The infusion of generative AI (GenAI) is already disrupting established services. This technology’s generative and agentic nature challenges the design and management of service routines, which have been previously handled primarily by frontline service employees. Guided by organizational routines theory, our longitudinal study (2020–2024) examines how the infusion of GenAI changes routines in customer support services. We gathered interview data from 41 employees, managers, and AI experts in two phases, pre- and post-GenAI . Based on the analysis of the qualitative data, we revealed seven recurring micro-level augmentation patterns, illustrating how GenAI-infused service routines function. The results show that GenAI is primarily embedded in the backstage of knowledge-intensive services, from which it then permeates the frontstage. We contribute to the literature on hybrid human–AI service delivery by identifying augmentation patterns and conceptualizing service permeation via two mechanisms: (1) simultaneous service permeation , which unfolds as employees leverage GenAI in real-time and integrate GenAI’s responses, recommendations, and adaptations into the frontstage; (2) sequential service permeation , which emerges as employees perform new routines of documentation and AI feeding to facilitate GenAI’s adaptability in frontstage and backstage operations. The MAPs and service permeation mechanisms guide practitioners in integrating GenAI into service routines and managing novel employee-GenAI collaborations.

Research on hydrogen permeation mechanism and transport properties in polyvinylidene fluoride pipes

Neuropathic pain is a chronic condition arising from lesions or dysfunction of the somatosensory nervous system and remains difficult to treat with conventional oral medications due to poor bioavailability and systemic side effects. Transdermal delivery provides a promising alternative that bypasses hepatic first-pass metabolism and allows sustained drug release. In recent years, nanogel based systems three dimensional, hydrophilic polymeric networks of nanoscale size have emerged as versatile carriers capable of encapsulating both hydrophilic and lipophilic drugs. Their large surface area, tunable porosity, and responsiveness to physiological stimuli enhance skin penetration and enable controlled release at targeted sites. Key emphasis is placed on polymer selection, transdermal permeation mechanisms, preclinical outcomes, and translational challenges. Current evidence suggests that nanogel systems containing gabapentin, pregabalin, and lidocaine demonstrate superior pharmacokinetic profiles and patient compliance compared with conventional gels. However, large scale manufacturing, stability, and regulatory standardization remain critical hurdles. Continuous innovation in polymer design and stimuli-responsive nanogels is expected to expand their clinical potential in chronic neuropathic pain therapy.

Permeation experiments reveal the mechanism of membrane permeation

Transdermal peptides, Engineered from bioactive peptides through rational sequence modification and structural optimization, transdermal peptides have emerged as a transformative strategy for enhancing the transdermal delivery of macromolecular drugs, proteins, and nucleic acids. This review outlines the structural classifications of bioactive peptides, including short, linear, cyclic, cationic, anionic, and neutral peptides, as well as their diverse biological sources. It focuses on the design principles and penetration mechanisms of transdermal peptides. These peptides interact dynamically with skin constituents, such as lipids and keratins, by fine-tuning the hydrophilic-hydrophobic balance, molecular weight, and conformational stability. This transiently disrupts the stratum corneum barrier and facilitates drug permeation via endocytosis and receptor-mediated pathways. They find applications in various pharmaceutical domains, including localized anticancer and antimicrobial therapies, as well as in cosmetics for whitening, anti-aging, and moisturizing. They are also being explored in innovative areas such as hair regeneration and wound healing. When combined with advanced delivery platforms, such as nanocarriers, microneedles, and microfluidic systems, transdermal peptides can significantly improve targeting efficacy and enable controlled release. Despite challenges related to peptide immunogenicity and scalable synthesis, the future integration of smart, stimuli-responsive technologies and artificial intelligence promises to Bioactive peptides, Skin permeation mechanisms, Skin transmission, Transdermal peptidesadvance personalized transdermal therapeutics.

