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Numerical simulations of the aerosol particles flow past a spherical droplet are carried out to determine the effect of particles Stokes number of 0.001 to 10 and the Reynolds number of 100 to 1000 on impaction efficiency, and to gain some insight into the particle dispersion pattern with different Stokes number under different flow conditions. The results suggest that there is a nonlinear relationship between the impaction efficiency and Stokes number. For particles with Stokes number greater than 0.01, the increase of Stokes number is beneficial to improve the impaction efficiency. For particles with Stokes number less than 0.01, the increase of Stokes number will inhibit the improvement of impaction efficiency. Reynolds number plays a significant role on back side impaction and particle dispersion, The larger the Reynolds number, the more prone to back side impaction. When Re = 1000, the angle of particle outward dispersion is the smallest. Copyright © 2023 American Association for Aerosol Research [ABSTRACT FROM AUTHOR]

A growing number of studies have shown that melatonin is a potent agonist of SIRT3 (sirtuin 3) and effectively protects mitochondria, suggesting melatonin as a promising therapeutic drug to treat sepsis-induced acute kidney injury (SAKI). In this study, we first included 48 sepsis patients for cross-sectional analysis and the result revealed that plasma melatonin levels are inversely proportional to the mitochondrial injury of renal tubular epithelial cells and directly proportional to the acute kidney injury recovery in sepsis patients. We further explored the effects of exogenous melatonin on SAKI and its mechanism in animal model of cecal ligation and puncture-treated mice, and cellular model of LPS-challenged HK-2 cells. The results demonstrate that the protective effect of melatonin on the progression of SAKI depends on SIRT3 activation as well as mitophagic flux. Mechanistically, TFAM (transcription factor A, mitochondrial)-K154 site deacetylation via SIRT3 is indispensable for melatonin-enhanced mitophagic flux on SAKI. Together, our study unveils a previously unappreciated mechanism of melatonin as agonists of SIRT3 to hold promise for treatment of patients with SAKI. AKI: acute kidney injury; ATP: adenosine triphosphate; BUN: blood urea nitrogen; CLP: cecal ligation and puncture; eGFR: estimated glomerular filtration rate; H&E: hematoxylin and eosin staining; LCN2/NGAL: lipocalin 2; LPS: lipopolysaccharide; LTL: lotus tetragonolobus lectin; mKeima: mitochondria-targeted Keima; mtDNA: mitochondrial DNA; PAS: periodic acid – Schiff staining; RTECs: renal tubular epithelial cells; SAKI: sepsis-induced acute kidney injury; Scr: serum creatinine; SIRT3: sirtuin 3; TFAM: transcription factor A, mitochondrial; TMRE: tetramethylrhodamine. [ABSTRACT FROM AUTHOR]

Background: Pain is a rapid response mechanism that compels organisms to retreat from the harmful stimuli and triggers a repair response. Nonetheless, when pain persists for extended periods, it can lead to adverse changes into in the individual's brain, negatively impacting their emotional state and overall quality of life. Microglia, the resident immune cells in the central nervous system (CNS), play a pivotal role in regulating a variety of pain‐related disorders. Specifically, recent studies have shed light on the central role that microglial purinergic ligand‐gated ion channel 7 receptor (P2X7R) plays in regulating pain. In this respect, the P2X7R on microglial membranes represents a potential therapeutic target. Aims: To expound on the intricate link between microglial P2X7R and pain, offering insights into potential avenues for future research. Methods: We reviewed 140 literature and summarized the important role of microglial P2X7R in regulating pain, including the structure and function of P2X7R, the relationship between P2X7R and microglial polarization, P2X7R‐related signaling pathways, and the effects of P2X7R antagonists on pain regulation. Results: P2X7R activation is related to M1 polarization of microglia, while suppressing P2X7R can transfer microglia from M1 into M2 phenotype. And targeting the P2X7R‐mediated signaling pathways helps to explore new therapy for pain alleviation. P2X7R antagonists also hold potential for translational and clinical applications in pain management. Conclusions: Microglial P2X7R holds promise as a potential novel pharmacological target for clinical treatments due to its distinctive structure, function, and the development of antagonists. [ABSTRACT FROM AUTHOR]

