Treatment of Syringomyelia Characterized by Focal Dilatation of the Central Canal Using Mesenchymal Stem Cells and Neural Stem Cells.

BACKGROUND: Syringomyelia is a progressive chronic disease that leads to nerve pain, sensory dissociation, and dyskinesia. Symptoms often do not improve after surgery. Stem cells have been widely explored for the treatment of nervous system diseases due to their immunoregulatory and neural replacement abilities. METHODS: In this study, we used a rat model of syringomyelia characterized by focal dilatation of the central canal to explore an effective transplantation scheme and evaluate the effect of mesenchymal stem cells and induced neural stem cells for the treatment of syringomyelia. RESULTS: The results showed that cell transplantation could not only promote syrinx shrinkage but also stimulate the proliferation of ependymal cells, and the effect of this result was related to the transplantation location. These reactions appeared only when the cells were transplanted into the cavity. Additionally, we discovered that cell transplantation transformed activated microglia into the M2 phenotype. IGF1-expressing M2 microglia may play a significant role in the repair of nerve pain. CONCLUSION: Cell transplantation can promote cavity shrinkage and regulate the local inflammatory environment. Moreover, the proliferation of ependymal cells may indicate the activation of endogenous stem cells, which is important for the regeneration and repair of spinal cord injury.

Distribution, seasonal variation and influencing factors of total dissolved inorganic arsenic in the middle and lower reaches of the Yellow River.

The concentrations of dissolved arsenate in natural water has an important impact on human health. The distributions, seasonal variation and major influencing factors of total dissolved inorganic arsenic (TDIAs) were studied in the Yellow River. The concentrations of TDIAs in the middle and lower reaches of the Yellow River ranged from 4.3 to 42.4 nmol/L, which met the standards for drinking water of WHO. The seasonal variation of TDIAs concentration in the middle and lower reaches of the Yellow River was highest in summer, followed by autumn and winter, and lowest in spring. The influencing factors of TDIAs concentration in the middle and lower reaches of the Yellow River mainly include the hydrological conditions, topographical variation, the adsorption and desorption of suspended particulate matter (SPM) and the intervention of human activities. The absorption of TDIAs by phytoplankton in the Xiaolangdi Reservoir (XLD) is an important factor affecting its distributions and seasonal variation. The annual flux of TDIAs transported from the Yellow River into the Bohai Sea ranged from 1.1 × 105 to 4.5 × 105 mol from 2016 to 2018, which is lower than the flux in 1985 and 2009. The carcinogenic risks (CR) of TDIAs for children and adults were all within acceptable levels (<10-6).

Grafted human-induced pluripotent stem cells-derived oligodendrocyte progenitor cells combined with human umbilical vein endothelial cells contribute to functional recovery following spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is a devastating disease that causes extensive damage to oligodendrocytes and neurons leading to demyelination and axonal degeneration. In this study, we co-transplanted cell grafts containing oligodendrocyte progenitor cells (OPCs) derived from human-induced pluripotent stem cells (iPSCs) combined with human umbilical vein endothelial cells (HUVECs), which were reported to promote OPCs survival and migration, into rat contusion models to promote functional recovery after SCI. METHODS: OPCs were derived from iPSCs and identified by immunofluorescence at different time points. Functional assays in vitro were performed to evaluate the effect of HUVECs on the proliferation, migration, and survival of OPCs by co-culture and migration assay, as well as on the neuronal axonal growth. A combination of OPCs and HUVECs was transplanted into the rat contusive model. Upon 8 weeks, immunofluorescence staining was performed to test the safety of transplanted cells and to observe the neuronal repairment, myelination, and neural circuit reconstruction at the injured area; also, the functional recovery was assessed by Basso, Beattie, and Bresnahan open-field scale, Ladder climb, SEP, and MEP. Furthermore, the effect of HUVECs on grafts was also determined in vivo. RESULTS: Data showed that HUVECs promote the proliferation, migration, and survival of OPCs both in vitro and in vivo. Furthermore, 8 weeks upon engraftment, the rats with OPCs and HUVECs co-transplantation noticeably facilitated remyelination, enhanced functional connection between the grafts and the host and promoted functional recovery. In addition, compared with the OPCs-alone transplantation, the co-transplantation generated more sensory neurons at the lesion border and significantly improved the sensory functional recovery. CONCLUSIONS: Our study demonstrates that transplantation of OPCs combined with HUVECs significantly enhances both motor and sensory functional recovery after SCI. No significance was observed between OPCs combined with HUVECs group and OPCs-alone group in motor function recovery, while the sensory function recovery was significantly promoted in OPCs combined with HUVECs groups compared with the other two groups. These findings provide novel insights into the field of SCI research.

