Integrative analysis of senescence-related genes identifies robust prognostic clusters with distinct features in hepatocellular carcinoma.

INTRODUCTION: Senescence refers to a state of permanent cell growth arrest and is regarded as a tumor suppressive mechanism, whereas accumulative evidence demonstrate that senescent cells play an adverse role during cancer progression. The scarcity of specific and reliable markers reflecting senescence level in cancer impede our understanding of this biological basis. OBJECTIVES: Senescence-related genes (SRGs) were collected for integrative analysis to reveal the role of senescence in hepatocellular carcinoma (HCC). METHODS: Consensus clustering was used to subtype HCC based on SRGs. Several computational methods, including single sample gene set enrichment analysis (ssGSEA), fuzzy c-means algorithm, were performed. Data of drug sensitivities were utilized to screen potential therapeutic agents for different senescence patients. Additionally, we developed a method called signature-related gene analysis (SRGA) for identification of markers relevant to phenotype of interest. Experimental strategies consisting quantitative real-time PCR (qRT-PCR), ß-galactosidase assay, western blot, and tumor-T cell co-culture system were used to validate the findings in vitro. RESULTS: We identified three robust prognostic clusters of HCC patients with distinct survival outcome, mutational landscape, and immune features. We further extracted signature genes of senescence clusters to construct the senescence scoring system and profile senescence level in HCC at bulk and single-cell resolution. Senescence-induced stemness reprogramming was confirmed both in silico and in vitro. HCC patients with high senescence were immune suppressed and sensitive to Tozasertib and other drugs. We suggested that MAFG, PLIN3, and 4 other genes were pertinent to HCC senescence, and MAFG potentially mediated immune suppression, senescence, and stemness. CONCLUSION: Our findings provide insights into the role of SRGs in patients stratification and precision medicine.

Morphology, crystal structure and adsorption performance of hydrothermally synthesized titania and titanate nanostructures.

Titania (TiO2) and sodium titanate nanostructures with controllable phases and morphologies were synthesized by a hydrothermal method with titanium disulfide (TiS2) as the starting material. Sodium titanate nanobelts could be synthesized under a relatively low alkaline concentration (1 mol L(-1) NaOH) and short duration (6 h). At 3 mol L(-1) HCl, rutile TiO2 nanorods were synthesized. Anatase TiO2 nanoparticles were obtained at pH values ranging between 2 and 13. FTIR analysis confirmed the phase change as the pH of the reacting medium increased from highly acidic to highly alkaline. The adsorption of Methylene Blue (MB) on the as-synthesized sodium titanate nanobelts fitted well with the Langmuir monolayer model, with an adsorption capacity as high as 312.5 mg g(-1). The kinetics of MB adsorption was found to be a pseudo-second-order kinetic model. In brief, this study demonstrates a simple method to control the phase and morphology of titanium-based oxides. Excellent performance has been shown in the MB adsorption test by the sodium titanate nanostructures.

The influence of oblique viewing on axial and peripheral refraction for emmetropes and myopes.

Refraction may be affected by the forces of lids and extraocular muscles when eye direction and head direction are not aligned (oblique viewing) which might potentially influence past findings on peripheral refraction of the eye. We investigated the effect of oblique viewing on axial and peripheral refraction. In a first experiment, cycloplegic axial refractions were determined when subjects' heads were positioned to look straight-ahead through an open-view autorefractor and when the heads were rotated to the right or left by 30 degrees with compensatory eye rotation (oblique viewing). Subjects were 16 young emmetropes (18-35 years), 22 young myopes (19-36 years) and 15 old emmetropes (45-60 years). In a second experiment, cycloplegic peripheral refraction measurements were taken out to +/-34 degrees horizontally from fixation while the subjects rotated their heads to match the peripheral refraction angles (eye in primary position with respect to the head) or the eyes were rotated with respect to the head (oblique viewing). Subjects were 10 emmetropes and 10 myopes. We did not find any significant changes in axial or peripheral refraction upon oblique viewing for any of the subject groups. In general for the range of horizontal angles used, it is not critical whether or not the eye is rotated with respect to the head during axial or peripheral refraction.