Background: Development of resistance to doxorubicin-based chemotherapy limits its curative effect in osteosarcoma. In the current study, we focused on investigating the mechanisms underlying the development of doxorubicin resistance in osteosarcoma.Methods: The human osteosarcoma cell line MG-63 and doxorubicin-resistant MG-63/Dox cells were used in this study. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of the long non-coding RNA LINC01116 in the two cell lines. Then, the specific shRNA for LINC01116 was employed to suppress LINC01116 expression in MG-63/Dox cells. Cell viability was assessed by the CCK-8 and colony formation assays. Cell migration and invasion were evaluated by the transwell assay. Moreover, the epithelial-mesenchymal transition (EMT)-related proteins, E-cadherin, vimentin, and N-cadherin were evaluated by Western blotting. The regulation of LINC01116 on miR-424-5p expression was examined using methylation-specific PCR, RNA immunoprecipitation, and Western blotting assay. The potential targeting of HMGA2 by miR-424-5p was predicted using the bioinformatics databases TargetScan and miRanda and verified by a dual-luciferase reporter assay.Results: LINC01116 was more highly expressed in MG-63/Dox cells than in MG-63 cells. Inhibition of LINC01116 suppressed cell viability, migration, and invasion, along with upregulating the expression of E-cadherin, downregulating vimentin, and attenuating doxorubicin resistance in MG-63/Dox cells. Further mechanism-related investigations indicated that LINC01116 regulated HMGA2 expression via the EZH2-associated silencing of miR-424-5p.Conclusion: LINC01116 exerts regulatory effects on doxorubicin resistance through the miR-424-5p axis, providing a potential approach to overcoming chemoresistance in osteosarcoma.

The tumor microenvironment (TME) is the internal environment that tumors depend on for survival and development. Tumor-associated macrophages (TAMs), as an important part of the tumor microenvironment, which plays a crucial role in the occurrence, development, invasion and metastasis of various malignant tumors and has immunosuppressant ability. With the development of immunotherapy, eradicating cancer cells by activating the innate immune system has yielded encouraging results, however only a minority of patients show a lasting response. Therefore, in vivo imaging of dynamic TAMs is crucial in patient-tailored immunotherapy to identify patients who will benefit from immunotherapy, monitor efficacy after treatment, and identify alternative strategies for non-responders. Meanwhile, developing nanomedicines based on TAMs-related antitumor mechanisms to effectively inhibit tumor growth is expected to become a promising research field. Carbon dots (CDs), as an emerging member of the carbon material family, exhibit unexpected superiority in fluorescence imaging/sensing, such as near infrared imaging, photostability, biocompatibility and low toxicity. Their characteristics naturally integrate therapy and diagnosis, and when CDs are combined with targeted chemical/genetic/photodynamic/photothermal therapeutic moieties, they are good candidates for targeting TAMs. We concentrate our discussion on the current learn of TAMs and describe recent examples of macrophage modulation based on carbon dot-associated nanoparticles, emphasizing the advantages of their multifunctional platform and their potential for TAMs theranostics.

With a focus on disease prevention and health promotion, a reactive and disease-centric healthcare system is revolutionized to a point-of-care model by the application of wearable devices. The convenience and low cost made it possible for long-term monitoring of health problems in long-distance traveling such as flights. While most of the existing health monitoring systems on aircrafts are limited for pilots, point-of-care systems provide choices for passengers to enjoy healthcare at the same level. Here in this paper, an airline point-of-care system containing hybrid electrocardiogram (ECG), breathing, and motion signals detection is proposed. At the same time, we propose the diagnosis of sleep apnea-hypopnea syndrome (SAHS) on flights as an application of this system to satisfy the inevitable demands for sleeping on long-haul flights. The hardware design includes ECG electrodes, flexible piezoelectric belts, and a control box, which enables the system to detect the original data of ECG, breathing, and motion signals. By processing these data with interval extraction-based feature selection method, the signals would be characterized and then provided for the long short-term memory recurrent neural network (LSTM-RNN) to classify the SAHS. Compared with other machine learning methods, our model shows high accuracy up to 84–85% with the lowest overfit problem, which proves its potential application in other related fields.

