Search Results (42,813)

Calcific aortic valve disease (CAVD) is an active pathological process driven by complex cellular and molecular mechanisms rather than passive aging. The disease is characterized by endothelial dysfunction, lipid infiltration, inflammation, extracellular matrix remodeling, and osteogenic differentiation of valvular interstitial cells, ultimately leading to hydroxyapatite deposition and progressive valve calcification. Key signaling pathways, including Notch, Wnt/β-catenin, BMP2, and TGF-β, play critical roles in osteogenic reprogramming, while inflammatory cytokines such as IL-6, IL-1β, and TNF-α contribute to a pro-calcific microenvironment. To summarize current knowledge on CAVD pathophysiology and emerging therapeutic strategies, relevant preclinical studies were identified through searches of PubMed, and clinical trials were identified through ClinicalTrials.gov. Evidence indicates that extracellular matrix remodeling, fibrosis, and dysregulated phosphate metabolism, particularly involving TNAP and DPP-4, further accelerate disease progression. Despite advances in understanding disease mechanisms, effective pharmacological therapies remain limited, with the current treatment largely restricted to valve replacement. Emerging therapeutic approaches targeting molecular pathways, including enzyme inhibition, RNA-based therapeutics, and advanced drug delivery systems, may offer promising strategies for disease modification. A deeper understanding of CAVD pathophysiology may facilitate the development of targeted therapies to delay or prevent disease progression. Full article

Cartilage is an important yet vulnerable tissue with limited self-healing capacity, where damage often progresses to joint degeneration, which eventually leads to severe osteoarthritis (OA). Current tissue engineering strategies focus on biocompatible scaffolds for cartilage regeneration, particularly amnion (or amniotic membrane), emerging as a promising biomaterial due to its wide availability, low immunogenicity, and naturally derived microenvironment that is advantageous for cartilage regeneration. This systematic review aims to evaluate the existing evidence on the efficacy of amnion as a tissue scaffolding material for cartilage regeneration in both preclinical and clinical studies. Using terms such as “cartilage damage”, “cartilage injuries”, “amnion” and “amniotic membrane”, 19 relevant studies were identified across three major databases (PubMed, Scopus and Web of Science) until 25 December 2025. All preclinical and clinical studies that utilized amnion for cartilage repair or as cartilage tissue engineering scaffolding materials were included. Evidence quality was assessed using the OHAT and MINORS risk of bias tool. This study is prospectively registered in the PROSPERO database under the ID 1178444. The findings consistently indicate that amniotic scaffolds, regardless of processing methods or cell seeding, yield favorable outcomes without adverse effects across different species. In vitro analysis revealed that treatment groups with amnion show better cell attachment, viability, and proliferation, and higher content of cartilage-related markers expressed by the seeded cells, either chondrocyte, bone marrow-derived mesenchymal stem cells (MSCs), adipose tissue-derived MSCs, placenta-derived MSCs, umbilical cord-derived MSCs, amniotic MSCs or amniotic epithelial cells. In in vivo and ex vivo studies, amnion-treated groups demonstrated improved quality of the treated cartilage, with better integration, as indicated by higher histological scores and the presence of type II collagen (COL-II). There was an inconsistency in the reporting of cartilage defect dimensions in the in vivo models across the different studies. Nevertheless, the outcome measurements were consistently reported with histological analysis, with or without International Cartilage Repair Society (ICRS) scoring and immunohistochemistry (IHC) analysis, across the studies. Clinically, most subjects show improvement in the Knee Injury and Osteoarthritis Outcome Score (KOOS) Sports and Recreation score and KOOS Quality of Life score, as well as reduced Visual Analogue Scale (VAS) average and maximum pain scores. In conclusion, preclinical and clinical studies support amnion as an ideal scaffold material for cartilage tissue engineering and regeneration. Future research should focus on optimizing and standardizing amnion scaffold preparation at a production scale to facilitate the translation of these positive outcomes into clinical applications. This study is funded by the Ministry of Higher Education Malaysia via Prototype Research Grant Scheme (PRGS/1/2021/SKK01/UM/02/1) and UM International Collaboration Grant—2023 SATU Joint Research Scheme Program: ST007-2024. Full article

