The sudden outbreak of 2019 novel coronavirus (2019-nCoV, later named SARS-CoV-2) in Wuhan, China, which rapidly grew into a global pandemic, marked the third introduction of a virulent coronavirus into the human society, affecting not only the healthcare system, but also the global economy. Although our understanding of coronaviruses has undergone a huge leap after two precedents, the effective approaches to treatment and epidemiological control are still lacking. In this article, we present a succinct overview of the epidemiology, clinical features, and molecular characteristics of SARS-CoV-2. We summarize the current epidemiological and clinical data from the initial Wuhan studies, and emphasize several features of SARS-CoV-2, which differentiate it from SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), such as high variability of disease presentation. We systematize the current clinical trials that have been rapidly initiated after the outbreak of COVID-19 pandemic. Whereas the trials on SARS-CoV-2 genome-based specific vaccines and therapeutic antibodies are currently being tested, this solution is more long-term, as they require thorough testing of their safety. On the other hand, the repurposing of the existing therapeutic agents previously designed for other virus infections and pathologies happens to be the only practical approach as a rapid response measure to the emergent pandemic, as most of these agents have already been tested for their safety. These agents can be divided into two broad categories, those that can directly target the virus replication cycle, and those based on immunotherapy approaches either aimed to boost innate antiviral immune responses or alleviate damage induced by dysregulated inflammatory responses. The initial clinical studies revealed the promising therapeutic potential of several of such drugs, including favipiravir, a broad-spectrum antiviral drug that interferes with the viral replication, and hydroxychloroquine, the repurposed antimalarial drug that interferes with the virus endosomal entry pathway. We speculate that the current pandemic emergency will be a trigger for more systematic drug repurposing design approaches based on big data analysis.

Background : Walking while performing cognitive and motor tasks simultaneously interferes with gait performance and may lead to falls in older adults with mild cognitive impairment (MCI). Executive function, which seems to play a key role in dual-task gait performance, can be improved by combined physical and cognitive training. Virtual reality (VR) has the potential to assist rehabilitation, and its effect on physical and cognitive function requires further investigation. The purpose of this study was to assess the effects of VR-based physical and cognitive training on executive function and dual-task gait performance in older adults with MCI, as well as to compare VR-based physical and cognitive training with traditional combined physical and cognitive training. Method : Thirty-four community-dwelling older adults with MCI were randomly assigned into either a VR-based physical and cognitive training (VR) group or a combined traditional physical and cognitive training (CPC) group for 36 sessions over 12 weeks. Outcome measures included executive function [Stroop Color and Word Test (SCWT) and trail making test (TMT) A and B], gait performance (gait speed, stride length, and cadence) and dual-task costs (DTCs). Walking tasks were performed during single-task walking, walking while performing serial subtraction (cognitive dual task), and walking while carrying a tray (motor dual task). The GAIT Up system was used to evaluate gait parameters including speed, stride length, cadence and DTCs. DTC were defined as 100 * (single-task gait parameters − dual-task gait parameters)/single-task gait parameters. Results : Both groups showed significant improvements in the SCWT and single-task and motor dual-task gait performance measures. However, only the VR group showed improvements in cognitive dual-task gait performance and the DTC of cadence. Moreover, the VR group showed more improvements than the CPC group in the TMT-B and DTC of cadence with borderline significances. Conclusion : A 12-week VR-based physical and cognitive training program led to significant improvements in dual-task gait performance in older adults with MCI, which may be attributed to improvements in executive function.

Negative selection-based circulating tumor cell (CTC) isolation is believed valuable to harvest more native, and in particular all possible CTCs without biases relevant to the properties of surface antigens on the CTCs. Under such a cell isolation strategy, however, the CTC purity is normally compromised. To address this issue, this study reports the integration of optically-induced-dielectrophoretic (ODEP) force-based cell manipulation, and a laminar flow regime in a microfluidic platform for the isolation of untreated, and highly pure CTCs after conventional negative selection-based CTC isolation. In the design, six sections of moving light-bar screens were continuously and simultaneously exerted in two parallel laminar flows to concurrently separate the cancer cells from the leukocytes based on their size difference and electric properties. The separated cell populations were further partitioned, delivered, and collected through the two flows. With this approach, the cancer cells can be isolated in a continuous, effective, and efficient manner. In this study, the operating conditions of ODEP for the manipulation of prostate cancer (PC-3) and human oral cancer (OEC-M1) cells, and leukocytes with minor cell aggregation phenomenon were first characterized. Moreover, performances of the proposed method for the isolation of cancer cells were experimentally investigated. The results showed that the presented CTC isolation scheme was able to isolate PC-3 cells or OEC-M1 cells from a leukocyte background with high recovery rate (PC-3 cells: 76-83%, OEC-M1 cells: 61-68%), and high purity (PC-3 cells: 74-82%, OEC-M1 cells: 64-66%) (set flow rate: 0.1 μl min(-1) and sample volume: 1 μl). The latter is beyond what is currently possible in the conventional CTC isolations. Moreover, the viability of isolated cancer cells was evaluated to be as high as 94 ± 2%, and 95 ± 3% for the PC-3, and OEC-M1 cells, respectively. Furthermore, the isolated cancer cells were also shown to preserve their proliferative capability. As a whole, this study has presented an ODEP-based microfluidic platform that is capable of isolating CTCs in a continuous, label-free, cell-friendly, and particularly highly pure manner. All these traits are found particularly meaningful for exploiting the harvested CTCs for the subsequent cell-based, or biochemical assays.

