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Purpose: Lipid raft facilitated progression of NSCLC and atorvastatin could break cholesterol. The purpose of this study was to determine the potential mechanism of atorvastatin through lipid raft mediation in NSCLC.Methods: A549 cells were first grouped as NC, methyl-β-cyclodextrin (MβCD, lipid raft inhibitor, 5mM and 10mM), atorvastatin (0, 5mM, 10mM and 15mM) and MβCD (10mM) with atorvastatin (15mM). Later 10mM MβCD treated A549 cells were divided into three groups: NC, 3BDO (mTOR agonist) (60μM) and 3BDO (60μM) with atorvastatin (15mM) group. Thereafter, FLOT-2, SLP-2 expressions were assessed with RT-qPCR，mTOR proteins were measured by western blot and cell viability by CCK-8 method. Meanwhile, apoptosis was analyzed by flow cytometry. Moreover, lipid raft isolation was performed for acquiring Fas and CD59 and concentrations were detected by ELISA.Results: MβCD treatment significantly inhibited FLOT-2 and SLP-2 RNA expressions and cell viability of A549 cells but up-regulated apoptosis. Besides that, Fas protein level was promoted and CD59 was suppressed. Atorvastatin also repressed FLOT-2 and SLP-2 RNA levels. Meanwhile, atorvastatin downregulated cell viability and accelerated apoptosis. Moreover, Fas was increased and CD59 was inhibited by atorvastatin and MβCD enhanced functions of atorvastatin. MβCD inhibited mTOR RNA expression in A549 cells was increased by 3BDO but atorvastatin restored 3BDO caused up-regulation of mTOR. Furthermore, up regulated cell viability of A549 by 3BDO was declined with atorvastatin and decreased apoptosis by 3BDO was reversed through atorvastatin. Fas suppressed by 3BDO and promotion of CD59 were also resumed by atorvastatin.Conclusion: Atorvastatin suppressed FLOT-2 and SLP-2 and mediated recruitments of Fas and CD59 with suppressing cell viability and facilitating apoptosis of A549 cells via mTOR signaling pathway.

Since the outbreak of the COVID-19 pandemic, there has been a noticeable shift towards telecommuting and online entertainment, which has created novel prospects for future employment and recreation. Furthermore, with the continual advancement of artificial intelligence (AI), it is expected that a significant number of models can be easily generated in the near future. In this context, the realization of a meta-universe that offers extraordinary immersive experiences may become a tangible possibility. This paper aims to investigate whether virtual reality (VR) games are more suitable for “simulating reality” or “deviating from reality” by focusing on VR Escape Room, a typical example of an immersive experience. Through multiple rounds of experiments and analysis, this study will compare the effects of “skeuomorphism” and “beyond skeuomorphism” in the game.

BackgroundIn the first-line treatment of advanced non-small cell lung cancer (NSCLC), for those patients with negative PD-L1 expression, which treatment strategy has the better efficacy and safety between chemotherapy combined with antiangiogenic and with immune checkpoint inhibitors (ICIs) is still unclear due to the absence of head-to-head clinical trials. This study aims to answer the question by performing a systematic review and network meta-analysis (NMA).MethodsElectronic databases (PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov) were systematically searched accordingly to extract eligible studies from inception to October 2022, as well as the abstracts from the most recent main oncology congresses (American Association for Cancer Research (AACR), American Society of Clinical Oncology (ASCO), World Conference on Lung Cancer (WCLC), and European Society for Medical Oncology (ESMO)). Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) of grades 3 to 5 were independently extracted and collected by two reviewers based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. We used Cochrane’s risk of bias tool for randomized controlled trials through RevMan 5.3 to ascertain the quality of the included studies. NMA with a Bayesian random-effects model was performed by R (version 4.0.4).ResultsAccording to the ranking list from OS-NMA, pembrolizumab combined with chemotherapy has the most effective ranking first (surface under the cumulative ranking (SUCRA) = 0.809844) (pooled HR = 0.65 [0.51–0.83]). On PFS, the triple combination of nivolumab/bevacizumab/chemotherapy ranks first (NMA estimate: HR = 0.35 [0.28–0.43]). On safety, in combination with chemotherapy, sintilimab has minimal toxicity, followed by pembrolizumab+chemo.ConclusionsIn advanced NSCLC patients with negative PD-L1 expression, pembrolizumab+chemo ranks first in the efficacy of OS and does not apparently increase the incidence of any grade ≥ 3 AE as compared with chemo alone. On PFS, pembrolizumab also has advantages, but for patients with squamous cell carcinoma, camrelizumab+chemo seems to be a better choice.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021231441.

Additional file 1.

Early diagnosis can significantly enhance the 5-year survival rates of lung cancer patients, while a large majority of lung cancer patients have advanced disease at the time of diagnosis. We tested our hypothesis that increased autofluorescence (AF) of skin may become a new diagnostic biomarker for lung cancer, which has generated the following findings: First, the AF intensity of untreated lung cancer group in certain regions of skin is significantly higher than that of the healthy group and the group of benign lung diseases; second, the percentage of the people with 3 or more regions with increased green AF is 11.1%, 47.06%, and 71.80% for the healthy group, the group of benign lung disease patients, and the group of untreated lung cancer patients, respectively; and third, the AF intensity at several regions of the skin of untreated lung cancer patients is significantly lower than that of acute ischemic stroke patients. Moreover, the AF increases in lung cancer may result from oxidative stress-induced increases in the AF of keratins. Collectively, our study has indicated that lung cancer patients have significant AF increases in certain regions of their skin, which may become a novel diagnostic biomarker for the illness. This approach could be used to diagnose both lung cancer and acute ischemic stroke, since we may differentiate these diseases based on the differences in both the patterns of their AF at multiple regions and their clinical symptoms. This non-invasive diagnostic approach may significantly increase the rate of early diagnosis of lung cancer.