Search Results (7,718)

Localized surface plasmon resonance biosensors are promising devices for label-free detection of live cells and biomolecules. However, typical plasmonic sensors have limited surface area, planar electromagnetic fields, and poor compatibility with three-dimensional (3D) interactions with cells or biomolecules. In this study, a 3D plasmonic sensor around microposts was developed using reversal nanoimprint lithography for highly sensitive cell and DNA detection. Au nanopillars were conformally integrated onto the bottom, sidewall, and top of microposts, forming additional sensing surface area along the sidewall of microposts for plasmonic sensing. The 3D plasmonic sensors exhibited tunable resonance peaks and refractive index (RI) sensitivities by varying the micropost height. The highest sensitivity of 1306 nm per RI unit was obtained from the sensor with 10 μm-tall microposts at a resonance wavelength of 1315 nm, which was significantly higher than that of typical planar plasmonic sensors. The platform was applied to live MC3T3-E1 cell detection, showing a resonance peak shift of 71 ± 11.6 nm at a cell concentration of 10⁶ cells/mL with a cell concentration ranging from 10² to 10⁶ cells/mL. In addition, DNA hybridization detection was demonstrated over a concentration range of 10⁻¹⁵–10⁻⁷ M complementary target DNA, with a resonance shift of 68 ± 2.5 nm observed at 10⁻⁷ M target DNA concentration. The 3D plasmonic sensor provides a scalable device for additional plasmonic biointerfaces with enhanced analyte accessibility and light–matter interactions. This platform offers high-sensitivity biosensing involving live cells, nucleic acids, and other biological targets. Full article

Background: Pregnancy after solid organ transplantation carries increased maternal and fetal risks, compounded by the teratogenicity, nephrotoxicity, and metabolic effects of available immunosuppressive agents. Belatacept, a calcineurin inhibitor-sparing T-cell costimulation blocker with favorable renal and metabolic profiles, has emerged as an alternative; however, evidence regarding its safety during pregnancy remains scarce. Methods: A scoping review was conducted per PRISMA-ScR recommendations. PubMed, Google Scholar, Web of Science, Scopus, and the Cochrane Library were searched (January 2015–March 2025), supplemented by citation searching, for studies reporting pregnancy outcomes in solid organ transplant recipients receiving belatacept. Methodological quality was assessed using Joanna Briggs Institute critical appraisal tools. Results: Three studies (one case series and two case reports) encompassing 21 pregnancies among 15 recipients were included, predominantly in kidney transplant recipients; several recipients contributed more than one pregnancy, so pregnancy-level outcomes are not statistically independent. Sixteen pregnancies resulted in live birth and five ended in miscarriage, at least four of which occurred in pregnancies with periconception mycophenolate exposure. No congenital malformations were reported among live-born infants, although the number of exposures is far too small to characterize teratogenic risk. Stable allograft function was reported in 14 of 19 pregnancies with available follow-up, with no rejection episodes during belatacept exposure. Maternal complications included preeclampsia (8 of 16 in the case series), gestational diabetes, cytomegalovirus reactivation, and acute kidney injury. Low birth weight (<2500 g) was reported in all live births, predominantly in the context of preterm delivery. Conclusions: The published cases have not identified congenital malformations to date, but the number of documented exposures is far too small to characterize teratogenic risk, and the overall certainty of evidence is very low. Because no comparative studies were available, maternal and neonatal outcomes cannot be assumed equivalent to those of conventional immunosuppression. Belatacept cannot be recommended for routine use during pregnancy; clinical decisions must remain individualized, and preconception counseling and prospective multicenter registries are urgently needed. Full article

