Event-Triggered Sliding Mode Impulsive Control for Lower Limb Rehabilitation Exoskeleton Robot Gait Tracking

Lower limb rehabilitation exoskeleton robots (LLRERs) play an important role in lower limb rehabilitation training and assistance walking for patients with lower limb movement disorders. In order to reduce and eliminate adverse effects on the accuracy of human motion gait tracking during walking with an LLRER, which is caused by the gravity and friction, the periodic ground shock force, and the human–exoskeleton interaction force, this paper proposes a feedforward–feedback hybrid control strategy of sliding mode impulsive control with gravity and friction compensation, based on the event-triggered mechanism of Lyapunov function. Firstly, to realize high-precision gait tracking with bounded error, some constraints on controller parameters are deduced by analyzing the Lyapunov-based stability. Secondly, the Zeno behavior of impulsive event triggers is excluded by the analysis of three different cases of the triggering time sequence. Finally, the effectiveness of the proposed hybrid controller is verified by the numerical simulation of the LLRER human–exoskeleton integrated system based on a three-link simplified model. It shows that an event-triggered sliding mode impulsive control strategy with gravity and friction compensation can achieve complete gait tracking with bounded error and has excellent dynamic performance under the constraints

Nasal Nanovaccines for SARS-CoV-2 to Address COVID-19

COVID-19 is still prevalent around the globe. Although some SARS-CoV-2 vaccines have been distributed to the population, the shortcomings of vaccines and the continuous emergence of SARS-CoV-2 mutant virus strains are a cause for concern. Thus, it is vital to continue to improve vaccines and vaccine delivery methods. One option is nasal vaccination, which is more convenient than injections and does not require a syringe. Additionally, stronger mucosal immunity is produced under nasal vaccination. The easy accessibility of the intranasal route is more advantageous than injection in the context of the COVID-19 pandemic. Nanoparticles have been proven to be suitable delivery vehicles and adjuvants, and different NPs have different advantages. The shortcomings of the SARS-CoV-2 vaccine may be compensated by selecting or modifying different nanoparticles. It travels along the digestive tract to the intestine, where it is presented by GALT, tissue-resident immune cells, and gastrointestinal lymph nodes. Nasal nanovaccines are easy to use, safe, multifunctional, and can be distributed quickly, demonstrating strong prospects as a vaccination method for SARS-CoV-2, SARS-CoV-2 variants, or SARS-CoV-n

Regulating the Expression of HIF-1α or lncRNA: Potential Directions for Cancer Therapy

Previous studies have shown that tumors under a hypoxic environment can induce an important hypoxia-responsive element, hypoxia-induced factor-1α (HIF-1α), which can increase tumor migration, invasion, and metastatic ability by promoting epithelial-to-mesenchymal transition (EMT) in tumor cells. Currently, with the deeper knowledge of long noncoding RNAs (lncRNAs), more and more functions of lncRNAs have been discovered. HIF-1α can regulate hypoxia-responsive lncRNAs under hypoxic conditions, and changes in the expression level of lncRNAs can regulate the production of EMT transcription factors and signaling pathway transduction, thus promoting EMT progress. In conclusion, this review summarizes the regulation of the EMT process by HIF-1α and lncRNAs and discusses their relationship with tumorigenesis. Since HIF-1α plays an important role in tumor progression, we also summarize the current drugs that inhibit tumor progression by modulating HIF-1α

Research Progress and Direction of Novel Organelle—Migrasomes

Migrasomes are organelles that are similar in structure to pomegranates, up to 3 μm in diameter, and contain small vesicles with a diameter of 50–100 nm. These membranous organelles grow at the intersections or tips of retracting fibers at the back of migrating cells. The process by which cells release migrasomes and their contents outside the cell is called migracytosis. The signal molecules are packaged in the migrasomes and released to the designated location by migrasomes to activate the surrounding cells. Finally, the migrasomes complete the entire process of information transmission. In this sense, migrasomes integrate time, space, and specific chemical information, which are essential for regulating physiological processes such as embryonic development and tumor invasion and migration. In this review, the current research progress of migrasomes, including the discovery of migrasomes and migracytosis, the structure of migrasomes, and the distribution and functions of migrasomes is discussed. The migratory marker protein TSPAN4 is highly expressed in various cancers and is associated with cancer invasion and migration. Therefore, there is still much research space for the pathogenesis of migratory bodies and cancer. This review also makes bold predictions and prospects for the research directions of the combination of migrasomes and clinical applications

