Waist-to-Height Ratio Is a Stronger Mediator in the Association between DASH Diet and Hypertension: Potential Micro/Macro Nutrients Intake Pathways.

Several studies have demonstrated that adhering to the Dietary Approaches to Stop Hypertension (DASH) diet may result in decreased blood pressure levels and hypertension risk. This may be an effect of a reduction in central obesity. In the current study, we explored the mediation role of multiple anthropometric measurements in association with DASH score and hypertension risk, and we investigated potential common micro/macro nutrients that react with the obesity-reduction mechanism. Our study used data from the National Health and Nutrition Examination Survey (NHANES). Important demographic variables, such as gender, race, age, marital status, education attainment, poverty income ratio, and lifestyle habits such as smoking, alcohol drinking, and physical activity were collected. Various anthropometric measurements, including weight, waist circumference, body mass index (BMI), and waist-to-height ratio (WHtR) were also obtained from the official website. The nutrient intake of 8224 adults was quantified through a combination of interviews and laboratory tests. We conducted stepwise regression to filter the most important anthropometric measurements and performed a multiple mediation analysis to test whether the selected anthropometric measurements had mediation effects on the total effect of the DASH diet on hypertension. Random forest models were conducted to identify nutrient subsets associated with the DASH score and anthropometric measurements. Finally, associations between common nutrients and DASH score, anthropometric measurements, and risk of hypertension were respectively evaluated by a logistic regression model adjusting for possible confounders. Our study revealed that BMI and WHtR acted as full mediators between DASH score and high blood pressure levels. Together, they accounted for more than 45% of the variation in hypertension. Interestingly, WHtR was found to be the strongest mediator, explaining approximate 80% of the mediating effect. Furthermore, we identified a group of three commonly consumed nutrients (sodium, potassium, and octadecatrienoic acid) that had opposing effects on DASH score and anthropometric measurements. These nutrients were also found to be associated with hypertension in the same way as BMI and WHtR in univariate regression models. The most important among these nutrients was sodium, which was negatively correlated with the DASH score (ß = -0.53, 95% CI = -0.56~-0.50, p < 0.001) and had a positive association with BMI (ß = 0.04, 95% CI = 0.01~0.07, p = 0.02), WHtR (ß = 0.06, 95% CI = 0.03~0.09, p < 0.001), and hypertension (OR = 1.09, 95% CI = 1.01~1.19, p = 0.037). Our investigation revealed that the WHtR exerts a greater mediating effect than BMI on the correlation between the DASH diet and hypertension. Notably, we identified a plausible nutrient intake pathway involving sodium, potassium, and octadecatrienoic acid. Our findings suggested that lifestyle modifications that emphasize the reduction of central obesity and the attainment of a well-balanced micro/macro nutrient profile, such as the DASH diet, could potentially be efficacious in managing hypertension.

Statistical inference for a relaxation index of stochastic dominance under density ratio model.

Stochastic dominance is usually used to rank random variables by comparing their distributions, so it is widely applied in economics and finance. In actual applications, complete stochastic dominance is too demanding to meet, so relaxation indexes of stochastic dominance have attracted more attention. The π index, the biggest gap between two distributions, can be a measure of the degree of deviation from complete dominance. The traditional estimation method is to use the empirical distribution functions to estimate it. Considering the populations under comparison are generally of the same nature, we can link the populations through density ratio model under certain condition. Based on this model, we propose a new estimator and establish its statistical inference theory. Simulation results show that the proposed estimator substantially improves estimation efficiency and power of the tests and coverage probabilities satisfactorily match the confidence levels of the tests, which show the superiority of the proposed estimator. Finally we apply our method to a real example of the Chinese household incomes.

Effects of natural 24-epibrassinolide on inducing apoptosis and restricting metabolism in hepatocarcinoma cells.

BACKGROUND: 24-epibrassinolide (EBR) is a ubiquitous steroidal phytohormone with anticancer activity. Yet the cytotoxic effects and mechanism of EBR on hepatocarcinoma (HCC) cells remain elusive. METHODS: Cell counting kit-8 (CCK-8) assay was performed to evaluate cell viability. Real-time cell analysis (RTCA) technology and colony formation assays were used to evaluate cell proliferation. The apoptosis ratio was measured by flow cytometry. Seahorse XFe96 was applied to detect the effects of EBR on cellular bioenergetics. RNA-seq analysis was performed to investigate differences in gene expression profiles. Western blot and qRT-PCR were used to detect the changes in target molecules. RESULTS: EBR induced apoptosis and caused energy restriction in HCC, both of which were related to insulin-like growth factor-binding protein 1 (IGFBP1). EBR rapidly and massively induced IGBFP1, part of which was transcribed by activating transcription factor-4 (ATF4). The accumulation of secreted and cellular IGFBP1 had different important roles, in which secreted IGFBP1 affected cell energy metabolism by inhibiting the phosphorylation of Akt, while intracellular IGFBP1 acted as a pro-survival factor to resist apoptosis. Interestingly, the extracellular signal-regulated kinase (ERK) inhibitor SCH772984 and MAP/ERK kinase (MEK) inhibitor PD98059 not only attenuated the EBR-induced IGFBP1 expression but also the basal expression of IGFBP1. Thus, the treatment of cells with these inhibitors further enhances the cytotoxicity of EBR. CONCLUSION: Taken together, these findings suggested that EBR can be considered as a potential therapeutic compound for HCC due to its pro-apoptosis, restriction of energy metabolism, and other anti-cancer properties. Meanwhile, the high expression of IGFBP1 induced by EBR in HCC contributes to our understanding of the role of IGFBP1 in drug resistance.

