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Both of exosomes derived from mesenchymal stem cells (MSCs) and glial cell line-derived neurotrophic factor (GDNF) show potential for the treatment of neuropathic pain. Here, the analgesic effects of exosomes derived from bone marrow MSCs (BMSCs) were investigated. BMSCs-derived exosomes were isolated and characterized. Chronic constriction injury (CCI) was constructed to induce neuropathic pain in rats, which were then treated with exosomes. Pain behaviors were evaluated by measuring paw withdrawal thresholds and latency. The changes of key proteins, including cytokines, were explored using Western blot and ELISA. Administration of BMSCs-derived exosomes alleviated neuropathic pain, as demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia, as well as the reduced secretion of pro-inflammatory cytokines in CCI rats. These effects were comparable to the treatment of GDNF alone. Mechanically, the exosomes suppressed the CCI-induced activation of TLR2/MyD88/NF-κB signaling pathway, while GDNF knockdown impaired their analgesic effects on CCI rat. BMSCs-derived exosomes may alleviate CCI-induced neuropathic pain and inflammation in rats by transporting GDNF. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationship between serum selenoprotein S (SelS) and obesity in patients with type 2 diabetes mellitus (T2DM). Methods Two hundred and nine T2DM patients who were managed by the National Metabolic Management Center (MMC) of the First Affiliated Hospital of Dalian Medical University from November 2017 to November 2019 and 55 healthy people as controls in the health examination center of our hospital were enrolled in the retrospective cross-sectional study. The general condition, biochemical indexes and obesity evaluation parameters were recorded. According to the serum SelS quartile, T2DM patients were divided into Q1 group: ≤95.10 ng/dl (53 cases), Q2 group: 95.12 to 111.62 ng/dl (52 cases), Q3 group: 112.46 to 130.97 ng/dl (52 cases), Q4 group: ≥131.33 ng/dl (52 cases). Analysis of variances, rank sum test and Chi-square test were used for comparison between groups. Multiple stepwise regression was used to analyze the influencing factors of obesity evaluation index. Results There was statistically significant difference in visceral fat index (VAI) among T2DM abdominal obesity group, non-abdominal obesity group and healthy control group (H=36.679, P<0.01), but there was no statistically significant difference in serum SelS. There was statistically significant difference in serum amyloid A (SAA) level among the SelS quartile groups (H=3.560, P<0.01), but there was no statistically significant difference in visceral fat area (VFA), subcutaneous fat area (SFA), visceral fat area to subcutaneous fat area ratio (VSR) and VAI. Serum SelS was positively correlated with VFA, VSR, VAI and SAA (r=0.158 to 0.448, all P<0.05). Serum SelS was an independent risk factor for VFA (β= 0.172, P=0.003), VSR (β=0.001, P=0.01) and VAI (β=0.009, P=0.038). Conclusion Serum SelS level in T2DM patients is positively correlated with VFA, VSR and VAI, which is an independent risk factor for abdominal obesity. [ABSTRACT FROM AUTHOR]

Ren, J.; Chen, B.; Li, Y.; Dai, J., and Men, L., 2020. Dynamic variation characteristics of the riparian zone temperature distribution under fluctuating water levels: Field experiments and numerical modeling. Journal of Coastal Research, 36(6), 1178–1196. Coconut Creek (Florida), ISSN 0749-0208. Understanding the variations in water and heat transfer along the riparian zone under water-level fluctuations is essential for river water management, groundwater extraction, and ecosystem sustainability. The main purpose of this study is to describe the dynamics of the temperature field of the Dongting Lake beach under the fluctuation in the water level and to quantify its main influencing factors. Taking the section of Dongting Lake beach as the research object, an in situ monitoring device was used to monitor the water level, water temperature, and temperature at different depths of the beach in real time for 55 days, and the hydrothermal coupling model of the Dongting Lake beach was calibrated and verified. The main factors affecting the temperature field of the beach were determined by the global sensitivity analysis method. The results show that the fluctuation in the continental beach temperature field is small in the horizontal direction, the stratification phenomenon is obvious in the vertical direction, the temperature gradually rises with increasing depth, and the daily changes are weakened. During the high water level, the deep temperature of the beach has no obvious gradient change in the vertical direction, and as the water level of the river decreases, the external environmental temperature has a greater influence on the internal temperature field of the beach, resulting in a relatively pronounced gradient change in the deep temperature at the low water level. The results of the Morris one at a time global sensitivity analysis show that the permeability coefficient (Ks) has the greatest influence on the sensitivity of the model, followed by the porosity (n) and soil thermal conductivity (λs). The saturated moisture content (θs), residual moisture content (θr), and soil-specific heat capacity (Cs) have no significant effect on the model. [ABSTRACT FROM AUTHOR]