Ovarian cancer (OC) is frequently diagnosed at an advanced stage and characterized by high rates of recurrence despite aggressive cytoreductive surgery and chemotherapy. Relapse is driven by microscopic residual tumors that are disseminated most often throughout the peritoneal cavity, posing significant challenges with conventional systemic therapy. Targeted alpha-particle therapy (TAT) combines molecular targeting with alpha-emitting radionuclides to deliver highly potent and localized cellular damage, uniquely suited for the eradication of small OC tumor clusters within the peritoneal cavity. We conducted an extensive literature search for clinical trials (clinicaltrials.gov) and pre-clinical studies (PubMed, Scopus, Google Scholar) between September 2025 and November 2025. Peer-reviewed articles published in English over the past 20 years that used OC mouse models with reported treatment data were included. Review articles without original data and clinical trials that have been terminated or withdrawn were excluded. In this review, we (1) summarize the biological and physical rationale supporting the use of TAT in OC, (2) discuss the relevant molecular and immunological anti-tumor mechanisms, and (3) critically evaluate early treatment outcomes of 19 pre-clinical and four clinical studies with respect to efficacy, safety, and feasibility. Despite the progress and promising survival outcomes, several challenges remain, including heterogeneous antigen expression, delivery and retention within the peritoneal cavity, off-target toxicity, radiation resistance, radionuclide availability, dosimetry uncertainties, and limitations in clinical trial design. We highlight future directions to overcome these barriers and the continued multidisciplinary efforts essential to translate TAT into effective clinical strategies to treat advanced stages of OC and other solid tumors resistant to conventional treatment. This work was supported with funding available to Kurt R. Zinn as the Hickman Family Endowed Chair in Oncology at Michigan State University. Full article

Urban last-mile logistics systems must improve service responsiveness while reducing environmental impact. While micromobility-based delivery fleets offer significant emission advantages compared to conventional vans, their operational efficiency depends on adaptive, data-driven capacity allocation. We develop and analyze a real-time optimization framework that explicitly integrates sustainability considerations into zone-level fleet allocation decisions. The continuous-time backlog dynamics admit a closed-form discrete-time prediction, enabling computationally efficient rolling-horizon fleet reallocation. Sustainability is explicitly embedded through zone-specific emission factors and a multi-criteria objective function balancing backlog reduction, environmental impact, and operational stability. In a ten-zone numerical case study with a fleet of 40 vehicles, the proposed method reduced backlog in all zones within a 15-min interval while preserving strict feasibility and stability (spectral radius is less than 1). The framework also demonstrated a controllable emission–service trade-off via sensitivity analysis. These results suggest the practical applicability and real-time suitability of the proposed Industry 4.0-aligned optimization approach. Full article

Chinese font generation is important for digital typography, cultural preservation, and personalized user interfaces. However, existing methods often face challenges in maintaining structural consistency, supporting diverse stylistic variations, and achieving computational efficiency simultaneously, especially in cloud-based environments. A key application is bandwidth-efficient font delivery, where compact structural templates replace large font files for on-demand style customization. To address these issues, this paper proposes Stroke2Font—a hierarchical vector model with AI-driven optimization for dynamic Chinese font generation. The core model decouples structural representation from style rendering through stroke element decomposition and Bézier curve parameterization. To further balance structural fidelity, style diversity, and real-time performance, we introduce a three-module optimization framework: (1) a reinforcement learning policy for dynamic selection of Bézier control parameters to minimize rendering latency; (2) a genetic algorithm for exploring style vector spaces and generating novel font variants; and (3) an adaptive complexity-aware optimization strategy that dynamically configures parameters based on character structural complexity. Experimental results on a dataset of 150 Chinese characters with 1123 stroke trajectories and 5287 feature points demonstrate that the adaptive complexity-aware optimization achieves the highest trajectory similarity of 65.2%, representing a 6.4% relative improvement over baseline (61.3%). The evaluation covers characters ranging from 1 to 18 strokes across 6 stroke types, with standard deviation reduced to ±5.7% (compared to ±6.5% baseline), indicating more consistent performance. Quantitative analysis confirms that the method generalizes effectively across varying character complexity, with the optimization showing stable improvement regardless of stroke count distribution. These results validate that Stroke2Font provides an effective solution for high-quality, efficient, and scalable Chinese font generation in cloud-based applications. Full article

