Optimal foraging behavior is a key component of successful adaptations to natural environments. Understanding how animals decide to stay near food or to leave it for another food patch gives us insights into the underlying cognitive mechanisms that govern adaptive behaviors. 3D pose tracking was used to determine how pigeons exploit a 4 square meter arena with two separate platforms (i.e. food patches) whose absolute and relative elevations were manipulated. Detailed kinematic features of foraging and traveling behaviors were quantified using automated video tracking, without a need for manual coding. Our computational approach captured continuous, high-dimensional movement patterns and enabled precise quantification of travel costs between patches. Combined with mixed-effects survival analysis, our fine-grained behavioral tracking provided detailed insight into the moment-by-moment dynamics of patch-leaving decisions of pigeons. As expected from behavior optimization models, our results showed a preference to visit a ground food platform first, and longer latencies to leave an elevated platform. Foraging activity significantly decreased throughout the session, with shorter visits, less pecks per visit, and a decrease in inter-peck variability. However, a mixed-effects Cox regression modeled pigeons' patch-leaving probability, demonstrating that current and cumulative foraging parameters between patches significantly enhanced the model's predictive power beyond patch accessibility (i.e., beyond travel costs). This suggests that pigeons integrate both current environmental cues and their individual foraging history when making patch-leaving decisions. Our findings are discussed in relation to the marginal value theorem and optimal foraging theory.
Spinal arachnoid cysts (SACs) are rare intraspinal lesions containing cerebrospinal fluid (CSF). Symptomatic SACs require surgical decompression, but excision can be complicated by iatrogenic dural tears (incidental durotomy), which occur in 1-17% of spinal surgeries. Effective, watertight closure is critical to prevent CSF leakage, infection, and recurrence. Long-term data exceeding 5 years on artificial dural patch repairs are scarce. A 50-year-old female presented with severe low back pain and left-leg radiating pain. Magnetic resonance imaging (MRI) revealed a T2-hyperintense intradural cystic lesion at L2-3 compressing the cauda equina, consistent with an arachnoid cyst. She underwent L2-3 posterior decompression and posterolateral fusion with microscopic cyst excision. During adhesiolysis, a significant dural tear occurred. The defect was repaired using a suturable artificial dural patch to achieve watertight closure. Postoperative recovery was uneventful. At the 10-year follow-up, the patient remained asymptomatic, and MRI confirmed a stable repair without cyst recurrence or pseudomeningocele. The imaging features supported a symptomatic intradural SAC. Literature mandates surgical intervention for symptomatic cases but emphasizes meticulous dural repair to minimize CSF leak risks. Our findings align with systematic reviews suggesting patch-reinforced closure yields lower leak rates (5.5%) compared to suture alone. The 10-year stability validates the biocompatibility and durability of the artificial patch. Artificial dural patch suturing delivered excellent, durable outcomes over a decade after intradural cyst excision. This technique is recommended for managing complex dural defects to ensure long-term success.
We study ionic charge localization and transport in electrolyte-filled nanochannels with heterogeneous walls. Localized charged patches at the channel boundaries trap counterions, enabling controlled charge accumulation in otherwise straight channels. Combining lattice-Boltzmann simulations with analytical modeling, we show that the stability and mobility of these charge clouds result from a balance between electrostatic forces, hydrodynamic drag, and diffusion. Under applied electric fields and pressure gradients, localized charge produces diode-like rectification. Pressure-driven flow shifts the dissociation threshold of the counterion cloud, yielding strongly asymmetric current-voltage characteristics. A minimal force-balance model quantitatively captures the rectification window and its linear dependence on the pressure gradient, demonstrating rectification in the absence of geometric asymmetry. We further examine dynamic control using moving wall patches. In the linear electrostatic regime, charge responds diffusively to patch motion, while strong wall potentials induce a strong colocalization and active charge transport. We identify drift- and diffusion-dominated transport regimes and a critical patch velocity beyond which charge localization fails. These results establish patchy wall potentials as a minimal mechanism for controlling ionic localization, rectification, and transport in nanochannels.
