Search Results (2,260)

Background: Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. At present, multi-agent chemotherapy and surgery provide only limited effects and the prognosis for patients with recurrent or metastatic disease remains poor, with 5-year survival rates below 30%. These challenges highlight the need for innovative therapeutic approaches targeting osteosarcoma more effectively. Fenretinide, a synthetic derivative of all-trans retinoic acid, has shown significant antitumor activity in various cancers. In a recent high-throughput drug screening study, fenretinide emerged as the most active molecule against diffuse midline glioma over more than 3500 compounds. Fenretinide also demonstrated cytotoxic activity against osteosarcoma cell lines in vitro and in preclinical models and is endowed with a favorable safety and toxicity profile. However, its poor water solubility and limited bioavailability have hindered its clinical translation. To improve fenretinide bioavailability and enhance tumor exposure, different nanotechnology-based drug delivery systems have been proposed. Here we propose a tertiary complex made of fenretinide, bovine serum albumin, and hydroxypropyl-betacyclodextrin, indicated as BSAF. Methods: BSAF was evaluated for the main physico-chemical parameters such as hydrodynamic size, zeta potential, stability to drug leakage, and the biological effect on the osteosarcoma cell line MG63. Results: BSAF showed hydrodynamic size at the nanoscale, enhanced drug solubilization, high drug loading and size stability to dilution, characteristics that make this complex useful for targeted therapy. When tested on the MG63 osteosarcoma cell line, BSAF demonstrated significantly enhanced cytotoxicity, with half-maximal inhibitory concentration (IC₅₀) values ~50% lower than free fenretinide. The complex was more efficient than free fenretinide in inhibiting cell migration as demonstrated by wound healing assay. Live-cell imaging analyses revealed a cytostatic effect at sub-cytotoxic concentrations. Specifically, treatment with concentrations below the IC₅₀ resulted in significantly prolonged cell doubling time, decreased cell divisions, increased cellular sphericity and thickness, and decreased cell area. These morphological changes are more consistent with cell cycle arrest rather than apoptosis. These findings were corroborated by stable dry mass measurements, an indication of a cytostatic state rather than progressive cell death. In addition, cell motility parameters (e.g., instantaneous velocity, track speed, and displacement) at the single-cell and population level were markedly reduced at sub-IC₅₀ concentrations, further supporting a cytostatic phenotype. Conclusion: Collectively, the new BSAF complex showed promise as a potential therapeutic agent for treating osteosarcoma cancer, due to the favorable physico-chemical characteristics and the cytotoxic/cytostatic effects on MG63 cells. BSAF effects may be therapeutically valuable, particularly in preventing tumor recurrence by suppressing the proliferative and migratory potential of residual drug-resistant clones. Unlike conventional anticancer agents that mainly rely on cell death, fenretinide, when complexed, demonstrates a dual capacity to induce both cytotoxic and cytostatic responses, depending on concentrations, potentially overcoming multiple resistance mechanisms that are generally associated with tumor exposure to drug sub-cytotoxic concentrations. Full article

Autoimmune ocular surface diseases represent a complex group of disorders in which systemic immune dysregulation triggers chronic inflammation, epithelial dysfunction, and progressive tissue fibrosis. Systemic lupus erythematosus, primary Sjögren’s syndrome, and ocular cicatricial pemphigoid are the principal entities linking systemic autoimmunity to ocular surface pathology. These conditions share convergent mechanisms—including dysregulated cytokine signaling (IFN-I, IL-6, and IL-17), complement activation, and epithelial–mesenchymal transition—culminating in tear film instability and visual impairment. Recent advances in molecular immunology and omics profiling have elucidated disease-specific pathways and identified actionable therapeutic targets. Conventional immunosuppressants such as corticosteroids and cyclosporine remain fundamental, yet emerging biologics targeting BAFF, IFNAR, and JAK/STAT signaling—alongside regenerative strategies employing mesenchymal and induced pluripotent stem cells—are transforming disease management. Parallel innovations in amniotic membrane transplantation, keratoprosthesis, and bioengineered corneal scaffolds integrate structural reconstruction with immune modulation. Furthermore, the convergence of multi-omics analytics, artificial intelligence-assisted diagnostics, and microbiome-based immunomodulation heralds a new era of precision ophthalmology. This review synthesizes current molecular insights, clinical observations, and translational advances that collectively redefine autoimmune ocular surface diseases—from chronic inflammatory disorders into a targetable, regenerative, and potentially reversible spectrum of conditions. Full article

