A single dose of lipopolysaccharide elicits autofluorescence in the mouse brain

One hallmark of aging is autofluorescence (AF) in the brain. However, the underlying mechanism for inducing AF remains unknown. This study aims to determine the cause(s) of this phenomenon. The endogenous expression pattern of AF in mice was examined at differing ages. Intraperitoneal injection of a single dose of lipopolysaccharide (LPS) was performed to induce AF. Copper sulfate was applied to remove AF to allow for further immunofluorescence staining. AF appeared in the mouse brain as early as 3 months of age. In the cortex, AF occurs in the lysosomes of microglia, astrocytes, endothelial cells, and oligodendrocyte lineage cells and its prevalence increases with age. Interestingly, AF never occurs in the pericytes of young or aged brains. LPS administration resulted in a rapid and marked induction of brain AF, similar to the normal aging process. Finally, age-related and induced AF can be eliminated by low concentrations of copper sulfate solution. This pre-treatment is safe for aging and lineage tracing studies. These findings depict that AF in the brain could be associated with the innate immune response against Gram-negative bacteria infection

Advanced glycation end products accelerate ischemia/reperfusion injury through receptor of advanced end product/nitrative thioredoxin inactivation in cardiac microvascular endothelial cells.

The advanced glycation end products (AGEs) are associated with increased cardiac endothelial injury. However, no causative link has been established between increased AGEs and enhanced endothelial injury after ischemia/reperfusion. More importantly, the molecular mechanisms by which AGEs may increase endothelial injury remain unknown. Adult rat cardiac microvascular endothelial cells (CMECs) were isolated and incubated with AGE-modified bovine serum albumin (BSA) or BSA. After AGE-BSA or BSA preculture, CMECs were subjected to simulated ischemia (SI)/reperfusion (R). AGE-BSA increased SI/R injury as evidenced by enhanced lactate dehydrogenase release and caspase-3 activity. Moreover, AGE-BSA significantly increased SI/R-induced oxidative/nitrative stress in CMECs (as measured by increased inducible nitric oxide synthase expression, total nitric oxide production, superoxide generation, and peroxynitrite formation) and increased SI/R-induced nitrative inactivation of thioredoxin-1 (Trx-1), an essential cytoprotective molecule. Supplementation of EUK134 (peroxynitrite decomposition catalyst), human Trx-1, or soluble receptor of advanced end product (sRAGE) (a RAGE decoy) in AGE-BSA precultured cells attenuated SI/R-induced oxidative/nitrative stress, reduced SI/R-induced Trx-1 nitration, preserved Trx-1 activity, and reduced SI/R injury. Our results demonstrated that AGEs may increase SI/R-induced endothelial injury by increasing oxidative/nitrative injury and subsequent nitrative inactivation of Trx-1. Interventions blocking RAGE signaling or restoring Trx activity may be novel therapies to mitigate endothelial ischemia/reperfusion injury in the diabetic population

Role of Human-Mediated Dispersal in the Spread of the Pinewood Nematode in China

Background: Intensification of world trade is responsible for an increase in the number of alien species introductions. Human-mediated dispersal promotes not only introductions but also expansion of the species distribution via long-distance dispersal. Thus, understanding the role of anthropogenic pathways in the spread of invading species has become one of the most important challenges nowadays. Methodology/Principal Findings: We analysed the invasion pattern of the pinewood nematode in China based on invasion data from 1982 to 2005 and monitoring data on 7 locations over 15 years. Short distance spread mediated by long-horned beetles was estimated at 7.5 km per year. Infested sites located further away represented more than 90% of observations and the mean long distance spread was estimated at 111–339 km. Railways, river ports, and lakes had significant effects on the spread pattern. Human population density levels explained 87% of the variation in the invasion probability (P,0.05).Since 2001, the number of new records of the nematode was multiplied by a factor of 5 and the spread distance by a factor of 2. We combined a diffusion model to describe the short distance spread with a stochastic,individual based model to describe the long distance jumps. This combined model generated an error of only 13% when used to predict the presence of the nematode. Under two climate scenarios (stable climate or moderate warming), projections of the invasion probability suggest that this pest could expand its distribution 40–55% by 2025. Conclusions/Significance: This study provides evidence that human-induced dispersal plays a fundamental role in the spread of the pinewood nematode, and appropriate control measures should be taken to stop or slow its expansion. This model can be applied to Europe, where the nematode had been introduced later, and is currently expanding its distribution. Similar models could also be derived for other species that could be accidentally transported by humans

Research on a Comprehensive Maintenance Optimization Strategy for an Offshore Wind Farm

Offshore wind is considered a crucial part in the future energy supply. However, influenced by weather conditions, the maintenance of offshore wind turbine system (OWTs) equipment is challenged by poor accessibility and serious failure consequences. It is necessary to study the optimized strategy of comprehensive maintenance for offshore wind farms, with consideration of the influences of incomplete equipment maintenance, weather accessibility and economic relevance. In this paper, a Monte Carlo algorithm-improved factor is presented to simulate the imperfect preventive maintenance activity, and waiting windows were created to study the accessibility of weather conditions. Based on a rolling horizon approach, an opportunity group maintenance model of an offshore wind farm was proposed. The maintenance correlations between systems and between equipment as well as breakdown losses, maintenance uncertainty, and weather conditions were taken into account in the model, thus realizing coordination of maintenance activities of different systems and different equipment. The proposed model was applied to calculate the maintenance cost of the Dafengtian Offshore Wind Farm in China. Results proved that the proposed model could realize long-term dynamic optimization of offshore wind farm maintenance activities, increase the total availability of the wind power system and reduce total maintenance costs

Palmitate lipotoxicity is closely associated with the fatty acid-albumin complexes in BV-2 microglia.