The nucleosome acidic patch is a hub of coordinated engagement by proteins that regulate genomic function. Here, we report that Saccharomyces cerevisiae Dot5 contains an arginine-rich HMGN-like motif that mediates nucleosome acidic patch binding and is required for the cell growth, DNA repair, and heterochromatin defects exhibited when the protein is overexpressed. The heterologous expression of camelid single-chain antibodies to the nucleosome acidic patch confers a similar range of phenotypes, with the most severe observed when an "arginine-anchor" mode of binding analogous to many endogenous factors is employed. This highlights a delicate balance between nucleosome acidic patch interactors critical for normal cellular function and dysregulated in disease.
The efficacy of current opioid overdose interventions is fundamentally limited by their reliance on bystander detection and administration, leaving unwitnessed overdoses, a predominant cause of fatalities, unaddressed. Herein, we developed an innovative fentanyl-responsive microneedle (MN) patch (iNal patch) engineered as an autonomous harm reduction tool to dynamically release naloxone on demand in response to fentanyl levels. Specifically, the iNal patch integrates mesoporous silica nanoparticles (MSNs) loaded with naloxone. The nanoparticle surfaces are modified by fentanyl-sensitive aptamers, allowing precise and dose-dependent drug release triggered by fentanyl exposure. The engineered MN matrix composed of swellable maleated poly(vinyl alcohol) facilitates rapid skin penetration and interstitial fluid access, ensuring immediate and sustained naloxone release. From in vitro and in vivo studies, the iNal patch was demonstrated to effectively reverse fentanyl-induced opioid overdose symptoms, rapidly restore normal physiological behaviors in mice, and enable multiple responsive drug-release cycles to prevent renarcotization. This proof-of-concept MN platform establishes a new paradigm for materials-based harm reduction, offering an autonomous safety net for high-risk populations independent of human supervision.
The Mre11/Rad50 (MR) complex uses ATP binding and hydrolysis to coordinate the recognition and processing of DNA double-strand breaks. Although Mre11 and DNA stimulate the relatively slow ATPase activity of Rad50, the mechanism by which this occurs remains incompletely understood. In the present study, we investigated a basic patch on bacteriophage T4 Rad50, consisting of Arg154, Arg155, and Lys156, that was predicted to contribute to DNA binding. Mutation of these residues caused only modest changes in DNA affinity, indicating that this region is unlikely to function primarily as a direct DNA-contact surface. In contrast, the effects on ATP hydrolysis were pronounced. R154A and the TripleA mutant displayed strong ATPase activation in the presence of Mre11 alone, approaching the activity of the WT MR complex bound to DNA. DNA titrations further showed that these mutants were relatively insensitive to increasing dsDNA concentrations, consistent with a shift in the conformational equilibrium toward an ATPase-active-like state. However, ATP-dependent stimulation of repetitive nucleotide excision was reduced for all mutants, with the strongest defect observed for TripleA, indicating that enhanced ATP hydrolysis alone is not sufficient to support processive nuclease activity. A mutation at Asp479 had a related but distinct effect, supporting long-range coupling within the T4 MR complex. Overall, the results support a model in which a basic patch near the base of the Rad50 coiled-coils contributes to an allosteric pathway linking Mre11 and DNA engagement with productive ATP hydrolysis and its coupling to nuclease output.