AC battery systems (ACBSs) based on multilevel converters (MLCs) have gained considerable attention in recent times for the provision of grid services due to high-power (HP) and high-energy (HE) capabilities. In a hybrid ACBS, multiple low-voltage ports provide DC interfaces for battery modules from the same or different chemistries, enabling flexible operation across a wide range of grid services. However, the design complexity increases substantially, due to (i) higher electrothermal coupling between heterogeneous battery modules and power electronic (PE) switches, (ii) grid compliance constraints and (iii) power quality requirements, which often leads to conservative oversizing and, consequently, increased total cost of ownership (TCO). To address these challenges, this paper proposes a co-design optimization framework for the sizing and selection of battery modules, PE components, and MLC architecture. A multi-fidelity modeling approach is presented to co-simulate the battery modules and MLC. The model captures electrochemical behavior, degradation dynamics, and power losses to enable accurate estimation of system-level energy efficiency. The framework then leverages a multi-objective nondominated sorting genetic algorithm (NSGA-II) to perform optimal cell-to-module sizing across different chemistries and MLC levels, while incorporating the inter-module balancing and AC power quality constraints. Comparative simulation studies show that the proposed co-design framework achieves life-cycle TCO reduction of 3.5%, 4.5% and 20% relative to non-hybrid (single chemistry) configurations based on LFP, NMC and LTO chemistries, respectively. The test results validate the effectiveness of the proposed co-design methodology for the optimal design of grid-tied AC battery systems. Full article

To address the integrated demands of structural reinforcement and energy-efficient retrofitting for existing buildings, a cementitious material modified with vitrified microspheres and SiO₂ aerogel was developed to realize the synergistic enhancement of thermal insulation and mechanical strength. By substituting fine sand with equal mass fractions of SiO₂ aerogel and vitrified microspheres in the cement matrix, this study systematically investigated the synergistic regulatory effects of this binary modification on two core performance metrics—thermal conductivity and compressive strength. All performance tests were conducted in triplicate, and the results are presented as the mean values. The results indicated that the thermal conductivity of the composite exhibited a trend of decreasing first and then increasing with the rise in aerogel content. At an aerogel dosage of 6%, the thermal conductivity dropped to 0.2237 W/(m·K), achieving optimal thermal insulation performance while retaining a compressive strength of 17.96 MPa. The subsequent incorporation of 15% vitrified microspheres further reduced the thermal conductivity to 0.1642 W/(m·K) while maintaining a compressive strength of 15.34 MPa, thereby achieving an optimal balance between thermal insulation and mechanical performance. Microstructural characterization revealed that the incorporation of aerogel significantly increased the internal porosity of the composite, effectively reducing thermal conductivity by obstructing heat transfer pathways. Vitrified microspheres enhance thermal resistance via their closed-cell structure and promote the formation and densification of C-S-H gel. Synergistically with SiO₂ aerogel, they construct a multi-scale porous composite system. By optimizing the interfacial bonding state and pore structure, this system achieves the synergistic optimization of mechanical strength and thermal insulation of cement-based composites, providing new materials and a theoretical basis for the functional integrated retrofitting of existing building structures. Full article

