FDA compound library screening Baicalin upregulates TREM2 for the treatment of cerebral ischemia-reperfusion injury.

Acute ischemic stroke (AIS) is a leading cause of global incidence and mortality rates. Oxidative stress and inflammation are key factors in the pathogenesis of AIS neuroinjury. Therefore, it is necessary to develop drugs that target neuroinflammation and oxidative stress in AIS. The Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), primarily expressed on microglial cell membranes, plays a critical role in reducing inflammation and oxidative stress in AIS. In this study, we employed a high-throughput screening (HTS) strategy to evaluate 2625 compounds from the (Food and Drug Administration) FDA library in vitro to identify compounds that upregulate the TREM2 receptor on microglia. Through this screening, we identified Baicalin as a potential drug for AIS treatment. Baicalin, a flavonoid compound extracted and isolated from the root of Scutellaria baicalensis, demonstrated promising results. Next, we established an in vivo mouse model of cerebral ischemia-reperfusion injury (MCAO/R) and an in vitro microglia cell of oxygen-glucose deprivation reperfusion (OGD/R) to investigate the role of Baicalin in inflammation injury, oxidative stress, and neuronal apoptosis. Our results showed that baicalin effectively inhibited microglia activation, reactive oxygen species (ROS) production, and inflammatory responses in vitro. Additionally, baicalin suppressed neuronal cell apoptosis. In the in vivo experiments, baicalin not only improved neurological functional deficits and reduced infarct volume but also inhibited microglia activation and inflammatory responses. Overall, our findings demonstrate the efficacy of Baicalin in treating MCAO/R by upregulating TREM2 to reduce inflammatory responses and inhibit neuronal apoptosis.

Association between serum osmolality and 28-day all-cause mortality in patients with heart failure and reduced ejection fraction: a retrospective cohort study from the MIMIC-IV database.

Background: Previous studies have not thoroughly explored the impact of serum osmolality levels on early mortality in heart failure and reduced ejection fraction (HFrEF) patients. The purpose of this study was to investigate the relationship between serum osmolality levels and early all-cause mortality in patients with HFrEF. Methods: The open access MIMIC-IV database was the source of data for our study. We collected demographic data, vital signs, laboratory parameters, and comorbidities of the included patients and divided them into 3 groups based on their initial serum osmolality on admission, with the primary outcome being all-cause mortality within 28 days of admission. Smoothing Spline Fitting Curve, the Kaplan-Meier survival curve, and Threshold effect analysis were used to assess the relationship between serum osmolality and early mortality in HFrEF patients. Results: A total of 6228 patients (55.31% male) were included. All-cause mortality within 28 days on admission was 18.88% in all patients. After adjusting for confounders, higher serum osmolality levels were independently associated with an increased risk of 28-days all-cause mortality compared with the reference group (Reference group Q2: 290-309 mmol/L, Q4: HR, 1.82 [95% CI 1.19-2.78] P<0.05, Q5: HR, 1.99 [95% CI 1.02-3.91] P<0.05). Smooth spline fitting revealed a U-shaped association between serum osmolality and 28-days all-cause mortality. Further threshold effect analysis results suggested that each unit increase in serum osmolality level was associated with a 2% increase in 28-days all-cause mortality when serum osmolality levels were ≥ 298.8 mmol/L (HR, 1.019 [95% CI 1.012-1.025] P<0.05). Conclusion: A U-shaped correlation between initial serum osmolality and 28-days all-cause mortality in HFrEF patients was identified, revealing higher osmolality levels significantly increase mortality risk. These results underscore serum osmolality's critical role in early mortality among HFrEF patients, highlighting the need for further, larger-scale studies for validation.

Substantial contribution of transported emissions to organic aerosol in Beijing.

Haze in Beijing is linked to atmospherically formed secondary organic aerosol, which has been shown to be particularly harmful to human health. However, the sources and formation pathways of these secondary aerosols remain largely unknown, hindering effective pollution mitigation. Here we have quantified the sources of organic aerosol via direct near-molecular observations in central Beijing. In winter, organic aerosol pollution arises mainly from fresh solid-fuel emissions and secondary organic aerosols originating from both solid-fuel combustion and aqueous processes, probably involving multiphase chemistry with aromatic compounds. The most severe haze is linked to secondary organic aerosols originating from solid-fuel combustion, transported from the Beijing-Tianjing-Hebei Plain and rural mountainous areas west of Beijing. In summer, the increased fraction of secondary organic aerosol is dominated by aromatic emissions from the Xi'an-Shanghai-Beijing region, while the contribution of biogenic emissions remains relatively small. Overall, we identify the main sources of secondary organic aerosol affecting Beijing, which clearly extend beyond the local emissions in Beijing. Our results suggest that targeting key organic precursor emission sectors regionally may be needed to effectively mitigate organic aerosol pollution.