Testing exponentiality based on the extropy of record values.

In this paper, we first present a characterization of exponential distribution based on the extropy of record values and next introduce a goodness-of-fit test for exponentiality. Monte Carlo simulation is used to compute the critical values of our proposed test for different sample sizes and significance levels. To show the advantage of the proposed test, we adopt 58 competitor tests and compute the adjusted power against different alternatives with distinct types of hazard function. The power results show that our proposed test has superior adjusted power if the alternatives have increasing failure rates or bathtub decreasing-increasing failure rates, especially when the sample size is small. Finally, three real examples are used to illustrate the applicability and robustness of our proposed test by monitoring the p-values of the tests.

6-methoxydihydroavicine, the alkaloid extracted from Macleaya cordata (Willd.) R. Br. (Papaveraceae), triggers RIPK1/Caspase-dependent cell death in pancreatic cancer cells through the disruption of oxaloacetic acid metabolism and accumulation of reactive oxygen species.

BACKGROUND: Many extracts and purified alkaloids of M. cordata (Papaveraceae family) have been reported to display promising anti-tumor effects by inhibiting cancer cell growth and inducing apoptosis in many cancer types. However, no evidence currently exists for anti-pancreatic cancer activity of alkaloids extracted from M. cordata, including a novel alkaloid named 6­methoxy dihydrosphingosine (6-Methoxydihydroavicine, 6-ME) derived from M. cordata fruits. PURPOSE: The aim of this study was to investigate the anti-tumor effects of 6-ME on PC cells and the underlying mechanism. METHODS: CCK-8, RTCA, and colony-formation assays were used to analyze PC cell growth. Cell death ratios, changes in MMP and ROS levels were measured by flow cytometry within corresponding detection kits. A Seahorse XFe96 was employed to examine the effects of 6-ME on cellular bioenergetics. Western blot and q-RT-PCR were conducted to detect changes in target molecules. RESULTS: 6-ME effectively reduced the growth of PC cells and promoted PCD by activating RIPK1, caspases, and GSDME. Specifically, 6-ME treatment caused a disruption of OAA metabolism and increased ROS production, thereby affecting mitochondrial homeostasis and reducing aerobic glycolysis. These responses resulted in mitophagy and RIPK1-mediated cell death. CONCLUSION: 6-ME exhibited specific anti-tumor effects through interrupting OAA metabolic homeostasis to trigger ROS/RIPK1-dependent cell death and mitochondrial dysfunction, suggesting that 6-ME could be considered as a highly promising compound for PC intervention.

A Novel Mechanism of Cannabidiol in Suppressing Hepatocellular Carcinoma by Inducing GSDME Dependent Pyroptosis.

Cannabidiol (CBD), a phytochemical derived from Cannabis sativa L., has been demonstrated to exhibit promising anti-tumor properties in multiple cancer types. However, the effects of CBD on hepatocellular carcinoma (HCC) cells remain unknown. We have shown that CBD effectively suppresses HCC cell growth in vivo and in vitro, and induced HCC cell pyroptosis in a caspase-3/GSDME-dependent manner. We further demonstrated that accumulation of integrative stress response (ISR) and mitochondrial stress may contribute to the initiation of pyroptotic signaling by CBD. Simultaneously, CBD can repress aerobic glycolysis through modulation of the ATF4-IGFBP1-Akt axis, due to the depletion of ATP and crucial intermediate metabolites. Collectively, these observations indicate that CBD could be considered as a potential compound for HCC therapy.

An immunogenomic signature for molecular classification in hepatocellular carcinoma.

Immunity plays an important role in tumor development. In this study, we aimed to investigate molecular classification and its prognostic value in hepatocellular carcinoma (HCC) based on immune signature. Gene set enrichment analysis (GSEA) was used to calculate scores of immune pathways for HCC and hierarchical clustering in two databases (The Cancer Genome Atlas [TCGA], Liver Cancer-RIKEN, JP [LIRI_JP]). The scores of the immune microenvironment and the proportions of 22 immune cells were also calculated. Single-sample GSEA (ssGSEA) was used to screen survival prognosis-related immune pathways and calculate the hazard radio of differentially expressed immune-related genes (IRGs), which were validated in clinical samples and multiple datasets. Based on the immune characteristics, we identified three HCC subtypes, namely immunity high (Immunity_H), immunity medium (Immunity_M), and immunity low (Immunity_L), and confirmed that the classification was reliable and predictable. Immunity_H with a higher immune and stromal score indicated better survival rate. Cox regression analysis showed that IL18RAP and IL7R were the protective genes. Immune risk score was the independent risk factor of overall survival in HCC patients. These results indicated that immunogenomic classification could distinguish HCC patients with different immune status, which could impact the prognosis of the patients with HCC.

