Search Results (359)

Titanium-based dental implants have evolved significantly, with the development of binary alloys like Ti-15Zr (Roxolid™) representing a pivotal advancement in mechanical performance. Current research focuses on biomimetic surface engineering to further accelerate osseointegration and optimize bone regeneration, particularly in clinically compromised sites. This review constitutes a narrative synthesis of how these strategies replicate the bone extracellular matrix (ECM) through a holistic framework of architectural, mechanical, and biochemical integration. A structured literature search across PubMed, Scopus, and Web of Science (2010–2026) identified relevant studies focusing on the synergy between Ti-15Zr substrates and surface modifications. Evidence confirms that the high fatigue strength of Roxolid™ alloys provides an ideal foundation for advanced, hierarchical surface engineering without compromising structural integrity. This strategy utilizes macro-topography for primary stability, nano-topography for protein adsorption, and bio-functionalization (e.g., RGD peptides and osteogenic ions) to direct mesenchymal stem cell (MSC) differentiation. This synergy accelerates the transition from passive to active osseointegration, effectively bridging the “biological gap” during early healing. Biomimetic engineering transforms implants into instructive biological platforms, improving outcomes for patients with compromised bone quality and facilitating predictable immediate loading protocols. Full article

Background/Objectives: Peritoneal metastases (PMs) arise from gastrointestinal, gynecologic, hepatobiliary, and colorectal origins and are associated with poor outcomes. Cytoreductive surgery (CRS) with intraperitoneal (IP) chemotherapy offers benefit for select patients, but survival remains limited. This review aims to summarize recent insights into the molecular and tumor microenvironmental (TME) changes characteristic of PMs and the impact of IP chemotherapy. Methods: A literature review was performed using recent clinical, translational, and preclinical studies examining alterations in molecular signaling, DNA repair alterations, metabolic pathways, and angiogenic factors in PMs before and after IP therapy. Results: Peritoneal metastases exhibit distinct biology after being treated with IP chemotherapy. Treatment induces alterations in gene expression, mutational patterns, and immune infiltrates. Heated intraperitoneal chemotherapy (HIPEC) has been associated with increased CD8+ T-cell activity, macrophage and NK cell shifts, and modulation of PD-1/PD-L1 signaling, which correlate with treatment response and survival. Emerging data on PIPAC similarly suggests induction of favorable gene expression changes with repeated treatment, though supporting evidence remains more limited than for HIPEC. Angiogenic pathways—particularly VEGF and HIF1α—remain key drivers of PM progression and predictors of post-operative outcomes. Early findings suggest potential synergy between IP chemotherapy and immunotherapy though clinical trials are ongoing. Conclusions: IP chemotherapy induces tumor microenvironmental changes that have potential to shape therapeutic response. Characterizing these measurable biologic changes may allow clinicians to improve patient selection and support the development of combination therapies to enhance outcomes. Full article

Implant macrogeometry and surface microstructure represent fundamental pillars for accelerating and enhancing the quality of osseointegration. The objective of this study was to evaluate the synergistic effect of three distinct implant designs, Strong (hybrid with trapezoidal threads), Unitite (hybrid with healing chambers), and Epikut (hybrid with active double threads), associated with two surface configurations (dual acid-etched [DAE] and nanohydroxyapatite [NanoHA]) on bone regeneration at 3 and 8 weeks. Twenty-four male rabbits randomly received forty-eight implants in their tibiae, yielding an equal accounting of n = 12 animals per experimental healing period (3 and 8 weeks) to ensure a balanced longitudinal and structural analysis. Biomechanical monitoring included final insertion torque (IT) and resonance frequency analysis (ISQ) at installation and euthanasia, while high-resolution micro-computed tomography (µCT) quantified the 3D intersection surface index (IS/TS) and trabecular microarchitecture (BV/TV, Tb.Th, Tb.Sp, and Connectivity). Regarding insertion torque, no significant differences were observed between macrogeometries (p = 0.557), ensuring a standardized mechanical baseline for biological comparison. For clinical stability (ISQ), the Epikut and Unitite designs demonstrated significant stability gains as early as 3 weeks (p < 0.05). µCT data confirmed a progressive, time-dependent structural reorganization, presenting a significant increase in trabecular thickness (Tb.Th) over time (p < 0.001), while the overall bone volume fraction (BV/TV, p = 0.861) and IS/TS index (p = 0.774) maintained statistical uniformity across all studied models. In conclusion, implant macrogeometry and surface nanotopography exert a distinct, chronologically shifted synergy during osseointegration. Clinically, these findings dictate target-specific selection: macrogeometric innovations accelerate early secondary clinical stabilization, whereas bioactive NanoHA coatings optimize subsequent long-term trabecular thickening within the established peri-implant architecture. Full article

