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GBM is one of the most malignant tumor in central nervous system. The resistance to temozolomide (TMZ) is inevitable in GBM and the characterization of TMZ resistance seriously hinders clinical treatment. It is worthwhile exploring the underlying mechanism of aggressive invasion and TMZ resistance in GBM treatment. Bioinformatic analysis was used to analyze the association between RND1 and a series of EMTrelated genes. Colony formation assay and cell viability assay were used to assess the growth of U87 and U251 cells. The cell invasion status was evaluated based on transwell and wound-healing assays. Western blot was used to detect the protein expression in GBM cells. Treatment targeted RND1 combined with TMZ therapy was conducted in nude mice to evaluate the potential application of RND1 as a clinical target for GBM. The overexpression of RND1 suppressed the progression and migration of U87 and U251 cells. RND1 knockdown facilitated the growth and invasion of GBM cells. RND1 regulated the EMT of GBM cells via inhibiting the phosphorylation of AKT and GSK3-ß. The promoted effects of RND1 on TMZ sensitivity was identified both in vitro and in vivo. This research demonstrated that the overexpression of RND1 suppressed the migration and EMT status by downregulating AKT/GSK3-ß pathway in GBM. RND1 enhanced the TMZ sensitivity of GBM cells both in vitro and in vivo. Our findings may contribute to the targeted therapy for GBM and the understanding of mechanisms of TMZ resistance in GBM. [ABSTRACT FROM AUTHOR]

This study aimed to explore the changes in blood lipids and nutritional indexes in acute myeloid leukemia patients before and after enteral nutritional support combined with induction therapy and assess the influences of blood lipids on prognosis. The clinical data from 210 patients with initial treatment results were retrospectively analyzed. Total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol are lower in acute myeloid leukemia patients compared to normal controls, while triglyceride levels are higher. Total cholesterol and low-density lipoprotein cholesterol levels in M2 were elevated compared to M4 and M5, and the triglyceride level in M1 was higher than M2 and M4 before therapy. High-density lipoprotein cholesterol in M2 was higher than in M1 and M5, and low-density lipoprotein cholesterol in M1 was higher than in M5. After enteral nutritional support combined with induction therapy, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and nutritional status were increased. Patients with total cholesterol ≥4.8 mmol/L after therapy had a longer overall survival. The dyslipidemia and nutritional status in newly diagnosed acute myeloid leukemia patients can be partially reversed after enteral nutritional support combined with the first induction therapy, and the rebound in total cholesterol level may reflect the longer overall survival in acute myeloid leukemia patients. [ABSTRACT FROM AUTHOR]

Objective • This study aimed to evaluate the expression of genes involved in cholesterol metabolism and establish their association with oxidative stress (OS). Methods • We employed an in vitro experimental design and cells were divided into six groups: C (control), CH (HepG2 + H2O2), CHN (HepG2 + H2O2 + NAC), F (FFAtreated HepG2), FH (FFA-treated HepG2 + H2O2), and FHN (FFA-treated HepG2 + H2O2 + NAC). Cell viability was assessed using the MTT assay, while successful FFA model establishment was confirmed via Oil Red staining and absorbance. Oxidative stress injury was gauged by measuring ROS, SOD activity, and MDA content. RNA transcription and protein expression of cholesterol-related (DHCR24, DHCR7) and oxidative stress-related (NFE2L2, HMOX1) genes were also examined via RT-qPCR and WB. Results • The impact of H2O2 on cell viability exhibited a time-dose-dependent pattern, paralleling the changes in reactive oxygen species (ROS) levels. Compared to the C group, FFA treatment led to an increase in Oil Red absorption and MDA content and decreased SOD activity. However, it did not result in a significant reduction in cell viability. The FH group exhibited reduced cell viability and SOD activity, along with a further elevation in MDA content compared to the F group. Furthermore, the increased SOD activity and decreased MDA content observed in the CH group were effectively reversed following NAC treatment. Such a reversal was not evident between the FHN and FH groups. Compared to the control group, genes associated with cholesterol metabolism and oxidative stress (OS) displayed heightened expression levels in the other treatment groups, with the FHN group showing lower expression levels than the FH group. Notably, changes in the protein expressions of DHCR24, DHCR7, NFE2L2, and HMOX1 were consistent and exhibited correlations. Conclusions • Cholesterol metabolism emerges as a potential mechanism underlying H2O2-induced oxidative stress injury in HepG2 cells treated with FFA. [ABSTRACT FROM AUTHOR]

Cellular traction forces (CTFs) are generated by adherent cells and involved in regulating migration, morphology, and homeostasis. Accurate measurement of CTFs is crucial for understanding fundamental biological processes such as morphogenesis, angiogenesis, and wound healing. However, directly measuring CTFs, which typically range in the nanonewton scale, is challenging. Cellular traction force microscopy (TFM) has been developed to quantify CTFs, but detailed operational procedures and complex data analysis limit its applicability. In this study, hydrogels embedded with fluo-spheres serve as the substrate for TFM measurement under a detailed TFM protocol. Additionally, we designed a user-friendly program for easy parameter setting. An open-source program called Python Fourier transform traction cytometry (pyFTTC) is introduced for data analysis, utilizing particle image velocimetry (PIV) to calculate the traction force from a batch of images. Cross-correlation based PIV and L2-regularized FTTC are applied to all images for data analysis. This article provides a straightforward protocol for quantifying CTFs in standard laboratories, facilitating both cell biology studies and biomaterials development. [ABSTRACT FROM AUTHOR]

The coalbed methane energy resources waste, environmental pollution and miner's health remain challenging problems in worldwide mining operations accompanied by coal-gas outbursts; thus, the safe and efficient yield of these resources plays a vital role in the world's energy market. The tectonic coal development is a significant geological feature of coal and gas outburst sites, and the study of coal and gas outburst mechanism should be based on more precise geological occurrence characteristics. In this paper, the geological characteristics of coal and gas outburst sites were analyzed. The failure law of coal body under the stratified occurrence of tectonic coal and raw coal seam with different thickness was studied. The mechanical equilibrium equation of non-synchronous deformation of tectonic coal and raw coal was constructed, the initiation criterion of coal and gas outburst was established based on the support body model, and a case study was carried out. The results show that with the thickness increase of the tectonic coal seam, the peak displacement of the driving face increases. The outburst start-up and development of coal and gas outburst, coal and gas extrusion outburst and coal and gas collapse outburst were deeply analyzed, as well as the internal reasons of the occurrence of coal-gas outburst portent are explained, based on the support body model. The development process from the start to the end of coal and gas outburst is revealed, and a new perspective is proposed for the prevention and control of coal and gas outburst: improving the strength of support body is also of great significance for the prevention and control of coal and gas outburst. • Asynchronous deformation induced coal-gas outburst mechanism. • The initiation criterion of coal and gas outburst was established. • The start and development process of the three types outburst were revealed. • New theoretical method and direction into dynamic disaster monitoring. [ABSTRACT FROM AUTHOR]