No abstract

Breast-conserving surgery (BCS) is the standard of care for early breast cancer patients, while the high ratio of reoperation is still a challenge due to inaccurate margin assessments. In patients with locally advanced or advanced breast cancer, radiotherapy is an important treatment for local control or improvement of quality of life. However, enhancing sensitization to radiotherapy is an unmet medical need. To solve the above clinical predicaments, a glutathione (GSH) exhausting virus-like silicon dioxide nanoprobe with Gd coating and folic acid (FA) modification is designed. After loading ICG in the mesopores, the VGd@ICG-FA probe efficiently targets tumor cells with high resolution, due to its virus-like morphology and folate acid anchoring. Especially, the fabricated nanoprobe enables the identification of tiny cancers and navigates precise surgery under NIR-II fluorescence imaging. Moreover, after the nanoprobes enter into the cytoplasm of cancer cells, tetrasulfide linkages in the silica framework are broken under the triggering of high GSH concentrations. In turn, the broken framework exhausts GSH to disrupt intracellular reactive oxygen species (ROS) homeostasis, and Gd produces more ROS under radiotherapy, further activating ferroptosis, and resulting in the enhancement of radiotherapy in breast cancer. Therefore, our nanoprobe exhibits tremendous potential as a NIR-II fluorescence imaging agent with no systematic side effects for precise cancer surgery and nanotherapeutics for boosting radiation sensitivity in future clinical translation of breast cancer.

No abstract

This study contributes to understanding the dynamic evolution process of green tourism industry, for which the evaluation system is constructed combining stakeholder theory with the characteristic of green tourism industry. Data from Mainland China from 2011 to 2017 are used to build the evaluation system of green tourism industry. The data are also analyzed comprehensively by applying entropy weighted TOPSIS and geospatial visualization. Following a horizontal comparison between provinces in Mainland China and a longitudinal comparison of the development history of these provinces, results show that the development of green tourism presents regional differences. Developed areas in the eastern region are superior to that in central and western regions in Mainland China. Interestingly, the relationship between green tourism development and the economy is non-linear. Green tourism resources, traffic accessibility, macroeconomic development level, and tourists’ characteristics will affect the development potential of green tourism. Ultimately, this study brings managerial implications to the development of green tourism.

Background Microglia, the major cell type that mediates active immune defence in the central nervous system (CNS), constantly survey the brain parenchyma through highly motile processes. Mounting evidence has implicated both beneficial and toxic roles of microglia when over-activated upon neuronal injury. Understanding the function of microglia in the brain may uncover the regulatory mechanisms for neuroinflammation and facilitate the development of a novel therapeutic strategy for Alzheimer's disease (AD). The ε4 allele of apolipoprotein E (APOE) is a major genetic risk factor for the late onset AD. ApoE, as the major cholesterol carrier in the brain, has been implicated in AD pathogenesis. However, how APOE and APOE isoforms directly regulate microglial functions remains largely unknown. Methods Using primary culture of microglia from Apoe knockout (KO) mice, APOE3 and APOE4 targeted replacement (TR) mouse, we investigated the characteristics of microglial secreted apoE particles and the biological effects of apoE isoforms on microglial inflammatory response, migratory ability, cell viability and proliferation. Meanwhile, microglia-neuron co-culture system was utilized to study the effects of apoE isoforms on neurite outgrowth.Results Herein, we found that microglia secret abundant lipidated apoE. Interestingly, apoE4 particles from primary microglia exhibited a higher lipidation status compared to apoE3 particles. Furthermore, apoE4 microglia exhibited a reduced migratory ability as well as enhanced inflammatory responses and neurotoxicity, indicating microglial apoE4 is involved in unfavourable functions. Conclusions Our findings revealed the critical roles for apoE and apoE isoforms in regulating microglial functions. Our results also indicate that targeting apoE-mediated microglial inflammatory responses may serve as a potential therapeutic strategy for AD.

