SciCombinator

Discover the most talked about and latest scientific content & concepts.

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To construct a three-dimensional structural model for the selectivity filter in the transient receptor pontential melastatin 8 (TRPM8) ion channel.

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Ion channels mediate ion transport across membranes, and play vital roles in processes of matter exchange, energy transfer and signal transduction in living organisms. Recently, structural studies of ion channels have greatly advanced our understanding of their ion selectivity and gating mechanisms. Structural studies of voltage-gated potassium channels elucidate the structural basis for potassium selectivity and voltage-gating mechanism; structural studies of voltage-gated sodium channels reveal their slow and fast inactivation mechanisms; and structural studies of transient receptor potential (TRP) channels provide complex and diverse structures of TRP channels, and their ligand gating mechanisms. In the article we summarize recent progress on ion channel structural biology, and outlook the prospect of ion channel structural biology in the future.

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As a non-invasive approach, sonogenetics is applied to control neuronal activity. The mechanosensitive channel(MSC), which has low threshold of responding to ultrasound, may be the alternative solution. Sonogenetics is the technique that activates the MSC expressed in targeted neurons by low intensity ultrasound, thus achieve the neuromodulation. In this review, we introduce the mechanosensitive channel of large conductance, transient receptor potential, channels of the two-pore-domain potassium family, Piezo and the recent progress on their application in sonogenetics.

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G protein-coupled receptors(GPCRs)represent the largest class of cell surface receptors,mediating wide range of cellular and physiological processes through their transducers,G proteins and the-arrestins participate in almost all pathological processes. Recent technological advances are revolutionizing the utility of cryo-electron microscopy(cryo-EM),leading to a tremendous progress in the structural studies of biological macromolecules and cryo-EM has played a leading role in the structural biology of GPCR signaling complex. New discoveries of high-resolution threedimensional structures of GPCR signaling complexes based on cryo-EM have emerged vigorously,which depict the common structural characteristics of intermolecular interaction between GPCR and G protein complex-the conformational changes of the transmembrane helix 6 of receptors,and also demonstrate the structural basis of G protein subtype selectivity. Single-particle cryo-EM becomes an efficient tool for identifying the molecular mechanism of receptor-ligand interaction,providing important information for understanding GPCR signaling and the structure-based drug design.

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Rifamycins, a group of bacterial RNA polymerase inhibitors, are the firstline antimicrobial drugs to treat tuberculosis. In light of the emergence of rifamycinresistant bacteria, development of new RNA polymerase inhibitors that kill rifamycinresistant bacteria with high bioavailability is urgent. Structural analysis of bacterial RNA polymerase in complex with inhibitors by crystallography and cryo-EM indicates that RNA polymerase inhibitors function through five distinct molecular mechanisms:inhibition of the extension of short RNA; competition with substrates; inhibition of the conformational change of the'bridge helix'; inhibition of clamp opening;inhibition of clamp closure. This article reviews the research progress of these five groups of RNA polymerase inhibitors to provide references for the modification of existing RNA polymerase inhibitors and the discovery of new RNA polymerase inhibitors.

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To investigate the expression of Wilms'tumor 1 (WT1) gene in patients with acute myeloid leukemia (AML), and to explore its application in predicting prognosis of AML in patients with wild or mutated nucleophosmin 1(NPM1) and Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD).

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Objective:To explore the effects of intrauterine infection on early growth and neurobehavioral development in neonatal rats. Methods:Escherichia coli (E. coli) was inoculated into uterine cervix of pregnant rats with gestation of 15 d to establish the intrauterine infection model, and the effect on the delivery of pregnant rats was observed. The neonatal rat brain tissue was stained with Hematoxylin-Eosin and the cerebral white matter damage was assessed. Immunohistochemical staining and Western blot analysis were performed to evaluate the expression of glial fibrillary acidic protein (GFAP), 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and neurofilament (NF) in pup brains. Birth weight and early growth development indices were monitored,and neurobehavioral tests were performed to access the change of neurobehavioral development in neonatal rats. Results:The white blood cell count increased significantly in the uterus and placenta of the pregnant rats after intrauterine E. coli infection and no significant impact was observed on the delivery of pregnant rats. Weak staining and focal rarefaction of cerebral white matter from rats at P7 in intrauterine infection group were observed. The expression of GFAP markedly increased (P<0.05) in infection group, while the level of CNPase and NF in pup brains at P7 significantly decreased (P<0.05 or P<0.01). Compared with control group, the neonatal rats in infection group had lower birth weight and slower weight gain during the suckling period (P<0.05 or P<0.01), and the completion times of ear opening, eye opening, surface righting, negative geotaxis, acoustic startle and swimming test in infection group were significantly delayed (P<0.05 or P<0.01). Conclussion:Intrauterine infection in pregnant rats can induce cerebral white matter damage and retardation of early growth and neurobehavioral development in neonatal rats.

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To explore the expression, localization and regulatory effect on mitochondrial calcium signaling of Rictor in embryonic stem cell-derived cardiomyocytes (ESC-CMs).

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To investigate the developmental characteristics of resilience in children aged 3-5, and to explore the relationship between temperament, parenting style and resilience.

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Objective:To investigate risk factors of death in newborns with congenital diaphragmatic hernia (CDH). Method:A total of 126 newborns with CDH from June 2012 to September 2018 were enrolled. Concomitant malformations were recorded by descriptive analysis. Newborns received surgical treatment (n=120) for CDH were divided into survival group and fatal group. The risk factors of death were analyzed by univariate and multivariate logistic regression and the ROC curve with generated with relevant variables. Result:There were 55 CDH newborns with concomitant malformations (43.7%), including 20 cases (15.9%) with multi-malformation. Logistic regression analysis showed that premature rupture of membranes (PROM), postoperative atelectasis, long duration of postoperative mechanical ventilation, postoperative high oxygenation index (OI) were related to death (all P<0.05), and the delayed surgery was a protective factor (P<0.05). In ROC analysis of postoperative OI in predicting death, the area under the curve (AUC) was 0.841, with the cutoff value of 5.74, the sensibility and specificity of OI was 81.0% and 75.0%, respectively(P<0.01). Conclusions:Newborns with CDH have a high rate of malformations. The risk factors of death were PROM, postoperative atelectasis, postoperative long duration of mechanical ventilation and higher postoperative OI, and delayed surgery may reduce mortality.