Circ_0008571 modulates the phenotype of vascular smooth muscle cells by targeting miR-145-5p in intracranial aneurysms.

BACKGROUND: The dysfunction of human vascular smooth cells (hVSMCs) is significantly connected to the development of intracranial aneurysms (IAs). By suppressing the activity of microRNAs (miRNAs), circular RNAs (circRNAs) participate in IA pathogenesis. Nevertheless, the role of hsa_circ_0008571 in IAs remains unclear. METHODS: circRNA sequencing was used to identify circRNAs from human IA tissues. To determine the function of circ_0008571, Transwell, wound healing, and cell proliferation assays were conducted. To identify the target of circ_0008571, the analyses of CircInteractome and TargetScan, as well as the luciferase assay were carried out. Furthermore, circ_0008571 knockdown and over-expression were performed to investigate its functions in IA development and the underlying molecular mechanisms. RESULTS: Both hsa_circ_0008571 and Integrin beta 8 (ITGB8) were downregulated, while miR-145-5p transcription was elevated in the aneurysm wall of IAs patients compared to superficial temporal artery tissues. In vitro, cell migration and growth were dramatically suppressed after hsa_circ_0008571 overexpression. Mechanistically, has_circ_0008571 could suppress miR-145-5p activity by direct sponging. Moreover, we found that ITGB8 expression and the activation of the TGF-ß-mediated signaling pathway were significantly enhanced. CONCLUSION: The hsa_circ_0008571-miR-145-5p-ITGB8 axis plays an essential role in IA progression.

Cytoskeleton-modulating nanomaterials and their therapeutic potentials.

The cytoskeleton, an intricate network of protein fibers within cells, plays a pivotal role in maintaining cell shape, enabling movement, and facilitating intracellular transport. Its involvement in various pathological states, ranging from cancer proliferation and metastasis to the progression of neurodegenerative disorders, underscores its potential as a target for therapeutic intervention. The exploration of nanotechnology in this realm, particularly the use of nanomaterials for cytoskeletal modulation, represents a cutting-edge approach with the promise of novel treatments. Inorganic nanomaterials, including those derived from gold, metal oxides, carbon, and black phosphorus, alongside organic variants such as peptides and proteins, are at the forefront of this research. These materials offer diverse mechanisms of action, either by directly interacting with cytoskeletal components or by influencing cellular signaling pathways that, in turn, modulate the cytoskeleton. Recent advancements have introduced magnetic field-responsive and light-responsive nanomaterials, which allow for targeted and controlled manipulation of the cytoskeleton. Such precision is crucial in minimizing off-target effects and enhancing therapeutic efficacy. This review explores the importance of research into cytoskeleton-targeting nanomaterials for developing therapeutic interventions for a range of diseases. It also addresses the progress made in this field, the challenges encountered, and future directions for using nanomaterials to modulate the cytoskeleton. The continued exploration of nanomaterials for cytoskeleton modulation holds great promise for advancing therapeutic strategies against a broad spectrum of diseases, marking a significant step forward in the intersection of nanotechnology and medicine.

Singular and Nonsingular Transitions in the Infrared Plasmons of Nearly Touching Nanocube Dimers.

Narrow gaps between plasmon-supporting materials can confine infrared electromagnetic energy at the nanoscale, thus enabling applications in areas such as optical sensing. However, in nanoparticle dimers, the nature of the transition between touching (zero gap) and nearly nontouching (nonzero gap ≲15 nm) regimes is still a subject of debate. Here, we observe both singular and nonsingular transitions in infrared plasmons confined to dimers of fluorine-doped indium oxide nanocubes when moving from touching to nontouching configurations depending on the dimensionality of the contact region. Through spatially resolved electron energy-loss spectroscopy, we find a continuous spectral evolution of the lowest-order plasmon mode across the transition for finite touching areas, in excellent agreement with the simulations. This behavior challenges the widely accepted idea that a singular transition always emerges in the near-touching regime of plasmonic particle dimers. The apparent contradiction is resolved by theoretically examining different types of gap morphologies, revealing that the presence of a finite touching area renders the transition nonsingular, while one-dimensional and point-like contacts produce a singular behavior in which the lowest-order dipolar mode in the touching configuration, characterized by a net induced charge in each of the particles, becomes unphysical as soon as they are separated. Our results provide valuable insights into the nature of dimer plasmons in highly doped semiconductors.

Nomograms for assessing the rupture risk of anterior choroid artery aneurysms based on clinical, morphological, and hemodynamic features.

