Human spinal cord models for development of spinal cord injury repair strategies

There is still no available cure for human spinal cord injury (SCI). After a SCI, neural cell loss, excitotoxicity, neuroinflammation, astrocytic and oligodendrocytic derived inhibiting factors contribute to a non-permissive spinal cord environment hindering neuroregeneration with little, if any, endogeneous functional improvement. Experimental studies based on nonhuman cells and tissues as well as in vivo models have significantly increased our understanding of the pathophysiological processes and repair mechanisms after SCI. However, this gained knowledge may not always be applicable in the human setting, due to species specific differences. Therefore, having access to relevant human models to supplement existing animal models would be beneficial. In vitro cellular and ex vivo tissue cultures may allow us to mimic, at least to some degree, in vivo conditions, and to further understand human-specific spinal cord development, pathological conditions as well as repair mechanisms. Therefore, in this thesis, human spinal cord models have been further developed to offer additional tools in the translation of treatment strategies from the experimental to clinical setting. In Paper I, we developed an ex vivo human spinal cord model referred to as human organotypic cultures (hOCs). Cellular, molecular and functional characteristics of the hOCs as well as human spinal cord-derived neural stem/progenitor cell (hNPC) allogeneic cell therapy were studied. The hOCs presented a relatively intact cytoarchitecture and functional viability and could to a certain level replicate the in situ human spinal cord microenvironment. We conclude that the hOC model has potential for future structural and functional studies of human spinal cord development or injury, and can be used as a platform for the study and further development of human SCI treatment strategies. To counteract the non-permissive spinal cord milieu after SCI, support host neural regeneration, modify the microenvironment, or offer drug or cell delivery, the application of biomaterials as part of a composite treatment strategy for SCI has been proposed. In the present thesis two different types of biomaterials with potential to serve as scaffolds for hNPC therapy was applied – hyaluronic acid (HA) hydrogels (bulk and granular HA hydrogels in Paper II and III) and recombinant spidroins (NT2RepCT and VN-NT2RepCT in Paper II). In Paper II, an in vitro model to, relatively resource effectively, evaluate the immunocompatibility of the above-mentioned biomaterials with human peripheral blood mononuclear cells (host) and/or allogenic hNPCs. The VN-NT2RepCT recombinant spidroin activated human B cells, CD4+ T cells and NK cells. We therefore suggest efforts to develop recombinant spidroin with reduced endotoxin contamination. The HA hydrogels with/without hNPCs did on the other hand not stimulate lymphocyte activation or proliferation, indicating that HA hydrogels may be a suitable scaffold for hNPC therapy in SCI. We suggest that this model can be used to evaluate human compatibility of novel biomaterials resource effectively early in the production process and when necessary, make alterations to minimize the risk of rejection. In Paper III, a 3D culture system was applied aiming to mimic the extracelular matrix (ECM) and support hNPC survival and differentiation utilizing HA hydrogels combined with laminin and brain-derived neurotrophic factor (BDNF). The granular HA hydrogel together with laminin and BDNF presented in preliminary studies beneficial features compared to bulk HA hydrogel in the context of physical property and the capability to support hNPC survival and differentiation. Human neuronal differentiation was observed to be supported up to 14 days in vitro in the granular HA hydrogel, which is promising for future clinical applications after SCI. In conclusion, the human spinal cord-derived in vitro model systems presented here have potential to supplement existing animal models for the study of human SCI, human biocompatibility, and for the translation of promising experimental SCI treatments to the clinic

High-sensitivity acoustic sensors from nanofibre webs

Considerable interest has been devoted to converting mechanical energy into electricity using polymer nanofibres. In particular, piezoelectric nanofibres produced by electrospinning have shown remarkable mechanical energy-to-electricity conversion ability. However, there is little data for the acoustic-to-electric conversion of electrospun nanofibres. Here we show that electrospun piezoelectric nanofibre webs have a strong acoustic-to-electric conversion ability. Using poly(vinylidene fluoride) as a model polymer and a sensor device that transfers sound directly to the nanofibre layer, we show that the sensor devices can detect low-frequency sound with a sensitivity as high as 266 mV Pa(-1). They can precisely distinguish sound waves in low to middle frequency region. These features make them especially suitable for noise detection. Our nanofibre device has more than five times higher sensitivity than a commercial piezoelectric poly(vinylidene fluoride) film device. Electrospun piezoelectric nanofibres may be useful for developing high-performance acoustic sensors

