Smart medicine最新文献

Silk fibroin (SF)-based hydrogels are promising multifunctional adhesive candidates for real-world applications in tissue engineering, implantable bioelectronics, artificial muscles, and artificial skin. However, developing conductive SF-based hydrogels that are suitable for the micro-physiological environment and maintain their physical and chemical properties over long periods of use remains challenging. Herein, we developed an ion-conductive SF hydrogel composed of glycidyl methacrylate silk fibroin (SilMA) and bioionic liquid choline acylate (ChoA) polymer chains, together with the modification of acrylated thymine (ThyA) and adenine (AdeA) functional groups. The resulting polymeric ion-conductive SF composite hydrogel demonstrated high bioactivity, strong adhesion strength, good mechanical compliance, and stretchability. The formed hydrogel network of ChoA chains can coordinate with the ionic strength in the micro-physiological environment while maintaining the adaptive coefficient of expansion and stable mechanical properties. These features help to form a stable ion-conducting channel for the hydrogel. Additionally, the hydrogel network modified with AdeA and ThyA, can provide a strong adhesion to the surface of a variety of substrates, including wet tissue through abundant hydrogen bonding. The biocompatible and ionic conductive SF composite hydrogels can be easily prepared and incorporated into flexible skin or epidermal sensing devices. Therefore, our polymeric SF-based hydrogel has great potential and wide application to be an important component of many flexible electronic devices for personalized healthcare.

Peptide spectrum matching is the process of linking mass spectrometry data with peptide sequences. An experimental spectrum can match thousands of candidate peptides with variable modifications leading to an exponential increase in candidates. Completing the search within a limited time is a key challenge. Traditional searches expedite the process by restricting peptide mass errors and variable modifications, but this limits interpretive capability. To address this challenge, we propose Dear-PSM, a peptide search engine that supports full database searching. Dear-PSM does not restrict peptide mass errors, matching each spectrum to all peptides in the database and increasing the number of variable modifications per peptide from the conventional 3-20. Leveraging inverted index technology, Dear-PSM creates a high-performance index table of experimental spectra and utilizes deep learning algorithms for peptide validation. Through these techniques, Dear-PSM achieves a speed breakthrough 7 times faster than mainstream search engines on a regular desktop computer, with a remarkable 240-fold reduction in memory consumption. Benchmark test results demonstrate that Dear-PSM, in full database search mode, can reproduce over 90% of the results obtained by mainstream search engines when handling complex mass spectrometry data collected from different species using various instruments. Furthermore, it uncovers a substantial number of new peptides and proteins. Dear-PSM has been publicly released on the GitHub repository https://github.com/jianweishuai/Dear-PSM.

Recent studies indicate a significant upregulation of gasdermin D (GSDMD) in acute kidney injury (AKI), a severe medical condition characterized by high morbidity and mortality globally. In this study, we identified and validated the therapeutic effects of small molecule inhibitors targeting the GSDMD pathway for AKI treatment. Using a drug screening assay, we evaluated thousands of small molecules from DrugBank against Lipopolysaccharide (LPS) and Nigericin-stimulated immortalized bone marrow-derived macrophages (iBMDMs) to discern GSDMD pathway activators. We simulated AKI in primary renal tubular epithelial cells using hydrogen peroxide (H₂O₂) exposure. Furthermore, AKI in mouse models was induced via cisplatin and ischemia/reperfusion. Our findings highlight stevioside as a potent GSDMD activator exhibiting minimal toxicity. Experimental results, both in vitro and in vivo, demonstrate stevioside's significant potential in alleviating renal tubular epithelial cell injury and AKI histological damage. After stevioside treatment, a notable decrease in cleaved GSDMD-N terminal levels was observed coupled with diminished inflammatory factor release. This observation was consistent in both cisplatin- and ischemia/reperfusion-induced AKI mouse models. Collectively, our research suggests that stevioside could be a promising candidate for modulating GSDMD signaling in AKI treatment.