Near-Infrared Light-Activatable DNA Tentacles for Efficient Inhibition of Tumor Metastasis by Bio-Orthogonal Cell Assembly.

Tumor metastasis remains a major challenge in cancer management. Among various treatment strategies, immune cell-based cancer therapy holds a great potential for inhibiting metastasis. However, its wide application in cancer therapy is restricted by complex preparations, as well as inadequate homing and controllability. Herein, we present a groundbreaking approach for bioorthogonally manipulating tumor-NK (natural killer) cell assembly to inhibit tumor metastasis. Multiple dibenzocyclootyne (DBCO) groups decorated long single-stranded DNA were tail-modified on core-shell upconversion nanoparticles (CSUCNPs) and condensed by photosensitive chemical linker (PC-Linker) DNA to shield most of the DBCO groups. On the one hand, the light-triggered DNA scaffolds formed a cross-linked network by click chemistry, effectively impeding tumor cell migration. On the other hand, the efficient cellular assembly facilitated the effective communication between tumor cells and NK-92 cells, leading to enhanced immune response against tumors and further suppression of tumor metastasis. These features make our strategy highly applicable to a wide range of metastatic cancers.

A model with multiple intracranial aneurysms: possible hemodynamic mechanisms of aneurysmal initiation, rupture and recurrence.

BACKGROUND: Hemodynamic factors play an important role in aneurysm initiation, growth, rupture, and recurrence, while the mechanism of the hemodynamic characteristics is still controversial. A unique model of multiple aneurysms (initiation, growth, rupture, and recurrence) is helpful to avoids the confounders and further explore the possible hemodynamic mechanisms of aneurysm in different states. METHODS: We present a model with multiple aneurysms, and including the states of initiation, growth, rupture, and recurrence, discuss the proposed mechanisms, and describe computational fluid dynamic model that was used to evaluate the likely hemodynamic effect of different states of the aneurysms. RESULTS: The hemodynamic analysis suggests that high flow impingement and high WSS distribution at normal parent artery was found before aneurysmal initiation. The WSS distribution and flow velocity were decreased in the new sac after aneurysmal growth. Low WSS was the risk hemodynamic factor for aneurysmal rupture. High flow concentration region on the neck plane after coil embolization still marked in recanalized aneurysm. CONCLUSIONS: Associations have been identified between high flow impingement and aneurysm recanalization, while low WSS is linked to the rupture of aneurysms. High flow concentration and high WSS distribution at normal artery associated with aneurysm initiation and growth, while after growth, the high-risk hemodynamics of aneurysm rupture was occurred, which is low WSS at aneurysm dome.

Evaluation of the EMBOPIPE flow diverter device: in vivo and in vitro experiments.

BACKGROUND: Although flow diverter device (FDD) has brought revolutionized advances in endovascular treatment of intracranial aneurysms, it also presents considerable drawbacks as well, as the innovation for novel device has never stopped. This preclinical research aims to evaluate the safety and efficacy of a newly developed FDD, the EMBOPIPE, through in vivo and in vitro experiments. METHODS: Aneurysms were induced in 20 New Zealand white rabbits which were randomized to three follow-up groups according to the time elapsed after EMBOPIPE implantation (28, 90, and 180 days). Additional EMBOPIPEs were implanted in the abdominal aorta to cover the renal artery in nine rabbits. Angiography was performed immediately after device placement in all groups. Aneurysm occlusion, patency of renal arteries, and pathological outcomes were assessed. For the in vitro experiments, we measured the thrombogenic potential of EMBOPIPEs (n = 5) compared with bare stents (n = 5) using the Chandler loop model. Evaluation indicators were the platelet counts, macroscopic observations and scanning electron microscopy. RESULTS: EMBOPIPEs were successfully deployed in 19 of 20 rabbit aneurysms (95.0%). The rates of complete or near-complete aneurysm occlusion were 73.3%, 83.3%, and 100% in the 28-, 90-, and 180-day groups, respectively. All renal arteries covered by EMBOPIPEs remained patent, and the mean difference in renal artery diameter before and after the device placement in the three groups was 0.07 mm, 0.10 mm, and 0.10 mm, respectively (p = 0.77). Renal pathology was normal in all cases. The pathological findings of the aneurysms were as follows: thickened and adequate neointimal coverage at the aneurysm neck, minimal inflammatory response, near-complete smooth muscle cell layer, and endothelialization along the device. In vitro experiments showed that the platelet counts were significantly higher in EMBOPIPE blood samples than in bare stent samples and that platelet adhesion to the device was lower in the EMBOPIPE stent struts compared with bare stent struts through macroscopic observations and scanning electron microscopy. CONCLUSIONS: The EMBOPIPE can achieve high rates of aneurysm occlusion while maintaining excellent branch artery patency. It exhibited wonderful pathological results. This novel device with phosphorylcholine surface modification could reduce platelet thrombus attached to the stent struts.

Left ventricular global longitudinal strain using a novel fully automated method: A head-to-head comparison with a manual layer-specific strain and establishment of normal reference ranges.