Nutrient changes in the Bohai Sea over the past two decades.

With the growing problem of eutrophication in the Bohai Sea, actions have been taken to reduce nutrient inputs, but it remains to be seen whether nutrient levels and structure have been ameliorated. In this study, the nutrient trends in the Bohai Sea are re-examined based on observations from 2000 to 2019. The results suggest that dissolved inorganic nitrogen (DIN) concentrations and DIN/DIP (dissolved inorganic phosphate) ratios gradually increased from 2000 to 2013 but dramatically decreased from 2013 to 2019. The increase and decrease rates of DIN concentrations decreased with increasing water depth, indicating that DIN concentrations in nearshore waters responded more rapidly to changes in human activities. However, DIP concentrations responded weakly to nutrient inputs, with their trends uncoupled. The DIN/DIP ratios have declined close to and in some seasons even below the canonical Redfield ratio in areas with water depths >20 m recently, implying that relative nutrient limitation in these areas may be shifting from relative phosphorus (P) limitation to absence of relative nutrient limitation or relative nitrogen (N) limitation. Atmospheric deposition, wastewater discharge, and riverine input were responsible for 66 %, 21 %, and 13 % of the variance in the decline of DIN concentration, respectively. Several environmental indicators responded positively to the decrease in DIN concentrations and DIN/DIP ratios, with varying degrees of recovery recently. Our study proves the phased success of various nutrient reduction measures taken by the Chinese government to improve the environment of the Bohai Sea over the past decade.

Transmission and infection risk of COVID-19 when people coughing in an elevator.

People in cities use elevators daily. With the COVID-19 pandemic, there are more worries about elevator safety, since elevators are often small and crowded. This study used a proven CFD model to see how the virus could spread in elevators. We simulated five people taking in an elevator for 2 min and analyzed the effect of different factors on the amount of virus that could be inhaled, such as the infected person's location, the standing positions of the persons, and the air flow rate. We found that the position of the infected person and the direction they stood greatly impacted virus transmission in the elevator. The use of mechanical ventilation with a flow rate of 30 ACH (air changes per hour) was effective in reducing the risk of infection. In situations where the air flow rate was 3 ACH, we found that the highest number of inhaled virus copies could range from 237 to 1186. However, with a flow rate of 30 ACH, the highest number was reduced to 153 to 509. The study also showed that wearing surgical masks decreased the highest number of inhaled virus copies to 74 to 155.

Suppression of TGFßR-Smad3 pathway alleviates the syrinx induced by syringomyelia.

BACKGROUND: Syringomyelia is a cerebrospinal fluid (CSF) disorder resulted in separation of pain and temperature, dilation of central canal and formation of syrinx in central canal. It is unclear about mechanisms of the dilation and syrinx formation. We aimed to investigate roles of ependymal cells lining central canal on the dilation, trying to reduce syrinx formation in central canal. METHODS: We employed 78 Sprague-Dawley (SD) rats totally with syringomyelia to detect the contribution of ependymal cells to the dilation of central canal. Immunofluorescence was used to examine the activation of ependymal cells in 54 syringomyelia rat models. BrdU was used to indicate the proliferation of ependymal cells through intraperitoneal administration in 6 syringomyelia rat models. 18 rats with syringomyelia were injected with SIS3, an inhibitor of TGFßR-Smad3, and rats injected with DMSO  were used as control. Among the 18 rats, 12 rats were used for observation of syrinx following SIS3 or DMSO administration by using magnetic resonance imaging (MRI) on day 14 and day 30 under syringomyelia without decompression. All the data were expressed as mean ± standard deviation (mean ± SD). Differences between groups were compared using the two-tailed Student's t-test or ANOVA. Differences were considered significant when *p < 0.05. RESULTS: Our study showed the dilation and protrusions of central canal on day 5 and enlargement from day 14 after syringomyelia induction in rats with activation of ependymal cells lining central canal. Moreover, the ependymal cells contributed to protrusion formation possibly through migration along with central canal. Furthermore, suppression of TGFßR-Smad3 which was crucial for migration reversed the size of syrnix in central canal without treatment of decompression, suggesting TGFßR-Smad3 signal might be key for dilation of central canal and formation of syrinx. CONCLUSIONS: The size of syrinx was decreased after SIS3 administration without decompression. Our study depicted the mechanisms of syrinx formation and suggested TGFßR-Smad3 signal might be key for dilation of central canal and formation of syrinx.