This paper describes a fast, low-cost but reliable process for the fabrication of microfluidic systems on soda-lime glass substrates. Instead of using an expensive metal or polisilicon/nitride layer as an etch mask, a thin layer of AZ 4620 positive photoresist (PR) is used for buffered oxide etching (BOE) of soda-lime glass. A novel two-step baking process prolongs the survival time of the PR mask in the etchant, which avoids serious peeling problems of the PR. A new process to remove precipitated particles generated during the etching process is also reported in which the glass substrate is dipped into a 1 M hydrochloride solution. A microfluidic channel with a depth of 35.95 ± 0.39 µm is formed after 40 min BOE in an ultrasonic bath. The resulting channel has a smooth profile with a surface roughness of less than 45.95 ± 7.96 Å. Glass chips with microfluidic channels are then bonded at 580 • C for 20 min to seal the channel while a slight pressure is applied. A new bonding process has been developed such that the whole process can be finished within 10 h. To our knowledge, this is the shortest processing time that has ever been reported. In the present study, an innovative microfluidic device, a 'micro flow-through sampling chip', has been demonstrated using the fabrication method. Successful sampling and separation of Cy5-labelled bovine serum albumin (BSA) and anti-BSA has been achieved. This simple fabrication process is suitable for fast prototyping and mass production of microfluidic systems.

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Amphetamines elevate extracellular dopamine, but the underlying mechanisms remain uncertain. Here we show in rodents that acute pharmacological inhibition of the vesicular monoamine transporter (VMAT) blocks amphetamine-induced locomotion and self-administration without impacting cocaine-induced behaviours. To study VMAT's role in mediating amphetamine action in dopamine neurons, we have used novel genetic, pharmacological and optical approaches in Drosophila melanogaster. In an ex vivo whole-brain preparation, fluorescent reporters of vesicular cargo and of vesicular pH reveal that amphetamine redistributes vesicle contents and diminishes the vesicle pH-gradient responsible for dopamine uptake and retention. This amphetamine-induced deacidification requires VMAT function and results from net H+ antiport by VMAT out of the vesicle lumen coupled to inward amphetamine transport. Amphetamine-induced vesicle deacidification also requires functional dopamine transporter (DAT) at the plasma membrane. Thus, we find that at pharmacologically relevant concentrations, amphetamines must be actively transported by DAT and VMAT in tandem to produce psychostimulant effects.

This study reports the utilisation of an optically switched dielectrophoretic (ODEP) force for the manipulation and assembly of cell-encapsulating alginate microbeads in a microfluidic perfusion cell culture system for bottom-up tissue engineering. One of the key features of this system is the ODEP force-based mechanism, which allows a commercial projector to be coupled with a computer to manipulate and assemble cell-encapsulating microbeads in an efficient, manageable, and user-friendly manner. Another distinctive feature is the design of the microfluidic cell culture chip, which allows the patterned cell-encapsulating microbeads to be cultivated on site under culture medium perfusion conditions. For demonstrating its application in bottom-up cartilage tissue engineering, chondrocyte-encapsulating alginate microbeads varying in encapsulated cell densities were generated. The manipulation forces associated with operating the alginate microbeads were experimentally evaluated. The results revealed that the measured manipulation forces increased with increases in both the applied electric voltage and the number of cells in the alginate microbeads. Nevertheless, the observed manipulation force was found to be independent of the size of the cell-free alginate microbeads. It can be speculated that the friction force may influence the estimation of the ODEP force within the experimental conditions investigated. In this study, chondrocyte-encapsulating alginate microbeads with three different cell densities were manipulated and assembled in the proposed microfluidic system to form a compact sheet-like cell culture construct that imitates the cell distribution in the cross-section of native articular cartilage. Moreover, the demonstration case also showed that the cell viability of the cultured cells in the microfluidic system remained as high as 96 ± 2%. In this study, four sheet-like cell culture constructs were stacked to create a larger assembled cell culture construct. The cell distribution inside the cell culture construct was further confirmed by a confocal microscopy observation, which showed that the distribution was similar to that in native articular cartilage. As a whole, the proposed system holds great promise as a platform for engineering tissue constructs with easily tunable inner cell distributions.

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