Despite the best treatment, approximately 10% of fractures still face undesirable repair. Recently, many studies have focused on the importance of macrophages in bone repair; however, the cellular mechanisms by which they work are not yet fully understood. In this study, we explored the functions of macrophage G-protein-coupled receptor interacting protein 1 (GIT1) in healing a tibial monocortical defect model. Using GIT1flox/flox Lyz2-Cre (GIT1 CKO) mice, we observed that a GIT1-deficiency in the macrophages led to an exacerbation of interleukin 1β (IL1β) production, more M1-like macrophage infiltration, and impaired intramembranous ossification in vivo. The results of in vitro assays further indicated that the macrophage GIT1 plays a critical role in several cellular processes in response to lipopolysaccharide (LPS), such as anti-oxidation, IL1β production alleviation, and glycolysis control. While GIT1 has been recognized as a scaffold protein, our data clarified that GIT1-mediated extracellular-signal-regulated kinase (ERK) phosphorylation could activate nuclear factor (erythroid-derived 2)-like 2 (NRF2) in macrophages after LPS treatment. Moreover, we demonstrated that macrophage GIT1-activated ERK/NRF2 negatively regulates the 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3), facilitating the decrease of glycolysis. Our findings uncovered a previously unrecognized role of GIT1 in regulating ERK/NRF2 in macrophages to control the inflammatory response, suggesting that GIT1 could be a potential target to improve bone regeneration. This article is protected by copyright. All rights reserved.Dermatofibrosarcoma protuberans (DFSP) is a rare neoplasm derived from fibroblasts and tumorigenic mechanism is mainly defined by the formation of a fusion gene between the α-helix domain of the collagen type 1 (COL1A1) gene and the platelet-derived growth factor-β (PDGFB) gene. We investigated the fusion site of COL1A1/PDGFB gene and its relationship with clinical findings in 30 patients with DFSP treated at our hospital. COL1A1/ PDGFB fusion was detected in 83% of DFSP patients. The breakpoint in the PDGFB gene was before exon 2 in all patients, while that in the COL1A1 gene was after exon 25 in five patients, exon 32 in four patients, exon 39 and 46 in two patients, and exons 7, 8, 14, 28, 29, 31, 33, 35, 37, 39, 43, 47 in one patient. In our cohort study, there was no correlation between the COL1A1 breakpoint and clinical findings. To the best of our knowledge, no report to date has described a case of DFSP with exon 28 in the COL1A1 gene.Background Limited data are available about the natural history of chronic spontaneous urticaria in children (CSU), and management guidelines are mostly extrapolated from evidence in adults. Methods The objective of this study was toevaluate the natural history of CSU in children and to identify predictors for remission. We performed an observational study, including patients aged 0 to 18 years with CSU diagnosed from January 2006 to July 2016. Disease activity was evaluated by the Urticaria Activity Score (UAS) and the Urticaria Activity Score 7 (UAS7); type of treatment and number of daily administrations were recorded. Results Eighty patients were included in the study. At 1, 3, and 5 years from the onset of symptoms, 29%, 55%, and 72% of the patients with CSU were in remission, respectively. A higher hazard ratio of non-remission both at 3 years (HR=1.7, 95%CI=1.2-2.4, p-value 0.004) and at 5 years (HR=1.7, 95%CI=1.2-2.7, p-value 0.001), was related to higher severity of CSU at the baseline. Remission ratdisease, CU often lasts for years. However, data on the natural historyof CU are lacking, particularly in children, and frequently are not specific to the different CU subtypes.Finally, management recommendations are mostly extrapolated from evidence in adults.An exponential diffusion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prompted Italian Institutions to take extraordinary healthcare restrictive measures since 8th March 2020, declaring quarantine for COVID-19 (1).Background Bronchiolitis is the leading cause of infant hospitalizations in the United States. Growing evidence supports the heterogeneity of bronchiolitis. However, little is known about the interrelationships between major respiratory viruses (and their species), host systemic metabolism, and disease pathobiology. Methods In an ongoing multicenter prospective cohort study, we profiled the serum metabolome in 113 infants (63 RSV-only, 21 RV-A, and 29 RV-C) hospitalized with bronchiolitis. We identified serum metabolites that are most discriminatory in the RSV-RV-A and RSV-RV-C comparisons using sparse partial least squares discriminant analysis. We then investigated the association between discriminatory metabolites with acute and chronic outcomes. Results In 113 infants with bronchiolitis, we measured 639 metabolites. Serum metabolomic profiles differed in both comparisons (Ppermutation less then 0.05). In the RSV-RV-A comparison, we identified 30 discriminatory metabolites, predominantly in lipid metabolism pathways (eg, sphingolipids and carnitines). In multivariable models, these metabolites were significantly associated with the risk of clinical outcomes (eg, tricosanoyl sphingomyelin, OR for recurrent wheezing at age of 3 years = 1.50; 95% CI 1.05-2.15). JAK inhibitor In the RSV-RV-C comparison, the discriminatory metabolites were also primarily involved in lipid metabolism (eg, glycerophosphocholines [GPCs], 12,13-diHome). These metabolites were also significantly associated with the risk of outcomes (eg, 1-stearoyl-2-linoleoyl-GPC, OR for positive pressure ventilation use during hospitalization = 0.47; 95% CI 0.28-0.78). Conclusion Respiratory viruses and their species had distinct serum metabolomic signatures that are associated with differential risks of acute and chronic morbidities of bronchiolitis. Our findings advance research into the complex interrelations between viruses, host systemic response, and bronchiolitis pathobiology.One of the current issues with thyroid tumor is early diagnosis as it makes the higher possibility of curing. This research was focused to detect and quantify the level of specific target sequence complementation of miR-222 with capture DNA sequence on interdigitated electrode (IDE) sensor. The aluminum electrode with the gap and finger sizes of 10 µm was fabricated on silicon wafer, further the surface was amine-functionalized for accommodating carboxylated-DNA probe. With DNA-target RNA complementation, the detection limit was attained to be 1 fM as estimated by a linear regression analysis [y = 1.5325x - 2.1171 R² = 0.9065] and the sensitivity was at the similar level. Current responses were higher by increasing the target RNA sequence concentrations. Control experiments with mismatched/noncomplementary sequences were failed to complement the capture DNA sequence immobilized on IDE, indicating the specific target validation. This research helps diagnosing and identifying the progression with thyroid tumor and miRNA being a potential "marker" in atypia diagnosis.