Acanthamoeba keratitis is a severe, sight-threatening corneal infection caused by free-living amoebae widely distributed in soil, natural waters, and domestic or recreational water systems. Following entry into the corneal microenvironment, disease develops within a redox conflict in which host-derived reactive oxygen species (ROS) and reactive nitrogen species (RNS) may contribute to parasite control while simultaneously promoting inflammation and tissue injury. Acanthamoeba responds through an adaptable defense network involving superoxide dismutases, catalase, thioredoxin- and glutathione-dependent systems, peroxiredoxins, and mitochondrial mechanisms. However, most mechanistic evidence derives from in vitro trophozoite studies, whereas the contribution of individual redox pathways to mature cyst survival and persistence in the infected cornea remains poorly defined. This review critically integrates evidence on host oxidative and nitrosative responses, parasite antioxidant adaptation, bidirectional redox crosstalk, and redox-modulating therapeutic strategies. Current data support neither indiscriminate suppression nor uncontrolled amplification of reactive species. Instead, future interventions should achieve spatially, temporally, and stage-specifically controlled redox modulation that weakens parasite defenses while preserving corneal integrity and essential innate immune functions. Progress will require causal validation of redox targets, separate assessment of trophozoites and mature cysts, long-term excystation and regrowth assays, evaluation across clinical isolates and genotypes, and parallel assessment of host-cell toxicity in clinically relevant corneal models. Full article

Autonomous robotic navigation in dynamic environments depends on sensor-derived occupancy maps that are often degraded by occlusion, localization error, dynamic blockage, incomplete observation, and perception noise. These uncertainties can make a nominally short route unsafe after deployment, motivating conservative route selection for collision-aware path planning under sensor-derived map uncertainty. We formulate Conservative Robust Route Selection (CRRS) as a finite-scenario robust optimization and route-selection framework for autonomous robotic path planning under this uncertainty. CRRS constructs a heterogeneous portfolio of candidate routes, scores each route using nominal and plausible-world information only, and applies a validation-frozen conservative override rule that defaults to the scenario ensemble unless a candidate route satisfies predefined feasibility, risk, clearance, and cost-ratio guards. The evaluation protocol separates implementation auditing, candidate-pool expansion, validation-based selector design, frozen confirmation, public-benchmark validation, simulated sensor-model validation, and a controlled validation–held-out mismatch stress test. On the generated 30-domain MovingAI-format benchmark, candidate-pool expansion finds strict-safe-superior candidates in 113/150 matched groups, and the frozen selector reduces plausible collision from 0.1250 to 0.0807 and held-out collision from 0.3053 to 0.2937. On an official long-distance MovingAI subset with 260 queries and a minimum start-goal distance of 100 cells, CRRS reduces the held-out collision from 0.9648 for the scenario ensemble to 0.8822, with 141 wins, zero losses, and 119 ties. In an additional LiDAR/SLAM-inspired simulated sensor-model validation on 200 routed official-query problems, CRRS reduces the held-out collision from 0.4059 to 0.3768 relative to the scenario ensemble. A validation–held-out mismatch stress ablation isolates the conservative override rule: CRRS differs from CVaR-only on 73/260 problems, obtains a lower or equal held-out collision in every comparison, and avoids the 18 harmful held-out losses incurred by CVaR-only relative to the scenario ensemble. The resulting claim is deliberately scoped: CRRS improves aggregate route robustness over a strong scenario-ensemble default on the evaluated robotic path-planning benchmarks, while real-time deployment, live sensor integration with calibrated sensors, physical robot validation, family-level variation, and benchmark-specific uncertainty models remain limitations. Full article