Limited drug permeation across the stratum corneum remains a major challenge in transdermal patch development, while integrated analyses linking physicochemical drug properties with formulation design are still scarce. This study aimed to synthesize the influence of physicochemical parameters on the effectiveness of transdermal patch systems through a descriptive analytical literature review of seven peer-reviewed articles published within the last decade. The analysis demonstrates that drugs with low molecular weight (<500 Da), optimal lipophilicity (log P 1–3), low melting point (<200°C), pKa compatible with skin pH, low polar surface area, and limited hydrogen bonding capacity exhibit considered superior transdermal permeability. Furthermore, interactions between drugs and formulation components including polymer matrices, plasticizers, and penetration enhancers were found to modulate skin permeation mechanisms and drug release profiles. This review highlights that the success of transdermal patches relies on the synergistic optimization of physicochemical drug properties and mechanism-based formulation strategies, providing a rational framework for the development of effective and clinically relevant transdermal delivery systems

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel activated by heat, acidity and chemical ligands. While molecular dynamics simulations have shed some light on the cation permeation processes of TRPV1, the mechanisms in the native-state structure under near-physiological conditions remain unestablished. Therefore, the present study conducted molecular dynamics simulations of near-full-length human TRPV1 under a membrane potential of − 100 mV. During permeation events, sodium ions transiently interacted with three binding sites within the channel pore and moved toward the intracellular side. Potential of mean force analyses revealed that sodium ions in the selectivity filter reduced the energy barrier at the hydrophobic gate, facilitating permeation through cooperative interactions. Additionally, mutation of N677, a pre-gate binding site residue, reduced permeation events. Interaction analysis demonstrated that this residue plays an important role in efficient permeation by mediating moderately strong interactions with sodium ions through their coordinated water molecules. These findings highlight the importance of sodium ion accommodation at the selectivity filter and its interaction with N677 for ion permeation through TRPV1. Our data provide new insights into the gating and conduction mechanisms of TRPV1 under near-physiological conditions.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-29092-1.

Two-dimensional(2D) materials emerge as promising alternativesto conventional polymer-based proton exchange membranes (PEMs) dueto their high proton conductivity, mechanical robustness, and surfacetunability. Here we present an integrated framework combining ab initiomolecular dynamics (AIMD) simulations and machine learning (ML) toaccelerate the discovery of proton- and hydrogen-transport propertiesover 866 nonmetallic 2D materials. Three ML models were trained usingAIMD-derived permeation barriers from 488 materials, with Random Forestachieving the highest accuracy and revealing structure–propertyrelationships that govern proton transport. Critical descriptors,including proton−atom distance, pore size, interlayer spacing,and electron affinity, emerged as key predictors of permeation behavior.H+/H2 selectivity through additional AIMD simulationsallowed identifying 18 promising candidates, including the experimentallystudied graphene and hexagonal boron nitride, thus supporting therobustness of our approach. Experimentally synthesized but barelyexplored materials, including 2D Si, Ge, TeC, TeCl, GeSe and CSe,emerged as strong candidates for proton conducting membranes. Theframework further highlights theoretically stable compounds as unexploredopportunities for PEMs. By integrating atomic-scale simulations withdata-driven models, this work provides both fundamental insights intoproton permeation mechanisms and practical guidance for designingselective, high-performance nanomaterials for hydrogen energy technologies.

