ABSTRACT Autoimmune thyroid diseases (AITD) are systemic conditions frequently associated with neurological manifestations, yet the underlying neural and immunological mechanisms remain unclear. This study focuses on thyroid eye disease (TED), a representative AITD, to provide a deeper insight into its neural mechanism. We first combined resting‐state functional magnetic resonance imaging (rs‐fMRI) data from a retrospective cohort of 116 TED patients with transcriptomic data from the Allen Human Brain Atlas. The analysis of rs‐fMRI data demonstrated significant alterations in frontal, parietal, subcortical, and brainstem regions in TED. By integrating rs‐fMRI data with regional transcriptomic profiles derived from the postmortem Allen Human Brain Atlas, enabling region‐level transcriptional inference, we revealed enriched pathways related to synaptic signaling, neurovascular regulation, and immune activation. Tissue and cellular level enrichment further showed close association with the cortex and neurons. Key neuroimaging findings identified in the retrospective cohort were subsequently validated in an independent prospective cohort of TED patients and healthy controls (TED: 39; HC: 42) using paired rs‐fMRI and peripheral blood RNA sequencing data, which identified significant associations between immune cell infiltration and neural activity patterns. Collectively, these findings delineate coordinated brain–immune associations in TED and generate hypotheses regarding neuroimmune interactions in AITD.

PURPOSE:This study aims to investigate retinal structure and vessel density (VD) alterations in the macular and optic nerve head (ONH) regions of patients with dysthyroid optic neuropathy (DON), and to assess their correlation with visual function. METHODS:A total of 133 thyroid eye disease (TED) patients (63 with DON and 70 without DON) and 24 healthy controls were enrolled. Retinal structural and vascular parameters were quantified using optical coherence tomography angiography (OCTA) in the macular (6 × 6 mm) and ONH (4 × 4 mm) regions. Visual function in TED patients was assessed by best corrected visual acuity (BCVA), visual field (VF), and visual evoked potentials. The diagnostic performance of OCTA parameters for identifying DON was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS:Compared with the non-DON patients, those with DON exhibited significantly decreased retinal VD in both macular and ONH regions, accompanied by thinner macular retina. The most pronounced changes were observed in macular whole retinal layer (WRL) and superficial retinal layer VD (P < 0.001). Both retinal VD and thickness correlated positively with BCVA and VF mean deviation. Furthermore, the macular WRL-VD demonstrated the highest diagnostic performance for DON (AUC = 0.833) and the combination parameters further improved accuracy (AUC = 0.861). CONCLUSIONS:OCTA reveals retinal microvascular and structural alterations in DON and may serve as a simple, precise, and noninvasive tool for early detection and clinical management to prevent irreversible visual loss.

According to the Solomon-Bloembergen-Morgan (SBM) theory, the number of coordinated water molecules (q) around the Gd3+ magnetic center plays an important role in the enhancement of magnetic resonance relaxivity. This coordination is significantly influenced by the surface structure of magnetic materials. Therefore, magnetic graphene quantum dots (GQDs), featuring diversified and controllable surface structures, have become a promising material for designing nanomaterials with high magnetic resonance relaxivity. In this work, we regulate the defect density of magnetic GQDs by selecting precursor topologies during the "bottom-up" preparation process, which modulates the number of coordinated water molecules in the magnetic Gd3+ center, thereby influencing its properties. The resulting longitudinal magnetic resonance relaxivity (r1) of the magnetic GQDs is enhanced to 46.5 mM-1 s-1 at 114 & micro;T, which is four times higher than that of commercial contrast agents at the same field strength (e.g., Gd-DTPA: r1 = 10.4 +/- 0.2 mM-1 s-1 at 114 & micro;T). On the basis of the low Gd3+ release rate and fluorescence characteristics of magnetic GQDs, we further demonstrate their potential application in fluorescent-MRI bimodal imaging.

