Reactive Astrocytes in Glial Scar Attract Olfactory Ensheathing Cells Migration by Secreted TNF-α in Spinal Cord Lesion of Rat

BACKGROUND:After spinal cord injury (SCI), the formation of glial scar contributes to the failure of injured adult axons to regenerate past the lesion. Increasing evidence indicates that olfactory ensheathing cells (OECs) implanted into spinal cord are found to migrate into the lesion site and induce axons regeneration beyond glial scar and resumption of functions. However, little is known about the mechanisms of OECs migrating from injection site to glial scar/lesion site. METHODS AND FINDINGS:In the present study, we identified a link between OECs migration and reactive astrocytes in glial scar that was mediated by the tumor necrosis factor-alpha (TNF-alpha). Initially, the Boyden chamber migration assay showed that both glial scar tissue and reactive astrocyte-conditioned medium promoted OECs migration in vitro. Reactive astrocyte-derived TNF-alpha and its type 1 receptor TNFR1 expressed on OECs were identified to be responsible for the promoting effect on OECs migration. TNF-alpha-induced OECs migration was demonstrated depending on activation of the extracellular signal-regulated kinase (ERK) signaling cascades. Furthermore, TNF-alpha secreted by reactive astrocytes in glial scar was also showed to attract OECs migration in a spinal cord hemisection injury model of rat. CONCLUSIONS:These findings showed that TNF-alpha was released by reactive astrocytes in glial scar and attracted OECs migration by interacting with TNFR1 expressed on OECs via regulation of ERK signaling. This migration-attracting effect of reactive astrocytes on OECs may suggest a mechanism for guiding OECs migration into glial scar, which is crucial for OECs-mediated axons regrowth beyond the spinal cord lesion site

AXL targeting restores PD-1 blockade sensitivity of STK11/LKB1 mutant NSCLC through expansion of TCF1+ CD8 T cells

Mutations in STK11/LKB1 in non-small cell lung cancer (NSCLC) are associated with poor patient responses to immune checkpoint blockade (ICB), and introduction of a Stk11/Lkb1 (L) mutation into murine lung adenocarcinomas driven by mutant Kras and Trp53 loss (KP) resulted in an ICB refractory syngeneic KPL tumor. Mechanistically this occurred because KPL mutant NSCLCs lacked TCF1-expressing CD8 T cells, a phenotype recapitulated in human STK11/LKB1 mutant NSCLCs. Systemic inhibition of Axl results in increased type I interferon secretion from dendritic cells that expanded tumor-associated TCF1+PD-1+CD8 T cells, restoring therapeutic response to PD-1 ICB in KPL tumors. This was observed in syngeneic immunocompetent mouse models and in humanized mice bearing STK11/LKB1 mutant NSCLC human tumor xenografts. NSCLC-affected individuals with identified STK11/LKB1 mutations receiving bemcentinib and pembrolizumab demonstrated objective clinical response to combination therapy. We conclude that AXL is a critical targetable driver of immune suppression in STK11/LKB1 mutant NSCLC.publishedVersio

Spatiotemporal Evolution of Evapotranspiration in China after 1998

Changes in water circulation and uneven distributions of water resources caused by global warming are prominent problems facing the world at present. It is important to understand the influencing factors, and evapotranspiration (ET) is a key parameter for measuring the water cycle. However, understanding of spatiotemporal changes in actual evapotranspiration and its mechanism is still limited by a lack of long-term and large-scale in situ datasets. Here, the evolution of evapotranspiration in typical East Asian monsoon areas in China from 1989 to 2005 was analyzed with global land ET synthesis products. Evapotranspiration in China showed evident interdecadal variations around 1998; it decreased before 1998 and subsequently increased, which is inversely related to global ET changes. We further divided China into water-control and energy-control regions to discuss the factors influencing ET changes in each region. The interdecadal variations in increasing ET after 1998 in China were dominated by increasing potential evaporation in the energy-control region. An analysis using the empirical orthogonal function (EOF) method found that this occurred because ET is mainly manifested as decadal changes controlled by climate warming in the energy-control region and as interannual variations in the water-control region. The different feedbacks of ET on climate change in the two regions were also reflected in the difference in energy partition. The change in the Bowen rate (BR) did not increase climatic differences between energy- and water-control zones, but increases in the BR in arid summers significantly affected local weather and climate

Thermodynamic Study of Choline Chloride-Based Deep Eutectic Solvents with Dimethyl Sulfoxide and Isopropanol