Cultivation of L. platensis under elevated CO₂ ensures CO₂ biofixation, while adding Na₂SeO₃ to the culture medium, produces valuable Se-enriched biomass. This study evaluated the effect of Na₂SeO₃ supplementation (20–640 mg/L) on the growth of L. platensis under 3 vol.% CO₂. The cultivation was carried out in 10 L column-type photobioreactors under continuous (24 h·d⁻¹) illumination with intensity of 220 µmol·m⁻²·s⁻¹, a constant temperature of 27 °C and aeration rate of 1 L/min. Two consecutive cultivation cycles (8 days each) were conducted: the first with the original strain and the second with an inoculum adapted to 20 mg/L (taken from the first cycle). The growth rate, cell viability, pH, and the concentrations of nitrates, phosphates, carbonates, bicarbonates, NH₄⁺ ion were investigated. It was established that under intensive cultivation at elevated CO₂, L. platensis is very sensitive to Na₂SeO₃ supplements: concentrations > 160 mg/L led to culture death within the first 2–4 days, while the acute toxicity threshold lies in the range of 80–100 mg/L. The highest biomass growth rate in the 1st and 2nd cycles was achieved in the control (0 mg/L of Na₂SeO₃): 329 and 239 mg·L⁻¹·d⁻¹ dry weight, respectively. At 20 mg/L, the growth rate drops to 289 and 208 mg·L⁻¹·d⁻¹ in the 1st and 2nd cycles, respectively. The percentage of live trichomes at the end of the 1st and 2nd cycles at 20 mg/L was 85 and 67%, respectively, indicating low adaptation capacity even to this concentration of Na₂SeO₃. The addition of Na₂SeO₃ did not lead to significant pH deviations from the control. Nitrates and phosphates consumption slowed down at Na₂SeO₃ concentrations of 40–60 mg/L. Bicarbonate and carbonate ions did not change significantly across all samples due to the maintenance of elevated CO₂ concentration. In a separate experiment under atmospheric CO₂ (0.04%), selenite toxicity was less pronounced than under 3% CO₂, and growth declined after day 4 due to carbon limitation rather than selenite toxicity. Full article

Neutrophils are key effectors of innate immunity. Although traditionally regarded as short-lived effector cells, recent evidence suggests they can undergo functional reprogramming after microbial stimulation, leading to trained immunity. We investigated whether lipopolysaccharide (LPS) or Candida albicans β-glucan induces memory-like inflammatory responses in adult peripheral and neonatal cord blood neutrophils. We used complementary molecular and functional approaches to characterize neutrophil responses following in vitro priming with LPS or β-glucan and subsequent LPS restimulation. Cytokine secretion, reactive oxygen species (ROS) production, glycolytic activity (via lactate production and glycolytic enzyme expression), and ERK1/2 and NF-κB signaling pathway activation were assessed. Priming with LPS or β-glucan enhanced neutrophil responsiveness to secondary stimulation, resulting in increased secretion of IL-1β, IL-6, IL-8, CXCL1, and CCL2, together with elevated ROS production. These effects were consistently more pronounced in neonatal than in adult neutrophils. Memory-like neutrophils also exhibited metabolic reprogramming, associated by increased hexokinase-2 and phosphofructokinase-1 mRNA expression, elevated lactate production, and enhanced ERK1/2 and NF-κB activation. Human neutrophils, particularly neonatal cells, develop memory-like characteristics following LPS or β-glucan priming, highlighting their functional and metabolic plasticity and suggesting a role for neutrophil training in early-life immune adaptation. Full article

Inflammasomes are central mediators of innate immune defense but can also drive pathological inflammation and pyroptotic cell death in numerous diseases. While several small-molecule inhibitors have been described, many selectively target individual inflammasomes or act through the adaptor protein ASC, leaving ASC-independent pathways unaffected. We previously identified thiomuscimol as a broad-spectrum inflammasome inhibitor that blocks both ASC-dependent and ASC-independent activation, although the structural basis for this activity remains unclear. Here, we examined the structure–activity relationship of thiomuscimol using related compounds and synthetic analogs. In primary macrophages, inflammasome activation and pyroptosis were assessed by live cell imaging of ASC speck formation, gasdermin D-mediated dye uptake, and cellular ATP levels. Structurally related sulfur-containing molecules, including taurine and isothiazole, failed to inhibit inflammasome activation, indicating that neither the sulfur in an electron-rich environment nor the heterocyclic scaffold confer activity. Replacement of the primary amine with a carbonyl group abolished activity, whereas substitution with a secondary amine preserved inhibitory potency comparable to thiomuscimol. Incorporation of the amine into an annulated piperidine ring reduced potency and revealed sensitivity to the precise positioning of the amine within the ring. Together, these findings identify key structural features required for thiomuscimol-mediated inflammasome inhibition and provide a framework for future studies to define its mechanism of action and guide the development of improved inhibitors. Full article