The optic nerve, a component of the central nervous system (CNS), comprises axons from retinal ganglion cells (RGCs) that exhibit limited regenerative capacity following injury. Recent advances have substantially deepened our understanding of the epigenetic mechanisms underlying RGC survival and axonal regeneration, encompassing DNA methylation, histone modifications, noncoding RNAs (ncRNAs), RNA methylation, and their complex interplay. Here, we review emerging research paradigms that underscore the potential of epigenetic modulation in RGC survival promotion and axonal regeneration. We further explore the dual roles of epigenetic interventions in enhancing regeneration via both RGC-intrinsic regenerative pathways and extracellular microenvironment remodeling. Moreover, we discuss recent clinical progress that underscores the translational promise of epigenetic strategies for precision diagnostics and targeted therapies in optic nerve repair.

Background: Proliferative diabetic retinopathy (PDR) often leads to tractional retinal detachment and vitreous hemorrhage, requiring vitrectomy. Poor visual outcomes are commonly caused by macular edema and proliferative vitreous retinopathy after vitrectomy. Intravitreal dexamethasone implant has shown promise in improving visual function after vitrectomy for diabetic macular edema, but its role in vitrectomy in PDR treatment remains unexplored. This study aims to assess the effectiveness of vitrectomy combined with intravitreal dexamethasone implant for PDR patients. Methods: We designed a single-blind, randomized controlled trial with 100 participants diagnosed with PDR requiring vitrectomy. Participants were randomly assigned to either the dexamethasone implant group or the control group. The dexamethasone implant group underwent vitrectomy combined with intravitreal dexamethasone implant, while the control group underwent vitrectomy alone. The single surgeon performed all the vitrectomy surgeries, the choice of intravitreal dexamethasone implant treatment was disclosed before the closure of scleral wounds. Primary and secondary outcomes were assessed at baseline, 4 weeks, and 8 weeks post-vitrectomy. Primary outcome measures included corrected visual acuity (Snellen visual chart) and central retinal thickness (optical coherence tomography OCT). Secondary outcomes included elevated intraocular pressure, post-vitrectomy hemorrhage, retinal detachment, and systemic complications requiring hospitalization. Discussion: This protocol seeks to enhance our understanding of the effects of combined intravitreal dexamethasone implant with vitrectomy on visual outcomes and macular morphology changes in treating late complications of PDR. The trail was registered at Chinese Clinical Trial Registry at May 11th 2022 with registration number ChiCTR2200059760.

Purpose:To investigate the alterations in the glymphatic system in patients with thyroid eye disease (TED) using diffusion tensor imaging (DTI) analysis along the perivascular space (ALPS) and to explore the correlation between the glymphatic system and clinical features of TED. Methods:The study included 47 patients with TED, including 20 active TED patients (AP) and 27 inactive TED patients (IP), along with 24 healthy controls (HC). Imaging data including DTI sequence were acquired using a 3.0 Tesla scanner. ALPS values were calculated based on the diffusivity of the bilateral superior corona radiata and superior longitudinal fasciculus. Correlation analysis were thus performed between ALPS values and clinical characteristics. Results:The DTI-ALPS analysis in the TED patient group collectively showed lower mean and left ALPS values compared to the HC, with statistically significant differences observed (mean ALPS: P=0.0308, left ALPS: P=0.0032). Among the TED subgroups, the IP had significantly lower left ALPS values than HC (P=0.006). Correlation analysis within the IP subgroup indicated that lower ALPS values were significantly associated with longer disease duration (P=0.015) and greater palpebral fissure height (P=0.028). Conclusions:Glymphatic system dysfunction is evident in TED patients, with its extent influenced by disease activity and duration.

Precise tumor therapy is essential for improving treatment specificity, enhancing efficacy, and minimizing side effects. Targeting organelles is a key strategy for achieving this goal and is a frontier research area attracting a considerable amount of attention. The concept of organelle targeting has a significant effect on the structural design of the nanodrugs employed. Most notably, the intricate interactions among different organelles in a tumor cell essentially create a unified system. Unfortunately, this aspect might have been somewhat overlooked when existing organelle-targeting nanodrugs were designed. In this review, we underscore the synergistic relationship among the various organelles and advocate for a holistic view of organelle-targeting design. Through the integration of biology and material science, recent advancements in organelle targeting, escaping, and collaborating are consolidated to offer fresh perspectives for the development of antitumor nanomedicines.

