Role of the LC arousal promoting neurons in maintaining brain criticality across the sleep-wake cycle.

Sleep control depends on a delicate interplay among brain regions. This generates a complex temporal architecture with numerous sleep-stage transi-tions and intermittent fluctuations to micro-states and brief arousals within sleep stages. These temporal dynamics exhibit hallmarks of criticality, suggest-ing that tuning to criticality is essential for spontaneous sleep-stage and arousal transitions. However, how the brain maintains criticality remains not under-stood. Here, we investigate dynamics of θ- and δ-bursts during the sleep-wake cycle of rats (Sprague-Dawley, adult male) with lesion in the wake-promoting locus coeruleus (LC). We show that, in control rats, θ- and δ-bursts exhibit duality of power-law (θ-bursts, active phase) and exponential-like (δ-bursts, quiescent phase) duration distributions, as well as power-law long-range tem-poral correlations (LRTC)-typical of non-equilibrium systems self-organizing at criticality. Further, consecutive θ- and δ-bursts durations are characterized by anti-correlated coupling, indicating a new class of self-organized critical- ity that emerges from underlying feedback between neuronal populations and brain areas involved in generating arousals and sleep states. In contrast, we uncover that LC lesion leads to alteration of θ- and δ-burst critical features, with change in duration distributions and correlation properties, and increase in θ-δ coupling. Notably, these LC-lesion effects are opposite to those observed for lesions in the sleep-promoting ventrolateral preoptic nucleus (VLPO). Our findings indicate that critical dynamics of θ- and δ-bursts arise from a bal-anced interplay of LC and VLPO, which maintains brain tuning to criticality across the sleep-wake cycle-a continuous non-equilibrium behavior in sleepSignificance statement Criticality has been associated with healthy brain function in both sleep and wake. However, how the sleep-wake control circuitry maintains criticality remains not un-derstood. Our analyses demonstrate that arousal promoting neurons in the LC play a key role in maintaining brain criticality across the sleep-wake cycle. The results show that lesions of the wake-promoting LC affect the critical dynamics of θ and δ bursts, altering duration distributions, correlation properties, and θ-δ coupling. The reported changes in criticality measures are opposite to those caused by lesions of the sleep-promoting VLPO. This suggests that feed-forward and feedback interactions among neuronal populations in the LC and VLPO are essential to maintain the brain tuned to criticality across the sleep-wake cycle.

Hsa_circ_0006677 regulates special AT-rich binding protein-2-mediated tumor-suppressive effect via functioning as a miR-1245a sponge in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is still one of the most challenging malignant tumors. Deregulation of circular RNAs (circRNAs) is associated with NSCLC progression. However, the regulatory mechanism of circRNAs in NSCLC still needs to be studied. We selected a differentially expressed hsa_circ_0006677 (circ_0006677) in NSCLC through analyzing the GSE158695 and GSE112214 datasets. Expression of circ_0006677 was evaluated by real-time quantitative polymerase-chain reaction (RT-qPCR). Effects of circ_0006677 overexpression on NSCLC cell proliferation, apoptosis, migration, invasion, and stemness were determined by clonogenic, 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, and sphere formation assays. The regulatory mechanism of circ_0006677 was predicted by bioinformatics analysis and verified by dual-luciferase reporter and RIP assays. Animal experiments were carried out to validate the function of circ_0006677 in vivo. We observed the downregulation of circ_0006677 in NSCLC samples and cells. Functionally, circ_0006677 overexpression decreased xenograft tumor growth and restrained NSCLC cell proliferation, invasion, migration, stemness, and induced NSCLC cell apoptosis in vitro. Molecular mechanism experiments exhibited that circ_0006677 functioned as a miR-1245a sponge and mediated SATB2 expression through adsorbing miR-1245a. Either miR-1245a overexpression or SATB2 knockdown weakened circ_0006677 overexpression-mediated repression on proliferation, invasion, migration, and stemness. In conclusion, circ_0006677 regulated SATB2-mediated tumor-suppressive effect via acting as a miR-1245a sponge in NSCLC, providing a new mechanism for understanding the progression of NSCLC.

[Analysis of Gene Variation in Thymoma by Microarray].

BACKGROUND: Thymoma is the most common malignant tumor in anterior mediastinum, and its specific pathogenesis is still unclear. This limits the study of targeted drugs for thymoma. The aim of the study is to investigate the genes and signal pathways of thymoma, and provide help for the research of thymic tumor pathogenesis using the technology of second-generation genechip to analyze thymoma. METHODS: From January 2015 to December 2017, we analyzed 31 cases of thymoma by CapitaBio mRNA expression profile genechip technology, and then confirmed the genes by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: We found some genes with different expression levels between thymoma and surrounding thymus tissue. Among them, six driving genes (FANCI, CAPD3, NCAPG, OXCT1, EPHA1 and MCM2) were significantly abnormal in thymoma. Some specific genes affected by copy-number variation were detected: E2F2, EphA1, CCL25 and MCM2 were significantly up-regulated, while IL-6, CD36, FABP4, SH2D1A and MYOC genes were significantly down-regulated. KEGG database analysis showed that the expression of 10 signaling pathway genes was generally up-regulated or down-regulated, such as systemic lupus erythematosus, viral oncogenes, primary immunodeficiency, cell cycle genes and p53 signaling pathway, which may be related to occurrence of thymoma. CONCLUSIONS: We found a variety of genes abnormally expressed in thymoma, which will provide reference for the study of pathogenesis and biomarkers of thymoma in the future.

