Unraveling the immunological landscape in acute pancreatitis progression to sepsis: insights from a Mendelian randomization study on immune cell traits.

Background: Acute pancreatitis (AP) is a severe digestive system disorder with a significant risk of progressing to sepsis, a major cause of mortality. Unraveling the immunological pathways in AP is essential for developing effective treatments, particularly understanding the role of specific immune cell traits in this progression. Methods: Employing a bidirectional two-sample Mendelian Randomization (MR) approach, this study first examined the causal relationship between AP and 731 immune cell traits to identify those significantly associated with AP. Subsequently, we explored the causal associations between 731 immune cell traits and sepsis. The analysis utilized extensive genome-wide association studies (GWAS) summary datasets, with a focus on identifying common immune cell traits with statistically significant causal associations between AP and sepsis. Results: Our investigation identified 44 immune cell traits unidirectionally associated with AP and 36 traits unidirectionally associated with sepsis. Among these, CD127 on CD28+ CD45RA- CD8+ T cells emerged as a common mediator, accounting for 5.296% of the increased risk of sepsis in AP patients. This finding highlights the significant role of specific memory CD8+ T cells in the pathophysiology of AP and its progression to sepsis. Conclusion: This study elucidates the critical role of specific immune cell traits, particularly CD127hi memory CD8+ T cells, in the progression of AP to sepsis. Our findings provide a foundation for future research into targeted immune-modulatory therapies, potentially improving patient outcomes in AP-related sepsis and offering new insights into the complex immunological dynamics of this condition.

MSCs-derived extracellular vesicles alleviate sepsis-associated liver dysfunction by inhibiting macrophage glycolysis-mediated inflammatory response.

Sepsis-associated liver dysfunction (SALD) aggravates the disease progression and prognosis of patients. Macrophages in the liver play a crucial role in the occurrence and development of SALD. Human umbilical cord mesenchymal stem cells (MSCs), by secreting extracellular vesicles (EVs), show beneficial effects in various inflammatory diseases. However, whether MSC-derived EVs (MSC-EVs) could ameliorate the inflammatory response in liver macrophages and the underlying mechanisms remain unclear. In this study, a mouse model of sepsis induced by lipopolysaccharide (LPS) challenge was used to investigate the immunomodulatory functions of MSC-EVs in SALD. LPS-stimulated primary Kupffer cells (KCs) and Raw264.7 were used to further explore the potential mechanisms of MSC-EVs in regulating the inflammatory response of macrophages. The results showed that MSC-EVs alleviated liver tissue injury and facilitated the polarization of M1 to M2 macrophages. Further in vitro studies confirmed that MSC-EVs treatment significantly downregulated the expression of several enzymes related to glycolysis and reduced the glycolytic flux by inhibiting hypoxia-inducible factor 1α (HIF-1α) expression, thus effectively inhibiting the inflammatory responses of macrophages. These findings reveal that the application of MSC-EVs might be a potential therapeutic strategy for treating SALD.

Factors associated with prolonged viral shedding of SARS-CoV-2 Omicron variant infection in Shanghai: A multicenter, retrospective, observational study.

Shanghai has faced an unprecedented COVID-19 pandemic with the BA.2.2 strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron infection. Comprehensive insights into its epidemiology, clinical manifestations, and viral shedding dynamics are currently limited. This study encompasses 208373 COVID-19 patients that were infected with the Omicron BA.2.2 sub-lineage in Shanghai, China. Demographic information, clinical symptoms, vaccination status, isolation status, as well as viral shedding time (VST) were recorded. Among the COVID-19 patients included in this study, 187124 were asymptomatic and 21249 exhibited mild symptoms. The median VST was 8.3 days. The common clinical symptoms included fever, persistent cough, phlegm, sore throat, and gastrointestinal symptoms. Factors such as advanced age, presence of comorbidities, mild symptomatology, and delayed isolation correlated with extended VST. Conversely, female gender and administration of two or three vaccine doses correlated with a reduction in VST. This investigation offers an in-depth characterization and analytical perspective on Shanghai's recent COVID-19 surge. Prolonged viral shedding of SARS-CoV-2 was observed in elderly, male, symptomatic patients, and those with comorbidity. Female, individuals with two or three vaccine doses, as well as those isolated early, shows an effective reduced VST.

Synergistic Engineering of Defects and Architecture in a Co@Co3O4@N-CNT Nanocage toward Li-Ion Batteries and HER.

The design and synthesis of hollow and porous nanostructured electrode materials is an effective strategy to improve the electrochemical performance of lithium-ion batteries and the hydrogen evolution reaction (HER). Herein, we synthesize hollow and porous Co@Co3O4 nanoparticles embedded in N-doped CNTs (N-CNTs) with rich surface defects through a two-step calcination strategy. The formation mechanism is explored. The influence of oxygen vacancies regulated by the nanoscale Kirkendall effect on the electrochemical performance of the electrode is elucidated. The Co@Co3O4@N-CNTs exhibit remarkable activity for catalyzing the HER with a low onset overpotential of 296 mV (a low Tafel slope of 116.2 mV dec-1), much better than Co3O4@N-CNTs (315 mV for overpotential and 124.2 mV dec-1 for Tafel slope). Significantly, the Co@Co3O4@N-CNTs deliver a high discharge capacity of 990 mA h g-1 after 600 cycles at 0.1 A g-1. Our nanostructure strategy can provide new insights into the strategy for high-rate and highly stable energy storage systems.