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Graphene quantum dots (GQDs) are nano-sized graphene slices. With their small size, lamellar and aromatic-ring structure, GQDs tend to enter into the cell nucleus and interfere with DNA activity. Thus, GQD alone is expected to be an anticancer reagent. Herein, we developed GQDs that suppress the growth of tumor by selectively damaging the DNA of cancer cells. The amine-functionalized GQDs were modified with nucleus targeting TAT peptides (TAT-NGs) and further grafted with cancer-cell-targeting folic acid (FA) modified PEG via disulfide linkage (FAPEG-TNGs). The resulting FAPEG-TNGs exhibited good biocompatibility, nucleus uptake, and cancer cell targeting. They adsorb on DNA via the π–π and electrostatic interactions, which induce the DNA damage, the upregulation of the cell apoptosis related proteins, and the suppression of cancer cell growth, ultimately. This work presents a rational design of GQDs that induce the DNA damage to realize high therapeutic performance, leading to a distinct chemotherapy strategy for targeted tumor therapy.Qi et al. develop nucleus targeting graphene quantum dots (GQDs) by modifying amine-functionalised GQDs with nucleus targeting TAT peptides. The resulting functionalised GQDs exhibit good biocompatibility, nucleus uptake, and cancer cell targeting. They can suppress growth of cancer cells by selectively inducing DNA damage.

Optic nerve regeneration remains challenging worldwide due to the limited intrinsic regenerative capacity of retinal ganglion cells (RGCs) and the inhibitory microenvironment. Oxidative stress, induced by excessive reactive oxygen species (ROS) following optic nerve injury, is associated with prolonged neuroinflammation, resulting in a secondary injury of RGCs and the impairment of axon regeneration. Herein, we developed a bionic nanocomposite scaffold (GA@PDA) with immunoregulatory ability for enhanced optic nerve regeneration. The ice-templating method was employed to fabricate biopolymer-based scaffolds with a directional porous structure, mimicking the optic nerve, which effectively guided the oriented growth of neuronal cells. The incorporation of bioinspired polydopamine nanoparticles (PDA NPs) further confers excellent ROS scavenging ability, thereby modulating the phenotype transformation of microglia/macrophages from pro-inflammatory M1 to anti-inflammatory M2. In a rat optic nerve crush model, the implantation of GA@PDA scaffold enhanced survival of RGCs and promoted axonal regeneration. Our study offers novel insights and holds promising potential for the advancement of engineered biomaterials in facilitating optic nerve regeneration.

Significance The change in peripheral refraction from hyperopic to myopic defocus following orthokeratology (OK) has been recognized as a main factor in myopia control. However, the impact of OK lenses on peripheral refraction at nearpoints in myopic eyes still requires further investigation. Purpose This study aims to investigate changes in peripheral refraction during accommodation in myopic adults after orthokeratology (OK) wear. Methods Twenty-four selected myopic adults (mean spherical equivalent: -2.70 ± 1.04 D) participated in this study. Peripheral refractions were measured by an auto-refractor with targets located at 25 cm and 50 cm from the eye. Measurements were performed across ± 30º of the horizontal field in 5º steps from the visual axis of subject’s right eye before and after wearing the OK lens. The statistical package SPSS was used to analyze the data to determine the relationship between peripheral refractions and accommodation. Results After wearing the OK lens, the peripheral refraction became more myopic with increasing eccentricity during accommodation (t > 2.80, p  < 0.01, N30º, N25º, N20º, T15º, T20º, T25º and T30º, for 25 cm and 50 cm). While relative hyperopic reflective errors were observed in the central (accommodative lag) and near peripheral (= < 15 º) retinal fields (t < -2.5, p  < 0.02, for 0º, N5º, N10º, N15º and T10º for 25 cm and 50 cm), relative myopic refractive errors were evident in the farther periphery (> 15 º). (for 25 cm, -0.45 ± 1.18, -0.71 ± 1.47, -1.00 ± 1.31 and -1.70 ± 2.16D, for N30º, T20º, T25º, and T30º; for 50 cm, -0.76 ± 1.28, -0.84 ± 1.05; -1.17 ± 1.30 and -2.15 ± 1.81D, for N30º, T20º, T25º, and T30º; t > 2.5, P  < 0.02). Conclusion The myopic shift of peripheral refraction from the OK lens was partly counteracted by an insufficient change in refractive power of the eye during accommodation. Even though the refractive errors become relative hyperopic in the central and near peripheral retinal fields, relative myopic refraction was still maintained in the farther periphery for the accommodated myopic eyes treated with OK lenses.