Background: With the global population aging, osteoporosis and associated vertebral compression fractures are increasingly prevalent. While bone mineral density (BMD) remains the standard clinical parameter for diagnosing osteoporosis, it provides an incomplete assessment of holistic spinal bone health. Paraspinal muscles are essential for spinal stability and movement. This narrative review aims to evaluate the interplay between paraspinal muscle status and lumbar spine BMD, thereby providing a scientific foundation for comprehensive bone health management. Methods: A comprehensive literature search was conducted in PubMed using relevant keywords to identify studies evaluating the functional and morphological interactions between paraspinal muscles and bone mineral density. Discussion: Current evidence demonstrates a significant negative correlation between paraspinal muscle FI and lumbar spine BMD. High FI is identified as an independent risk factor for osteoporotic vertebral fractures and a robust predictor of postoperative complications. The relationship between paraspinal muscle CSA and BMD remains debated. Nevertheless, targeted high-impact and resistance training generate substantial mechanical loading through muscle contraction, providing biological stimuli for trabecular BMD preservation. Conclusions: Evidence highlights a critical synergy between paraspinal muscle status and bone mineral density, with muscle fat infiltration acting as a key marker for bone loss and fracture susceptibility. Integrating these muscle parameters with traditional BMD measurements improves fracture risk stratification and osteoporosis management. Full article

Staphylococcus epidermidis is a major cause of periprosthetic and other implant-associated orthopedic infections because of its ability to adhere to biomaterial surfaces and form biofilm. Tranexamic acid (TXA) is routinely used in arthroplasty to reduce perioperative blood loss; however, emerging evidence suggests that it may also modulate bacterial behavior and antibiotic activity. This study investigated the in vitro effects of TXA in combination with teicoplanin on planktonic growth and biofilm biomass formation in clinical Staphylococcal isolates. Clinical Staphylococcal isolates were evaluated using disk diffusion assays, microtiter plate-based planktonic growth assays, and crystal violet biofilm biomass assays. Microplate-based growth and biofilm assays were performed using five clinical isolates, whereas disk diffusion assays were performed using a separate set of seven clinical staphylococcal isolates. Teicoplanin was tested at literature-based low concentrations of 0.1 and 0.4 µg/mL, either alone or in combination with TXA at 10 and 50 mg/mL. In disk diffusion assays, inhibition zone diameters were quantified using ImageJ. Planktonic growth was assessed by optical density at 600 nm, and biofilm biomass accumulation was quantified by crystal violet staining at 570 nm. Disk diffusion data were analyzed using paired t-tests, while microplate-based growth and biofilm data were analyzed using two-way analysis of variance (ANOVA) followed by Tukey’s multiple-comparisons test. In disk diffusion assays, TXA co-application was associated with larger teicoplanin inhibition zones on both blood agar and Mueller–Hinton agar, suggesting an increased apparent inhibitory zone under agar-based conditions. In microplate-based planktonic growth assays, responses were isolate-dependent. However, co-exposure to TXA, particularly at 50 mg/mL, was associated with reduced OD600-based bacterial growth in several isolates compared with teicoplanin alone. A similar isolate-dependent pattern was observed for crystal violet-based biofilm biomass accumulation. In most tested isolates, teicoplanin combined with 50 mg/mL TXA was associated with lower biofilm biomass than teicoplanin alone, whereas one isolate showed minimal responsiveness. Under the tested in vitro conditions, TXA–teicoplanin co-exposure was associated with reduced planktonic growth and crystal violet-based biofilm biomass accumulation in several clinical staphylococcal isolates. However, because TXA-only controls were not available across the full experimental framework and formal synergy assays were not included, these findings do not establish synergistic activity or distinguish combination-specific effects from TXA-associated effects alone. Further studies are needed to clarify the biological and translational relevance of these observations. Full article

As the world moves toward a circular bioeconomy, starch nanoparticles (SNPs) have emerged as key components for sustainable development. Traditional production methods have historically relied on harsh acid treatments; however, their substantial environmental footprint has catalyzed a much-needed shift toward “green” chemistry. This review explores the rise of eco-friendly synthesis strategies—including high-power ultrasound, mechanical milling, nanoprecipitation, and enzymatic hydrolysis—and explains how these “clean” methods allow us to precisely define the nanoparticles’ properties. Furthermore, the functional applications of SNPs are analyzed, focusing on their role as reinforcing agents in biodegradable packaging, natural stabilizers in food emulsions, and encapsulation matrices for targeted nutrient delivery. By connecting recent breakthroughs, this work identifies technological synergy, the integration of physical and biological methods, as the most promising route to overcome current yield and scalability limitations. Finally, a future perspective is proposed, focusing on what is needed to move these innovations from the lab to industrial applications, ensuring they are safe, effective, and truly sustainable for the global food sector. Full article