BackgroundPsoriasis is a long-term inflammatory skin disorder that significantly impacts the physical and psychological well-being of those affected. Curcumin (Cur) is a natural compound that holds promise for the topical management of psoriasis. However, the barrier property of the stratum corneum (SC) and the insufficient retention ability of the drug in the skin have severely restricted the clinical efficacy of Cur. To overcome these limitations, we introduced mussel adhesive protein (MAP) for its superior bioadhesive properties, and developed Cur-loaded MAP modified Pluronic F127 micelles (MAP-F127/Cur) to improve the skin permeation and retention of Cur and enhance the therapeutic effect on psoriasis.MethodsIn this study, MAP-F127 was synthesized via chemical synthesis. MAP-F127/Cur was prepared using the thin-film hydration method, and the physicochemical properties of the formulation were characterized. In addition, porcine skin was employed as an in vitro model to evaluate the skin permeation of the formulation and to elucidate the interaction mechanism between the formulation and the skin. Furthermore, the therapeutic efficacy of the formulation against psoriasis was assessed using an imiquimod-induced psoriasis mouse model.ResultsThe prepared MAP-F127/Cur had a regular spherical shape and good dispersion, and could efficiently load Cur in the amorphous form. The skin retention of MAP-F127/Cur was notably elevated in comparison to both the Cur-loaded Pluronic F127 micelles (F127/Cur) and Cur solution (p<0.01). Studies on the skin permeation mechanism showed that MAP-F127/Cur could break through the restriction of the skin barrier by regulating lipid arrangement and keratin conformation in the SC, forming a long-acting drug reservoir in the epidermal layer. Furthermore, in the imiquimod-induced psoriasis mouse model, MAP-F127/Cur demonstrated a significantly enhanced therapeutic effect.Conclusion: This study not only provides a new delivery strategy for Cur in the treatment of psoriasis, but also offers an important reference for designing transdermal delivery systems for other dermatological drugs.

Elucidating the mechanism of phenol exclusion and water permeation in graphyne anopore membranes: A combined DFT and reactive MD simulation study

Spectroelectrochemical analysis of membrane permeation mechanisms of cell-penetrating peptide-modified fluorescent proteins.

Lipid-based nanocarriers have emerged as highly promising systems in the development of advanced pharmaceutical formulations aimed at improving therapeutic efficacy, drug penetration, and safety profiles. Their intrinsic biocompatibility, biodegradability, and structural resemblance to biological membranes allow these carriers to encapsulate both hydrophilic and lipophilic drugs efficiently while minimizing systemic toxicity. Transdermal drug delivery, an important route for managing local and systemic conditions affecting the skin, eyes, rectum, and vagina, benefits greatly from these nanoscale systems due to their ability to overcome the barrier properties of the stratum corneum. The inherent flexibility, small size, and lipid composition of nanocarriers such as liposomes, transferosomes, invasomes, and ethosomes facilitate deeper skin penetration and controlled or sustained release of therapeutic agents. As a result, lipid-based nanocarriers enhance drug stability, prolong residence time, and improve patient compliance when compared to conventional dosage forms. Their application extends across various therapeutic areas, including dermatological disorders, inflammatory conditions, localized infections, and targeted chemotherapy. This review provides a comprehensive overview of the types of lipid-based nanocarriers employed in transdermal drug delivery, highlighting their structural characteristics, mechanisms of skin permeation, advantages, and inherent limitations. Furthermore, it discusses commonly used preparation techniques, including thin-film hydration, ethanol injection, ultrasonication, high-pressure homogenization, and microemulsion methods, along with key characterization parameters such as vesicle size, zeta potential, entrapment efficiency, deformability, and stability. Overall, the paper emphasizes the growing significance of lipid-based nanocarriers as versatile, effective, and innovative tools for enhancing transdermal drug delivery and expanding the future possibilities of topical and systemic therapeutic interventions.

Advancing next-generation electrochemical systems for energy conversion requires a comprehensive understanding of the coupled processes of charge carrier generation, electron and ion transport, and interfacial electrochemical reactions. In this work, we integrate ab initio and machine learning-enhanced molecular dynamics simulations to investigate electrocatalytic water oxidation and selective species transport in photoelectrochemical and photocatalytic systems. For halide perovskite photoabsorbers with long carrier lifetimes, we demonstrate that spontaneous polarization domains and lattice dynamics govern charge separation and carrier dynamics. In colloidal suspension-type photocatalytic systems, we examine how the chemistry and geometry of protective oxide coatings influence the transport of reactants and redox shuttles through nanopores, revealing mechanisms of selective permeation that are potentially critical to Z-scheme photocatalysis. Furthermore, grand-canonical DFT simulations on IrO₂ surfaces under varying potentials reveal that surface hydrogen coverage directly modulates oxygen evolution reaction (OER) barriers and Tafel behavior. A continuum microkinetic model incorporating voltage-dependent surface coverage and active site accessibility successfully reproduces experimental current-voltage characteristics. Together, these findings highlight the synergistic effects of electrostatics, solvation, and surface chemistry on electrocatalytic performance, providing a rational framework for catalyst–overlayer interface design in water splitting and related reactions.This work was partially performed under the auspices of the U.S. DOE by Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344 and supported by the U.S. DOE, Office of Energy Efficiency and Renewable Energy, Hydrogen and Fuel Cell Technologies Office as well as Office of Science, Basic Energy Science Program.

