Ferroptosis-related gene HIC1 in the prediction of the prognosis and immunotherapeutic efficacy with immunological activity

BackgroundHypermethylated in Cancer 1 (HIC1) was originally confirmed as a tumor suppressor and has been found to be hypermethylated in human cancers. Although growing evidence has supported the critical roles of HIC1 in cancer initiation and development, its roles in tumor immune microenvironment and immunotherapy are still unclear, and no comprehensive pan-cancer analysis of HIC1 has been conducted.MethodsHIC1 expression in pan-cancer, and differential HIC1 expression between tumor and normal samples were investigated. Immunohistochemistry (IHC) was employed to validate HIC1 expression in different cancers by our clinical cohorts, including lung cancer, sarcoma (SARC), breast cancer, and kidney renal clear cell carcinoma (KIRC). The prognostic value of HIC1 was illustrated by Kaplan-Meier curves and univariate Cox analysis, followed by the genetic alteration analysis of HIC1 in pan-cancer. Gene Set Enrichment Analysis (GSEA) was conducted to illustrate the signaling pathways and biological functions of HIC1. The correlations between HIC1 and tumor mutation burden (TMB), microsatellite instability (MSI), and the immunotherapy efficacy of PD-1/PD-L1 inhibitors were analyzed by Spearman correlation analysis. Drug sensitivity analysis of HIC1 was performed by extracting data from the CellMiner™ database.ResultsHIC1 expression was abnormally expressed in most cancers, and remarkable associations between HIC1 expression and prognostic outcomes of patients in pan-cancer were detected. HIC1 was significantly correlated with T cells, macrophages, and mast cell infiltration in different cancers. Moreover, GSEA revealed that HIC1 was significantly involved in immune-related biological functions and signaling pathways. There was a close relationship of HIC1 with TMB and MSI in different cancers. Furthermore, the most exciting finding was that HIC1 expression was significantly correlated with the response to PD-1/PD-L1 inhibitors in cancer treatment. We also found that HIC1 was significantly correlated with the sensitivity of several anti-cancer drugs, such as axitinib, batracylin, and nelarabine. Finally, our clinical cohorts further validated the expression pattern of HIC1 in cancers.ConclusionsOur investigation provided an integrative understanding of the clinicopathological significance and functional roles of HIC1 in pan-cancer. Our findings suggested that HIC1 can function as a potential biomarker for predicting the prognosis, immunotherapy efficacy, and drug sensitivity with immunological activity in cancers

Robust A-Optimal Subsampling for Massive Data Robust Linear Regression

This thesis is concerned with massive data analysis via robust A-optimally efficient non-uniform subsampling. Motivated by the fact that massive data often contain outliers and that uniform sampling is not efficient, we give numerous sampling distributions by minimizing the sum of the component variances of the subsampling estimate. And these sampling distributions are robust against outliers. Massive data pose two computational bottlenecks. Namely, data exceed a computer’s storage space, and computation requires too long waiting time. The two bottle necks can be simultaneously addressed by selecting a subsample as a surrogate for the full sample and completing the data analysis. We develop our theory in a typical setting for robust linear regression in which the estimating functions are not differentiable. For an arbitrary sampling distribution, we establish consistency for the subsampling estimate for both fixed and growing dimension( as high dimensionality is common in massive data). We prove asymptotic normality for fixed dimension. We discuss the A-optimal scoring method for fast computing. We conduct large simulations to evaluate the numerical performance of our proposed A-optimal sampling distribution. Real data applications are also performed

Weight Discrimination Experienced Prior to Enrolling in a Behavioral Obesity Intervention is Associated with Treatment Response among Black and White Adults in the Southeastern U.S.

Background: The current study evaluated the associations between history of weight discrimination and race on pre-treatment depressive symptoms, treatment session attendance, and weight loss among Black and White adults enrolled in a 16-week obesity intervention. Methods: Participants (N = 271; mean BMI = 35.7 kg/m2; 59% Black; 92% women) reported prior experiences of weight discrimination and completed the Center for Epidemiological Studies Depression (CES-D) Scale at baseline. Weekly attendance at group sessions was recorded, and weight was measured at baseline and post-treatment. All models adjusted for baseline BMI, age, and sex. Results: Participants with a history of weight discrimination scored 2.4 points higher on the CES-D (B = 2.432, p = .012) and lost 2% less weight relative to those without weight discrimination (B = 0.023, p = .002). Race modified the association between weight discrimination and treatment session attendance, such that Black individuals attended fewer sessions if they had prior experience of weight discrimination, but prior weight discrimination was not significantly associated with treatment attendance among White individuals. Conclusion: Weight discrimination is associated with pre-treatment depressive symptoms and may hinder weight loss regardless of race. Black individuals may attend fewer weight loss treatment sessions if they have prior experience of weight discrimination

Predicting program attendance and weight loss in obesity interventions: Do triggering events help?

Medical events that “trigger” motivation to lose weight may improve treatment outcomes compared to non-medical or no triggering events. However, previous findings include only long-term successful participants, not those initiating treatment. The current study compared those with medical triggering events or non-medical triggering events to no triggering events on attendance and weight loss during a weight management program. Medical-triggering-event participants lost 1.8 percent less weight (p = 0.03) than no-triggering-event participants. Non-medical-triggering-event participants attended 1.45 more sessions (p = 0.04) and were 1.83 times more likely to complete the program (p = 0.03) than no-triggering-event participants. These findings fail to support the benefit of medical triggering events when beginning treatment for obesity

Effects of Dietary Ferulic Acid Supplementation on Hepatic Injuries in Tianfu Broilers Challenged with Lipopolysaccharide

Lipopolysaccharide (LPS) is an endotoxin that can cause an imbalance between the oxidation and antioxidant defense systems and then induces hepatic damages. Ferulic acid (FA) has multiple biological functions including antibacterial and antioxidant activities; however, the effect of FA on lipopolysaccharide-induced hepatic injury remains unknown. The purpose of this study was to investigate the mechanism of action of dietary Ferulic acid against Lipopolysaccharide-induced hepatic injuries in Tianfu broiler chickens. The results showed that supplementation of FA in daily feed increased body weight (BW) and decreased the feed conversion ratio (FCR) in LPS treatment broilers significantly (p < 0.05). Additionally, supplement of FA alleviated histological changes and apoptosis of hepatocytes in LPS treatment broilers. Supplement of FA significantly decreases the activities of ROS. Interestingly, the levels of antioxidant parameters including total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC), and glutathione (GSH) in LPS group were significantly increased by the FA supplementation (p < 0.05). Nevertheless, administration of LPS to broilers decreased the expressions of Nrf2, NQO1, SOD, GSH-Px, CAT and Bcl-2, whereas it increased the expressions of Bax and Caspase-3 (p < 0.05). Moreover, the expressions of Nrf2, NQO1, SOD, CAT, Bcl-2 were significantly upregulated and Caspase-3 were significantly downregulated in the FL group when compared to LPS group (p < 0.05). In conclusion, supplementation of FA in daily feed improves growth performance and alleviates LPS-induced oxidative stress, histopathologic changes, and apoptosis of hepatocytes in Tianfu broilers