Background: Cardiorenal syndrome (CRS) represents a complex clinical entity characterized by the bidirectional dysfunction of the heart and kidneys. Despite advances in pharmacological therapy, CRS remains associated with high morbidity and mortality. Pathophysiological drivers, including oxidative stress, chronic inflammation, and mitochondrial derangements, create a self-perpetuating cycle of organ damage that necessitates multitarget therapeutic approaches. Objective: This review synthesizes current preclinical evidence regarding the protective roles of plant-derived polyphenols—specifically bergamot, curcumin, quercetin, catechins, and resveratrol—in mitigating the cardiorenal continuum. Methods: An analysis of recent literature was conducted, focusing on the molecular mechanisms by which these bioactives modulate redox balance, inflammatory signaling, and mitochondrial homeostasis in experimental models of CRS. Results: Polyphenols act at the crossroads of several stress-response pathways. Key mechanisms include the activation of the Nrf2/HO-1 axis to enhance endogenous antioxidant defenses, the suppression of the NLRP3 inflammasome to attenuate systemic “inflammaging”, and the preservation of mitochondrial quality through SIRT1/PINK1/Parkin-mediated mitophagy. Furthermore, emerging evidence highlights the role of polyphenols in modulating the gut-kidney-heart axis by reducing microbiota-derived uremic toxins. Conclusions: Preclinical data suggest that polyphenols are potent multifunctional agents capable of breaking the feedback loops of cardiorenal injury. While bioavailability remains a significant translational challenge, novel nano-delivery systems and synthetic analogs offer promising strategies for clinical application. Integrating these bioactives into CRS management could provide a decisive adjunctive strategy to improve metabolic homeostasis and prevent end-stage organ failure. Full article

Boron neutron capture therapy (BNCT) is a biologically targeted, high–linear energy transfer radiotherapy that selectively delivers cytotoxic α-particles to boron-loaded tumor cells and has re-emerged with the development of hospital-compatible accelerator neutron sources and improved boron carriers. We performed a structured literature review of PubMed, Embase, and the Cochrane Library through October 2025 to summarize the radiobiological rationale, boron delivery strategies, and clinical outcomes of BNCT in glioblastoma (GBM) and other high-grade central nervous system tumors. Eligible clinical and translational studies were screened independently, and data on patient populations, boron agents, neutron source technologies, dosimetry, survival, response, and toxicity were extracted. Contemporary series and phase II trials indicate that BNCT is technically feasible and generally well tolerated, with encouraging survival outcomes in selected newly diagnosed and recurrent GBM, meaningful activity in recurrent high-grade meningiomas, and acceptable safety in limited pediatric cohorts. Current practice relies primarily on second-generation carriers such as boronophenylalanine and sodium borocaptate, while third-generation molecular and nanocarrier platforms remain in preclinical development. Overall, BNCT represents a promising high-LET, pharmacologically targeted modality for heavily pretreated and radioresistant CNS tumors, and ongoing prospective studies are needed to define its comparative effectiveness and optimal integration into patient care. Full article

