Search Results (364)

Background: Nanomedicine has demonstrated great potential to improve drug delivery across various diseases. However, accurately monitoring the real-time trafficking of organic nanoparticles (NPs) within biological systems remains a significant challenge. Current detection methods rely heavily on fluorescence, while high-resolution, label-free imaging is often precluded by the limited optical contrast of organic materials, limiting a comprehensive understanding of NP fate. Metallic doping allows simultaneous detection of carriers using multiple imaging and analysis techniques. This study presents a novel approach to prepare gold-doped hybrid NPs compatible with multimodal imaging, thus facilitating multimodal tracking. Methods: Gold-doped NPs were successfully synthesized via nanoprecipitation, yielding stable, monodisperse carriers with optimal size, confirmed by Dynamic Light Scattering and Nanoparticle Tracking Analysis. UV/Vis spectroscopy confirmed effective gold-doping, with doping efficiency of approximately 50%. Transmission Electron Microscopy (TEM) showed gold NP accumulation throughout the polymer core and near the lipid shell. Results: Although gold doping resulted in a slight increase in NP size and zeta potential, no effects on cytocompatibility or cellular uptake by glioblastoma and microglia cells were observed. Furthermore, the optical properties (i.e., the refractive index and the UV spectrum) of the NPs were successfully modified to enable tracking across complementary imaging modalities. Real-time, label-free visualization of NP accumulation in the cytoplasm of U87 cells was achieved via holotomography by exploiting the enhanced refractive index after gold-doping. This observation was confirmed through correlation with fluorescence confocal microscopy, using fluorescently labelled gold-doped NPs. Furthermore, the high electron density of the gold tracer facilitated the precise localization of NPs within intracellular compartments via TEM, bypassing the inherently low contrast of organic NPs. Conclusions: These findings validated the gold-doped NPs as versatile nanoplatforms for multimodal imaging, showcasing their potential for non-invasive, high-resolution tracking and more accurate quantification of intracellular accumulation using diverse analytical techniques. Full article

Background: Eczematous dermatitis refers to a group of inflammatory skin disorders—including seborrheic, atopic, and contact dermatitis—characterized by epidermal barrier dysfunction and chronic inflammation. Disrupting the itch–scratch cycle and reversing microscopic skin changes are key to improving patient outcomes and quality of life. Aims: This study aimed to assess the clinical and microscopic effects of a topical medical device containing N-butanoyl glutathione (GSH-C4) and hyaluronic acid in patients with inflammatory eczematous dermatitis, combining clinical scores with in vivo confocal and OCT imaging. Methods: A prospective clinical trial enrolled 30 patients with active eczematous lesions. Participants applied a GSH-C4/hyaluronic acid-based product (GSEBA^®) for 28 days. Clinical improvement was evaluated at baseline, day 14, and day 28 using the Investigator’s Global Assessment (IGA), a Visual Analog Scale (VAS) for itching, and a self-reported index of disease impact on quality of life (IDL). Microscopic changes were assessed using optical coherence tomography (OCT) and reflectance confocal microscopy (RCM). Results: After 28 days, the mean IGA score improved from 2.48 to 0.18 (p < 0.001), VAS itching score decreased from 4.52 to 0.32 (p < 0.001), and IDL dropped from 4.86 to 0.79 (p < 0.001). RCM analysis showed significant reductions in key inflammatory features such as spongiosis, vesiculation, and inflammatory infiltrate. OCT revealed a significant decrease in vascularization at 150 μm depth, with no change in collagen density. Conclusions: The GSH-C4/hyaluronic acid-based mousse (GSEBA^®) demonstrated strong clinical efficacy and excellent tolerability in managing eczematous dermatitis. It effectively reduced both symptoms and microscopic markers of inflammation without compromising dermal structure. Full article

