Closed-loop artificial pancreas systems have recently been proposed as a solution for treating stage I diabetes by reproducing the function of the pancreas. However, there are many unresolved issues associated with their development, including monitoring and controlling oxygen, immune responses, and the optimization of glucose, all of which need to be monitored and controlled to produce an efficient and viable artificial organ that can become integrated in the patient and maintain homeostasis. This research focused on monitoring the oxygen concentration, specifically achieving this kinetically as the oxygen gradient in an artificial pancreas made of alginate spheres containing islet cells. Functional nanoparticles (NPs) for measuring the oxygen gradient in different hydrogel cellular environments using fluorescence-based (F) microscopy were developed and tested. By the ester bond, a linker Pluronic F127 was conjugated with a carboxylic acid-modified polystyrene NP (510 nm). A hydrophilic/hydrophobic interaction between the commercially available oxygen-sensitive fluorophore and F127 results in fluorescence-based nano-oxygen particles (FNOPs). The in-house synthesized FNOP was calibrated inside electrosprayed alginate-filled hydrogels and demonstrated a good broad dynamic range (2.73-22.23) mg/L as well as a resolution of -0.01 mg/L with an accuracy of ±4%. The calibrated FNOP was utilized for continuous measuring of the oxygen concentration gradient for cell lines RIN-m5F/HeLa for more than 5 days in alginate hydrogel spheres in vitro.

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The aim of the present study was to investigate the effectiveness of electroacupuncture (ea) on ovariectomy-induced osteoporotic rats to elucidate potential mechanisms by which ea regulates acetylation of histones in caput femoris. a total of 40 female Sprague-dawley rats were randomly allocated into four groups: Sham operation, ovariectomy-induced osteoporosis (oVX), ea and 17β-estradiol (e2) treatments. after 8 weeks of intervention, the trabecular morphology of each group was measured by micro-computed tomography. Biomarkers of bone metabolism in serum were detected. The protein expression of histone deacetylase 2 (Hdac2), histone H3, ac-histone H3 and downstream cytokines involved in osteoblast and osteoclast differentiation were detected. The results showed that ea and e2 both prevented bone loss and improved trabecular morphology in oVX rats. ea was found to suppress the protein expression of Hdac2 and promoted the acetylation of histone H3 compared with the oVX model group. The results indicated that ea promoted the differentiation of osteoblasts, and suppressed that of osteoclasts, thereby improving the trabecular morphology. e2 was shown to regulate the expression of runt-related transcription factor 2 and receptor activator of nuclear factor-κB ligand without modulating the expression of Hdac2, and therefore diverged mechanistically from ea. overall, the results of the present study suggested that the mechanisms through which ea improved bone mineral density and trabecular morphology may involve the modulation of histone H3 acetylation and regulation of osteoblast and osteoclast differentiation.

ObjectiveCentral glucagon-like peptide-1 (GLP-1) is a target in treating obesity due to its effect on suppressing appetite, but the possible downstream key genes that GLP-1 regulated have not been studied in depth. This study intends to screen out the downstream feeding regulation genes of central GLP-1 neurons through bioinformatics analysis and verify them by chemical genetics, which may provide insights for future research.Materials and methodsGSE135862 genetic expression profiles were extracted from the Gene Expression Omnibus (GEO) database. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were carried out. STRING database and Cytoscape software were used to map the protein-protein interaction (PPI) network of the differentially expressed genes (DEGs). After bioinformatics analysis, we applied chemogenetic methods to modulate the activities of GLP-1 neurons in the nucleus tractus solitarius (NTS) and observed the alterations of screened differential genes and their protein expressions in the hypothalamus under different excitatory conditions of GLP-1 neurons.ResultsA total of 49 DEGs were discovered, including 38 downregulated genes and 11 upregulated genes. The two genes with the highest expression scores were biglycan (Bgn) and mitogen-activated protein kinase activated protein kinase 3 (Mapkapk3). The results of GO analysis showed that there were 10 molecular functions of differential genes. Differential genes were mainly localized in seven regions around the cells, and enriched in 10 biology processes. The results of the KEGG signaling pathway enrichment analysis showed that differential genes played an important role in seven pathways. The top 15 genes selected according to the Cytoscape software included Bgn and Mapkapk3. Chemogenetic activation of GLP-1 in NTS induced a decrease in food intake and body mass, while chemogenetic inhibition induced the opposite effect. The gene and protein expression of GLP-1 were upregulated in NTS when activated by chemogenetics. In addition, the expression of Bgn was upregulated and that of Mapkapk3 was downregulated in the hypothalamus.ConclusionOur data showed that GLP-1 could modulate the protein expression of Bgn and Mapkapk3. Our findings elucidated the regulatory network in GLP-1 to obesity and might provide a novel diagnostic and therapeutic target for obesity.

Preterm delivery is greatly associated with perinatal mortality and morbidity, while there is no objective way to identify high-risk newborns currently. This study aimed at discovering the risk factor for Apgar score less than 7 at 1 minute of preterm neonates born with vaginal delivery. A retrospective study was performed in single pregnancy women with a vaginal delivery before 37 weeks of gestation. All the preterm infants were categorized into three types: very preterm birth (28 to 32 weeks), moderate preterm birth (32 to 34 weeks) and late preterm birth (34 to 37 weeks). Risk factors were identified through logistic regression analysis in every category of newborns mentioned above. And the receiver operating characteristic analysis was used in continuous variables to determine the best threshold of the outcome. On the basis of the selected factors, the predicting models are created and its prognosticating ability is compared by the area under the curve. A nomogram was established for the proved best model. A total of 981 cases were investigated, of whom 55 were found with 1 min Apgar scores less than 7. The nomogram was set for the predicting model with larger area under the receiver operating characteristic curve, of which is 0.742(95% confidence interval = 0.670–0.805) in very preterm birth, with the variables of first and second labor stage(> = 1.6 hours), birthweight and MgSO4(magnesium sulfate), and is 0.807(95% confidence interval = 0.776–0.837) in late preterm birth, with the variables of second labor stage(> = 1.23 hours), birthweight, a history of previous cesarean delivery, fetal distress and placental abruption. The combination of first and second labor stage, newborn weight and MgSO4 use can predict 74.2% of 1 minute Apgar score < 7 in very preterm neonates. And 80.7% high-risk infants can be identified when second labor stage, newborn weight, VBAC (vaginal birth after cesarean) and the occur of placental abruption and fetal distress were combined in the predicting model for late preterm birth. These predicting models would bring out great assistance towards obstetricians and reduce unnecessary adverse fetal outcomes.