Inhibition of PIM kinase in tumor associated macrophages suppresses inflammasome activation and sensitizes prostate cancer to immunotherapy.

Immunotherapy has changed the treatment paradigm for many types of cancer, but immune checkpoint inhibitors (ICIs) have not shown benefit in prostate cancer (PCa). Chronic inflammation contributes to the immunosuppressive prostate tumor microenvironment (TME) and is associated with poor response to ICIs. The primary source of inflammatory cytokine production is the inflammasome.

The HSmacropa Series: Increasing the Chemical Softness of Hmacropa with Sulfur Atoms to Chelate Radiometals [Bi]Bi and [Pb]Pb for Radiopharmaceutical Applications.

The effects of replacing nitrogen with sulfur atoms in the 18-membered macrocycle of the Hmacropa chelator on the binding affinity and stability of "intermediate" (radio)metal [Pb]Pb and [Bi]Bi complexes are investigated. The 1,4,10,13-tetraoxo-7,16-diazacyclooctadecane backbone was replaced with derivatives containing sulfur in the 1,4- or the 1,4,10,13-positions to yield the novel chelators HSmacropa (NOS) and HSmacropa (NOS), respectively. Trends on the Pb- and Bi-complex stability constants, coordination chemistry, radiolabeling, and kinetic inertness were assessed via potentiometric titrations, UV-vis spectroscopy, NMR spectroscopy, X-ray crystallography and density functional theory (DFT) calculations.

Anti-ovarian cancer migration and toxicity characteristics of a platinum(IV) pro-drug with axial HDAC inhibitor ligands in zebrafish models.

Ovarian cancer is the fifth leading cause of cancer related death in the United States. Cisplatin is a platinum-based anti-cancer drug used against ovarian cancer that enters malignant cells and then damages DNA causing cell death. Typically, ovarian cancer cells become resistant to cisplatin making it necessary to increase subsequent dosage, which usually leads to side-effects including irreversible damage to kidney and auditory system tissue.

Statistical mechanics of stochastic quantum control: d-adic Rényi circuits.

The dynamics of quantum information in many-body systems with large onsite Hilbert space dimension admits an enlightening description in terms of effective statistical mechanics models. Motivated by this fact, we reveal a connection between three separate models: the classically chaotic d-adic Rényi map with stochastic control, a quantum analog of this map for qudits, and a Potts model on a random graph. The classical model and its quantum analog share a transition between chaotic and controlled phases, driven by a randomly applied control map that attempts to order the system.

Chelation of [In]In with the dual-size-selective macrocycles py-macrodipa and py-macrodipa.

Indium-111 (In) is a diagnostic radiometal that is important in nuclear medicine for single-photon emission computed tomography (SPECT). In order to apply this radiometal, it needs to be stably chelated and conjugated to a targeting vector that delivers it to diseased tissue. Identifying effective chelators that are capable of binding and retaining [In]In is an important research area.

Supramolecular delivery of dinuclear ruthenium and osmium MCU inhibitors.

The transmembrane protein known as the mitochondrial calcium uniporter (MCU) mediates the influx of calcium ions (Ca) into the mitochondrial matrix. An overload of mitochondrial Ca ( Ca) is directly linked to damaging effects in pathological conditions. Therefore, inhibitors of the MCU are important chemical biology tools and therapeutic agents.

Chelator-Assisted Precipitation-Based Separation of the Rare Earth Elements Neodymium and Dysprosium from Aqueous Solutions.

The rare earth elements (REEs) are critical resources for many clean energy technologies, but are difficult to obtain in their elementally pure forms because of their nearly identical chemical properties. Here, an analogue of macropa, G-macropa, was synthesized and employed for an aqueous precipitation-based separation of Nd and Dy. G-macropa maintains the same thermodynamic preference for the large REEs as macropa, but shows smaller thermodynamic stability constants.

Who needs a tourniquet? And who does not? Lessons learned from a review of tourniquet use in the Russo-Ukrainian war.

Background: Extremity tourniquets have proven to be lifesaving in both civilian and military settings and should continue to be used by first responders for trauma patients with life-threatening extremity bleeding. This is especially true in combat scenarios in which both the casualty and the first responder may be confronted by the imminent threat of death from hostile fire as the extremity hemorrhage is being treated. Not every extremity wound, however, needs a tourniquet.

