Amphotericin B Ocular Films for Fungal Keratitis and a Novel 3D-Printed Microfluidic Ocular Lens Infection Model.

Fungal keratitis (FK), a severe eye infection that leads to vision impairment and blindness, poses a high risk to contact lens users, and remains the most common underpinning fungal pathogen in temperate climates. Patients are initially treated empirically (econazole 1% drops hourly for 24-48 h), and if there is no response, amphotericin B (AmB) 0.15% eye drops (extemporaneously manufactured to be stable for a week) are the gold-standard treatment.

Artificial Intelligence (AI) Applications in Drug Discovery and Drug Delivery: Revolutionizing Personalized Medicine.

Artificial intelligence (AI) encompasses a broad spectrum of techniques that have been utilized by pharmaceutical companies for decades, including machine learning, deep learning, and other advanced computational methods. These innovations have unlocked unprecedented opportunities for the acceleration of drug discovery and delivery, the optimization of treatment regimens, and the improvement of patient outcomes. AI is swiftly transforming the pharmaceutical industry, revolutionizing everything from drug development and discovery to personalized medicine, including target identification and validation, selection of excipients, prediction of the synthetic route, supply chain optimization, monitoring during continuous manufacturing processes, or predictive maintenance, among others.

3D Printing Technologies in Personalized Medicine, Nanomedicines, and Biopharmaceuticals.

3D printing technologies enable medicine customization adapted to patients' needs. There are several 3D printing techniques available, but majority of dosage forms and medical devices are printed using nozzle-based extrusion, laser-writing systems, and powder binder jetting. 3D printing has been demonstrated for a broad range of applications in development and targeting solid, semi-solid, and locally applied or implanted medicines.

Drug Stability: ICH versus Accelerated Predictive Stability Studies.

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), along with the World Health Organization (WHO), has provided a set of guidelines (ICH Q1A-E, Q3A-B, Q5C, Q6A-B) intended to unify the standards for the European Union, Japan, and the United States to facilitate the mutual acceptance of stability data that are sufficient for registration by the regulatory authorities in these jurisdictions. Overall, ICH stability studies involve a drug substance tested under storage conditions and assess its thermal stability and sensitivity to moisture. The long-term testing should be performed over a minimum of 12 months at 25 °C ± 2 °C/60% ± 5% or at 30 °C ± 2 °C/65% ± 5% .

Extended-Release Naltrexone and Case Management for Treatment of Alcohol Use Disorder in the Emergency Department.

Study Objective: To assess the feasibility of initiating treatment for alcohol use disorder with extended-release naltrexone and case management services in the emergency department (ED) and measure the intervention's impact on daily alcohol consumption and quality of life.

Methods: This is a 12-week prospective open-label single-arm study of a multimodal treatment for alcohol use disorder consisting of monthly extended-release naltrexone injections and case management services initiated at an urban academic ED. Participants were actively drinking adult patients in ED with known or suspected alcohol use disorder and an AUDIT-C score more than 4.

Screen for Small-Molecule Modulators of Circadian Rhythms Reveals Phenazine as a Redox-State Modifying Clockwork Tuner.

A high-throughput cell-based screen identified redox-active small molecules that produce a period lengthening of the circadian rhythm. The strongest period lengthening phenotype was induced by a phenazine carboxamide (VU661). Comparison to two isomeric benzquinoline carboxamides (VU673 and VU164) shows the activity is associated with the redox modulating phenazine functionality.

Rare-Earth Supported Nickel Catalysts for Alkyne Semihydrogenation: Chemo- and Regioselectivity Impacted by the Lewis Acidity and Size of the Support.

Bimetallic catalysts of nickel(0) with a trivalent rare-earth ion or Ga(III), NiML (where L is [PrPCHNPh], and M is Sc, Y, La, Lu, or Ga), were investigated for the selective hydrogenation of diphenylacetylene (DPA) to ()-stilbene. Each bimetallic complex features a relatively short Ni-M bond length, ranging from 2.3395(8) Å (Ni-Ga) to 2.

Multiple Bonds in Uranium-Transition Metal Complexes.

Novel heterobimetallic complexes featuring a uranium atom paired with a first-row transition metal have been computationally predicted and analyzed using density functional theory and multireference wave function based methods. The synthetically inspired metalloligands U{(PrPCHNAr)tacn} () and U(PrPCHNPh) () are explored in this study. We report the presence of multiple bonds between uranium and chromium, uranium and manganese, and uranium and iron.

Bimetallic nickel-lutetium complexes: tuning the properties and catalytic hydrogenation activity of the Ni site by varying the Lu coordination environment.

We present three heterobimetallic complexes containing an isostructural nickel center and a lutetium ion in varying coordination environments. The bidentate and nonadentate ligands were used to prepare the Lu metalloligands, Lu(PrPCHNPh) () and Lu{(PrPCHNAr)tacn} (), respectively. Reaction of Ni(COD) (where COD is 1,5-cyclooctadiene) and afforded NiLu(PrPCHNPh) (), with a Lu coordination number (CN) of 4 and a Ni-Lu distance, (Ni-Lu), of 2.

A strategy for dual inhibition of the proteasome and fatty acid synthase with belactosin C-orlistat hybrids.

The proteasome, a validated cellular target for cancer, is central for maintaining cellular homeostasis, while fatty acid synthase (FAS), a novel target for numerous cancers, is responsible for palmitic acid biosynthesis. Perturbation of either enzymatic machine results in decreased proliferation and ultimately cellular apoptosis. Based on structural similarities, we hypothesized that hybrid molecules of belactosin C, a known proteasome inhibitor, and orlistat, a known inhibitor of the thioesterase domain of FAS, could inhibit both enzymes.

Polystyrenesulfonate-catalyzed synthesis of novel pyrroles through Paal-Knorr reaction.

Background: The classical Paal-Knorr reaction is one of the simplest and most economical methods for the synthesis of biologically important and pharmacologically useful pyrrole derivatives.

Results: Polystyrenesulfonate-catalyzed simple synthesis of substituted pyrroles following Paal-Knorr reaction has been accomplished with an excellent yield in aqueous solution. This method also produces pyrroles with multicyclic polyaromatic amines.