Identification of molecular subtypes, risk signature, and immune landscape mediated by necroptosis-related genes in non-small cell lung cancer

BackgroundNon-small cell lung cancer (NSCLC) is a highly heterogeneous malignancy with an extremely high mortality rate. Necroptosis is a programmed cell death mode mediated by three major mediators, RIPK1, RIPK3, and MLKL, and has been shown to play a role in various cancers. To date, the effect of necroptosis on NSCLC remains unclear.MethodsIn The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we downloaded transcriptomes of lung adenocarcinoma (LUAD) patients and their corresponding clinicopathological parameters. We performed multi-omics analysis using consensus clustering based on the expression levels of 40 necroptosis-related genes. We constructed prognostic risk models and used the receiver operating characteristic (ROC) curves, nomograms, and survival analysis to evaluate prognostic models.ResultsWith the use of consensus clustering analysis, two distinct subtypes of necroptosis were identified based on different mRNA expression levels, and cluster B was found to have a better survival advantage. Correlation results showed that necroptosis was significantly linked with clinical features, overall survival (OS) rate, and immune infiltration. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis confirmed that these differential genes were valuable in various cellular and biological functions and were significantly enriched in various pathways such as the P53 signaling pathway and cell cycle. We further identified three genomic subtypes and found that gene cluster B patients had better prognostic value. Multivariate Cox analysis identified the 14 best prognostic genes for constructing prognostic risk models. The high-risk group was found to have a poor prognosis. The construction of nomograms and ROC curves showed stable validity in prognostic prediction. There were also significant differences in tumor immune microenvironment, tumor mutational burden (TMB), and drug sensitivity between the two risk groups. The results demonstrate that the 14 genes constructed in this prognostic risk model were used as tumor prognostic biomarkers to guide immunotherapy and chemotherapy. Finally, we used qRT-PCR to validate the genes involved in the signature.ConclusionThis study promotes our new understanding of necroptosis in the tumor microenvironment of NSCLC, mines prognostic biomarkers, and provides a potential value for guiding immunotherapy and chemotherapy

Study on the Modification of Silty Soil Sites Using Nanosilica and Methylsilicate

The special particle grading properties of silt lead to the strong water sensitivity and low soil strength of silt sites, many of which are severely damaged and urgently need to be repaired. This article takes the powder soil from a certain burial site area in Xizhu Village, Luoyang as the research object, which is improved by adding nanosilica and potassium methylsilicate. The modified soil is studied through mechanical and waterproof performance tests, and the mechanism of action of the modified material is analyzed through SEM and XRD. The experimental results show that the mechanical properties and waterproof properties of the composite modified soil were improved when the nanosilica content was 2% and the potassium methylsilicate content was 0.5%; the durability of the composite modified soil is improved, making this the optimum ratio. The mechanical properties and water resistance of the silty soil were significantly improved by adding the appropriate amount of nanosilica and potassium methylsilicate. Nanosilica can be evenly dispersed in the soil matrix, absorb a small amount of water to form a gel state, fill the pores in the silt aggregates, and improve soil compactness. In addition, nanosilica aggregates can attach to the surface of the soil particles and extend from the particle surface to the particle edge. By increasing the contact between soil particles and increasing the particle size, the mechanical properties of the modified soil are improved. When potassium methylsilicate solution is added to the soil, it reacts with water and carbon dioxide, decomposes into methylsilicate, and quickly generates a polymethylsiloxane film to cover the surface of soil particles, forming a waterproof film on the surface and thereby improving the waterproof performance of modified soil. Our research results can provide a reference for the restoration and protection of silty and silt-like sites. The next step is to apply the composite modified soil in engineering restoration through field tests in order to study the repairing ability of composite modified soil and its actual protective effects

Trends in the prevalence of hypertension according to severity and phenotype in Chinese adults over two decades (1991‐2015)

Abstract Until recently, few studies have reported the secular trend and associated factors of hypertension severities and phenotypes in China. In this study, the authors aimed to assess the trend in the prevalence of hypertension according to severity and phenotype in Chinese adults from 1991 to 2015 and to explore potential cardiometabolic factors. From the China Health and Nutrition Survey (CHNS), the authors included 164 682 records of adults (≥18 years). The prevalence of hypertension by severity (stage 1 and stage 2 hypertension) and by phenotype (isolated systolic hypertension [ISH], isolated diastolic hypertension [IDH], isolated diastolic hypertension [IDH, and systolic‐diastolic hypertension [SDH]), during 1991‐2015 was explored. The potential effects of demographic, socioeconomic, geographic, and cardiometabolic factors on hypertension severities and phenotypes were assessed by multivariable logistic regression. During 1991‐2015, the overall prevalence of hypertension increased dramatically from 15.7% to 23.3%. For stage 1 and stage 2 hypertension, the age‐standardized prevalence increased from 10.1% to 15.6% and from 5.5% to 7.4%, respectively. For ISH and SDH, the age‐standardized prevalence rates rose from 3.6% to 6.4% and from 6.9% to 10.4%, respectively. Advanced age and medium/high urbanization were positively associated factors, whereas females, higher educational attainments, and residing in Southern China were negatively associated factors. Additionally, general obesity, central obesity, diabetes, and elevated triglyceride levels were linked to ISH, IDH, and SDH. The present study documents an increasing trend in the prevalence of hypertension, including different severities and phenotypes, among Chinese adults over more than two decades. Efforts for the prevention and management of hypertension are in urgent need in China

The effect of noise exposure on insulin sensitivity in mice may be mediated by the JNK/IRS1 pathway