Melanoma is among the most lethal forms of skin cancer, where early and accurate diagnosis significantly improves patient survival. Traditional diagnostic pathways, including clinical inspection and dermoscopy, are constrained by interobserver variability and limited access to expertise. Between 2020 and 2025, advances in artificial intelligence (AI) and medical imaging technologies have substantially redefined melanoma diagnostics. This narrative review synthesizes key developments in AI-based approaches, emphasizing the progression from convolutional neural networks to vision transformers and multimodal architectures that incorporate both clinical and imaging data. We examine the integration of AI with non-invasive imaging techniques such as reflectance confocal microscopy, high-frequency ultrasound, optical coherence tomography, and three-dimensional total body photography. The role of AI in teledermatology and mobile applications is also addressed, with a focus on expanding diagnostic accessibility. Persistent challenges include data bias, limited generalizability across diverse skin types, and a lack of prospective clinical validation. Recent regulatory frameworks, including the European Union Artificial Intelligence Act and the United States Food and Drug Administration’s guidance on adaptive systems, are discussed in the context of clinical deployment. The review concludes with perspectives on explainable AI, federated learning, and strategies for equitable implementation in dermatological oncology. Full article

Background/Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor with dismal prognosis and limited treatment options. Immunotherapy, including personalized approaches using tumor-infiltrating lymphocytes (TILs) and allogeneic natural (NK) or engineered killer cells (chimeric antigen receptor NK, NK-CAR), and oncolytic viruses (OV), has shown some potential in GBM. Combining different therapeutic strategies may enhance treatment efficacy. Here, we present a xenograft GBM mouse model with multiparametric detection for various immunotherapy research applications. Methods: In a xenograft GBM NOD-Prkdcs scid Il2rgem1/Smoc (NSG) mouse model based on orthotopic transplantation of patient-derived GBM cultures retaining tumor heterogeneity, intravenous and intratumor immunotherapeutic interventions by TIL and OV therapy were performed. Xenograft engraftment was evaluated using intravital MRI; delivery of OV and TILs to the tumor and changes in the tumor and peritumoral space were assessed using intravital confocal microscopy; and metabolic and structural changes in the tumor and peritumoral environment were assessed via fluorescence lifetime imaging microscopy (FLIM) and optical coherence tomography (OCT). The intravital imaging data were compared with the results of preliminary and final histological and immunocytochemical data. Results: Both OV and TILs demonstrated tumor-specific targeting and delivery across the blood–brain barrier. Further, we showed that in this model the xenograft response to both therapeutic treatments can be assessed using FLIM and OCT. Conclusions: Overall, this work presents an optimized mouse model suitable for assessing the effect of combined TIL immunotherapy and OV on GBM in translational studies. Full article

This paper provides an overview of artificial intelligence (AI) applications in ophthalmology, with a focus on diagnosing dry eye disease (DED). We aim to synthesize studies that explicitly compare AI-based diagnostic models with clinical tests employed by ophthalmologists, examine results obtained using similar imaging modalities, and identify recurring limitations to propose recommendations for future work. We conducted a systematic literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines across four databases: Google Scholar, PubMed, ScienceDirect, and the Cochrane Library. We targeted studies published between 2020 and 2025 and applied predefined inclusion criteria to select 30 original peer-reviewed articles. We then analyzed each study based on the AI models used, development strategies, diagnostic performance, correlation with clinical parameters, and reported limitations. The imaging modalities covered include videokeratography, smartphone-based imaging, tear film interferometry, anterior segment optical coherence tomography, infrared meibography, in vivo confocal microscopy, and slit-lamp photography. Across modalities, deep learning models (e.g., U-shaped Convolutional Network (U-Net), Residual Network (ResNet), Densely Connected Convolutional Network (DenseNet), Generative Adversarial Networks (GANs), transformers) demonstrated promising performance, often matching or surpassing clinical assessments, with reported accuracies ranging from 82% to 99%. However, few studies performed external validations or addressed inter-expert variability. The findings confirm AI’s potential in DED diagnosis, but emphasize gaps in data diversity, clinical use, and reproducibility. It offers practical recommendations for future research to bridge these gaps and support AI deployment in routine eye care. Full article