Washable and Flexible Screen-Printed Ag/AgCl Electrode on Textiles for ECG Monitoring

Electrocardiogram (ECG) electrodes are important sensors for detecting heart disease whose performance determines the validity and accuracy of the collected original ECG signals. Due to the large drawbacks (e.g., allergy, shelf life) of traditional commercial gel electrodes, textile electrodes receive widespread attention for their excellent comfortability and breathability. This work demonstrated a dry electrode for ECG monitoring fabricated by screen printing silver/silver chloride (Ag/AgCl) conductive ink on ordinary polyester fabric. The results show that the screen-printed textile electrodes have good and stable electrical and electrochemical properties and excellent ECG signal acquisition performance. Furthermore, the resistance of the screen-printed textile electrode is maintained within 0.5 Ω/cm after 5000 bending cycles or 20 washing and drying cycles, exhibiting excellent flexibility and durability. This research provides favorable support for the design and preparation of flexible and wearable electrophysiological sensing platforms

Research on Incentive and restraint mechanism of capital operation of power grid enterprises under new development pattern

Under the new development pattern of dual circulation economy, the reform of state-owned enterprises has entered the deep water area, and the operating environment of power grid enterprises has changed significantly, which has a profound impact on the capital operation strategy and effect of the enterprises. This paper analyzes the new characteristics of capital operation of power grid enterprises under the new development pattern, constructs the incentive and restriction index system of capital operation of power grid enterprises, designs the incentive and restraint mechanism of capital operation of power grid enterprises, and verifies the scientificity and applicability of the mechanism by financial evaluation and analysis. The research results enrich the theory of capital operation management based on financial evaluation, and provide theoretical basis and practical reference for grid enterprises to optimize the distribution of capital investment and improve the efficiency of capital operation

Single-cell RNA sequencing reveals the mediatory role of cancer-associated fibroblast PTN in hepatitis B virus cirrhosis-HCC progression

Abstract Background Cancer-associated fibroblasts (CAFs) are essential stromal components in the tumor microenvironment of hepatocellular carcinoma (HCC). Hepatitis B virus (HBV) infection induces pathological changes such as liver fibrosis/cirrhosis and HCC. The aim of this research was to explore the novel mediators of CAFs to modulate HBV cirrhosis-HCC progression. Methods The single-cell transcriptome data of HCC were divided into subsets, and the significant subset related to fibrotic cells, along with biological function, and clinical information of HCC was revealed by integrated data analyses. The cell communication, cells communicated weight analysis of signaling pathways, and key genes in signaling pathways analysis of significant CAFs subclasses were conducted to discover the novel gene of CAFs. Bioinformatics, vitro and HBV transfection assays were used to verify the novel gene is an important target for promoting the progression HBV cirrhosis-HCC progression. Results Fibroblasts derived from HCC single-cell data could be separated into three cell subclasses (CAF0-2), of which CAF2 was associated with the HCC clinical information. Fibroblasts have opposite developmental trajectories to immune B cells and CD8 + T cells. CAF0-2 had strong interaction with B cells and CD8 + T cells, especially CAF2 had the highest interaction frequency and weight with B cells and CD8 + T cells. Moreover, PTN participated in CAF2-related pathways involved in the regulation of cell communication, and the interactions among CAF2 and PTN contributed the most to B cells and CD8 + T cells. Furthermore, the genes of PTN, SDC1, and NCL from PTN signaling were highest expression in CAF2, B cells, and CD8 + T cells, respectively, and the interaction of PTN- SDC1 and PTN- NCL contributed most to the interaction of CAF2- B cells and CAF2-CD8 + T cells. Bioinformatics and vitro experiments confirm PTN was upregulated in HCC and promoted the proliferation of tumor cells, and HBV infection could initiate PTN to perform cirrhosis-HCC progression. Conclusion Our findings revealed CAF was associated with hepatocarcinogenesis, and the functional importance of B cells and CD8 + T cells in modulating CAF in HCC. Importantly, PTN maybe a novel mediator of CAF to mediate HBV cirrhosis-HCC progression