Proton exchange membrane water electrolyzers (PEMWEs) offer a promising pathway to produce hydrogen with low carbon footprint. However, cost, efficiency and durability are still barriers to the commercialization of this technology. The use of thin membranes under differential pressure remains a major challenge due to significant hydrogen crossover from the cathode to the anode. This not only slightly reduces system efficiency but also poses a safety hazard, as the presence of more than 4% hydrogen in oxygen at the anode forms a flammable gas mixture. Therefore, to safely and efficiently operate PEMWEs, it is essential to implement gas recombination catalysts (GRC) that combine hydrogen with oxygen, thereby lowering the hydrogen concentration at the anode. Designing such GRC strategies that effectively consume H2 requires a comprehensive understanding of gas crossover in these systems.In our previous work, we found that PEMWEs exhibit noticeable hydrogen oxidation current (HOR) under differential pressure.1 These HOR currents, only observed at differential pressures, are diffusion-limited and consume a significant portion of permeated hydrogen. Therefore, we combined in-operando gas chromatography measurements at the anode outlet with HOR current measurements to calculate hydrogen crossover rates as a function of cathode backpressure and current density for various PEMWE architectures. Our results show that H2 crossover rates increase as a function of differential pressure as well as current density revealing two distinct gas permeation mechanisms- diffusion or pressure driven pathway and supersaturation or concentration driven pathway (Figure 1). The effect of current density is slightly weaker at high current densities (above 2 A.cm-2), where supersaturation competes with the water permeation from anode to cathode due to the electroosmotic drag. Additionally, we will also present our findings on the effect of the GRC architecture and the location of the GRC in the membrane on reducing the H2 content at the anode.Acknowledgements: This research is supported by the U.S. Department of Energy (DOE) Hydrogen and Fuel Cell Technologies Office (HFTO) through the Hydrogen from Next-generation Electrolyzers of Water (H2NEW) consortium.

Bamboo, a fast-growing and biodegradable industrial crop, exhibits excellent mechanical properties, which facilitate its widespread use in construction, furniture, and decorative applications. However, its inherently limited permeability hinders processing during drying, chemical modification, dyeing, and impregnation. Although previous studies have explored structural and treatment-related aspects, few have offered a comprehensive and integrative overview that bridges anatomical structure, permeation mechanisms, performance evaluation, and treatment strategies. This review synthesizes 126 publications from 1997 to 2024 to provide a comprehensive, multidimensional analysis of bamboo permeability. Structure–function relationships are examined by assessing how vessels, sieve tubes, perforation plates, pits, and bamboo nodes influence permeability, with an emphasis on quantitative correlations. Capillarity, diffusion, and viscous resistance are integrated into a unified theoretical framework, proposing a model that couples longitudinal capillary rise with transverse diffusion. Detection approaches, including both direct techniques (weight gain, microscopy, tracer elements, fluorescence imaging) and indirect techniques (porosity measurement, Micro-CT), with their respective advantages, limitations, and applications. Enhancement strategies are categorized into chemical, physical, and biological methods, with assessments of their effectiveness, environmental impact, and energy consumption. Overall, this review provides a holistic perspective on bamboo permeability and offers valuable guidance for future research and engineering applications.

