The third-generation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), represented by osimertinib, has achieved remarkable clinical outcomes in the treatment of non-small-cell lung cancer (NSCLC) with EGFR mutation. However, resistance eventually emerges in most patients and the underlying molecular mechanisms remain to be fully understood. In this study, we generated an osimertinib-acquired resistant lung cancer model from a NSCLC cell line H1975 harboring EGFR L858R and T790M mutations. We found that the capacity of DNA damage repair was compromised in the osimertinib resistant cells, evidenced by increased levels of γH2AX and higher intensity of the comet tail after withdrawal from cisplatin. Pharmacological inhibiting the activity or genetic knockdown the expression of DNA-PK, a key kinase in DNA damage response (DDR), sensitized the resistant cells to osimertinib. Combination of osimertinib with the DNA-PK inhibitor, PI-103, or NU7441, synergistically suppressed the proliferation of the resistant cells. Mechanistically, we revealed that DNA-PK inhibitor in combination with osimertinib resulted in prolonged DNA damage and cell cycle arrest. These findings shed new light on the mechanisms of osimertinib resistance in the aspect of DNA repair, and provide a rationale for targeting DNA-PK as a therapeutic strategy to overcome osimertinib-acquired resistance in NSCLC.Vagal circuit-α7 nicotinic acetylcholine receptor (α7nAChR, coded by Chrna7) signaling can modulate lung proinflammatory responses. Arginase 1 (ARG1) plays a crucial role in the resolution of lung inflammation. However, whether vagal-α7nAChR signaling can regulate lung inflammation and ARG1 expression during an influenza infection is elusive. Here, we found that lung and spleen IL-4+ cells and lung ARG1 expression were reduced; however, bronchoalveolar lavage (BAL) protein and leukocytes and lung inflammatory cytokines were increased in PR8 (A/Puerto Rico/8/1934, H1N1)-infected vagotomized mice when compared to the control. In PR8-infected α7nAChR-deficient mice, lung Arg1, Il10, and Socs3 expression and BAL Ly6C+CD206+ cells were reduced. PR8-infected Chrna7+/+ recipient mice reconstituted with Chrna7-/- bone marrow had a lower survival as compared to PR8-infected Chrna7+/+ recipient mice reconstituted with Chrna7+/+ bone marrow. Mechanistically, the activation of α7nAChR by its agonist GTS-21 could enhance IL-4-induced Arg1 expression, reduced Nos2, and TNF-α expression in PR8-infected bone marrow-derived macrophages (BMDM). Stimulation with IL-4 increased phosphorylation of STAT6 and activation of α7nAChR increased STAT6 binding with the ARG1 promoter and relieved IL-4-induced H3K27me3 methylation by increasing JMJD3 expression in PR8-infected BMDM. Inhibition of JMJD3 increased H3K27me3 methylation and abolished α7nAChR activation and IL-4 induced ARG1 expression. Activation of α7nAChR also reduced phosphorylation of AKT1 and contained FOXO1 in the nucleus. Knockdown of Foxo1a reduced α7nAChR activation and IL-4 induced Arg1 expression in PR8-infected BMDM. Therefore, vagal-α7nAChR signaling is a novel therapeutic target for treating lung inflammatory responses during an influenza infection.Ischemic brain injuries are frequent and difficult to detect reliably or early. We present the multi-modal data set containing cardiovascular (blood pressure, blood flow, electrocardiogram) and brain electrical activities to derive electroencephalogram (EEG) biomarkers of corticothalamic communication under normal, sedation, and hypoxic/ischemic conditions with ensuing recovery. We provide technical validation using EEGLAB. We also delineate the corresponding changes in the electrocardiogram (ECG)-derived heart rate variability (HRV) with the potential for future in-depth analyses of joint EEG-ECG dynamics. We review an open-source methodology to derive signatures of coupling between the ECoG and electrothalamogram (EThG) signals contained in the presented data set to better characterize the dynamics of thalamocortical communication during these clinically relevant states. The data set is presented in full band sampled at 2000 Hz, so the additional potential exists for insights from the full-band EEG and high-frequency oscillations under the bespoke experimental conditions. Future studies on the dataset may contribute to the development of new brain monitoring technologies, which will facilitate the prevention of neurological injuries.Aortic pulse wave velocity (aPWV) is a measure of aortic stiffness, which is an indicator of vascular aging and prognostic marker for cardiovascular complications. aPWV can be measured with various methods, but with different reference values depending on the technique used. Therefore, we decided to evaluate age-related values of aPWV, measured by Doppler echocardiography. Selleck AZD9291 We included 134 healthy adults (mean age 44.1 ± 13.2 years, 54% of females) divided into five groups based on age decades (D1 21-30 years, n = 29; D2 31-40 years, n = 24; D3 41-50 years, n = 34; D4 51-60 years, n = 25; and D5 61-70 years, n = 22). With the use of a cardiac probe and ECG tracing, ten Doppler waveforms were sequentially recorded, first in the distal aortic arch, and than in the left external iliac artery. Transit time was measured as a delay of the foot of the Doppler waveform in the distal, relative to the proximal location. The distance was measured over the body surface. aPWV was calculated as distance/transit time. Median aPWV in the whole group was 5.05 m/s [4.55-5.99] and did not differ according to sex (females, 5.28 m/s [4.50-6.1] vs. males, 4.95 m/s [4.59-5.77], p = 0.46). Mean aPWV values with 95% confidence intervals (95% CI) for each decade were as follows D1, 4.54 m/s (4.37-4.72), D2, 4.61 m/s (4.36-4.87), D3, 5.11 m/s (4.89-5.33), D4, 6.04 m/s (5.63-6.45), and D5, 6.77 m/s (6.35-7.19). We report age-related values of aPWV, in a healthy population, measured by Doppler echocardiography. This may be helpful in future research exploring the associations between aortic stiffness, cardiac function, and cardiovascular risk.