Search Results (150)

Diabetic foot ulcers (DFU) are among the most severe complications of diabetes, resulting from a combination of metabolic dysregulation, vascular insufficiency, neuropathy, chronic inflammation, and impaired tissue repair, whereas diabetic foot infection (DFI) may develop within this compromised wound environment and frequently involves polymicrobial communities and biofilms. This review evaluates the mechanistic and translational basis for the use of antimicrobial peptides (AMP) in DFU and DFI, with emphasis on the diabetic wound microenvironment, polymicrobial ecology, endogenous AMP dysregulation, mechanisms of action, therapeutic development, and barriers to clinical translation. Hyperglycemia, ischemia, oxidative and proteolytic stress, and impaired innate immunity sustain inflammation, delay tissue repair, and promote microbial persistence. These conditions may also complicate antibiotic treatment through impaired tissue exposure and biofilm-associated tolerance. Depending on the peptide and experimental context, AMP may provide direct antimicrobial or antibiofilm activity and may also exert immunomodulatory or pro-reparative effects involving inflammatory signaling, angiogenesis, keratinocyte and fibroblast migration, and re-epithelialization. Approaches under investigation include engineered peptides, combination regimens, and local biomaterial-based platforms, including hydrogels, dressings, scaffolds, and nanoparticle-conjugated systems. Clinical translation remains constrained by proteolytic instability, potential host-tissue toxicity, limited selectivity, limited predictive value of preclinical models, heterogeneous clinical populations, nonstandardized endpoints, and manufacturing and regulatory requirements. Preclinical evidence supports further evaluation of approaches for local delivery of AMP, whereas clinical evidence in DFU and DFI remains limited and heterogeneous, with no AMP-based intervention yet demonstrating sufficiently consistent clinical benefit to support routine use. Full article

Efficient operation of interconnected production systems requires accurate modeling of upstream–downstream interactions to support informed operational decision-making. This study proposes an interconnected Adaptive Neuro-Fuzzy Inference System (ANFIS) framework consisting of two sequentially linked ANFIS models representing the upstream manufacturing stage and the downstream packaging stage, where the output of the first model is incorporated as an input to the second model. The framework uses operational Key Performance Indicators (KPIs), including mean time between failures (MTBF), mean time to repair (MTTR), uptime, reject rate, short stops, and long stops, to capture the nonlinear relationships between manufacturing and packaging operations. Unlike conventional single-model approaches, the proposed methodology represents the manufacturing and packaging stages as interconnected neuro-fuzzy subsystems, explicitly modeling their operational dependencies while maintaining model interpretability. Following data preprocessing and conditioning, two ANFIS models were developed using real industrial data and integrated into a MATLAB/Simulink environment for scenario-based analysis. The developed ANFIS models achieved low testing errors and satisfactory predictive performance on real industrial data. Simulation-based analyses were subsequently conducted to evaluate the effects of stoppage behavior and maintenance-related improvements on production-line uptime. The results indicate that the proposed framework captures upstream–downstream production dependencies and provides an interpretable decision-support tool for evaluating operational improvement scenarios in manufacturing environments. Full article

A collision-free path is not sufficient for visibility-dependent mobile robot tasks: a moving obstacle can block the camera–target line of sight and cause inspection or visual-servoing failure even when the robot remains physically safe. Maintaining visual contact with targets is therefore important in Industry 4.0 environments, yet visibility-preserving maneuvers can conflict with navigation progress and collision avoidance. This work presents the Visibility-Informed Safety and Target Awareness framework with control barrier function filtering and occlusion-evasive local replanning (VISTA-CBF+ELR). The architecture combines visibility-risk planning, target-bearing control, an ELR supervisor, and a CBF quadratic program that keeps collision constraints hard while relaxing field-of-view and occlusion requirements through slack. Counterproductive interventions are limited through persistence, benefit–cost and feasibility gates, progress protection, bounded dwell, recovery, and cooldown. In locked factory simulations, redesigned VISTA achieved 67% and 73% strict-goal success under clean and nominal sensing, whereas Visibility-CEM-2D achieved 87% and 86% but with lower clearance. In matched Gazebo trials, strict success was 19/30 for redesigned VISTA, 26/30 without ELR, and 16/30 for Nav2 Smac+MPPI; zero-clearance collisions were 8/30, 3/30, and 14/30, with no difference surviving multiplicity correction. A separate CEM stress test sustained 6.875 Hz optimization, missed 26.31% of 100 ms deadlines, and held commands on 31.35% of ticks. The results demonstrate repair of the ELR pathology and conditional visibility-risk reduction while exposing safety–visibility trade-offs, transfer limitations, and real-time constraints. Full article

