Effects of Different Types of Electric Fields on Mechanical Properties and Microstructure of Ex Vivo Porcine Brain Tissues.

Electrotherapy plays a crucial role in regulating neuronal activity. Nevertheless, the relevant therapeutic mechanisms are still unclear; thus, the effects of electric fields on brain tissue's mechanical properties and microstructure need to be explored. In this study, focusing on the changes in mechanical properties and microstructure of ex vivo porcine brain tissues under different types of electric fields, directional and alternating electric fields (frequencies of 5, 20, 50, and 80 Hz, respectively) integrate with a custom-designed indentation device. The experimental results showed that for the ex vivo brain tissue, the directional electric field (DEF) can reduce the elastic properties of brain tissue. Simultaneously, the DEF can increase the cell spacing and reduce the proteoglycan content. The transmission electron microscope (TEM) analysis observed that the DEF can reduce the integrity of the plasma membrane, the endoplasmic reticulum's stress response, and the myelin lamella's separation. The alternating electric field (AEF) can accelerate the stress relaxation process of brain tissue and change the time-dependent mechanical properties of brain tissue. Meanwhile, with the increase in frequency, the cell spacing decreased, and the proteoglycan content gradually approached the control group without electric fields. TEM analysis observed that with the increase in frequency, the integrity of the plasma membrane increases, and the separation of the myelin lamella gradually disappears. Understanding the changes in the mechanical properties and microstructure of brain tissue under AEF and DEF enables a preliminary exploration of the therapeutic mechanism of electrotherapy. Simultaneously, the essential data was provided to support the development of embedded electrodes. In addition, the ex vivo experiments build a solid foundation for future in vivo experiments.

Aberrant Chloride Intracellular Channel 4 Expression Is Associated With Adverse Outcome in Cytogenetically Normal Acute Myeloid Leukemia.

Background and Methods: Acute myeloid leukemia (AML), which starts in the bone marrow, is a group of hematopoietic stem cell disorders. Chloride intracellular channel 4 (CLIC4) is regulated by p53, c-Myc, and TGF-ß. It induces the NF-κB-dependent activation of HIF (hypoxia-inducible factor) and participates in tumor growth through its microenvironmental function. However, its prognostic value in AML remains unclear, as well as its co-expression biomarkers. In this study, we evaluated the prognostic significance of CLIC4 expression using two independent large cohorts of cytogenetically normal AML (CN-AML) patients. Multivariable analysis and multi-omics analysis with weighted correlation network analysis (WGCNA) in the CN-AML group were also presented. Based on CLIC4 and its related genes, microRNA-target gene interaction network analysis and downstream gene ontology analysis were performed to unveil the complex functions behind CLIC4. Results: We demonstrated that the overexpression of CLIC4 was notably associated with unfavorable outcome in the two independent cohorts of CN-AML patients [overall survival (OS) and event-free survival (EFS): P < 0.0001, n = 185; OS: P = 0.016, n = 232], as well as in the European LeukemiaNet (ELN) Intermediate-I group (OS: P = 0.015, EFS: P = 0.012, n = 115), the National Comprehensive Cancer Network Intermediate Risk AML group (OS and EFS: P < 0.0001, n = 225), and the non-M3 AML group (OS and EFS: P < 0.0001, n = 435). Multivariable analysis further validated CLIC4 as a high-risk factor in the CN-AML group. Multi-omics analysis presented the overexpression of CLIC4 as associated with the co-expression of the different gene sets in leukemia, up/downregulation of the immune-related pathways, dysregulation of microRNAs, and hypermethylation around the CpG islands, in open sea regions, and in different gene structural fragments including TSS1500, gene body, 5'UTR region, 3'UTR region, and the first exon. By further performing WGCNA on multi-omics data, certain biomarkers that are co-expressed with CLIC4 were also unveiled. Conclusion: We demonstrated that CLIC4 is a novel, potential unfavorable prognosticator and therapeutic target for CN-AML. As having a key role in CN-AML, the interactions between CLIC4 and other genomics and transcriptomics data were confirmed by performing microRNA-target gene interaction network analysis and gene ontology enrichment analysis. The experimental result provides evidence for the clinical strategy selection of CN-AML patients.

Acidic leucine-rich nuclear phosphoprotein-32A expression contributes to adverse outcome in acute myeloid leukemia.

