A novel telomere-related genes model for predicting prognosis and treatment responsiveness in diffuse large B-cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) is a highly heterogeneous disease with diverse clinical and molecular features. Telomere maintenance is widely present in tumors, but there is a lack of relevant reports on the role of telomere-related genes (TRGs) in DLBCL. In this study, we used consensus clustering based on TRGs expression to identify two molecular clusters with distinct prognoses and immune cell infiltration. We developed a TRGs scoring model using univariate Cox regression and LASSO regression in the GSE10846 training cohort. DLBCL patients in the high-risk group had a worse prognosis than those in the low-risk group, as revealed by Kaplan-Meier curves. The scoring model was validated in the GSE10846 testing cohort and GSE87371 cohort, respectively. The high-risk group was characterized by elevated infiltration of activated DCs, CD56 dim natural killer cells, myeloid-derived suppressor cells, monocytes, and plasmacytoid DCs, along with reduced infiltration of activated CD4 T cells, Type 2 T helper cells, γδ T cells, NK cells, and neutrophils. Overexpression of immune checkpoints, such as PDCD1, CD274, and LAG3, was observed in the high-risk group. Furthermore, high-risk DLBCL patients exhibited increased sensitivity to bortezomib, rapamycin, AZD6244, and BMS.536924, while low-risk DLBCL patients showed sensitivity to cisplatin and ABT.263. Using RT-qPCR, we found that three protective model genes, namely TCEAL7, EPHA4, and ELOVL4, were down-regulated in DLBCL tissues compared with control tissues. In conclusion, our novel TRGs-based model has great predictive value for the prognosis of DLBCL patients and provides a promising direction for treatment optimization.

A novel angiogenesis-related scoring model predicts prognosis risk and treatment responsiveness in diffuse large B-cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) is a highly heterogeneous disease with varying therapeutic responses and prognoses. Angiogenesis is a crucial factor in lymphoma growth and progression, but no scoring model based on angiogenesis-related genes (ARGs) has been developed for prognostic evaluation of DLBCL patients. In this study, we used univariate Cox regression to identify prognostic ARGs and found two distinct clusters of DLBCL patients in the GSE10846 dataset based on the expression of these prognostic ARGs. These two clusters had different prognoses and immune cell infiltration. Using LASSO regression analysis, we constructed a novel seven-ARG-based scoring model in GSE10846 dataset, and it was further validated in the GSE87371 dataset. The DLBCL patients were divided into high- and low-score groups based on the median risk score as a cut-off. The high-score group had a worse prognosis and showed higher expression of immune checkpoints, M2 macrophages, myeloid-derived suppressor cells, and regulatory T cells, indicating a stronger immunosuppressive environment. DLBCL patients in high-score group were resistant to doxorubicin and cisplatin, which are components of frequently used chemotherapy regimens, but more sensitive to gemcitabine and temozolomide. Using RT-qPCR, we found that two candidate risk genes, RAPGEF2 and PTGER2, were over-expressed in DLBCL tissues compared with control tissues. Taken together, the ARG-based scoring model provides a promising direction for the prognosis and immune status of DLBCL patients, and benefits the development of personalized treatment for DLBCL patients.

Origin of two-band chorus in the radiation belt of Earth.

Naturally occurring chorus emissions are a class of electromagnetic waves found in the space environments of the Earth and other magnetized planets. They play an essential role in accelerating high-energy electrons forming the hazardous radiation belt environment. Chorus typically occurs in two distinct frequency bands separated by a gap. The origin of this two-band structure remains a 50-year old question. Here we report, using NASA's Van Allen Probe measurements, that banded chorus waves are commonly accompanied by two separate anisotropic electron components. Using numerical simulations, we show that the initially excited single-band chorus waves alter the electron distribution immediately via Landau resonance, and suppress the electron anisotropy at medium energies. This naturally divides the electron anisotropy into a low and a high energy components which excite the upper-band and lower-band chorus waves, respectively. This mechanism may also apply to the generation of chorus waves in other magnetized planetary magnetospheres.