Dual modules-molecularly imprinted patch-enabled enantioselectively controlled release of racemic drugs for transdermal delivery.

Over 90 % of chiral drugs applied in transdermal drug delivery system (TDDS) are racemates, significantly increasing risks of side effects. Herein, we designed a chiral molecularly imprinted patch (CMIP) that achieved enantioselectively controlled release of S-enantiomers (eutomers) and inhibited the release of R-enantiomers (distomers) for transdermal drug delivery. It is composed of chiral pressure sensitive adhesive (PSA) and molecularly imprinted polymers (MIP), showing better transdermal delivery of S-enantiomers than that of R-enantiomers in vitro (1.

Individuals with anxiety and depression use atypical decision strategies in an uncertain world.

Previous studies on reinforcement learning have identified three prominent phenomena: (1) individuals with anxiety or depression exhibit a reduced learning rate compared to healthy subjects; (2) learning rates may increase or decrease in environments with rapidly changing (i.e. volatile) or stable feedback conditions, a phenomenon termed ; and (3) reduced learning rate adaptation is associated with several psychiatric disorders.

Morning resting hypothalamus-dorsal striatum connectivity predicts individual differences in diurnal sleepiness accumulation.

While the significance of obtaining restful sleep at night and maintaining daytime alertness is well recognized for human performance and overall well-being, substantial variations exist in the development of sleepiness during diurnal waking periods. Despite the established roles of the hypothalamus and striatum in sleep-wake regulation, the specific contributions of this neural circuit in regulating individual sleep homeostasis remain elusive. This study utilized resting-state functional magnetic resonance imaging (fMRI) and mathematical modeling to investigate the role of hypothalamus-striatum connectivity in subjective sleepiness variation in a cohort of 71 healthy adults under strictly controlled in-laboratory conditions.

Locus coeruleus microstructural integrity is associated with vigilance vulnerability to sleep deprivation.

Insufficient sleep compromises cognitive performance, diminishes vigilance, and disrupts daily functioning in hundreds of millions of people worldwide. Despite extensive research revealing significant variability in vigilance vulnerability to sleep deprivation, the underlying mechanisms of these individual differences remain elusive. Locus coeruleus (LC) plays a crucial role in the regulation of sleep-wake cycles and has emerged as a potential marker for vigilance vulnerability to sleep deprivation.

A longitudinal study on the effect of labor values on benign/malicious envy: the mindfulness reperceiving model.

This study investigates the relationship between labor values and two forms of envy-benign and malicious-as well as the potential mediating role of mindfulness using a mindfulness reperceiving model. Two thousand three hundred sixty three Chinese teenagers participated in a longitudinal study over an eight-month period, completing questionnaires measuring labor values, benign envy, malicious envy, and mindfulness. The cross-sectional data showed that labor values had an immediate negative effect on malicious envy, with mindfulness partially mediating this relationship.

Extreme Li-Mg selectivity via precise ion size differentiation of polyamide membrane.

Achieving high selectivity of Li and Mg is of paramount importance for effective lithium extraction from brines, and nanofiltration (NF) membrane plays a critical role in this process. The key to achieving high selectivity lies in the on-demand design of NF membrane pores in accordance with the size difference between Li and Mg ions, but this poses a huge challenge for traditional NF membranes and difficult to be realized. In this work, we report the fabrication of polyamide (PA) NF membranes with ultra-high Li/Mg selectivity by modifying the interfacial polymerization (IP) process between piperazine (PIP) and trimesoyl chloride (TMC) with an oil-soluble surfactant that forms a monolayer at oil/water interface, referred to as OSARIP.

Preparation of -Crocetin with High Solubility, Stability, and Oral Bioavailability by Incorporation into Three Types of Cyclodextrins.

Crocetin (CRT), an active compound isolated from saffron, exhibits several pharmacological activities, including anti-tumor and immune-regulatory activities, and is effective against myocardial ischemia and coronary heart disease; however, its low stability and solubility limit its clinical application. Therefore, we investigated CRT inclusion complexes (ICs) with three cyclodextrins-α-CD, HP-β-CD, and γ-CD-suitable for oral administration prepared using an ultrasonic method. Fourier transform infrared spectroscopy and powder X-ray diffraction indicated that the crystalline state of CRT in ICs disappeared, and intermolecular interactions were observed between CRT and CDs.

Ternary Deep Eutectic Solvents System of Colchicine, 4-Hydroxyacetophenone, and Protocatechuic Acid and Characterization of Transdermal Enhancement Mechanism.

