TxNIP (Thioredoxin-interacting protein) is considered as a potential drug target for type 2 diabetes. Although TxNIP expression is correlated with hyperglycemia and glucotoxicity in pancreatic β cells, its regulation in liver cells has been less investigated. In the current study, we aim at providing a better understanding of Txnip regulation in hepatocytes in response to physiological stimuli and in the context of hyperglycemia in db/db mice. We focused on regulatory pathways governed by ChREBP (Carbohydrate Responsive Element Binding Protein) and FoxO1 (Forkhead box protein O1), transcription factors that play central roles in mediating the effects of glucose and fasting on gene expression, respectively. Studies using genetically modified mice reveal that hepatic TxNIP is up-regulated by both ChREBP and FoxO1 in liver cells and that its expression strongly correlates with fasting, suggesting a major role for this protein in the physiological adaptation to nutrient restriction.Systemic metabolic homeostasis is regulated by inter-organ metabolic cycles involving multiple organs. Obesity impairs inter-organ metabolic cycles, resulting in metabolic diseases. The systemic landscape of dysregulated inter-organ metabolic cycles in obesity has yet to be explored. Here, we measured the transcriptome, proteome, and metabolome in the liver and skeletal muscle and the metabolome in blood of fasted wild-type and leptin-deficient obese (ob/ob) mice, identifying components with differential abundance and differential regulation in ob/ob mice. By constructing and evaluating the trans-omic network controlling the differences in metabolic reactions between fasted wild-type and ob/ob mice, we provided potential mechanisms of the obesity-associated dysfunctions of metabolic cycles between liver and skeletal muscle involving glucose-alanine, glucose-lactate, and ketone bodies. Our study revealed obesity-associated systemic pathological mechanisms of dysfunction of inter-organ metabolic cycles.Aminoacyl-tRNA synthetases (AARS) participate in decoding the genome by catalyzing conjugation of amino acids to their cognate tRNAs. During evolution, biochemical and environmental conditions markedly influenced the sequence and structure of the 20 AARSs, revealing adaptations dictating canonical and orthogonal activities. Here, we investigate the function of the appended Zn2+-binding domain (ZBD) in the bifunctional AARS, glutamyl-prolyl-tRNA synthetase (GluProRS). We developed GluProRS mutant mice by CRISPR-Cas9 with a deletion of 29 C-terminal amino acids, including two of four Zn2+-coordinating cysteines. Homozygous ZBD mutant mice die before embryonic day 12.5, but heterozygous mice are healthy.  https://www.selleckchem.com/products/AP24534.html  ZBD disruption profoundly reduces GluProRS canonical function by dual mechanisms it induces rapid proteasomal degradation of the protein and inhibits ProRS aminoacylation activity, likely by sub-optimal positioning of ATP in the spatially adjacent catalytic domain. Collectively, our studies reveal the ZBD as a critical determinant of ProRS activity and GluProRS stability in vitro and in vivo.Autosomal recessive mutations in G6PC3 cause isolated and syndromic congenital neutropenia which includes congenital heart disease and atypical inflammatory bowel disease (IBD). In a highly consanguineous pedigree with novel mutations in G6PC3 and MPL, we performed comprehensive multi-omics analyses. Structural analysis of variant G6PC3 and MPL proteins suggests a damaging effect. A distinct molecular cytokine profile (cytokinome) in the affected proband with IBD was detected. Liquid chromatography-mass spectrometry-based proteomics analysis of the G6PC3-deficient plasma samples identified 460 distinct proteins including 75 upregulated and 73 downregulated proteins. Specifically, the transcription factor GATA4 and LST1 were downregulated while platelet factor 4 (PF4) was upregulated. GATA4 and PF4 have been linked to congenital heart disease and IBD respectively, while LST1 may have perturbed a variety of essential cell functions as it is required for normal cell-cell communication. Together, these studies provide potentially novel insights into the pathogenesis of syndromic congenital G6PC3 deficiency.In this paper, we report a finding that substrate affects the adhesion of charged super-repellent surfaces. Water droplet impacting on a super-repellent surface produces surface charge, whose expression depends on the substrate. The charged super-repellent surface is sticky to droplets for a suspended substrate made of dielectric materials, while it has low adhesion for a conducting substrate or stage attached at the bottom because of electrostatic induction. Theoretical analysis and simulation are conducted to elucidate the mechanism of substrate effect on surface adhesion. Finally, we develop a new approach to reversibly tune the adhesion of super-repellent surface by combining surface-charge-induced adhesion increase and electrostatic-induction-regulated express of net surface charge. As a proof-of-concept experiment, we demonstrate that droplet sorting and manipulations can be realized by using this controllable surface adhesion tuning approach, which has potential applications in advanced lab-on-a-drop platform.In contrast to the conventional pulsatile neuromodulation that excites neurons, galvanic or direct current stimulation can excite, inhibit, or sensitize neurons. The vestibular system presents an excellent system for studying galvanic neural interface due to the spontaneously firing afferent activity that needs to be either suppressed or excited to convey head motion sensation. We determine the cellular mechanisms underlying the beneficial properties of galvanic vestibular stimulation (GVS) by creating a computational model of the vestibular end organ that elicits all experimentally observed response characteristics to GVS simultaneously. When GVS was modeled to affect the axon alone, the complete experimental data could not be replicated. We found that if GVS affects hair cell vesicle release and axonal excitability simultaneously, our modeling results matched all experimental observations. We conclude that contrary to the conventional belief that GVS affects only axons, the hair cells are likely also affected by this stimulation paradigm.