Oxidation-prone omega-3 acid ethyl esters offer biologically attractive lipid cues for skin repair and dermocosmetic applications; however, their topical translation is constrained by poor aqueous compatibility, chemical lability, and limited residence at the skin interface. Herein, a coaxially electrospun core-shell nanofiber patch was developed to compartmentalize docosahexaenoic/eicosapentaenoic acid (DHA/EPA)-containing omega-3 ethyl esters within an Eudragit L100 (EL100) core while presenting a sodium alginate-κ-carrageenan (SA-CRG) polysaccharide shell. Electrospinning parameters were systematically optimized by tuning the EL100 concentration, the ethanol/N,N-dimethylformamide ratio, and the core/shell flow rates, yielding smooth, bead-free fibers with a continuous core-shell architecture, as verified by SEM and TEM. Although Ca2⁺-mediated ionic crosslinking enhanced shell compactness and tensile integrity, FTIR/DSC and surface-wettability changes indicated DHA/EPA oxidation and lipid redistribution during aqueous post-treatment; therefore, the non-crosslinked 25EL100(5:5)-DHA + EPA/SA-CRG mats were selected for delivery and biological evaluation. The optimized fibers combined a hydrophilic skin-contacting surface with controlled swelling at pH 4.0 and sustained omega-3 release over 120 h, reaching cumulative DHA and EPA release of 88.5% and 72.9%, respectively. Release kinetics were best described by the Korsmeyer-Peppas model (R2 = 0.9912 for DHA; R2 = 0.9884 for EPA), with n values below 0.45, indicating predominantly diffusion-governed transport. The nanofibers were cytocompatible with human dermal fibroblasts, maintaining 91.81% viability for the DHA/EPA-loaded formulation versus 97.65% for the placebo, and promoted fibroblast wound-closure behavior in scratch assays. Complementary microplate-based turbidimetric assays further indicated that the antibacterial performance of the DHA/EPA-loaded mats was influenced by lipid oxidative status. Oxidized DHA/EPA-loaded mats exhibited concentration-dependent suppression of bacterial growth, with a stronger effect against the Gram-positive Staphylococcus aureus than against the Gram-negative Escherichia coli, whereas non-oxidized mats showed weaker activity. Overall, EL100/SA-CRG core-shell nanofibers provide a dry, handleable, and biologically tolerated platform for sustained topical delivery of labile omega-3 ethyl esters, thereby supporting their further development as advanced dermal patches for skin repair and dermocosmetic applications.
Neutrophil gelatinase-associated lipocalin (NGAL) is a promising early biomarker for acute kidney injury (AKI), yet current biosensors lack the capability for minimally invasive, in situ, real-time analysis of interstitial fluid (ISF)-a key medium suitable for reliable continuous monitoring. Herein, we propose an aptamer-directed assembly strategy for the preparation of a nanocomposite microneedle patch. Briefly, a DNA1-decorated microneedle is successively modified with DNA-modified carbon dot (CD-DNA2) and gold nanoparticle (AuNP-DNA3, NGAL aptamer) via complementary base pairing. This triggers nanoparticle-based surface energy transfer between a luminescent donor (CD) and an absorbing acceptor (AuNP), quenching CD fluorescence. When the nanocomposite microneedle patch is transdermally applied to AKI mice for ISF sampling, recognition of NGAL by its aptamer triggers dissociation of the DNA2-DNA3 duplex, leading to AuNP release and CD fluorescence restoration. The captured irregular fluorescence images of the microneedle microarray with background interference are processed using a U-Net-based deep learning model for precise identification and signal extraction. This model establishes a strong positive correlation between fluorescence recovery and NGAL concentration (R2 = 0.9936), significantly outperforming the direct analysis of raw images (R2 = 0.5668). Therefore, this detection strategy precisely reveals elevated NGAL levels (∼80.7 ng/mL) as early as day 1 after modeling, signaling AKI onset 2-3 days earlier than clinical serum creatinine measurements using a commercial handheld analyzer or detection kit. In addition, this nanocomposite microneedle sensor possesses other advantages like minimal invasion and rather fast ISF collection (<15 min). This study offers an unprecedented diagnostic platform and pipeline for early AKI.