The hyporheic zone (HZ) is a saturated sediment layer connecting groundwater (GW) and surface water (SW) along a riverbed and river channel. The HZ plays an important role in connecting SW and GW in a river ecosystem, thereby helping maintain the ecological health of rivers. Studies on the HZ have therefore increased in many disciplines. This study used the VFLUX 2 software to assess vertical fluid flux in the HZ, in which the Hatch, Kerry, McCallum, and Luce models were applied and compared. The simulations were calibrated against data measured by the US Geological Survey at a water diversion channel within the Walker River Basin in Nevada. Using COMSOL Multiphysics, we developed a two-dimensional coupled numerical model of the saturated seepage and temperature fields, calibrated against measured temperature data. We also determined the vertical seepage velocity and compared the simulations with those of the analytical models in VFLUX 2. The results showed that the temperature field distribution of the HZ is obviously nonuniform in space. With a deeper monitoring point, the thermal response of each temperature measurement pointed to periodic temperature fluctuations of the SW, which exhibited attenuation and hysteresis characteristics. When the vertical flow velocity of GW was sufficiently large, an error in the accuracy of the Kerry model amplitude ratio was observed, regardless of the heat dispersion coefficient used. Under conditions of local GW recharge by SW and a heterogeneous permeability coefficient, the use of the amplitude ratio method is recommended to quantify the vertical GW flow rate in the HZ. [ABSTRACT FROM AUTHOR]

Background/Aims: VCP-interacting membrane selenoprotein (VIMP), an ER resident selenoprotein, is highly expressed in β-cells, however, the role of VIMP in β-cells has not been characterized. In this study, we studied the relationship between VIMP deficiency and β-cell survival in MIN6 insulinoma cells. Methods: To determine the role of VIMP in β-cells, lentiviral VIMP shRNAs were used to knock down (KD) expression of VIMP in MIN6 cells. Cell death was quantified by propidium iodide (PI) staining followed by flow cytometric analyses using a FACS Caliber and FlowJo software. Cell apoptosis and proliferation were determined by TUNEL assay and Ki67 staining, respectively. Cell cycle was analyzed after PI staining. Results: The results show that 1) VIMP suppression induces β-cell apoptosis, which is associated with a decrease in Bcl-xL, and the β-cell apoptosis induced by VIMP suppression can be inhibited by overexpression of Bcl-xL; 2) VIMP knockdown (KD) decreases cell proliferation and G1 cell cycle arrest by accumulating p27 and decreasing E2F1; 3) VIMP KD suppresses unfolded protein response (UPR) activation by regulating the IRE1α and PERK pathways; 4) VIMP KD increases insulin secretion. Conclusion: These results suggest that VIMP may function as a novel regulator to modulate β-cell survival, proliferation, cell cycle, UPR and insulin secretion in MIN6 cells. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction, partly induced by inflammatory mediators, is known to initiate and promote several cardiovascular diseases. Selenoprotein S (SelS) has been identified in endothelial cells and is associated with inflammation; however, its function in inflammation-induced endothelial dysfunction has not been described. We first demonstrated that the upregulation of SelS enhances the levels of nitric oxide and endothelial nitric oxide synthase in tumor necrosis factor- (TNF-) α-treated human umbilical vein endothelial cells (HUVECs). The levels of TNF-α-induced endothelin-1 and reactive oxygen species are also reduced by the upregulation of SelS. Furthermore, SelS overexpression blocks the TNF-α-induced adhesion of THP-1 cells to HUVECs and inhibits the increase in intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Moreover, SelS overexpression regulates TNF-α-induced inflammatory factors including interleukin-1β, interleukin-6, interleukin-8, and monocyte chemotactic protein-1 and attenuates the TNF-α-induced activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways. Conversely, the knockdown of SelS with siRNA results in an enhancement of TNF-α-induced injury in HUVECs. These findings suggest that SelS protects endothelial cells against TNF-α-induced dysfunction by inhibiting the activation of p38 MAPK and NF-κB pathways and implicates it as a possible modulator of vascular inflammatory diseases. [ABSTRACT FROM AUTHOR]

