Artificial intelligence (AI) and computational modeling have transformed modern pharmaceutical development by replacing empirical paradigms with data-driven workflows. Naproxen is a potent nonsteroidal anti-inflammatory drug (NSAID) that has serious gastrointestinal side effects when taken orally. Topical gel preparations are an ideal medium for localized, non-invasive pain management. However, conventional topical gel production is limited by resource-intensive, trial-and-error optimization over a multidimensional space of ingredient combinations. In this study, a closed-loop intelligent pharmaceutical design framework was established by coupling an Artificial Neural Network (ANN) with hybrid metaheuristic engines (particle swarm optimization (PSO) and Genetic Algorithms (GA)) to systematically design high-performance naproxen gels. A systematic literature screening protocol across the major indexing databases for the period of 2015-2025 was performed to determine the initial boundary variables. Predictive ANNs were built from data variations that mapped gelling agents, penetration enhancers, and surfactants with Critical Quality Attributes (CQAs) such as thixotropic viscosity, transdermal flux, and extended stability. The optimized formulation showed rapid convergence of the algorithm, leading to optimal spreadability profiles and a high cumulative in vitro drug release, which was strongly correlated with the simulated skin permeation dynamics. Furthermore, the platform has high biomedical importance as it provides a robust template for the facile incorporation of biocompatible green nanomaterials and plant-derived bioactive complexes in the design of next-generation drug delivery systems. Overall, this study provides a highly scalable and translational blueprint that successfully bridges molecular modeling, artificial intelligence, and experimental pharmaceutics to accelerate advanced topical therapeutic discovery.

Diabetes mellitus is among the strongest independent risk factors for severe influenza, hospitalization, and influenza-associated acute respiratory distress syndrome (ARDS). The mechanistic basis of this association, and its clinical implications for immunomodulatory therapy, has been examined extensively in basic immunology and virology but is rarely synthesized for the practicing intensivist. This narrative review synthesizes the mechanistic basis by which diabetes predisposes to severe influenza and to translate the established pathogen-driven versus host-driven lung injury framework into a bedside-relevant heuristic for immunomodulatory decision-making. PubMed/MEDLINE and the Cochrane Library were searched from inception through April 2026, integrating evidence across innate and adaptive immunology, viral pathogenesis, and clinical trial data. The review was guided by the SANRA framework. Diabetes plausibly impairs early antiviral containment through disruption of type I interferon signaling, alveolar macrophage function, neutrophil-mediated barrier defense, and CD8[+] T-cell responses, predominantly demonstrated in vitro and in murine models with supportive observational human data. The resulting prolonged viral replication, superimposed on baseline endothelial vulnerability, may contribute to rapid, severe lung injury. The framework applies most directly to type 2 diabetes; mechanistic differences between type 1 and type 2, and between acute glucose-driven and chronic structural mechanisms, are addressed. Available observational and meta-analytic evidence consistently associates corticosteroids with worse outcomes in influenza pneumonia. Selective adjunctive strategies, most notably mTOR inhibition with sirolimus and combination clarithromycin-naproxen-oseltamivir, show early hypothesis-generating signals but require confirmatory trials. This synthesis is intended as hypothesis-generating, not definitive.

Photoactivated periodate (PI)-based advanced oxidation processes (AOPs) are effective for removing refractory micropollutants, but PI can hardly be activated by visible light alone. This study employed ubiquitous aquatic humic acid (HA) to boost visible light-driven PI activation. 2 mgC/L HA increased naproxen (NAP) removal in the Vis460/PI system from 10% to 75.8% at pH 7.0. The kobs of NAP rose from 0.064 min[-1] to 0.185 min[-1] with the PI concentration increasing from 25 μM to 100 μM. Quenching and probe experiments verified hydroxyl radicals (HO[•]) and ozone (O3) as the dominant species, with their contributions at 77.6%-93.2% and 13.9%-20.6% across pH 4.0-9.0, respectively. The excited triplet state ([3]HA*) was the key photoproduced reactive intermediate for PI activation. Longer visible wavelengths inhibited NAP degradation due to lower photon energy, while acidic conditions facilitated the reaction via higher PI quantum yield. Higher HA concentration generated more [3]HA* to accelerate PI activation, and aromatic ketones were more likely precursors of the triplet excited state. The system efficiently degraded seven micropollutants, and Suwannee River NOM shared a similar activation role. This work offers a reliable approach for improving the visible light-activated PI system and novel insights into HA photochemical behaviors.

