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Summary: Although intraperitoneal injection of monosodium urate (MSU) is an effective model for studying peritonitis, its establishment remains challenging. Here, we present a protocol for using MSU to activate the NLRP3 inflammasome in bone-marrow-derived macrophages (BMDMs) and to induce peritonitis in mice. We describe steps for isolating and culturing BMDMs, preparing MSU crystals, and activating the NLRP3 inflammasome using western blot and ELISA. We then detail procedures for inducing peritonitis and testing for relevant indicators using flow cytometry and ELISA.For complete details on the use and execution of this protocol, please refer to Huang et al. (2023).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Programmed cell death (PCD) is regarded as a pathological form of cell death with an intracellular program mediated, which plays a pivotal role in maintaining homeostasis and embryonic development. Pyroptosis is a new paradigm of PCD, which has received increasing attention due to its close association with immunity and disease. Pyroptosis is a form of inflammatory cell death mediated by gasdermin that promotes the release of proinflammatory cytokines and contents induced by inflammasome activation. Recently, increasing evidence in studies shows that pyroptosis has a crucial role in inflammatory conditions like cardiovascular diseases (CVDs), cancer, neurological diseases (NDs), and metabolic diseases (MDs), suggesting that targeting cell death is a potential intervention for the treatment of these inflammatory diseases. Based on this, the review aims to identify the molecular mechanisms and signaling pathways related to pyroptosis activation and summarizes the current insights into the complicated relationship between pyroptosis and multiple human inflammatory diseases (CVDs, cancer, NDs, and MDs). We also discuss a promising novel strategy and method for treating these inflammatory diseases by targeting pyroptosis and focus on the pyroptosis pathway application in clinics.

Primary liver cancer, mainly comprising hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), remains a major global health problem. Although ICC is clinically different from HCC, their molecular differences are still largely unclear. In this study, precision N‐glycoproteomic analysis was performed on both ICC and HCC tumors as well as paracancer tissues to investigate their aberrant site‐specific N‐glycosylation. By using our newly developed glycoproteomic methods and novel algorithm, termed ‘StrucGP’, a total of 486 N‐glycan structures attached on 1235 glycosites were identified from 894 glycoproteins in ICC and HCC tumors. Notably, glycans with uncommon LacdiNAc (GalNAcβ1‐4GlcNAc) structures were distinguished from their isomeric glycans. In addition to several bi‐antennary and/or bisecting glycans that were commonly elevated in ICC and HCC, a number of LacdiNAc‐containing, tri‐antennary, and core‐fucosylated glycans were uniquely increased in ICC. More interestingly, almost all LacdiNAc‐containing N‐glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1‐4 GalNAc transferases in ICC at both mRNA and protein expression levels. The novel N‐glycan alterations uniquely detected in ICC provide a valuable resource for future studies regarding to the discovery of ICC diagnostic biomarkers, therapeutic targets, and mechanism investigations.

In the smart grid, the end-users have the opportunity to integrate renewable energy sources (RESs) and participate in two-way energy trading. At the same time, an increasing number of flexible loads (FLs) have been developed for use on the demand side. Thus, this article considers joint energy trading and load scheduling at a end-user with integrated renewable generation. With unknown statistics on renewable generation, loads and electricity prices, we aim at optimizing both energy trading and load scheduling to maximize the long-term average profit of the end-user, subject to load delay constraints. We employ the Lyapunov optimization theory to solve this stochastic problem with a series of problem corrections and transformations that enable us to design a dynamic energy trading and load scheduling algorithm. Within the performance analysis of the algorithm, we further demonstrate that the algorithm not only provides a bounded performance guarantee to the optimal solution that has complete future information, but is also asymptotically equivalent to it as the battery capacity or the delay time of FLs tend to infinity. The simulation results show that the proposed algorithm is superior to other algorithms both in terms of performance and service delay. Moreover, we can achieve a trade-off between comfort and total profit by adjusting the values of the parameters, and analyze the effect of battery capacity on algorithm performance to provide a theoretical basis for the end-user to determine battery capacity.

