Joint Optimization of Bandwidth and Power Allocation in Uplink Systems with Deep Reinforcement Learning.

Wireless resource utilizations are the focus of future communication, which are used constantly to alleviate the communication quality problem caused by the explosive interference with increasing users, especially the inter-cell interference in the multi-cell multi-user systems. To tackle this interference and improve the resource utilization rate, we proposed a joint-priority-based reinforcement learning (JPRL) approach to jointly optimize the bandwidth and transmit power allocation. This method aims to maximize the average throughput of the system while suppressing the co-channel interference and guaranteeing the quality of service (QoS) constraint. Specifically, we de-coupled the joint problem into two sub-problems, i.e., the bandwidth assignment and power allocation sub-problems. The multi-agent double deep Q network (MADDQN) was developed to solve the bandwidth allocation sub-problem for each user and the prioritized multi-agent deep deterministic policy gradient (P-MADDPG) algorithm by deploying a prioritized replay buffer that is designed to handle the transmit power allocation sub-problem. Numerical results show that the proposed JPRL method could accelerate model training and outperform the alternative methods in terms of throughput. For example, the average throughput was approximately 10.4-15.5% better than the homogeneous-learning-based benchmarks, and about 17.3% higher than the genetic algorithm.

GNAQ T96S mutation abrogates the ability of wild-type GNAQ to induce apoptosis by phosphorylating annexin A2 in natural killer/T cell lymphoma.

Our previous study identified annexin A2 (ANXA2) as a Gaq-interacting partner in natural killer/T cell lymphoma (NKTCL) cells transfected with the GNAQ T96S mutation vector by immunoprecipitation and mass spectrometry; however, the detailed molecular mechanisms by which GNAQ T96S might regulate ANXA2 remain to be defined in NKTCL. Herein, we found that the GNAQ T96S mutation significantly promotes the phosphorylation of ANXA2 at the Y24 site, whereas phosphorylation of ANXA2 abolishes the ability of WT GNAQ to trigger cell apoptosis. Further investigation revealed that a GNAQ T96S peptide inhibitor induced apoptosis by competing with ANXA2 binding to GNAQ T96S in NKTCL cells. In vivo animal experiments showed that a GNAQ T96S peptide inhibitor suppresses the growth of NKTCL cells carrying the GNAQ T96S mutation. Our current data suggest a role for GNAQ T96S/Src/ANXA2 in mediating the apoptosis of NKTCL cells, and the GNAQ T96S peptide could be a promising agent for therapy in NKTCL patients.

The expression and clinical significance of PLK1/p-PLK1 protein in NK/T cell Lymphoma.

AIMS: To investigate the expression of polo-like kinase 1 protein (PLK1) and its phosphorylation level (p-PLK1) in extranodal NK/T cell lymphoma (NKTCL) and their correlation with clinical characteristics and prognosis. METHODS: We collected 40 cases of NKTCL (referred to as the experimental group), which received diagnoses at the First Affiliated Hospital of Zhengzhou University between January 2018 and October 2022. Concurrently, we assembled a control group, including 20 cases afflicted with nasopharyngeal mucosal lymphoid hyperplasia diseases during the same timeframe. We utilized immunohistochemical techniques to evaluate the levels of PLK1 and p-PLK1 expression in both the experimental and control groups. Subsequently, we conducted an analysis to identify disparities in their expression and explore their relationships with clinical characteristics and patient prognosis. RESULTS: Among the 40 NKTCL patients, there were 27 males and 11 females, with a median age of 51 years (range 12-80 years). Compared to the control group, the tissue samples of NKTCL patients exhibited significantly elevated expression levels and active phosphorylation levels of PLK1 (P < 0.05). Correlation analysis of the immunohistochemical H score and Ki-67 positive rate of PLK1 and p-PLK1, revealed a significant positive correlation for both (P < 0.0001, each). No statistically significant differences were observed in the distribution of PLK1 and p-PLK1 expression in NKTCL patients with respect to gender, age, Ann Arbor stage, PINK-E score, B-symptoms, lactate dehydrogenase, ß2-microglobulin, blood EBV-DNA, bone marrow invasion, and lymph node metastasis (p > 0.05). Grouping based on PLK1 and p-PLK1 immunohistochemical H-scores revealed that the high expression of PLK1 and p-PLK1 was associated with poor prognosis. CONCLUSIONS: The expression levels and active phosphorylation levels of PLK1 were significantly increased in NK/T cell lymphoma, and patients with overexpression of PLK1 and p-PLK1 had a poorer prognosis.