Research Progress and Direction of Novel Organelle—Migrasomes

Migrasomes are organelles that are similar in structure to pomegranates, up to 3 μm in diameter, and contain small vesicles with a diameter of 50–100 nm. These membranous organelles grow at the intersections or tips of retracting fibers at the back of migrating cells. The process by which cells release migrasomes and their contents outside the cell is called migracytosis. The signal molecules are packaged in the migrasomes and released to the designated location by migrasomes to activate the surrounding cells. Finally, the migrasomes complete the entire process of information transmission. In this sense, migrasomes integrate time, space, and specific chemical information, which are essential for regulating physiological processes such as embryonic development and tumor invasion and migration. In this review, the current research progress of migrasomes, including the discovery of migrasomes and migracytosis, the structure of migrasomes, and the distribution and functions of migrasomes is discussed. The migratory marker protein TSPAN4 is highly expressed in various cancers and is associated with cancer invasion and migration. Therefore, there is still much research space for the pathogenesis of migratory bodies and cancer. This review also makes bold predictions and prospects for the research directions of the combination of migrasomes and clinical applications

The potential, analysis and prospect of ctDNA sequencing in hepatocellular carcinoma

Background The genome map of hepatocellular carcinoma (HCC) is complex. In order to explore whether circulating tumor cell DNA (ctDNA) can be used as the basis for sequencing and use ctDNA to find tumor related biomarkers, we analyzed the mutant genes of ctDNA in patients with liver cancer by sequencing. Methods We used next-generation targeted sequencing technology to identify mutations in patients with liver cancer. The ctDNA from 10 patients with hepatocellular carcinoma (including eight cases of primary hepatocellular carcinoma and two cases of secondary hepatocellular carcinoma) was sequenced. We used SAMtools to detect and screen single nucleotide polymorphisms (SNPs) and insertion deletion mutations (INDELs) and ANNOVAR to annotate the structure and function of the detected mutations. Screening of pathogenic and possible pathogenic genes was performed using American College of Medical Genetics and Genomics (ACMG) guidelines. GO analysis and KEGG analysis of pathogenic and possible pathogenic genes were performed using the DAVID database, and protein–protein interaction network analysis of pathogenic and possible pathogenic genes was performed using the STRING database. Then, the Kaplan–Meier plotter database, GEPIA database and HPA database were used to analyse the relationship between pathogenic and possible pathogenic genes and patients with liver cancer. Results Targeted capture and deep sequencing of 560 cancer-related genes in 10 liver cancer ctDNA samples revealed 8,950 single nucleotide variation (SNV) mutations and 70 INDELS. The most commonly mutated gene was PDE4DIP, followed by SYNE1, KMT2C, PKHD1 and FN1. We compared these results to the COSMIC database and determined that ctDNA could be used for sequencing. According to the ACMG guidelines, we identified 54 pathogenic and possible pathogenic mutations in 39 genes in exons and splice regions of 10 HCC patients and performed GO analysis, KEGG analysis, and PPI network analysis. Through further analysis, four genes significantly related to the prognosis of liver cancer were identified. Conclusion In this study, our findings indicate that ctDNA can be used for sequencing. Our results provide some molecular data for the mapping of genetic variation in Chinese patients with liver cancer, which enriches the understanding of HCC pathogenesis and provides new ideas for the diagnosis and prognosis of HCC patients

TrkB phosphorylation by Cdk5 is required for activity-dependent structural plasticity and spatial memory

The neurotrophin brain-derived neurotrophic factor (BDNF) and its receptor TrkB participate in diverse neuronal functions, including activity-dependent synaptic plasticity that is crucial for learning and memory. On binding to BDNF, TrkB is not only autophosphorylated at tyrosine residues but also undergoes serine phosphorylation at S478 by the serine/threonine kinase cyclin-dependent kinase 5 (Cdk5). However, the in vivo function of this serine phosphorylation remains unknown. We generated knock-in mice lacking this serine phosphorylation (Trkb S478A/S478A mice) and found that the TrkB phosphorylation-deficient mice displayed impaired spatial memory and compromised hippocampal long-term potentiation (LTP). S478 phosphorylation of TrkB regulates its interaction with the Rac1-specific guanine nucleotide exchange factor TIAM1, leading to activation of Rac1 and phosphorylation of S6 ribosomal protein during activity-dependent dendritic spine remodeling. These findings reveal the importance of Cdk5-mediated S478 phosphorylation of TrkB in activity-dependent structural plasticity, which is crucial for LTP and spatial memory formation