This study aimed to prepare colchicine (CO), 4-hydroxyacetophenone (HA), and protocatechuic acid (CA) contained in transdermal rubber plasters into a more releasable and acrylate pressure-sensitive adhesive (PSA) to optimize traditional Touguling rubber plasters (TOU) with enhanced transdermal permeability by using deep eutectic solvents (DES) technology. We compared the difference in the release behavior of CO between rubber plaster and PSA, determined the composition of the patch through pharmacodynamic experiments, explored the transdermal behavior of the three components, optimized the patch formula factors, and improved the penetration of CO through the skin. We also focused on elucidating the interactions among the three components of DES and the intricate relationship between DES and the skin.

The enantioselective enhancing effect and mechanistic insights of chiral enhancers in transdermal drug delivery.

Overlook of chiral consideration in transdermal drug delivery increases administrated dose and risk of side effects, decreasing therapeutical effects. To improve the transdermal delivery efficiency of eutomer, this work focused on investigating the law and mechanism of enantioselective enhancing effects of chiral permeation enhancers on drug enantiomers. Chiral nonsteroidal anti-inflammatory drugs and terpene permeation enhancers were selected as model drug and enhancers.

Sleep deprivation attenuates neural responses to outcomes from risky decision-making.

Sleep loss impacts a broad range of brain and cognitive functions. However, how sleep deprivation affects risky decision-making remains inconclusive. This study used functional MRI to examine the impact of one night of total sleep deprivation (TSD) on risky decision-making behavior and the underlying brain responses in healthy adults.

Sleep Architecture and Sleep EEG Alterations are Associated with Impaired Cognition Under Sleep Restriction.

Purpose: Many studies have investigated the cognitive, emotional, and other impairments caused by sleep restriction. However, few studies have explored the relationship between cognitive performance and changes in sleep structure and electroencephalography (EEG) during sleep. The present study aimed to examine whether changes in sleep structure and EEG can account for cognitive impairment caused by sleep restriction.

Enhanced amygdala-cingulate connectivity associates with better mood in both healthy and depressive individuals after sleep deprivation.

Sleep loss robustly disrupts mood and emotion regulation in healthy individuals but can have a transient antidepressant effect in a subset of patients with depression. The neural mechanisms underlying this paradoxical effect remain unclear. Previous studies suggest that the amygdala and dorsal nexus (DN) play key roles in depressive mood regulation.

Construction of Imatinib Controlled Release Film-Forming System Based on Drug Ion-Pair and Oligomeric Ionic Liquids for the Long Local Therapy of Cutaneous Melanoma.

An imatinib controlled release film-forming system (FFS) was developed based on the drug ion-pair and newly designed oligomeric ionic liquids (OILs) for the topical therapy of cutaneous melanoma, which avoided the systemic side-effect of oral administration and maintained a long local therapy effect. The OILs significantly improved the drug release capacity about 1.5-fold, and the formability and stability of FFSs (verified by AFM/PLM).

Controlled Interfacial Polymer Self-Assembly Coordinates Ultrahigh Drug Loading and Zero-Order Release in Particles Prepared under Continuous Flow.

Microparticles are successfully engineered through controlled interfacial self-assembly of polymers to harmonize ultrahigh drug loading with zero-order release of protein payloads. To address their poor miscibility with carrier materials, protein molecules are transformed into nanoparticles, whose surfaces are covered with polymer molecules. This polymer layer hinders the transfer of cargo nanoparticles from oil to water, achieving superior encapsulation efficiency (up to 99.

A skin pharmacokinetics study of permeation enhancers: The root cause of dynamic enhancement effect on in vivo drug permeation.

Skin pharmacokinetics (SPK) of permeation enhancers can answer the question of why enhancement effects different at the kinetic level. Herein, SPK of permeation enhancers were classified into two categories, namely, lateral elimination (elimination to surrounding stratum corneum (SC)) and longitudinal elimination (elimination to deep epidermal (EP)). They were evaluated with a specific parameter for permeation enhancers, diffusion ratio (DR), according to results of tissue-distribution test, molecular dynamic (MD) simulation, and confocal laser scanning microscopy (CLSM).

Donepezil accelerates the release of PLGA microparticles via catalyzing the polymer degradation regardless of the end groups and molecular weights.

Poly (lactic-co-glycolic acid) (PLGA) is one of the most successful polymers for sustained parenteral drug products in the market. However, rational selection of PLGA in the formulations is still challenging due to the lack of fundamental studies. The present study aimed to investigate the influence of donepezil (DP) on the in-vitro and in-vivo performance of PLGA sustained microspheres.

