Engineered 3D tumour model for study of glioblastoma aggressiveness and drug evaluation on a detachably assembled microfluidic device.

3D models of tumours have emerged as an advanced technique in pharmacology and tumour cell biology, in particular for studying malignant tumours such as glioblastoma multiforme (GBM). Herein, we developed a 3D GBM model on a detachably assembled microfluidic device, which could be used to study GBM aggressiveness and for anti-GBM drug testing. Fundamental characteristics of the GBM microenvironment in terms of 3D tissue organisation, extracellular matrices and blood flow were reproduced in vitro by serial manipulations in the integrated microfluidic device, including GBM spheroid self-assembly, embedding in a collagen matrix, and continuous perfusion culture, respectively. We could realize multiple spheroids parallel manipulation, whilst, compartmentalized culture, in a highly flexible manner. This method facilitated investigations into the viability, proliferation, invasiveness and phenotype transition of GBM in a 3D microenvironment and under continuous stimulation by drugs. Anti-invasion effect of resveratrol, a naturally isolated polyphenol, was innovatively evaluated using this in vitro 3D GBM model. Temozolomide and the combination of resveratrol and temozolomide were also evaluated as control. This scalable model enables research into GBM in a more physiologically relevant microenvironment, which renders it promising for use in translational or personalised medicine to examine the impact of, or identify combinations of, therapeutic agents.

Research on economic and social impact of carbon emissions in the construction industry at a regional scale: a case of Shandong, China.

To identify the impact of carbon emissions in the construction industry on the society and economy at a regional scale is of great significance for the sustainable development of the construction industry. Taking Shandong, China, as an example, this study uses a process-based carbon emission assessment method to calculate the carbon emissions of the construction industry in Shandong from 2010 to 2020. Based on specific situations at different phases, ten major factors affecting the society and economy have been analyzed and identified. Then, the Seemingly Uncorrelated Regression (SUR) model was used to analyze carbon emissions and economic and social factors at each stage. The results show the following: (1) The overall carbon emissions of the construction industry in Shandong are on an increasing trend, the carbon emission intensity is on a decreasing trend, and the material production and operation stages are the main source of carbon emissions; (2) There is a significant relationship between carbon emissions in the construction phase and all influencing factors, so it should be the main phase for macro-regulation; (3) Unlike in the Ordinary Least Square (OLS) model, the error terms of the gross output value of the construction industry and the total turnover of the main building materials equations are independent; however, there is an interaction between the error terms of the remaining equations. The results provide a theoretical reference for governmental departments to set up environmental targets and make policy regulations.

Human neural stem cells repress glioma cell progression in a paracrine manner by downregulating the Wnt/ß-catenin signalling pathway.

Neural stem cells (NSCs) play crucial roles in neurological disorders and tissue injury repair through exerting paracrine effects. However, the effects of NSC-derived factors on glioma progression remain unclear. This study aimed to evaluate the effects of human NSC-conditioned medium (NSC-CM) on the behaviour of glioma cells using an in vitro co-culture system. Cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays revealed that NSC-CM inhibited glioma cell proliferation and growth in a fetal bovine serum (FBS)-independent manner. In addition, our wound-healing assay demonstrated that NSC-CM repressed glioma cell migration, while results from transwell and 3D spheroid invasion assays indicated that NSC-CM also reduced the invasion capacity of glioma cells. Flow cytometry showed that NSC-CM prevented cell cycle progression from the G1 to S phase and promoted apoptosis. Western blotting was used to show that the expression of Wnt/ß-catenin pathway-related proteins, including ß-catenin, c-Myc, cyclin D1, CD44 and Met, was remarkably decreased in NSC-CM-treated glioma cells. Furthermore, the addition of a Wnt/ß-catenin pathway activator, CHIR99021, significantly induced the expression of ß-catenin and Met and increased the proliferative and invasive capabilities of control medium-treated glioma cells but not those of NSC-CM-treated glioma cells. The use of enzyme-linked immunosorbent assays (ELISA) revealed the secretion of some antitumour factors in human and rat NSCs, including interferon-α and dickkopf-1. Our data suggest that NSC-CM partially inhibits glioma cell progression by downregulating Wnt/ß-catenin signalling. This study may serve as a basis for developing future antiglioma therapies based on NSC derivatives.

Analysis of the decoupling state and driving forces of China's construction industry under the carbon neutrality target.

The essential to achieving the 2060 carbon neutrality target in China lies in the performance of the construction industry. Decoupling economic development from CO2 emissions is the main strategy for reducing emissions in the construction industry. This paper is based on panel data for China and its 30 provinces during 2009-2019. A Tapio decoupling model is constructed to analyze the decoupling state of economic development and CO2 emissions in the construction industry. The logarithmic mean Divisia index model is constructed to continue the decomposition of the drivers of the decoupling state and CO2 emissions. The results show that (1) the economic development level of most provinces is positively correlated with their CO2 emissions; (2) Beijing and Jiangsu reach the ideal strong decoupling state, and Heilongjiang has the worst decoupling state. The same type of decoupling state shows a certain aggregation phenomenon in space; (3) economic output plays a critical role in promoting CO2 emissions and decoupling of the construction industry in China and the provinces. The main driver of decoupling is indirect carbon intensity; (4) energy intensity has a greater impact on CO2 emissions reduction in regions with more developed economic levels. Understanding the drivers of the decoupling state in China's construction industry provides a valuable basis for energy efficiency and emission reduction efforts in China and other countries.

A neurovascular unit-on-a-chip: culture and differentiation of human neural stem cells in a three-dimensional microfluidic environment.

Biological studies typically rely on a simple monolayer cell culture, which does not reflect the complex functional characteristics of human tissues and organs, or their real response to external stimuli. Microfluidic technology has advantages of high-throughput screening, accurate control of the fluid velocity, low cell consumption, long-term culture, and high integration. By combining the multipotential differentiation of neural stem cells with high throughput and the integrated characteristics of microfluidic technology, an in vitro model of a functionalized neurovascular unit was established using human neural stem cell-derived neurons, astrocytes, oligodendrocytes, and a functional microvascular barrier. The model comprises a multi-layer vertical neural module and vascular module, both of which were connected with a syringe pump. This provides controllable conditions for cell inoculation and nutrient supply, and simultaneously simulates the process of ischemic/hypoxic injury and the process of inflammatory factors in the circulatory system passing through the blood-brain barrier and then acting on the nerve tissue in the brain. The in vitro functionalized neurovascular unit model will be conducive to central nervous system disease research, drug screening, and new drug development.

Neuroregeneration and functional recovery after stroke: advancing neural stem cell therapy toward clinical application.

Stroke is a main cause of death and disability worldwide. The ability of the brain to self-repair in the acute and chronic phases after stroke is minimal; however, promising stem cell-based interventions are emerging that may give substantial and possibly complete recovery of brain function after stroke. Many animal models and clinical trials have demonstrated that neural stem cells (NSCs) in the central nervous system can orchestrate neurological repair through nerve regeneration, neuron polarization, axon pruning, neurite outgrowth, repair of myelin, and remodeling of the microenvironment and brain networks. Compared with other types of stem cells, NSCs have unique advantages in cell replacement, paracrine action, inflammatory regulation and neuroprotection. Our review summarizes NSC origins, characteristics, therapeutic mechanisms and repair processes, then highlights current research findings and clinical evidence for NSC therapy. These results may be helpful to inform the direction of future stroke research and to guide clinical decision-making.