Long-acting drug delivery systems depend on crystalline suspensions with tightly controlled particle size to ensure reliable delivery and long-term stability, yet producing sub-10μm crystals with narrow and persistent size distributions remains challenging. Here we introduce a bottom-up crystallization strategy in which monodisperse, pH-switchable structured emulsions act as transient microreactors that template active pharmaceutical ingredient microcrystals during anti-solvent crystallization. Confinement of droplets within a yield-stress soft-matter matrix enables the formation of highly uniform naproxen microcrystals (∼7μm). In contrast to conventional wet-bead milling, the resulting suspensions exhibit substantially reduced Ostwald ripening under accelerated stability conditions while preserving crystal form and injectability-relevant size. The method is readily scalable via membrane emulsification and supports downstream solid dosage formats, demonstrated by redispersible thin films. Together, this work establishes structured emulsions as a generalizable platform for engineering stable, monodisperse crystalline suspensions for long-acting drug delivery.

Constructed wetlands are widely recognized as nature-based solutions for improving water quality in systems receiving treated wastewater. However, their effectiveness depends primarily on hydrological connectivity, contaminant properties, and hydraulic residence time. In Mediterranean wetlands, where strong hydrological variability and seasonal water scarcity influence water quality dynamics, understanding attenuation processes under contrasting water-circulation scenarios is relevant for protecting sensitive downstream ecosystems. This study assessed the capacity of a semi-natural pond system i.e., a series of interconnected shallow ponds comprising both natural and managed water bodies that receive treated wastewater while retaining natural wetland characteristics, located upstream of the Fuente de Piedra Ramsar wetland main basin (southern Spain) to reduce nutrients and emerging contaminants under contrasting water-circulation scenarios. Across 26 sampling events, substantial reductions were observed when treated wastewater flowed through the semi-natural pond system before reaching the main wetland basin, including decreases of 75% in total nitrogen. Marked attenuation was detected for emerging contaminants with shorter environmental half-lives, such as trimethoprim, naproxen, caffeine and selected triazine metabolites showed removals exceeding 70-90%, whereas more persistent substances, including carbamazepine and gemfibrozil, exhibited limited reduction. In contrast, negligible changes occurred during a temporary bypass configuration put in place for restoration works, in which treated wastewater avoided most of the semi-natural ponds before reaching the main wetland basin. Dry-season conditions enhanced contaminant attenuation, largely reflecting lower flows and extended hydraulic residence times. Cumulative ecotoxicological risk, estimated using risk quotients (RQsample) based on measured environmental concentrations and the lowest predicted no-effect concentrations for freshwater organisms, declined downstream under the regular flow pathway, particularly for pesticides, but moderate risk persisted under the bypass scenario. Overall, the semi-natural pond system demonstrates a strong but hydrologically dependent capacity to mitigate nutrient and emerging contaminant loads entering a Mediterranean Ramsar wetland. Nevertheless, elevated phosphorus concentrations and the persistence of certain emerging contaminants highlight the limitations of natural attenuation alone and support the integration of complementary management and treatment strategies to ensure long-term ecosystem protection.

We report a silver(I)-catalyzed three-component A3-coupling strategy for the synthesis of 2-chloro-(phenylvinyl)imidazo[1,2-a]pyridines from 2-aminopyridines, terminal alkynes, and β-chlorovinyl aldehydes. The transformation proceeds under mild conditions with high regioselectivity, broad substrate scope, and excellent functional-group tolerance. Notably, retention of the vinylic C-Cl bond in the products provides access to structurally important chlorovinyl-substituted imidazo[1,2-a]pyridines. The retained chlorovinyl motif may offer potential value for further diversification and for the development of medicinal chemistry-oriented scaffolds and pharmacophores. The protocol is operationally simple and scalable, as demonstrated by gram-scale synthesis. Its synthetic utility is further highlighted through the late-stage functionalization of complex molecules, including Naproxen and Gemfibrozil, as well as the synthesis of amino acid-derived 2-chloro-(phenylvinyl)imidazo[1,2-a]pyridines. These results underscore the versatility of the protocol and its potential applications in medicinal chemistry, molecular diversification, and drug discovery.

