biosensor. The biosensors selectively recognized and captured CEA biomolecules with a detection limit of 0.06 and 0.09 ng mL−1 of CEA for oxygen plasma-treated (E2) and untreated (E1) bioreceptors, respectively. The sensitivity was estimated at 102 and 79 Hz, respectively, for E2 and E1. Clinical serum samples were analysed and the results were found in good agreement with the ELISA analysis. Long term stability was also found to be excellent. Langmuir adsorption isotherm was also conducted using the experimental results

Fixed-time control of delayed neural networks with impulsive perturbations

This paper is concerned with the fixed-time stability of delayed neural networks with impulsive perturbations. By means of inequality analysis technique and Lyapunov function method, some novel fixed-time stability criteria for the addressed neural networks are derived in terms of linear matrix inequalities (LMIs). The settling time can be estimated without depending on any initial conditions but only on the designed controllers. In addition, two different controllers are designed for the impulsive delayed neural networks. Moreover, each controller involves three parts, in which each part has different role in the stabilization of the addressed neural networks. Finally, two numerical examples are provided to illustrate the effectiveness of the theoretical analysis

Emergent Incident Response for Unmanned Warehouses with Multi-agent Systems*

Unmanned warehouses are an important part of logistics, and improving their operational efficiency can effectively enhance service efficiency. However, due to the complexity of unmanned warehouse systems and their susceptibility to errors, incidents may occur during their operation, most often in inbound and outbound operations, which can decrease operational efficiency. Hence it is crucial to to improve the response to such incidents. This paper proposes a collaborative optimization algorithm for emergent incident response based on Safe-MADDPG. To meet safety requirements during emergent incident response, we investigated the intrinsic hidden relationships between various factors. By obtaining constraint information of agents during the emergent incident response process and of the dynamic environment of unmanned warehouses on agents, the algorithm reduces safety risks and avoids the occurrence of chain accidents; this enables an unmanned system to complete emergent incident response tasks and achieve its optimization objectives: (1) minimizing the losses caused by emergent incidents; and (2) maximizing the operational efficiency of inbound and outbound operations during the response process. A series of experiments conducted in a simulated unmanned warehouse scenario demonstrate the effectiveness of the proposed method.Comment: 13 pages, 7 figure

A high performance surface acoustic wave visible light sensor using novel materials: Bi2S3 nanobelts

Low dimensional Bi2S3 materials are excellent for use in photodetectors with excellent stability and fast response time. In this work, we developed a visible light sensor with good performance based on surface acoustic wave (SAW) devices using Bi2S3 nanobelts as the sensing materials. The SAW delay-line sensor was fabricated on ST-cut quartz with a designed wavelength of 15.8 microns using conventional photolithography techniques. The measured center frequency was 200.02 MHz. The Bi2S3 nanobelts prepared by a facile hydrothermal process were deposited onto SAW sensors by spin-coating. Under irradiation of 625 nm visible light with a power intensity of 170 μW cm−2, the sensor showed a fast and large response with a frequency upshift of 7 kHz within 1 s. The upshift of the frequency of the SAW device is mainly attributed to the mass loading effect caused by the desorption of oxygen from the Bi2S3 nanobelts under visible light radiation

Sentiment Analysis and Political Party Classification in 2016 U.S. President Debates in Twitter

We introduce a framework of combining tweet sentiment analysis with available default user profiles to classify political party of users who posted tweets in 2016 U.S. president debates. The main works focus on extracting event-related information in short event period instead of collecting tweets in a long-time period as most previous works do. Our framework is not limited in debate event, it can be used by researchers to build rationale of other events study. In sentiment analysis, we show that all three Naïve Bayes classifiers with different distributions obtain accuracy above 75% and the results reveal positive tweets most likely follow Gaussian or Multinomial distributions while negative tweets most likely follow Bernoulli distribution in our training data. We also show that under unbalanced sparse term document setting, instead of using “Add-1” parameter, tuning Laplace smoothing parameter to adjust the weights of new terms in a tweet can help improve the classifier’s performance in targeted direction. Finally, we show sentiment might help classifying political part

A high performance surface acoustic wave visible light sensor using novel materials: Bi2S3 nanobelts

Low dimensional Bi2S3 materials are excellent for use in photodetectors with excellent stability and fast response time. In this work, we developed a visible light sensor with good performance based on surface acoustic wave (SAW) devices using Bi2S3 nanobelts as the sensing materials. The SAW delay-line sensor was fabricated on ST-cut quartz with a designed wavelength of 15.8 microns using conventional photolithography techniques. The measured center frequency was 200.02 MHz. The Bi2S3 nanobelts prepared by a facile hydrothermal process were deposited onto SAW sensors by spin-coating. Under irradiation of 625 nm visible light with a power intensity of 170 μW cm−2, the sensor showed a fast and large response with a frequency upshift of 7 kHz within 1 s. The upshift of the frequency of the SAW device is mainly attributed to the mass loading effect caused by the desorption of oxygen from the Bi2S3 nanobelts under visible light radiation