050). PBNs/M0 macrophages from SA released more S100A9 than those from non-SA patients. PBNs from asthmatic patients induced S100A9 production by AECs, which further activated AECs via the extracellular signal-regulated kinase (ERK) pathway, stimulated NET formation, and induced M1 macrophage polarization. Higher S100A9 levels in sera, bronchoalveolar lavage fluid, and lung tissues were observed in the mouse model of NA but not in the other mouse models. These results suggest that S100A9 is a potential serum biomarker and therapeutic target for NA.In this study, we hypothesized that deregulation in the maintenance of the pool of coenzyme A (CoA) may play a crucial role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Specific deletion of Acot12 (Acot12-/-), the major acyl-CoA thioesterase, induced the accumulation of acetyl-CoA and resulted in the stimulation of de novo lipogenesis (DNL) and cholesterol biosynthesis in the liver. KEGG pathway analysis suggested PPARα signaling as the most significantly enriched pathway in Acot12-/- livers. Surprisingly, the exposure of Acot12-/- hepatocytes to fenofibrate significantly increased the accumulation of acetyl-CoA and resulted in the stimulation of cholesterol biosynthesis and DNL. Interaction analysis, including proximity-dependent biotin identification (BioID) analysis, suggested that ACOT12 may directly interact with vacuolar protein sorting-associated protein 33A (VPS33A) and play a role in vesicle-mediated cholesterol trafficking and the process of lysosomal degradation of cholesterol in hepatocytes. In summary, in this study, we found that ACOT12 deficiency is responsible for the pathogenesis of NAFLD through the accumulation of acetyl-CoA and the stimulation of DNL and cholesterol via activation of PPARα and inhibition of cholesterol trafficking.Obesity is a critical issue in patients with schizophrenia, which is considered to be brought about by both environmental and genetic factors.  https://www.selleckchem.com/products/disodium-r-2-hydroxyglutarate.html  Apolipoprotein E (APOE) gene polymorphisms might be involved in the pathogenesis of schizophrenia, however, the effect of APOE gene polymorphism on obesity has never been investigated in Chinese aging with schizophrenia. This cross-sectional study was to investigate the effect of obesity on cognitive and psychiatric symptoms in elderly participants with schizophrenia. At the same time, we also discussed the inner link between APOE E4 and obesity. 301 elderly participants with schizophrenia and 156 normal controls were included in the study. Their cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), and APOE gene polymorphism was determined by polymerase chain reaction (PCR). The prevalence of obesity in elderly schizophrenic patients and healthy controls accounted for 15.9% (48/301) and 10.3% (16/156), respectively, with no statistically significant difference. By using stepwise linear regression analysis, we found that elevated fasting blood glucose, hypertension, and hyperlipidemia were risk factors for obesity in elderly schizophrenic patients. Although there was no direct correlation between APOE E4 and obesity in patients with schizophrenia, it was significantly correlated with hyperlipemia(r = - 0.154, p = 0.008), suggesting that APOE E4 may induce obesity in elderly patients with schizophrenia through hyperlipemia, However, the above conclusions do not apply to the normal elderly. What's more, we did not find a link between obesity and cognitive function or mental symptoms for both patients with schizophrenia and normal controls. APOE E4 is associated with hyperlipidemia in elderly schizophrenic patients, which may be a risk factor for obesity, however, the above conclusion does not apply to the normal elderly.To develop a predictive model and a nomogram for predicting postoperative hemorrhage in preoperative patients undergoing laparoscopic pancreaticoduodenectomy (LPD). A total of 409 LPD patients that underwent LPD by the same surgical team between January 2014 and December 2020 were included as the training cohort. The preoperative data of patients were statistically compared and analyzed for exploring factors correlated with postoperative hemorrhage. The predictive model was developed by multivariate logistic regression and stepwise (stepAIC) selection. A nomogram based on the predictive model was developed. The discriminatory ability of the predictive model was validated using the receiver operating characteristic (ROC) curve and leave-one-out method. The statistical analysis was performed using R 3.5.1 ( www.r-project.org ). The predictive model including the risk-associated factors of postoperative hemorrhage was as follows 2.695843 - 0.63056 × (Jaundice = 1) - 1.08368 × (DM = 1) - 2.10445 × (Hepatitis = 1) + 1.152354 × (Pancreatic tumor = 1) + 1.071354 × (Bile duct tumor = 1) - 0.01185 × CA125 - 0.04929 × TT - 0.08826 × APTT + 26.03383 × INR - 1.9442 × PT + 1.979563 × WBC - 2.26868 × NEU - 2.0789 × LYM - 0.02038 × CREA + 0.00459 × AST. A practical nomogram based on the model was obtained. The internal validation of ROC curve was statistically significant (AUC = 0.7758). The validation by leave-one-out method showed that the accuracy of the model and the F measure was 0.887 and 0.939, respectively. The predictive model and nomogram based on the preoperative data of patients undergoing LPD can be useful for predicting the risk degree of postoperative hemorrhage.Neurotrophic tropomyosin receptor kinase (NTRK) gene fusions are rare oncogenic drivers in solid tumours. This study aimed to interrogate a large real-world database of comprehensive genomic profiling data to describe the genomic landscape and prevalence of NTRK gene fusions. NTRK fusion-positive tumours were identified from the FoundationCORE® database of >295,000 cancer patients. We investigated the prevalence and concomitant genomic landscape of NTRK fusions, predicted patient ancestry and compared the FoundationCORE cohort with entrectinib clinical trial cohorts (ALKA-372-001 [EudraCT 2012-000148-88]; STARTRK-1 [NCT02097810]; STARTRK-2 [NCT02568267]). Overall NTRK fusion-positive tumour prevalence was 0.30% among 45 cancers with 88 unique fusion partner pairs, of which 66% were previously unreported. Across all cases, prevalence was 0.28% and 1.34% in patients aged ≥18 and less then 18 years, respectively; prevalence was highest in patients less then 5 years (2.28%). The highest prevalence of NTRK fusions was observed in salivary gland tumours (2.