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Glioma is characterized by rapid cell proliferation, aggressive invasion, altered apoptosis and a poor prognosis. β-Sitosterol, a kind of phytosterol, has been shown to possess anticancer activities. Our current study aims to investigate the effects of β-sitosterol on gliomas and reveal the underlying mechanisms. Our results show that β-sitosterol effectively inhibits the growth of U87 cells by inhibiting proliferation and inducing G2/M phase arrest and apoptosis. In addition, β-sitosterol inhibits migration by downregulating markers of epithelial-mesenchymal transition (EMT). Mechanistically, network pharmacology and transcriptomics approaches illustrate that the EGFR/MAPK signaling pathway may be responsible for the inhibitory effect of β-sitosterol on glioma. Afterward, the results show that β-sitosterol effectively suppresses the EGFR/MAPK signaling pathway. Moreover, β-sitosterol significantly inhibits tumor growth in a U87 xenograft nude mouse model. β-Sitosterol inhibits U87 cell proliferation and migration and induces apoptosis and cell cycle arrest in U87 cells by blocking the EGFR/MAPK signaling pathway. These results suggest that β-sitosterol may be a promising therapeutic agent for the treatment of glioma.

The relationship between tissue-specific DNA methylation and cancer risk remains inadequately elucidated. Leveraging resources from the Genotype-Tissue Expression consortium, here we develop genetic models to predict DNA methylation at CpG sites across the genome for seven tissues and apply these models to genome-wide association study data of corresponding cancers, namely breast, colorectal, renal cell, lung, ovarian, prostate, and testicular germ cell cancers. At Bonferroni-corrected P < 0.05, we identify 4248 CpGs that are significantly associated with cancer risk, of which 95.4% (4052) are specific to a particular cancer type. Notably, 92 CpGs within 55 putative novel loci retain significant associations with cancer risk after conditioning on proximal signals identified by genome-wide association studies. Integrative multi-omics analyses reveal 854 CpG-gene-cancer trios, suggesting that DNA methylation at 309 distinct CpGs might influence cancer risk through regulating the expression of 205 unique cis-genes. These findings substantially advance our understanding of the interplay between genetics, epigenetics, and gene expression in cancer etiology. The relationship between tissue-specific DNA methylation and cancer risk remains to be elucidated. Here, the authors predict DNA methylation at CpG sites for seven cancer types and investigate how these influence cancer risk. [ABSTRACT FROM AUTHOR]

Background: Venous thromboembolism (VTE) is one of the most common and serious complications of cesarean section in parturients. Norepinephrine (NE) has been shown to activate coagulation. The aim of this study was to compare the effect of a fixed-rate prophylactic norepinephrine infusion and a fixed-rate prophylactic phenylephrine（PHE） infusion under spinal anesthesia for caesarean section on the prethrombotic response., Materials and Methods: Sixty-six women undergoing cesarean section under spinal anesthesia were randomly assigned to the NE group or PHE group, starting simultaneously with the administration of the subarachnoid solution, a "study drug" solution containing either NE or PHE was pumped intravenously at a constant rate of 15 ml/h until the end of the operation. Plasma coagulation factor VIII activity (FVIII: C), Fibrinogen, and D-dimer levels were measured in blood samples obtained on admission to the operating theatre and at the end of the procedure., Results: Compared with preoperative levels, there were no significant differences in postoperative fibrinogen and D-dimer levels in the NE group, except for a decrease in FVIII: C levels (P = 0.003). However, postoperative levels of FVIII: C (P = 0.009), fibrinogen (P = 0.035) and D-dimer (P = 0.025) were increased in the NE group compared with postoperative levels in the PHE group., Conclusions: NE does not affect the maternal prethrombotic response and can be safely used in cesarean sections. Compared with PHE infusion, NE infusion increased the level of coagulation molecules, suggesting that NE maybe more beneficial for women with high intraoperative bleeding requiring hemostasis., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Peripheral vasodilation causes a redistribution of body temperature from the core to the periphery, resulting in shivering and hypothermia. These are normal pathological and physiological processes during spinal anaesthesia. Two drugs, norepinephrine and phenylephrine, have peripheral vasoconstrictive effects. It is unclear the effects of norepinephrine and phenylephrine on shivering and hypothermia in patients undergoing caesarean section under spinal anaesthesia., Methods Analysis: 240 eligible parturients will be recruited for this randomised, double-blind, controlled trial and randomly assigned to either the norepinephrine or phenylephrine groups. The primary outcome will be the incidence of shivering while secondary outcomes will include the severity of shivering, rectal temperature, incidence of hypothermia and umbilical artery blood pH value., Ethics and Dissemination: The Institutional Ethics Committee of The Second People's Hospital of Hefei approved the trial protocol (ID: 2023-093). The results will be published in a compliant journal. The original data will be released in December 2029 on the ResMan original data-sharing platform of the China Clinical Trial Registry (http://www.medresman.org.cn)., Trial Registration Number: ChiCTR2300077164., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Emerging evidence points to the exceptional importance and value of m 7 G alteration in the diagnosis and prognosis of cancers. Nonetheless, a biomarker for precise screening of various cancer types has not yet been developed based on serum m 7 G-harboring miRNAs. Methods: A total of 20,702 serum samples, covering 12 cancer types and consisting of 7,768 cancer samples and 12,934 cancer-free samples were used in this study. A m 7 G target miRNA diagnostic signature (m 7 G-miRDS) was established through the least absolute shrinkage and selection operator (LASSO) analyses in a training dataset ( n = 10,351), and validated in a validation dataset ( n = 10,351). Results: The m 7 G-miRDS model, a 12 m 7 G-target-miRNAs signature, demonstrated high accuracy and was qualified for cancer detection. In the training and validation cohort, the area under the curve (AUC) reached 0.974 (95% CI 0.971-0.977) and 0.972 (95% CI 0.969-0.975), respectively. The m 7 G-miRDS showed superior sensitivity in each cancer type and had a satisfactory AUC in identifying bladder cancer, lung cancer and esophageal cancer. Additionally, the diagnostic performance of m 7 G-miRDS was not interfered by the gender, age and benign disease. Conclusion: Our results greatly extended the value of serum circulating miRNAs and m 7 G in cancer detection, and provided a new direction and strategy for the development of novel biomarkers with high accuracy, low cost and less invasiveness for mass cancer screening, such as ncRNA modification., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Xie, Bi, Ci, Li and Liu.)

Metal sulfides for hydrogen evolution catalysis typically suffer from unfavorable hydrogen desorption properties due to the strong interaction between the adsorbed H and the intensely electronegative sulfur. Here, we demonstrate a general strategy to improve the hydrogen evolution catalysis of metal sulfides by modulating the surface electron densities. The N modulated NiCo 2 S 4 nanowire arrays exhibit an overpotential of 41 mV at 10 mA cm -2 and a Tafel slope of 37 mV dec -1 , which are very close to the performance of the benchmark Pt/C in alkaline condition. X-ray photoelectron spectroscopy, synchrotron-based X-ray absorption spectroscopy, and density functional theory studies consistently confirm the surface electron densities of NiCo 2 S 4 have been effectively manipulated by N doping. The capability to modulate the electron densities of the catalytic sites could provide valuable insights for the rational design of highly efficient catalysts for hydrogen evolution and beyond.