Noninvasive transcranial brain stimulation (NTBS) has emerged as a potential therapeutic approach for eye diseases and visual dysfunctions. This systematic review evaluates the evidence from 23 randomized controlled trials examining the application of NTBS, including transcranial electrical stimulation and transcranial magnetic stimulation, in conditions such as amblyopia, myopia, visual field defects, glaucoma, diabetic retinopathy, macular degeneration, and blepharospasm. Studies assessed outcomes such as visual acuity, contrast sensitivity, and visual perception, with variable effects observed across trials. Most studies reported no serious adverse events, indicating that NTBS is safe and feasible. However, conclusive evidence regarding its efficacy remains elusive due to varied interventions, inconsistent outcome measures, and methodological limitations. Future research with higher methodological rigor is needed to optimize stimulation parameters and explore integration with adjunctive therapies.

Radiomics holds great potential in medical image analysis for various ophthalmic diseases. In recent times, there have been numerous endeavors in this area of research. This systematic review aims to provide a comprehensive assessment of the strengths and limitations of radiomics in ophthalmology. Conforming to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, we conducted a systematic review with a pre-registered protocol (PROSPERO: CRD42023446317). We explored the PubMed, Embase, and Cochrane databases for original studies on this topic and made a comprehensive descriptive integration. Furthermore, the included studies underwent quality assessment by the radiomics quality score (RQS). A total of 41 articles from an initial search of 227 studies were finally selected for further analysis. These articles included research across five disease categories and covered seven imaging modalities. The radiomics models demonstrated robust performance, with area under the curve (AUC) values mostly falling within 0.7–1.0. The moderate RQS (mean score: 11.17/36) indicated that most studies were retrospectively, single-center analyses without external validation. Radiomics holds promising utility in the field of ophthalmology, assisting diagnosis, early-stage screening, and prognostication of treatment response. Artificial intelligence algorithms significantly contribute to the construction of radiomics models in ophthalmology. This study highlights the strengths and challenges of radiomics in ophthalmology and suggests potential avenues for future improvement. Radiomics represents a valuable approach for generating innovative imaging markers, enhancing efficiency in clinical diagnosis and treatment, and aiding decision-making in clinical contexts of many ophthalmic diseases, thereby improving overall patient prognosis.

Background: Optic nerve imaging is crucial for diagnosing and understanding optic neuropathies because it provides detailed visualization of the nerve's structure and pathologies through advanced modalities. This study conducted a bibliometric analysis within the field of optic nerve imaging, aiming to pinpoint the latest research trends and focal points in optic nerve imaging. Methods: The core literature on optic nerve imaging published between January 1991 and August 2023 was retrieved from the Web of Science Core Collection. The analysis and visualization of scientific productivity and emerging trends were facilitated through the utilization of Bibliometrix software, CiteSpace, Gephi, VOSviewer, R software, and Python. Results: In total, 15,247 publications on optic nerve imaging were included in the analysis. Notably, the top 3 journals contributing to this field were Investigative Ophthalmology & Visual Science, , Ophthalmology, , and the British Journal of Ophthalmology. . This research on optic nerve imaging extended across 97 countries, with the USA leading in research endeavors. Noteworthy burst term analysis revealed that "Segmentation" and "Machine learning" are gaining attention. Additionally, the Latent Dirichlet Allocation model indicated that image processing has been a hotspot in recent years. Conclusions: This study revealed the research trends, hotspots, and emerging topics in optic nerve imaging through bibliometric analysis and network visualization. At present, the research focus is directed towards employing artificial intelligence for image post-processing. The findings of this study offer valuable insights into future research direction and clinical applications.