Spinning disk confocal microscopy enables fast optical sectioning with low phototoxicity but is often inaccessible due to high hardware costs. We present a lower-cost solution using a 25-megapixel machine vision CMOS camera and a custom-built spinning disk. This camera uses a back-illuminated sensor with high quantum efficiency and low read noise. High-resolution images of Thy1-GFP mouse brain slices, Drosophila embryos and larvae, and H&E-stained rat testis verified performance across 3D tissue volumes. The measured resolution was 215.8 nm in X, Y and 521.9 nm in Z with a 60×/1.42 NA objective. The custom disk, made with 18 µm pinholes (180 µm pitch) on a chrome photomask and mounted to an optical chopper motor, enables stable, near-telecentric imaging at lower magnifications. Micromanager software integration allows synchronized control of all hardware, which demonstrates that affordable CMOS sensors can potentially replace sCMOS in spinning disk microscopy, offering an open-access, scalable solution for advanced imaging. Full article

Background: Fungal keratitis remains a serious threat to vision, often progressing despite medical therapy and requiring surgical intervention. Therapeutic deep anterior lamellar keratoplasty (DALK) and therapeutic penetrating keratoplasty (TPK), are frequently required but carry risks of infection recurrence and graft rejection. As timely identification of the etiological agent is essential for improving the outcomes in infectious keratitis, in vivo confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT) are instrumental in providing insights that can guide better therapeutic decision-making and improving outcomes in fungal keratitis. Case Description: We report the cases of two previously healthy patients (case one, 56-year-old woman; case two, 38-year-old man), who have presented in our service with unilateral infectious keratitis after ocular trauma with vegetable matter during outdoor activities, with a visual acuity of counting fingers and hand motion, respectively. Slit-lamp examination revealed unilateral extensive corneal infiltrates suggestive for fungal etiology in both cases. In vivo confocal microscopy (HRT-3, Heidelberg Retina Tomograph 3/Rostock Cornea Module, Heidelberg Engineering, Heidelberg, Germany) identified lesions suggestive for Candida Albicans and Acanthamoeba coinfection in case one and filamentous fungal keratitis in case two. Anterior segment optical coherence tomography (MS-39, CSO, Italy) was used to monitor the extent and morphology of the infiltrates. The patients underwent therapeutic DALK and TPK, respectively, with good results at the one-year follow-up. Conclusions: Our cases illustrate the advantages of incorporating IVCM and AS-OCT as complementary imaging techniques into clinical practice. IVCM and AS-OCT in fungal keratitis could lead to an earlier diagnosis, more accurate dynamic treatment response evaluation, and the identification of high-risk features for aggressive fungi for a more tailored medical and surgical management. Full article

Background/Objectives: Glaucoma is a neurodegenerative optic disorder which occurs due to persistent elevation of the intraocular pressure. It leads to permanent blindness and currently affects over 75 million individuals worldwide. Nowadays, topical ocular medications are the leading therapy despite their poor ocular penetration and short residence time. Methods: The purpose of this research is to formulate bisoprolol hemifumarate-loaded polylactic-co-glycolic acid (PLGA) nanoparticles and improve their ocular penetration and bioavailability for the treatment of glaucoma by enhancing the delivery of the drug to the posterior part of eye. By using the solvent displacement method, formulations were prepared and optimum formula was elected using Design-Expert^® software. Results: In vitro characterization demonstrated that the optimum formula contained 25 mg BSP, 22.5 mg PLGA, and 60 mg Tween80, yielding high values of drug encapsulation (75%) and zeta potential (−18.7 ± 0.41 mV), with a low particle size (105 ± 0.35 nm) and polydispersity index (0.411 ± 0.71). Transmission electron microscopy and atomic force microscopy showed smooth and spherical nanosized particles. X-ray diffraction, differential scanning calorimetry, and Fourier-transform infrared spectroscopy revealed successful encapsulation of the drug inside the polymeric matrix. Ex vivo confocal laser scanning microscopy proved that there was better uptake of the drug upon using PLGA-NPs. In vitro release profiles indicated biphasic drug release from the PLGA-NPs, confirming a sustained drug release over 12 h. In vivo studies showed that BSP-PLGA-NPs significantly reduced the IOP compared to bisoprolol solution. Quantitative immunohistochemistry showed lower retinal GFAP expression with BSP-PLGA-NPs compared with induced controls and drug solution, which is indicative of attenuated glial activation. Conclusions: These data support improved ocular delivery and an improved pharmacodynamic effect; however, they demonstrate association rather than a direct mechanistic suppression of glial pathways. Full article