Global agriculture faces a dual imperative: increase food production to meet rising demand while simultaneously reducing environmental impacts and resource inefficiencies. Addressing this challenge requires repositioning ruminant nutrition as the intelligent nexus linking crop and livestock production within Integrated Crop–Livestock Systems (ICLS). In this role, nutrition becomes central to restoring ecological, nutritional, and economic synergies that have been fragmented by decades of agricultural specialization. While ICLS provides the ecological foundation, Precision Livestock Farming delivers the technological and analytical infrastructure necessary to operationalize integration at the individual-animal level. Real-time sensing, Internet of Things platforms, and Artificial Intelligence (AI) enable dynamic monitoring of animal physiology, behavior, and environmental interactions across scales. A key advancement in this evolution is the development of Hybrid Intelligent Mechanistic Models (HIMM), which integrate biologically grounded mechanistic models with data-driven AI approaches. By combining interpretability with adaptive learning, HIMM enhances predictive accuracy, extrapolative capacity, and decision transparency, enabling the creation of digital twins that simulate biological responses before management interventions are implemented. Such architectures extend precision nutrition beyond feed efficiency and methane mitigation to include nutrient density and product quality, thereby linking different ecosystem processes directly to human dietary needs. Integrating nutrition with advanced modeling and monitoring tools can help livestock systems move beyond static “net-zero” benchmarks toward sustainable strategies that are responsive to local production contexts. In this reframed paradigm, nutrition is not merely a production input but the central analytical framework that computationally links biological mechanisms, environmental stewardship, technological innovation, and human health within sustainable ruminant systems. Full article

Background: Renal vasculitis encompasses a heterogeneous spectrum of disorders where vascular inflammation leads to organ dysfunction. Given that renal involvement is the primary determinant of long-term morbidity, timely diagnosis and intervention are paramount. This review aims to synthesize recent pathogenic insights and evaluate how these mechanistic breakthroughs are reshaping current diagnostic and therapeutic paradigms. Methods: A narrative review of the literature was performed to analyze the pathophysiology, diagnosis, and management of pediatric renal vasculitis. The analysis synthesizes current clinical guidelines and recent trial data, highlighting the transition toward biomarker-driven precision medicine for refined disease assessment and management. Results: Diagnosis remains multimodal, necessitating the integration of clinical, laboratory, and histopathological data. In ANCA-associated vasculitis (AAV), recent evidence has challenged the traditional “pauci-immune” concept. Management of pediatric IgA vasculitis utilizes a risk-stratified approach, whereas cryoglobulinemic vasculitis requires targeted trigger elimination. Across all pediatric syndromes, there is a shift toward minimizing corticosteroid exposure and utilizing individualized frameworks. Conclusions: Despite substantial progress in targeted biological therapies and reduced corticosteroid burden, the long-term morbidity of pediatric renal vasculitis remains substantial. Outcomes are dictated by a synergy of disease-specific and patient-specific factors. Addressing persistent unmet needs in the field requires further refinement of individualized management protocols and the continued validation of dynamic biomarkers, alongside the implementation of pediatric-specific guidelines and age-appropriate outcome measures. Full article

Background/Objectives. Breast cancer is the most frequently diagnosed cancer worldwide, with approximately 15% classified as Triple-Negative Breast Cancer (TNBC). TNBC is characterized by the absence of estrogen receptor (ER) and progesterone receptor (PR), and the lack of HER2 overexpression, limiting use of targeted therapies. Current TNBC treatment relies heavily on chemotherapy, most commonly taxanes including paclitaxel that stabilize microtubules, disrupt chromosome separation and induce apoptosis. TNBCs frequently develop chemoresistance after multiple treatment cycles, highlighting a critical unmet need for novel therapeutic strategies. This study addresses this challenge by targeting salt-inducible kinase 2 (SIK2), which is overexpressed in 85% of TNBCs compared to normal breast tissue. Methodes. In collaboration with Arrien Pharmaceuticals and Greenfire Biologics, we developed ARN-3261/GRN-300, a novel orally bioavailable SIK2 inhibitor and evaluated its ability to sensitize TNBC cells to paclitaxel in vitro and in vivo. Results. GRN-300 demonstrated strong synergy with paclitaxel in all eight TNBC cell lines tested, as indicated by favorable combination indices. In xenograft models, the combination therapy significantly enhanced tumor growth inhibition and prolonged survival compared to either agent alone. Mechanistic studies showed that GRN-300 disrupts the anaphase-promoting complex/cyclosome (APC/C) pathway by downregulating key mitotic regulators, including CDC27, CDK1, and PLK1, thereby potentiating G2/M cell cycle arrest and apoptosis. Conclusions. Together, these findings establish GRN-300 as a promising therapeutic agent that enhances paclitaxel efficacy through complementary disruption of mitotic regulatory pathways, providing strong preclinical rationale for clinical development in TNBC. Full article