Pt-based catalysts play a significant role in the advancement of direct methanol fuel cells (DMFCs). However, their inefficient reaction kinetics, low resistance to CO poisoning, and unstable performance hinder the commercialization of DMFCs. To address these issues and enhance both the catalytic efficiency and stability of Pt-based catalysts for the methanol oxidation reaction (MOR), in this work MnO–Co@Pt nanocomposites were prepared by encapsulating them into N-doped porous carbon (NPC), which was confirmed through physicochemical characterizations, such as HR-TEM, XRD, and XPS. The catalyst structures were controllably synthesized by adjusting the calcination temperature and reaction time of galvanic replacement. MnO–Co@Pt NPCs demonstrated significantly improved performance compared to Pt/C catalysts for the MOR. The mass activity of 925.72 mA mgPt−1 and current density after a 3600 s I–t test of MnO–Co@Pt NPC 800 15 min 15% were 3.3 times and 3.8 times higher than those of the Pt/C catalyst, respectively. The peak potential of CO electrooxidation exhibited a negative shift of 73 mV when compared with the Pt/C catalyst. The exceptional MOR performance of MnO–Co@Pt NPCs can be attributed to the binding and encapsulation effects of the NPCs, which facilitate the isolation, preventing the sintering and expansion of MnO–Co@Pt nanoparticles. This study not only presents a simple method for developing low Pt nanostructures but also offers possibilities for designing nanocomposites with carbon protection layers and coated catalysts incorporating different transition metals. These advancements significantly improve the performance of Pt-based electrocatalysts for the MOR process. [ABSTRACT FROM AUTHOR]

Objective: Increased Toll‐like receptor 7 (TLR‐7) signaling leading to the production of type I interferon (IFN) is an important contributor to human systemic lupus erythematosus (SLE). Protein kinase C and casein kinase substrate in neurons 1 (PACSIN1), a molecule that regulates synaptic vesicle recycling, has been linked to TLR‐7/TLR‐9–mediated type I IFN production in humans and mice, but the underlying mechanism is unknown. We undertook this study to explore the pathogenicity and underlying mechanism of a de novo PACSIN1 missense variant identified in a child with SLE. Methods: PACSIN1 Q59K de novo and null variants were introduced into a human plasmacytoid dendritic cell line and into mice using CRISPR/Cas9 editing. The effects of the variants on TLR‐7/TLR‐9 signaling in human and mouse cells, as well as PACSIN1 messenger RNA and IFN signature in SLE patients, were assessed using real‐time polymerase chain reaction and flow cytometry. Mechanisms were investigated using luciferase reporter assays, RNA interference, coimmunoprecipitation, and immunofluorescence. Results: We established that PACSIN1 forms a trimolecular complex with tumor necrosis factor receptor–associated factor 4 (TRAF4) and TRAF6 that is important for the regulation of type I IFN. The Q59K mutation in PACSIN1 augments binding to neural Wiskott‐Aldrich syndrome protein while it decreases binding to TRAF4, leading to unrestrained TRAF6‐mediated activation of type I IFN. Intriguingly, PACSIN1 Q59K increased TLR‐7 but not TLR‐9 signaling in human cells, leading to elevated expression of IFNβ and IFN‐inducible genes. Untreated SLE patients had high PACSIN1 expression in peripheral blood cells that correlated positively with IFN‐related genes. Introduction of the Pacsin1 Q59K mutation into mice caused increased surface TLR‐7 and TRAIL expression in B cells. Conclusion: PACSIN1 Q59K increases IFNβ activity through the impairment of TRAF4‐mediated inhibition of TLR‐7 signaling, possibly contributing to SLE risk. [ABSTRACT FROM AUTHOR]