Reliable prediction of the Remaining Useful Life (RUL) of lithium-ion batteries (LIBs) plays a pivotal role in maintaining safe operation, enhancing system dependability, and supporting economically sustainable lifecycle planning in electric mobility and stationary energy storage applications. However, battery aging is governed by highly nonlinear, interacting, and chemistry-dependent processes, which pose significant challenges for conventional data-driven prognostic models. In this study, a unified RUL prediction framework is proposed by integrating multi-domain feature engineering, a Multi-Criteria Adaptive Selection (MCAS) strategy, and a Bidirectional Long Short-Term Memory (Bi-LSTM) network enhanced with dual multi-head attention. Degradation-relevant descriptors extracted from time, frequency, and chaotic domains are employed to capture complementary aging dynamics across battery cycling. In addition, a novel degradation-consistency indicator, termed the M-score, is introduced to characterize the regularity and stability of degradation behavior using observable electrical, thermal, and statistical signals. The MCAS mechanism systematically identifies informative and temporally stable features while suppressing redundancy, thereby improving both predictive robustness and interpretability. The resulting architecture jointly exploits adaptive feature refinement and attention-based temporal modeling to enhance the RUL estimation accuracy. The proposed framework is validated using two widely adopted benchmark datasets: the Toyota Research Institute (TRI) dataset, representing fast-charging lithium iron phosphate (LFP) cells, and the Sandia National Laboratories (SNL) dataset, which includes multiple chemistries, such as LFP, NMC, and NCA. Experimental results demonstrate substantial improvements in the RUL prediction accuracy compared with baseline Bi-LSTM and single-attention models, while systematic ablation studies confirm the individual contributions of the M-score and MCAS components. Within the evaluated datasets and operating conditions, the results suggest that the proposed framework offers a robust and interpretable data-driven solution for battery RUL estimation. However, extending its generalizability and validating its performance on unseen datasets and in real-world scenarios remain important areas for future research. Full article

Three-dimensional (3D) cultured cells can mimic the in vivo tumor microenvironment more accurately than conventional monolayer cultures. Therefore, they are essential in cancer research and drug discovery. However, high-sensitivity fluorescence imaging of 3D spheroids remains challenging owing to their limited contact with the observation surface and the low penetration depth of total internal reflection fluorescence microscopy (TIRFM). In this study, we developed a microfluidic device equipped with a water-driven balloon actuator that enables the hydrostatic compression of 3D-cultured spheroids. This system gently presses spheroids against a glass surface, significantly enhancing the contact area and improving TIRFM and epifluorescence imaging quality, with more evident improvement observed in TIRFM. Our results show that hydrostatic compression markedly enhances optical accessibility in spheroids while preserving cell viability and structural integrity. The method is designed to complement volumetric imaging techniques, including confocal and light-sheet microscopy, by enabling high-contrast visualization of cell–surface molecular dynamics. Although the current system focuses on surface accessibility, future studies will incorporate rotational mechanisms and automated pressure control to facilitate multi-angle, high-throughput imaging. This platform offers a promising strategy for the dynamic observation of cell–surface interactions in living 3D systems. Full article

Introduction: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and remains a leading cause of cancer-related mortality worldwide. Despite recent advances in immunotherapy and targeted agents, treatment efficacy is frequently limited by tumor heterogeneity, drug resistance, and systemic toxicity. Natural products, particularly carotenoid-derived compounds, have emerged as promising multi-target anticancer agents. Xanthophylls, a class of oxygenated carotenoids, exhibit pleiotropic biological activities that are relevant to cancer therapy; however, their potential against HCC remains incompletely explored. This study aimed to systematically evaluate the anti-HCC potential of xanthophyll-rich extracts from Garcinia dulcis pulp using integrated metabolomic, in silico, and in vitro approaches. Methods: Xanthophyll-rich extracts from G. dulcis pulp were prepared using microwave-assisted extraction. Phytochemical profiling was performed using UHPLC–ESI–MS/MS. In silico analyses included bioactivity prediction, ADMET profiling, target identification, network pharmacology, pathway enrichment, and molecular docking against key HCC-related proteins (EGFR, BCL-2, and mTOR). In vitro antiproliferative activity was assessed using MTT assays on HepG2 and Huh7 hepatocellular carcinoma cell lines, with THLE-2 normal hepatocytes used as controls. Results: Metabolomic analysis revealed a xanthophyll-dominated profile, with zeaxanthin and lutein as the major constituents, alongside fucoxanthin, astaxanthin, β-cryptoxanthin, β-carotene, and canthaxanthin. In silico predictions demonstrated high antineoplastic and pro-apoptotic activities, with strong involvement in the HIF-1, EGFR, PD-1/PD-L1, JAK–STAT, and mTOR signaling pathways. Molecular docking confirmed stable and high-affinity interactions of xanthophylls with EGFR, BCL-2, and mTOR. In vitro assays showed selective cytotoxicity against HCC cells, with IC₅₀ values of 42.8 ± 3.6 µg/mL (HepG2) and 58.4 ± 4.9 µg/mL (Huh7), while exhibiting significantly lower toxicity toward normal hepatocytes. Conclusions: Xanthophyll-rich extracts from Garcinia dulcis pulp exhibit potent and selective anti-hepatocellular carcinoma activity through multi-target mechanisms involving oncogenic signaling, apoptosis regulation, and tumor metabolism. These findings support the translational potential of G. dulcis xanthophylls as promising natural candidates for further development in HCC therapy. Full article