Osteosarcoma (OS) is a primary malignant bone tumor that occurs mainly in adolescents. Researchers are devoting to develop combination therapy methods in a multifunctional nanoplatform for the treatment of osteosarcoma. The results of previous research have shown that up-regulation of miR-520a-3p could induce anticancer effects in osteosarcoma. In order to improve the effect of gene therapy (GT), we attempted to carry miR-520a-3p in a multifunctional vector for comprehensive therapy. Fe₂O₃ is a type of magnetic resonance imaging (MRI) contrast that is widely used as a drug delivery agent. When coated with polydopamine (PDA), it can also be used as a photothermal therapy (PTT) agent (Fe₂O₃@ PDA). To deliver nanoagents targeted to a tumor site, folic acid (FA) conjugated with Fe₂O₃ @PDA was manufactured as FA-Fe₂O₃@PDA. FA was chosen as the target molecule to enhance utilization and reduce toxicity of nanoparticles. However, the therapeutic efficacy of FA-Fe₂O₃-PDA combined with miR-520a-3p has not yet been studied. In this study, we synthesized FA-Fe₂O₃@PDA-miRNA and investigated the potential of combining PDA regulated PTT and miR-520a-3p regulated GT to kill osteosarcoma cells. The results indicated that down-regulation of interleukin 6 receptor (IL6R) by miR-520a-3p and the photothermal ability of PDA could induce satisfactory anticancer effects in osteosarcoma, and the curative ratio was better than that used alone PTT or GT. Moreover, as a kind of T ₂ magnetic contrast, miRNA-Fe₂O₃@PDA-FA can be used for MRI. These findings indicated that miRNA-Fe₂O₃@PDA-FA is an effective anti-tumor nanovector for PTT combined with GT.

Objective: To assess the feasibility of utilizing parameters derived from a multimodal apparent diffusion (MAD) model to distinguish between low- and high-grade clear cell renal cell carcinoma (ccRCC).Method: Diffusion-weighted imaging (DWI) scans with 12 b-values (0 - 3000 s/mm²) were conducted on 54 patients diagnosed with ccRCC (30 low-grade and 24 high-grade). The MAD model parameters, including diffusion coefficients (D_r, D_h, D_ui, D_f) representing restricted diffusion, hindered diffusion, unimpeded diffusion, and flow, respectively, were computed. Proportions corresponding to these diffusion types (f_r, f_h, f_ui, f_f) and the heterogeneous nature of hindered diffusion (α_h) were also obtained. Parameters were compared between low- and high-grade groups. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of these parameters, compared with the apparent diffusion coefficient (ADC) from a mono-exponential model.Result: Significant differences between low- and high-grade ccRCC were observed in D_h (low-grade: 1.360 ± 0.11 μm²/ms; high-grade group, 1.254 ± 0.13 μm²/ms; P = 0.0327), f_r (low-grade: 0.06 ± 0.005; high-grade: 0.08 ± 0.009; P = 0.0233), and α_h (low-grade: 0.872 ± 0.22; high-grade: 0.896 ± 0.39; P = 0.0294). Additionally, the ADC values (low-grade: 0.924 ± 0.08 μm²/ms; high-grade group, 0.854 ± 0.04 μm²/ms; P = 0.0323) showed statistical significance. The combination of D_h, f_r, and α_h provided the highest diagnostic accuracy of 0.667, with a sensitivity of 0.750, specificity of 0.734, and area under the curve of 0.796, outperforming individual parameters and ADC.Conclusion: The MAD diffusion model shows promise as a non-invasive imaging tool for distinguishing between low- and high-grade ccRCC, which may aid in preoperative planning and personalized treatment strategies.