Follicular Helper CD4+ T Cells in Human Neuroautoimmune Diseases and Their Animal Models

Follicular helper CD4+ T (TFH) cells play a fundamental role in humoral immunity deriving from their ability to provide help for germinal center (GC) formation, B cell differentiation into plasma cells and memory cells, and antibody production in secondary lymphoid tissues. TFH cells can be identified by a combination of markers, including the chemokine receptor CXCR5, costimulatory molecules ICOS and PD-1, transcription repressor Bcl-6, and cytokine IL-21. It is difficult and impossible to get access to secondary lymphoid tissues in humans, so studies are usually performed with human peripheral blood samples as circulating counterparts of tissue TFH cells. A balance of TFH cell generation and function is critical for protective antibody response, whereas overactivation of TFH cells or overexpression of TFH-associated molecules may result in autoimmune diseases. Emerging data have shown that TFH cells and TFH-associated molecules may be involved in the pathogenesis of neuroautoimmune diseases including multiple sclerosis (MS), neuromyelitis optica (NMO)/neuromyelitis optica spectrum disorders (NMOSD), and myasthenia gravis (MG). This review summarizes the features of TFH cells, including their development, function, and roles as well as TFH-associated molecules in neuroautoimmune diseases and their animal models

Effects of xylo-oligosaccharide and flavomycin on the immune function of broiler chickens

This study investigated the effects of xylo-oligosaccharide (XOS) and flavomycin (FLA) on the performance and immune function of broiler chickens. A total of 150 ArborAcres broilers were randomly divided into three groups and fed for six weeks from one day of age in cascade cages. The diets of each test group were (1) a basal diet, (2) the basal diet supplemented with 2 mg/kg FLA, and (3) the basal diet supplemented with 2 mg/kg XOS. At 21 and 42 days, the growth performance index values and short-chain fatty acid (SCFA) concentrations in the cecum were quantified. Furthermore, immunoglobulin G (IgG) and plasma interleukin 2 (IL-2) as well as mRNA expression of LPS-Induced TNF-alpha Factor (LITAF), Toll-like receptor-5 (TLR5) and interferon gamma (IFNγ) in the jejunum were quantified. The results showed that administration of XOS or FLA to chickens significantly improved the average daily gain. Supplementation with XOS increased acetate and butyrate in the cecum, while FLA supplementation increased propionate in the cecum. An increase in plasma IgG was observed in XOS-fed 21-day-old broilers, but FLA supplementation decreased IgG in the plasma of 42-day-old broilers and increased plasma IL-2. Furthermore, FLA or XOS supplementation downregulated mRNA expression of IFNγ, LITAF and TLR5. The above data suggest that addition of XOS and FLA to the diet could improve the growth performance of broilers and reduce the expression of cytokine genes by stimulating SCFA

A federated learning-enabled predictive analysis to forecast stock market trends

This article proposes a federated learning framework to build Random Forest, Support Vector Machine, and Linear Regression models for stock market prediction. The performance of the federated learning is compared against centralised and decentralised learning frameworks to figure out the best fitting approach for stock market prediction. According to the results, federated learning outperforms both centralised and decentralised frameworks in terms of Mean Square Error if Random Forest (MSE = 0.021) and Support Vector Machine techniques (MSE = 37.596) are used, while centralised learning (MSE = 0.011) outperforms federated and decentralised frameworks if a linear regression model is used. Moreover, federated learning gives a better model training delay as compared to the benchmarks if Linear Regression (time = 9.7 s) and Random Forest models (time = 515 s) are used, whereas decentralised learning gives a minimised model training delay (time = 3847 s) for Support Vector Machine