BACKGROUND: Acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) is a novel regulator of histone H3 acetylation and promotes leukemogenesis in acute myeloid leukemia (AML). However, its prognostic value in AML remains unclear. METHODS: In this study, we evaluated the prognostic significance of ANP32A expression using two independent large cohorts of cytogenetically normal AML (CN-AML) patients. Multivariable analysis in CN-AML group was also presented. Based on the ANP32A expression, its related genes, dysregulation of pathways, interaction network analysis between microRNAs and target genes, as well as methylation analysis were performed to unveil the complex functions behind ANP32A. RESULTS: Here we demonstrated overexpression of ANP32A was notably associated with unfavorable outcome in two independent cohorts of CN-AML patients (OS: P=0.012, EFS: P=0.005, n=185; OS: P=0.041, n=232), as well as in European Leukemia Net (ELN) Intermediate-I group (OS: P=0.018, EFS: P=0.045, n=115), National Comprehensive Cancer Network (NCCN) Intermediate Risk AML group (OS: P=0.048, EFS: P=0.039, n=225), and non-M3 AML group (OS: P=0.034, EFS: P=0.011, n=435). Multivariable analysis further validated ANP32A as a high-risk factor in CN-AML group. Multi-omics analysis presented overexpression of ANP32A was associated with aberrant expression of oncogenes and tumor suppressor, up/down-regulation of metabolic and immune-related pathways, dysregulation of microRNAs, and hypomethylation on CpG island and 1st Exon regions. CONCLUSIONS: We proved ANP32A as a novel, potential unfavorable prognosticator and therapeutic target for AML.

The effect of ferrous-chelating hairtail peptides on iron deficiency and intestinal flora in rats.

BACKGROUND: Chelating agents, such as small peptides, can decrease free iron content and increase iron bioavailability. They may have promising therapeutic potential and may prevent the pro-oxidant effects of low molecular weight iron. Hairtail is a species of fish that is rich in easily digestible proteins. We extended this strategy for iron delivery by using an enzymatic hydrolysate of hairtail as the chelating agent and found that the ferrous-chelating hairtail peptides have anti-anaemic activity in Sprague-Dawley rats with anaemia. RESULTS: The anti-anaemic activity of ferrous-chelating hairtail peptides prepared by enzymatic hydrolysis of the hairtail and ferrous chelation was studied in rat models of iron deficiency anaemia. After the end of the 35 d experiment, we noted significant differences in haemoglobin, mean corpuscular volume, haemoglobin distribution width, and ferritin concentrations between those animals supplemented with ferrous-chelating hairtail peptides and FeSO4 and healthy animals. There were no negative side effects on the animals' growth or behaviour. There was no obvious inflammation in the intestinal mucosa lamina propria and no unbalance of intestinal flora. CONCLUSION: The novel ferrous-chelating hairtail peptides may be a suitable fortificant for improving iron-deficiency status. Our findings demonstrated that this multi-tracer technique has many applications in nutritional research. © 2015 Society of Chemical Industry.

Multisensory Competition Is Modulated by Sensory Pathway Interactions with Fronto-Sensorimotor and Default-Mode Network Regions.

Multisensory information competes for preferential access to consciousness. It remains unknown what neural processes cause one particular modality to win multisensory competition and eventually dominate behavior. Thus, in a paradigm in which human participants sought to make simultaneous auditory and visual detection responses, we sought to identify prestimulus and poststimulus neural signals that were associated with auditory and visual dominance on each trial. Behaviorally, visual detection responses preceded auditory responses more frequently than vice versa. Even when visual responses were preceded by auditory responses, they recovered more quickly from previous responses, indicating the dominance of vision over audition. Neurally, visual precedence was associated with increased prestimulus activity in the prefrontal cortex and reduced prestimulus activity in the default-mode network, and increased poststimulus connectivity between the prefrontal cortex and the visual system. Moreover, the dorsal visual stream showed not only increased activity in post-perceptual phases but also enhanced connectivity with the sensorimotor cortex, indicating the functional role of the dorsal visual stream in prioritizing the flow of visual information into the motor system. In contrast, auditory precedence was associated with increased prestimulus activity in the auditory cortex and increased poststimulus neural coupling between the auditory and the sensorimotor cortex. Finally, whenever one modality lost multisensory competition, the corresponding sensory cortex showed enhanced connectivity with the default-mode network. Overall, the outcome of audiovisual competition depended on dynamic interactions between sensory systems and both the fronto-sensorimotor and the default-mode network. Together, these results revealed both the neural causes and the neural consequences of visual and auditory dominance during multisensory competition.

[Research on chemical constituents of xuefu zhuyu decoction].

OBJECTIVE: To investigate the chemical constituents of Xufu Zhuyu decoction. METHODS: Silica gel column chromatography, Sephadex LH-20 chromatography and crystallization were employed for the isolation and purification. The structures were elucidated by physicochemical properties and spectral analysis. RESULTS: Eleven compounds were isolated and identified as follows: palmitic acid (1), stearic acid (2), beta-sitosterol (3), oleanolic acid (4), pregnenolone (5), tangeratin (6), 4-hydroxy-3-butylphthalide (7), sorhamnetin (8), friedelinol (9), beta-ecdysone (10), ferulic acid (11). CONCLUSION: All these compounds are isolated from Xuefu Zhuyu decoction for the first time.