BMPRIA mediated signaling is essential for temporomandibular joint development in mice

The central importance of BMP signaling in the development and homeostasis of synovial joint of appendicular skeleton has been well documented, but its role in the development of temporomandibular joint (TMJ), also classified as a synovial joint, remains completely unknown. In this study, we investigated the function of BMPRIA mediated signaling in TMJ development in mice by transgenic loss-of- and gain-of-function approaches. We found that BMPRIA is expressed in the cranial neural crest (CNC)-derived developing condyle and glenoid fossa, major components of TMJ, as well as the interzone mesenchymal cells. Wnt1-Cre mediated tissue specific inactivation of BmprIa in CNC lineage led to defective TMJ development, including failure of articular disc separation from a hypoplastic condyle, persistence of interzone cells, and failed formation of a functional fibrocartilage layer on the articular surface of the glenoid fossa and condyle, which could be at least partially attributed to the down-regulation of Ihh in the developing condyle and inhibition of apoptosis in the interzone. On the other hand, augmented BMPRIA signaling by Wnt1-Cre driven expression of a constitutively active form of BmprIa (caBmprIa) inhibited osteogenesis of the glenoid fossa and converted the condylar primordium from secondary cartilage to primary cartilage associated with ectopic activation of Smad-dependent pathway but inhibition of JNK pathway, leading to TMJ agenesis. Our results present unambiguous evidence for an essential role of finely tuned BMPRIA mediated signaling in TMJ development

Perioperative cerebral blood flow measured by arterial spin labeling with different postlabeling delay in patients undergoing carotid endarterectomy: a comparison study with CT perfusion

BackgroundArterial spin labeling (ASL) is a non-invasive technique for measuring cerebral perfusion. Its accuracy is affected by the arterial transit time. This study aimed to (1) evaluate the accuracy of ASL in measuring the cerebral perfusion of patients who underwent carotid endarterectomy (CEA) and (2) determine a better postlabeling delay (PLD) for pre- and postoperative perfusion imaging between 1.5 and 2.0 s.MethodsA total of 24 patients scheduled for CEA due to severe carotid stenosis were included in this study. All patients underwent ASL with two PLDs (1.5 and 2.0 s) and computed tomography perfusion (CTP) before and after surgery. Cerebral blood flow (CBF) values were measured on the registered CBF images of ASL and CTP. The correlation in measuring perioperative relative CBF (rCBF) and difference ratio of CBF (DRCBF) between ASL with PLD of 1.5 s (ASL1.5) or 2.0 s (ASL2.0) and CTP were also determined.ResultsThere were no significant statistical differences in preoperative rCBF measurements between ASL1.5 and CTP (p = 0.17) and between ASL2.0 and CTP (p = 0.42). Similarly, no significant differences were found in rCBF between ASL1.5 and CTP (p = 0.59) and between ASL2.0 and CTP (p = 0.93) after CEA. The DRCBF measured by CTP was found to be marginally lower than that measured by ASL2.0_1.5 (p = 0.06) and significantly lower than that measured by ASL1.5_1.5 (p = 0.01), ASL2.0_2.0 (p = 0.03), and ASL1.5_2.0 (p = 0.007). There was a strong correlation in measuring perioperative rCBF and DRCBF between ASL and CTP (r = 0.67–0.85, p < 0.001). Using CTP as the reference standard, smaller bias can be achieved in measuring rCBF by ASL2.0 (−0.02) than ASL1.5 (−0.07) before CEA. In addition, the same bias (0.03) was obtained by ASL2.0 and ASL1.5 after CEA. The bias of ASL2.0_2.0 (0.31) and ASL2.0_1.5 (0.32) on DRCBF measurement was similar, and both were smaller than that of ASL1.5_1.5 (0.60) and ASL1.5_2.0 (0.60).ConclusionStrong correlation can be found in assessing perioperative cerebral perfusion between ASL and CTP. During perioperative ASL imaging, the PLD of 2.0 s is better than 1.5 s for preoperative scan, and both 1.5 and 2.0 s are suitable for postoperative scan

Variations of brain functional connectivity in alcohol-preferring and non-preferring rats with consecutive alcohol training or acute alcohol administration

