An ecological remediation model combining optimal substrate amelioration and native hyperaccumulator colonization in non-ferrous metal tailings pond.

The vegetation deterioration and pollution expansion from non-ferrous metal tailings pond have been found in many countries leading to water soil erosion and human health risk. Conventional ecological remediation technologies of mine tailings such as capping were costly and elusive. This study provided an economic and effective model as an alternative by substrate amelioration and vegetation restoration. A field experiment was carried out on a silver tailings pond in southwest China. Tailings substrate was ameliorated by adding organic matter (decomposed chicken manure, DCM), structural conditioner (polyacrylamide, PAM), water-retaining agent (acrylic acid-bentonite water-retaining agent, AAB), and heavy metal immobilizer (biofuel ash, BFA), which were optimized by laboratory experiment. Native heavy metal hyperaccumulator, Bidens pilosa, was colonized. Vegetation coverage and plant height of Bidens pilosa reached about 80% and over 30 cm respectively after 3 months, and the turbidity of tailings leaching solution decreased by 60%. The practice showed that the proportion of available heavy metals in tailings substrate was significantly lower than that in the soil surrounding mining area. Immobilization didn't have stabilization effect on Cd, Zn, and Pb, and As was only 0.002%, phytoremediation had stabilization effect of Cd, Zn, As, and Pb were 2.5-3.5%, 1-2%, 0.25-0.5%, and 0.25-0.75%. Phytoremediation was more effective significantly in controlling heavy metal pollution risk of tailings than immobilization. These results provided a new ecological remediation OSA-NHC model, meaning a combination of optimal substrate amelioration and native hyperaccumulator colonization, which could achieve vegetation restoration and augment heavy metal pollution control in non-ferrous metal tailings pond.

[The Prognostic Value of FOSB Gene in Acute Myeloid Leukemia].

AbstractObjective: To analyze the expression of FOSB in acute myeloid leukemia （AML） and its correlation with prognosis of the patient based on the large sample data. METHODS: The genome, transcriptome, gene chip and clinical information from multiple public databases were statistical analyzed. RESULTS: The expression of FOSB gene in AML patients was significantly higher than that in normal people. The prognostic analysis of the 163 patients showed that the patients with high FOSB expression showed longer OS and EFS than those with FOSB low expression. The patients were further divided into chemotherapy group and allogeneic hematopoietic stem cell transplantation (allo-HSCT) group according to the treatment method, and then each group was divided into two subgroups (FOSBhigh, FOSBlow) according to the median expression level of FOSB. In the allo-HSCT group, the patients with FOSB high expression was longer event-free survival (EFS: P=0.017) and overall survival (OS: P=0029). At the same time, allo-HSCT in patients with high FOSB expression could improve the prognosis of the patients (Chemotherapy vs Allo-HSCT, OS: P<0.001, EFS: P=0.007). Multivariate analysis showed that the high expression of FOSB was an independent favorable prognostic factor for EFS and OS (EFS: HR=0.501， P=0.019; OS: HR=0.461， P=0.009) of the patients. CONCLUSION: The high expression of FOSB indicated a good prognosis for acute myeloid leukemia.

SenseBack - An Implantable System for Bidirectional Neural Interfacing.

Chronic in-vivo neurophysiology experiments require highly miniaturized, remotely powered multi-channel neural interfaces which are currently lacking in power or flexibility post implantation. To resolve this problem we present the SenseBack system, a post-implantation reprogrammable wireless 32-channel bidirectional neural interfacing device that can enable chronic peripheral electrophysiology experiments in freely behaving small animals. The large number of channels for a peripheral neural interface, coupled with fully implantable hardware and complete software flexibility enable complex in-vivo studies where the system can adapt to evolving study needs as they arise. In complementary \textit{ex-vivo} and \textit{in-vivo} preparations, we demonstrate that this system can record neural signals and perform high-voltage, bipolar stimulation on any channel. In addition, we demonstrate transcutaneous power delivery and Bluetooth 5 data communication with a PC. The SenseBack system is capable of stimulation on any channel with 20 V of compliance and up to 315 A of current, and highly configurable recording with per-channel adjustable gain and filtering with 8 sets of 10-bit ADCs to sample data at 20 kHz for each channel. To our knowledge this is the first such implantable research platform offering this level of performance and flexibility post-implantation (including complete reprogramming even after encapsulation) for small animal electrophysiology. Here we present initial acute trials, demonstrations and progress towards a system that we expect to enable a wide range of electrophysiology experiments in freely behaving animals.

Assessing a novel, lab-free, point-of-care test for SARS-CoV-2 (CovidNudge): a diagnostic accuracy study.