A breakthrough in the performance of bionic optical structures will only be achieved if we can obtain an in-depth understanding of the synergy mechanisms operating in natural optical structures and find ways to imitate them. In this work, inspired by feline eyes, an optical substrate that takes advantage of a synergistic effect that occurs between resonant and reflective structures was designed. The synergistic effect between the reflective and resonant components leads to a Raman enhancement factor (EF) of 1.16 x 10(7), which is much greater than that achieved using the reflective/resonant cavities on their own. Finite-difference time-domain (FDTD) simulations and experimental results together confirm that the mechanism of this synergistic effect is achieved by realizing multiple reflections and repeated absorptions of light, generating a strong local electric field. Thus, a 2-3 order of magnitude increase in sensitivity could be achieved. More importantly, with the homemade centrifugal device, above optical substrates were further used to develop a rapidly highly sensitive household health monitoring system (detection time <3 min). It can thus be used to give early warning of acute diseases with high risk (e.g., acute myocardial infarction (AMI) and cerebral peduncle). Due to the good reusability and storability (9% and 8% reduction in EF after washing 30 times and 9 months of storage, respectively) of the substrates, the substrates thus reduce detection costs (to similar to$1), making them much cheaper to use than the current gold-standard methods (e.g., similar to$16 for gout detection).

Thyroid eye disease (TED) is the most common orbital disease in adults. Ocular motility restriction is the primary complaint of patients, while its evaluation is quite difficult. The present study aimed to introduce an artificial intelligence (AI) model based on orbital computed tomography (CT) images for ocular motility score. A total of 410 sets of CT images and clinical data were obtained from the hospital. To build a triple classification predictive model for ocular motility score, multiple deep learning models were employed to extract features of images and clinical data. Subgroup analyses based on pertinent clinical features were performed to test the efficacy of models. The ResNet-34 network outperformed Alex-Net and VGG16-Net in prediction of ocular motility score, with the optimal accuracy (ACC) of 0.907, 0.870, and 0.890, respectively. Subgroup analyses indicated no significant difference in ACC between active or inactive phase, functional visual field diplopia or peripheral visual field diplopia (p > 0.05). However, in the gender subgroup, the prediction model performed more accurately in female patients than males (p = 0.02). In conclusion, the AI model based on CT images and clinical data successfully realized automatic scoring of ocular motility in TED patients. This approach potentially enhanced the efficiency and accuracy of ocular motility evaluation, thus facilitating clinical application.

AIMS:To investigate the alterations of the optic nerve and visual cortex in dysthyroid optic neuropathy (DON), a subgroup of thyroid eye disease (TED). METHODS:Multiple orbital imaging biomarkers related to optic nerve compression and the amplitude of low-frequency fluctuations (ALFF) of the brain were obtained from 47 patients with DON, 56 TED patients without DON (nDON), and 37 healthy controls (HC). Correlation analyses and diagnostic tests were implemented. RESULTS:Compared with HC, the nDON group showed alterations in orbital imaging biomarkers related to optic nerve compression in posterior segments, as well as ALFF of the right inferior temporal gyrus and left fusiform gyrus. DON differed from nDON group mainly in the modified muscle index of the posterior segment of optic nerve, and ALFF of orbital part of right superior frontal gyrus, right hippocampus, and right superior temporal gyrus. Orbital and brain imaging biomarkers were significantly correlated with each other. Diagnostic models attained an area under a curve of 0.80 for the detection of DON. CONCLUSION:The combined orbital and brain imaging study revealed alterations of the visual pathway in patients with TED and DON as well as provided diagnostic value. The initiation of alterations in the visual cortex in TED may precede the onset of DON.