Transdermal Hydrogen Sulfide Delivery Enabled by Open-Metal-Site Metal-Organic Frameworks.

Hydrogen sulfide (HS) is an endogenously produced gasotransmitter involved in many physiological processes that are integral to proper cellular functioning. Due to its profound anti-inflammatory and antioxidant properties, HS plays important roles in preventing inflammatory skin disorders and improving wound healing. Transdermal HS delivery is a therapeutically viable option for the management of such disorders.

Gas Delivery Relevant to Human Health using Porous Materials.

Gases are essential for various applications relevant to human health, including in medicine, biomedical imaging, and pharmaceutical synthesis. However, gases are significantly more challenging to safely handle than liquids and solids. Herein, we review the use of porous materials, such as metal-organic frameworks (MOFs), zeolites, and silicas, to adsorb medicinally relevant gases and facilitate their handling as solids.

Insights into the enigma of oral streptococci in carcinogenesis.

SUMMARYThe genus consists of a taxonomically diverse group of Gram-positive bacteria that have earned significant scientific interest due to their physiological and pathogenic characteristics. Within the genus viridans group streptococci (VGS) play a significant role in the oral ecosystem, constituting approximately 80% of the oral biofilm. Their primary role as pioneering colonizers in the oral cavity with multifaceted interactions like adherence, metabolic signaling, and quorum sensing contributes significantly to the complex dynamics of the oral biofilm, thus shaping oral health and disease outcomes.

Construction of the Bioconjugate Py-Macrodipa-PSMA and Its In Vivo Investigations with Large La and Small Sc Radiometal Ions.

To harness radiometals in clinical settings, a chelator forming a stable complex with the metal of interest and targets the desired pathological site is needed. Toward this goal, we previously reported a unique set of chelators that can stably bind to both large and small metal ions, via a conformational switch. Within this chelator class, py-macrodipa is particularly promising based on its ability to stably bind several medicinally valuable radiometals including large La, Bi, and small Sc.

Oral streptococci and induce distinct morphological, inflammatory, and metabolic signatures in macrophages.

Oral streptococci, key players in oral biofilm formation, are implicated in oral dysbiosis and various clinical conditions, including dental caries, gingivitis, periodontal disease, and oral cancer. Specifically, is associated with esophageal, gastric, and pharyngeal cancers, while is linked to oral cancer. However, no study has investigated the mechanistic links between these species and cancer-related inflammatory responses.

An injectable subcutaneous colon-specific immune niche for the treatment of ulcerative colitis.

As a chronic autoinflammatory condition, ulcerative colitis is often managed via systemic immunosuppressants. Here we show, in three mouse models of established ulcerative colitis, that a subcutaneously injected colon-specific immunosuppressive niche consisting of colon epithelial cells, decellularized colon extracellular matrix and nanofibres functionalized with programmed death-ligand 1, CD86, a peptide mimic of transforming growth factor-beta 1, and the immunosuppressive small-molecule leflunomide, induced intestinal immunotolerance and reduced inflammation in the animals' lower gastrointestinal tract. The bioengineered colon-specific niche triggered autoreactive T cell anergy and polarized pro-inflammatory macrophages via multiple immunosuppressive pathways, and prevented the infiltration of immune cells into the colon's lamina propria, promoting the recovery of epithelial damage.

Investigation of Cobalt(III) Cage Complexes as Inhibitors of the Mitochondrial Calcium Uniporter.

The mitochondrial calcium uniporter (MCU) mediates uptake of calcium ions (Ca) into the mitochondria, a process that is vital for maintaining normal cellular function. Inhibitors of the MCU, the most promising of which are dinuclear ruthenium coordination compounds, have found use as both therapeutic agents and tools for studying the importance of this ion channel. In this study, six Co cage compounds with sarcophagine-like ligands were assessed for their abilities to inhibit MCU-mediated mitochondrial Ca uptake.

Measurement and Feedback Driven Entanglement Transition in the Probabilistic Control of Chaos.

We uncover a dynamical entanglement transition in a monitored quantum system that is heralded by a local order parameter. Classically, chaotic systems can be stochastically controlled onto unstable periodic orbits and exhibit controlled and uncontrolled phases as a function of the rate at which the control is applied. We show that such control transitions persist in open quantum systems where control is implemented with local measurements and unitary feedback.