The spring-like effect of microRNA-31 in balancing inflammatory and regenerative responses in colitis

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders caused by the disruption of immune tolerance to the gut microbiota. MicroRNA-31 (MIR31) has been proven to be up-regulated in intestinal tissues from patients with IBDs and colitis-associated neoplasias. While the functional role of MIR31 in colitis and related diseases remain elusive. Combining mathematical modeling and experimental analysis, we systematically explored the regulatory mechanism of MIR31 in inflammatory and epithelial regeneration responses in colitis. Level of MIR31 presents an “adaptation” behavior in dextran sulfate sodium (DSS)-induced colitis, and the similar behavior is also observed for the key cytokines of p65 and STAT3. Simulation analysis predicts MIR31 suppresses the activation of p65 and STAT3 but accelerates the recovery of epithelia in colitis, which are validated by our experimental observations. Further analysis reveals that the number of proliferative epithelial cells, which characterizes the inflammatory process and the recovery of epithelia in colitis, is mainly determined by the inhibition of MIR31 on IL17RA. MIR31 promotes epithelial regeneration in low levels of DSS-induced colitis but inhibits inflammation with high DSS levels, which is dominated by the competition for MIR31 to either inhibit inflammation or promote epithelial regeneration by binding to different targets. The binding probability determines the functional transformation of MIR31, but the functional strength is determined by MIR31 levels. Thus, the role of MIR31 in the inflammatory response can be described as the “spring-like effect,” where DSS, MIR31 action strength, and proliferative epithelial cell number are regarded as external force, intrinsic spring force, and spring length, respectively. Overall, our study uncovers the vital roles of MIR31 in balancing inflammation and the recovery of epithelia in colitis, providing potential clues for the development of therapeutic targets in drug design

An African-Specific Variant of TP53 Reveals PADI4 as a Regulator of p53-Mediated Tumor Suppression

TP53 is the most frequently mutated gene in cancer, yet key target genes for p53-mediated tumor suppression remain unidentified. Here, we characterize a rare, African-specific germline variant of TP53 in the DNA-binding domain Tyr107His (Y107H). Nuclear magnetic resonance and crystal structures reveal that Y107H is structurally similar to wild-type p53. Consistent with this, we find that Y107H can suppress tumor colony formation and is impaired for the transactivation of only a small subset of p53 target genes; this includes the epigenetic modifier PADI4, which deiminates arginine to the nonnatural amino acid citrulline. Surprisingly, we show that Y107H mice develop spontaneous cancers and metastases and that Y107H shows impaired tumor suppression in two other models. We show that PADI4 is itself tumor suppressive and that it requires an intact immune system for tumor suppression. We identify a p53–PADI4 gene signature that is predictive of survival and the efficacy of immune-checkpoint inhibitors. Significance: We analyze the African-centric Y107H hypomorphic variant and show that it confers increased cancer risk; we use Y107H in order to identify PADI4 as a key tumor-suppressive p53 target gene that contributes to an immune modulation signature and that is predictive of cancer survival and the success of immunotherapy

Persistent sulfate formation from London Fog to Chinese haze

Sulfate aerosols exert profound impacts on human and ecosystem health, weather, and climate, but their formation mechanism remains uncertain. Atmospheric models consistently underpredict sulfate levels under diverse environmental conditions. From atmospheric measurements in two Chinese megacities and complementary laboratory experiments, we show that the aqueous oxidation of SO2 by NO2 is key to efficient sulfate formation but is only feasible under two atmospheric conditions: on fine aerosols with high relative humidity and NH3 neutralization or under cloud conditions. Under polluted environments, this SO2 oxidation process leads to large sulfate production rates and promotes formation of nitrate and organic matter on aqueous particles, exacerbating severe haze development. Effective haze mitigation is achievable by intervening in the sulfate formation process with enforced NH3 and NO2 control measures. In addition to explaining the polluted episodes currently occurring in China and during the 1952 London Fog, this sulfate production mechanism is widespread, and our results suggest a way to tackle this growing problem in China and much of the developing world

Spatial variability of soil water content and related factors across the Hexi Corridor of China

Soil water is a key factor limiting ecosystem sustainability in arid and semi-arid areas of the Hexi Corridor of China, which is characterized by an ecological environment that is vulnerable to climate change. However, there is a knowledge gap regarding the large-scale spatial distribution of soil water in this region. The specific objectives of this study were to determine the spatial distribution patterns of soil water content (SWC) across the entire Hexi Corridor and identify the factors responsible for spatial variation of SWC at a regional scale. This study collected and analyzed SWC in the 0&ndash;100 cm soil profile from 109 field sampling sites (farmland, grassland and forestland) across the Hexi Corridor in 2017. We selected 17 factors, including land use, topography (latitude, longitude, elevation, slope gradient, and slope aspect), soil properties (soil clay content, soil silt content, soil bulk density, saturated hydraulic conductivity, field capacity, and soil organic carbon content), climate factors (mean annual precipitation, potential evaporation, and aridity index), plant characteristic (vegetation coverage) and planting pattern (irrigation or rain-fed), as possible environmental variables to analyze their effects on SWC. The results showed that SWC was 0.083 (&plusmn;0.067) g/g in the 0&ndash;100 cm soil profile and decreased in the order of farmland, grassland and forestland. The SWC in the upper soil layers (0&ndash;20, 20&ndash;40 and 40&ndash;60 cm) had obvious difference when the mean annual precipitation differed by 200 mm. The SWC decreased from southeast to northwest following the same pattern as precipitation, and had a moderate to strong spatial dependence in a large effective range (75&ndash;378 km). The SWC showed a similar distribution and had no significant difference between soil layers in the 0&ndash;100 cm soil profile. The principal component analysis showed that the mean annual precipitation, geographical position (longitude and latitude) and soil properties (soil bulk density and soil clay content) were the main factors dominating the variance of environmental variables. A stepwise linear regression equation showed that plant characteristic (vegetation coverage) and soil properties (soil organic carbon content, field capacity and soil clay content) were the optimal factors to predict the variation of SWC. Soil clay content could better explain SWC variation in the deeper soil layers compared with other factors.</p

Combined Feature Extraction and Random Forest for Laser Self-Mixing Vibration Measurement without Determining Feedback Intensity

To measure the vibration of a target by laser self-mixing interference (SMI), we propose a method that combines feature extraction and random forest (RF) without determining the feedback strength (C). First, the temporal, spectral, and statistical features of the SMI signal are extracted to characterize the original SMI signal. Secondly, these interpretable features are fed into the pretrained RF model to directly predict the amplitude and frequency (A and f) of the vibrating target, recovering the periodic vibration of the target. The results show that the combination of RF and feature extraction yields a fit of more than 0.94 for simple and quick measurement of A and f of unsmooth planar vibrations, regardless of the feedback intensity and the misalignment of the retromirror. Without a complex optical stage, this method can quickly recover arbitrary periodic vibrations from SMI signals without C, which provides a novel method for quickly implementing vibration measurements