暂无摘要（点击查看详情）
Gastric cancer is the fifth most diagnosed cancer worldwide and is the fifth most deadly. An essential part of the diagnosis and prognosis of cancer is the histopathological tissue classification. Pathologists classify tissue samples, but this is labour-intensive and can produce inconsistent results. In this study, we analyse the performance of CTransPath, a Swin Transformer model, for eight-class tissue classification after being pretrained on 15 million histopathological images, using the HMU-GC-HE-30K dataset, which contains 31,096 samples of gastric tissues. In a tenfold stratified cross-validation, we use a two-stage transfer learning model with a custom combination of histopathology-related data augmentation, class-weighted loss, and cosine annealing. The model reaches a macro AUC of 96.82% (±0.23%) (bootstrap 95% CI 96.70-96.91%) with patch-level accuracy of 76.74% (95% CI 76.27-77.20%) and macro F1 of 76.73% (95% CI 76.27-77.17%), indicating strong patch-level discriminative ability across the eight tissue classes in this internal single-institution evaluation. A dedicated calibration analysis (Brier score 0.325, expected calibration error 0.027 at 15 bins, calibration slope 1.14) shows that the predicted probabilities are reasonably well calibrated, with a mild tendency towards over-confidence. Additionally, a 4-variant ablation study shows that unfreezing the backbones provides a 3.4 to 3.6 percentage-point improvement over fixed-backbone models. Compared to multiple data models and architectures including the recently published pathology models UNI (ViT-L, 100M+ patches) and Virchow2 (ViT-H, 3.1M slides), CTransPath has the least parameters and provides the best performance within this controlled internal patch-level comparison. Under the same threefold protocol, CTransPath retained a statistically significant patch-level accuracy advantage over ImageNet-pretrained Swin-T and ResNet-50 (paired bootstrap p < 0.001 ), as well as over the much larger UNI and Virchow2 foundation models (paired bootstrap p < 0.001 and p = 0.002 , respectively). Task-oriented model design and domain-specific pretraining appeared at least as effective as simply increasing model size for this task. Additionally, Grad-CAM, SHAP, t-SNE, and UMAP analyses provide qualitative evidence that the model attends to histologically meaningful regions as qualitative interpretability checks, not as confirmation of clinically validated reasoning. Because the public dataset lacks slide- and patient-level identifiers, these results should be interpreted strictly as single-institution, patch-level internal validation; potential data leakage from visually related patches cannot be excluded, and external multi-institution validation with slide-/patient-level evaluation is required before any clinical use. Our methodology and results provide a reproducible research benchmark for computational pathology research focused on gastric cancer.
Electrical stimulation of the dorsal genital nerve (DGN) using a patch electrode is effective in treating bowel dysfunction (BD) with faecal urgency and/or incontinence and overactive bladder (OAB). Keeping the patch electrode in place during stimulation may be challenging. This study evaluated the feasibility and safety of inserting a novel genital bar electrode for DGN stimulation. A vertical clitoral hood piercing with a specially designed genital bar electrode was inserted under aseptic conditions with topical anaesthesia in women who had undergone DGN stimulation via a patch electrode, and reported subjective symptom improvement. After a 4-week healing period, stimulation with the bar electrode was initiated, followed by completion of a similar symptom diary to that with the patch electrode. All 14 patients included in the study completed it. No procedure-related complications occurred. During the healing period, 10 patients experienced minor transient adverse events: mild bleeding or pain (n = 7 each), swelling (n = 4), redness (n = 3), and isolated numbness, irritation, or itching (n = 1 each). Nine patients experienced stimulation-related adverse events, mainly local pain or discomfort. Granulation tissue developed in one case. Urgency and incontinence episodes were reduced by a median of 70% and 59%, respectively, during genital bar electrode stimulation, with symptom responses similar to those observed with patch electrode stimulation. Inserting a genital bar electrode is feasible and safe. Preliminary results indicate a symptom response comparable to patch electrode stimulation in the majority.
