The neural signals produced by varying electrical stimulation parameters lead to characteristic neural circuit responses. However, the characteristics of neural circuits reconstructed by electrical ...signals remain poorly understood, which greatly limits the application of such electrical neuromodulation techniques for the treatment of spinal cord injury. Here, we develop a dual electrical stimulation system that combines epidural electrical and muscle stimulation to mimic feedforward and feedback electrical signals in spinal sensorimotor circuits. We demonstrate that a stimulus frequency of 10-20 Hz under dual stimulation conditions is required for structural and functional reconstruction of spinal sensorimotor circuits, which not only activates genes associated with axonal regeneration of motoneurons, but also improves the excitability of spinal neurons. Overall, the results provide insights into neural signal decoding during spinal sensorimotor circuit reconstruction, suggesting that the combination of epidural electrical and muscle stimulation is a promising method for the treatment of spinal cord injury.
In this letter, we propose the phase-locked loop with discrete wavelet transform filtering and redesigned Kalman filters (KFs) to enhance the global navigation satellite system signal carrier ...tracking robustness under ionospheric scintillation, being of the paramount importance in safety critical applications and advanced receivers. By normalizing the discriminator in the loop using the signal amplitude estimated with the discrete wavelet transform filtering, the phase variation due to scintillation is well estimated. The adaptive KF is modified with an additional amplitude state to copy with the scintillation-induced disturbance so as to stably track the fluctuated phases. Simulations are offered to verify the performance improvement of the proposed method versus the previous ones in the case of ionospheric scintillation.
Depression is a serious public-health issue. Recent reports have suggested higher susceptibility to viral infections in depressive patients. However, how depression affects antiviral innate immune ...signaling remains unknown. Here, we revealed a reduction in expression of Abelson helper integration site 1 (AHI1) in the peripheral blood mononuclear cells (PBMCs) and macrophages from the patients with major depressive disorder (MDD), which leads to attenuated antiviral immune response. We found that depression-related arginine vasopressin (AVP) induces reduction of AHI1 in macrophages. Further studies demonstrated that AHI1 is a critical stabilizer of basal type-I-interferon (IFN-I) signaling. Mechanistically, AHI1 recruits OTUD1 to deubiquitinate and stabilize Tyk2, while AHI1 reduction downregulates Tyk2 and IFN-I signaling activity in macrophages from both MDD patients and depression model mice. Interestingly, we identified a clinical analgesic meptazinol that effectively stimulates AHI1 expression, thus enhancing IFN-I antiviral defense in depression model mice. Our study promotes the understanding of the signaling mechanisms of depression-mediated antiviral immune dysfunction, and reveals meptazinol as an enhancer of antiviral innate immunity in depressive patients.
Anal adenocarcinoma (AA) represents a rare condition, and little is known about the predictive factors of the outcomes or the optimal TNM staging system for curable AA. Using population-based data, ...we preliminarily sought to determine the prognostic factors and evaluate the existing T and N staging criteria of AA.
We analyzed the Surveillance, Epidemiology, and End Results 18 database to identify patients 20-80 years old who were diagnosed with AA or rectal adenocarcinoma (RA) and underwent abdominal perineal resection between 2004 and 2012. The difference between Kaplan-Meier survival curves was estimated by a log-rank test. A Cox proportional hazard regression model was used to adjust the effects of other covariates on survival in the propensity score-matched cohort, including age, gender, race, marital status, histology, grade of differentiation, tumor size, number of positive lymph nodes, radiotherapy, and chemotherapy.
Compared to patients with RA, patients with AA had a worse CSS after controlling for other covariates (hazard ratio HR, 1.96; 95% confidence interval CI, 1.25-3.07; P<0.01). For AA, the increasing tumor size (2-5 cm: HR, 0.62; 95% CI, 0.29-1.32; P>0.05; >5 cm: HR, 1.01; 95% CI, 0.49-2.07; P>0.05) had no significant influence on survival. The number of positive lymph nodes (1-3: HR, 2.93; 95% CI, 1.55-5.53; P<0.01; ≥4: HR, 4.24; 95% CI, 2.08-8.62; P<0.01) significantly influenced survival.
AA confers a worse prognosis than RA does. The T staging criteria of anal carcinoma, dominated by tumor size, seem to be invalid for AA, while the number of positive lymph nodes is a prognostic factor.
Cardiac differentiation from human pluripotent stem cells provides a unique opportunity to study human heart development in vitro and offers a potential cell source for cardiac regeneration. Compared ...to the large body of studies investigating cardiac maturation and cardiomyocyte subtype-specific induction, molecular events underlying cardiac lineage commitment from pluripotent stem cells at early stage remain poorly characterized.