BACKGROUND: A novel automated method for measuring left ventricular (LV) global longitudinal strain (GLS) along the endocardium has advantages in terms of its rapid application and excellent reproducibility. However, it remains unclear whether the available normal range for conventional GLS using the manual method is applicable to the automated GLS method. This study aimed to compare automated GLS head-to-head with manual layer-specific GLS, and to identify whether a specialized normal reference range for automated GLS is needed and explore the main determinants. METHODS: In total, 1683 healthy volunteers (men, 43%; age, 18-80 years) were prospectively enrolled from 55 collaborating laboratories. LV GLS was measured using both manual layer-specific and automated methods. RESULTS: Automated GLS was higher than endocardial, mid-myocardial, and epicardial GLS. Women had a higher automated GLS than men. GLS had no significant age dependency in men, but first increased and then decreased with age in women. Accordingly, sex- and age-specific normal ranges for automated GLS were proposed. Moreover, GLS appeared to have different burdens in relation to dominant determinants between the sexes. GLS in men showed no dominant determinants; however, GLS in women correlated with age, body mass index, and heart rate. CONCLUSIONS: Using the novel automated method, was LV GLS higher than when using the manual GLS method. The normal ranges of automated GLS stratified according to sex and age were provided, with dominant determinants showing sex disparities that require full consideration in clinical practice.

Wound microenvironment self-adaptive all-in-one hydrogel for rapid healing of the diabetic wound.

The natural healing of diabetic wounds is collectively impeded by multiple factors, including hyperglycemia, angiogenesis disorders, acute oxidative stress, and prolonged inflammation. Although considerable effort has been devoted to solving these problems, the treatment of diabetic wounds remains a major clinical obstacle. In light of this, we developed an innovative wound microenvironment self-adaptive hydrogel to promote the healing of diabetic wounds. The hydrogel was constructed by the crosslinking of 3-aminobenzeneboronic acid (PBA)-modified gelatin (Gel) and polyvinyl alcohol (PVA) by borate ester bonds, which showed high responsiveness to glucose. Meanwhile, the liposomes that encapsulated metformin, L-arginine, and L(+)-ascorbic acid were incorporated into the hydrogel framework. The hydrogel@lipo composite demonstrated shape adaptability, glucose responsiveness, and all-in-one capability, thereby effectively improving the intricate microenvironment of diabetic wounds. In vitro and in vivo experiments demonstrated the ability of hydrogel@lipo to mitigate oxidative stress, enhance angiogenesis, and attenuate inflammatory responses. Consequently, the hydrogel@lipo could accelerate diabetic wound healing (within two weeks). The cumulative findings strongly suggest the potential of hydrogel@lipo as a highly promising therapeutic dressing for advancing diabetic wound recovery.

Appraising the causal association among depression, anxiety and intracranial aneurysms: Evidence from genetic studies.

BACKGROUND: The risk of intracranial aneurysms (IAs) is increased in individuals with depression and anxiety. This indicates that depression and anxiety may contribute to the development of physical disorders. Herein, to investigate the association between genetic variants related to depression and anxiety and the risk of IA, two-sample Mendelian randomization was performed. METHODS: The genome-wide association study (GWAS) comprised genome-wide genotype data of 2248 clinically well-characterized patients with anxiety and 7992 ethnically matched controls from four European countries. Sex-specific summary-level outcome data were obtained from the GWAS of IA, including 23 cohorts with a total of 10,754 cases and 306,882 controls of European and East Asian ancestry. To improve validity, five varying Mendelian randomization techniques were used in the analysis, namely Mendelian randomization-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode. RESULTS: The inverse variance weighted results indicated the causal effect of depression on IA (P = 0.03, OR = 1.32 [95 % CI, 1.03-1.70]) and unruptured IA (UIA) (P = 0.02, OR = 1.68 [95 % CI, 1.08-2.61]). However, the causal relationship between depression and subarachnoid hemorrhage (SAH) was not found (P = 0.16). We identified 43 anxiety-associated single-nucleotide polymorphisms as genetic instruments and found no causal relationship between anxiety and IA, UIA, and SAH. LIMITATIONS: Potential pleiotropy, possible weak instruments, and low statistical power limited our findings. CONCLUSION: Our MR study suggested a possible causal effect of depression on the increased risk of UIAs. Future research is required to investigate whether rational intervention in depression treatment can help to decrease the societal burden of IAs.

Risk of unruptured aneurysms in subarachnoid hemorrhage patients with multiple intracranial aneurysms: a multicenter, longitudinal, comparative study from China.

BACKGROUND: In aneurysmal subarachnoid hemorrhage patients with multiple intracranial aneurysms (aSAH-MIA patients), the risk of secondary unruptured intracranial aneurysms is inconsistent. This study aimed to explore the risk of unruptured aneurysms in Chinese aSAH-MIA patients. METHODS: The medical records and angiographic images of aSAH-MIA patients from eight cerebrovascular centers in China were retrospectively reviewed and analyzed. Patients with a single unruptured intracranial aneurysm (UIA) and no prior aSAH were used as controls. Propensity score matching (PSM) was employed to balance the differences in age, gender, aneurysm size, aneurysm site, and follow-up duration between the two groups. RESULTS: The study included 267 unruptured aneurysms from 204 aSAH-MIA patients and 769 single UIA. After PSM, 201 aneurysms were enrolled in the aSAH-MIA group and 201 aneurysms in the control group. The mean follow-up was 2.2 years. Thirty-four aneurysm instability events (28 growth and 6 rupture, 16.9%) occurred during follow-up in the aSAH-MIA group and 16 instability events (13 growth and 3 rupture, 8%) occurred in the control group. Risk factors for aneurysmal instability were aneurysm irregularity (OR 2.53; 95% CI 1.18 to 4.31), higher size ratio (OR 1.23; 95% CI 1.37 to 4.39), and middle cerebral artery location (OR 1.86; 95% CI 1.03 to 3.17). The risk of aneurysmal instability was substantially elevated in the aSAH-MIA group (HR 2.07; 95% CI 1.12 to 3.02). CONCLUSIONS: Unruptured aneurysms in Chinese aSAH-MIA patients exhibited higher risks of growth and rupture than in patients with a single UIA. Middle cerebral artery location, higher size ratio and irregular shape were associated with higher risk of growth or rupture.