Insights into Proton Permeation Mechanism in Graphene and Graphene Oxide for PEM Fuel Cells

Layered graphene oxide (GO) has emerged as an ideal membrane structure for water desalination. In GO-stacked structures, the slit gaps between GO nanosheets can serve as critical pathways for molecule permeation. Exploring the permeation mechanisms of functionalized GO nanoslits is critical for improving the separation performance. Herein, molecular simulations were performed to investigate the water permeation and ion rejection for six types of ionic solutions by considering edge-amino functionalized GO (NGO) slit membranes. The NGO slit exhibits higher ion retention while maintaining reasonable water permeability. Edge amine groups can interact strongly with water molecules and immobilize ions, thus enhancing ion rejection. The thermodynamic free energy for ion passing was simulated to explain the unique ion rejection mechanism of amine-functionalized GO slits. The thermodynamic barrier for ion rejection can be considered as the delicate combination of the ion dehydration effect and the slit-generated attraction. The ion dehydration accounts for a repulsive contribution, which is the controlling portion in governing the free-energy profile. Overall, our work is important and valuable for the development and design of new-type layered GO membranes.

The selectivity filter (SF) of aquaporins (AQPs) governs substrate specificity and permeation efficiency. Despite its functional importance, the mechanistic basis of SF-mediated water transport remains poorly understood, primarily due to the challenge of analyzing the local chemical environment surrounding the SF region. In this study, we employed an integrated approach combining functional measurements, magic-angle spinning solid-state nuclear magnetic resonance (MAS ssNMR) spectroscopy, and computational tools to perform comparative analyses of wild-type and variants of Arg189, a highly conserved residue in the SF region of Escherichia coli aquaporin Z (AqpZ). Our findings reveal that Arg189 plays an indispensable role in stabilizing the hydrogen-bond network and maintaining the proper electrostatic potential distribution along the channel. Specifically, interactions mediated by Arg189 are essential for establishing a continuous, single-file water chain, ensuring efficient water permeation. These results provide atomic-level mechanistic insights into how the SF region fine-tunes the function of AQPs.

The passive membrane permeation of small-molecule drugs and small hydrophobic peptides is relatively well understood. In contrast, how long polar peptides can pass through a membrane has remained a mystery. This process can be achieved with permeation enhancers, contributing significantly to the oral transcellular absorption of important peptide drugs like semaglutide — the active pharmaceutical ingredient in Ozempic, which is used as Rybelsus in a successful oral formulation. Here we now provide a detailed, plausible molecular mechanism of how such a polar peptide can realistically pass through a membrane paired with the permeation enhancer salcaprozate sodium (SNAC). We provide both simulation results, obtained with scalable continuous constant pH molecular dynamics (CpHMD) simulations, and experimental evidence (NMR, DOSY, and DLS) to support this unique permeation mechanism. Our combined evidence points toward the formation of permeation-enhancer-filled, fluid membrane defects, in which the polar peptide can be submerged in a process analogous to quicksand.

Steroidal sodium channel agonist batrachotoxin (BTX), one of the most potent animal toxins, dramatically increases calcium permeation and alters other channel characteristics. In a cryoEM structure of rat sodium channel Nav1.5 with two BTX-B molecules, one toxin binds between repeats III and IV and exposes to the pore lumen two oxygen atoms and protonatable nitrogen. The mechanism of ion permeation and selectivity in BTX-bound channel is unclear. Here Monte Carlo energy-minimized profiles of sodium and calcium ions pulled through the pore were computed in models with various protonated states of the DEKA lysine and BTX-B. The only model where the ions readily passed by the DEKA lysine and BTX-B involved their deprotonated nitrogens. In this model, electronegative atoms of BTX-B attracted a permeant cation that stabilized the “dunked” lysine through electrostatic interactions and nearby water molecules. This would retard reprotonation of the lysine and its “uplifting” to the DEKA carboxylates, which otherwise attracts calcium. The results suggest how sodium and calcium ions pass through BTX-bound sodium channel and why BTX increases calcium permeation. The study supports an earlier hypothesis that during the sodium ion permeation cycle, the DEKA lysine alternates between uplifted and dunked conformations in the protonated and deprotonated states, respectively, while the sodium-displaced proton and the sodium ion nullify the net electrical charge at the DEKA region.