An inhalable composite particulate system for targeted delivery of therapeutics deep into small airways: in vitro and in vivo evaluation.

Chronic obstructive pulmonary disease (COPD) is characterized by the airflow limitation due to chronic inflammation and excessive airway mucus secretion. Targeted delivery of therapeutics deep into small airways is the key step in treatment of COPD. In this study, we designed an inhalable composite particulate system with nano in micro structure for targeted delivery of therapeutics deep into small airways.

Catheter-Integrated Fractal Microelectronics for Low-Voltage Ablation and Minimally Invasive Sensing.

Pulse field ablation (PFA) has become a popular technique for treating tens of millions of patients with atrial fibrillation, as it avoids many complications associated with traditional radiofrequency ablation. However, currently, limited studies have used millimeter-scale rigid electrodes modified from radiofrequency ablation to apply electrical pulses of thousands of volts without integrated sensing capabilities. Herein, we combine fractal microelectronics with biomedical catheters for low-voltage PFA, detection of electrode-tissue contact, and interventional electrocardiogram recording.

ncRNAs-Mediated Pyroptosis in Cerebral Ischemia-Reperfusion Injury: Pathophysiology, Mechanisms, and Therapeutic Perspectives.

Cerebral ischemia-reperfusion injury (CIRI) is a complex pathological process triggered by transient obstruction of blood flow and subsequent reperfusion, ultimately leading to intracellular disturbances such as oxidative stress, inflammatory responses, and programmed cell death. Among the various types of cell death, pyroptosis (an inflammatory kind of regulated cell death) has received increasing attention due to its involvement in key neurovascular unit cells, including endothelial cells, neurons, microglia, and astrocytes. Intriguingly, accumulating evidence demonstrates that non-coding RNAs (ncRNAs), including long non-coding RNAs, microRNAs, and circular RNAs, can modulate multiple stages of pyroptosis in CIRI.

Dissecting the molecular landscape of Parkinson's disease and Parkinson's disease dementia using highly efficient snRNA-seq (HIF-snRNA-seq).

This study presents a transcriptomic analysis of the cingulate cortex (CING) in Parkinson's disease (PD) and Parkinson's disease dementia (PDD) using a High-efficiency single-nucleus RNA sequencing (HiF-snRNA-seq) protocol optimized for post-mortem brain samples. RNA quality prediction, poly-A tailing, and dCas9-targeted depletion enabled analysis of 77 high-quality samples from 240 cases, yielding over 2 million nuclei classified into seven major cell types. Disease conditions revealed altered astrocyte and microglia proportions, implicating their roles in neuroinflammation.

Test-retest reliability of coupling between cerebrospinal fluid flow and global brain activity after normal sleep and sleep deprivation.

The glymphatic system (GS) plays a key role in maintaining brain homeostasis by clearing metabolic waste during sleep, with the coupling between global blood-oxygen-level-dependent (gBOLD) and cerebrospinal fluid (CSF) signals serving as a potential marker for glymphatic clearance function. However, the test-retest reliability and spatial heterogeneity of gBOLD-CSF coupling after different sleep conditions remain unclear. In this study, we assessed the test-retest reliability of gBOLD-CSF coupling following either normal sleep or total sleep deprivation (TSD) in 64 healthy adults under controlled laboratory conditions.

Impact of childhood maltreatment on adolescents' mental health- a longitudinal study based on dual-factor model.

The dual-factor model (DFM) of mental health has received increasing support in recent years. However, researchers have limited knowledge regarding the longitudinal changes in the DFM of mental health. This study considered the dual-factor mental health among adolescents using latent profile analysis (LPA).

Biochemical strategy-based hybrid hydrogel dressing-mediated in situ synthesis of selenoproteins for DFU immunity-microbiota homeostasis regulation.

Chronic consequences of diabetes that are most commonly encountered are diabetic foot ulcers (DFUs), driven by microbiota-immune system dyshomeostasis, eventually leading to delayed wound healing. Available therapies, such as systemic or topical administration of anti-inflammatory or antimicrobial agents, are limited due to antibiotic resistance and immune dysfunction. Herein, a hybrid hydrogel dressing is developed as the artificial bioadhesive barrier at wound sites to maintain microbial and immunological homeostasis locally and have potent anti-inflammatory effects.

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).