STING Agonist cGAMP Attenuates Sleep Deprivation-Induced Neuroinflammation and Cognitive Deficits via TREM2 Up-Regulation.

Sleep deprivation (SD) has been associated with several adverse effects, including cognitive deficit. Emerging evidence suggests microglia-associated neuroinflammation is a potential trigger of cognitive deficit after SD. Stimulator of interferon genes (STING) constitutes an important factor in host immune response to pathogenic organisms and is found in multiple cells, including microglia. STING is involved in neuroinflammation during neuronal degeneration, although how STING signaling affects SD-induced neuroinflammation remains unexplored. In the present study, the chronic sleep restriction (CSR) model was applied to examine the effects of STING signaling on cognition. The results revealed that cGAMP, a high-affinity and selective STING agonist, significantly improved cognitive deficit, alleviated neural injury, and relieved neuroinflammation in CSR mice by activating the STING-TBK1-IRF3 pathway. Moreover, triggering receptor expressed on myeloid cells 2 (TREM2) was upregulated in CSR mice treated with cGAMP, and this effect was abolished by STING knockout. TREM2 upregulation induced by cGAMP regulated the microglia from pro-inflammatory state to anti-inflammatory state, thereby relieving neuroinflammation in CSR mice. These findings indicate cGAMP-induced STING signaling activation alleviates SD-associated neuroinflammation and cognitive deficit by upregulating TREM2, providing a novel approach for the treatment of SD-related nerve injury.

Development and validation of a nomogram to predict Chinese breast cancer risk based on clinical serum biomarkers.

Background: This study investigated and compared clinical serum biomarkers and developed a diagnostic nomogram for breast cancer. Methods: A total of 1224 breast cancer and 1280 healthy controls were enrolled. Univariate and multivariate analyses were performed to identify factors and a nomogram was developed. Discrimination, accuracy and clinical utility values were evaluated by receiver operating characteristic, Hosmer-Lemeshow, calibration plots, decision curve analysis and clinical impact plots. Results: carcinoembryonic antigen, CA125, CA153, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio, fibrinogen and platelet distributing width were effectively identified to predict breast cancer. The nomogram showed the area under the curve of 0.708 and 0.710 in the training and validation set. Calibration plots, Hosmer-Lemeshow, decision curve analysis and clinical impact plots confirmed great accuracy and clinical utility. Conclusion: We developed and validated a nomogram that is effectively used for risk prediction of Chinese breast cancer.

Machine learning and BP neural network revealed abnormal B cell infiltration predicts the survival of lung cancer patients.

FAM83A gene is related to the invasion and metastasis of various tumors. However, the abnormal immune cell infiltration associated with the gene is poorly understood in the pathogenesis and prognosis of NSCLC. Based on the TCGA and GEO databases, we used COX regression and machine learning algorithms (CIBERSORT, random forest, and back propagation neural network) to study the prognostic value of FAM83A and immune infiltration characteristics in NSCLC. High FAM83A expression was significantly associated with poor prognosis of NSCLC patients (p = 0.00016), and had excellent prognostic independence. At the same time, the expression level of FAM83A is significantly related to the T, N, and Stage. Subsequently, based on machine learing strategies, we found that the infiltration level of naive B cells was negatively correlated with the expression of FAM83A. The low infiltration of naive B cells was significantly related to the poor overall survival rate of NSCLC (p = 0.0072). In addition, Cox regression confirmed that FAM83A and naive B cells are risk factors for the prognosis of NSCLC patients. The nomogram combining FAM83A and naive B cells (C-index = 0.748) has a more accurate prognostic ability than the Stage (C-index = 0.651) system. Our analysis shows that abnormal infiltration of naive B cells associated with FAM83A is a key factor in the prognostic prediction of NSCLC patients.

[RP-HPLC analysis of single, merging, and boiled together Lonicera japonica and Forsythia suspense].

OBJECTIVE: Utilizing RP-HPLC analysis of single, merging and simultaneously boiled Lonicera japonica and Forsythia suspense to find out their identity and difference. METHOD: Samples were separated by Alltech-C18 column (4. 6 mm x 250 mm, 5 microm) with a mixture solution of acetonitrile-water (containing 0.2% ethanoic acid) as mobile phase, 1.0 mL x min(-1) as flow-rate, 280 nm as detected wave-length, room temperature as temperature of column, 10 microL as injected volume. RESULT: The linear ranges of chlorogenic acid and forsythoside A were 0.980-9.800 microg (r = 0.999 9) and 0.972-9. 720 microg (r = 0.999 9), respectively. The average recoveries of chlorogenic acid and forsythoside A were 99.85% (n = 6, RSD 2.0%) and 100.87% (n = 6, RSD 1.6%), respectively. Major peaks were confirmed to the two component herbs, contents of chlorogenic acid and forsythoside A were determinated, ingredients were represented by following peaks were compared qualitatively: peaks k, m, n: L. japonica > merging sample > boiled sample; peaks g, h: Forsythia suspense > merging sample > boiled sample; peaks d, e, i: boiled sample > L. japonica, boiled sample > merging sample. CONCLUSION: Difference and identities among 4 experimental samples of RP-HPLC separations show that Yinqiao, L. japonica and F. suspense' substances are difference and identities, which offered direction for investigating further the topic-pharmacodynamic substance of Yinqiao, provided increasing experimental evidence for clinic medicine and pharmaceutics and supplied reference for the complex prescription of traditional Chinese medicine.