Background: Dendritic and histiocytic cell sarcoma (DHCS) and clear cell sarcoma (CCS) are ultra-rare soft-tissue sarcomas characterized by diagnostic ambiguity, limited treatment guidelines, and poor outcomes. Their rarity has restricted the development of evidence-based management strategies, leaving clinical decisions reliant on small case series and institutional experience. DHCS typically presents without a unifying molecular driver and is often misclassified without comprehensive immunophenotyping. CCS is defined by EWSR1-ATF1/CREB1 fusions but exhibits low responsiveness to conventional chemotherapy. There remains a clear need to clarify natural history, therapeutic responses, and molecular characteristics in both. Methods: We conducted a retrospective cohort study of adult patients with histologically confirmed DHCS or CCS seen at The Ohio State University Comprehensive Cancer Center between 2010 and 2022. Demographics, treatment modalities, clinical outcomes, and molecular profiles were extracted and analyzed descriptively. Time to progression (TTP) and progression rates by treatment modality were recorded. A structured literature review was conducted to provide context for the findings. Results: Outcomes are descriptive and cohort-specific, reflecting institutional experience rather than generalizable estimates. Total of 10 patients with DHCS and 5 with CCS were evaluable. Most DHCS patients presented with metastatic disease. Among DHCS patients who received systemic therapies, five of eight (62.5%) experienced progression during or shortly after treatment. Among CCS patients who received systemic therapies, three of four (75%) progressed during or shortly after treatment. Overall mortality occurred in 4 of 10 DHCS patients (40%) and 3 of 5 CCS patients (60%). TP53 mutations were identified in four of seven next-generation sequencing (NGS)-tested DHCS cases, and PD-L1 positivity was detected in five of seven tested DHCS cases and one of five tested CCS cases. Conclusions: Despite multimodal treatment, this referral-based cohort of patients with ultra-rare DHCS and CCS showed high rates of progression and mortality. Our findings underscore the urgent need for multi-institutional collaboration and biomarker-driven clinical trials to guide management of these ultra-rare sarcoma subtypes. Full article

Influenza A virus remains a major global health threat, causing annual epidemics and occasional pandemics. Programmed cell death, including apoptosis, pyroptosis, and necroptosis, with emerging evidence for ferroptosis, plays a dual role in influenza pathogenesis, both limiting viral replication and contributing to immunopathology. Most mechanistic insights have been derived from murine genetic models, which have been invaluable for establishing causal roles of these pathways. However, murine models and cancer-derived cell lines differ significantly from human physiology. This review systematically compares influenza-induced programmed cell death across human-relevant platforms, including primary cells, immortalized non-cancerous lines, co-cultures, organoids, and precision-cut lung slices. The increasing complexity of these models reveals distinct aspects of pathway activation, bystander effects, cell-type vulnerability, and spatial dynamics. We highlight critical divergences between model systems, identify gaps in comparative analyses across viral strains and experimental platforms, and outline future directions leveraging advanced model systems, multi-omics, and functional genomics to enhance translational relevance and guide the development of host-directed therapies. Full article