The choice of suitable color palettes is a central task in thematic cartography. Established palette libraries such as ColorBrewer 2.0 provide cartographically proven color schemes, but they account only to a limited extent for the specific visual context of a background map. Particularly in web-based mapping environments, basemaps vary widely in lightness, colorfulness, texture, and semantic density. This paper introduces CartoPalette v4.2, a basemap-dependent tool for generating thematic color palettes. The system combines a trained Conditional Variational Autoencoder model (CVAE) with explicit scoring, minimum domain checks, constrained reranking, and optional CIELAB-color-space-based repair. The goal is not the automation of cartographic design, but a transparent, traceable decision aid. The benchmark comprised 40 basemaps from held-out test locations, drawn from the ten map styles included in the training data, together with two palette types and four class counts. In this setting, 90% of CartoPalette’s suggestions scored higher than the corresponding best available ColorBrewer palette. In about 83% of cases, the visual contrast to the background map was greater than with ColorBrewer. The results show that explicitly incorporating the basemap context offers a clear added value over classical palette libraries. These findings therefore refer to previously unseen locations within basemap styles represented during training. Transfer to entirely new styles has not yet been evaluated. Full article

The formation of anti-permeability is a critical step in the in-situ repair of organic anti-corrosion coatings under seawater, yet it is significantly influenced by the surrounding marine environment, particularly seawater temperature and applied cathodic polarization potential. In this study, we systematically investigated the effects of temperature and cathodic polarization potential on the permeability of curing epoxy coatings in simulated shallow seawater. Our results demonstrate that the anti-permeability formation process is governed by the competition between seawater penetration and coating curing. At lower temperatures, the EIS-derived evolution of coating resistance suggested heterogeneous electrolyte uptake across the coating surface, whereas at elevated temperatures, the electrochemical response indicated a more uniform progression of ionic ingress. Moreover, enhanced cathodic polarization accelerated both seawater penetration and the curing reaction of the epoxy coating. The underlying mechanisms of temperature- and polarization-dependent permeability formation were discussed in detail, providing theoretical insights into the top-down permeation process during underwater curing, which may inform the development of more effective in situ repair strategies for organic coatings. Full article

Ionizing radiation can induce DNA damage through direct or indirect mechanisms and activate the DNA damage response network, thereby influencing cellular repair, cell cycle regulation and cell fate determination. MicroRNAs (miRNAs), as key post-transcriptional regulatory factors, play a vital role in modulating the radiation response and cell fate. This review summarizes radiation-induced changes in miRNA expression and the molecular regulatory mechanisms they mediate, and further discusses recent advances in their application in the assessment of radiation damage, the prediction of radiotherapy response, and therapeutic interventions. Although miRNAs possess significant translational value, their multi-target regulatory characteristics, tissue- and environment-dependence, as well as limitations in clinical detection and delivery systems, continue to hinder their application. In the future, the integration of multi-omics technologies, artificial intelligence analysis and precision delivery strategies is expected to further elucidate the miRNA-mediated radiation response network and advance their application in precision radiology. Full article

Cannabis use has increased substantially in the United States, driven by broader legalization, decriminalization, and expanding medical and recreational availability. For facial plastic surgeons, the clinical implications remain difficult to define because “cannabis use” encompasses heterogeneous products and routes, including smoked flower, vaping, concentrates, edibles, pharmaceutical cannabinoids, topical cannabidiol (CBD), and frequent co-use with tobacco or nicotine. Current evidence suggests that systemic cannabis use, particularly inhaled or heavy perioperative use, may be associated with increased surgical complications in selected populations; however, existing studies are limited by retrospective design, inconsistent exposure definitions, inadequate dose and route characterization, and confounding by tobacco use and comorbidities. Cannabinoids exert biologic effects through the endocannabinoid system, particularly CB1 and CB2 receptors, which are expressed in the central nervous system, immune cells, vasculature, and skin. These pathways influence inflammation, keratinocyte proliferation, fibroblast activity, angiogenesis, immune surveillance, pain signaling, and tissue remodeling. The net effect of cannabinoid exposure on wound healing is likely context dependent, varying based on receptor expression, wound-healing phase, route of administration, cannabinoid composition, local tissue environment, and patient-specific risk factors. Preclinical and early dermatologic literature suggests potential therapeutic roles for topical cannabinoids, especially CBD, in modulating inflammation and epithelial repair. In contrast, systemic perioperative cannabis use has been associated in several surgical cohorts with infection, delayed healing, hematoma, nonunion, and reoperation. Evidence specific to facial plastic surgery remains sparse. The most directly relevant study evaluated cannabis and tobacco use in patients undergoing operative mandibular fracture repair. Cannabis-only use was not associated with increased complications, although the cohort was small; concurrent cannabis and tobacco use was associated with higher rates of surgical site infection, facial nonunion, abscess, debridement, and malocclusion. To date, no published studies address cannabis-associated outcomes in rhinoplasty, rhytidectomy, blepharoplasty, browlift, or facial rejuvenation. This review summarizes the biologic rationale, available surgical evidence, and clinical considerations for incorporating cannabis use into individualized perioperative risk assessment in facial plastic surgery. Full article

