Magnetic Nanozyme Based on Loading Nitrogen-Doped Carbon Dots on Mesoporous Fe3O4 Nanoparticles for the Colorimetric Detection of Glucose.

The simple and accurate monitoring of blood glucose level is of great significance for the prevention and control of diabetes. In this work, a magnetic nanozyme was fabricated based on loading nitrogen-doped carbon dots (N-CDs) on mesoporous Fe3O4 nanoparticles for the colorimetric detection of glucose in human serum. Mesoporous Fe3O4 nanoparticles were easily synthesized using a solvothermal method, and N-CDs were then prepared in situ and loaded on the Fe3O4 nanoparticles, leading to a magnetic N-CDs/Fe3O4 nanocomposite. The N-CDs/Fe3O4 nanocomposite exhibited good peroxidase-like activity and could catalyze the oxidation of the colorless enzyme substrate 3,3',5,5'-tetramethylbenzidine (TMB) to blue TMB oxide (ox-TMB) in the presence of hydrogen peroxide (H2O2). When the N-CDs/Fe3O4 nanozyme was combined with glucose oxidase (Gox), Gox catalyzed the oxidization of glucose, producing H2O2 and leading to the oxidation of TMB under the catalysis of the N-CDs/Fe3O4 nanozyme. Based on this mechanism, a colorimetric sensor was constructed for the sensitive detection of glucose. The linear range for glucose detection was from 1 to 180 µM, and the limit of detection (LOD) was 0.56 µM. The recovered nanozyme through magnetic separation showed good reusability. The visual detection of glucose was also realized by preparing an integrated agarose hydrogel containing the N-CDs/Fe3O4 nanozyme, glucose oxidase, and TMB. The colorimetric detection platform has an enormous potential for the convenient detection of metabolites.

Nanotechnology-enabled sonodynamic therapy against malignant tumors.

Sonodynamic therapy (SDT) is an emerging approach for malignant tumor treatment, offering high precision, deep tissue penetration, and minimal side effects. The rapid advancements in nanotechnology, particularly in cancer treatment, have enhanced the efficacy and targeting specificity of SDT. Combining sonodynamic therapy with nanotechnology offers a promising direction for future cancer treatments. In this review, we first systematically discussed the anti-tumor mechanism of SDT and then summarized the common nanotechnology-related sonosensitizers and their recent applications. Subsequently, nanotechnology-related therapies derived using the SDT mechanism were elaborated. Finally, the role of nanomaterials in SDT combined therapy was also introduced.

AI-Based multimodal Multi-tasks analysis reveals tumor molecular heterogeneity, predicts preoperative lymph node metastasis and prognosis in papillary thyroid carcinoma: A retrospective study.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the predominant form of thyroid cancer globally, especially when lymph node metastasis (LNM) occurs. Molecular heterogeneity, driven by genetic alterations and tumor microenvironment components, contributes to the complexity of PTC. Understanding these complexities is essential for precise risk stratification and therapeutic decisions. METHODS: This study involved a comprehensive analysis of 521 patients with PTC from our hospital and 499 patients from The Cancer Genome Atlas (TCGA). The real-world cohort 1 comprised 256 patients with stage I-III PTC. Tissues from 252 patients were analyzed by DNA-based next-generation sequencing, and tissues from four patients were analyzed by single-cell RNA sequencing (scRNA-seq). Additionally, 586 PTC pathological sections were collected from TCGA, and 275 PTC pathological sections were collected from the real-world cohort 2. A deep learning multimodal model was developed using matched histopathology images, genomic, transcriptomic, and immune cell data to predict LNM and disease-free survival (DFS). RESULTS: This study included a total of 1,011 PTC patients, comprising 256 patients from cohort 1, 275 patients from cohort 2, and 499 patients from TCGA. In cohort 1, we categorized PTC into four molecular subtypes based on BRAF, RAS, RET, and other mutations. BRAF mutations were significantly associated with LNM and impacted DFS. ScRNA-seq identified distinct T cell subtypes and reduced B cell diversity in BRAF-mutated PTC with LNM. The study also explored cancer-associated fibroblasts and macrophages, highlighting their associations with LNM. The deep learning model was trained using 405 pathology slides and RNA sequences from 328 PTC patients and validated with 181 slides and RNA sequences from 140 PTC patients in the TCGA cohort. It achieved high accuracy, with an AUC of 0.86 in the training cohort, 0.84 in the validation cohort, and 0.83 in the real-world cohort 2. High-risk patients in the training cohort had significantly lower DFS rates (P<0.001). Model AUCs were 0.91 at 1 year, 0.93 at 3 years, and 0.87 at 5 years. In the validation cohort, high-risk patients also had lower DFS (P<0.001); the AUCs were 0.89, 0.87, and 0.80 at 1, 3, and 5 years. We utilized the GradCAM algorithm to generate heatmaps from pathology-based deep learning models, which visually highlighted high-risk tumor areas in PTC patients. This enhanced clinicians' understanding of the model's predictions and improved diagnostic accuracy, especially in cases with lymph node metastasis. CONCLUSION: The AI-based analysis uncovered vital insights into PTC molecular heterogeneity, emphasizing BRAF mutations' impact. The integrated deep learning model shows promise in predicting metastasis, offering valuable contributions to improved diagnostic and therapeutic strategies.