A multi-scale feedback ratio analysis of heartbeat interval series in healthy vs. cardiac patients.

The second-order difference plot, as a modified Poincaré plot, is one of the important approaches for assessing the dynamics of heart rate variability. However, corresponding quantitative analysis methods are relatively limited. Based on the second-order difference plot, we propose a novel method, called the multi-scale feedback ratio analysis, which can measure the feedback properties of heart rate fluctuations on different temporal scales. The index [R(TF([τ(1), τ(2)]) is then defined to quantify the average feedback ratio through a definite scale range. Analysis of Gaussian white, 1/f and Brownian noises show that the feedback ratios are indeed on different levels. The method is then applied to heartbeat interval series derived from healthy subjects, subjects with congestive heart failure and subjects with atrial fibrillation. Results show that, for all groups, the feedback ratios vary with increasing time scales, and gradually reach relatively stable states. The R(TF)([10,20]) values of the three groups are significantly different. Thus, R(TF)([10,20]) becomes an effective parameter for distinguishing healthy and pathologic states. In addition, RTF([10,20]) for healthy, congestive failure and atrial fibrillation subjects are close to those of the 1/f, Brownian and white noises respectively, indicating different intrinsic dynamics.

Combination of equiprobable symbolization and time reversal asymmetry for heartbeat interval series analysis.

Symbolic dynamics method and time reversal asymmetry analysis are both important approaches in the study of heartbeat interval series. However, there is limited research work reported on combining these two methods. We provide a method of time reversal asymmetry analysis which focuses on the differences between the forward and backward embedding "m words" after the operation of equiprobable symbolization. To investigate the total amplitude as well as the distribution features of the difference, four indices are proposed. Based on the application to simulation series, we found that these measures can successfully detect time reversal asymmetry in chaos series. With application to human heartbeat interval series (RR series), it is suggested that the distribution features of the forward-backward difference can sensitively capture the dynamical changes caused by diseases or aging. In particular, the index E(D), which reflects the random degree of the forward-backward difference distribution, can significantly discriminate healthy subjects from diseased ones. We conclude that RR series from healthy subjects show more asymmetry in temporal structure on the original time scale from the perspective of equiprobable symbolization, whereas diseases account for loss of this asymmetry.

[A design of a portable acquistion system for autonomic nervous function data].

In this paper, a design of the portable acquisition system for autonomic nervous function data based on the microcontroller is introduced. The system contains an electrocardiogram amplifier and an AD convertor, using SD memory card as its storage device and thus it can record data for a longer time and exchange data with PC easily. The system with a simple structure realizes its miniaturization and low energy consumption.

[Mid-, and long-term effects of video-assisted thoracoscopic and transsternal thymectomy in treatment of non-thymomatous myasthenia gravis: analysis of 204 cases].

OBJECTIVE: To evaluate the mid-, and long-term effects of video-assisted thoracoscopic thymectomy and transsternal thymectomy in treatment of myasthenia gravis (MG) and to identify the prognostic factors for thymectomy success. METHODS: 161 patients with non-thymomatous MS, 84 males and 120 females, aged 33, underwent transsternal thymectomy and were followed up for 5 years; and 43 patients with non-thymomatous MS A retrospective, 1 male and 25 females, 21 being aged >40 during operation, underwent thoracoscopic thymectomy and were followed up for 3 years. RESULTS: The mean operating time of the thoracoscopic group was (132 +/- 32) min minutes, significantly longer than that of the transsternal thymectomy group [(96 +/- 18) min, P = 0.000]. Four patients in the transsternal thymectomy group and 41 in the transsternal thymectomy group developed myasthenic crises (P = 0.023). The complete stable remission (CSR) rates 1, 2, and 3 years after operation of the thoracoscopic thymectomy group were 34.9%, 41.9%, and 46.5% respectively; and CSR rates 1, 2, 3, and 5 years after operation of the transsternal thymectomy group were 26.7%, 31.7%, 35.4%, and 40.4% respectively, without significant differences between these 2 groups. CONCLUSION: Both thoracoscopic and transsternal approaches to thymectomy in patients with MG are effective in terms of remission. The authors advocate adopting the thoracoscopic approach early.