The demand for high-quality products and core technologies in economic transformation and upgrading is growing, and the improvement of residents' living standards also promotes the demand for high-end living products. Restricted by the development level of domestic related industries, these demands have not been well met, resulting in imbalance between supply and demand. This topic measures the high-quality development level of Xiamen's cultural tourism economy, analyzes its development status, compares and draws on the experience of cultural tourism economic development in other regions at home and abroad, and looks for the cultivation path of new growth points of Xiamen's cultural tourism economy, so as to lay a foundation for Xiamen to transform its resource advantages into economic advantages.

Background: Triple-negative breast cancer (TNBC) has the highest recurrence and distant metastasis rates among breast cancer molecular types. In breast-conserving surgery, the insensitivity discrimination of negative margins correlating with locoregional recurrence and poor patient outcomes. As for immunotherapy, only 20 %-40 % of the patients respond to the atezolizumab treatment due to the change of PDL1 receptor. Meanwhile, TNBC has radiotherapy resistance. Novel radiosensitization targets need to be found to enhance both the local and systematic benefits of radiotherapy. Objectives and rationale: We aim to construct an “all in one” multi-functional nanoprobe (MSN-Gd@Aptamer-ICG, NPs) using mesoporous silica as the framework. The mesoporous silica nanospheres are co-doped with gadolinium (Gd3+), loads indocyanine green (ICG) in its mesoporous channel, and conjugates with a specific PDL1 targeting aptamer on the surface. The biocompatible and biodegradable NPs are capable of release ICG by the reaction of intracellular high GSH and tetrasulfide bonds in silica frame. In the diagnosis, NIR II fluorescent imaging of ICG with the high resolution and deep tissue penetration depth screens out PDL1 highly expressed tumors. In surgical resection, it can show a real-time cancerous tissues margin in intraoperative scenarios and the tumors are successfully remove under the navigation of NIR II fluorescent imaging. During metastasis therapy of post-operation, the released Gd3+ effectively deposits X-rays and produces abundant hydroxyl radicals (•OH) and oxidative stress to induce radiosensitizing effects. More importantly, the therapy efficiency is monitored by NIR II fluorescent imaging. Therefore, our multifunctional NPs have roles in the accurate diagnosis of PDL1 expression of tumor in early stage, intraoperative navigation for radical excision, and metastasis eradication with radiosensitization efficiency enhanced, which lays a solid foundation for clinical TNBC therapy. Methods: The probe was 50 nm and it was successfully synthesized and certified. MTT assay suggested that it was nontoxic to normal breast cells and TNBC cells. Transmission Electron Microscope images showed that the probe was stable at the extracellular fluid and was degradable at tumor intracellular conditions. The leaching of ICG and Gd3+ was negligible at the extracellular fluid. The tumor targeting capability of the probe in vitro was evaluated on 4T1 (TNBC, PDL1 low expressed) and MDA-MB-231 (TNBC, PDL1 high expressed) cells by flow cytometry and laser confocal microscope. In vivo, the NIR II fluorescence imaging with a high resolution and tissue penetration depth successfully distinguished 4T1 and MDA-MB-231 bearing mice indicated the superior diagnostic capability of PDL1 via aptamer. In the surgical resection, the NIR II fluorescence imaging of NPs guided to remove the tumor with precisely discriminate the boundary of the tumor. When combined with RT, IHC staining of Ki67 showed that the NPs exhibited superior radiosensitizing effects under NIR II fluorescent imaging guidance in comparison with undoped Gd mesoporous silica nanoprobes. TUNEL fluorescent staining and H&E staining further confirmed that NPs radiation therapy induced more •OH and extensive DNA double-strand breaks. Results and Conclusion: Our biocompatible and biodegradable platform is nontoxic, can screen out PDL1 high expression tumors, and navigate the precise resection in the operation. Besides, it enhances the radioimmunotherapy efficacy of breast metastasis. Our platform is potential to provide new hope for breast cancer diagnostic, guiding resection, and radiosensitization under NIR II fluorescent imaging. Citation Format: Min Wei, Peiyuan Wang, Guojun Zhang. Diagnosis, navigation, treatment: A versatile biocompatible and biodegradable mesoporous silica platform of NIR II fluorescence imaging for early diagnosis, breast cancer precisely surgery, and radiosensitization [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-02-08.