Background/Objectives: Treatment disruptions and discontinuations during systemic cancer therapy are common and can compromise treatment delivery and outcomes. Structured exercise and mind–body interventions improve cancer-related symptoms, but their impact on treatment disruptions and discontinuations remains unclear. This secondary analysis of the IMPROVE trial evaluated whether participation in Integrative Medicine at Home (IM@Home), a digital multimodal mind–body and structured exercise program, was associated with differences in treatment discontinuation and related treatment disruption outcomes among patients undergoing systemic therapy. Methods: A total of 127 adults with solid tumors were randomized to IM@Home (n = 64) or enhanced usual care (EUC; n = 63) for 12 weeks. Treatment discontinuation, dose delays, dose reductions, and overall treatment disruptions were compared between arms using chi-square tests and regression models adjusted for cancer type and disease stage. Results: In unadjusted analyses, treatment discontinuation occurred less frequently in the IM@Home group compared with EUC (9.4% vs. 22.6%; p = 0.043), but this association was attenuated after adjustment for cancer type and disease stage (aOR 0.41, 95% CI 0.13–1.17; p = 0.105). The proportion of patients experiencing any treatment disruption, as well as rates of dose delays and dose reductions, did not differ significantly between groups (p = 0.16, p = 0.18, and p = 0.85, respectively). In contrast, IM@Home participants experienced fewer treatment disruption events per patient (adjusted RR 0.58, 95% CI 0.35–0.96; p = 0.036). Conclusions: These exploratory findings suggest that digital structured exercise and mind–body programs may help mitigate treatment interruptions during systemic cancer therapy and should be explored further in an adequately powered prospective trial to confirm these promising findings. Full article

Background: Given global population growth and aging, it is imperative to prioritize early eye disease detection and treatment. However, as patient volume increases, providers are facing a shortage of workforce capacity, particularly in areas where eye doctors are already scarce, making it important to consider alternative innovative solutions that could help increase eye screening capabilities. This study compared virtual reality (VR) platform of vision screening exams that are used to evaluate ocular health, such as 24-2 perimetry, Ishihara tiles, and the Amsler grid, against their in-clinic counterparts. Methods: A total of 86 subjects were recruited from Mount Sinai’s ophthalmology clinic (New York, USA) for a comparison trial that was internally controlled across healthy eyes and those with glaucoma and retinal diseases. VR and in-office tests were administered to the patients during their clinical visit, including 24-2 perimetry, Ishihara tiles, and the Amsler grid in a randomized order, and the results were compared for each test. Results: Perimetry results from Humphrey Visual Field Analyzer (HVFA) and VR suprathreshold testing demonstrated a good sensitivity both overall (80% OD, 84% OS) and across control (86% OD, 89% OS), glaucoma (69% OD, 78% OS), and retinal disease (76% OD, 80% OS) groups. A Garway-Heath anatomical map showed an overall 70–80% agreement. Ishihara plate tests did not show a significant difference between the two testing modalities (p = 0.12; Mann–Whitney U test), which remained true across all groups. Amsler grid testing differences were also non-significant within each subgroup (p = 0.81; Mann–Whitney U test). Patient time required to complete VR exams was significantly improved (p < 0.0001; Welch’s t-test) compared to the clinical standard tests. Conclusions: All VR-based exams tested in this study showed high sensitivity and percent agreement when compared to their in-office standards. Given the results of this study, VR has a promising potential in visual function screening, which, in addition to its portable design and easy use, could assist eye doctors in screening for prevalent diseases such as glaucoma and retinal conditions. Translational Relevance: VR-based vision exams that test vision fields, color vision and visual distortions provide comparable results in healthy patients, as well as those with glaucoma and retinal diseases, indicating its potential as a screening technology for different ocular pathologies. Given VR’s portable and low-profile features, it is important to consider leveraging VR to augment delivery of vision care. Full article