Investigating proton transport at the interface in an excited state facilitates the mechanistic investigation and utilization of nanomaterials. However, there is a lack of suitable tools for in-situ and interfacial analysis. Here we addresses this gap by in-situ observing the proton transport of graphene quantum dots (GQDs) in an excited state through reduction of magnetic resonance relaxation time. Experimental results, utilizing 0.1 mT ultra-low-field nuclear magnetic resonance relaxometry compatible with a light source, reveal the light-induced proton dissociation and acidity of GQDs’ microenvironment in the excited state (Hammett acidity function: –13.40). Theoretical calculations demonstrate significant acidity enhancement in –OH functionalized GQDs with light induction ( $${{\mathrm{p}}}{K}_{{\text{a}}}^{*}$$ = –4.62, stronger than that of H2SO4). Simulations highlight the contributions of edge and phenolic –OH groups to proton dissociation. The light-induced superacidic microenvironment of GQDs benefits functionalization and improves the catalytic performances of GQDs. Importantly, this work advances the understanding of interfacial properties of light-induced sp2–sp3 carbon nanostructure and provides a valuable tool for exploring catalyst interfaces in photocatalysis. Understanding interfacial proton transport in an excited state is crucial for catalytic and diagnostic applications of nanomaterials. Here, the authors combine ultra-low-field NMR relaxometry with a light source to study the light-induced proton dissociation of graphene quantum dots.

Osteosarcoma is the most frequent malignant primary bone tumor with a poor prognosis and remains a significant issue in clinics due to the unrepairable bone defect following surgery and the lingering tumor cells. Photodynamic therapy (PDT) with its non-invasive nature and spatiotemporally controllable feature exhibits specific therapeutic efficiency, but it is limited by phototoxicity caused by prolonged laser exposure. Herein, we design and engineer an irradiation-free bifunctional PDT scaffold (BG@SAO-RB) by integrating persistent luminescence material (SrAl2O4:Eu, Dy) and photosensitizer (rose bengal) into a 3D-printed bioactive glass scaffold for stepwise osteosarcoma elimination and bone defect repair. Owing to the design of a rechargeable internal light source, the constructed scaffolds with reactive oxygen species generation ability attain long-term and efficient PDT for osteosarcoma, leading to tumor cell killing and proliferative inhibition. The findings from tumor growth characteristics and pathological sections also confirm that BG@SAO-RB scaffolds achieve successful osteosarcoma ablation through long-term PDT in tumor-bearing nude mice. Notably, the as-designed scaffolds promote osteogenic differentiation of rat bone marrow mesenchymal stem cells and accelerate bone regeneration, which was evidenced by the improved radiological and histological manifestations. This work broadens the biomedical application of persistent luminescence materials and implicates an efficient treatment paradigm for osteosarcoma elimination and subsequent bone tissue regeneration.

Phototoxicity poses a substantial challenge in photodynamic therapy, resulting in intolerable skin damage, visual impairment, and reduced quality of life. Current coping strategies, primarily focus on avoiding inappropriate photoactivation and developing targeted photosensitizers, have not effectively addressed this problem. Hence, this study aims to develop a "sunlight-friendly" photodynamic therapy strategy. Here, 1-methoxyphenazine methosulfate (MPMS) is innovatively identified as a key substance in achieving modified oxygen metabolism. MPMS demonstrates efficient catalytic shuttling under abnormal intracellular H2O2 levels, introducing a novel protective approach for oxygen metabolism and numerous life processes. By controlling MPMS administration, the switch of the photosensitizer states between "ON" (killing tumor cells) and "OFF" (safeguarding normal cells) can be achieved. This approach effectively mitigated phototoxicity and holds the potential for widespread clinical application.

Therapeutic antibodies are extensively used to treat fundus diseases by intravitreal injection, as eyedrop formu-lation has been rather challenging due to the presence of ocular barriers. Here, an innovative penetrating carrier was developed for antibody delivery in eyedrop formulations. We found that fluorocarbon-modified chitosan (FCS) would self-assemble with proteins to form nanocomplexes, which could effectively pass across the com-plicated ocular structure to reach the posterior eye segments in both mice and rabbits. In a choroidal melano-ma-bearing mouse model, eyedrops containing FCS/anti-PDL1 could induce stronger antitumor immune responses than those triggered by intravenous injection of anti-PDL1. Moreover, in choroidal neovasculariza-tion-bearing mouse and rabbit models, FCS/anti-VEGFA eyedrops effectively inhibited vascular proliferation, achieving comparable therapeutic responses to those observed with intravitreal injection of anti-VEGFA. Our work presents an effective delivery carrier to treat fundus diseases using eyedrop of therapeutic proteins, which may enable at-home treatment of many eye diseases with great patient compliance.