A retrospective study on the clinicopathological and molecular features of 22 cases of natural killer/T-cell lymphoma in children and adolescents.

Natural killer/T-cell lymphoma (NKTCL) in children and adolescents is a rare type of T/NK cell neoplasms. The aim of the present study was to analyze the clinicopathological and genetic features of this rare entity of lymphoma. We evaluated the clinical, histopathological and molecular features of 22 young people with NKTCL, including 15 males and 7 females, with a median age of 15 years. The results revealed that the nasal site was the most involved region while non-nasal sites were observed in 27.3% out of all cases. The tumor cells were composed of small­sized to large cells and 19 (86.4%) cases exhibited coagulative necrosis. The neoplastic cells in all patients were positive for CD3 and the cytotoxic markers. Nineteen (86.4%) cases were positive for CD56. Reduced expression of CD5 was observed in all available cases. CD30 was heterogeneously expressed in 15 (75.0%) cases. All 22 patients were EBV positive. Seven (36.8%) out of all the 19 patients during the follow-up died of the disease, and the median follow­up period was 44 months. Moreover, patients treated with radiotherapy/chemotherapy showed significantly inferior OS compared with the untreated patients. High mutation frequencies were detected including KMT2C (5/5), MST1 (5/5), HLA-A (3/5) and BCL11A (3/5), which involved in modifications, tumor suppression and immune surveillance. These results suggest that NKTCL in children and adolescents exhibits histopathological and immunohistochemical features similar to the cases in adults. Active treatment is necessary after the diagnosis of NKTCL is confirmed. Furthermore, genetic analyse may provide a deep understanding of this rare disease.

Comprehensive Analysis of the Expression and Prognosis for E2Fs in Human Clear Cell Renal Cell Carcinoma.

Background: E2F transcription factors is a family of transcription factors, and lots of studies have shown that they play a key role in the occurrence and development of many tumors. However, the association between expression, prognostic value, and immune infiltration in the tumor microenvironment of the eight E2Fs members in ccRCC is still unclear. Method: s. We used online databases, such as ONCOMINE, UALCAN, Kaplan-Meier plotter, GEPIA, Metascape, TIMER, and cBioPortal, to analyze the effect of mRNA expression of E2Fs family members in ccRCC on the prognosis of patients and the relationship with immune infiltration. Results: Except for E2F5, other seven members of the family of E2Fs mRNA expression levels in ccRCC tissues were significantly higher than control tissues. And the high expression of E2Fs mRNA in ccRCC patients was related to cancer stage and tumor grade. Survival analysis results suggested that elevated mRNA expression levels of E2F1/2/3/4/7/8 were significantly related to the shorter overall survival (OS) in ccRCC patients (P = 3.9E - 06), while high mRNA expression of E2F6 is not related to OS (P = 0.061). Mutations of E2Fs were correlated with shorter OS of ccRCC patients (P = 7.094E - 5). In addition, mRNA expression of E2F1/2/3/4/7/8 was positively correlated with infiltration of six types of immune cells, including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Conclusions: These results indicate that E2F1/2/3/4/7/8 may be used as a prognostic marker for the survival of ccRCC patients and laid the foundation for studying the immune infiltration role of E2Fs family members in tumors.