Among the most structurally diverse biomacromolecules, polysaccharides have attracted increased attention as nanocarriers for precision medicine due to their inherent biocompatibility and versatility in functionalization. Molecular features, such as monomer composition, glycosidic linkages, charge density, and chemical modification, essentially determine the nanoscale assembly process of these biopolymers, as well as their biological compatibility. This review highlights the role of these properties in the assembly process of polysaccharide-based nanocarriers leading to a variety of self-assembled nanostructures, such as polyelectrolyte complexes, protein–polysaccharide complexes, amphiphilic micelles, vesicles, hybrid systems, and nanogels, which are extensively discussed throughout the review. This review also focuses on the structure–property–function relationships of nanocarriers as applied to the rapidly developing area of precision medicine, emphasizing the problems of sustainability and reproducibility. By combining the principles of molecular engineering, supramolecular assembly, and measurable properties, this work aims to present a unified view of the molecular engineering of polysaccharide-based nanocarriers for enhanced translation potential, as well as to outline a coherent framework for the rational development of next-generation polysaccharide-based nanocarriers with improved clinical relevance. Full article

Hypoxic pulmonary hypertension (HPH), classified as Group 3 pulmonary hypertension in the current clinical classification system, represents a complex and progressive cardiopulmonary disorder characterized by elevated pulmonary arterial pressure due to chronic alveolar hypoxia. This condition significantly contributes to morbidity and mortality in patients with chronic lung diseases and individuals residing at high altitudes. The pathogenesis of HPH involves a multifactorial interplay between sustained hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, endothelial dysfunction, and inflammatory responses. This review provides a comprehensive synthesis of recent advances in HPH pathophysiology and their clinical translation, with a focus on integrating molecular mechanisms with emerging therapeutic strategies. The pathogenesis of HPH involves a complex interplay of hypoxia-inducible factor (HIF) signaling, mechanosensitive ion channel dysregulation (particularly TRPC channels), metabolic reprogramming featuring glycolytic shift and mitochondrial dysfunction, immune–inflammatory mechanisms including macrophage-centered immunopathology, and dysregulation of the nitroxidergic system. Recent clinical advances include refined risk stratification using advanced echocardiographic techniques, identification of novel biomarkers such as lactylation-associated proteins, and development of targeted therapies including immunomodulatory approaches, metabolic modulators, and epigenetic interventions. Ongoing clinical trials are investigating innovative strategies ranging from iron supplementation to nanoparticle-based drug delivery systems. Despite these advances, significant translational challenges remain, including limitations of preclinical models, patient heterogeneity, and the need for HPH-specific outcome measures. This review bridges the gap between mechanistic insights and clinical applications, offering an integrated framework that highlights precision medicine approaches, emerging therapeutic targets, and priority research directions for improving outcomes in this challenging condition. Full article

Natural and sustainable cosmetics represent a rapidly evolving frontier in dermatological science, integrating plant-derived bioactive compounds with advanced delivery technologies and environmentally conscious formulation design. Botanical ingredients, including polyphenols, flavonoids, terpenoids, alkaloids, and polysaccharides, modulate key biological pathways involved in oxidative stress, inflammation, extracellular matrix remodeling, pigmentation, and immune responses, thereby supporting skin regeneration, protection, and homeostasis. To overcome limitations related to instability, compositional variability, and limited skin penetration, these compounds are increasingly incorporated into advanced delivery systems such as nanoemulsions, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), vesicular systems, microneedle platforms, three-dimensional matrices, and plant-derived extracellular vesicles (PDEVs). These technologies enhance cutaneous bioavailability, enable controlled release, and improve tissue targeting, linking formulation design to exposure–response relationships. In parallel, sustainability has become a critical component of product development. Circular economy strategies, including the upcycling of agro-industrial by-products, green extraction technologies, biodegradable packaging, and life cycle assessment, are reshaping cosmetic innovation. Regulatory frameworks are also evolving to address safety, efficacy, and transparency of natural claims, as well as the challenges of botanical standardization. This narrative review, conducted through a structured literature search, provides a mechanistically oriented analysis of botanical ingredients in dermatology, emphasizing molecular pathways, skin delivery science, and safety considerations. Rather than cataloguing ingredients, it proposes a translational framework linking phytochemistry, delivery science, safety-by-design principles, and sustainability to support the rational development of effective and safe dermatological formulations. Full article