The long-term durability of repair systems combining normal concrete (NC) and ultra-high-performance concrete (UHPC) in marine environments depends on the response of the near-interface composite region to sequential carbonation and seawater exposure. However, the effects of seawater immersion following pre-carbonation remain insufficiently understood. This study compared an unexposed reference (REF), specimens carbonated for 28 d (C28), and specimens carbonated for 28 d and then immersed in simplified artificial seawater for 60 d (C28-SW60) using X-ray diffraction, thermogravimetry, backscattered electron imaging with energy-dispersive X-ray spectroscopy, and mercury intrusion porosimetry. Pre-carbonation promoted portlandite consumption, carbonate formation, and pore refinement. Subsequent seawater immersion further enhanced calcite-related diffraction and carbonate decomposition signals, while no typical crystalline salt-attack product was detected as dominant. The initial Ca-rich-to-Si-rich gradient from the NC side through the overlay transition zone to the UHPC side was accompanied by marked Cl accumulation and further S and Mg enrichment and redistribution. After seawater immersion, the measured total intrusion volume increased from 0.026 to 0.043 mL/g, the volume-based median pore-entry diameter increased from 27.49 to 58.42 nm, and the >1000 nm pore-volume fraction reached 39.82%, a change consistent with a shift toward coarser mercury-accessible pore entries. Together, the results link the initial heterogeneity of the NC–Overlay transition zone (OTZ)–UHPC region to a sequence-dependent response in which carbonate enrichment coexisted with multi-ion redistribution and transport-relevant defects, distinguishing carbonate accumulation from sustained near-interface refinement. Full article

Background: The clinical translation of cell-based therapies for knee articular cartilage repair is fundamentally restricted by the severe biological unpredictability of autologous cell sources, inherent manufacturing bottlenecks, and the rapid phenotypic dedifferentiation of cells expanded in conventional 2D monolayers. To overcome these translational hurdles, this study engineered a scaffold-free, 3D formulation of highly characterized allogeneic FE002-Cart chondroprogenitor spheroids. Methods: We systematically investigated the specific microenvironmental cues and Good Manufacturing Practice (GMP) formulation parameters required to direct functional chondrogenesis. The structural and biochemical performance of this allogeneic formulation was benchmarked against multiple primary adult autologous chondrocyte types. Finally, we evaluated the phenotypic resilience of the microtissues in simulated osteoarthritic (OA) environments and investigated both short-term liquid storage and advanced terminal preservation strategies to establish off-the-shelf logistical viability. Results: Precise microenvironmental regulation proved to be a critical biological prerequisite. The synergistic combination of physiological hypoxia (2% O₂) and stringent glucocorticoid limitation (10 nM dexamethasone) induced robust glycosaminoglycan (GAG) deposition and a > 200-fold upregulation of ACAN and COL2, while suppressing the terminal hypertrophic drift observed in adult chondrocytes. Benchmarking revealed that the allogeneic FE002-Cart formulation substantially mitigates the profound morphological and biochemical unpredictability inherent to adult autologous cell sources. Furthermore, the scaffold-free spheroid geometry yielded a 10-fold increase in GAG production per cell compared to traditional matrix-seeded (MACI) platforms. Transitioning to a GMP-compatible manufacturing process revealed extreme cellular sensitivities; excipients within standard pharmaceutical-grade dexamethasone severely aborted chondrogenic differentiation, emphasizing the necessity of rigorous raw-material qualification. Functionally, the 3D architecture acted as a protective physical shield, sustaining high cellular viability when subjected to severe inflammatory stress and 100% OA patient synovial fluid. Logistically, the viable spheroids maintained matrix integrity and inter-spheroid fusion potential for up to 7 days at ambient temperature in transport medium. Finally, advanced spheroid preservation via lyophilization and high-dose gamma irradiation eliminated biological viability but successfully transitioned the microtissues into highly organized, terminally irradiated matrices capable of heterologous in vitro structural merging. Conclusions: These findings define the critical biological thresholds for manufacturing, demonstrate the enhanced in vitro biosynthetic efficiency of 3D allogeneic microtissues compared to specific autologous and matrix-dependent baselines, and establish a highly practical, off-the-shelf logistical framework for the regenerative treatment of large knee chondral defects. Full article

