Circ_0003611 regulates apoptosis and oxidative stress injury of Alzheimer's disease via miR-383-5p/KIF1B axis.

Alzheimer's disease (AD) is a high incidence neurodegenerative disease. Emerging evidence suggests that circular RNAs (circRNAs) play an important modulator in the pathogenesis of AD. The aim of this paper was to reconnoiter the effects of circular RNA_0003611 (circ_0003611) on Aß-triggered neuronal injury in AD. In this work, the abundance of circ_0003611 was augmented in AD patients and SH-SY5Y and SK-N-SH cells treated with Aß. Aß-mediated cell proliferation, apoptosis, inflammatory response, oxidative stress, and glycolysis were abolished through circ_0003611 silencing. Circ_0003611 worked as a miR-383-5p sponge, and the protective role of circ_0003611 absence on Aß-triggered neuronal injury was overturned by releasing miR-383-5p. Meanwhile, miR-383-5p directly targeted KIF1B, and miR-383-5p upregulation might relieve Aß-triggered neuronal injury by reducing KIF1B expression. Mechanical analysis discovered that circ_0003611 served as a sponge of miR-383-5p to impact KIF1B expression. These findings indicated that circ_0003611 improved Aß-triggered neuronal injury in AD through targeting the miR-383-5p/KIF1B axis, which might deliver innovative therapy targeting for AD.

Evolutionary Reinforcement of Polymer Networks: A Stepwise-Enhanced Strategy for Ultrarobust Eutectogels.

Gel materials are appealing due to their diverse applications in biomedicine, soft electronics, sensors, and actuators. Nevertheless, the existing synthetic gels are often plagued by feeble network structures and inherent defects associated with solvents, which compromise their mechanical load-bearing capacity and cast persistent doubts about their reliability. Herein, combined with attractive deep eutectic solvent (DES), a stepwise-enhanced strategy is presented to fabricate ultrarobust eutectogels. It focuses on the continuous modulation and optimization of polymer networks through complementary annealing and solvent exchange processes, which drives a progressive increase in both quantity and mass of the interconnected polymer chains at microscopic scale, hence contributing to the evolutionary enhancement of network structure. The resultant eutectogel exhibits superb mechanical properties, including record-breaking strength (31.8 MPa), toughness (76.0 MJ m-3 ), and Young's modulus (25.6 MPa), together with exceptional resistance ability to tear and crack propagation. Moreover, this eutectogel is able to be further programmed through photolithography to in situ create patterned eutectogel for imparting specific functionalities. Enhanced by its broad applicability to various DES combinations, this stepwise-enhanced strategy is poised to serve as a crucial template and methodology for the future development of robust gels.

Hematoporphyrin derivative-mediated photodynamic techniques for the diagnosis and treatment of chordoma.

BACKGROUND: Chordoma is a rare congenital low-grade malignant tumor characterized by infiltrative growth. It often tends to compress important intracranial nerves and blood vessels, making its surgical treatment extremely difficult. Besides, the efficacy of radiotherapy and chemotherapy is limited. The photosensitizer hematoporphyrin derivative (HPD) can emit red fluorescence under 405 nm excitation and produce reactive oxygen species for tumor therapy under 630 nm excitation. Herein, we investigated the effects of the photosensitizer hematoporphyrin derivative (HPD) on different cell lines of chordoma and xenograft tumors under 405 nm and 630 nm excitation. METHODS: The photosensitizer hematoporphyrin derivative (HPD) and Two different chordoma cell lines (U-CH1, JHC7) were used for the test. The in vitro experiments were as follows: (1) the fluorescence intensity emitted by chordoma cells excited by different 405 nm light intensities was observed under a confocal microscope; (2) the Cell Counting Kit-8 (CCK-8) assay was performed to detect the effects of different photosensitizer concentrations and 630 nm light energy densities on the activity of chordoma cells. In the in vivo experiments, (3) Fluorescence visualization of chordoma xenograft tumors injected with photosensitizer via tail vein under 405 nm excitation; (4) Impact of 630 nm excitation of photosensitizer on the growth of chordoma xenograft tumors. RESULTS: (1) The photosensitizers in chordoma cells and chordoma xenografts of nude mice were excited by 405 nm to emit red fluorescence; (2) 630 nm excitation photosensitizer reduces chordoma cell activity and inhibits chordoma xenograft tumor growth in chordoma nude mice. CONCLUSION: Photodynamic techniques mediated by the photosensitizer hematoporphyrin derivatives can be used for the diagnosis and treatment of chordoma.