Background and purpose: A notable prevalence of subarachnoid hemorrhage is evident among patients with anterior choroidal artery aneurysms in clinical practice. To evaluate the risk of rupture in unruptured anterior choroidal artery aneurysms, we conducted a comprehensive analysis of risk factors and subsequently developed two nomograms. Methods: A total of 120 cases of anterior choroidal artery aneurysms (66 unruptured and 54 ruptured) from 4 medical institutions were assessed utilizing computational fluid dynamics (CFD) and digital subtraction angiography (DSA). The training set, consisting of 98 aneurysms from 3 hospitals, was established, with an additional 22 cases from the fourth hospital forming the external validation set. Statistical differences between the two data sets were thoroughly compared. The significance of 9 clinical baseline characteristics, 11 aneurysm morphology parameters, and 4 hemodynamic parameters concerning aneurysm rupture was evaluated within the training set. Candidate selection for constructing the nomogram models involved regression analysis and variance inflation factors. Discrimination, calibration, and clinical utility of the models in both training and validation sets were assessed using area under curves (AUC), calibration plots, and decision curve analysis (DCA). The DeLong test, net reclassification index (NRI), and integrated discrimination improvement (IDI) were employed to compare the effectiveness of classification across models. Results: Two nomogram models were ultimately constructed: model 1, incorporating clinical, morphological, and hemodynamic parameters (C + M + H), and model 2, relying primarily on clinical and morphological parameters (C + M). Multivariate analysis identified smoking, size ratio (SR), normalized wall shear stress (NWSS), and average oscillatory shear index (OSIave) as optimal candidates for model development. In the training set, model 1 (C + M + H) achieved an AUC of 0.795 (95% CI: 0.706 ~ 0.884), demonstrating a sensitivity of 95.6% and a specificity of 54.7%. Model 2 (C + M) had an AUC of 0.706 (95% CI: 0.604 ~ 0.808), with corresponding sensitivity and specificity of 82.4 and 50.3%, respectively. Similarly, AUCs for models 1 and 2 in the external validation set were calculated to be 0.709 and 0.674, respectively. Calibration plots illustrated a consistent correlation between model evaluations and real-world observations in both sets. DCA demonstrated that the model incorporating hemodynamic parameters offered higher clinical benefits. In the training set, NRI (0.224, p = 0.007), IDI (0.585, p = 0.002), and DeLong test (change = 0.089, p = 0.008) were all significant. In the external validation set, NRI, IDI, and DeLong test statistics were 0.624 (p = 0.063), 0.572 (p = 0.044), and 0.035 (p = 0.047), respectively. Conclusion: Multidimensional nomograms have the potential to enhance risk assessment and patient-specific treatment of anterior choroidal artery aneurysms. Validated by an external cohort, the model incorporating clinical, morphological, and hemodynamic features may provide improved classification of rupture states.

Clinical Outcomes On Tubridge Flow Diverter in Treatmenting Intracranial Aneurysms: a Retrospective Multicenter Registry Study.

PURPOSE: In China, the application of nitinol Tubridge flow diverter (TFD) has become popular for treating intracranial aneurysms (IAs). In this study, we investigated the safety outcomes of the application of TFD for treating IAs in real-world scenarios. METHODS: We retrospectively analyzed aneurysms treated with TFD in 235 centers throughout China between April 2018 and April 2020. The primary endpoint was the event-free survival rate at 12 months, defined as the occurrence of morbidity (spontaneous rupture, intraparenchymal hemorrhage (IPH), ischemic stroke, and permanent cranial neuropathy) or death. Univariate and multivariate analyses were performed to assess the risk factors. A good outcome was defined as a modified Rankin Score (mRS) of 0-2. RESULTS: We included 1281 unruptured aneurysms treated with TFD. The overall neurological morbidity and death rates after 12 months were 5.4 and 2.8%, respectively. Ischemic strokes were the most common complication (4.2%, P < 0.001). Cranial neuropathy, IPH, and spontaneous rupture occurred in 0.3%, 0.3%, and 0.5% of aneurysms, respectively. Univariate and multivariate analyses indicated that the male gender, older age, larger aneurysm diameter, and aneurysm located on BA were the independent risk factors for neurologic events. Aneurysm located on BA was the independent risk factor for ischemic strokes. Most patients (1222) had access to the mRS, and 93.2% of them achieved good outcomes. CONCLUSION: Treatment of IAs with TFD was associated with low morbidity and mortality, most of which were ischemic events. Large posterior aneurysms might be associated with a higher complication rate. TRIAL REGISTRATION: Retrospectively registered.

Gekko Coil System for Intracranial Aneurysms Treatment in China (GREAT-China): A Prospective Randomized Controlled Open-Label Noninferiority Trial.

OBJECTIVE: This study aimed to evaluate the safety and efficacy of the Gekko coil system in treating intracranial aneurysms (IAs) in clinical practice. METHODS: A prospective multicenter randomized open-label parallel positive control noninferiority trial was conducted by 11 centers in China. Patients with a target IA were randomized 1:1 to coiling with either Gekko or Axium coils. The primary outcome was successful aneurysm occlusion at 6 months postoperative follow-up, whereas the secondary outcomes included the successful occlusion aneurysm rate in the immediate postoperative period, recanalization rate at the 6 months follow-up, and technical success and security. RESULTS: Between May 2018 and September 2020, 256 patients were enrolled and randomized. Per-protocol analysis showed that the successful aneurysm occlusion rate at 6 months was 96.08% for the Gekko coil group compared with 96.12% in the Axium coil group, with a difference of -0.04% (P = 0.877). The successful immediate aneurysm occlusion rates were 86.00% and 77.45% in the Gekko coil group and the Axium coil group, respectively, showing no significant difference between the 2 groups (P = 0.116), whereas the recanalization rates during the 6 months follow-up were 2.02% and 1.96% in the Gekko and Axium coil groups, respectively, which was not statistically significant (P = 1.000). CONCLUSIONS: This trial showed that the Gekko coil system was noninferior to the Axium coil system in terms of efficacy and safety for IA embolization. In clinical practice, the Gekko coil system can be considered safe and effective for treating patients with IA.