Mitogen Activated Protein Kinase Activated Protein Kinase 2 Regulates Actin Polymerization and Vascular Leak in Ventilator Associated Lung Injury

Mechanical ventilation, a fundamental therapy for acute lung injury, worsens pulmonary vascular permeability by exacting mechanical stress on various components of the respiratory system causing ventilator associated lung injury. We postulated that MK2 activation via p38 MAP kinase induced HSP25 phosphorylation, in response to mechanical stress, leading to actin stress fiber formation and endothelial barrier dysfunction. We sought to determine the role of p38 MAP kinase and its downstream effector MK2 on HSP25 phosphorylation and actin stress fiber formation in ventilator associated lung injury. Wild type and MK2−/− mice received mechanical ventilation with high (20 ml/kg) or low (7 ml/kg) tidal volumes up to 4 hrs, after which lungs were harvested for immunohistochemistry, immunoblotting and lung permeability assays. High tidal volume mechanical ventilation resulted in significant phosphorylation of p38 MAP kinase, MK2, HSP25, actin polymerization, and an increase in pulmonary vascular permeability in wild type mice as compared to spontaneous breathing or low tidal volume mechanical ventilation. However, pretreatment of wild type mice with specific p38 MAP kinase or MK2 inhibitors abrogated HSP25 phosphorylation and actin polymerization, and protected against increased lung permeability. Finally, MK2−/− mice were unable to phosphorylate HSP25 or increase actin polymerization from baseline, and were resistant to increases in lung permeability in response to HVT MV. Our results suggest that p38 MAP kinase and its downstream effector MK2 mediate lung permeability in ventilator associated lung injury by regulating HSP25 phosphorylation and actin cytoskeletal remodeling

Characteristics and geological significance of biomarkers from the Paleogene source rocks in Bozhong Sag, Bohai Bay Basin

The Bozhong Sag is located in the central and eastern part of the Bohai Bay Basin, and source rocks of the first and third Member of the Paleogene Shahejie Formation (E2s1 and E2s3) and the third Member of the Donying Formation (E3d3) are mainly developed, indicative of good oil and gas exploration prospects. Previous studies on organic geochemical characteristics of the Bozhong Sag are mainly based on cutting samples, and study on biomarker characteristics using core samples is insufficient. By utilizing both core and cuttings samples, this study integrates organic carbon, rock pyrolysis, chloroform bitumen "A", saturated hydrocarbon chromatography-mass spectrometry and other organic geochemical analysis.Organic matter abundance, type, maturity, source materials and depositional environment of the E3d3, E2s1 and E2s3 source rocks in the Bozhong Sag were studied, and the geochemical characteristics and depositional factors of the three source rocks were studied.The combination characteristics of typical biomarker compounds to distinguish the three source rocks are established, in order to provide a theoretical basis for further clarifying the development pattern and spatial distribution of high-quality source rocks in this area, which is beneficial to the exploration of oil and gas in this area.The results show that the hydrocarbon generation potential of the three source rocks is different, where the generation potential is as E2s3>E2s1>E3d3. The E2s3 source rock has the highest organic matter abundance, typeⅠand Ⅱ1 kerogen, and is currently in the mature stage. The E2s1 is medium to good source rock, with organic matter type Ⅱ1 and Ⅱ2, and is also inmature stage. The E3d3 is a medium source rock, with organic matter typeⅡ1 and Ⅱ2, and is in the stage of low maturity to medium maturity. The biomarker parameters, including Pr/Ph value, gammacerane index, C27-C28-C29 regular sterane content, 4-methylsterane index and other parameters indicate that the source material input and depositional environment are the main factors controlling the different development of three lacustrine source rocks. The input of freshwater algae sources and good preservation conditions are the keys to the development of high-quality source rocks in the E2s3. The input of low-level aquatic organisms and strong reducing preservation conditions are the keys to the development of high-quality source rocks in the E2s1. Mixed source input and good preservation conditions are the key to the development of high-quality source rocks in the E3d3

Predicting the Distributions of <i>Morus notabilis</i> C. K. Schneid under Climate Change in China

