The role of KDM4A-mediated histone methylation on temozolomide resistance in glioma cells through the HUWE1/ROCK2 axis.

Temozolomide (TMZ) resistance presents a significant challenge in the treatment of gliomas. Although lysine demethylase 4A (KDM4A) has been implicated in various cancer-related processes, its role in TMZ resistance remains unclear. This study aims to elucidate the contribution of KDM4A to TMZ resistance in glioma cells and its potential implications for glioma prognosis. We assessed the expression of KDM4A in glioma cells (T98G and U251MG) using qRT-PCR and Western blot assays. To explore the role of KDM4A in TMZ resistance, we transfected siRNA targeting KDM4A into drug-resistant glioma cells. Cell viability was assessed using the CCK-8 assay and the TMZ IC50 value was determined. ChIP assays were conducted to investigate KDM4A, H3K9me3, and H3K36me3 enrichment on the promoters of ROCK2 and HUWE1. Co-immunoprecipitation confirmed the interaction between HUWE1 and ROCK2, and we examined the levels of ROCK2 ubiquitination following MG132 treatment. Notably, T98G cells exhibited greater resistance to TMZ than U251MG cells, and KDM4A displayed high expression in T98G cells. Inhibiting KDM4A resulted in decreased cell viability and a reduction in the TMZ IC50 value. Mechanistically, KDM4A promoted ROCK2 transcription by modulating H3K9me3 levels. Moreover, disruption of the interaction between HUWE1 and ROCK2 led to reduced ROCK2 ubiquitination. Inhibition of HUWE1 or overexpression of ROCK2 counteracted the sensitization effect of si-KDM4A on TMZ responsiveness in T98G cells. Our findings highlight KDM4A's role in enhancing TMZ resistance in glioma cells by modulating ROCK2 and HUWE1 transcription and expression through H3K9me3 and H3K36me3 removal.

Optimize Injection-Molding Process Parameters and Build an Adaptive Process Control System Based on Nozzle Pressure Profile and Clamping Force.

The injection-molding process is a non-linear process, and the product quality and long-term production stability are affected by several factors. To stabilize the product quality effected by these factors, this research establishes a standard process parameter setup procedure and an adaptive process control system based on the data collected by a nozzle pressure sensor and a tie-bar strain gauge to achieve this goal. In this research, process parameters such as the V/P switchover point, injection speed, packing pressure, and clamping force are sequentially optimized based on the characteristics of the pressure profile. After the optimization process, this research defines the standard quality characteristics through the optimized process parameters and combines it with the adaptive process control system in order to achieve the purpose of automatic adjustment of the machine and maintain high-quality production. Finally, three different viscosity materials are used to verify the effectiveness of the optimization procedure and the adaptive process control system. With the system, the variation of product weight was reduced to 0.106%, 0.092%, and 0.079%, respectively.

Transsphenoidal surgery for prolactinomas in male patients: a retrospective study.

Male patients with prolactinomas usually present with typical hyperprolactinemia symptoms, including sexual dysfunction and infertility. However, clinical factors related to sexual dysfunction and surgical outcomes in these patients remain unclear. This study aimed to investigate the outcomes of male patients with prolactinomas after transsphenoidal surgery and the risk factors affecting sexual dysfunction. This study was conducted on 58 male patients who underwent transsphenoidal surgery for prolactinomas between May 2014 and December 2020 at the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. We evaluated the sexual function of patients before and after surgery through International Index of Erectile Function-5 scores, libido, and frequency of morning erection. Of the 58 patients, 48 (82.8%) patients had sexual intercourse preoperatively. Among those 48 patients, 41 (85.4%) patients presented with erectile dysfunction. The preoperative International Index of Erectile Function-5 scores in patients with macroprolactinomas were significantly higher than those in patients with giant prolactinomas (17.63 ± 0.91 vs 13.28 ± 1.43; P = 0.01). Postoperatively, the incidence of erectile dysfunction was 47.9%, which was significantly lower than that preoperatively (85.4%; P = 0.01). Twenty-eight (68.3%) patients demonstrated an improvement in erectile dysfunction. Tumor size and invasiveness were significantly correlated with the improvement of erectile dysfunction. Preoperative testosterone <2.3 ng ml-1 was an independent predictor of improvement in erectile dysfunction. In conclusion, our results indicated that tumor size and invasiveness were important factors affecting the improvement of sexual dysfunction in male patients with prolactinoma. The preoperative testosterone level was an independent predictor related to the improvement of erectile dysfunction.

Injection Barrel/Nozzle/Mold-Cavity Scientific Real-Time Sensing and Molding Quality Monitoring for Different Polymer-Material Processes.

Scientific injection molding technologies involve the integration and collaboration of cyber-physical systems and smart manufacturing. In order to achieve adaptive process control and production optimization, injection molding systems with real-time sensing have gradually become the development- and application-trend of smart injection molding. At the same time, this technology is a highly non-linear process in which many factors affect the product quality during long-run fabrication processes. Therefore, in order to grasp changes in the characteristics of plastic materials and product quality monitoring, the injection process has become an important research topic. We installed sensors in the molding machine (injection barrel, nozzle, and mold-cavity) to collect the melting pressure and used different materials (semi-crystalline and amorphous polymer; the melting-fill-index (MFI) is unified to 14.5 ± 0.5 g/10 min) to explore the influences of melting pressure variation and its viscosity index on the quality characteristics of molded products. The experiment reveals that a combination of barrel, nozzle, and mold-cavity sensing on the melt-pressure trend-based injection process-control incorporated with viscosity index monitoring can confirm the weight and shrinkage variation of the injection product. At the same time, the pressure and viscosity index value measured and calculated during the melt-filling of two materials with similar MI resulted in significant variations in the amorphous polymer. This study showed the possibility of mastering and controlling the rheology (barrel position) and shrinkage properties of polymers and successful application in various product-quality monitoring platforms.