BACKGROUND: Access to rapid diagnosis is key to the control and management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory RT-PCR testing is the current standard of care but usually requires a centralised laboratory and significant infrastructure. We describe our diagnostic accuracy assessment of a novel, rapid point-of-care real time RT-PCR CovidNudge test, which requires no laboratory handling or sample pre-processing. METHODS: Between April and May, 2020, we obtained two nasopharyngeal swab samples from individuals in three hospitals in London and Oxford (UK). Samples were collected from three groups: self-referred health-care workers with suspected COVID-19; patients attending emergency departments with suspected COVID-19; and hospital inpatient admissions with or without suspected COVID-19. For the CovidNudge test, nasopharyngeal swabs were inserted directly into a cartridge which contains all reagents and components required for RT-PCR reactions, including multiple technical replicates of seven SARS-CoV-2 gene targets (rdrp1, rdrp2, e-gene, n-gene, n1, n2 and n3) and human ribonuclease P (RNaseP) as sample adequacy control. Swab samples were tested in parallel using the CovidNudge platform, and with standard laboratory RT-PCR using swabs in viral transport medium for processing in a central laboratory. The primary analysis was to compare the sensitivity and specificity of the point-of-care CovidNudge test with laboratory-based testing. FINDINGS: We obtained 386 paired samples: 280 (73%) from self-referred health-care workers, 15 (4%) from patients in the emergency department, and 91 (23%) hospital inpatient admissions. Of the 386 paired samples, 67 tested positive on the CovidNudge point-of-care platform and 71 with standard laboratory RT-PCR. The overall sensitivity of the point-of-care test compared with laboratory-based testing was 94% (95% CI 86-98) with an overall specificity of 100% (99-100). The sensitivity of the test varied by group (self-referred healthcare workers 94% [95% CI 85-98]; patients in the emergency department 100% [48-100]; and hospital inpatient admissions 100% [29-100]). Specificity was consistent between groups (self-referred health-care workers 100% [95% CI 98-100]; patients in the emergency department 100% [69-100]; and hospital inpatient admissions 100% [96-100]). Point of care testing performance was similar during a period of high background prevalence of laboratory positive tests (25% [95% 20-31] in April, 2020) and low prevalence (3% [95% 1-9] in inpatient screening). Amplification of viral nucleocapsid (n1, n2, and n3) and envelope protein gene (e-gene) were most sensitive for detection of spiked SARS-CoV-2 RNA. INTERPRETATION: The CovidNudge platform was a sensitive, specific, and rapid point of care test for the presence of SARS-CoV-2 without laboratory handling or sample pre-processing. The device, which has been implemented in UK hospitals since May, 2020, could enable rapid decisions for clinical care and testing programmes. FUNDING: National Institute of Health Research (NIHR) Imperial Biomedical Research Centre, NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at Oxford University in partnership with Public Health England, NIHR Biomedical Research Centre Oxford, and DnaNudge.

The MSC-Derived Exosomal lncRNA H19 Promotes Wound Healing in Diabetic Foot Ulcers by Upregulating PTEN via MicroRNA-152-3p.

Mesenchymal stem cells (MSCs) have been reported to hold promise to accelerate the wound-healing process in diabetic foot ulcer (DFU) due to the multilineage differentiation potential. Hence, this study intended to explore the wound healing role of MSC-derived exosomes containing long noncoding RNA (lncRNA) H19 in DFU. lncRNA H19 was predicated to bind to microRNA-152-3p (miR-152-3p), which targeted phosphatase and tensin homolog (PTEN) deleted on chromosome ten. Fibroblasts in DFU samples exhibited highly expressed miR-152-3p and poorly expressed lncRNA H19 and PTEN, along with an activated phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt1) signaling pathway. The fibroblasts were cocultured with lncRNA H19-transfected MSCs and MSC-derived exosomes to assess the effect of the lncRNA H19/miR-152-3p/PTEN axis on the biological activities and inflammation in fibroblasts. Mouse models of DFU were developed by streptozotocin, which was injected with MSC-derived exosomes overexpressing lncRNA H19. lncRNA H19 in MSCs was transferred through exosomes to fibroblasts, the mechanism of which improved wound healing in DFU, corresponded to promoted fibroblast proliferation and migration, as well as suppressed apoptosis and inflammation. Wound healing in mice with DFU was facilitated following the injection of MSC-derived exosomes overexpressing lncRNA H19. Taken together, MSC-derived exosomal lncRNA H19 prevented the apoptosis and inflammation of fibroblasts by impairing miR-152-3p-mediated PTEN inhibition, leading to the stimulated wound-healing process in DFU.

Compact standalone platform for neural recording with real-time spike sorting and data logging.

