Heterogeneous associations of multiplexed environmental factors and multidimensional aging metrics.

Complicated associations between multiplexed environmental factors and aging are poorly understood. We manipulated aging using multidimensional metrics such as phenotypic age, brain age, and brain volumes in the UK Biobank. Weighted quantile sum regression was used to examine the relative individual contributions of multiplexed environmental factors to aging, and self-organizing maps (SOMs) were used to examine joint effects. Air pollution presented a relatively large contribution in most cases. We also found fair heterogeneities in which the same environmental factor contributed inconsistently to different aging metrics. Particulate matter contributed the most to variance in aging, while noise and green space showed considerable contribution to brain volumes. SOM identified five subpopulations with distinct environmental exposure patterns and the air pollution subpopulation had the worst aging status. This study reveals the heterogeneous associations of multiplexed environmental factors with multidimensional aging metrics and serves as a proof of concept when analyzing multifactors and multiple outcomes.

Using a Gene Network of Pyroptosis to Quantify the Responses to Immunotherapy and Prognosis for Neuroblastoma Patients.

Background: Pyroptosis, as an inflammatory form of cell death, is involved in many physiological and pathological processes. Neuroblastoma is the most common extra-cranial solid tumor in children. In this study, the relationship between pyroptosis and tumor microenvironment in neuroblastoma was systematically studied. Methods: We integrated four datasets of neuroblastomas. Through robust clustering of the mRNA expression profiles of 24 pyroptosis-related genes, a total of three pyroptosis patterns were identified. We then constructed a novel scoring method named as pyroscore to quantify the level of pyroptosis in neuroblastoma. Multi-omics data and single-cell RNA sequencing were used to accurately and comprehensively evaluate the effectiveness of pyroscore. Clinical data sets were used to evaluate the use of pyroscore to predict the responsiveness of immune checkpoint treatment. Results: High pyroscore was associated with good prognosis, immune activation, and increased response to checkpoint blockade immunotherapy. Multivariate Cox analysis revealed that the pyroscore was an independent prognostic biomarker and could increase the accuracy of clinical prediction models. Etoposide, a drug picked up by our analysis, could increase the sensitivity of neuroblastoma cells to pyroptosis. External verification using four cohorts of patients who had received immunotherapy showed that high pyroscore was significantly associated with immunotherapy treatment benefit. Conclusions: Taken together, this study revealed that pyroptosis-related gene network could quantify the response of neuroblastoma to immune checkpoint blockade therapy and prognosis, and it may be helpful for clinical practitioners to choose treatment strategies for neuroblastoma patients.

LncRNA PCGEM1 accelerates non-small cell lung cancer progression via sponging miR-433-3p to upregulate WTAP.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors all over the world. In recent years, long non-coding RNAs (lncRNAs) have been proven to participate in the development of different cancers, including NSCLC. PCGEM1 prostate-specific transcript (PCGEM1) is the lncRNA which is associated with the progression of several cancers. Nevertheless, in NSCLC, the specific functions of PCGEM1 are not yet clear. METHODS: The real-time quantitative polymerase chain reaction (qPCR) was utilized to test the expression of PCGEM1 in NSCLC cells. Functional experiments, including cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry analysis and transwell assays were utilized to estimate cell proliferation, migration, invasion and apoptosis. Meanwhile, RNA pull down assay and luciferase reporter assay were utilized to evaluate the correlation of miR-433-3p with PCGEM1 or WT1 associated protein (WTAP). RESULT: PCGEM1 was highly expressed in NSCLC cells, while miR-433-3p was lowly expressed in NSCLC cells. PCGEM1 silencing or miR-433-3p overexpression inhibited cell proliferation, migration and invasion but accelerated cell apoptosis. MiR-433-3p was proven be sponged by PCGEM1. Besides, WTAP was the target of miR-433-3p and it accelerated the progression of NSCLC. In the end, rescue experiments indicated that overexpression of WTAP or knockdown of miR-433-3p reversed the inhibited roles of silencing PCGEM1 on cell behavior. CONCLUSIONS: PCGEM1 accelerates NSCLC progression via sponging miR-433-3p to upregulate WTAP.

Electrochemically initiated oxidative amination of benzoxazoles using tetraalkylammonium halides as redox catalysts.

An electrochemically promoted coupling of benzoxazoles and amines has been developed, leading directly to the formation of 2-aminobenzoxazoles. The chemistry utilizes catalytic quantities of a tetraalkylammonium halide redox catalyst and is carried out under constant current conditions in a simple undivided cell. The use of excess chemical oxidant or large amounts of supporting electrolyte is avoided. This greatly simplifies the workup and isolation process and leads to a reduction in waste.