Kinase–substrate Edge Biomarkers Provide A More Accurate Prognostic Prediction in ER-negative Breast Cancer

The estrogen receptor (ER)-negative breast cancer subtype is aggressive with few treatment options available. To identify specific prognostic factors for ER-negative breast cancer, this study included 705,729 and 1034 breast invasive cancer patients from the Surveillance, Epidemiology, and End Results (SEER) and The Cancer Genome Atlas (TCGA) databases, respectively. To identify key differential kinase–substrate node and edge biomarkers between ER-negative and ER-positive breast cancer patients, we adopted a network-based method using correlation coefficients between molecular pairs in the kinase regulatory network. Integrated analysis of the clinical and molecular data revealed the significant prognostic power of kinase–substrate node and edge features for both subtypes of breast cancer. Two promising kinase–substrate edge features, CSNK1A1–NFATC3 and SRC–OCLN, were identified for more accurate prognostic prediction in ER-negative breast cancer patients.     

Robust Swing‐Structured Triboelectric Nanogenerator for Efficient Blue Energy Harvesting

Ocean wave energy is a promising renewable energy source, but harvesting such irregular, “random,” and mostly ultra‐low frequency energies is rather challenging due to technological limitations. Triboelectric nanogenerators (TENGs) provide a potential efficient technology for scavenging ocean wave energy. Here, a robust swing‐structured triboelectric nanogenerator (SS‐TENG) with high energy conversion efficiency for ultra‐low frequency water wave energy harvesting is reported. The swing structure inside the cylindrical TENG greatly elongates its operation time, accompanied with multiplied output frequency. The design of the air gap and flexible dielectric brushes enable mininized frictional resistance and sustainable triboelectric charges, leading to enhanced robustness and durability. The TENG performance is controlled by external triggering conditions, with a long swing time of 88 s and a high energy conversion efficiency, as well as undiminished performance after continuous triggering for 4 00 000 cycles. Furthermore, the SS‐TENG is demonstrated to effectively harvest water wave energy. Portable electronic devices are successfully powered for self‐powered sensing and environment monitoring. Due to the excellent performance of the distinctive mechanism and structure, the SS‐TENG in this work provides a good candidate for harvesting blue energy on a large scale.     

Molecular mechanisms of An-Chuan Granule for the treatment of asthma based on a network pharmacology approach and experimental validation

An-Chuan Granule (ACG), a traditional Chinese medicine (TCM) formula, is an effective treatment for asthma but its pharmacological mechanism remains poorly understood. In the present study, network pharmacology was applied to explore the potential mechanism of ACG in the treatment of asthma. The tumor necrosis factor (TNF), Toll-like receptor (TLR), and Th17 cell differentiation-related, nucleotide-binding oligomerization domain (NOD)-like receptor, and NF-kappaB pathways were identified as the most significant signaling pathways involved in the therapeutic effect of ACG on asthma. A mouse asthma model was established using ovalbumin (OVA) to verify the effect of ACG and the underlying mechanism. The results showed that ACG treatment not only attenuated the clinical symptoms, but also reduced inflammatory cell infiltration, mucus secretion and MUC5AC production in lung tissue of asthmatic mice. In addition, ACG treatment notably decreased the inflammatory cell numbers in bronchoalveolar lavage fluid (BALF) and the levels of pro-inflammatory cytokines (including IL-6, IL-17, IL-23, TNF-alpha, IL-1beta and TGF-beta) in lung tissue of asthmatic mice. In addition, ACG treatment remarkably down-regulated the expression of TLR4, p-P65, NLRP3, Caspase-1 and adenosquamous carcinoma (ASC) in lung tissue. Further, ACG treatment decreased the expression of receptor-related orphan receptor (RORγt) in lung tissue but increased that of Forkhead box (Foxp3). In conclusion, the above results demonstrate that ACG alleviates the severity of asthma in a ´multi-compound and multi-target’ manner, which provides a basis for better understanding of the application of ACG in the treatment of asthma.