Protectin conjugates in tissue regeneration 1 alleviates sepsis-induced acute lung injury by inhibiting ferroptosis

Background: Acute lung injury (ALI) is a common and serious complication of sepsis with high mortality. Ferroptosis, categorized as programmed cell death, contributes to the development of lung injury. Protectin conjugates in tissue regeneration 1 (PCTR1) is an endogenous lipid mediator that exerts protective effects against multiorgan injury. However, the role of PCTR1 in the ferroptosis of sepsis-related ALI remains unknown. Methods: A pulmonary epithelial cell line and a mouse model of ALI stimulated with lipopolysaccharide (LPS) were established in vitro and in vivo. Ferroptosis biomarkers, including ferrous (Fe2+), glutathione (GSH), malondialdehyde (MDA) and 4-Hydroxynonenal (4-HNE), were assessed by relevant assay kits. Glutathione peroxidase 4 (GPX4) and prostaglandin-endoperoxide synthase 2 (PTGS2) protein levels were determined by western blotting. Lipid peroxides were examined by fluorescence microscopy and flow cytometry. Cell viability was determined by a CCK-8 assay kit. The ultrastructure of mitochondria was observed with transmission electron microscopy. Morphology and inflammatory cytokine levels predicted the severity of lung injury. Afterward, related inhibitors were used to explore the potential mechanism by which PCTR1 regulates ferroptosis. Results: PCTR1 treatment protected mice from LPS-induced lung injury, which was consistent with the effect of the ferroptosis inhibitor ferrostatin-1. PCTR1 treatment decreased Fe2+, PTGS2 and lipid reactive oxygen species (ROS) contents, increased GSH and GPX4 levels and ameliorated mitochondrial ultrastructural injury. Administration of LPS or the ferroptosis agonist RSL3 resulted in reduced cell viability, which was rescued by PCTR1. Mechanistically, inhibition of the PCTR1 receptor lipoxin A4 (ALX), protein kinase A (PKA) and transcription factor cAMP-response element binding protein (CREB) partly decreased PCTR1 upregulated GPX4 expression and a CREB inhibitor blocked the effects ofPCTR1 on ferroptosis inhibition and lung protection. Conclusion: This study suggests that PCTR1 suppresses LPS-induced ferroptosis via the ALX/PKA/CREB signaling pathway, which may offer promising therapeutic prospects in sepsis-related ALI

Zambia Signal Functions study 2016 dataset

This dataset contains information related to health facilities’ infrastructure, staffing, equipment, supplies, and capacity to perform various clinical functions related to reproductive and maternal health service provision. The study was conducted in Central Province, Zambia and its primary aim was to assess facilities’ capacity to provide termination of pregnancy services. EMBARGOED UNTIL 31st DEC 201

Inhibition the ubiquitination of ENaC and Na,K-ATPase with erythropoietin promotes alveolar fluid clearance in sepsis-induced acute respiratory distress syndrome

Sepsis-induced acute respiratory distress syndrome (ARDS) causes significant fatalities worldwide and lacks pharmacological intervention. Alveolar fluid clearance (AFC) plays a pivotal role in the remission of ARDS and is markedly impaired in the pathogenesis of ARDS. Here, we demonstrated that erythropoietin could effectively ameliorate lung injury manifestations and lethality, restore lung function and promote AFC in a rat model of lipopolysaccharide (LPS)-induced ARDS. Moreover, it was proven that EPO-induced restoration of AFC occurs through triggering the total protein expression of ENaC and Na,K-ATPase channels, enhancing their protein abundance in the membrane, and suppressing their ubiquitination for degeneration. Mechanistically, the data indicated the possible involvement of EPOR/JAK2/STAT3/SGK1/Nedd4–2 signaling in this process, and the pharmacological inhibition of the pathway markedly eliminated the stimulating effects of EPO on ENaC and Na,K-ATPase, and subsequently reversed the augmentation of AFC by EPO. Consistently, in vitro studies of alveolar epithelial cells paralleled with that EPO upregulated the expression of ENaC and Na,K-ATPase, and patch-clamp studies further demonstrated that EPO substantially strengthened sodium ion currents. Collectively, EPO could effectively promote AFC by improving ENaC and Na,K-ATPase protein expression and abundance in the membrane, dependent on inhibition of ENaC and Na,K-ATPase ubiquitination, and resulting in diminishing LPS-associated lung injuries

Reliability experiment on the calculation of natural gas hydrate saturation using acoustic wave data

