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Background Cerebral infarction is a disorder of blood supply to the local brain tissue area caused by various causes. Tongnao Decoction is approved and used in Jiangsu Province Hospital of Chinese Medicine for the treatment of cerebral infarction. However, the specific mechanisms underlying its action remain unclear. Objective To explain the mechanism of Tongnao Decoction in the treatment of cerebral infarction through network pharmacology and clinical trails. Methods From January 2019 to June 2020, a total of 199 patients with cerebral infarction admitted to Jiangsu Province Hospital of Chinese Medicine were included in the clinical study. and divided into the control group (97 cases) and experimental group (102 cases) according to the method of random number table. Both groups received standardized treatment for stable cerebral infarction, and the experimental group was treated with Tongnao Decoction. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the degree of functional impairment caused by stroke, and the modified Rankin Scale (mRS) was used to assess the recovery of neurological function for both groups before treatment and at 2 weeks of treatment. The chemical compounds of Tongnao Decoction were screened from TCMSP and literature, and those with bioavailability (OB) ≥30% and drug-like properties (DL) ≥0.18 requirements were selected to find the active ingredient of the prescription. OMIM and GeneCards databases were used to analyze the molecular targets of Tongnao Decoction for the treatment of cerebral infarction. After screening the common targets, Cytoscape software, String database were used to plot the network of compounds and target proteins, construct protein-protein interaction (PPI) network, gene ontology (GO) function, and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis, respectively. Molecular docking experiments were finally performed to identify the main active ingredients of Tongnao Decoction for the treatment of cerebral infarction. Results After treatment, the scores of NIHSS and mRS in the experimental group were lower than those in the control group (P

Wearable flexible strain sensors have attracted considerable attention in recent years, while it is still a significant challenge to fabricate wearable flexible strain sensors with high sensitivity and wide sensing range simultaneously. In this work, a high-performance wearable flexible strain sensor based on a thermoplastic polyurethane electrospun nanofibers (TPUNFs) film embedded with a silver nanowires/reduced graphene oxide (AgNWs/rGO) composite conductive material was fabricated via a simple drop-coating technique. The effect of the amount of AgNWs/rGO composite conductive material on the strain sensing range of the AgNWs/rGO/TPUNFs film flexible strain sensor was investigated, the strain sensing range of AgNWs/rGO/TPUNFs film flexible strain sensor was compared with that of the AgNWs/TPUNFs and GO/TPUNFs film flexible strain sensor, and the strain sensing properties of the AgNWs/rGO/TPUNFs film flexible strain sensor were measured. The results showed that the AgNWs/rGO/TPUNFs film flexible strain sensor with high sensitivity and wide sensing range simultaneously was achieved by compounding AgNWs and the reduced graphene oxide (rGO) conductive material. The strain sensing range of the AgNWs/rGO/TPUNFs film flexible strain sensor could be improved by increasing the amount of the AgNWs/rGO composite conductive material, and it was obviously better than that of AgNWs/TPUNFs and the rGO/TPUNFs film flexible strain sensor. The obtained AgNWs/rGO/TPUNFs film flexible strain sensor possessed high sensitivity (the gauge factor could reach a maximum of 2513.23.) as well as a wide sensing range (∼187%). Furthermore, the obtained AgNWs/rGO/TPUNFs film flexible strain sensor had a fast response/recovery time (200 ms/300 ms) and good cycling stability (∼3,000 cycles). Benefitting from the outstanding strain sensing performance, the AgNWs/rGO/TPUNFs film flexible strain sensor could detect large human motions such as finger, wrist, and knee bending as well as expression, which demonstrates great potential applications in wearable devices.

Ectopic epigenetic mechanisms play important roles in facilitating tumorigenesis. Here, we first demonstrated that ANKDD1A is a functional tumor suppressor gene, especially in the hypoxia microenvironment. ANKDD1A directly interacts with FIH1 and inhibits the transcriptional activity of HIF1α by upregulating FIH1. In addition, ANKDD1A decreases the half-life of HIF1α by upregulating FIH1, decreases glucose uptake and lactate production, inhibits glioblastoma multiforme (GBM) autophagy, and induces apoptosis in GBM cells under hypoxia. Moreover, ANKDD1A is highly frequently methylated in GBM. The tumor-specific methylation of ANKDD1A indicates that it could be used as a potential epigenetic biomarker as well as a possible therapeutic target.

BackgroundDespite the overwhelming number of investigations on AKT, little is known about lncRNA on AKT regulation, especially in GBM cells.MethodsRNA-binding protein immunoprecipitation assay (RIP) and RNA pulldown were used to confirm the binding of LINC00470 and fused in sarcoma (FUS). Confocal imaging, co-immunoprecipitation (Co-IP) and GST pulldown assays were used to detect the interaction between FUS and AKT. EdU assay, CCK-8 assay, and intracranial xenograft assays were performed to demonstrate the effect of LINC00470 on the malignant phenotype of GBM cells. RT-qPCR and Western blotting were performed to test the effect of LINC00470 on AKT and pAKT.ResultsIn this study, we demonstrated that LINC00470 was a positive regulator for AKT activation in GBM. LINC00470 bound to FUS and AKT to form a ternary complex, anchoring FUS in the cytoplasm to increase AKT activity. Higher pAKT activated by LINC00470 inhibited ubiquitination of HK1, which affected glycolysis, and inhibited cell autophagy. Furthermore, higher LINC00470 expression was associated with GBM tumorigenesis and poor patient prognosis.ConclusionsOur findings revealed a noncanonical AKT activation signaling pathway, i.e., LINC00470 directly interacts with FUS, serving as an AKT activator to promote GBM progression. LINC00470 has an important referential significance to evaluate the prognosis of patients.

Membrane-bound transcription factors (MTFs) are transcription factors (TFs) that are anchored in membranes in a dormant state. Activated by external or internal stimuli, MTFs are released from parent membranes and are transported to the nucleus. Existing research indicates that some plasma membrane (PM)-bound proteins and some endoplasmic reticulum (ER) membrane-bound proteins have the ability to enter the nucleus. Upon specific signal recognition cues, some PM-bound TFs undergo proteolytic cleavage to liberate the intracellular fragments that enter the nucleus to control gene transcription. However, lipid-anchored PM-bound proteins enter the nucleus in their full length for depalmitoylation. In addition, some PM-bound TFs exist as full-length proteins in cell nucleus via trafficking to the Golgi and the ER, where membrane-releasing mechanisms rely on endocytosis. In contrast, the ER membrane-bound TFs relocate to the nucleus directly or by trafficking to the Golgi. In both of these pathways, only the fragments of the ER membrane-bound TFs transit to the nucleus. Several different nuclear trafficking modes of MTFs are summarized in this review, providing an effective supplement to the mechanisms of signal transduction and gene regulation. Moreover, targeting intracellular movement pathways of disease-associated MTFs may significantly improve the survival of patients.