The pathogenesis of noncystic fibrosis bronchiectasis in adults is complex, and the relevant molecular mechanisms remain unclear. In this study, we constructed a panoramic map of bronchiectasis mRNA, explored the potential molecular mechanisms, and identified potential therapeutic targets, thus providing a new clinical perspective for the preventive management of bronchiectasis and its acute exacerbation.
Brief Introduction: This article summarizes a case of successful radiofrequency ablation of atrial tachycardia in a patient with dextrocardia in combination with intracardiac echocardiography, and summarizes the relevant experience.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Beta-Secondary and solvent deuterium kinetic isotope effects have been determined for the steady-state kinetic parameters V/K and V for turnover of a depsipeptide substrate, m-[[(phenylacetyl)glycyl]-oxy]benzoic acid, and of a beta-lactam substrate, penicillanic acid, by three typical class A beta-lactamases and a class C beta-lactamase. The isotope effects on alkaline hydrolysis of these substrates have been used as a frame of reference. The effect of the transition state conformation of the substrates in determining the beta-secondary isotope effects has been explicitly considered. The inverse beta-secondary isotope effects on both V/K and V for the class A enzymes with both substrates indicate transition states where the carbonyl group of the scissile bond has become tetrahedral and therefore reflect typical acyl-transfer transition states. The solvent isotope effects indicate that enzyme deacylation (as reflected in V for the Staphylococcus aureus PC1 beta-lactamase) may be a classical general-base-catalyzed hydrolysis but that there is little proton motion in the enzyme acylation transition state (as revealed by V/K) for the TEM beta-lactamase and Bacillus cereus beta-lactamase I. These results provide kinetic support for the conjecture made on structural grounds that class A beta-lactamases employ an asymmetric double-displacement mechanism. The isotope effects on V/K for the class C beta-lactamase of Enterobacter cloacae P99 suggest an acyl-transfer transition state for the penicillin, although, as for the class A enzymes, without significant proton motion. On the other hand, the V/K transition state for depsipeptide does not seem to involve covalent chemistry. Suggestive of this conclusion are the measured beta-secondary isotope effect of 1,002 +/- 0.012 and the inverse solvent isotope effect. These results provide an example of a significant difference between the kinetics of turnover of a beta-lactam and a depsipeptide by a beta-lactamase. The V transition state for both substrates with the P99 beta-lactamase probably involves acyl-transfer (deacylation) where the conformation of the acyl-enzyme is closely restricted. The conformations of acyl-enzymes of the PC1 and P99 beta-lactamases correlate to the (different) dispositions of general base catalysts at their active sites.
Background Dysregulation of feeding behavior leads to a variety of pathological manifestations ranging from obesity to anorexia. The foraging behavior of animals affected by food deficiency is not fully understood. Methods Home-Cage system was used to monitor the behaviors. Immunohistochemical staining was used to monitor the trend of neuronal activity. Chemogenetic approach was used to modify neuronal activity. Results We described here a unique mouse model of foraging behavior and unveiled that food deprivation significantly increases the general activities of mice with a daily rhythmic pattern, particularly foraging behavior. The increased foraging behavior is potentiated by food cues (mouthfeel, odor, size, and shape) and energy deficit, rather than macronutrient protein, carbohydrate, and fat. Notably, energy deficiency increases nocturnal neuronal activity in paraventricular hypothalamic nucleus (PVH), accompanying a similar change in rhythmic foraging behavior. Activating neuronal activity in PVH enhances the amplitude of foraging behavior in mice. Conversely, inactivating neuronal activity in PVH decreases the amplitude of foraging behavior and impairs the rhythm of foraging behavior. Discussion These results illustrate that energy status and food cues regulate the rhythmic foraging behavior via PVH neuronal activity. Understanding foraging behavior provides insights into the underlying mechanism of eating-related disorders.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Abstract Background As a novel type of the prevalent post-transcriptional modifications, N7-methylguanosine (m7G) modification is essential in the tumorigenesis, progression, and invasion of many cancers, including bladder cancer (BCa). However, the integrated roles of m7G-related lncRNAs in BCa remain undiscovered. This study aims to develop a prognostic model based on the m7G-related lncRNAs and explore its predictive value of the prognosis and anti-cancer treatment sensitivity. Methods We obtained RNA-seq data and corresponding clinicopathological information from the TCGA database and collected m7G-related genes from previous studies and GSEA. Based on LASSO and Cox regression analysis, we developed a m7G prognostic model. The Kaplan–Meier (K-M) survival analysis and ROC curves were performed to evaluate the predictive power of the model. Gene set enrichment analysis (GSEA) was conducted to explore the molecular mechanisms behind apparent discrepancies between the low- and high-risk groups. We also investigated immune cell infiltration, TIDE score, TMB, the sensitivity of common chemotherapy drugs, and the response to immunotherapy between the two risk groups. Finally, we validated the expression levels of these ten m7G-related lncRNAs in BCa cell lines by qRT-PCR. Results We developed a m7G prognostic model (risk score) composed of 10 m7G-related lncRNAs that are significantly associated with the OS of BCa patients. The K-M survival curves revealed that the high-risk group patients had significantly worse OS than those in the low-risk group. The Cox regression analysis confirmed that the risk score was a significant independent prognostic factor for BCa patients. We found that the high-risk group had higher the immune scores and immune cell infiltration. Furthermore, the results of the sensitivity of common anti-BCa drugs showed that the high-risk group was more sensitive to neoadjuvant cisplatin-based chemotherapy and anti-PD1 immunotherapy. Finally, qRT-PCR revealed that AC006058.1, AC073133.2, LINC00677, and LINC01338 were significantly downregulated in BCa cell lines, while the expression levels of AC124312.2 and AL158209.1 were significantly upregulated in BCa cell lines compared with normal cell lines. Conclusion The m7G prognostic model can be applied to accurately predict the prognosis and provide robust directions for clinicians to develop better individual-based and precise treatment strategies for BCa patients.
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