In order to uncover key molecular events and regulators controlling cardiac lineage commitment from a pluripotent state during differentiation, we performed single-cell RNA-Seq sequencing and obtained high-quality data for 6879 cells collected from 6 stages during cardiac differentiation from human embryonic stem cells and identified multiple cell subpopulations with distinct molecular features. Through constructing developmental trajectory of cardiac differentiation and putative ligand-receptor interactions, we revealed crosstalk between cardiac progenitor cells and endoderm cells, which could potentially provide a cellular microenvironment supporting cardiac lineage commitment at day 5. In addition, computational analyses of single-cell RNA-Seq data unveiled ETS1 (ETS Proto-Oncogene 1) activation as an important downstream event induced by crosstalk between cardiac progenitor cells and endoderm cells. Consistent with the findings from single-cell analysis, chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq) against ETS1 revealed genomic occupancy of ETS1 at cardiac structural genes at day 9 and day 14, whereas ETS1 depletion dramatically compromised cardiac differentiation.
Together, our study not only characterized the molecular features of different cell types and identified ETS1 as a crucial factor induced by cell-cell crosstalk contributing to cardiac lineage commitment from a pluripotent state, but may also have important implications for understanding human heart development at early embryonic stage, as well as directed manipulation of cardiac differentiation in regenerative medicine.
•Responses of insect to grassland degradation are guild-specific.•Sensitivities of each guild to degraded levels are different in grasslands.•Insect guilds and degradation levels should be considered ...to identify good indicator.
Grassland insect diversity in many parts of the world is severely threatened by recent deterioration caused by global change and human activities. Insect species richness and abundance are likely sensitive to grassland degradation because of changes in vegetation structure and microclimates, and yet, our understanding of how diversity of insect community, particularly insect guilds responds to grassland degradation is still limited. Here, we conducted a field experiment to examine the responses of richness and abundance of total insects and different insect guilds along degraded levels (i.e., non-degraded, moderately, and severely degraded site) in meadow steppe at northeastern China. We found that higher species richness of total insects was detected in the moderately degraded sites, and there was no difference in abundance between the three sites. Furthermore, the responses of richness and abundance of each insect guild were significantly different. Hemiptera richness was significantly higher at moderately degraded sites, and Orthoptera richness was higher in severely degraded sites. Abundance of Hemiptera and Orthoptera increased with the increasing levels of degraded grasslands, but the abundance of Hymenoptera and Coleoptera decreased. Moreover, effect size of grassland degradation on Orthoptera abundance was larger from non-degraded to moderately degraded grassland; and larger effect size on Coleoptera abundance from moderately to severely degraded grassland. The different responses of insect guilds to grassland degradation are mainly attributed to changes in food and microclimate availability. In the light of convenience and operability, the finding from the study suggested that the abundance of an insect guild, rather than total insects and insect diversity seem to be a useful ecological indicator when assessing the levels of grassland degradation.
Emerging evidence has revealed significant roles for small nucleolar RNAs (snoRNAs) in tumorigenesis. However, the genetic and pharmacogenomic landscape of snoRNAs has not been characterized. Using ...the genotype and snoRNA expression data from The Cancer Genome Atlas, we characterized the effects of genetic variants on snoRNAs across 29 cancer types and further linked related alleles with patient survival as well as genome-wide association study risk loci. Furthermore, we characterized the impact of snoRNA expression on drug response in patients to facilitate the clinical utility of snoRNAs in cancer. We also developed a user-friendly data resource, GPSno (http://hanlab.uth.edu/GPSno), with multiple modules for researchers to visualize, browse, and download multi-dimensional data. Our study provides a comprehensive genetic and pharmacogenomic landscape of snoRNAs, which will shed light on future clinical considerations for the development of snoRNA-based targeted therapies.
To overcome the poor water solubility of total flavones of Arisaematis rhizoma, microemulsions (MEs) can be used as a carrier for transdermal administration to promote their solubilization and skin ...permeability. Here, we investigated the physical compatibility of MEs in hydrogels and their skin permeation-enhancing effects. Transparency of microemulsion-based hydrogels (MBGs) was analyzed to evaluate ME compatibility with different hydrogel matrices. Transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectroscopy were used to explore the microstructures of MBGs and ME-hydrogel combinations. Uniform and transparent MBG was obtained by adding 1% sodium hyaluronate (SH) to the optimized ME. MBG prepared with SH as a matrix expressed pseudoplastic-fluid and shear-thinning characteristics, making it easy to apply in clinical settings. No new FTIR peak occurred in the MBG compared with ME and hydrogel matrix, indicating a physical combination of ME and the polymer network gel. Nanoscale droplets of ME migrated in the gel network, and the migration capacity and in vitro transdermal permeation flux negatively correlated with SH concentration in the gel system. In conclusion, in MBGs, ME can keep nanoscale droplets migrating in the hydrogel network, thereby enhancing transdermal drug delivery.
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