In this study, we report for the first time the cloning and identification of three melatonin receptors (PgMtnr1a, PgMtnr1b, and PgMtnr1c) from the freeze-resistant fish Perccottus glenii, all of which encode typical GPCR proteins. These receptors are expressed widely in high-metabolism tissues such as the liver. During the freezing and recovery process at −2 °C, the expression of liver receptors exhibited dynamic changes: PgMtnr1a and PgMtnr1c were significantly upregulated during the middle of resuscitation, while PgMTNR1A reached its peak expression in the later stages, suggesting its involvement in stress repair. In vitro experiments confirmed that melatonin significantly enhances the activity of liver antioxidant enzymes in a receptor-dependent manner, an effect that can be inhibited by the antagonist luzindole. Anti-inflammatory analyses indicate that melatonin primarily inhibits inflammation-related genes through Mtnr1a and Mtnr1b. Furthermore, the overexpression of PgMTNR1A can synergistically activate ERK in the presence of melatonin, inhibit the JNK/p38 MAPK pathway, and downregulate the expression of NF-κB and COX2. Pathway inhibition experiments further validated that the MAPK/NF-κB axis, including ERK, JNK, and p38 pathways, mediates the anti-inflammatory effects of melatonin. This study systematically elucidates the molecular mechanisms by which the melatonin receptors of P. glenii play crucial antioxidant and anti-inflammatory roles during the later stages of freeze–thaw resuscitation, particularly by regulating the MAPK/NF-κB signaling axis through MTNR1A, thereby providing a novel basis for understanding the adaptation of vertebrates to extreme environments. Full article

Decentralized multi-robot navigation in grid-based industrial environments must reach goals and avoid collisions without centralized control or direct communication. We study a hybrid framework pairing an offline Rapidly-Exploring Random Tree (RRT) expert with a Behavior Cloning (BC) local policy and route reuse, evaluated in a reproducible simulator; collisions are predicted blocked-move events, not physical contacts. Our central result is a quantitative analysis of environment-specific route-library adaptation: a route library generated for one map and deployed on another leaves robots blocked by unfamiliar obstacles, whereas regenerating it on the deployment map cuts collisions by 38–85% and task failures by 43–70% across two- to ten-robot fleets, and replicates on a third corridor layout (30 seeds; Mann–Whitney $p<{10}^{-5}$; permutation $p_{\mathrm{perm}}<0.001$). Simpler remedies, filtering or repairing invalid routes, recover most of this gain, and a non-learning scripted connector matches the trained policy: the effect lives in the route library itself. A centralized prioritized-planning baseline bounds all communication-free variants from above; capping the online RRT baseline’s planning budget preserves its per-task collision quality but sharply raises task failures. A collision-history-sharing add-on coordinating through a shared map rather than messaging gives a limited, layout-dependent benefit not surviving multiple-comparison correction. Full article

Since the discovery and characterization of mesenchymal stem cells (MSC) some 40 years ago and the development of induced pluripotent stem cells (iPSC), opportunities to advance repair and potentially regenerate injured or diseased connective tissues of the musculoskeletal (MSK) system have been intensely investigated. While some advances have been made with some tissues, progress has not been as great as was hoped following the availability of such stem-like cells. Optimizing cell-biomaterial composites in vitro for features such as cell state or extracellular vesicle cargo, structure, composition, biomechanical integrity are likely to be only part of the story and optimizing the environments where such composites have been implanted has not received the same attention. Thus, implanting optimized or near optimized cell-biomaterial composites in acutely or chronically affected implantation sites can compromise the efficacy of such composites to effectively repair/regenerate MSK tissues. This may be due to inflammatory processes, alterations to the remaining tissues in the injury site during development of chronicity, waiting too long to repair residual tissue, or other host factors. Thus, success in realizing the potential of MSC and iPSC may depend, in significant part, on the environment at the implantation site. Further attention to optimizing the implantation site may enhance outcome success with long-term return to tissue function. Furthermore, heterogeneity in patient populations regarding natural factors influencing healing outcomes after injury may also require changes to clinical trial design to assess efficacy of cell therapies. Full article

