SARM (sterile α‐ and armadillo‐motif‐containing protein), the fifth identified TIR (Toll–interleukin 1 receptor (IL‐1R)) domain‐containing adaptors in humans, downregulates NF‐κB and IRF3 (interferon‐regulatory factor 3)‐mediated TLR3 and TLR4 signaling. SARM was characterized as a negative regulator of the TRIF (TIR‐domain‐containing adaptor protein inducing IFN‐β)‐dependent pathway via its interaction with TRIF. However, the precise mechanism of action of SARM remains unclear. Here, we demonstrate that SARM inhibits MAPK activation in human embryonic kidney 293 cells, and U937 cells. Both the TRIF‐ and MyD88‐mediated, as well as basal MAPK activity, were repressed, indicating that SARM‐mediated inhibition may not be exclusively directed at TRIF or MyD88, but that SARM may also directly inhibit MAPK phosphorylation. The MAPK inhibition effect was verified by RNAi, which increased the basal level of AP‐1. Furthermore, LPS challenge upregulated SARM at both the mRNA and protein levels. Finally, we provide evidence to show that truncated SARM changes its subcellular localization, suggesting the importance of the N‐terminal and sterile alpha motif domains in the autoregulation of SARM activity.

Most models of neoadjuvant chemotherapy (NACT) for breast cancer (BC) suffer from insufficient data and lack interpretability. Additionally, there is a notable absence of reports from China in this field. This study is also the first to integrate the Advanced Lung Cancer Inflammation Index (ALI) into such a model to evaluate its effectiveness. Data from 3,036 female BC patients receiving NACT at Heilongjiang Provincial Tumor Hospital (2008-2019, median follow-up 7.28 years) were analyzed. After screening, 2,909 patients were randomized into training and validation cohorts (7:3). Using eXtreme Gradient Boosting (XGBoost), Gradient Boosting Classifier (GBC), Support Vector Machine (SVM) models, and SHapley Additive exPlanations (SHAP), the best predicting pathological complete response (pCR) model was identified, and key features were interpreted. The Least Absolute Shrinkage and Selection Operator (LASSO) Cox algorithm, combined with XGBoost and Random Forest (RF) models, identified 9 overlapping prognostic features, enhancing the nomogram's predictive accuracy for overall survival (OS). Kaplan-Meier (KM) analysis revealed varying prognostic outcomes. The XGBoost model performed best in predicting pCR, with Area Under Curve (AUC) values of 0.88 and 0.72 in the training and validation sets, respectively. SHAP analysis indicated that ER, HER2 status, ALI, and albumin (Alb) level were the four most important features. The prognostic model was also validated by high AUC values in both training and test sets. KM analysis indicated that lower ALI, non-pCR, and triple-negative BC manifested as worse clinical outcomes. However, the adverse impact of ALI on the prognosis of this cohort was mainly reflected in the long-term recurrence outcomes and non-pCR groups. This study is the first to introduce ALI into the prediction model for BC completing NACT and develop a large-sample model based on XGBoost. Owing to the particularity of the indicators, training and validation were conducted on real clinical data.

Exposure to air pollution is associated with the development of numerous neonatal diseases (NDs). This study aimed to evaluate the worldwide changes in the burden of NDs attributable to air pollution from 1990 to 2021. The 2021 Global Burden of Disease Study (GBD) reported neonatal deaths attributable to air pollution and the associated age-standardized rates and disability-adjusted life years (DALYs). To assess the global burden of NDs and the subtypes, age-standardized DALY rates (ASDARs) and age-standardized death rates (ASDRs) were employed. The estimated annual percentage change (EAPC) was used to track global and regional temporal trends from 1990 to 2021. Spearman’s rank correlation coefficients were applied to evaluate the relationship between the sociodemographic index (SDI), ASDARs, and ASDRs for NDs. The slope inequality index and concentration index were derived from health inequality analyses to measure international disparities. Finally, frontier analysis were employed to determine optimal burden for NDs at corresponding SDI levels. In 2021, the air pollution-related NDs resulted in 496,966 deaths and 44,737,311 DALYs worldwide. The burden for NDs showed a decreasing trend globally in past three decades. Neonatal preterm birth was the most severe subtype of NDs in 2021. With the global and regional increase in the SDI, the ASDR and ASDAR for five NDs subtypes have decreased. Significant absolute and relative income disparities in the burden of DALYs and mortality due to NDs were observed worldwide. Frontier analysis indicated inverse correlations between the ASDR/ASDAR and SDI, with the Solomon Islands, a low SDI country, showing the smallest overall differences. Although the burden of air pollution-induced NDs has decreased, it remains a significant public health concern, with regional disparities. More nuanced policies and preventive measures are needed to reduce the burden of NDs.

The classical abscopal effect is defined here as objective regression of a verified non-irradiated tumor lesion following local radiotherapy. An immune abs