Bioinspired Integrated Auxetic Elastomers Constructed by a Dual Dynamic Interfacial Healing Strategy.

Auxetic materials are appealing due to their unique characteristics of transverse expansion while being axially stretched. Nevertheless, current auxetic materials are often produced by the introduction of diverse geometric structures through cutting or other pore-making processes, which heavily weaken their mechanical performance. Inspired by the skeleton-matrix structures in natural organisms, this study reports an integrated auxetic elastomer (IAE) composed of high-modulus cross-linked poly(urethane-urea) as a skeleton and low-modulus non-cross-linked poly(urethane-urea) as a complementary-shape matrix. Benefiting from disulfide bonds and hydrogen-bond-promoted dual dynamic interfacial healing, the resulting IAE is flat, void-free, and has no sharp soft-to-hard interface. Its fracture strength and elongation at the break are increased to 400% and 150%, respectively, of the values of corrugated re-entrant skeleton alone, while the negative Poisson's ratio (NPR) reserves within a strain range of 0%-104%. In addition, the advantageous mechanical and auxetic properties of this elastomer are further confirmed by finite element analysis. The concept of combining two dissimilar polymers into an integrated hybrid material solves the problem of the deterioration in mechanical performance of auxetic materials after subtractive manufacturing, while preserves the NPR effect in a large deformation, which provides a promising approach to robust auxetic materials for engineering applications.

Transcranial alternating current stimulation combined with sound stimulation improves the cognitive function of patients with Alzheimer's disease: A case report and literature review.

Transcranial alternating current stimulation (tACS) is a relatively new non-invasive brain electrical stimulation method for the treatment of patients with Alzheimer's disease (AD), but it has poor offline effects. Therefore, we applied a new combined stimulation method to observe the offline effect on the cognitive function of patients with AD. Here, we describe the clinical results of a case in which tACS combined with sound stimulation was applied to treat moderate AD. The patient was a 73-year-old woman with a 2-year history of persistent cognitive deterioration despite the administration of Aricept and Sodium Oligomannate. Therefore, the patient received tACS combined with sound stimulation. Her cognitive scale scores improved after 15 sessions and continued to improve at 4 months of follow-up. Although the current report may provide a new alternative therapy for patients with AD, more clinical data are needed to support its efficacy. Trial registration: Clinicaltrials.gov, NCT05251649.

GSK-3ß Regulates the Expression of P21 to Promote the Progression of Chordoma.

PURPOSE: Chordoma is a rare malignant bone tumor transformed from the remnants of notochord. It is characterized as highly aggressive and locally invasive, difficult to be completely removed by surgery, and has a poor clinical prognosis. Glycogen synthase kinase 3 beta (GSK-3ß) is involved in many cellular processes. GSK-3ß overexpression has been shown to promote the development of many cancers, according to previous studies. However, the role of GSK-3ß in chordoma remains unclear. METHODS: Immunohistochemistry (IHC) and Western blotting (WB) were performed on clinical specimens to measure GSK-3ß expression in chordoma, and immunofluorescence and quantitative real-time polymerase chain reaction (QRT-PCR) were performed to examine the expression of GSK-3ß and P21 in cell lines. Cell proliferation was detected by the CCK-8 assay and colony formation analysis, cell migration and invasion checked by Transwell experiments, and cell apoptosis was determined by Annexin V/propidium iodide staining. P21 was predicted as a downstream target gene of GSK-3ß using STRING and UNIHI databases. Moreover, we used immunoprecipitation to confirm that GSK-3ß and P21 interacted with each other. The double luciferase reporter gene assay showed that GSK-3ß could regulate the promoter activity of P21. Finally, the role of the GSK-3ß -P21 pathway in chordoma tumorigenesis was analyzed in vivo in nude mice. RESULTS: Our study showed that GSK-3ß was significantly higher in chordoma tissues than in paracancer tissues, and siRNA knockdown of GSK-3ß inhibited chordoma cell proliferation and promoted cell apoptosis. Additionally, our research found that GSK-3ß bound and downregulated the expression of the P21 gene, and the expression of silencing P21 partially reversed the inhibitory effect of knockdown GSK-3ß on chordoma. Furthermore, xenografts showed that knockdown GSK-3ß inhibited the formation of chordomas in vivo. CONCLUSION: Our results indicated that the GSK-3ß-P21 axis may be an important signaling pathway for the occurrence and development of chordoma, providing a new therapeutic target for the clinical treatment of this disorder.