Low-Dose Taxol Promotes Neuronal Axons Extension and Functional Recovery after Spinal Cord Injury.

Axonal regeneration has been the research focus in the field of clinical treatment for spinal cord injury (SCI). The growth and extension of neuronal axons is a dynamic biological process mediated by the cytoskeleton, and microtubule plays an important role in axonal growth. Moderate stabilization of microtubule promotes axonal growth and eliminates various intra- and extracellular mechanisms that impede axonal regeneration. After SCI, the damaged axons rapidly form a growth cone, wherein the stability of tubulin decreases, impairing axonal regeneration. Taxol with proven clinical safety is commonly used as a broad-spectrum antitumor drug. Importantly, Taxol can promote axonal extension by enhancing and stabilizing the microtubule assembly. In our study, we systematically investigated the differentiation of neural stem cells (NSCs) in vitro and functional recovery in injured rats in vivo following Taxol treatment. Low-dose Taxol promoted differentiation of NSCs to neurons and significantly extended the axons in vitro. In vivo, Taxol promoted the expression of ßIII-tubulin in the injured areas and motor function recovery after SCI. Low-dose Taxol is a promising clinical agent to promote axonal regeneration after SCI.

Resection of Scar Tissue in Rats With Spinal Cord Injury Can Promote the Expression of ßâ ¢-tubulin in the Injured Area.

BACKGROUND: Previous research shows that scar tissue formed in the injured area after spinal cord injury blocks nerve regeneration and functional recovery. However, those researchers tried to prevent the formation of scar after spinal cord injury to promote nerve regeneration, but it ran counter to their desire, indicating that the formation of scar might play a role in functional recovery after spinal cord injury. METHODS: To investigate roles of scar formation on functional repair after spinal cord injury, we selected several different key time points to resect the scar tissue formed after spinal cord injury based on the rat models of the T8-T9 transection injury of spinal cord. First, the recovery of motor function was evaluated by Basso Beattie Bresnahan score and electrophysiologic examination; second, the pathologic features of functional recovery were analyzed mainly by immunofluorescence ßⅢ-tubulin staining; finally, the genes related to the recovery of motor function were predicted by high-throughput sequencing analysis. RESULTS: Immunofluorescence results showed that the resection of scar tissue promoted significantly the recovery of motor function and the expression of ßⅢ-tubulin in the injured area in the second week after spinal cord injury. Furthermore, RNA-seq studies showed that Tubb3 and Tubb6 gene expression and other neural regeneration pathways were significantly different in the tissue before and after early resection. CONCLUSIONS: Excision of scar tissue in the second week promoted nerve regeneration after spinal cord injury. Tubb3 and Tubb6 genes might be the potential targets for spinal cord injury therapy in our study.

Role of CAST-Drp1 Pathway in Retinal Neuron-Regulated Necrosis in Experimental Glaucoma.