The thermodynamic properties of four binary mixtures of deep eutectic solvent (DES), i.e., ChCl/Gly (choline chloride + glycerol at a molar ratio of 1:2) and ChCl/EG (choline chloride + ethylene glycol at a molar ratio of 1:2) with two common co-solvents, i.e., dimethyl sulfoxide (DMSO) and isopropanol (IPA), were studied. Density and viscosity were determined at temperatures from 288.15 to 323.15 K, while measuring the enthalpy of mixing was performed at 308.15 and 318.15 K. The volumetric properties (i.e., excess molar volume and excess partial molar volume) and excess viscosities (i.e., viscosity deviation and logarithmic excess viscosity) were further calculated to investigate the effects of temperature, types of co-solvent and DES, and their contents on the non-ideal behavior of these systems, where the influence of treating the DES as a mixture of two components or a pseudo-component was discussed. The results of volumetric properties indicate that the combined influence of packing effects and H-bonding interactions between the DES and co-solvents led to the contraction of mixture volume, and the results of excess viscosities show H-bonding interactions play an important role in their variations. The results of enthalpy of mixing show that the mixing of DES with IPA is endothermic, while the mixing of DES with DMSO is exothermic. Furthermore, the nonrandom two-liquid (NRTL) model and Gibbs-Helmholtz equation were combined to represent the experimental results of the enthalpy of mixing, and the total average relative deviation (ARD) of all studied systems is 5.43%.Validerad;2024;Nivå 2;2024-03-28 (hanlid);Funder: State Key Laboratory of Material-Oriented Chemical Engineering in China; National Natural Science Foundation of China (22011530112);Full text license: CC BY 4.0</p

The Response of Cloud-Precipitation Recycling in China to Global Warming

Cloud water is an important geophysical quantity that connects the hydrological and radiation characteristics of climate systems and plays an essential role in the global circulation of the atmosphere, water, and energy. However, compared to the contribution of water vapor to precipitation, the understanding of cloud-precipitation transformation and its climate feedback mechanism remains limited. Based on precipitation and temperature datasets of the National Meteorological Observatory and MODIS (Moderate Resolution Imaging Spectroradiometer) satellite remote sensing products, the evolution characteristics of cloud water resources in China over the last twenty years of the 21st century were evaluated. Significant decreasing trends of −3.3 and −4.89 g/m2 decade−1 were found for both the liquid and ice water path. In humid areas with high precipitation, the cloud water path decreased fast. In semiarid areas with an annual precipitation ranging from 500–800 mm, the decreasing trend of the cloud water path was the lowest. The cloud-water period was calculated to represent the relative changes in clouds and precipitation. The national average cloud-water period in China is approximately 12.4 h, with obvious seasonal changes. Over the last 20 years, the cloud water path in dry regions decreased more slowly than that in wet regions, and the cloud-precipitation efficiency significantly increased, which narrowed the climate difference between the dry and wet regions. Finally, the mechanism of the cloud-water period evolution in the different regions were examined from the perspectives of the dynamic and thermal contributions, respectively. Due to the overall low upward moisture flux (UMF) in the dry region, the response of the cloud-water period to the lower tropospheric stability (LTS) mainly first increased and then decreased, which was the opposite in the wet region. The increase in cloud-precipitation efficiency in the dry region of Northwest China is accompanied by a continuous decrease in LTS. The different configurations of regional UMF and LTS play a crucial role in the evolution of cloud-precipitation, which can be used as a diagnostic basis to predict changes in the precipitation intensity to a certain extent

Effect of Mold Opening Process on Microporous Structure and Properties of Microcellular Polylactide–Polylactide Nanocomposites

Cell structure is a key factor that determines the final properties of microcellular polylactide (PLA) product. In the mold opening process, adjusting the rate of mold opening can effectively control cell structure. PLA and PLA composites with a void fraction as high as 50% were fabricated using the mold opening technique. The effects of mold opening rate and the addition of nanoclay on the cell structure, mechanical properties, and surface quality of microcellular PLA and PLA composites samples were investigated. The results showed that finer cell structure was received in the microcellular PLA samples and the surface quality was improved effectively when decreasing the rate of mold opening. The effect of mold opening rate on the foaming behavior of microcellular PLA&ndash;nanoclay was the same as that of microcellular PLA. The addition of 5 wt % nanoclay significantly improved the foaming properties, such as cell density, cell size, and structural uniformity, which consequently enhanced the mechanical properties of foams and the surface quality

Hierarchical WMoC nano array with optimal crystal facet as a non-noble metal cathode for proton exchange membrane water electrolyser

Highly efficient non-noble metal hydrogen evolution reaction (HER) catalysts are of particular importance for cost-effective proton exchange membrane water electrolyser (PEMWE). Here, hierarchical WMoC nano arrays (NAs) with superhydrophilic surface and optimal crystal facet is synthesized. Mo plays a crucial role in preferred growth of active crystal facet and the formation of NA. Thanks to the optimal crystal facet and unique structure, WMoC NA exhibits an enhanced HER activity and stability under high current density. PEMWE single cell based on WMoC cathode shows an outstanding performance, which obtains a current density of 1 A cm-2 at voltage of 1.888 V with N117 at 80 degrees C, making it one of the best PEMWEs using non-noble metal cathode. The single cell also shows a stable operation under 1A cm-2 at 80 degrees C over 700 h, demonstrating WMoC cathode's great potential for application use