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

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

The nutrition-based comprehensive intervention study on childhood obesity in China (NISCOC): a randomised cluster controlled trial

<p>Abstract</p> <p>Background</p> <p>Childhood obesity and its related metabolic and psychological abnormalities are becoming serious health problems in China. Effective, feasible and practical interventions should be developed in order to prevent the childhood obesity and its related early onset of clinical cardiovascular diseases. The objective of this paper is to describe the design of a multi-centred random controlled school-based clinical intervention for childhood obesity in China. The secondary objective is to compare the cost-effectiveness of the comprehensive intervention strategy with two other interventions, one only focuses on nutrition education, the other only focuses on physical activity.</p> <p>Methods/Design</p> <p>The study is designed as a multi-centred randomised controlled trial, which included 6 centres located in Beijing, Shanghai, Chongqing, Shandong province, Heilongjiang province and Guangdong province. Both nutrition education (special developed carton style nutrition education handbook) and physical activity intervention (Happy 10 program) will be applied in all intervention schools of 5 cities except Beijing. In Beijing, nutrition education intervention will be applied in 3 schools and physical activity intervention among another 3 schools. A total of 9750 primary students (grade 1 to grade 5, aged 7-13 years) will participate in baseline and intervention measurements, including weight, height, waist circumference, body composition (bioelectrical impendence device), physical fitness, 3 days dietary record, physical activity questionnaire, blood pressure, plasma glucose and plasma lipid profiles. Data concerning investments will be collected in our study, including costs in staff training, intervention materials, teachers and school input and supervising related expenditure.</p> <p>Discussion</p> <p>Present study is the first and biggest multi-center comprehensive childhood obesity intervention study in China. Should the study produce comprehensive results, the intervention strategies would justify a national school-based program to prevent childhood obesity in China.</p> <p>Trial Registration</p> <p>Chinese clinical trial registry (Primary registry in the WHO registry network) Identifier: ChiCTR-TRC-00000402</p

A living WHO guideline on drugs for covid-19

CITATION: Agarwal, A. et al. 2022. A living WHO guideline on drugs for covid-19. British Medical Journal, 370. doi:10.1136/bmj.m3379The original publication is available at https://jcp.bmj.com/This living guideline by Arnav Agarwal and colleagues (BMJ 2020;370:m3379, doi:10.1136/bmj.m3379) was last updated on 22 April 2022, but the infographic contained two dosing errors: the dose of ritonavir with renal failure should have read 100 mg, not 50 mg; and the suggested regimen for remdesivir should have been 3 days, not 5-10 days. The infographic has now been corrected.Publishers versio

Structure, Physicochemical Property, and Functional Activity of Dietary Fiber Obtained from Pear Fruit Pomace (Pyrus ussuriensis Maxim) via Different Extraction Methods

In this study, soluble dietary fiber (SDF) and insoluble dietary fiber (IDF) were extracted from Pyrus ussuriensis Maxim pomace via three methods including enzymic extraction (EE), microwave-assisted enzymatic extraction (MEE), and three-phase partitioning (TPP). The effects of different extraction methods on the structure, physicochemical property, and functional activity of the extracted dietary fiber were evaluated. The results showed that different extraction methods had significant effects on the extraction yield, molecular weight distribution, thermal stability, antioxidant activity, and hypoglycemic activity in vitro, but resulted in no difference in the structure and composition of functional groups. It is noteworthy that SDF extracted by TPP has a more complex and porous structure, lower molecular weight, and higher thermal stability, as well as better physicochemical properties and in vitro hypoglycemic activity. IDF extracted by MEE showed the greatest water and oil holding capacity; the highest adsorption capacity for glucose, cholesterol, and nitrite ion; as well as the strongest inhibitory activity on &alpha;-amylase. These results suggest that PUP may be a source of cheap natural dietary fiber

Recent advances in carbon-supported non-precious metal single-atom catalysts for energy conversion electrocatalysis

Non-precious metal single-atom catalysts (NPM-SACs) with unique electronic structures and coordination environments have gained much attention in electrocatalysis owing to their low cost, high atomic utilization, and high performance. NPM-SACs on carbon support (NPM-SACs/CS) are promising because of the carbon substrate with a large surface area, excellent electrical conductivity, and high chemical stability. This review provides an overview of recent developments in NPM-SACs/CS for the electrocatalytic field. First, the state-of-the-art synthesis methods and advanced characterization techniques of NPM-SACs/CS are discussed in detail. Then, the structural adjustment strategy of NPM-SACs/CS for optimizing electrocatalytic performance is introduced concisely. Furthermore, we provide a comprehensive summary of recent advances in developing NPM-SACs/CS for important electrochemical reactions, including carbon dioxide reduction reaction, hydrogen evolution reaction, oxygen evolution reaction, oxygen reduction reaction, and nitrogen reduction reaction. In the end, the existing challenges and future opportunities of NPM-SACs/CS in the electrocatalytic field are highlighted

An Underwater Triboelectric Biomechanical Energy Harvester to Power the Electronic Tag of Marine Life

Implantable electronic tags are crucial for the conservation of marine biodiversity. However, the power supply associated with these tags remains a significant challenge. In this study, an underwater flexible triboelectric nanogenerator (UF-TENG) was proposed to harvest the biomechanical energy from the movements of marine life, ensuring a consistent power source for the implantable devices. The UF-TENG, which is watertight by the protection of a hydrophobic poly(tetrafluoroethylene) film, consists of high stretchable carbon black-silicone as electrode and silicone as a dielectric material. This innovative design enhances the UF-TENG’s adaptability and biocompatibility with marine organisms. The UF-TENG’s performance was rigorously assessed under various conditions. Experimental data highlight a peak output of 14 V, 0.43 μA and 38 nC, with a peak power of 2.9 μW from only one unit. Notably, its performance exhibited minimal degradation even after three weeks, showing its excellent robustness. Furthermore, the UF-TENG is promising in the self-powered sensing of the environmental parameter and the marine life movement. Finally, a continuous power supply of an underwater temperature is achieved by paralleling UF-TENGs. These findings indicate the broad potential of UF-TENG technology in powering implantable electronic tags