Conventional thrust vector control nozzles are severely constrained by a single-pivot deflection paradigm, which induces asymmetric shock reflections and adverse boundary layer separation at large angles. Multi-segmented serial configurations offer a promising alternative to overcome these limitations by distributing the total deflection across multiple joint interfaces, thereby achieving large terminal angles and smooth flow-path curvatures. To realize such a configuration, this study draws inspiration from the abdominal bending mechanism of the damselfly Ischnura elegans during mating wheel formation. Real-time video recording and morphological characterizations identified abdominal segments VI and VII as critical for high-amplitude bending under load. Finite element analysis under muscular actuation elucidated the biomechanical synergy, which was rigorously verified through mesh convergence and material property sensitivity checks. Inspired by this biological system, a multi-segmented nozzle configuration incorporating discrete elastic elements and a centralized cable-driven layout was designed and evaluated using multibody dynamics and computational fluid dynamics. The nozzle achieved a continuous 61.20° deflection within 8 s under subsonic exhaust conditions, successfully stabilizing periodic supersonic shock structures and completely suppressing adverse boundary layer separation. These findings turn biological bending into a thrust vectoring method, giving insights for next-generation agile aerospace propulsion systems. Full article

The long-term success of orthopedic implants is fundamentally dependent on the synergy between mechanical performance and biological integration. Thus, a comprehensive investigation of both mechanical characteristics and microstructural parameters is essential for the development of reliable implant systems in hip arthroplasty, both in human medicine and veterinary practice. The present study provides a detailed analysis of the mechanical properties, microstructure, and chemical composition of a Ti-6Al-4V-based femoral implant using nanoindentation, scanning electron and optical microscopy, and energy-dispersive X-ray spectroscopy. Then, using finite element analysis, the influence of Young’s modulus on the stress–strain state of the endoprosthesis was evaluated. Dynamic loading conditions were considered by analyzing an impact on a cantilever beam, simulating an animal’s jump onto a supporting limb. For reliable numerical simulation, the model geometry was constructed utilizing computed X-ray microtomography. The numerical simulations were performed for three material cases: reference Ti-6Al-4V, experimentally characterized Ti-6Al-4V (with properties determined by nanoindentation), and CoCrMo alloy, which is also widely used in endoprosthetic applications. The influence of the founded mechanical characteristics on the stress–strain state of the prostheses was assessed. In particular, the results indicate that under dynamic loading conditions, the load-bearing capacity of CoCrMo is lower by approximately 30% and 21% compared to the reference and experimentally characterized Ti-6Al-4V, respectively. Full article

Background/Objectives: The integration of locoregional and systemic therapies represents a promising strategy in hepatocellular carcinoma (HCC). Yttrium-90 (Y-90) radioembolization provides durable local tumor control, while immune checkpoint inhibitors (ICIs) improve systemic disease outcomes. This review evaluates the biological rationale, clinical evidence, and emerging role of combination Y-90 radioembolization and immunotherapy in HCC. Methods: A semi-systematic (PRISMA-informed) literature review of PubMed/MEDLINE through September 2025 was conducted, including clinical trials, retrospective and prospective studies, and translational investigations evaluating Y-90 radioembolization, immunotherapy, and their combination. Results: Preclinical and translational studies demonstrate that Y-90 radioembolization induces immunogenic cell death, enhances antigen presentation, and activates immune pathways including interferon signaling and STING-mediated responses, supporting a mechanistic basis for potential synergy with ICIs. Early clinical studies, including phase I/II trials, report objective response rates ranging from approximately 30% to 41.5% and median overall survival up to 20.9 months in selected populations. Treatment-related grade ≥ 3 adverse events range from 10% to 25%, comparable to monotherapy approaches. However, outcomes vary across heterogeneous patient populations, and cross-trial comparisons remain limited. Ongoing prospective trials are evaluating combination strategies incorporating contemporary first-line regimens, including atezolizumab plus bevacizumab and the STRIDE regimen. Conclusions: Combination Y-90 radioembolization and immunotherapy demonstrates a strong biological rationale and encouraging early clinical signals, with acceptable safety profiles. However, current evidence remains preliminary and derived from non-randomized studies. Ongoing randomized trials are required to define optimal patient selection, treatment timing, and sequencing, and to establish whether combination therapy provides meaningful benefit over current standards of care. Full article

