Self-Powered and Self-Healable Extraocular-Muscle-Like Actuator Based on Dielectric Elastomer Actuator and Triboelectric Nanogenerator.

Although dielectric elastomer actuators (DEAs) are promising artificial muscles for use as visual prostheses in patients with oculomotor nerve palsy (ONP), high driving voltage coupled with vulnerable compliant electrodes limits their safe long-term service. Herein, a self-healable polydimethylsiloxane compliant electrode based on reversible imine bonds and hydrogen bonds is prepared and coated on an acrylic ester film to develop a self-healable DEA (SDEA), followed by actuation with a high-output triboelectric nanogenerator (TENG) to construct a self-powered DEA (TENG-SDEA). Under 135.9 kV mm-1 , the SDEA exhibits an elevated actuated strain of 50.6%, comparable to the actuation under DC power. Moreover, the mechanically damaged TENG-SDEA displays a self-healing efficiency of over 90% for 10 cycles. The TENG ensures the safe using of TENG-SDEAs and an extraocular-muscle-like actuator with oriented motion ability integrated by several TENG-SDEAs is constructed. Additionally, the SDEA is directly used as a flexible capacitive sensor for real-time monitoring of the patient's muscle movement. Accordingly, a medical aid system based on a conjunction of the extraocular-muscle-like actuator and a flexible capacitive sensor is manufactured to help the patients suffering from ONP with physical rehabilitation and treatment.

Escaping but not the inactive X-linked protein complex coding genes may achieve X-chromosome dosage compensation and underlie X chromosome inactivation-related diseases.

X chromosome dosage compensation (XDC) refers to the process by which X-linked genes acquire expression equivalence between two sexes. Ohno proposed that XDC is achieved by two-fold upregulations of X-linked genes in both sexes and by silencing one X chromosome (X chromosome inactivation, XCI) in females. However, genes subject to two-fold upregulations as well as the underlying mechanism remain unclear. It's reported that gene dosage changes may only affect X-linked dosage-sensitive genes, such as protein complex coding genes (PCGs). Our results showed that in human PCGs are more likely to escape XCI and escaping PCGs (EsP) show two-fold higher expression than inactivated PCGs (InP) or other X-linked genes at RNA and protein levels in both sexes, which suggest that EsP may achieve upregulations and XDC. The higher expressions of EsP possibly result from the upregulations of the single active X chromosome (Xa), rather than escaping expressions from the inactive X chromosome (Xi). EsP genes have relatively high expression levels in humans and lower dN/dS ratios, suggesting that they are likely under stronger selection pressure over evolutionary time. Our study also suggests that SP1 transcription factor is significantly enriched in EsP and may be involved in the up-regulations of EsP on the active X. Finally, human EsP genes in this study are enriched in the toll-like receptor pathway, NF-kB pathway, apoptotic pathway, and abnormal mental, developmental and reproductive phenotypes. These findings suggest misregulations of EsP may be involved in autoimmune, reproductive, and neurological diseases, providing insight for the diagnosis and treatment of these diseases.

Chemerin/CMKLR1 ameliorates nonalcoholic steatohepatitis by promoting autophagy and alleviating oxidative stress through the JAK2-STAT3 pathway.

Nonalcoholic steatohepatitis (NASH) is a global public health challenge. Overwhelmed oxidative stress and impaired autophagy play an important role in the progression of NASH. Chemerin is an adipokine that has attracted much attention in inflammation and metabolic diseases. This study aimed to examine the effects of chemerin in NASH and its association with oxidative stress and autophagy. In this study, chemerin was found to significantly ameliorate high-fat diet (HFD) induced NASH, marked by decreased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α), decreased insulin resistance (IR) and leptin resistance (LR), and improved liver lesions. Besides, chemerin prevented enhanced oxidative stress in NASH mice by regulating the antioxidant defense system (MDA downregulation and upregulation of superoxide dismutase (SOD)). Moreover, chemerin contributed to the alleviation of NASH through autophagy activation (p62 downregulation, and upregulation of beclin-1 and LC3). Furthermore, these effects were related to increased phosphorylation of JAK2-STAT3 stimulated by chemerin, which could be inhibited by the CMKLR1 specific inhibitor α-NETA. In conclusion, excess chemerin highly probably ameliorated NASH by alleviating oxidative stress and promoting autophagy, the mechanism responsible for this process was related, at least in part, to the increased phosphorylation of JAK2-STAT3 stimulated by chemerin/CMKLR1. Rh-chemerin may represent promising therapeutic targets in the treatment of NASH.

Breed Differences in Pig Liver Esterase (PLE) between Tongcheng (Chinese Local Breed) and Large White Pigs.