Multi-stack Polymer electrolyte Membrane Fuel Cell (PEMFC) systems are increasingly adopted in heavy-duty mobility to overcome the power limitations and thermal instability of single-stack configurations. However, the overall energy efficiency, hydrogen utilization, and thermal behavior of multi-stack fuel cell trucks are highly dependent on the applied Power Management System (PMS). In this study, high-fidelity, system-level dynamic model of multi-stack fuel cell truck was developed using Matlab/Simscape^TM, and three PMS approaches (rule-based control, state-machine control, and fuzzy logic control) were comparatively evaluated. The analysis includes coolant temperature regulation, hydrogen consumption, battery State of Charge (SoC) dynamics, and the parasitic power demand of Balance of Plant (BoP) components. Results show that the fuzzy logic PMS provides the most balanced operating profile by smoothing transient fuel cell loading and actively leveraging the battery during high-demand periods. In the thermal domain, the fuzzy logic PMS reduced temperature overshoot by up to 61.20%, demonstrating the most stable thermal control among the three strategies. Hydrogen consumption decreased by 3.08% and 0.89% compared with the rule-based and state-machine PMS, respectively, while parasitic power consumption decreased by 7.12% and 3.32%, confirming improvements in overall energy efficiency. TOPSIS-based multi-criteria decision analysis further showed that the fuzzy logic PMS achieved the highest closeness coefficient (0.9112), indicating superior system-level performance. These findings highlight the importance of PMS design for achieving energy-optimal and thermally stable operation of multi-stack PEMFC trucks and provide practical guidance for future control strategies, heavy-duty mobility applications, and next-generation hydrogen powertrain optimization. Full article

Anti-Müllerian hormone (AMH), a member of the transforming growth factor-β (TGF-β) superfamily, has been widely recognized for its role in reproductive endocrinology and is regarded as one of the “gold standards” for evaluating ovarian age and fertility potential. In recent years, the focus of research on AMH has gradually expanded from the reproductive system to the skeletal system. Although the specific mechanism of its action in bone-metabolism-related diseases and associated signaling pathways still requires in-depth exploration, existing studies have confirmed—through cell experiments, animal models, and clinical data—the important role of AMH in maintaining bone health. Here, the significance of AMH in research on female osteoporosis is reviewed, the current signaling pathway mechanisms by which AMH regulates bone metabolism are summarized, and the relevant clinical research results are discussed. This work features three unique contributions: first, the logical progression of AMH research from reproductive regulation to bone metabolism is explicitly clarified; second, multi-level evidence is integrated to form a complete regulatory network, avoiding fragmented discussions of individual findings; and third, concrete clinical translation pathways and targeted solutions for existing limitations are proposed, rather than merely outlining general directions. This review aims to identify new biomarkers for the early screening of osteoporosis and therapeutic targets, ultimately promoting the formulation of personalized prevention and treatment strategies. Additionally, as a key factor linking ovarian function and bone health, the AMH research concepts and methods summarized herein can be extended to other hormone-related bone metabolism disorders. Full article

Acute myeloid leukemia (AML) is a biologically heterogeneous and clinically aggressive hematologic malignancy defined by the clonal expansion of immature myeloid progenitors, resulting in progressive bone marrow (BM) failure, peripheral cytopenias, and fatal infectious or hemorrhagic sequelae. The adverse clinical outcomes associated with AML arise from the combined effects of disrupted physiological hematopoiesis, persistence of therapy-refractory leukemic stem cells (LSCs), and extensive inter- and intratumoral genetic and epigenetic heterogeneity that underlies rapid disease progression and relapse. AML constitutes a prototypical disorder of hematopoietic dysregulation, wherein aberrant self-renewal capacity and arrested differentiation programs drive malignant transformation through the integrated influence of recurrent genomic lesions, epigenetic reprogramming, metabolic alterations, dysregulated signaling cascades, and reciprocal interactions with the BM microenvironment. These processes collectively reconfigure transcriptional landscapes and cellular hierarchies within the leukemic compartment. The objectives of this review are to provide an integrated framework for understanding AML pathobiology encompassing chromosomal abnormalities, transcriptional and epigenetic regulatory networks, and microenvironmental cues and to emphasize emerging analytical paradigms, including integrative multi-omics, single-cell and spatial technologies, and system-level approaches, which are reshaping conceptual models of malignant hematopoiesis and accelerating the development of mechanism-based therapeutic strategies. Full article

