Causal relationship between immune cells and the risk of myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis: A Mendelian randomization study.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease categorized as antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The majority of patients are ANCA-positive, predominantly against myeloperoxidase (MPO). Previous studies have predominantly concentrated on the association between EGPA and neutrophils, but recent research has emphasized the role of lymphocytes in the development of EGPA. The objective of our research was to examine the causal association between immune cells and MPO + ANCA EGPA. A two-sample bidirectional Mendelian randomization (MR) analysis was performed, which included 159 MPO + ANCA EGPA cases and 6688 controls and utilized Genome-Wind Associaton Studies (GWAS) summary statistics of immune traits from approximately 3757 individuals, encompassing around 22 million single nucleotide polymorphisms (SNPs). Our findings revealed that 23 immunophenotypes were associated with MPO + ANCA EGPA. Furthermore, the reverse MR analysis showed that MPO + ANCA EGPA had significant causal effects on three immunophenotypes within the Treg panel. By integrating existing research, our study unveiled the contributions of Tregs, B cells, and monocytes to the development of EGPA. Subgroup analysis specifically examined the roles of lymphocyte subtypes, cytokines, and their surface molecules in the pathogenic mechanisms of the disease. This comprehensive approach provides a novel perspective on the biological mechanisms and early intervention strategies for MPO + ANCA EGPA by focusing on immune cells.

The connection between autophagy and ferroptosis in AKI: recent advances regarding selective autophagy.

Acute kidney injury (AKI) is a significant issue in public health, displaying a high occurrence rate and mortality rate. Ferroptosis, a form of programmed cell death (PCD), is characterized by iron accumulation and intensified lipid peroxidation. Recent studies have demonstrated the pivotal significance of ferroptosis in AKI caused by diverse stimuli, including ischemia-reperfusion injury (IRI), sepsis and toxins. Autophagy, a multistep process that targets damaged organelles and macromolecules for degradation and recycling, also plays an essential role in AKI. Previous research has demonstrated that autophagy deletion in proximal tubules could aggravate tubular injury and renal function loss, indicating the protective function of autophagy in AKI. Consequently, finding ways to stimulate autophagy has become a crucial therapeutic strategy. The recent discovery of the role of selective autophagy in influencing ferroptosis has identified new therapeutic targets for AKI and has highlighted the importance of understanding the cross-talk between autophagy and ferroptosis. This study aims to provide an overview of the signaling pathways involved in ferroptosis and autophagy, focusing on the mechanisms and functions of selective autophagy and autophagy-dependent ferroptosis. We hope to establish a foundation for future investigations into the interaction between autophagy and ferroptosis in AKI as well as other diseases.

Short-term effects of ambient air pollution on daily emergency room visits for abdominal pain: a time-series study in Wuhan, China.

Short-term exposure to ambient air pollution has been proven to result in respiratory, cardiovascular, and digestive diseases, leading to increased emergency room visits (ERVs). Abdominal pain complaints provide a large proportion of the ERVs, as yet few studies have focused on the correlations between ambient air pollution and abdominal pain, especially in emergency departments within China. Daily data for daily ERVs were collected in Wuhan, China (from January 1, 2016 to December 31, 2018), including air pollution concentration (SO2, NO2, PM2.5, PM10, CO, and O3), and meteorological variables. We conducted a time-series study to investigate the potential correlation between six ambient air pollutants and ERVs for abdominal pain and their effects, in different genders, ages, and seasons. A total of 16,318 abdominal pain ERVs were identified during the study period. A 10-µg/m3 increase in concentration of SO2, NO2, PM2.5, PM10, CO, and O3 corresponded respectively to incremental increases in abdominal pain of 4.89% (95% confidence interval [CI]: - 1.50-11.70), 1.85% (95% CI: - 0.29-4.03), 0.83% (95% CI: - 0.05-1.72), - 0.22% (95% CI: - 0.73-0.30), 0.24% (95% CI: 0.08-0.40), and 0.86% (95% CI: 0.04 - 1.69). We observed significant correlations between CO and O3 and increases in daily abdominal pain ERVs and positive but insignificant correlations between the other pollutants and ERVs (except PM10). The effects were stronger for females (especially SO2 and O3: 13.53% vs. - 2.46%; 1.20% vs. 0.47%, respectively) and younger people (especially CO and O3: 0.25% vs. 0.01%; 1.36% vs. 0.15%, respectively). Males (1.38% vs. 0.87%) and elders (1.27% vs. 0.99%) were more likely to be affected by PM2.5. The correlations with PM2.5 were stronger in cool seasons (1.25% vs. - 0.07%) while the correlation with CO was stronger in warm seasons (0.47% vs. 0.14%). Our time-series study suggests that short-term exposure to air pollution (especially CO and O3) was positively correlated with ERVs for abdominal pain in Wuhan, China, and that the effects varied by season, gender and age. These data can add evidence on how air pollutants affect the human body and may prompt hospitals to take specific precautions on polluted days and maintain order in emergency departments made busier due to the pollution.

Selective C-H acylation of indoles with α-oxocarboxylic acids at the C4 position by palladium catalysis.

The first Pd-catalyzed direct C-H acylation of indoles at the C4 position with α-oxocarboxylic acids using a ketone directing group is described. This reaction exhibits high regioselectivity with the tolerance of a wide scope of functional groups to afford diverse acylated indoles in moderate-to-good yields. The control experiments evidence the generation of acyl radicals via K2S2O8 promoted decarboxylation of α-oxocarboxylic acids and the involvement of a PdII/PdIV catalytic cycle. Importantly, the synthetically useful selectivity observed might be applied to prepare indole derivatives with anti-tumor activity as tubulin inhibitors.