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n ALK3 or MMP-13 expression between the control and degenerative disks (p&gt;.05). Stratifying the degenerative specimens according to their vertebral level showed no significant differences in expression levels between the lumbar and cervical disks (p&gt;.05).<br />BMP-2 and pSMAD1/5/8 signaling activity was significantly upregulated in the human degenerative specimens, while ALK3 and MMP-13 expression were not significantly changed. The expression levels of BMP-2 and pSMAD1/5/8 correlate positively with the degree of disk degeneration measured according to the Pfirrmann MRI grading system.<br />BMP-SMAD signaling represents a promising therapeutic target to restore IVD composition and function in the setting of disk degeneration.<br />BMP-SMAD signaling represents a promising therapeutic target to restore IVD composition and function in the setting of disk degeneration.<br />The objective of this study was to measure the incidence of arterial oxygen desaturation during rapid sequence induction intubation in children following apnoeic oxygenation via transnasal humidified rapid-insufflation ventilatory exchange (THRIVE).<br />In this prospective observational study, arterial desaturation &lt; 95% SaO<br />before intubation was recorded following apnoeic RSI combining an intravenous hypnotic agent, suxamethonium and THRIVE (used during the apnoeic period). The incidence of desaturation was calculated in the whole cohort and according to patients' age (older or younger than 1 year).<br />Complete data were collected for 79 patients, 1 day to 15 years of age. Nine patients (11.4%) exhibited arterial desaturation before tracheal intubation and received active facemask ventilation. Patients exhibiting desaturation were more likely to be less than 1 year of age (9/9, (100%) versus 37/70, (52.9%); P = 0.005), to be reported as difficult intubations (5/9, (55.6%) versus 1/70, (1.4%), p &lt; 0.001), and to have regurgitation at induction (2/9, (22.2%) versus 0/70, (0%), p = 0.01).<br />Results of the current study indicated that almost 91% of RSI can be performed without desaturation when THRIVE is used. A comparative controlled study is required to confirm these findings. Specific situations and conditions limiting the efficacy of THRIVE during RSI should also be investigated.<br />Results of the current study indicated that almost 91% of RSI can be performed without desaturation when THRIVE is used. A comparative controlled study is required to confirm these findings. Specific situations and conditions limiting the efficacy of THRIVE during RSI should also be investigated.Hypertrophic growth of cardiomyocytes is one of the major compensatory responses in the heart after physiological or pathological stimulation. Protein synthesis enhancement, which is mediated by the translation of messenger RNAs, is one of the main features of cardiomyocyte hypertrophy. Although the transcriptome shift caused by cardiac hypertrophy induced by different stimuli has been extensively investigated, translatome dynamics in this cellular process has been less studied. Here, we generated a nucleotide-resolution translatome as well as transcriptome data from isolated primary cardiomyocytes undergoing hypertrophy. More than 10,000 open reading frames (ORFs) were detected from the deep sequencing of ribosome-protected fragments (Ribo-seq), which orchestrated the shift of the translatome in hypertrophied cardiomyocytes. Our data suggest that rather than increase the translational rate of ribosomes, the increased efficiency of protein synthesis in cardiomyocyte hypertrophy was attributable to an increased quantity of ribosomes. In addition, more than 100 uncharacterized short ORFs (sORFs) were detected in long noncoding RNA genes from Ribo-seq with potential of micropeptide coding. In a random test of 15 candidates, the coding potential of 11 sORFs was experimentally supported. Three micropeptides were identified to regulate cardiomyocyte hypertrophy by modulating the activities of oxidative phosphorylation, the calcium signaling pathway, and the mitogen-activated protein kinase (MAPK) pathway. Our study provides a genome-wide overview of the translational controls behind cardiomyocyte hypertrophy and demonstrates an unrecognized role of micropeptides in cardiomyocyte biology.mRNA vaccines induce potent immune responses in preclinical models and clinical studies. Adjuvants are used to stimulate specific components of the immune system to increase immunogenicity of vaccines. We utilized a constitutively active mutation (V155M) of the stimulator of interferon (IFN) genes (STING), which had been described in a patient with STING-associated vasculopathy with onset in infancy (SAVI), to act as a genetic adjuvant for use with our lipid nanoparticle (LNP)-encapsulated mRNA vaccines. mRNA-encoded constitutively active STINGV155M was most effective at maximizing CD8+ T cell responses at an antigen/adjuvant mass ratio of 51. STINGV155M appears to enhance development of antigen-specific T cells by activating type I IFN responses via the nuclear factor κB (NF-κB) and IFN-stimulated response element (ISRE) pathways. [https://www.selleckchem.com/products/SU11274.html SU11274] mRNA-encoded STINGV155M increased the efficacy of mRNA vaccines encoding the E6 and E7 oncoproteins of human papillomavirus (HPV), leading to reduced HPV+ TC-1 tumor growth and prolonged survival in vaccinated mice. This proof-of-concept study demonstrated the utility of an mRNA-encoded genetic adjuvant.An emerging view regarding cancer metabolism is that it is heterogeneous and context-specific, but it remains to be elucidated in breast cancers. In this study, we characterized the energy-related metabolic features of breast cancers through integrative analyses of multiple datasets with genomics, transcriptomics, metabolomics, and single-cell transcriptome profiling. Energy-related metabolic signatures were used to stratify breast tumors into two prognostic clusters cluster 1 exhibits high glycolytic activity and decreased survival rate, and the signatures of cluster 2 are enriched in fatty acid oxidation and glutaminolysis. The intertumoral metabolic heterogeneity was reflected by the clustering among three independent large cohorts, and the complexity was further verified at the metabolite level. In addition, we found that the metabolic status of malignant cells rather than that of nonmalignant cells is the major contributor at the single-cell resolution, and its interactions with factors derived from the tumor microenvironment are unanticipated.