Alcohol addiction is regarded as a series of dynamic changes to neural circuitries. A comparison of the global network during different stages of alcohol addiction could provide an efficient way to understand the neurobiological basis of addiction. Two animal models (P-rats screened from an alcohol preference family, and NP-rats screened from an alcohol non-preference family) were trained for alcohol preference with a two-bottle free choice method for 4 weeks. To examine the changes in the neural response to alcohol during the development of alcohol preference and acute stimulation, different trials were studied with resting-state fMRI methods during different periods of alcohol preference. The correlation coefficients of 28 regions in the whole brain were calculated, and the results were compared for alcohol preference related to the genetic background/training association. The variety of coherence patterns was highly related to the state and development of alcohol preference. We observed significant special brain connectivity changes during alcohol preference in P-rats. The comparison between the P- and NP-rats highlighted the role of genetic background in alcohol preference. The results of this study support the alterations of the neural network connection during the formation of alcohol preference and confirm that alcohol preference is highly related to the genetic background. This study could provide an effective approach for understanding the neurobiological basis of alcohol addiction

Altered FGF Signaling Pathways Impair Cell Proliferation and Elevation of Palate Shelves

In palatogenesis, palatal shelves are patterned along the mediolateral axis as well as the anteroposterior axis before the onset of palatal fusion. Fgf10 specifically expressed in lateral mesenchyme of palate maintains Shh transcription in lateral epithelium, while Fgf7 activated in medial mesenchyme by Dlx5, suppressed the expansion of Shh expression to medial epithelium. How FGF signaling pathways regulate the cell behaviors of developing palate remains elusive. In our study, we found that when Fgf8 is ectopically expressed in the embryonic palatal mesenchyme, the elevation of palatal shelves is impaired and the posterior palatal shelves are enlarged, especially in the medial side. The palatal deformity results from the drastic increase of cell proliferation in posterior mesenchyme and decrease of cell proliferation in epithelium. The expression of mesenchymal Fgf10 and epithelial Shh in the lateral palate, as well as the Dlx5 and Fgf7 transcription in the medial mesenchyme are all interrupted, indicating that the epithelial-mesenchymal interactions during palatogenesis are disrupted by the ectopic activation of mesenchymal Fgf8. Besides the altered Fgf7, Fgf10, Dlx5 and Shh expression pattern, the reduced Osr2 expression domain in the lateral mesenchyme also suggests an impaired mediolateral patterning of posterior palate. Moreover, the ectopic Fgf8 expression up-regulates pJak1 throughout the palatal mesenchyme and pErk in the medial mesenchyme, but down-regulates pJak2 in the epithelium, suggesting that during normal palatogenesis, the medial mesenchymal cell proliferation is stimulated by FGF/Erk pathway, while the epithelial cell proliferation is maintained through FGF/Jak2 pathway

A reactive oxygen species–related signature to predict prognosis and aid immunotherapy in clear cell renal cell carcinoma

BackgroundClear cell renal cell carcinoma (ccRCC) is a malignant disease containing tumor-infiltrating lymphocytes. Reactive oxygen species (ROS) are present in the tumor microenvironment and are strongly associated with cancer development. Nevertheless, the role of ROS-related genes in ccRCC remains unclear.MethodsWe describe the expression patterns of ROS-related genes in ccRCC from The Cancer Genome Atlas and their alterations in genetics and transcription. An ROS-related gene signature was constructed and verified in three datasets and immunohistochemical staining (IHC) analysis. The immune characteristics of the two risk groups divided by the signature were clarified. The sensitivity to immunotherapy and targeted therapy was investigated.ResultsOur signature was constructed on the basis of glutamate-cysteine ligase modifier subunit (GCLM), interaction protein for cytohesin exchange factors 1 (ICEF1), methionine sulfoxide reductase A (MsrA), and strawberry notch homolog 2 (SBNO2) genes. More importantly, protein expression levels of GCLM, MsrA, and SBNO2 were detected by IHC in our own ccRCC samples. The high-risk group of patients with ccRCC suffered lower overall survival rates. As an independent predictor of prognosis, our signature exhibited a strong association with clinicopathological features. An accurate nomogram for improving the clinical applicability of our signature was constructed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the signature was closely related to immune response, immune activation, and immune pathways. The comprehensive results revealed that the high-risk group was associated with high infiltration of regulatory T cells and CD8+ T cells and more benefited from targeted therapy. In addition, immunotherapy had better therapeutic effects in the high-risk group.ConclusionOur signature paved the way for assessing prognosis and developing more effective strategies of immunotherapy and targeted therapy in ccRCC