Investigation on vitamin D knowledge, attitude and practice of university students in Nanjing, China.

OBJECTIVE: To investigate university students' knowledge, attitudes and practice (KAP) regarding vitamin D. DESIGN: The students were requested to answer a questionnaire related to vitamin D and sun exposure. The consumption frequency of foods rich in vitamin D was assessed. Additionally, the intake of vitamin D-containing supplements was recorded. SETTING: A medical university in Nanjing, China. SUBJECTS: Five hundred and fifteen medical students were included. RESULTS: The highest rate of correct responses for the quiz was 68·0 %, while the lowest was 9·6 %. Most students lacked sun exposure because they did not want to get tanned; 82·7 % of students used some sun protection and sunscreen use was more popular in the female group. The consumption frequency of foods rich in vitamin D was low and 5·6 % of the students used vitamin D supplements. The students' knowledge on vitamin D was derived mainly from the media and health professionals. Most of the students were interested to know more about vitamin D. CONCLUSIONS: The present study suggested that medical students had little knowledge and unfavourable behaviours. They should get more health education through the media and health professionals. It is advisable to increase their consumption of foods rich in vitamin D.

Synthesis of Homoleptic Neopentoxide and Hydrido-Neopentoxide Trirhenium(III) Clusters.

The purpose of this study was to synthesize Re(3)(&mgr;-OCH(2)CMe(3))(3)(OCH(2)CMe(3))(6) and to determine if it could serve as a source of Re(3)(&mgr;-OCH(2)CMe(3))(3)(H)(OCH(2)CMe(3))(5) by analogy to Re(3)(&mgr;-O-i-Pr)(3)(O-i-Pr)(6), a previously reported cluster that exists in solution as an equilibrium mixture with Re(3)(&mgr;-O-i-Pr)(3)(H)(O-i-Pr)(5) and acetone. The halide Re(3)(&mgr;-Cl)(3)Cl(6)(THF)(3) reacts at room temperature in THF with 9 equiv of NaOCH(2)CMe(3) to give Re(3)(&mgr;-OCH(2)CMe(3))(3)(OCH(2)CMe(3))(6). An X-ray crystallographic study shows that the core of the homoleptic cluster has virtual D(3h) symmetry, which is consistent with solution NMR data. In refluxing THF, Re(3)(&mgr;-Cl)(3)Cl(6)(THF)(3) reacts with 10 equiv of NaOCH(2)CMe(3) to give [Na(THF)(2)][Re(3)(&mgr;-OCH(2)CMe(3))(3)(H)(OCH(2)CMe(3))(6)]. The same anionic hydride cluster is also produced when Re(3)(&mgr;-OCH(2)CMe(3))(3)(OCH(2)CMe(3))(6) reacts with excess NaOCH(2)CMe(3) in hot THF. Spectroscopic and X-ray crystallographic data show that [Re(3)(&mgr;-OCH(2)CMe(3))(3)(H)(OCH(2)CMe(3))(6)](-) has virtual C(s)() core symmetry with a terminal hydride and two terminal alkoxides located at the unique rhenium atom. The hydride and one of the alkoxides have a trans-H-Re-OR arrangement, and in the solid state structure the terminal alkoxide ligands at the unique rhenium atom interact with [Na(THF)(2)](+). It is proposed [Na(THF)(2)][Re(3)(&mgr;-OCH(2)CMe(3))(3)(H)(OCH(2)CMe(3))(6)] forms when Re(3)(&mgr;-OCH(2)CMe(3))(3)(H)(OCH(2)CMe(3))(5) or its pivaldehyde adduct, which is generated by neopentoxide beta-hydrogen elimination from Re(3)(&mgr;-OCH(2)CMe(3))(3)(OCH(2)CMe(3))(6), is trapped by NaOCH(2)CMe(3). Crystal data are as follows. C(45)H(99)O(9)Re(3) at -50 degrees C: Pbca (orthorhombic); a = 19.570(2), b = 28.192(3), c = 21.203(3) Å; Z = 8. Na(+)[C(45)H(100)O(9)Re(3)](-).2C(4)H(8)O at -50 degrees C: P&onemacr; (triclinic); a = 13.040(2), b = 14.716(2), c = 19.653(4) Å; alpha = 92.38(1), beta = 92.30(1), gamma = 113.42(1) degrees; Z = 2.