Three-dimensional multi-color optical nanoscopy at sub-10-nm resolution based on small-molecule organic probes.

Achieving nanometer-scale resolution remains challenging in expansion microscopy due to photon loss. To address this concern, here we develop a multi-color expansion stimulated emission depletion technique based on small-molecule probes to realize high labeling density and intensity. Our method substantially lowers the barrier to visualizing diverse intracellular proteins and their interactions in three dimensions.

Perceptual similarity of psychopathy and marital quality in Chinese married couples: The mediating role of couple communication.

Previous studies have shown that psychopathy, one of the Dark Triad personality traits, is associated with relationship dissatisfaction. However, the similarity of psychopathy among romantic couples remains uncertain with regard to relationship outcomes. This study examined the effect of the perceptual similarity of psychopathy on marital quality in a sample of 245 heterosexual married couples, using intraclass correlation coefficients as the method for assessing couples' similarity.

Pharmacokinetic Drug-Drug Interaction Studies Between Trilaciclib and Midazolam, Metformin, Rifampin, Itraconazole, and Topotecan in Healthy Volunteers and Patients with Extensive-Stage Small-Cell Lung Cancer.

Background And Objective: Trilaciclib is a cyclin-dependent kinase 4/6 inhibitor indicated to decrease the incidence of chemotherapy-induced myelosuppression in patients with extensive-stage small-cell lung cancer. Trilaciclib is a substrate and time-dependent inhibitor of cytochrome P450 3A4 and an inhibitor of multidrug and toxin extrusion 1, multidrug and toxin extrusion 2-K, organic cation transporter 1, and organic cation transporter 2. Here, we investigate the pharmacokinetic drug-drug interaction potential of trilaciclib.

Assessment of an accessorized pre-filled syringe for home-administered benralizumab in severe asthma.

Background: Patients prefer at-home subcutaneous administration of biologics across different diseases, yet no biologic is approved for at-home use for severe, uncontrolled asthma.

Objective: We assessed at-home functionality, reliability, and performance of an accessorized pre-filled syringe (APFS) for subcutaneous benralizumab administration, an anti-eosinophil monoclonal antibody indicated for add-on maintenance treatment of patients with severe eosinophilic asthma.

Materials And Methods: Patients (N=116) with severe, uncontrolled asthma despite receiving medium- or high-dosage inhaled corticosteroids and long-acting β-agonists received up to 5 APFS-administered subcutaneous doses (Weeks 0, 4, 8, 12, and 16) of benralizumab 30 mg.

Pharmacokinetics and Pharmacodynamics of the SGLT2 Inhibitor Remogliflozin Etabonate in Subjects with Mild and Moderate Renal Impairment.

Remogliflozin etabonate (RE), the prodrug of remogliflozin, is an inhibitor of the sodium glucose-dependent renal transporter 2 (SGLT2), enabling urinary glucose excretion to reduce hyperglycemia for the treatment of type 2 diabetes. Renal function declines more rapidly in patients with type 2 diabetes, making it difficult or unsafe to continue on some antidiabetic therapeutics. In an initial effort to understand the potential utility of RE in patients with renal impairment, the pharmacodynamics and pharmacokinetics of RE were evaluated in a single oral dose (250 mg) in patients with renal impairment as compared with control subjects.

Utility of concentration-effect modeling and simulation in a thorough QT study of losmapimod.

A thorough QT study was conducted in healthy volunteers with losmapimod. Four treatment regimens were included: a therapeutic dose (7.5 mg BID for 5 days), a supratherapeutic dose (20 mg QD for 5 days), a positive control (400 mg moxifloxacin single dose on Day 5), and placebo for 5 days.

Safety, pharmacokinetics and pharmacodynamics of remogliflozin etabonate, a novel SGLT2 inhibitor, and metformin when co-administered in subjects with type 2 diabetes mellitus.

Background: The sodium-dependent glucose co-transporter-2 (SGLT2) is expressed in absorptive epithelia of the renal tubules. Remogliflozin etabonate (RE) is the prodrug of remogliflozin, the active entity that inhibits SGLT2. An inhibitor of this pathway would enhance urinary glucose excretion (UGE), and potentially improve plasma glucose concentrations in diabetic patients.

Regional gastrointestinal delivery of remogliflozin etabonate in humans.

Remogliflozin etabonate (RE) is the prodrug of remogliflozin (R), an inhibitor of renal glucose transport designed to reduce blood glucose concentrations for the treatment of type 2 diabetes. This open-label, randomized, single-dose, four-way crossover study, (with one add-on arm) in eight healthy men evaluated the regional gastrointestinal absorption of RE, the systemic appearance of the active entity R, and an active metabolite, GSK279782. The InteliSite(®) Companion Capsule was used to administer a single dose of RE 100 mg to the mid-small intestine or cecum/colon.

Assessment of the drug interaction risk for remogliflozin etabonate, a sodium-dependent glucose cotransporter-2 inhibitor: evidence from in vitro, human mass balance, and ketoconazole interaction studies.

Remogliflozin etabonate is the ester prodrug of remogliflozin, a selective sodium-dependent glucose cotransporter-2 inhibitor. This work investigated the absorption, metabolism, and excretion of [(14)C]remogliflozin etabonate in humans, as well as the influence of P-glycoprotein (Pgp) and cytochrome P450 (P450) enzymes on the disposition of remogliflozin etabonate and its metabolites to understand the risks for drug interactions. After a single oral 402 ± 1.

Effects of mu opioid receptor antagonism on cognition in obese binge-eating individuals.

Rationale: Translational research implicates the mu opioid neurochemical system in hedonic processing, but its role in dissociable high-level cognitive functions is not well understood. Binge-eating represents a useful model of 'behavioural addiction' for exploring this issue.

Objective: The aim of this study was to objectively assess the cognitive effects of a mu opioid receptor antagonist in obese individuals with binge-eating symptoms.

Opioid receptor modulation of hedonic taste preference and food intake: a single-dose safety, pharmacokinetic, and pharmacodynamic investigation with GSK1521498, a novel μ-opioid receptor inverse agonist.

Endogenous opioids and µ-opioid receptors have been linked to hedonic and rewarding aspects of palatable food intake. The authors examined the safety, pharmacokinetic, and pharmacodynamic profile of GSK1521498, a µ-opioid receptor inverse agonist that is being investigated primarily for the treatment of overeating behavior in obesity. In healthy participants, GSK1521498 oral solution and capsule formulations were well tolerated up to a dose of 100 mg.