Bronchial asthma (BA) is a chronic inflammatory airway disease for which conventional drug delivery routes show limited therapeutic efficacy. Herbal acupoint application offers targeted therapeutic benefits by combining pharmacological effects with specific acupoint stimulation; however, conventional patches are limited by poor sustained release and low patient compliance. Sinapine thiocyanate, a natural alkaloid with anti-inflammatory properties, has potential for asthma treatment, yet its poor bioavailability hinders its therapeutic application. To address these gaps, we developed sinapine thiocyanate‑loaded dissolvable microneedles (ST‑DMN) using polyvinylpyrrolidone K30 (PVP‑K30) and chondroitin sulfate (CS) as matrix materials, and polyvinyl alcohol (PVA) as the backing layer, designed for acupoint administration to achieve sustained drug release and improve therapeutic outcomes. ST-DMN patches with drug loadings ranging from 0.25 to 2.0 mg/patch were prepared, and a dose-response relationship was established in a rat model of BA to identify the optimal drug loading. The results demonstrated that ST-DMN at 1.5 and 2.0 mg/patch significantly improved the behavioral status of asthmatic rats, increased immune organ coefficients, and reduced the expression of IgE, TNF-α, and IL-1β. Based on a comprehensive assessment of efficacy and safety, 1.5 mg/patch was selected as the optimal dose. Network pharmacology analysis predicted that the PI3K/AKT signaling pathway was highly relevant to the anti-asthmatic effects of sinapine thiocyanate. Subsequent validation in animal models confirmed that the optimal dose of ST-DMN effectively ameliorated lung tissue pathology and reduced inflammatory cell infiltration. Furthermore, ST-DMN treatment significantly decreased the expression levels of key inflammatory factors and inhibited PI3K and AKT phosphorylation. The current findings suggest that ST-DMN at 1.5 mg/patch exerts therapeutic effects against BA through acupoint administration, likely by modulating the PI3K/AKT signaling pathway and suppressing inflammatory responses.
The efficacy of cholinesterase inhibitors varies depending on the severity of Alzheimer disease. We examined the effects of the disease severity on the efficacy of donepezil 27.5 mg patches in Japanese patients with Alzheimer disease. A post hoc analysis of covariance using per-protocol set in a noninferiority study of donepezil 27.5 mg patches with donepezil hydrochloride 5 mg tablets (JapicCTI-194582) was conducted after imputation of missing data using multiple imputations. No apparent imbalances in the extracted confounding factors were observed between the 2 treatment groups. The baseline value of the Alzheimer Disease Assessment Scale (Japanese version) cognitive subscale was adjusted using analysis of covariance. Least-squares mean of changes from baseline in the Alzheimer Disease Assessment Scale (Japanese version) cognitive subscale at week 24 for each group were -1.661 (-2.681 to -0.640) (donepezil patch) and 0.065 (-0.987 to 1.117) (donepezil hydrochloride tablet). The difference in the least-squares mean (95% CI) between 2 groups was -1.726 (-3.1913 to -0.2602, P=0.021). A post hoc analysis of covariance using the per-protocol set suggested that donepezil patches may be more effective than donepezil tablets in slowing cognitive decline in patients with mild Alzheimer disease.
Vision foundation models excel at general segmentation but underperform sharply when positive instances occupy a vanishing fraction of the input-a regime that arises across small-lesion and rare-event medical segmentation, with neonatal hypoxic-ischemic encephalopathy (HIE) as a representative extreme case (lesions <1% of brain volume; positive-to-negative voxel ratio >99:1). We present SparseMed3D, a framework for adapting vision foundation models to this extreme-sparsity regime through three coupled components: (i) parameter-efficient multi-channel patch-embedding adaptation; (ii) diffusion-based multi-channel image fusion with a provable descent property; and (iii) patch-based inference with variance bounds and concentration inequalities under arbitrarily correlated patch predictions. The unified theoretical analysis characterizes aggregation variance through an effective sample size that quantifies the correlation penalty between overlapping patches, and yields an end-to-end error bound that couples fusion and aggregation errors. We instantiate the framework on the BONBID-HIE 2023 benchmark, where the empirical aggregation variance closely matches the theoretical scaling across stride configurations (std 0.024 vs. 0.233), and the resulting model doubles baseline SAM-Med3D Dice (0.24 → 0.48), recovering 77% of state-of-the-art specialized-pipeline performance without ensembles, task-specific architectural redesign, or extensive fine-tuning of the foundation backbone.