Purpose: This study aimed to explore the effect of biomaterials with different stiffness on Adipose Derived Mesenchymal Stem Cells (ADSC)-macrophage crosstalk in bone tissue engineering and its role in bone repair.Methods: Biomaterials with Young's modulus of 64 and 0.2 kPa were selected, and the crosstalk between ADSCs and macrophages was investigated by means of conditioned medium treatment and cell co-culture, respectively. Polymerase chain reaction (PCR) and flow cytometry were used to evaluate the polarization of macrophages. Alkaline phosphatase (ALP) and alizarin red staining (ARS) solutions were used to evaluate the osteogenic differentiation of ADSCs. Transwell assay was used to evaluate the chemotaxis of ADSCs and macrophages. Moreover, mass spectrometry proteomics was used to analyze the secreted protein profile of ADSCs of different substrates and macrophages in different polarization states.Results: On exploring the influence of biomaterials on macrophages from ADSCs on different substrates, we found that CD163 and CD206 expression levels in macrophages were significantly higher in the 64-kPa group than in the 0.2-kPa group in conditioned medium treatment and cell co-culture. Flow cytometry showed that more cells became CD163(+) or CD206(+) cells in the 64-kPa group under conditioned medium treatment or cell co-culture. The Transwell assay showed that more macrophages migrated to the lower chamber in the 64-kPa group. The proteomic analysis found that ADSCs in the 64-kPa group secreted more immunomodulatory proteins, such as LBP and RBP4, to improve the repair microenvironment. On exploring the influence of biomaterials on ADSCs from macrophages in different polarization states, we found that ALP and ARS levels in ADSCs were significantly higher in the M2 group than in the other three groups (NC, M0, and M1 groups) in both conditioned medium treatment and cell co-culture. The Transwell assay showed that more ADSCs migrated to the lower chamber in the M2 group. The proteomic analysis found that M2 macrophages secreted more extracellular remodeling proteins, such as LRP1, to promote bone repair.Conclusion: In bone tissue engineering, the stiffness of repair biomaterials can affect the crosstalk between ADSCs and macrophages, thereby regulating local repair immunity and affecting bone repair.

Purpose The purpose of this study was to explore the role of cathepsin K positive (CTSK+) periosteal stem cells (PSCs) in orbital bone repair and to clarify the source of endogenous stem cells for orbital bone self-repair. Methods Periosteum samples obtained by clinical orbital bone repair surgery were analyzed, after which immunofluorescence and immunohistochemical staining were used to detect the content of bone marrow-derived cells and CTSK+ PSCs in periosteum as well as the mobilization of PSCs. CTSK+ PSCs were characterized by flow cytometry. Transcriptome sequencing was used to compare the transcriptomic characteristics of CTSK+ PSCs and bone marrow mesenchymal stem cells (BMSCs). Results The orbital periosteum contained CTSK+CD200+ cell lineage, including CD200+CD105− PSCs and CD200+CD105+ progenitor cells. CTSK and osteocalcin (OCN) colocalized in the inner layer of the orbital periosteum, suggesting the osteogenic differentiation potential of CTSK+ PSCs. CTSK expression was much higher in periosteum after mobilization. Immunofluorescence showed low amounts of scattered CD31+ and CD45+ cells in the orbital periosteum. The stem cell characteristics of CTSK+ PSCs were verified by multidirectional differentiation. Flow cytometry found CD200+CD105− CTSK+ PSCs and CD200variantCD105+ progenitor cells. Transcriptome sequencing of CTSK+ PSCs and BMSCs found 3613 differential genes with significant differences. Gene Ontology (GO) analysis showed the differences between the two types of stem cells, revealing that PSCs were more suitable for intramembranous osteogenesis. Conclusions CTSK+ PSCs may be endogenous stem cells for orbital bone repair. They are mobilized after orbital fracture and have unique features suitable for intramembranous osteogenesis, completely different from BMSCs.