Myocardial tissue and metabolism characterization in men with alcohol consumption by cardiovascular magnetic resonance and 11C-acetate PET/CT

Background: Chronic alcohol consumption initially leads to asymptomatic left ventricular dysfunction, but can result in myocardial impairment and heart failure if ongoing. This study sought to characterize myocardial tissues and oxidative metabolism in asymptomatic subjects with chronic alcohol consumption by quantitative cardiovascular magnetic resonance (CMR) and 11C-acetate positron emission tomography (PET)/computed tomography (CT). Methods: Thirty-four male subjects (48.8 +/- 9.1 years) with alcohol consumption > 28 g/day for > 10 years and 35 age-matched healthy male subjects (49.5 +/- 9.7 years) underwent CMR and 11C-acetate PET/CT. Native and post T1 values and extracellular volume (ECV) from CMR and Kmono and K1 from PET imaging were measured. Quantitative measurements by CMR and PET imaging were compared between subjects with moderate to heavy alcohol consumption and healthy controls, and their correlations were also analyzed. Results: Compared to healthy controls, subjects with alcohol consumption showed significantly shorter native T1 (1133 +/- 65 ms vs. 1186 +/- 31 ms, p 0.05). In contrast, subjects with heavy alcohol consumption showed significantly lower Kmono values compared to those with moderate alcohol consumption (52.9 +/- 12.1 min(- 1) x 10(- 3) vs. 63.7 +/- 9.2 min(- 1) x 10(- 3), p = 0.012). Strong and moderate correlations were found between K1 and ECV in healthy controls (r = 0.689, p = 0.013) and subjects with moderate alcohol consumption (r = 0.518, p = 0.048), respectively. Conclusion: Asymptomatic men with heavy alcohol consumption have detectable structural and metabolic changes in myocardium on CMR and 11C-acetate PET/CT. Compared with quantitative CMR, 11C-acetate PET/CT imaging may be more sensitive for detecting differences in myocardial damage among subjects with moderate to heavy alcohol consumption.</div

Hydrothermal Preparation of Ag/Ag1.69Sb2.27O6.25 Sesame-Hollow-Ball-Type Nanocomposites: The Formation Mechanism of Metallic Ag in the Ag-H2O System at 400 K

Ag/Ag1.69Sb2.27O6.25 sesame-hollow-ball-type nanocomposites were prepared via a facile one-step hydrothermal method at 400 K. Power X-ray diffraction analysis shows that all diffraction peaks were well consistent with JCPDS card no: 89-6552 of Ag1.69Sb2.27O6.25. Scanning electron microscopy and high-resolution transmission electron microscopy images of the composites indicate that some smaller metallic Ag particles with size∼18.3 nm uniformly dense on the surface of Ag1.69Sb2.27O6.25 hollow nanospheres with a mean size of about 170 nm, producing Ag/Ag1.69Sb2.27O6.25 hollow-sesame-ball nanocomposites. The surface chemical state of Ag/Ag1.69Sb2.27O6.25 is investigated by XPS, and all peaks of Ag 3d, O 1s, and Sb 3d show their different chemical states. The BET surface area of the sample is 7.268 m2/g, and the pore sizes of nanocomposites are more than 5 nm. The light absorption property of as-prepared materials is studied by UV-vis/DRS, and the adsorption band is located at 445 nm, and the estimated energy band gap (Eg) is 2.55 eV. The calculated partial φ-pH diagrams in the Ag-H2O system at 400 K predict that the Ag+ ion can react with H2 to form metallic Ag

Simulation of electro-slag re-melting process of 120 t large ingot for nuclear power station and its application

Further research on metallic materials for the super critical rotator and the main pipe line of a nuclear power station is very important for developing the nuclear power industry. In this study, the mathematical model for 120 t large ingot was established, and the computer program ESR3D was developed to simulate the whole electro-slag re-melting (ESR) process. This includes the electrode melting, metallic droplet falling, metal pool forming, metal pool and slag pool rising and moving, installation of top crystallizer, ingot solidifying, etc. The simulated average melting rate of the electrode was in good agreement with that in practical production. The optimized parameters were used to produce 80-120 t large ingots, and the quality of the ingots satisfied the specifications of nuclear power and the super critical generating unit