OBJECTIVE: Numerous studies have indicated that excitatory amino acid toxicity, such as glutamate toxicity, is involved in glaucoma. In addition, excessive glutamate can lead to an intracellular calcium overload, resulting in regulated necrosis. Our previous studies have found that the calpastatin (CAST)-calpain pathway plays an important role in retinal neuron-regulated necrosis after glutamate injury. Although inhibition of the calpain pathway can decrease regulated necrosis, necrotic cells remain. It has been suggested that there are other molecules that participate in retinal neuron-regulated necrosis. CAST is an important regulator of dynamin-related protein 1 (Drp1)-mediated mitochondrial defects. Thus, the aim of this study was to determine whether the CAST-Drp1 pathway may be an underlying signaling axis in neuron-regulated necrosis. METHODS: Using cultured retinal neurons and in an in-vivo glaucoma model induced by glutamate overload, members of the CAST-Drp1 pathway were assessed by immunofluorescence, Western blotting, Phos-tagTM SDS-PAGE, and co-immunoprecipitation assays. Moreover, the black and white box test was performed on the rats. RESULTS: We found that more retinal neuron-regulated necrosis and Drp1 activation as well as lower CAST levels were present in the glutamate-induced glaucoma model. Rats with glutamate-induced glaucoma exhibited impaired visual function. We also observed retinal neuron-regulated necrosis and Drp1 activity decreased, and impaired vision recovered after CAST active peptide application, indicating that the CAST-Drp1 pathway plays a critical role in retinal neuron-regulated necrosis and visual function. CONCLUSION: The results of this study indicate that the CAST-Drp1 pathway protects against retinal neuron-regulated necrosis, which may expand the therapeutic targets for the treatment of neurodegenerative disorders involving dysfunction of glutamate metabolism, such as glaucoma.

Interannual variations in the nutrient cycle in the central Bohai Sea in response to anthropogenic inputs.

In recent decades, there has been growing concern regarding the effects of human activities on the coastal nutrient cycle. However, interannual variations in the coastal nutrient cycle in response to anthropogenic nutrient input have rarely been quantified. In this study, a hydrodynamic-ecological model capable of describing the nitrogen and phosphorus cycles was used to analyze interannual variations in the nutrient cycle in the central Bohai Sea, a typical semi-enclosed sea in the Northwest Pacific. The results showed an increasing trend of dissolved inorganic nitrogen and particulate nitrogen from 1998 to 2017, whereas different forms of phosphorus showed no obvious interannual variations. The annual nutrient budgets were also quantitatively estimated from 1998 to 2017. This indicates that atmospheric nitrogen deposition plays an important role in interannual variations in the nitrogen cycle. A large amount of nitrogen from anthropogenic inputs was mainly removed by sedimentation processes instead of increasing the standing stock of nitrogen in the sea. With the reduction of anthropogenic inputs, the model showed that a variety of forms of nitrogen concentration decreased linearly, whereas phosphorus concentration increased slightly. Therefore, although environmental governance can effectively alleviate water eutrophication, it is necessary to avoid the situation where the dissolved inorganic nitrogen concentration in the sea becomes too low for phytoplankton to grow, which may determine the primary productivity and eventually affect fishery resources.

Application of data-driven RANS model in simulating indoor airflow.

The indoor environment has a significant impact on our wellbeing. Accurate prediction of the indoor air distribution can help to create a good indoor environment. Reynolds-averaged Navier-Stokes (RANS) models are commonly used for indoor airflow prediction. However, the Boussinesq hypothesis used in the RANS model fails to account for indoor anisotropic flows. To solve this problem, this study developed a data-driven RANS model by using a nonlinear model from the literature. An artificial neural network (ANN) was used to determine the coefficients of high-order terms. Three typical indoor airflows were selected as the training set to develop the model. Four other cases were used as testing sets to verify the generalizability of the model. The results show that the data-driven model can better predict the distributions of air velocity, temperature, and turbulent kinetic energy for the indoor anisotropic flows than the original RANS model. This is because the nonlinear terms are accurately simulated by the ANN. This investigation concluded that the data-driven model can correctly predict indoor anisotropic flows and has reasonably good generalizability.

HDAC6 Inhibition Alleviates Anesthesia and Surgery-Induced Less Medial Prefrontal-Dorsal Hippocampus Connectivity and Cognitive Impairment in Aged Rats.