Background: Depression remains a major global health burden, yet fragmented care often leads to waiting times and unmet needs. Therefore, the Belgian collaborative Integrated Depression Care (IDECA) project strengthened primary care depression management by introducing a Reference Person Mental Wellbeing (RPMW) who functions as a case manager, supported by shared-care tools, structured psychoeducation modules, and targeted training for general practitioners (GPs). This study examines normalization in primary care practice. Methods: A single-arm, mixed-method study was implemented over 18 months in two Flemish Primary Care Zones (PCZ). Implementation outcomes were assessed every four months using the NoMAD questionnaire and analyzed using Wilcoxon signed-rank tests. Peer review sessions with professionals and interviews with patients were analyzed thematically. Caseload and service delivery were assessed using process evaluation logs. Results: Twenty-two professionals (17 GPs, two RPMWs, and three PCZ staff members) completed the NoMAD questionnaire. Intervention familiarity increased during the first eight months (T0–T1: p < 0.001; T1–T2: p = 0.022) and continued to rise thereafter (T3–T4: p = 0.008). Integration into daily practice and perceived impact on professional work improved progressively, reaching near-ceiling scores. Peer review sessions highlighted the RPMW’s central role in trust-building and care coordination. Over 12 months, one full-time equivalent RPMW supported 175 patients (mean age 40.7 years; 75% female), with an average of five consultations per patient. Patients reported high satisfaction, emphasizing accessibility, empathy, and practical support. Conclusions: Sustained results suggest successful normalization and support the potential of collaborative, low-threshold depression care. Future work will assess clinical and economic outcomes. Full article

Insulators are essential components in high-voltage transmission lines and require regular inspection to ensure reliable power delivery. Traditional manual inspection methods are inefficient and labor intensive, highlighting the need for intelligent and automated solutions. In this study, we propose a missing insulator detection method that integrates Unmanned Aerial Vehicle (UAV) imaging with deep learning techniques. Firstly, an improved Faster Region-based Convolutional Neural Network (Faster R-CNN) is employed to detect and localize insulators in aerial images. Secondly, the localized insulators are segmented using an improved U-Net to reduce background interference. A bounding box regression approach is adopted to obtain the minimum enclosing rectangles, and the insulators are aligned vertically. Adaptive thresholding is then applied to extract binary images of the insulators. These binary images are further transformed into defect curves, from which missing insulators are identified based on curve distribution. To address the limited availability of labeled samples, a transfer learning-based strategy is adopted to improve model generalization. A dataset of glass insulators was collected using a DJI M300 UAV equipped with an H20T camera along a 330 kV overhead transmission line. On the collected UAV insulator dataset, the proposed method achieved an AP@0.5 of 99.85% and an average IoU of 88.56% for insulator string detection, while the improved U-Net achieved an mIoU of 89.73% for insulator string segmentation. Outdoor flight experiments further verified performance under varying backgrounds and illumination conditions in our UAV inspection scenarios. Full article

Low-concentration methane emissions from landfills, manure management, wastewater treatment, and ventilation streams are difficult to mitigate using conventional capture and oxidation because of high air-to-fuel ratios, variable flows, and unfavorable economics. Methanotrophic bioreactors provide an aerobic biological route to oxidize methane at ambient conditions and, in selected cases, enable valorization into biomass and bioproducts. This review synthesizes methanotrophic reactor technologies for dilute methane, emphasizing the design and operational constraints that control performance. We classify systems into (i) fixed-film gas–solid configurations (biofilters, biocovers, biotrickling filters, and bioscrubbers), (ii) suspended-growth gas–liquid reactors (stirred tanks, bubble columns, and loop/airlift designs), (iii) membrane-based and intensified contactors that decouple methane and oxygen delivery and enhance mass transfer, and (iv) hybrid and in situ approaches for diffuse sources. This review presents key metrics and discusses how mass transfer, moisture and temperature control, nutrient supply, and microbial ecology interact to define achievable removal. We further summarize recent techno-economic and life-cycle studies to identify dominant cost drivers, particularly air handling and gas–liquid transfer, and the concentration regimes where biological oxidation is competitive with catalytic or thermal alternatives. Full article