Microbial spoilage and foodborne pathogens remain central challenges in food safety, driven by the metabolic resilience and ecological adaptability of bacteria, yeasts, and molds across diverse food matrices. Active antimicrobial packaging has emerged as a biologically informed strategy that directly targets microbial physiology through controlled release or contact-mediated mechanisms. These systems employ natural antimicrobials, bacteriocins, essential oils, and metal nanoparticles to disrupt cell membranes, inhibit enzymatic pathways, generate reactive oxygen species, or interfere with quorum sensing, resulting in substantial reductions in microorganisms such as Listeria monocytogenes, Salmonella spp., E. coli O157:H7, Pseudomonas spp., Brochothrix thermosphacta, and spoilage fungi. In real food environments, these interventions achieve multi-log reductions and attenuate microbial metabolism, though efficacy varies with pH, water activity, fat content, and storage temperature. Oxygen scavengers further reshape microbial ecology by suppressing aerobic spoilage organisms while inadvertently favoring anaerobic competitors. Despite promising outcomes, concerns regarding nanoparticle migration, microbial resistance potential, and matrix-dependent performance highlight the need for deeper microbiological validation. Future progress will require integrative research linking microbial ecology, packaging material science, and mechanistic toxicology. By aligning with microbial behavior at the cellular and ecosystem levels, active antimicrobial packaging represents a powerful, biologically grounded approach to mitigating foodborne risks. Full article

The rapid expansion of smart city infrastructures and Internet of Things (IoT) networks has led to extremely dense wireless deployments, driving unsustainable energy consumption and exacerbating environmental concerns. To improve sustainability in the long term, future wireless systems must fundamentally prioritize energy-efficient and autonomous operation. Integrated sensing and communication (ISAC) is emerging as a key enabler for next-generation systems by jointly supporting sensing and communication through shared spectrum, hardware, and signal processing resources. In IoT systems, sensing of target parameters, e.g., range, angle, velocity and identity, etc., form the basis of autonomous and environment-aware applications. However, this integration increases overall power consumption due to the added coordination overhead and the workload placed on shared hardware components. To this end, backscatter communication provides a low-power alternative that enables passive data transmission through energy harvesting and sharply reduces the need for active radio circuits. However, the coexistence of sensing and backscatter functions introduces mutual interference, which often requires large multiple-input multiple-output (MIMO) arrays for effective mitigation. Furthermore, sensing performance depends heavily on line-of-sight conditions, while backscatter links operate only over short ranges. Although increasing array size or transmit power can extend coverage, it imposes substantial energy and hardware costs and undermines sustainability goals. To address these limitations, cell-free MIMO is emerging as a promising candidate technology for next-generation systems. Cell-free MIMO relies on a dense deployment of distributed access points that cooperate to serve devices across a wide area. This cooperation enables effective beamforming and interference management, providing spatial diversity comparable to large, centralized antenna arrays without incurring their associated hardware or power costs. They also enable aggregation of weak double-hop reflections, reduced effective-illumination distances, multi-view sensing, and robustness to blockage, which is invaluable to backscatter communication. This perspective article introduces the foundations, challenges, and architectural considerations of cell-free backscatter-aided integrated sensing and communication (CF-BISAC) systems. By leveraging the advantages of battery-less backscatter IoT devices and the distributed nature of cell-free MIMO, CF-ISABC aims to maximize sensing and communication performance under strict energy constraints, contributing toward energy-aware ISAC systems capable of supporting high-density, low-power wireless applications. Full article

Sickle cell disease (SCD) is the most common inherited clinically relevant blood disorder. Although a deceptively simple monogenetic disorder, the associated complications have multiple downstream effects. In this review, we explore the many facets of SCD, with a particular focus on its impact on the vascular system. Despite progress in understanding the underlying mechanisms of SCD, including Hemoglobin S polymerization, microvascular occlusion, and inflammation, there are still many questions surrounding the condition, especially predicting which affected individuals will acquire specific complications in order to personalize treatments. While current standard of care treatments, including hydroxyurea and chronic red blood cell transfusions, have been proven to be disease-modifying, newer therapies like crizanlizumab and voxelotor have only proven to manage symptoms. Newer gene therapies have been approved; however, it is not clear what impact these will have long-term on the end-organ complications of SCD. There is still a significant need to understand how we optimize and personalize therapies to improve outcomes for patients. This review highlights the importance of recognizing SCD as a vascular disease to understand its multi-organ complications and heterogeneity of effects. Full article