To investigate the underlying mechanisms of postoperative cognitive dysfunction and the impairment of medial prefrontal cortex-hippocampus connectivity. Postoperative cognitive dysfunction frequently affects elderly following surgery. The role of inter-brain-region connectivity abnormality after anesthesia and surgery on postoperative cognitive dysfunction development remains unclear. Medial prefrontal cortex-hippocampus connectivity of aged and adult rats was evaluated by injecting neurotracer biotinylated dextranamine (BDA) into bilateral hippocampus 3 days before partial hepatectomy, and biotinylated dextranamine positive cells of medial prefrontal cortex 2 days after hepatectomy were counted. HDAC6 shRNA was injected into medial prefrontal cortex and hippocampus bilaterally before hepatectomy or an HDAC6 activity inhibitor Tubastatin A was administered systemically after hepatectomy. Neuroinflammation and HDAC6 down-target ac-tubulin in medial prefrontal cortex and hippocampus were detected. Learning and memory of rats were evaluated by Barnes Maze task during 2-5 days after surgery and delayed matching-to-place water maze task during 10-23 days after surgery. Compared to the age-matched normal controls, anesthesia and surgery significantly decreased BDA-positive neurons in medial prefrontal cortex of aged rats, but not young adult rats. Local HDAC6 knockdown and systemic HDAC6 inhibition both increased BDA-positive neurons number of medial prefrontal cortex, alleviated learning and memory impairment in the Barnes Maze task and water maze task, decreased HDAC6 expression, inflammatory cytokines, astrocyte and microglial activation, and increased ac-tubulin expression in aged rats which received surgery. Our data indicated that anesthesia and surgery impaired medial prefrontal cortex-hippocampus connectivity and cognition which was associated with HDAC6 overexpression.

Airborne transmission of COVID-19 virus in enclosed spaces: An overview of research methods.

Since the outbreak of COVID-19 in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has spread worldwide. This study summarized the transmission mechanisms of COVID-19 and their main influencing factors, such as airflow patterns, air temperature, relative humidity, and social distancing. The transmission characteristics in existing cases are providing more and more evidence that SARS CoV-2 can be transmitted through the air. This investigation reviewed probabilistic and deterministic research methods, such as the Wells-Riley equation, the dose-response model, the Monte-Carlo model, computational fluid dynamics (CFD) with the Eulerian method, CFD with the Lagrangian method, and the experimental approach, that have been used for studying the airborne transmission mechanism. The Wells-Riley equation and dose-response model are typically used for the assessment of the average infection risk. Only in combination with the Eulerian method or the Lagrangian method can these two methods obtain the spatial distribution of airborne particles' concentration and infection risk. In contrast with the Eulerian and Lagrangian methods, the Monte-Carlo model is suitable for studying the infection risk when the behavior of individuals is highly random. Although researchers tend to use numerical methods to study the airborne transmission mechanism of COVID-19, an experimental approach could often provide stronger evidence to prove the possibility of airborne transmission than a simple numerical model. All in all, the reviewed methods are helpful in the study of the airborne transmission mechanism of COVID-19 and epidemic prevention and control.

Optical-feedback cavity ring-down spectroscopy for NO2 extinction coefficient measurement using a continuous wave laser diode.

Optical-feedback (OF) cavity ring-down spectroscopy consisting of a linear cavity is developed by employing a continuous wave laser diode (LD) with multi-longitudinal modes. Due to the OF effect caused by the cavity output laser back into the LD, the laser frequency is locked, and the intracavity laser intensity is enhanced. We use different concentrations of NO2 gases to test the apparatus, and the results show good agreement with theoretical values. Owing to the compactness of the laser source and high detection accuracy, the device can be used for detection of low-concentration absorbent gases in the environmental monitoring field.

Corrigendum to "Evaluation of different air distribution systems in a commercial airliner cabin in terms of comfort and COVID-19 infection risk" Build. Environ., Volume 208, January 2022, 108590.

[This corrects the article DOI: 10.1016/j.buildenv.2021.108590.].

Investigation of airborne particle exposure in an office with mixing and displacement ventilation.