Human carboxylesterases has been proven to be age and race-related and a sound basis of clinical medication. PLE involve in signal transduction and highly catalyze hydrolysis. Therefore, the expression level of PLE most probably exist age and breed difference and lead to significant differences of pharmacology and physiology. Four age groups of Tongcheng (TC) and Large White (LW) pigs were selected to explore PLE breed and age differences, and it was found that PLE mRNA was most abundant in liver in both breeds. In liver, PLE levels and hydrolytic activities increased with age, and PLE levels (except for 3 month) and the hydrolytic activities were higher in LW than in TC across all age groups. Abundance of PLE isoenzymes was obvious different between breeds and among age groups. The most abundant PLE isoenzyme in LW and TC pigs was PLE-A1 (all age groups) and PLE-B9 (three early age groups) or PLE-G3 (adult groups), respectively. 103 new PLE isoenzymes were found, and 55 high-frequency PLE isoenzymes were accordingly classified into seven categories (A-G). The results of this research provide a necessary basis not only for clinical medication of pigs but also for pig breeding purposes.

Enterococcus faecium HDRsEf1 Protects the Intestinal Epithelium and Attenuates ETEC-Induced IL-8 Secretion in Enterocytes.

The probiotic Enterococcus faecium HDRsEf1 (Ef1) has been shown to have positive effects on piglet diarrhoea, but the mechanism has not yet been elucidated. In this study, using the IPEC-J2 cell line to mimic intestinal epithelial cells and enterotoxigenic Escherichia coli (ETEC) K88ac as a representative intestinal pathogen, the mechanism underlying Ef1 protection against an enteropathogen was investigated. The results demonstrated that Ef1 was effective in displacing K88ac from the IPEC-J2 cell layer. Moreover, Ef1 and its cell-free supernatant (S-Ef1) modulate IL-8 released by IPEC-J2 cells. Ef1 and its cell-free supernatant showed the potential to protect enterocytes from an acute inflammatory response. In addition, Ef1 and its cell-free supernatant increased the transepithelial electrical resistance (TEER) of the enterocyte monolayer, thus strengthening the intestinal barrier against ETEC. These results may contribute to the development of therapeutic interventions using Ef1 in intestinal disorders of piglets.

The Role of Porcine Monocyte Derived Dendritic Cells (MoDC) in the Inflammation Storm Caused by Streptococcus suis Serotype 2 Infection.

BACKGROUND: Streptococcus suis is an important swine pathogen and zoonotic agent. Infection with this highly pathogenic strain can cause streptococcal toxic shock-like syndrome (STSLS), characterized by a Th-1 inflammatory cytokine storm, and a high mortality rate. Monocyte derived dendritic cells (MoDCs) are known to stimulate Th-1 cell differentiation, but the role of MoDCs in STSLS remains to be elucidated. METHODOLOGY AND FINDINGS: Porcine CD14-positive monocytes, purified from peripheral blood mononuclear cells (PBMCs), were used to generate MoDCs using granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). Highly pure MoDCs were generated, as proved by their morphology, phenotype analysis, phagocytic ability, and induction of T cells proliferation. The MoDCs were further stimulated by the virulent S. suis serotype 2 (SS2) SC19 strain which triggered a strong release of several pro-inflammatory cytokines, including IL-1ß, IL-8, TNF-α, IFN-γ, and IL-12. Furthermore, the stimulated MoDCs induced CD4+ T cell differentiation towards Th-1 cells in vitro. CONCLUSIONS: The results of this study indicated that the porcine MoDCs stimulated by SS2 could release high levels of Th-1 inflammatory cytokines and induce CD4+ T cell differentiation towards Th-1 cells. Hence, it is likely that porcine MoDCs play an important role in the STSLS caused by SS2.

Identification of key regulators in glycogen utilization in E. coli based on the simulations from a hybrid functional Petri net model.

BACKGROUND: Glycogen and glucose are two sugar sources available during the lag phase of E. coli, but the mechanism that regulates their utilization is still unclear. METHODS: Attempting to unveil the relationship between glucose and glycogen, we propose an integrated hybrid functional Petri net (HFPN) model including glycolysis, PTS, glycogen metabolic pathway, and their internal regulatory systems. RESULTS AND CONCLUSIONS: By comparing known biological results to this model, basic necessary regulatory mechanism for utilizing glucose and glycogen were identified as a feedback circuit in which HPr and EIIAGlc play key roles. Based on this regulatory HFPN model, we discuss the process of glycogen utilization in E. coli in the context of a systematic understanding of carbohydrate metabolism.

Glycogen is the primary source of glucose during the lag phase of E. coli proliferation.

In the studies of Escherichia coli (E. coli), metabolomics analyses have mainly been performed using steady state culture. However, to analyze the dynamic changes in cellular metabolism, we performed a profiling of concentration of metabolites by using batch culture. As a first step, we focused on glucose uptake and the behavior of the first metabolite, G6P (glucose-6-phosphate). A computational formula was derived to express the glucose uptake rate by a single cell from two kinds of experimental data, extracellular glucose concentration and cell growth, being simulated by Cell Illustrator. In addition, average concentration of G6P has been measured by CE-MS. The existence of another carbon source was suggested from the computational result. After careful comparison between cell growth, G6P concentration, and the computationally obtained curve of glucose uptake rate, we predicted the consumption of glycogen in lag phase and its accumulation as an energy source in an E. coli cell for the next proliferation. We confirmed our prediction experimentally. This behavior indicates the importance of glycogen participation in the lag phase for the growth of E. coli. This article is part of a Special Issue entitled: Computational Methods for Protein Interaction and Structural Prediction.