Oxidative stress is considered as a major factor causing retinal pigment epithelium (RPE) dysfunction and finally leading to retinal diseases such as age-related macular degeneration (AMD). Developing hydrogels for RPE cell delivery, especially those with antioxidant feature, is emerging as a promising approach for AMD treatment. Herein, a readily prepared antioxidant alginate-based hydrogel was developed to serve as a cytoprotective agent for RPE cells against oxidative damage. Alg-BOB was synthesized via conjugation of benzoxaborole (BOB) to the polysaccharide backbone. Hydrogels were formed through self-crosslinking of Alg-BOB based on benzoxaborole-diol complexation. The resulting hydrogel showed porous micro-structure, pH dependent mechanical strength and excellent self-healing, remolding, and injectable properties. Moreover, the hydrogel exhibited excellent cytocompatibility and could efficiently scavenge reactive oxygen species (ROS) to achieve an enhanced viability of ARPE-19 cells under oxidative condition. Altogether, our study reveals that the antioxidant Alg-BOB hydrogel represents an eligible candidate for RPE delivery and AMD treatment.

Patients afflicted with dry eye disease (DED) experience significant discomfort. The underlying cause of DED is the excessive accumulation of ROS on the ocular surface. Here, we investigated the nitrogen doped-graphene quantum dots (NGQDs), known for their ROS-scavenging capabilities, as a treatment for DED. NGQDs were prepared by using citric acid and urea as precursors through hydrothermal method. The antioxidant abilities of NGQDs were evaluated through: scavenging the ROS both extracellular and intracellular, regulating the nuclear factor-erythroid 2-related factor (Nrf2) antioxidant pathway of human corneal epithelial cells (HCECs) and their transcription of inflammation related genes. Furthermore, NGQDs were modified by Arg-Gly-Asp-Ser (RGDS) peptides to obtain RGDS@NGQDs. , both the NGQDs and RGDS@NGQDs were suspended in 0.1% Pluronic F127 (w/v) and delivered as eye drops in the scopolamine hydrobromide-induced DED mouse model. Preclinical efficacy was compared to the healthy and DPBS treated DED mice. These NGQDs demonstrated pronounced antioxidant properties, efficiently neutralizing free radicals and activating the intracellular Nrf2 pathway. In vitro studies revealed that treatment of H O -exposed HCECs with NGQDs induced a preservation in cell viability. Additionally, there was a reduction in the transcription of inflammation-associated genes. To prolong the corneal residence time of NGQDs, they were further modified with RGDS peptides and suspended in 0.1% Pluronic F127 (w/v) to create RGDS@NGQDs F127 eye drops. RGDS@NGQDs exhibited superior intracellular antioxidant activity even at low concentrations (10 μg/mL). Subsequent in vivo studies revealed that RGDS@NGQDs F127 eye drops notably mitigated the symptoms of DED mouse model, primarily by reducing ocular ROS levels. Our findings underscore the enhanced antioxidant benefits achieved by modifying GQDs through nitrogen doping and RGDS peptide tethering. Importantly, in a mouse model, our novel eye drops formulation effectively ameliorated DED symptoms, thereby representing a novel therapeutic pathway for DED management.

Graves' ophthalmopathy (GO) is an autoimmune disorder marked by orbital inflammation and tissue remodeling, leading to irreversible disfigurement and vision loss. The current first‐line glucocorticoid therapy remains palliative, underscoring the critical need for mechanism‐based interventions. Autoantibodies against thyrotropin receptor (TSHR) in GO patients highlight its therapeutic potential, yet TSHR inhibitor development faces challenges, including low potency, off‐target effects, and mechanistic constraints. To overcome this therapeutic void, YC3, a TSHR‐targeting nucleic acid aptamer, has been developed through an innovative approach that combines protein‐targeting cell‐SELEX with functional selection. YC3 exhibits nanomolar affinity alongside robust pharmacodynamic efficacy. In vitro, YC3 significantly reverses thyroid‐stimulating antibodies (TSAbs)‐driven hyperactivation in primary human orbital fibroblasts, thereby suppressing pathogenic hallmarks of fibroblasts. In vivo, therapeutic administration of YC3 significantly alleviates ocular symptoms in a GO mouse model. Mechanistic investigations reveal that YC3 binds to a previously unidentified allosteric site within the leucine‐rich repeat domain of TSHR, consequently inhibiting receptor activation. Collectively, this study not only identifies YC3 as a promising TSHR‐targeting therapeutic candidate but also unveils a novel allosteric site for next‐generation inhibitors. These findings highlight the potential of aptamers in both dissecting receptor mechanisms and uncovering cryptic druggable sites, thereby bridging structural biology with targeted drug development.