Background: In vivo confocal microscopy (IVCM) provides high-resolution corneal imaging that may enhance preoperative and postoperative assessment in refractive surgery. This pilot study aimed to evaluate the diagnostic utility of IVCM in identifying subclinical corneal abnormalities that could influence surgical qualification and outcomes. Methods: A total of 7 patients (3 males, 4 females; mean age 48.8 ± 14.5 years) undergoing qualification or follow-up for refractive surgery were prospectively examined between May 2021 and March 2025. Each participant underwent a comprehensive ophthalmic evaluation, including slit-lamp biomicroscopy, corneal topography, anterior segment optical coherence tomography (AS-OCT), and IVCM using the Heidelberg Retina Tomograph II with Rostock Cornea Module. Patients with prior ocular surgery, active infection, or systemic corneal disease were excluded. Results: IVCM revealed subtle epithelial, stromal, and endothelial abnormalities undetectable by conventional methods. Findings such as Thygeson’s keratitis, pre-Descemet’s dystrophy, and subclinical herpes simplex keratitis led to modifications of surgical plans or disqualification in selected cases. The technique also aided postoperative evaluation of epithelial–stromal interface disorders. Conclusions: IVCM proved to be a valuable adjunct in detecting subclinical corneal pathology, refining patient selection, and improving safety in refractive surgery. Larger multicenter studies are warranted to validate its clinical role and define standardized indications for preoperative screening. Full article

Advanced manufacturing places stringent demands on measurement technologies, requiring ultra-high precision, non-contact operation, high throughput, and real-time adaptability. Optical metrology, with its distinct advantages, has become a key enabler in this context. This paper reviews optical metrology techniques from the perspective of precision manufacturing applications, emphasizing precision positioning and surface topography measurement while noting the limitations of traditional contact-based methods. For positioning, interferometers, optical encoders, and time-of-flight methods enable accurate linear and angular measurements. For surface characterization, techniques such as interferometry, structured light profilometry, and confocal microscopy provide reliable evaluation across scales, from large structures to micro- and nano-scale features. By integrating these approaches, optical metrology is shown to play a central role in bridging macroscopic and nano-scale characterization, supporting both structural assessment and process optimization. This review highlights its essential contribution to advanced manufacturing, and offers a concise reference for future progress in high-precision and intelligent production. Full article

Cell migration through confined spaces is a critical step in cancer metastasis, yet the spatial regulation of endocytosis and adhesion dynamics during this process remains poorly understood. To investigate this, we adapted a microfluidic platform that generates stable, spatially linear biochemical gradients across 5 μm-tall migration channels. COMSOL simulations and optical calibration using FITC-dextran confirmed that gradients form reliably within 5 min. The microdevice also supports long-term live imaging and is compatible with both spinning disk confocal and total internal reflection fluorescence structured illumination microscopy modalities, enabling high-resolution visualization of adhesion and endocytic structures. By leveraging this platform for spatially restricted drug delivery, we locally applied the endocytic inhibitor Dyngo-4a to either the front or rear of migrating cells. This revealed that front-targeted endocytic inhibition preserved or increased leading-edge enrichment of paxillin and the clathrin adaptor AP-2, whereas rear-targeted inhibition eliminated paxillin polarity and reduced AP-2 polarity. These changes were accompanied by a significant increase in cell migration speed under front-targeted inhibition, while rear-targeted inhibition had no significant effect on speed and neither treatment altered persistence. Together, these findings suggest that endocytic polarity regulates adhesion dynamics and cell migration under confinement, offering a mechanistic insight into processes relevant to cancer cell invasion. Full article