Soundscapes in coral reef ecosystems are influenced by species richness and environmental conditions. Shallow coral reef soundscapes have been analyzed in various world regions, but most studies focus on environments exceeding 10 m depth. Additionally, remote locations have received limited attention and often lack recordings that span multiple days. Here, soundscapes were continuously recorded during 24-h periods at two nearby Acropora patches located ∼8 m apart in water depths ∼2 m within fringing reefs on the northwest coast of Moorea, French Polynesia. One patch was degraded from a bleaching event in 2019, whereas the other had greater coral coverage. A diel pattern was observed at both high and low frequencies and exhibited a strong dawn chorus. When comparing sites, the degraded patch exhibited sound levels ∼10 dB lower than the patch with higher coral coverage at frequencies below 2.5 kHz. The magnitude of the local acoustic particle velocity inferred from hydrophone measurements as well as array beamforming confirmed that the soundscapes were distinct with unique acoustic signatures despite proximity. These results provide evidence of measurably distinct soundscapes for close-by coral ecosystems, suggesting differing ecological community structures.
Prospecting for future breeding sites is a key aspect of making informed dispersal decisions. The aim of our study is to investigate the role of prospecting in mediating species co-occurrence or competitive exclusion in a metacommunity, thereby altering the dispersal-diversity relationship. An individual-based model (IBM) was developed to simulate a small mammal metacommunity, composed of 10 theoretical species, incorporating local resource competition and regional breeding dispersal. The model included three scenarios of prospecting effort (measured as the number of patches prospected) across the metacommunity: uniform prospecting effort, interspecific differences in prospecting effort, and intraspecific differences in prospecting effort. We also tested the role of potential inheritance for the latter trait. The study further considered costs associated with prospecting and dispersal, including mortality risk during prospecting and integration costs in the new patch. Informed settlement significantly influenced the relationship between dispersal rate and metacommunity diversity. Low prospecting effort led to a steady increase in diversity with higher dispersal rates, while higher prospecting effort resulted in a hump-shaped relationship. High prospecting effort led to rapid colonization of and settlement in high-quality patches, increasing competition and reducing establishment success, especially for species with high resource demands. Introducing dispersal costs, particularly integration costs, reduced metacommunity diversity, but increased prospecting effort partially mitigated this loss. Species-specific prospecting effort, correlated with body mass, resulted in a hump-shaped relationship between dispersal rate and diversity, highlighting the role of prospecting for the competition-colonization trade-off. In contrast, when individual variation in prospecting behaviour was considered a heritable trait, the highest species diversity was observed at increasing dispersal rates, with prospecting efforts stabilising at low levels. The study demonstrates that informed dispersal, specifically prospecting effort, plays a crucial role in shaping metacommunity diversity by mediating competitive species interactions in an individual-based metacommunity simulation model.
Approximately 50% of the estimated 14 million people eligible for lung cancer screening (LCS) currently smoke. Gaps in knowledge regarding optimal tobacco treatment interventions in the context of LCS remain. Research Questions; What are the most value-efficient, evidence-based combination of tobacco treatment component(s) for people seeking LCS who smoke? Study Design and Methods; Cessation and Screening to Save Lives (CASTL) is an optimization randomized clinical trial conducted at 17 LCS sites in the United States. Eligible participants ages 50-80, scheduled for LCS, and currently smoking were randomized to one of 16 combinations of tobacco treatment components: enhanced standard care, motivational interviewing, nicotine patch/ lozenge and message framing. The primary outcome was self-reported abstinence at 6 months follow-up. The cost of each combination of components was estimated as a function of time and resources. Results; At enrollment (N=758), about 5% of participants were not interested in quitting, 59% were considering quitting and 38% already making changes in their smoking. Most (79%) reported smoking within 30 minutes of waking, indicating high level of addiction. Although there were no significant differences among the intervention components, the most value-efficient intervention with respect to expected abstinence was loss-framed messaging, nicotine patch and lozenge (expected abstinence rate = 30%; mean cost = $287.41). Among the less-costly combinations, a value-efficient alternative included gain-framed messaging only (abstinence = 13%; cost = $51.29).