Abstract In this paper, we investigate the problem of dynamic power allocation for a multiuser transmitter supplied by hybrid energy sources in details. Specifically, we focus on the hybrid energy sources which include both the traditional power grid and various renewable sources whereby there are a few issues in considerations: (1) The energy harvested jointly from various renewable sources is time-varying and possibly unpredictable and is stored in a limited capacity buffer with battery leakage. (2) At the meantime, the data arrives randomly to the transmitter and queues according to the individual receivers to wait to be transmitted. (3) In addition, the wireless channels fluctuate randomly due to fading. Taking into account the time variant and dynamic features of this system, we develop a dynamic power allocation algorithm for the transmitter with the aim of minimizing the average amount of energy consumption from the power grid over an infinite horizon, subject to all data in queues cannot exceed a given deadline of receivers. The research question is formulated as a stochastic optimization problem, then we utilize Lyapunov optimization to exploit an online algorithm with low complexity, and it does not require prior statistical knowledge of the stochastic processes. Performance analysis of the proposed algorithm is carried out in theory, which shows that the proposed algorithm performs arbitrarily close to the optimal objective value; meanwhile, the algorithm ensures that the maximum delay of all data queues cannot exceed a given value. Finally, performance comparison shows that our proposed algorithm provides not only better performance but also less time delay than other two algorithms.

Korean pine nut protein (PNP) has a variety of biological activities, which are good for human health, but its ability to preventing diabetes has not been reported. This study evaluated the effects of water-soluble proteins of Korean pine nut obtained from a dilute alkali extract on carbohydrate metabolism of type 2 diabetic mice on a model of diabetes induced using a high fat diet combined with streptozotocin. The results showed that the hypoglycemic effect of PNP at a middle dose was the most significant, which was 38.7% lower than that of control. The extract significantly improved the oral glucose tolerance and liver indexes, increased the activity of the carbohydrate metabolism enzymes, and regulated the expression of the function of key genes for carbohydrate metabolism. It had a positive effect on both insulin resistance and glycolytic/gluconeogenesis signaling. In conclusion, PNP can regulate fasting blood glucose, improve insulin resistance, correct the glucose metabolism disorder in diabetic mice, and have a positive regulatory role. As the functional food, it has the potential to be beneficial in the treatment of type 2 diabetes mellitus as a new hypoglycemic functional food.

Plastic film mulching (PM) is widely utilized for maize production in China. However, the effect of PM on the grain yield of crops has not been established, and the biochemical mechanism underlying the increase or decrease in grain yield under PM is not yet understood. Grain filling markedly affects the grain yield. The objective of this study was to investigate the effects of PM on maize grain filling under different irrigation levels and the relationship of such effects with hormonal changes. In the present study, PM was compared with traditional nonmulching management (TN) under 220 mm, 270 mm and 320 mm irrigation amount, and the grain filling characters of the grains located in various parts of the ear and the hormonal changes in the grains were measured. The results indicated that at 220 mm irrigation, PM significantly increased the grain filling rate of the middle and basal grains and decreased the grain filling rate of the upper grains. At 270 mm irrigation, the PM significantly increased the grain filling rate of the all grains. At 320 mm irrigation, the PM only significantly increased the grain filling rate of the upper grains. The IAA, Z+ZR and ABA content in the grains was positively correlated with the grain weight and grain-filling rates; however, the ETH evolution rate of the grains was negatively correlated with the grain weight and grain-filling rates. These results show that the effect of PM on maize grain filling is related to the irrigation amount and that the grain position on the ear and the grain filling of the upper grains was more sensitive to PM and irrigation than were the other grains. In addition, the PM and irrigation regulated the balance of hormones rather than the content of individual hormones to affect the maize grain filling.

Ferroptosis is a form of iron-dependent, lipid peroxidation-driven regulatory cell death that has been implicated in the pathogenesis of multiple diseases, including organ injury, ischemia/reperfusion, and neurodegenerative diseases. However, inhibitors that directly and specifically target ferroptosis are not yet available. Here, we identify the compound AS-252424 (AS) as a potent ferroptosis inhibitor through kinase inhibitor library screening. Our results show that AS effectively inhibits lipid peroxidation and ferroptosis in both human and mouse cells. Mechanistically, AS directly binds to the glutamine 464 of ACSL4 to inhibit its enzymatic activity, resulting in the suppression of lipid peroxidation and ferroptosis. By using nanoparticle-based delivery systems, treatment with AS-loaded nanoparticles effectively alleviate ferroptosis-mediated organ injury in mouse models, including kidney ischemia/reperfusion injury and acute liver injury (ALI). Thus, our results identify that AS is a specific and targeted inhibitor of ACSL4 with remarkable antiferroptosis function, providing a potential therapeutic for ferroptosis-related diseases. [ABSTRACT FROM AUTHOR]