Groundwater–surface water interaction, particularly on exchange fluxes between streams and aquifers, plays a large role in the prerequisite conditions for the study of contaminants and nutrients in the hyporheic zone. One way to quantify these fluxes is by using heat as an environmental tracer. This study quantitatively analyzes the spatial heterogeneity and uncertainty of the vertical turbulent flow of a canopy in the Walker River Basin in Nevada, USA, using the thermal tracer method and the VFLUX software tool. Using the high spatial resolution temperature data measured by the US Geological Survey in the Walker River Basin in Nevada, with the finite element software, COMSOL Multiphysics, it establishes a two-dimensional, full-transect, water-thermal coupling calculation model for the river. The results show that long-term vertical hyporheic flux is between − 111.78 and 86.07 L/m2/d. The average vertical hyporheic flux under seasonal conditions was − 44.35 L/m2/d and − 36.78 L/m2/d in summer and winter, respectively, and the flux exhibits a non-monotonic change with increasing depth. By observing the similarity between the spatial distribution of streambed hyporheic exchange fluxes in winter and summer, as well as the distribution of the streambed profile temperature field, it was found that the spatial distribution of the average streambed hyporheic exchange fluxes can be clearly shown by the streambed profile temperature field in the corresponding season. [ABSTRACT FROM AUTHOR]

Soil thermal conductivity (λ) is an important thermal property which serves as an indicator for the coupling of soil, water, heat, and solutes in a numerical model. The objective of this study is to develop a new empirical model for estimating soil thermal conductivity. There are several methods for estimating λ available, but they are complicated and can produce relatively large errors. Using published datasets, the performance of the new estimate was evaluated along with nine other normalized models, and the advantages and disadvantages of each model and its relevant soil types were analyzed and compared. The results showed that the new empirical model is suitable for studying the thermal conductivities of soils of different textures. In the comparisons, it had the best performance among the ten models considered, with a minimum standard deviation (SD) of 0.074 W m−1 K−1, the coefficient of determination (R2) from 0.929 to 0.983 with a mean of 0.964, and relative error (Re), from 5.210 to 9.900% with a mean of 7.335%. The new model has been shown to improve the reliability of estimation of soil thermal conductivity and has application in agricultural science, environmental science, earth science and engineering research. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) is the most abundant mRNA modification. However, the role of m6A in regulating β-cell function is unknown. To address the functional role of METTL14, a key component of the m6A methyltransferase complex, in β-cells, we generated an METTL14 β-cell specific knockout mouse in adult MIP-CreERT transgenic mice. 4 weeks after tamoxifen treatment (100 mg/kg for 3 times every other day), the feeding glucose of βKO mice were 55.1% higher in βKO mice. βKO mice are also glucose intolerant. The AUC was increased by 54.7% in βKO mice (P<0.01). The fasting glucose were 307.5 ± 24.3 mg/dl in βKO mice and 219.0 ± 7.8 mg/dl in control mice (P<0.001). The response to insulin was similar between βKO and control mice. The feeding insulin levels in βKO mice were significantly decreased by 58.9% (P<0.01). The serum insulin levels from βKO mice were significantly lower at 0, 15 and 30 minutes after glucose challenge. In addition, the insulin secretion from βKO islets was less than 50% of control islets after incubated at 16.7 mM glucose. Surprisingly, β-cell mass in βKO mice was 55.9% higher than that in control mice (P<0.05). In addition, we did not detect β-cell death in βKO islets. However, β-cell proliferation in βKO islets was increased by 1.3-fold. To understand the molecular mechanism, we performed RNA-seq to detect the gene expression in βKO and control islets from male mice 8 weeks after tamoxifen treatment. Among 106 altered genes in βKO islets, 104 genes were upregulated (P<0.001) and 2 genes were downregulated. The genes response to ER stress such as Pdia4, Itpr1, Thbs1, Ire1α and Igfbp5 were among the top up-regulated genes. We applied m6A-seq in MIN6 cells and confirmed that Ire1α was modified by m6A in its last exon and 3' UTR region. We further showed that both mRNA and protein of Ire1α and spliced XBP-1 were significantly increased in βKO islets. In conclusion, METTL14 plays an important role in regulating insulin secretion, and METTL14 deficiency in β-cells induces diabetes by increasing ER stress. Disclosure: L. Men: None. J. Sun: None. D. Ren: None. Funding: National Institutes of Health (P30DK020595) [ABSTRACT FROM AUTHOR]