In this paper, compression wave velocity, shear wave velocity and their change during the formation of natural gas hydrate in unconsolidated sand and mud sediments were measured through petrophysical experiments to discuss the reliability of calculating natural gas hydrate saturation by using acoustic velocity data. Then, a computation model of natural gas hydrate saturation during the experiments was established based on the material balance equation, combined with the PVT (pressure, volume, temperature) state equation and its test conditions. On this basis, the changing law of the acoustic velocity of the unconsolidated sediments with the increase of natural gas hydrate saturation was analyzed. Finally, natural gas hydrate saturation was calculated by using the modified Lee's weight sonic formula, and was compared with that measured in the experiments. And the following research results were obtained. First, the acoustic data can be used to calculate the natural gas hydrate saturation when the content of natural gas hydrate reaches a certain extent. Second, the compression and shear wave velocities of unconsolidated sand and mud sediments increase with the rise of their natural gas hydrate content, and they are in a good relationship of linear correlation. And third, the natural gas hydrate saturation calculated based on the acoustic data is close to that measured in the laboratory with much smaller errors. It is concluded that the research results provide a basis for the calculation of natural gas hydrate saturation using the actual acoustic logging data. Keywords: Natural gas hydrate, Porous media, Unconsolidated sediment, Petrophysical experiment, Saturation, Computation model, Acoustic velocity, PVT state equatio

Source apportionment of priority PAHs in 11 lake sediment cores from Songnen Plain, Northeast China

Elevated concentrations of polycyclic aromatic hydrocarbons (PAHs) have been observed with rapid agricultural and industrial development in the Songnen Plain, Northeast China, but the prospective sources have not been yet apportioned. The concentration of PAHs was measured in 31 sediment samples from 11 Songnen Plain lakes in 2015. The background flux of PAHs in these lake sediments is\u202f<\u202f463\u202f\u3bcg\u202fm 122 year 121. The maximal concentration of 16 U.S. EPA priority PAHs (599\u202fng\u202fg 121) recorded in this study is lower or similar to that found in most of the lake sediments across China, but higher than remote areas, such as North America Rocky Mountains. Both concentration and flux of PAHs increased after the 1950s, which correspond to the industrial development in this area and would probably mark the beginning of the Anthropocene in this region. A chemical mass balance model estimated that straw burning was a major source of \u3a313PAH (3\u20136 rings) during the past 200 years, with an average contribution of 22.1%, followed by forest fire (21.2%), burning of gasoline (19.1%), coal (12.2%), coke (4.8%) and diesel (3.9%), whereas the contribution from crude oil and natural gas was negligible (<1%). Straw burning (20.2\u201325.2%) and forest fire (16.7\u201330.6%) were major sources of PAHs and contributed increasing flux in the past 200 years. The elevated level of PAH recorded after 1950s in this region are also from burning of gasoline (26.1\u201326.4%), coal (15.3\u201315.8%), and coke (5.1\u20139.0%). The contribution of petrogenic sources (e.g., direct oil spill) to the concentration of \u3a313PAH seemed to be ignorable, at least in these lakes

Paleoenvironment of marine-continental transitional shales in the lower Permian Shanxi formation, southeastern Ordos Basin, China

The paleoenvironment of shales can be reconstructed to some extent using the combinations or concentrations of elements that correlate strongly with environmental conditions. In this study, we analyzed rare earth elements (REEs), major elements, and trace elements in the marine-continental transitional shales (transitional shales for short) of the Shan 23 submember of the Shanxi Formation in the southeastern Ordos Basin. The purpose is to deduce the paleoenvironmental conditions of the shales, encompassing paleoredox, paleoclimate, paleoproductivity, and paleo-provenance. The Shan 23 submember comprises four sections, namely Shan 23-1, Shan 23-2, Shan 23-3, and Shan 23-4. The Ba/Al, P/Al, and Cu/Al ratios, along with biogenic barium (Babio), indicate that the paleoproductivity of the submember peaked during the Shan 23-1 deposition and exhibited a downtrend upward in other sections. Trends in the Uau and the Ni/Co, V/Cr, U/Th, and V/Sc ratios suggest that suboxic conditions prevailed during the Shan 23-1 deposition, with the oxidation level gradually increasing from Shan 23-1 to Shan 23-4. C-value and the Sr/Cu vs. Ga/Rb cross-plot indicate a warm and arid paleoclimate during the Shan 23-1 deposition, which transitioned to cooler, drier conditions during the deposition of other sections. Indicators sensitive to paleoclimate, such as the K/Rb and Th/U ratios, along with the ICV, PIA, and Chemical Index of Alteration (CIA), highlight elevated weathering from Shan 23-2 to Shan 23-4, with Shan 23-1 exhibiting the weakest weathering during its deposition. As suggested by the REE data, the Zr/Sc vs. Th/Sr cross-plot, provenance discriminant functions, and the cross-plots of Hf vs. La/Th, Th vs. Hf–Co, and ∑REE vs. La/Yb, the sedimentary provenance for the transitional shales of the Shan 23 submember is of multiple origins, with significant contributions from the Upper Continental Crust (UCC). Discriminant diagrams, including those of Th–Co–Zr/10, Th–Sc–Zr/10, La–Th–Sc, and K2O/Na2O vs. SiO2, suggest that the transitional shales of the Shan 23 submember were primarily deposited under tectonic settings such as continental island arcs (CIAs) and passive continental margins (PCMs)