Green synthesis of silver nanoparticles (CP-AgNPs) using Calotropis procera (CP) offers a sustainable approach to producing multifunctional therapeutic nanomaterials. This study aimed to synthesize CP-AgNPs and evaluate their antimicrobial, antioxidant, anti-inflammatory, and anticancer potential, with a focus on Helicobacter pylori and gastric cancer cells. CP-AgNPs were prepared by phytochemical reduction using CP leaf extract and characterized by UV–Vis, XRD, FTIR, SEM, EDX, TEM, and Zeta. Antibacterial activity against H. pylori, time-kill kinetics, and SEM imaging of membrane damage were performed. Antioxidant (DPPH, ABTS) and anti-inflammatory assays, together with cytotoxicity studies in AGS cells (DAPI, AO/EtBr, and SEM), were also conducted. CP-AgNPs exhibited an SPR peak at 432 nm, face-centered cubic crystallinity, and spherical morphology (8–32 nm). They showed strong, dose-dependent antibacterial activity against H. pylori, surpassing metronidazole at higher doses. Time-kill assays and SEM confirmed membrane disruption. Antioxidant activity was notable (IC₅₀: 40 µg/mL for DPPH; 60 µg/mL for ABTS). CP-AgNPs demonstrated significant anti-inflammatory effects and dose-dependent cytotoxicity in AGS cells, inducing apoptosis and morphological alterations. The broad biological activity of CP-AgNPs likely arises from the synergy between silver ions and CP phytochemicals. Their superior antibacterial effects, combined with antioxidant and anti-inflammatory properties, indicate strong therapeutic potential for gastric diseases. Anticancer activity in AGS cells suggests additional biomedical relevance, which may involve ROS-associated and apoptosis-related pathways, as suggested by previous studies. CP-AgNPs represent a promising natural nanoplatform for managing H. pylori infection, oxidative stress, inflammation, and gastric cancer, warranting further mechanistic and in vivo studies. Full article

The deployment of lightweight object detectors on remote sensing edge platforms is severely constrained by the rigid trade-off between perception capacity and metabolic expenditure. To solve this fundamental challenge, we draw inspiration from the superior energy efficiency of the mammalian brain and the principles of connectomics to introduce CONERSLite. By emulating the dual mode synergy of biological neural systems, CONERSLite integrates a Compact Anatomical Backbone (CAB) representing the stable anatomical connectome and a Functional Connectome Router (FCR) that mimics the plasticity of the functional connectome. Our framework achieves a peak mAP of 82.35% on the DOTA-v1.0 dataset with only 28.3 M parameters and 195 G FLOPs, effectively establishing a new accuracy–efficiency Pareto frontier for remote sensing. On the HRSC2016 dataset, it reaches a state-of-the-art mAP of 98.62% while reducing the total parameter count by approximately 45% compared to high-precision optimized models like RTMDet. These results demonstrate that the application of connectomics principles provides a biologically grounded and highly efficient solution for resource-constrained remote sensing object detection. Full article

Biological activity of diets consisting of dietary fibers, peptides and polyphenols is largely mediated by the gut microbiota, which converts these compounds into bioactive metabolites. This review examines the microbiota–epigenome axis, highlighting gut microbiota-derived metabolites, including short-chain fatty acids (SCFAs), urolithins, and phenolic acids, that modulate host gene expression through DNA methylation, histone modifications, and non-coding RNA regulation. Current evidence from molecular and microbiome studies indicates that these metabolites influence key metabolic and inflammatory pathways, including lipid absorption via CD36, SIRT1 activation, and one-carbon metabolism involving folate and S-adenosylmethionine (SAM). Inter-individual variability in metabolic responses is associated with differences in microbial composition and metabotypes, which determine the magnitude of epigenetic regulation. Furthermore, dietary polyphenols derived from pomegranate, berries, tea, cocoa, and grapes are shown to modulate gut microbiota composition and enhance epigenetic effects. A “butyrate–polyphenol synergy” model is proposed, in which combined microbial metabolites optimize host epigenetic programming. Overall, agri-food by-products are suggested to function as modulators of the host epigenetic landscape, providing a framework for microbiome-targeted dietary strategies to improve metabolic and inflammatory health. Full article