The interaction between the soluble programmed death ligand-1 (sPD-L1) and PD-1+ regulator B cells mediates immunosuppression in triple-negative breast cancer

Accumulating evidence suggests that regulatory B cells (Bregs) play important roles in inhibiting the immune response in tumors. Programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) are important molecules that maintain the balance of the immune response and immune tolerance. This study aims to evaluate the soluble form of PD-L1 and its function in inducing the differentiation of B lymphocytes, investigate the relationship between soluble PD-L1 (sPD-L1) and B-cell subsets, and explore the antitumor activity of T lymphocytes after PD-L1 blockade in coculture systems. In an effort to explore the role of sPD-L1 in human breast cancer etiology, we examined the levels of sPD-L1 and interleukin-10 (IL-10) in the serum of breast tumor patients and the proportions of B cells, PD-1+ B cells, Bregs, and PD-1+ Bregs in the peripheral blood of patients with breast tumors and assessed their relationship among sPD-L1, IL-10, and B-cell subsets. The levels of sPD-L1 and IL-10 in serum were found to be significantly higher in invasive breast cancer (IBCa) patients than in breast fibroadenoma (FIBma) patients. Meanwhile, the proportions and absolute numbers of Bregs and PD-1+ Bregs in the peripheral blood of IBCa patients were significantly higher than those of FIBma patients. Notably, they were the highest in triple-negative breast cancer (TNBC) among other subtypes of IBCa. Positive correlations of sPD-L1 and IL-10, IL-10 and PD-1+ Bregs, and also sPD-L1 and PD-1+ Bregs were observed in IBCa. We further demonstrated that sPD-L1 could induce Breg differentiation, IL-10 secretion, and IL-10 mRNA expression in a dose-dependent manner in vitro. Finally, the induction of regulatory T cells (Tregs) by Bregs was further shown to suppress the antitumor response and that PD-L1 blockade therapies could promote the apoptosis of tumor cells. Together, these results indicated that sPD-L1 could mediate the differentiation of Bregs, expand CD4+ Tregs and weaken the antitumor activity of CD4+ T cells. PD-L1/PD-1 blockade therapies might be a powerful therapeutic strategy for IBCa patients, particularly for TNBC patients with high level of PD-1+ Bregs

Physical Layer Security Performance Analysis of IRS-Aided Cognitive Radio Networks

Cognitive radio (CR) acts as a significant player in enhancing the spectral efficiency (SE) of wireless telecommunications; simultaneously, the intelligent reflecting surface (IRS) technique is a valid technique for increasing the confidentiality properties of wireless telecommunications systems through the modulation of the amplitude and phase shift of the channel. Therefore, we take into consideration an IRS-assisted multiple-input single-output (MISO) CR system to raise the confidentiality rate, which is composed of a primary network with a primary receiver (PR) and an eavesdropping link, as well as a secondary network with a secondary receiver (SR) and SR transmitter (SR-TX). In particular, we minimize the SR’s transmit power under the interference temperature (IT) and confidentiality capacity constraints via the joint optimization of the beamforming vector and artificial noise (AN) constraint matrix at SR-TX together with the phase shift matrix of IRS. Numerical outcomes indicate that various transmit antenna values and the IRS element numbers at SR-TX can greatly reduce transmit power while assuring secure communication

CuZr Metal Glass Powder as Electrocatalysts for Hydrogen and Oxygen Evolution Reactions

For the practical application of water electrolysis, it is essential to develop cost-effective and high efficiency electrocatalysts for both hydrogen evolution reaction (HER) and oxygen evaluation reaction (OER). In this work, we applied CuZr metallic glass powder, after chemical dealloying treatment, as electrocatalysts. The as-prepared sample had both the increased specific area and optimized surface composition of an efficient catalyst. During the HER and OER processes, the dealloyed CuZr sample displayed overpotential of 195 mV and 310 mV at current density of 10 mA cm−2, respectively. A two-electrode water splitting cell, using the as-prepared CuZr sample, exhibited high stability towards a high current density of 500 mA cm−2, and lower overpotential, compared to a Pt/C//IrO2 cell, during the 10 mA cm−2 constant current density aging test

CuZr Metal Glass Powder as Electrocatalysts for Hydrogen and Oxygen Evolution Reactions

For the practical application of water electrolysis, it is essential to develop cost-effective and high efficiency electrocatalysts for both hydrogen evolution reaction (HER) and oxygen evaluation reaction (OER). In this work, we applied CuZr metallic glass powder, after chemical dealloying treatment, as electrocatalysts. The as-prepared sample had both the increased specific area and optimized surface composition of an efficient catalyst. During the HER and OER processes, the dealloyed CuZr sample displayed overpotential of 195 mV and 310 mV at current density of 10 mA cm−2, respectively. A two-electrode water splitting cell, using the as-prepared CuZr sample, exhibited high stability towards a high current density of 500 mA cm−2, and lower overpotential, compared to a Pt/C//IrO2 cell, during the 10 mA cm−2 constant current density aging test

The CDK inhibitor AT7519 inhibits human glioblastoma cell growth by inducing apoptosis, pyroptosis and cell cycle arrest

Abstract Glioblastoma multiforme (GBM) is the most lethal primary brain tumor with a poor median survival of less than 15 months. However, clinical strategies and effective therapies are limited. Here, we found that the second-generation small molecule multi-CDK inhibitor AT7519 is a potential drug for GBM treatment according to high-throughput screening via the Approved Drug Library and Clinical Compound Library (2718 compounds). We found that AT7519 significantly inhibited the cell viability and proliferation of U87MG, U251, and patient-derived primary GBM cells in a dose-dependent manner. Furthermore, AT7519 also inhibited the phosphorylation of CDK1/2 and arrested the cell cycle at the G1-S and G2-M phases. More importantly, AT7519 induced intrinsic apoptosis and pyroptosis via caspase-3-mediated cleavage of gasdermin E (GSDME). In the glioblastoma intracranial and subcutaneous xenograft assays, tumor volume was significantly reduced after treatment with AT7519. In summary, AT7519 induces cell death through multiple pathways and inhibits glioblastoma growth, indicating that AT7519 is a potential chemical available for GBM treatment