Titanium and its alloys are widely used in modern medical devices because of their favorable biocompatibility and mechanical properties. Allergic reactions to titanium-based implants are considered rare, and their diagnosis is hampered by the poor dermal penetration of metallic allergens. A 29-year-old female patient with seronegative myasthenia gravis requiring parenteral nutrition presented with persistent inflammatory dermatitis overlying a titanium port catheter (X-Port BARD Titan low-profile) 4 weeks after implantation in July 2023. Despite initial diagnostic uncertainty and sequential management modifications, her condition continued to deteriorate. Similar eruptions developed after re-implantation of the same titanium port model on the contralateral thorax. Rigorous patch testing incorporating standardized tape-stripping and extended reading intervals revealed positive sensitization to the titanium port body, while all other port components and an alternative plastic port system (BARD SlimPort M.R.I. Ultra Low-Profile) tested negative. Energy-dispersive X-ray spectroscopy confirmed the titanium body composition as a Ti-Al6-V4 alloy. Substitution with the plastic port catheter in February 2025 resulted in complete symptom resolution, with sustained clinical remission through July 2025. Although very uncommon, contact sensitization to titanium medical devices can occur and may present significant diagnostic and therapeutic challenges. Rigorous patch testing methodology, incorporating standardized tape-stripping and extended 168-hour readings, appears essential for detecting delayed-type hypersensitivity to metallic implants. Clinical resolution following biocompatible device substitution supports an allergic etiology in this case.
Diabetic wounds, prone to infection and delayed healing, represent a major clinical challenge. Traditional nanosilver-based antibacterial agents remain challenging, including complex preparation, tendency to agglomerate, and poor biocompatibility. Herein, we synthesized lactoferrin-silver oxide nanoparticles (LF-Ag2O2 NPs) via a one-step biomimetic mineralization method using lactoferrin (LF) as a dispersant. This approach significantly improved the dispersibility, stability, and biocompatibility of Ag2O2 NPs while enabling synergistic antibacterial activity. Furthermore, we developed a core-shell microneedle patch (LAg&FGF@CP MN) for programmed drug release to achieve sequential treatment of diabetic wounds. The patch employs a layered loading strategy: the shell layer of the microneedle releases LF-Ag2O2 NPs rapidly in the acidic wound microenvironment, generating reactive oxygen species (ROS) and Ag+ that act synergistically with LF to eliminate bacteria efficiently; The inner core layer of the microneedle degrades upon exposure to ROS, slowly releasing fibroblast growth factor (bFGF). This promotes cell proliferation, M2 macrophage polarization, and angiogenesis to facilitate tissue regeneration. This programmed drug delivery system effectively disrupts the "infection-inflammation" vicious cycle and significantly accelerates diabetic wound healing. Collectively, this work offered a novel and efficient strategy for managing refractory diabetic wounds.
Proton gradients power diverse biological processes, yet how interfacial proton migration is regulated remains unclear. Here we quantify how membrane composition controls interfacial proton migration using an approach that releases protons directly at the surface of a membrane patch via an embedded ionophore. Fluorometrically monitoring proton arrival at a distant patch across neutral, negatively charged, and positively charged membranes, we confirm that both the lateral surface diffusion coefficient and the activation barrier for proton release into the bulk vary rather modestly. In contrast to membrane electrostatics, membrane incorporation of glycolipids typical of thylakoid membranes-digalactosyldiacylglycerol and sulfoquinovosyldiacylglycerol-leads to a more pronounced reduction of the lateral proton diffusion coefficient, with comparatively small effects on the surface-to-bulk release barrier. Thus, interfacial proton migration is governed primarily by hydration-layer properties rather than membrane charge. These results establish membrane-anchored sugars as potent modulators of long-range proton conduction and provide a mechanistic framework for localized proton coupling in glycolipid-rich biological membranes.