Exploring the mechanism of empathy on lens language and linguistic landscape on movie-induced tourism: The moderating effect of cultural differences.

Since the development of film-induced tourism, scholars have increasingly shifted their attention to examining film-induced tourism from different perspectives. However, little research has been devoted to the underlying mechanisms by which audiences empathize with movie scenes. Current research believes that the lens language of movies is helpful for the communication between the movie and the audience. It not only helps the audience to shape the imagination of the movie scene, but also contributes to the construction of a virtual language landscape, and promotes the audience's cognition of the movie scene. Bringing their emotions and self-expression into the story ultimately enhances the audience's perception of where it was filmed. In exploring the framework of the transformation of empathy in lens language to landscape language, cultural differences are also proposed as the boundary conditions for the relationship between lens language and empathy. Structural equation modeling with PLS-SEM was employed to test the proposed hypotheses. The findings suggest that lens language positively predicts language landscape and empathy positively mediates the aforementioned relationship. Furthermore, the interaction term of cultural differences amplifies the relationship between lens language and empathy. Finally, we discuss theoretical and practical implications.

A Comprehensive Analysis of Programmed Cell Death-Associated Genes for Tumor Microenvironment Evaluation Promotes Precise Immunotherapy in Patients with Lung Adenocarcinoma.

Immune checkpoint inhibitors (ICIs) represent a new hot spot in tumor therapy. Programmed cell death has an important role in the prognosis. We explore a programmed cell death gene prognostic model associated with survival and immunotherapy prediction via computational algorithms. Patient details were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases. We used LASSO algorithm and multiple-cox regression to establish a programmed cell death-associated gene prognostic model. Further, we explored whether this model could evaluate the sensitivity of patients to anti-PD-1/PD-L1. In total, 1342 patients were included. We constructed a programmed cell death model in TCGA cohorts, and the overall survival (OS) was significantly different between the high- and low-risk score groups (HR 2.70; 95% CI 1.94-3.75; p < 0.0001; 3-year OS AUC 0.71). Specifically, this model was associated with immunotherapy progression-free survival benefit in the validation cohort (HR 2.42; 95% CI 1.59-3.68; p = 0.015; 12-month AUC 0.87). We suggest that the programmed cell death model could provide guidance for immunotherapy in LUAD patients.

RBC membrane camouflaged boron nitride nanospheres for enhanced biocompatible performance.

Boron nitride nanospheres (BNNS) have attracted increasing attention in many fields due to their unique physicochemical properties. Biomedical application of BNNS has also been explored recently. However, limited by the hydrophobicity and poor dispersity of BNNS, their biocompatible performance especially the in vivo biosafety has rarely been reported and is still unclear now. In this work, BNNS were firstly camouflaged with red blood cell membrane by physical extrusion (CM-BNNS). CM-BNNS were then incubated with cells as well as intravenously injected into the mice to uncover their potential in vitro and in vivo toxicity. Results were promising as CM-BNNS exhibited better dispersion and stability compared with pristine BNNS. In vitro data demonstrated the relatively enhanced biosafety of CM-BNNS. The red blood cell membrane coating endowed BNNS with markedly prolonged blood circulation and decreased accumulation in the lung. In addition, CM-BNNS showed no adverse effects on all the evaluated hematic parameters and tissues of treated mice at a dose of 10 mg/kg. Taken together, our work demonstrated the optimal biocompatibility of CM-BNNS and pave the way for their future biomedical applications.

Metformin Attenuates Cyclosporine A-induced Renal Fibrosis in Rats.

BACKGROUND: The aim of the present study was to investigate the therapeutic potential of metformin in preventing cyclosporine A (CsA)-induced nephrotoxicity. METHODS: Three groups of adult male Sprague-Dawley rats were treated with vehicle, CsA, and CsA + metformin for 4 weeks following 1 week on low sodium diet, respectively. At the end of treatment, all animals were euthanized, and the samples of kidney, urine, and blood were collected for functional, morphological, and molecular biological evaluation. RESULTS: Metformin effectively prevented CsA-induced renal dysfunction with increased creatinine clearance rate and reduced blood urea nitrogen and serum creatinine, as well as less proteinuria in comparison to the CsA group. Morphologically, metformin ameliorated CsA-induced renal fibrosis and tissue collapse in the areas of arteries, glomeruli, and proximal tubules. We further demonstrated that the antifibrotic effects of metformin in kidneys treated with CsA were associated with decreased phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2). CONCLUSIONS: In conclusion, our study revealed new therapeutic potential of metformin to attenuate calcineurin inhibitor-induced renal fibrosis, which was closely related to the suppression of MEK/ERK1/2 pathway.