Effective ventilation could reduce COVID-19 infection in buildings. By using a computational fluid dynamics technique and advanced experimental measurement methods, this investigation studied the air velocity, air temperature, and particle number concentration in an office under a mixing ventilation (MV) system and a displacement ventilation (DV) system with different ventilation rates. The results show reasonably good agreement between the computed results and measured data. The air temperature and particle number concentration under the MV system were uniform, while the DV system generated a vertical stratification of the air temperature and particle number concentration. Because of the vertical stratification of the particle number concentration, the DV system provided better indoor air quality than the MV system. An increase in ventilation rate can reduce the particle concentration under the two systems. However, the improvement was not proportional to the ventilation rate. The increase in ventilation rate from 2 ACH to 4 ACH and 6 ACH for MV system reduced the particle concentration by 20% and 60%, respectively. While for the DV system, increasing the ventilation rate from 2 ACH to 4 ACH and 6 ACH reduced the particle concentration by only 10% and 40%, respectively. The ventilation effectiveness of the MV system was close to 1.0, but it was much higher for the DV system. Therefore, the DV system was better than the MV system.

Characterization of Human-Induced Neural Stem Cells and Derivatives following Transplantation into the Central Nervous System of a Nonhuman Primate and Rats.

Neural stem cells (NSCs) and derivatives are potential cellular sources to treat neurological diseases. In the current study, we reprogrammed human peripheral blood mononuclear cells into induced NSCs (iNSCs) and inserted GFP gene into the AAVS1 site for graft tracing. Targeted integration of GFP does not affect the proliferation and differentiation capacity of iNSCs. iNSC-GFP can be further differentiated into dopaminergic precursors (DAPs) and motor neuron precursors (MNPs), respectively. iNSCs were engrafted into the motor cortex and iNSC-DAPs into the striatum and substantia nigra (SN) of a nonhuman primate, respectively. The surviving iNSCs could respond to the microenvironment of the cortex and spontaneously differentiate into mature neurons that extended neurites. iNSC-DAPs survived well and matured into DA neurons following transplantation into the striatum and SN. iNSC-MNPs could also survive and turn into motor neurons after being engrafted into the spinal cord of rats. The results suggest that iNSCs and derivatives have a potential to be used for the treatment of neurological diseases.

Evaluation of airborne particle exposure for riding elevators.

Social distancing is a key factor for health during the COVID-19 pandemic. In many indoor spaces, such as elevators, it is difficult to maintain social distancing. This investigation used computational-fluid-dynamics (CFD) to study airborne particle exposure in riding an elevator in a typical building with 35 floors. The elevator traveled from the ground floor to the 35th floor with two stops on floor 10 and floor 20, comprising 114 s. The CFD simulated the dispersion of the aerosolized particles exhaled by an index person while breathing in both lobby and elevator areas. The study calculated the accumulated dose of susceptible riders riding in elevators with the index person under different conditions including different ventilation rates, air supply methods, and elevator cab geometries. This investigation also studied a case with a single cough from the index person as the person entered the elevator. The results show that, due to the short duration of the average elevator ride, the number of particles inhaled by a susceptible rider was low. For the reference case with a 72 ACH (air changes per hour) ventilation rate, the highest accumulated particle dose by a susceptible passenger close to the index person was only 1.59. The cough would cause other riders to inhale approximately 8 orders of magnitude higher particle mass than from continuous breathing by the index person for the whole duration of the ride.

Evaluation of different air distribution systems in a commercial airliner cabin in terms of comfort and COVID-19 infection risk.

The air distribution system in an airliner plays a key role in maintaining a comfortable and healthy environment in the aircraft cabin. To evaluate the performance of a novel displacement ventilation (DV) system and a traditional mixing ventilation (MV) system in an airliner cabin, this study conducted experiments and simulations in a seven-row cabin mockup. This investigation used ultrasonic anemometers and T-thermocouples to measure the air velocity, temperature and distribution of 1 µm and 5 µm particles. Simulation verifications were performed for these operating conditions, and additional scenarios with different occurrence source locations were also simulated. This study combined the Wells-Riley equation with a real case based on a COVID-19 outbreak among passengers on a long-distance bus to obtain the COVID-19 quanta value. Through an evaluation of the airflow organization, thermal comfort, and risk of COVID-19 infection, the two ventilation systems were compared. This investigation found that polydisperse particles should be used to calculate the risk of infection in airliner cabins. In addition, at the beginning of the pandemic, the infection risk with DV was lower than that with MV. In the middle and late stages of the epidemic, the infection risk with MV can be reduced when passengers wear masks, leading to an infection risk approximately equal to that of DV.