Persistent Ventral Anterior Cingulate Cortex and Resolved Amygdala Hyper-responses to Negative Outcomes After Depression Remission: A Combined Cross-sectional and Longitudinal Study.

Background: Major depressive disorder (MDD) is a highly prevalent mood disorder affecting more than 300 million people worldwide. Biased processing of negative information and neural hyper-responses to negative events are hallmarks of depression. This study combined cross-sectional and longitudinal experiments to explore both persistent and resolved neural hyper-responses to negative outcomes from risky decision making in patients with current MDD (cMDD) and remitted MDD (rMDD).

High drug-loading and controlled-release hydroxyphenyl-polyacrylate adhesive for transdermal patch.

Long-acting transdermal drug delivery system (TDDS) requires high drug-loading and drug controlled-release. To simultaneously improve drug-polymer miscibility and realize drug controlled-release, this work aimed to develop a new pressure sensitive adhesive modified with hydroxyphenyl (HP-PSA) by introducing doubly ionic H-bond into drug-PSA interaction. Eight model drugs divided into RN, RNH and no N type were chosen to understand the characteristics of the HP-PSA and inner mechanism.

Probing Pharmaceutical Strategies to Promote the Skin Delivery of Asiatic Acid from Hydrogels: Enhancement Effects of Organic Amine Counterions, Chemical Enhancers, and Microneedle Pretreatment.

Asiatic acid (AA) is a pentacyclic triterpene isolated from Centella asiatica, holding great promise for treating a variety of skin disorders. However, the dermal application of AA is limited by its poor solubility and permeability. This study aimed to identify a hydrogel formulation for AA and improve its skin penetration by various penetration enhancement methods.

The role of hydrophilic/hydrophobic group ratio of polyvinyl alcohol on the miscibility of amlodipine in orodispersible films: From molecular mechanism study to product attributes.

The miscibility of the therapeutic drug in the polymer matrix is the key to the successful design and development of orodispersible films (ODFs). In the present study, four hydrolyzed polyvinyl alcohols (PVAs) with identical polymerization degree were investigated as carriers for Amlodipine (AML) ODFs systematically. The drug-polymer miscibility and the intermolecular interaction were investigated by Flory-Huggins theory, Gordon-Taylor theory, molecular simulation, FTIR, Raman and H NMR.

Fe(III)-coordinated N-[tris(hydroxymethyl)methyl]acrylamide-modified acrylic pressure-sensitive adhesives with enhanced adhesion and cohesion for efficient transdermal application.

Pressure-sensitive adhesives are critical to the product's safety, efficacy, and quality in transdermal drug delivery systems. However, many defects of transdermal patches (e.g.

Efficacy and safety of permeation enhancers: A kinetic evaluation approach and molecular mechanism study in the skin.

This study sought to provide approach for evaluating and predicting the efficacy and safety of permeation enhancers on the basis of their kinetic distribution behavior in the skin dictated by physicochemical properties. Herein, the efficacy-safety regularity of eight permeation enhancers were studied with ex vivo skin permeation study, small-angle X-ray scattering, MTT assay, H&E staining, and in vivo skin erythema analysis, classifying into the following three categories: high enhancement-low irritation, medium enhancement-high irritation, and low enhancement-low irritation. These three modes were positively correlated with the distribution amount of permeation enhancers in the skin layers and verified by the in vitro tape-stripping study.

Development and preliminary validation of the chronic obstructive pulmonary disease scale quality of life instruments for chronic diseases-chronic obstructive pulmonary disease based on classical test theory and generalizability theory.

Quality of life (QOL) in patients with Chronic obstructive pulmonary disease (COPD) is a major global concern in respiratory care with the specific instruments used rarely being developed using a modular approach. This paper is aimed to develop the COPD scale of the system of QOL Instruments for Chronic Diseases (QLICD-COPD) by the modular approach based on Classical Test Theory and Generalizability Theory (GT). 114 inpatients with COPD were used to provide the data measuring QOL three times before and after treatments.

Colloidal Jamming by Interfacial Self-Assembled Polymers: A Robust Route for Ultrahigh Efficient Encapsulation.

The control of cargo phase-transfer is of interest for many applications in science and technology. Herein, we report a simple, versatile and robust method to block the phase-transfer of cargo colloids by interfacial self-assembled amphiphilic polymer molecules. After simply increasing the concentration of amphiphilic polymers, the orientation of interfacial polymer molecules changed from flat to upright, forming a thick three-dimensional polymer layer at the oil-water interface.