Keratoacanthoma (KA) is a rapidly growing epithelial neoplasm characterized by clinical and histopathological features that often overlap with well-differentiated squamous cell carcinoma (SCC), posing diagnostic challenges. This review provides a comprehensive overview of KA, emphasizing advances in non-invasive diagnostic techniques such as dermoscopy, reflectance confocal microscopy (RCM), and line-field confocal optical coherence tomography (LC-OCT), which improve lesion characterization and differentiation from SCC. We discuss the histopathological phases of KA and highlight key features aiding in diagnosis. Furthermore, we explore the emerging role of human papillomavirus (HPV), particularly β-genus types, as a cofactor in KA carcinogenesis through modulation of apoptosis and DNA damage response pathways, especially under ultraviolet (UV) radiation exposure. Therapeutic strategies remain centered on complete surgical excision; however, alternative treatments, including radiotherapy, cryotherapy, topical agents, and systemic retinoids, are discussed with their respective benefits and limitations. Finally, we review current HPV vaccines and novel vaccine candidates targeting a broad spectrum of mucosal and cutaneous HPV types. This review underscores the importance of integrated diagnostic and therapeutic approaches to optimize KA management and highlights future directions in understanding its pathogenesis and treatment. Full article

The optical microscope is an indispensable observation instrument that has fundamentally contributed to progress in science and technology. Dark-field microscopy and scattered light imaging techniques enable high-contrast observation of nanoparticles in water. However, the scattered light is focused by the optical lenses, resulting in a blurred image of the nanoparticle structure. Here, we developed a projection optical microscope (PROM), which directly observes the scattered light from the nanoparticles without optical lenses. In this method, the sample is placed below the focus position of the microscope’s objective lens and the projected light is detected by an image sensor. This enables direct observation of the sample with a spatial resolution of approximately 20 nm. Using this method, changes in the aggregation state of nanoparticles in solution can be observed at a speed faster than the video frame rate. Moreover, the mechanism of such high-resolution observation may be related to the quantum properties of light, making it an interesting phenomenon from the perspective of optical engineering. We expect this method to be applicable to the observation and analysis of samples in materials science, biology and applied physics, and thus to contribute to a wide range of scientific, technological and industrial fields. Full article

Erbium (${\mathrm{Er}}^{3+}$) emitters are relevant for optical applications due to their narrow emission line directly in the telecom C-band due to the ⁴I_13/2 → ⁴I_15/2 transition at 1.54 μm. Additionally, they are promising candidates for future quantum technologies when embedded in thin film silicon-on-insulator (SOI) to achieve fabrication scalability and CMOS compatibility. In this paper we integrate Er³⁺ emitters in SOI metasurfaces made of closely spaced arrays of nanodisks, to study their spontaneous emission via room and cryogenic temperature confocal microscopy, off-resonance and in-resonance photoluminescence excitation at room temperature and time-resolved spectroscopy. This work demonstrates the possibility to adopt CMOS-compatible and fabrication-scalable metasurfaces for controlling and improving the collection efficiency of the spontaneous emission from the Er³⁺ transition in SOI and that they could be adopted in similar technologically advanced materials. Full article

The Chengyang City (城阳城) site in Xinyang, Henan Province, China, was a significant northern military stronghold of the Chu state during the Warring States period (475/403–221 BCE). The lacquered armor unearthed from Tomb M18 provides critical material evidence for studying ancient military technology and lacquer craftsmanship. In this study, a comprehensive analytical approach combining ultra-depth optical microscopy, Fourier-transform infrared spectroscopy (FTIR), confocal micro-Raman spectroscopy, scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDS) and pyrolysis–gas chromatography/mass spectrometry (Py-GC/MS) were employed to systematically characterize the structural and compositional features of the armor samples. The results indicate that the armor was constructed with a leather substrate and lacked any lacquer ash layer, while the surface exhibited multiple layers of mixed laccol and urushiol-based lacquer coatings. Cinnabar (HgS) was identified as the primary red pigment, and no carbon black or iron-based blackening agents were detected in the dark lacquer layers. Notably, the presence of laccol suggests that such lacquer resources may have also been produced in mainland China, offering new perspectives on the prevailing view that associates laccol exclusively with “Vietnamese lacquer.” This study elucidates the technological characteristics of mid-Warring States period lacquered armor, provides scientific insights into ancient lacquering techniques, and contributes valuable data for the conservation and restoration of similar cultural heritage artifacts. Full article