Modern terrain rendering frameworks often struggle with the inherent trade-off between geometric continuity and hardware utilization. State-of-the-art watertight tessellation methods typically rely on explicit adjacency management and multi-pass synchronization, which severely restrict GPU parallelism and induce significant performance spikes during rapid camera transitions. In this paper, we propose a high-throughput, decoupled terrain rendering architecture that ensures visual continuity without the need for horizontal dependency tracking. Our framework leverages a linearized binary tree maintained within a 1D Unordered Access View (UAV), enabling each GPU thread to perform refinement and geometric reconstruction in total isolation. To resolve T-junction artifacts, we introduce an adjacency-blind directional stitching mechanism that utilizes localized hierarchical flags and per-edge error metrics to perform deterministic geometric repair in a single execution pass. Experimental results demonstrate that the proposed method achieves a stable rendering throughput of over 170 FPS on a large-scale $8192\times 8192$ dataset. Notably, our approach provides a 14% improvement in frame-rate stability during instantaneous camera teleportation compared to existing watertight frameworks, while simultaneously reducing the average triangle count by 21% through optimized boundary repair. These results confirm that our decoupled pipeline offers a robust and scalable solution for real-time spatial computing and high-performance simulation environments. Full article

Restoration of the osteochondral unit remains a major challenge in regenerative orthopaedics, largely due to the limited intrinsic healing capacity of articular cartilage and the complex, multilayered nature of the cartilage–bone interface. Osteochondral regeneration must accommodate differences in cellular composition, vascularization, metabolic demand, and mechanical properties between cartilage and bone, while simultaneously recreating a stable, functional interface. While exogenous mesenchymal stem cell (MSC) therapies have dominated the field, their clinical translation has been hindered by donor variability, phenotypic instability, logistical complexity, and inconsistent long-term outcomes. Resident stem cells from sources such as articular cartilage, bone marrow, periosteum, synovium, synovial fluid, and adipose tissue (infrapatellar fat pad) can act as potential targets for in situ osteochondral regenerative therapies. Joint-resident MSCs are adapted to the biomechanical and biochemical environment of the joint and may therefore represent a promising cell source for osteochondral regeneration; however, much of the supporting evidence remains preclinical. Effective osteochondral repair depends on the precise orchestration of stem cell recruitment, maintenance of chondrogenic phenotypes, induction of osteogenic differentiation in the subchondral compartment, and modulation of local immune responses. Patient-specific factors, including age, inflammatory status, and the severity of osteoarthritis, can significantly influence the regenerative potential of resident MSC populations and should therefore guide biomaterial design strategies. The proposed niche-by-design framework integrates stem cell biology with advanced biomaterial engineering, offering a rational roadmap for developing next-generation therapies that promote endogenous osteochondral regeneration through targeted activation of joint-resident progenitor cells. Full article

Microbial reduction of soluble selenium oxyanions is a sustainable strategy for remediating selenium-contaminated environments, yet the molecular mechanisms underlying selenite tolerance in the genus Rhodococcus remain poorly understood. In this study, we investigated the proteomic adaptation of the highly tolerant strain Rhodococcus qingshengii PM1 under high-concentration selenite stress (50 mM Na₂SeO₃) using a data-independent acquisition (DIA)-based quantitative proteomics approach. A total of 3335 proteins were identified, and 3310 proteins were retained for downstream analysis. Comparative proteomics revealed 1411 differentially expressed proteins, including 972 upregulated and 439 downregulated proteins in the selenite-treated group. These changes indicate extensive systems-level proteomic reprogramming and support a growth–defense trade-off strategy. Strain PM1 strongly upregulated ferredoxin and multiple respiratory-chain- and oxidoreductase-associated proteins, suggesting a ferredoxin-associated electron-transfer network that may contribute to Se(IV) transformation and intracellular redox adjustment. In parallel, proteins involved in sulfur assimilation, cysteine/methionine and selenocompound metabolism, ergothioneine biosynthesis, GSH-associated metabolism, Trx/MSH thiol-redox systems, peroxidase/Ohr-Prx detoxification, metalloid/oxyanion resistance, urease-associated pH adaptation, DNA repair, and cell-envelope remodeling were induced, indicating activation of multilayered defense and homeostasis mechanisms. Conversely, proteins associated with central carbon metabolism, carbohydrate uptake, and ribosome-dependent translation were repressed, suggesting reduced growth investment and energy conservation under severe selenite pressure. Overall, this study provides a systems-level proteomic framework for understanding Se(IV) resistance in R. qingshengii PM1 and identifies candidate targets for future functional validation, strain engineering, and selenium/metal(loid) bioremediation. Full article