Background/objectives: Delayed wound healing, along with excessive scar formation, is the major clinical drawback due to the presence of stubborn bacteria, oxidative stress, prolonged inflammation, and irregular tissue regeneration. Utilizing nanomaterial-based wound dressings offers significant advancements and minimal cytotoxicity, but also presents issues such as poor biocompatibility, low solubility, and reduced permeability. These factors limit the effectiveness of nanomaterial-based wound dressings in promoting complete tissue regeneration. To overcome these limitations, plant-derived bioactives are integrated with nanomaterials within a hydrogel cage to enhance antibacterial activity, mitigate oxidative stress and inflammation, and promote tissue regeneration. Methods: A multifunctional alginate–gelatin hydrogel incorporating silver nanoparticles and plant extracts (AG-AgNP-PE) was developed to promote scar-free wound healing, alongside a plant extract-free silver nanoparticles-loaded hydrogel for comparative evaluation of the functional contribution of plant bioactives. The biological performance of the formulated hydrogels was systematically evaluated through antioxidant, antimicrobial, and antibiofilm assays, while in vitro cytocompatibility and proregenerative activity were assessed using MTT and Alamar Blue assays, live/dead cell imaging, and a scratch-wound assay, complemented by in vivo evaluation in zebrafish embryos. Results: Pro-angiogenic activity was further investigated using the CAM model, and therapeutic efficacy was validated in an in vivo rat burn wound model through microscopic wound assessment, histopathological examination, and biochemical assays. Conclusions: Among the hydrogels, AG-AgNP-PE exhibited superior performance across all key properties, highlighting the synergistic effect of the nanomaterial combined with plant extracts within hydrogel cages and positioning it as a promising multifunctional wound dressing for rapid tissue regeneration and scar-free wound healing, suitable for advanced wound management. Full article

Engineered mesenchymal stem cells (MSCs) have emerged as promising therapeutic platforms for healthspan-relevant applications. As agents of tissue repair and modulators of biological aging, MSCs have been widely studied for their capacity to enhance regeneration, restore immune homeostasis, and reduce chronic inflammation associated with age-related decline. This review examines emerging bioengineering strategies designed to overcome key age-related limitations in MSC homing, survival, and paracrine signaling, which have historically constrained their in vivo efficacy. We discuss major engineering approaches, including genetic modification, surface engineering, metabolic reprogramming, and preconditioning, with particular attention to their contributions to longevity-focused applications. Preclinical studies have demonstrated that engineered MSCs and their extracellular vesicles (EVs) yield measurable improvements in therapeutic performance. Reported benefits include prolonged persistence in inflamed tissues, partial reversal of senescence-associated phenotypes, and modulation of pro-aging inflammatory pathways. While MSC-derived EVs may offer potential safety advantages and could reduce certain risks associated with live-cell administration, this remains to be confirmed in well-controlled clinical studies, and significant challenges persist in terms of manufacturing scalability, cargo consistency, and process standardization. The current literature, which is predominantly preclinical, supports the potential of engineered MSC platforms to improve healthspan-relevant outcomes; direct evidence of healthspan extension in humans is not yet available. However, successful clinical translation will require a standardized manufacturing process to ensure therapeutic safety, reproducibility, and efficacy in age-related conditions. Full article

Background/Objectives: People living with HIV (PLWH) are at substantially increased risk of anal high-grade squamous intraepithelial lesions (HSIL), a recognized precursor of anal cancer. Although the ANCHOR trial demonstrated that treatment reduces progression to invasive disease, important uncertainties remain regarding durability of response, recurrence patterns, and treatment-related toxicity across available therapeutic strategies. Methods: We conducted a systematic review of studies evaluating treatment outcomes for anal HSIL published between 2000 and 2026. PubMed, Embase, and the Cochrane Library were searched according to PRISMA guidelines, with a particular focus on studies involving PLWH. Results: A total of 45 studies comprising 6093 patients, including five randomized controlled trials, met the inclusion criteria. Definitions of treatment response, recurrence, and adverse events varied considerably across studies, together with differences in assessment methods and follow-up, limiting direct comparisons between treatment modalities. Ablative, topical, and surgical approaches achieved variable short-term clearance; however, no modality demonstrated consistent durable disease control. Recurrence rates were high, frequently exceeding 50% in PLWH, consistent with the chronic and relapsing nature of HPV-driven disease in this population. Serious adverse events were uncommon, although treatment-related morbidity was frequent and varied across modalities. Conclusions: Randomized evidence supports treatment of biopsy-confirmed anal HSIL in PLWH for prevention of squamous cell carcinoma of the anus. However, comparative evidence remains limited by few randomized trials, heterogeneous study designs, and inconsistent outcome reporting. High recurrence rates and limited durability of response support the need for improved therapeutic strategies, biomarker-driven risk stratification, and longitudinal management approaches. Full article

Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit to the host. Research has traditionally focused on bacterial species, particularly Lacticaseibacillus and Bifidobacterium, whose mechanisms are well-characterised. However, probiotic yeasts represent a functionally distinct category, with Saccharomyces boulardii as the most studied representative and Kluyveromyces marxianus as an emerging candidate. Bacterial and yeast probiotics differ in cell biology, antibiotic susceptibility, immune receptor engagement, and metabolic output. Bacterial strains provide mucosal adhesion and direct short-chain fatty acid (SCFA) generation but are susceptible to antibacterial therapy. Yeast strains are intrinsically antibiotic-resistant, offer enzymatic activities such as β-galactosidase and glycosidases, and exert indirect bifidogenic effects that amplify luminal SCFA concentrations beyond what either category achieves alone. These non-overlapping profiles support a complementary rather than competitive conceptualisation of their use. When combined with prebiotic substrates such as fructooligosaccharides or galactooligosaccharides, this integrated approach addresses the principal axes of intestinal homeostasis more comprehensively than any single-organism intervention. Prospective randomised trials are needed to determine whether this mechanistic complementarity translates into additive or synergistic clinical benefit. This review synthesises the available evidence and proposes a framework for their complementary use. The proposed framework is hypothesis-generating: it rests largely on mechanistic and preclinical data, and its clinical validity requires confirmation in adequately powered controlled trials. Full article

Chronic kidney disease (CKD), one of the major global public health burdens, continues to exhibit a rising prevalence worldwide. The growing population of patients with end-stage renal disease (ESRD) has led to an increasing demand for renal replacement therapy (RRT). Although dialysis effectively prolongs survival, it fails to fully replicate kidney function. In addition, the persistent shortage of donor kidneys results in prolonged waiting periods for kidney transplantation. Emerging renal replacement strategies, such as kidney organoids, have demonstrated considerable potential. However, multiple technical limitations continue to hinder their near-term clinical translation. Bioartificial kidneys (BAKs), which integrate engineering and biological technologies, generally consist of artificial filtration membranes and living-cell bioreactors designed to mimic native kidney function. Advances in nanotechnology, biomaterials, and tissue engineering have accelerated the development of implantable bioartificial kidneys (iBAKs), making them an important research direction in renal replacement therapy. These innovations have improved membrane performance, biocompatibility, and cellular integration; however, substantial challenges remain regarding long-term stability, immune compatibility, and clinical validation before translation into human applications. Specifically, limited cell sources and uncertain long-term biocompatibility remain major barriers to iBAK development. In the future, biosensors and artificial intelligence (AI) technologies may be incorporated into bioartificial kidneys to enable personalized precision therapy. This review focuses on the developmental and major challenges of bioartificial kidneys, with detailed discussion of recent progress in implantable artificial kidneys. Full article