Inhibition of phosphodiesterase-4 or 5 (PDE4 or PDE5) increases cyclic adenosine monophosphate (cAMP)- or cyclic guanosine monophosphate (cGMP), respectively, which activates cAMP response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF)/neuropeptide VGF (non-acryonimic) signaling and produces antidepressant-like effects on behavior. However, causal links among these actions have not been established. In the present study, mice were evaluated for the effects of etazolate and sildenafil, the inhibitor of PDE4 or PDE5, respectively, on depressive-like behavior induced by chronic unpredictable mild stress (CUMS) in the forced-swimming test (FST) and tail suspension test (TST), in the presence or absence of the inhibitor of protein kinase A (PKA) or protein kinase G (PKG) via intracerebroventricular (i.c.v.) infusions. The levels of cAMP, cGMP and expression of pCREB, CREB, BDNF and VGF in both the hippocampus and prefrontal cortex were determined. The results showed that etazolate at 5.0 mg/kg or sildenafil at 30 mg/kg significantly reversed CUMS-induced depressive-like behavior; the effects were paralleled with the increased levels of cAMP/pCREB/BDNF/VGF or cGMP/pCREB/BDNF/VGF signaling, respectively. These effects were completely abolished following inhibition of PKA or PKG, respectively. The results suggest that inhibition of PDE4 by etazolate or PDE5 by sildenafil produced antidepressant-like effects in CUMS-treated animals via cAMP or cGMP signaling, which shares the common downstream signal pathway of CREB/BDNF/VGF.

The current study was designed to investigate the effect of abstinence in combination with environmental enrichment (EE) on cardiac and renal toxicity induced by 2 weeks of ketamine self-administration (SA) in rodents. In Experiment 1, one group of rats underwent ketamine SA for 14 days. In Experiment 2, the animals completed 2 weeks of ketamine SA followed by 2 and 4 weeks of abstinence. In Experiment 3, animals underwent 14 days of ketamine SA and 4 weeks of abstinence in which isolated environment (IE) and EE was introduced. The corresponding control groups were included for each experiment. Two weeks of ketamine SA caused significant increases in organ weight, Apoptosis Stimulating Fragment/Kidney Injury Molecule-1 and apoptotic level of heart and kidney. The extended length of withdrawal from ketamine SA partially reduced toxicity on the heart and kidney. Finally, introduction of EE during the period of abstinence greatly promoted the effect of abstinence on ketamine-induced cardiac and renal toxicity. The interactive effect of EE and abstinence was promising to promote the recovery of cardiac and renal toxicity of ketamine.

A new alkaloid (orychophragvioline A) and nine known compounds were yielded from the seeds of Orychophragmus violaceus. Their structures were determined by various spectroscopic techniques and single-crystal X-ray diffraction. Orychophragvioline A is a rare alkaloid with an unusual 1-methyl-4-phenyl-2,3-diketopiperazine skeleton connected with a guanidine group via an amide bond. The results of antitumor tests in vitro showed that it exhibited prominent cytotoxicity against Hela cells with an IC50 value of 11.95 ± 1.52 μM. Further investigations suggested that it significantly inhibited cellular proliferation, migration, and invasion in a dose-dependent manner, thus inducing the apoptosis of Hela cells. These findings indicate that orychophragvioline A can be regarded as a potential natural leading compound against cervical cancer.

In this work, we demonstrate a method for rapid synthesis of high‐quality CT images from unpaired, low‐quality CBCT images, permitting CBCT‐based adaptive radiotherapy. We adapt contrastive unpaired translation (CUT) to be used with medical images and evaluate the results on an institutional pelvic CT dataset. We compare the method against cycleGAN using mean absolute error, structural similarity index, root mean squared error, and Frèchet Inception Distance and show that CUT significantly outperforms cycleGAN while requiring less time and fewer resources. The investigated method improves the feasibility of online adaptive radiotherapy over the present state‐of‐the‐art.