The use of subcutaneous and intramuscular progesterone injections for non-therapeutic purposes has become increasingly common in Africa, particularly in Angola, where weak regulation allows unsupervised use. We report the case of a 26-year-old Angolan woman who developed lipomembranous panniculitis after six months of daily subcutaneous progesterone injections for libido enhancement at a non-medical center. She presented with erythematous-brown nodules and plaques, and a skin biopsy confirmed granulomatous inflammation and adipocyte death. Treatment with prednisolone and naproxen resolved the inflammation, but hyperpigmentation persisted. This case highlights the serious risks of off-label progesterone injections, particularly in unregulated aesthetic procedures, and underscores the need for stricter regulations and public health interventions.

Recent evidence suggests that low-dose methotrexate might have antipsychotic properties. However, it remains unknown whether low-dose methotrexate is associated with a reduced risk of incident recorded psychosis in real-world data, whether these associations extend to other putatively immune-related common psychiatric conditions, or whether similar associations are observed with other disease-modifying anti-rheumatic drugs (DMARDs).

Herein, we disclose a three-component tandem reaction wherein organoboron and DMSO mediate the ring-opening of cyclopropenones to trigger the subsequent acrylation of alkyl (pseudo)halides. A series of cyclopropenones with various aryl groups, together with diverse alkyl (pseudo)halides bearing primary, secondary, and tosylate-based leaving groups, are converted into trisubstituted E-acrylates under transition metal-free conditions. Using B2pin2 as the promoter and Cs2CO3 as the base in DMSO at 40°C, the desired products are obtained in moderate to excellent yields (up to 99%) without the need for exclusion of air or moisture. DMSO serves as both the solvent and the oxygen atom source, while trace amounts of water in the reaction system donates the alkenyl hydrogen atom. The reaction exhibits high functional group tolerance and good scalability, and is applicable to late-stage modification of pharmaceuticals such as indomethacin and naproxen. Furthermore, mechanistic investigations, including isotope labeling experiments and control studies provide insights into the possible mechanistic steps. This formal three-component coupling joins two electrophiles via an exogenous oxygen atom, thus bypassing the need to pre‑match electrophiles with nucleophilic partners.

Unmet medical needs form the basis for the discovery of diagnostic tools and drugs for diseases that elude existing treatment options. Herein, we provide a perspective on the current trends in diagnosis and treatment using conventional and state-of-the-art diagnostic drugs. Our report highlights the evolution of diagnosis and therapy, more so in the form of after pulmonary combining the drug discovery process with diagnostics known as "drug-diagnostic codevelopment", which has opened the doors for precision medicine. Modern-age diagnostic drugs, such as conjugating a drug to fluorophores via a covalent bond, have the potential to both detect and treat diseases. However, fluorescence quenching in solutions is a major bottleneck. This can be addressed using quantum dots (QDs) conjugated to drugs such as cadmium telluride (CdTe) QDs conjugated to 5-fluorouracil (5-FU), naproxen, and celecoxib. However, these conjugates could get aggregated, and they may also pose health risks due to the involvement of heavy metals. Supramolecular chemistry could play a pivotal role in addressing both the aggregation and safety issues without compromising its utility. The discovery of supramolecular aggregation-induced emission (AIE) probes and their applications to drug conjugates have been demonstrated in a few studies. Taken together, this report summarizes the significance of advanced diagnostic drugs possessing AIE-conjugated probes for use in diagnosis and therapy.

A mesoporous silica-encapsulated wheat straw-derived carbon dots functionalized with Schiff base silane pockets (m-SiO2_ws-CDs@SBs) has been developed. m-SiO2_ws-CDs@SBs provides a synergistic platform that integrates the benefits of each component, including the optical properties of CDs, the high surface area and robustness of m-SiO2, and the molecular recognition capabilities of Schiff bases. The fluorescence of m-SiO2_ws-CDs@SBs remained constant, whereas upon the addition of aspirin (ASP), the fluorescence of m-SiO2_ws-CDs@SBs was quenched. m-SiO2_ws-CDs@SBs exhibit high sensitivity (limit of detection = 3.69 nM), linearity over a concentration range between 18-140 nM with R [2] of 0.9809. The m-SiO2_ws-CDs@SBs showed pronounced fluorescence quenching towards ASP and excellent selectivity for ASP in the presence of other pharmaceutical drugs, i.e., diclofenac, ibuprofen, naproxen, and mefenamic acid. Moreover, it displayed negligible interference from common excipients and metal ions at 1 : 1 and 1 : 10 molar ratios of ASP and interferent, respectively. The fluorescent probe has been used to analyze ASP in an aspirin drug product available at a local pharmacy, as well as in tap water and river water with an excellent recovery of 95.00-99.44%.