As one of the common mulberry tree species, Morus notabilis C. K. Schneid plays a significant role in various industries such as silkworm rearing, papermaking, and medicine due to its valuable mulberry leaves, fruits, and wood. This study utilizes the maximum entropy (MaxEnt) model to predict the potential distribution of M. notabilis in China under future environmental changes. By integrating the relative percentage contribution score of environmental factors with jackknife test analysis, important variables influencing the distribution of M. notabilis were identified along with their optimal values. The results indicate that Annual Precipitation (bio12), Precipitation of Driest Month (bio14), Min Temperature of Coldest Month (bio6), Temperature Annual Range (bio5–bio6) (bio7), Precipitation of Warmest Quarter (bio18), and Precipitation of Coldest Quarter (bio19) are the primary environmental variables affecting its potential distribution. Currently, M. notabilis exhibits high suitability over an area spanning 11,568 km2, while medium suitability covers 34,244 km2. Both current and future suitable areas for M. notabilis are predominantly concentrated in Sichuan, Yunnan, and Guizhou provinces, as well as Chongqing city in southwest China. Under the SSP5-8.5 scenario representing high greenhouse gas concentrations by 2050s and 2090s, there is an increase in high suitability area by 2952 km2 and 3440 km2, with growth rates reaching 25.52% and 29.74%, respectively. Notably, these two scenarios exhibit substantial expansion in suitable habitats for this species compared to others analyzed within this study period

Structural Insights into RIP3-Mediated Necroptotic Signaling

RIP3 is an essential upstream kinase in necroptosis. The pseudokinase MLKL functions as a substrate of RIP3 to mediate downstream signaling. The molecular mechanism by which RIP3 recognizes and phosphorylates MLKL remains unknown. Here, we report the crystal structures of the mouse RIP3 kinase domain, the MLKL kinase-like domain, and a binary complex between the two. Both RIP3 and MLKL adopt the canonical kinase fold. Free RIP3 exists in an active conformation, whereas MLKL-bound RIP3 is stabilized by AMP-PNP to adopt an inactive conformation. The formation of the RIP3-MLKL complex, involving their respective N- and C-lobes, is accompanied by pronounced conformational changes of the αC helix and activation loop in RIP3 and the corresponding structural elements in MLKL. RIP3-mediated MLKL phosphorylation, though important for downstream signaling, is dispensable for stable complex formation between RIP3 and MLKL. Our study serves as a framework for mechanistic understanding of RIP3-mediated necroptotic signaling

A Combined Method for Estimating Continuous Runoff by Parameter Transfer and Drainage Area Ratio Method in Ungauged Catchments

Continuous runoff needs to be estimated in ungauged catchments to interpret hydrological phenomena and manage water resources. Researchers have used various methods to estimate runoff in ungauged catchments, but few combined different methods to improve the estimation. A model parameter-based method named the parameter transfer (PT) method and a flow-based method of area ratio (AR) were combined and tested in eight catchments in a lake basin. The performance of the PT method depended on the model simulation and donors, which were related to physical and climate characteristics of the catchments. Two AR methods were compared and the results showed that the standard AR method was suitable in this study area with the area ratio between donor and target ranging from 0.46 to 1.41. ENS and R2 values suggested that the PT method used in this study showed a better result than the AR method in 75% of the considered sites, but the total runoff deviation was lower for the standard AR method than that for the PT method. We used the standard AR method weighted by the PT method, and compared three versions weighted with daily, monthly, and average ENS values of the PT and AR methods and one unweighted version. The results of the combined methods were promising. The version weighted with daily ENS performed best and gave improved R2 and daily ENS values for 75% of the receivers. The unweighted combined method performed stable in all sites. The combined method gave better simulation of daily and monthly continuous runoff in ungauged catchments than each individual method

Hydrological Characteristics of Ordovician Karst Top in a Deep Region and Evaluation of Its Threat to Coal Mining: A Case Study for the Weibei Coalfield in Shaanxi Province, China

Widely distributed in North China, Ordovician karst is characterized by having high thickness, nonuniform aquosity, and significant water pressure-bearing properties. Deep mining in North China is threatened by associated water hazards; hence, research on the hydrogeological characteristics of deep Ordovician karst is needed. In this study, the Weibei coalfield in Shaanxi Province, China, was selected as the study area, especially mines in the Hancheng and Chenghe mining areas. In situ experiments, including water pumping, water drainage, water injecting and water pressure, and laboratory experiments, were conducted to study the hydrogeological characteristics of the Ordovician karst top in the study area. A comprehensive analysis was conducted on controlling factors for the development of the Ordovician karst top in the study area, and a method for evaluating the water inrush risk in coal mining areas based on karst hydrogeological characteristics was proposed. The research results indicated that the Ordovician karst top in the study area was characterized by heterogeneity, vertical zonation, and partially filled properties, which were mainly controlled by two factors: sedimentation and tectonism. The hydrogeological conditions of the Ordovician karst could be divided into three types: nonfilled and nonsignificant tectonism, filled and nonsignificant tectonism, and significant tectonism. Among them, the filled and nonsignificant tectonism type Ordovician karst top type had a filling thickness of 20 m. Based on karst hydrogeological characteristics, the methods were proposed to evaluate the water inrush risk in the coal mining floor. The practical tests verified the methods