Objective To evaluate the diagnostic value of endobronchial ultrasound-guided transbronchial needle biopsy (EBUS-TBNA) in intrathoracic tuberculosis(TB).Methods We retrospectively analyzed patients underwent EBUS-TBNA with a final diagnosis of intrathoracic TB at Shanghai Chest Hospital from October 2009 to March 2013 and observed that the diagnostic efficacy by pathology and microbiology and safety of EBUS-TBNA for intrathoracic TB.Results 75 patients were diagnosed with pulmonary TB or intrathoracic tuberculous lymphadenitis,and accuracy was 80％ (60/75) by EBUS TBNA.A total of 60 patients had pathology,acid-fast bacilli(AFB) staining and mycobacterial culture test results,of whom 52 (86.67％)were diagnosed.Pathological findings were consistent with TB in 77.33％ patients (58/75),in 20.31％ (13/64) the smear were positive for AFB and in 46.67％ (28/60) were positive for cuhure.One hundred and twenty-nine mediastinal or hilar lymph nodes and 10 intrapulmonary lesions were biopsied in 75 patients,the average target number of per patient were 1.85.Pathological findings were consistent with TB in 66.19％ samples(92/139),in 13.91％ (16/115) were positive for AFB and in 38.32％ (41/107) were positive for culture.Multivariate regression revealed that short-axis diameter was an independent risk factor associated with positive pathology,smear and euhure.Additionally,more aspiration times cause higher pathology positive rate,pathology showing necrosis and positive smear were independent risk factors associated with positive cuhure.There were two patients occurred complications during operation.Conclusion EBUS-TBNA was a safe and effective method for the diagnosis of intrathoracic tuberculosis.

Brassinosteroids, a group of plant steroid hormones, regulate many aspects of plant growth and development. We and other have previously solved the crystal structures of BRI1(LRR) in complex with brassinolide, the most active brassinosteroid identified thus far. Although these studies provide a structural basis for the recognition of brassinolide by its receptor BRI1, it still remains poorly understood how the hormone differentiates among its conserved receptors. Here we present the crystal structure of the BRI1 homolog BRL1 in complex with brassinolide. The structure shows that subtle differences around the brassinolide binding site can generate a striking effect on its recognition by the BRI1 family of receptors. Structural comparison of BRL1 and BRI1 in their brassinolide-bound forms reveals the molecular basis for differential binding of brassinolide to its different receptors, which can be used for more efficient design of plant growth regulators for agricultural practice. On the basis of our structural studies and others' data, we also suggest possible mechanisms for the activation of BRI1 family receptors.
Amino Acid Sequence ; Arabidopsis ; metabolism ; Arabidopsis Proteins ; chemistry ; metabolism ; Binding Sites ; Brassinosteroids ; chemistry ; Crystallography, X-Ray ; Molecular Sequence Data ; Protein Kinases ; chemistry ; metabolism ; Protein Structure, Tertiary ; Recombinant Proteins ; genetics ; Sequence Alignment ; Steroids, Heterocyclic ; chemistry

Recent studies have unequivocally established the link between FTO and obesity. FTO was biochemically shown to belong to the AlkB-like family DNA/RNA demethylase. However, FTO differs from other AlkB members in that it has unique substrate specificity and contains an extended C-terminus with unknown functions. Insight into the substrate selection mechanism and a functional clue to the C-terminus of FTO were gained from recent structural and biochemical studies. These data would be valuable to design FTO-specific inhibitors that can be potentially translated into therapeutic agents for treatment of obesity or obesity-related diseases.
AlkB Homolog 1, Histone H2a Dioxygenase ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO ; Amino Acid Motifs ; Animals ; Catalytic Domain ; DNA ; metabolism ; DNA Repair Enzymes ; metabolism ; Humans ; Methylation ; Obesity ; genetics ; Proteins ; chemical synthesis ; classification ; genetics ; RNA ; metabolism ; Substrate Specificity

Objective To analyze the regulation of gene expression by adenosine deaminase RNA specific 1(ADAR1)in cervical cancer cell line Hela using RNA-seq technology and provide theoretical basis for understanding the role of ADAR1 in the occurrence and progression of cervical cancer.Methods RNA-seq sequencing of normal and ADAR1 knockdown Hela cell lines to identify differentially expressed genes.By conducting enrichment analysis using KEGG Pathway,GO cellular,and GSEA,the study analyzes the relevant signaling pathways and biological processes involving ADAR1 in Hela cell lines.Results Differentially expressed genes are mainly enriched in immune and inflammation-related signaling pathways(such as TNF-α/NF-κB,NIK/NF-κB,Jak/Stat-IL-6),Hippo signaling pathway,TGF-β signaling pathway,and are involved in interferon response,cellular amino acid metabo-lism regulation,protein ubiquitination/deubiquitination,viral transcription,and other biological processes.Further analysis of the NF-κB signaling pathway revealed a significant increase in the mRNA expression levels of NF-κB1 and TRAF5 after ADAR1 knockdown.Conclusion ADAR1 may regulate the expression of NF-κB signaling pathway-related factors and thereby regulate the occurrence and development of cervical cancer.

Arabidopsis ; chemistry ; genetics ; metabolism ; Arabidopsis Proteins ; chemistry ; genetics ; metabolism ; Crystallography, X-Ray ; Intercellular Signaling Peptides and Proteins ; chemistry ; genetics ; metabolism ; Protein Conformation ; Protein-Serine-Threonine Kinases ; chemistry ; genetics ; metabolism

Cryoelectron Microscopy ; methods ; Crystallography, X-Ray ; Image Processing, Computer-Assisted ; methods ; Models, Molecular ; Molecular Conformation

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.