The paradigm of craniomaxillofacial (CMF) reconstruction is shifting from traditional bone grafting and biochemical adjuncts toward a nucleomechanical framework that leverages the cell nucleus as a mechanosensitive organelle. By utilizing computer-aided design and computer-aided manufacturing (CAD/CAM)-derived scaffolds with 10 µm micropillar arrays and specific interfacial stiffness (25–40 kPa), surgeons can physically manipulate the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex to achieve a nuclear aspect ratio above 2.5. This structural deformation mechanically expands nuclear pores to trigger cytoskeletal and molecular responses, such as Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) translocation. Resultantly, this physical tension pulls open chromatin fibers to activate master osteogenic regulators like RUNX2, effectively bypassing the risks and limitations associated with supraphysiologic growth factor delivery (e.g., rhBMP-2). Clinically, translating these principles involves moving away from absolute rigid internal fixation toward advanced resorbable biomaterials that permit controlled micro-motions (100–200 µm) under functional masticatory loads. This review provides a structured synthesis of the field, outlining deterministic topographic criteria, clinical boundary conditions, and the potential strategies needed to overcome age-related mechanosensory blockades. Ultimately, we establish a multidisciplinary framework that bridges precision bioengineering with native oral and maxillofacial surgical realities to drive living, biophysically mediated bone repair. Full article

Mucosal microbiota contribute broadly to host defense and immune homeostasis, while the lung and gut microbiota form a particularly important bidirectional ecological and immunological network that shapes pulmonary host defense, inflammatory injury, and tissue repair. In pneumonia, loss of colonization resistance and altered microbial metabolite production may weaken innate and adaptive immunity; respiratory infection, antibiotics, and critical-care exposures can, in turn, remodel both microbial communities. In acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), intestinal barrier failure, circulating microbial products, immune cell trafficking and, in selected settings, lymphatic or hematogenous dissemination of gut-derived organisms may aggravate alveolar–capillary injury. Alveolar macrophages integrate these signals through pattern-recognition, metabolic, and epigenetic pathways, linking microbial ecology to pathogen clearance and inflammatory resolution. The evidence, however, remains uneven. Mechanistic causality rests largely on animal studies, most human data are associative, and trials of microbiota-directed interventions are heterogeneous and strain-specific. This Review examines bacterial and viral pneumonia, sepsis-associated ALI and ventilator-associated injury; separates mechanistic, observational, and interventional evidence; and evaluates probiotics, live biotherapeutic products, microbial metabolites, and dietary approaches. Translation will depend on longitudinal sampling, source-resolved microbial tracking, metabolite-informed patient stratification, and adequately powered trials with clinically relevant endpoints. Full article

Gut microbiota research in inflammatory bowel disease (IBD) is transitioning from holistic community-level associations toward causal validation of individual bacteria and their metabolites. However, existing causal evidence is dispersed across diverse pathways and experimental models, lacking systematic integration and comparative assessment of evidence strength. Building on the concept of grading causal evidence in microbiome studies, we extend this approach into a five-tier progressive validation framework that covers the entire causal chain—from initial association discovery to the identification of specific effector metabolites. Using this framework, we systematically collate the single-bacterium–metabolite–host target axes that have been validated by high-level experimental methods. Focusing on four major pathways—AhR/tryptophan metabolism, bile acid/nuclear receptor signaling, short-chain fatty acid/vitamin/energy metabolism, and cell death-related pathogenic mechanisms—we integrate the molecular mechanisms through which specific bacteria and their causally linked metabolites regulate intestinal barrier integrity, immune responses, and inflammation resolution. We further discuss the modulatory influences of host genetics, diet, and medications on these axes, as well as therapeutic strategies such as live bacterial preparations, engineered probiotics, and postbiotics. Causal studies on individual bacteria and metabolites in IBD have progressed from isolated mechanistic discoveries towards systematic consolidation. It should be acknowledged, however, that most of the high-level evidence summarized in this review derives from animal models and preclinical studies, whereas robust human validation remains limited. In addition, protective mechanisms appear to considerably outnumber pathogenic ones, suggesting a marked imbalance in the current evidence base. To bridge the gap between mechanistic validation and clinical application, future research should focus on validating causal chains from animal models in well-designed human cohorts, exploring pathogenic mechanisms that drive disease onset, and clarifying interactions among different metabolites. By synthesizing available evidence, identifying key research gaps, and acknowledging translational limitations, this review aims to provide a foundational reference for researchers, while recognizing that further translational efforts are needed to move these preclinical findings toward clinical application. Full article