Competing Easy-Axis Anisotropies Impacting Magnetic Tunnel Junction-Based Molecular Spintronics Devices (MTJMSDs)

Molecular spintronics devices (MSDs) attempt to harness molecules’ quantum state, size, and configurable attributes for application in computer devices—a quest that began more than 70 years ago. In the vast number of theoretical studies and limited experimental attempts, MSDs have been found to be suitable for application in memory devices and futuristic quantum computers. MSDs have recently also exhibited intriguing spin photovoltaic-like phenomena, signaling their potential application in cost-effective and novel solar cell technologies. The molecular spintronics field’s major challenge is the lack of mass-fabrication methods producing robust magnetic molecule connections with magnetic electrodes of different anisotropies. Another main challenge is the limitations of conventional theoretical methods for understanding experimental results and designing new devices. Magnetic tunnel junction-based molecular spintronics devices (MTJMSDs) are designed by covalently connecting paramagnetic molecules across an insulating tunneling barrier. The insulating tunneling barrier serves as a mechanical spacer between two ferromagnetic (FM) electrodes of tailorable magnetic anisotropies to allow molecules to undergo many intriguing phenomena. Our experimental studies showed that the paramagnetic molecules could produce strong antiferromagnetic coupling between two FM electrodes, leading to a dramatic large-scale impact on the magnetic electrode itself. Recently, we showed that the Monte Carlo Simulation (MCS) was effective in providing plausible insights into the observation of unusual magnetic domains based on the role of single easy-axis magnetic anisotropy. Here, we experimentally show that the response of a paramagnetic molecule is dramatically different when connected to FM electrodes of different easy-axis anisotropies. Motivated by our experimental studies, here, we report on an MCS study investigating the impact of the simultaneous presence of two easy-axis anisotropies on MTJMSD equilibrium properties. In-plane easy-axis anisotropy produced multiple magnetic phases of opposite spins. The multiple magnetic phases vanished at higher thermal energy, but the MTJMSD still maintained a higher magnetic moment because of anisotropy. The out-of-plane easy-axis anisotropy caused a dominant magnetic phase in the FM electrode rather than multiple magnetic phases. The simultaneous application of equal-magnitude in-plane and out-of-plane easy-axis anisotropies on the same electrode negated the anisotropy effect. Our experimental and MCS study provides insights for designing and understanding new spintronics-based devices

Defining the Role of the Gut Microbiome in the Pathogenesis and Treatment of Lymphoid Malignancies

The gut microbiome is increasingly being recognized as an important immunologic environment, with direct links to the host immune system. The scale of the gut microbiome’s genomic repertoire extends the capacity of its host’s genome by providing additional metabolic output, and the close communication between gut microbiota and mucosal immune cells provides a continued opportunity for immune education. The relationship between the gut microbiome and the host immune system has important implications for oncologic disease, including lymphoma, a malignancy derived from within the immune system itself. In this review, we explore past and recent discoveries describing the role that bacterial populations play in lymphomagenesis, diagnosis, and therapy. We highlight key relationships within the gut microbiome-immune-oncology axis that present exciting opportunities for directed interventions intended to shape the microbiome for therapeutic effect. We conclude with a limited summary of active clinical trials targeting the microbiome in hematologic malignancies, along with future directions on gut microbiome investigations within lymphoid malignancies

Defining the Role of the Gut Microbiome in the Pathogenesis and Treatment of Lymphoid Malignancies

The gut microbiome is increasingly being recognized as an important immunologic environment, with direct links to the host immune system. The scale of the gut microbiome’s genomic repertoire extends the capacity of its host’s genome by providing additional metabolic output, and the close communication between gut microbiota and mucosal immune cells provides a continued opportunity for immune education. The relationship between the gut microbiome and the host immune system has important implications for oncologic disease, including lymphoma, a malignancy derived from within the immune system itself. In this review, we explore past and recent discoveries describing the role that bacterial populations play in lymphomagenesis, diagnosis, and therapy. We highlight key relationships within the gut microbiome-immune-oncology axis that present exciting opportunities for directed interventions intended to shape the microbiome for therapeutic effect. We conclude with a limited summary of active clinical trials targeting the microbiome in hematologic malignancies, along with future directions on gut microbiome investigations within lymphoid malignancies

A Novel Triple-Action Inhibitor Targeting B-Cell Receptor Signaling and BRD4 Demonstrates Preclinical Activity in Chronic Lymphocytic Leukemia

B-cell chronic lymphocytic leukemia (CLL) results from intrinsic genetic defects and complex microenvironment stimuli that fuel CLL cell growth through an array of survival signaling pathways. Novel small-molecule agents targeting the B-cell receptor pathway and anti-apoptotic proteins alone or in combination have revolutionized the management of CLL, yet combination therapy carries significant toxicity and CLL remains incurable due to residual disease and relapse. Single-molecule inhibitors that can target multiple disease-driving factors are thus an attractive approach to combat both drug resistance and combination-therapy-related toxicities. We demonstrate that SRX3305, a novel small-molecule BTK/PI3K/BRD4 inhibitor that targets three distinctive facets of CLL biology, attenuates CLL cell proliferation and promotes apoptosis in a dose-dependent fashion. SRX3305 also inhibits the activation-induced proliferation of primary CLL cells in vitro and effectively blocks microenvironment-mediated survival signals, including stromal cell contact. Furthermore, SRX3305 blocks CLL cell migration toward CXCL-12 and CXCL-13, which are major chemokines involved in CLL cell homing and retention in microenvironment niches. Importantly, SRX3305 maintains its anti-tumor effects in ibrutinib-resistant CLL cells. Collectively, this study establishes the preclinical efficacy of SRX3305 in CLL, providing significant rationale for its development as a therapeutic agent for CLL and related disorders