National Science Review最新文献

Implanted pressure sensors can provide pressure information to assess localized health conditions of specific tissues or organs, such as the intra-articular pressure within knee joints. However, the prerequisites for implanted sensors pose greater challenges than those for wearables or for robots: aside from biocompatibility and tissue-like softness, they must also exhibit humidity insensitivity and high-pressure resolution across a broad pressure spectrum. Iontronic sensors can provide superior sensing properties, but they undergo property degradation in wet environments due to the hygroscopic nature of their active component: ionogels. Herein, we introduce a humidity-insensitive iontronic sensor array based on a hydrophobic and tough ionogel polymerized in a hydrophobicity transition yielding two hydrophobic phases: a soft liquid-rich phase that enhances ionic conductivity and ductility, and a stiff polymer-rich phase that contributes to superior toughness. We demonstrate the in vivo implantation of these sensor arrays to monitor real-time intra-articular pressure distribution in a sheep model, while assessing knee flexion with an angular resolution of 0.1° and a pressure resolution of 0.1%. We anticipate that this sensor array will find applications in various orthopedic surgeries and implantable medical devices.

Fluorinated nucleosides are an important class of modified nucleosides that have demonstrated therapeutic potential for treating various human diseases, especially viral infections and cancer. Many fluorinated nucleosides have advanced into clinical trials or have been approved by the FDA for use in patients. Among these fluorinated nucleosides, azvudine, developed by us, has been officially approved by the National Medical Products Administration for the treatment of coronavirus disease 2019 (COVID-19) and human immunodeficiency virus, indicating the therapeutic promise of fluorinated nucleosides. In view of the therapeutic promise of fluorinated nucleosides for antiviral and anticancer therapy, in this Review we will provide a comprehensive overview of well-established 2'-fluorinated nucleosides approved for use in the market or those in clinical stages for antiviral and antitumor therapies, highlighting the drug discovery strategies, structure-activity relationship studies, mechanisms of action, and preclinical/clinical studies and also discuss the challenges and future directions for nucleoside-based new drug discovery.

FLASH radiotherapy (FLASH-RT) is a new modality of radiotherapy that delivers doses with ultra-high dose rates. The FLASH effect was defined as the ability of FLASH-RT to suppress tumor growth while sparing normal tissues. Although the FLASH effect has been proven to be valid in various models by different modalities of irradiation and clinical trials of FLASH-RT have achieved promising initial success, the exact underlying mechanism is still unclear. This article summarizes mainstream hypotheses of the FLASH effect at physicochemical and biological levels, including oxygen depletion and free radical reactions, nuclear and mitochondria damage, as well as immune response. These hypotheses contribute reasonable explanations to the FLASH effect and are interconnected according to the chronological order of the organism's response to ionizing radiation. By collating the existing consensus, evidence and hypotheses, this article provides a comprehensive overview of potential mechanisms of the FLASH effect and practical guidance for future investigation in the field of FLASH-RT.

Protein glycosylation, the most universal post-translational modification, is thought to play a crucial role in regulating multiple essential cellular processes. However, the low abundance of glycoproteins and the heterogeneity of glycans complicate their comprehensive analysis. Here, we develop a rapid and large-scale glycopeptide enrichment strategy via bioorthogonal ligation and trypsin cleavage. The enrichment process is performed in one tube to minimize sample loss and time costs. This method combines convenience and practicality, identifying over 900 O-GlcNAc sites from a 500 μg sample. Surprisingly, it allows simultaneous identification of N-glycosites, O-GlcNAc sites, O-GalNAc sites and N-glycans via a two-step enzymatic release strategy. Combined with quantitative analysis, it reveals the distinct O-GlcNAcylation patterns in different compartments during oxidative stress. In summary, our study offers a convenient and robust tool for glycoproteome and glycome profiling, facilitating in-depth analysis to elucidate the biological functions of glycosylation.

Biomedical devices are indispensable in modern healthcare, significantly enhancing patients' quality of life. Recently, there has been a drastic increase in innovations for the fabrication of biomedical devices. Amongst these fabrication methods, the thermal drawing process has emerged as a versatile and scalable process for the development of advanced biomedical devices. By thermally drawing a macroscopic preform, which is meticulously designed and integrated with functional materials, hundreds of meters of multifunctional fibers are produced. These scalable flexible multifunctional fibers are embedded with functionalities such as electrochemical sensing, drug delivery, light delivery, temperature sensing, chemical sensing, pressure sensing, etc. In this review, we summarize the fabrication method of thermally drawn multifunctional fibers and highlight recent developments in thermally drawn fibers for modern biomedical application, including neural interfacing, chemical sensing, tissue engineering, cancer treatment, soft robotics and smart wearables. Finally, we discuss the existing challenges and future directions of this rapidly growing field.