Endothelial dysfunction is an initiating key step for diabetic macrovascular complications, and it is closely related to the hemodynamic microenvironment in vivo. However, diabetic patients usually coexist with other cardiovascular risk factors, and the more powerful targeting strategy for protecting endothelium is still limited. Selenoprotein S (SelS) was found in our previous study that could increase vascular endothelial cells resistance to oxidative stress associated with protein kinase C α (PKCα). Thus, in this study, we constructed a diabetic vascular endothelial bionic microenvironment mimicking hyperglycemia and/or hyperlipidemia based on microfludic chip through modulating the concentration of medium glucose and oxidized low density lipoproteins. Our results showed that under diabetic vascular endothelial bionic microenvironment, the upregulation of SelS enhanced nitric oxide synthase (eNOS) expression and reduced endothelin-1 level in human aortic endothelial cells (HAECs), accompany with increase in cell viability and SOD1 and SOD2 activity, and decrease in ROS. Furthermore, SelS overexpression attenuated the activation of PKCα, which subsequently promoted the activation of PI3K/Akt/eNOS pathway. Conversely, the knockdown of SelS resulted in an enhancement of endothelial injury. These findings suggest that SelS could protect endothelial cells from oxidative stress injury under diabetic vascular endothelial bionic microenvironment through PKCα and PI3K/Akt/eNOS pathway. Our results offer a promising and biomimetic platform for investigation on endothelial protection, and provide evidence of SelS as potential novel target to treat diabetic macrovascular complications. Disclosure: S. Yu: None. Y. Zhong: None. L. Men: None. J. Yao: None. J. Du: None. Funding: National Natural Science Foundation of China (81570727) [ABSTRACT FROM AUTHOR]

The hyporheic zone is a transition zone for the exchange of matter and energy between surface water and subsurface water. The study of trends and sensitivities of bed hyporheic exchanges to the various influencing factors is of great significance. The surface−groundwater flow process was simulated using a multiphysics computational fluid dynamics (CFD) method and compared to previous flume experiments. Based on that, the single-factor effects of flow velocity (u), water depth (H), dune wave height (h), and bed substrate permeability (κ) on hyporheic exchange in the bed hyporheic zone were investigated. The sensitivity analysis of various factors (H, u, dune wavelength (L), h, bed substrate porosity (θ), κ, and the diffusion coefficient of solute molecules (Dm)) in the surface−subsurface water coupling model was done using orthogonal tests. The results indicated that u, h, and κ were positively related, whereas H was negatively related to hyporheic exchange. H and u showed large effects, whereas κ, Dm, and θ had moderate effects, and L and h showed small effects on hyporheic exchange. This study provides valuable references for the protection and recovery of river ecology. [ABSTRACT FROM AUTHOR]