OBJECTIVE: Longitudinal observation of single unit neural activity from large numbers of cortical neurons in awake and mobile animals is often a vital step in studying neural network behaviour and towards the prospect of building effective brain-machine interfaces (BMIs). These recordings generate enormous amounts of data for transmission and storage, and typically require offline processing to tease out the behaviour of individual neurons. Our aim was to create a compact system capable of: (1) reducing the data bandwidth by circa 2 to 3 orders of magnitude (greatly improving battery lifetime and enabling low power wireless transmission in future versions); (2) producing real-time, low-latency, spike sorted data; and (3) long term untethered operation. APPROACH: We have developed a headstage that operates in two phases. In the short training phase a computer is attached and classic spike sorting is performed to generate templates. In the second phase the system is untethered and performs template matching to create an event driven spike output that is logged to a micro-SD card. To enable validation the system is capable of logging the high bandwidth raw neural signal data as well as the spike sorted data. MAIN RESULTS: The system can successfully record 32 channels of raw neural signal data and/or spike sorted events for well over 24 h at a time and is robust to power dropouts during battery changes as well as SD card replacement. A 24 h initial recording in a non-human primate M1 showed consistent spike shapes with the expected changes in neural activity during awake behaviour and sleep cycles. SIGNIFICANCE: The presented platform allows neural activity to be unobtrusively monitored and processed in real-time in freely behaving untethered animals-revealing insights that are not attainable through scheduled recording sessions. This system achieves the lowest power per channel to date and provides a robust, low-latency, low-bandwidth and verifiable output suitable for BMIs, closed loop neuromodulation, wireless transmission and long term data logging.

A 64-Channel Versatile Neural Recording SoC With Activity-Dependent Data Throughput.

Modern microtechnology is enabling the channel count of neural recording integrated circuits to scale exponentially. However, the raw data bandwidth of these systems is increasing proportionately, presenting major challenges in terms of power consumption and data transmission (especially for wireless systems). This paper presents a system that exploits the sparse nature of neural signals to address these challenges and provides a reconfigurable low-bandwidth event-driven output. Specifically, we present a novel 64-channel low-noise (2.1 V), low-power (23  W per analogue channel) neural recording system-on-chip (SoC). This features individually configurable channels, 10-bit analogue-to-digital conversion, digital filtering, spike detection, and an event-driven output. Each channel's gain, bandwidth, and sampling rate settings can be independently configured to extract local field potentials at a low data-rate and/or action potentials (APs) at a higher data rate. The sampled data are streamed through an SRAM buffer that supports additional on-chip processing such as digital filtering and spike detection. Real-time spike detection can achieve 2 orders of magnitude data reduction, by using a dual polarity simple threshold to enable an event driven output for neural spikes (16-sample window). The SoC additionally features a latency-encoded asynchronous output that is critical if used as part of a closed-loop system. This has been specifically developed to complement a separate on-node spike sorting coprocessor to provide a real-time (low latency) output. The system has been implemented in a commercially available 0.35-m CMOS technology occupying a silicon area of 19.1 mm (0.3 mm gross per channel), demonstrating a low-power and efficient architecture that could be further optimized by aggressive technology and supply voltage scaling.

Neuromodulation: present and emerging methods.

Neuromodulation has wide ranging potential applications in replacing impaired neural function (prosthetics), as a novel form of medical treatment (therapy), and as a tool for investigating neurons and neural function (research). Voltage and current controlled electrical neural stimulation (ENS) are methods that have already been widely applied in both neuroscience and clinical practice for neuroprosthetics. However, there are numerous alternative methods of stimulating or inhibiting neurons. This paper reviews the state-of-the-art in ENS as well as alternative neuromodulation techniques-presenting the operational concepts, technical implementation and limitations-in order to inform system design choices.

A charge-metering method for voltage-mode neural stimulation.

Electrical neural stimulation is the technique used to modulate neural activity by inducing an instantaneous charge imbalance. This is typically achieved by injecting a constant current and controlling the stimulation time. However, constant voltage stimulation is found to be more energy-efficient although it is challenging to control the amount of charge delivered. This paper presents a novel, fully integrated circuit for facilitating charge-metering in constant voltage stimulation. It utilises two complementary stimulation paths. Each path includes a small capacitor, a comparator and a counter. They form a mixed-signal integrator that integrates the stimulation current onto the capacitor while monitoring its voltage against a threshold using the comparator. The pulses from the comparator are used to increment the counter and reset the capacitor. Therefore, by knowing the value of the capacitor, threshold voltage and output of the counter, the quantity of charge delivered can be calculated. The system has been fabricated in 0.18 µm CMOS technology, occupying a total active area of 339 µm × 110 µm. Experimental results were taken using: (1) a resistor-capacitor EEI model and (2) platinum electrodes with ringer solution. The viability of this method in recruiting action potentials has been demonstrated using a cuff electrode with Xenopus sciatic nerve. For a 10 nC target charge delivery, the results of (2) show a charge delivery error of 3.4% and a typical residual charge of 77.19pC without passive charge recycling. The total power consumption is 45 µW. The performance is comparable with other publications. Therefore, the proposed stimulation method can be used as a new approach for neural stimulation.