Abstract Background Epidemiological studies have suggested that noise exposure may increase the risk of type 2 diabetes mellitus (T2DM), and experimental studies have demonstrated that noise exposure can induce insulin resistance in rodents. The aim of the present study was to explore noise-induced processes underlying impaired insulin sensitivity in mice. Methods Male ICR mice were randomly divided into four groups: a control group without noise exposure and three noise groups exposed to white noise at a 95-dB sound pressure level for 4 h/day for 1, 10, or 20 days (N1D, N10D, and N20D, respectively). Systemic insulin sensitivity was evaluated at 1 day, 1 week, and 1 month post-noise exposure (1DPN, 1WPN, and 1MPN) via insulin tolerance tests (ITTs). Several insulin-related processes, including the phosphorylation of Akt, IRS1, and JNK in the animals’ skeletal muscles, were examined using standard immunoblots. Biomarkers of inflammation (circulating levels of TNF-α and IL-6) and oxidative stress (SOD and CAT activities and MDA levels in skeletal muscles) were measured via chemical analyses. Results The data obtained in this study showed the following: (1) The impairment of systemic insulin sensitivity was transient in the N1D group but prolonged in the N10D and N20D groups. (2) Noise exposure led to enhanced JNK phosphorylation and IRS1 serine phosphorylation as well as reduced Akt phosphorylation in skeletal muscles in response to exogenous insulin stimulation. (3) Plasma levels of TNF-α and IL-6, CAT activity, and MDA concentrations in skeletal muscles were elevated after 20 days of noise exposure. Conclusions Impaired insulin sensitivity in noise-exposed mice might be mediated by an enhancement of the JNK/IRS1 pathway. Inflammation and oxidative stress might contribute to insulin resistance after chronic noise exposure

Angiography-based hemodynamic features predict recurrent ischemic events after angioplasty and stenting of intracranial vertebrobasilar atherosclerotic stenosis.

Acknowledgements: The authors gratefully acknowledge the participants of the study and clinical staff of Jinling Hospital who contributed to patient recruitment and data collection.OBJECTIVES: To assess the predictive value of hemodynamic features for stroke relapse in patients with intracranial vertebrobasilar atherosclerotic stenosis treated with percutaneous transluminal angioplasty and stenting (PTAS) using quantitative digital subtraction angiography (q-DSA). METHODS: In this retrospective longitudinal study, patients with intracranial vertebrobasilar atherosclerotic stenosis and who underwent PTAS treatment between January 2012 and May 2020 were enrolled. The q-DSA assessment was performed before and after PTAS. ROIs 1-4 were placed along the vertebral artery, proximal and distal basilar artery, and posterior cerebral artery; ROIs 5-8 were in 5 mm and 10 mm proximal and distal to the lesion, respectively. Relative time to peak (rTTP) was defined as the difference in TTP between ROIs. Cox regression analyses were performed to determine risk factors for recurrent stroke. RESULTS: A total of 137 patients (mean age, 62 years ± 10 [standard deviation], 83.2% males) were included, and 26 (19.0%) patients had stroke relapse during follow-up (median time of 42.6 months [interquartile range, 19.7-60.7]). Preprocedural rTTP4-1 (adjusted hazard ratio (HR) = 2.270; 95% CI 1.371-3.758; p = 0.001) and preprocedural rTTP8-5 (adjusted HR = 0.240; 95% CI 0.088-0.658; p = 0.006) were independently associated with the recurrent stroke. These hemodynamic parameters provided an incremental prognostic value for stroke relapse (AUC, 0.817 [0.704-0.931]; the net reclassification index, 0.431 [0.057-0.625]; and the integrated discrimination index, 0.140 [0.035-0.292]). CONCLUSIONS: In patients with intracranial vertebrobasilar atherosclerosis treated with PTAS, preprocedural prolonged TTP of the target vessel and shortened trans-stenotic TTP difference were associated with stroke relapse. Q-DSA-defined hemodynamic parameters provided incremental predictive value over conventional parameters for stroke recurrence. CLINICAL RELEVANCE STATEMENT: Quantitative DSA analysis enables intuitive observation and semi-quantitative evaluation of peri-therapeutic cerebral blood flow. More importantly, quantitative DSA-defined hemodynamic parameters have the potential for risk stratification of patients with intracranial atherosclerotic stenosis. KEY POINTS: Semi-quantitative angiography-based parameters can reflect pre- and postprocedural subtle changes in blood flow in patients with intracranial atherosclerotic stenosis. Although angioplasty procedures can significantly improve blood flow status, patients with more restricted baseline blood flow still show a higher risk of stroke recurrence. Angiography-based hemodynamic features possess prognostic value and can serve as clinical markers to assess stroke risk of patients with intracranial atherosclerotic stenosis

Chronic noise-exposure exacerbates insulin resistance and promotes the manifestations of the type 2 diabetes in a high-fat diet mouse model.

Epidemiological studies have revealed that noise exposure was associated with an increased risk of type 2 diabetes mellitus (T2DM). However, the exact nature of that association remains to be elucidated. The present study is designed to examine the effects of chronic noise exposure on the development of T2DM in combination with a high-fat-diet (HFD) in mice. Here we show that chronic noise exposure at 85 dB SPL (4 h /day, below the safety limit for occupational noise exposure) exaggerated multiple metabolic abnormalities induced by HFD in C57BL/6J male mice, including worsened glucose intolerance, insulin resistance, fasting hyperglycemia and dyslipidemia. Furthermore, noise exposure exhibited a paradoxical impact on fat accumulation and circulating levels of free fatty acid, indicating a potential stimulating effect of noise on lipolysis. These results provide first in vivo supporting evidence for the causative role of noise exposure in diabetogenesis and pinpoint a noise-associated increase in blood free fatty acid levels as a possible mediator accelerating the effect of noise on the development of insulin resistance and T2DM