Palmitic acid (PA) is considered a major contributor to the inflammation in many metabolic diseases; however, this role has been questioned recently for the complicated procedures in preparing PA-bovine serum albumin (BSA) complex. This study is aimed to evaluate the effect of PA-BSA complexing methods on cell viability and inflammatory responses of BV-2 cells. Three commercially available BSA brands and two types of solvents were compared for their effects on the expression of inflammatory cytokines. Three commonly used proportions of PA-BSA were tested for cell viability and inflammatory responses. We found that all the three types of BSA were proinflammatory. Both ethanol and isopropanol dampened inflammation except that 1% isopropanol treatment increased the IL-1β level by 26%. When reducing the BSA content in PA-BSA solutions from 3:1 to 5:1, a marked increase in cell viability (11%) was seen. To our surprise, reducing BSA content in PA-BSA solutions from 5:1 to 10:1 decreased cell viability by 11%. The 5:1 group exhibited the lowest inflammatory profile. Either PA-BSA or BSA alone increased the entry of LPS to the cytosol, which further caused pyroptosis. In summary, we found 5:1 (PA:BSA) to be the best binding ratio for studying inflammation in BV-2 microglia. The presence of LPS in the cytosol in the context of BSA might be the reason for confounding results from palmitate studies

Palmitoleic acid protects microglia from palmitate-induced neurotoxicity in vitro.

Although palmitoleic acid (POA) is a lipokine with beneficial effects on obesity and is produced as a byproduct from the manufacture of prescription omega-3 fatty acids, its role in nervous system inflammation is still unknown. This study aims to examine the mechanisms and protective effects of POA against palmitic acid (PA)-induced microglial death. PA-induced microglial death was used as a model for POA intervention. Various inhibitors were employed to suppress potential routes of PA entry into the cell. Immunofluorescence staining and Western blotting were conducted to elucidate the protective pathways involved. The results suggest POA has the potential to eliminate PA-induced lactate dehydrogenase (LDH) release, which decreases the overall number of propidium iodide (PI)-positive cells compared with control. Moreover, POA has the potential to significantly increase lipid droplets (LDs) in the cytoplasm, without causing any lysosomal damage. POA inhibited both canonical and non-canonical gasdermin D (GSDMD)-mediated pyroptosis and gasdermin E (GSDME)-mediated pyroptosis, which PA typically induces. Additionally, POA inhibited the endoplasmic reticulum (ER) stress and apoptosis-related proteins induced by PA. Based on the findings, POA can exert a protective effect on microglial death induced by PA via pathways related to pyroptosis, apoptosis, ER stress, and LDs

Analysis of Thermal Insulation Thickness for a Container House in the Yanqing Zone of the Beijing 2022 Olympic and Paralympic Winter Games

A large number of temporary housings (THs) were used in the Yanqing zone of the Beijing 2022 Olympic and Paralympic Winter Games. Taking a kind of container house (CH) used in Yanqing zone as a model, the objective of this paper is to analyze the effect of insulation thickness on heating energy consumption and corresponding carbon emission. The effect of service life of THs on economic thickness was also discussed. The simulation model was developed using EnergyPlus and the heating energy consumption with different insulation materials was simulated based on the meteorological parameters of the top of Xiaohaituo Mountain (2177.5 m) and the Olympic/Paralympic Village (950 m) in Yanqing zone. In the simulation process, the thermal insulation performance of the CH was enhanced with reference to the requirements of GB/T 51350-2019 Technical Standard for Nearly Zero Energy Buildings (NZEB) on one hand. Additionally, the insulation performance was evaluated in terms of payback period and carbon emission. On the other hand, the economic thickness of different insulation materials (rock wool (RW), extruded polystyrene (XPS), polyurethane (PU)) and the high performance vacuum insulation panel (HVIP)) for different service lives of CH was studied. Results show that the U-values of the envelope meeting the NZEB standard can decrease approximately 21.4–32.8% of the heating energy consumption, compared with the original envelope. When the service life of CH is extended to 20 years, the carbon emission is reduced by 18.5% and 29.5%. The payback period of HVIP is longest, up to 31.4 a, and the results of economic thickness show that when the service life of the CH ranges from 1 year to 20 years, the economic thickness range of RW is 47–235 mm, XPS is 41–197 mm, PU is 33–149 mm and HVIP is 4–18 mm at the altitude of 2177.5 m. At the altitude of 950 m, the economic thickness range of RW is 28–158 mm, XPS is 26–131 mm, PU is 25–118 mm, and HVIP is 2–12 mm. From an economic point of view, the service life of a CH has a significant impact on the choice of insulation thickness

POA protects PA-induced cell death via pyroptotic pathways.

(A, B) Cells were treated with BSA, 200 μM PA, 200 μM PA+200 μM POA for four hours, and protein levels of cleaved caspase-11 (c-casp11), GSDMD-N, NLRP3, ASC, cleaved caspase-1 (c-casp1), cleaved IL-1β (c-IL 1β), GSDME-N were subsequently detected by Western blot. (C, D) Concentrations of IL-1β and IL-18 in cell culture supernatants were determined via ELISA. Data are shown as mean ± SD. *p p p p < 0.0001.</p