Remodeling of the periodontal ligament and alveolar bone during axial tooth movement in mice with type 1 diabetes

ObjectivesTo observe the elongation of the axial tooth movement in the unopposed rodent molar model with type 1 diabetes mellitus and explore the pathological changes of periodontal ligament and alveolar bone, and their correlation with tooth axial movement.MethodsThe 80 C57BL/6J mice were randomly divided into the streptozotocin(STZ)-injected group (n = 50) and the control group (n = 30). Mice in the streptozotocin(STZ)-injected group were injected intraperitoneal with streptozotocin (STZ), and mice in the control group were given intraperitoneal injection of equal doses of sodium citrate buffer. Thirty mice were randomly selected from the successful models as the T1DM group. The right maxillary molar teeth of mice were extracted under anesthesia, and allowed mandibular molars to super-erupt. Mice were sacrificed at 0, 3, 6,9, and 12 days. Tooth elongation and bone mineral density (BMD) were evaluated by micro-CT analysis(0,and 12 days mice). Conventional HE staining, Masson staining and TRAP staining were used to observe the changes in periodontal tissue(0, 3, 6, 9, and 12 days mice). The expression differences of SPARC, FGF9, BMP4, NOGGIN, and type I collagen were analyzed by RT-qPCR.ResultsAfter 12 days of tooth extraction, our data showed significant super-eruption of mandibular mouse molars of the two groups. The amount of molar super-eruption in the T1DM group was 0.055mm( ± 0.014mm), and in the control group was 0.157( ± 0.017mm). The elongation of the T1DM mice was less than that of the control mice(P<0.001). It was observed that the osteoclasts and BMD increased gradually in both groups over time. Compared with the control group, the collagen arrangement was more disordered, the number of osteoclasts was higher (P<0.05), and the increase of bone mineral density was lower(2.180 ± 0.007g/cm3 vs. 2.204 ± 0.006g/cm3, P<0.001) in the T1DM group. The relative expression of SPARC, FGF9, BMP4, and type I collagen in the two groups increased with the extension of tooth extraction time while NOGGIN decreased. The relative expression of all of SPARC, FGF9, BMP4, and type I collagen in the T1DM group were significantly lower, and the expression of NOGGIN was higher than that in the control group (P<0.05).ConclusionThe axial tooth movement was inhibited in type 1 diabetic mice. The result may be associated with the changes of periodontal ligament osteoclastogenic effects and alveolar bone remodeling regulated by the extracellular matrix and osteogenesis-related factors

Structural analysis of the regulatory GAF domains of cGMP phosphodiesterase elucidates the allosteric communication pathway

Regulation of photoreceptor phosphodiesterase (PDE6) activity is responsible for the speed, sensitivity, and recovery of the photoresponse during visual signaling in vertebrate photoreceptor cells. It is hypothesized that the physiological differences in the light responsiveness of rods and cones may result in part from differences in the structure and regulation of the distinct isoforms of rod and cone PDE6. Although rod and cone PDE6 catalytic subunits share a similar domain organization consisting of tandem GAF domains (GAFa and GAFb) and a catalytic domain, cone PDE6 is a homodimer whereas the rod PDE6 catalytic dimer is composed of two homologous catalytic subunits. Here we provide the x-ray crystal structure of cone GAFab regulatory domain solved at 3.3 Å resolution in conjunction with chemical cross-linking and mass spectrometric analysis of conformational changes to GAFab induced upon binding of cGMP and the PDE6 inhibitory γ-subunit (Pγ). Ligand-induced changes in cross-linked residues implicate the α4-helix of GAFa (close to the cGMP binding site) and the β1/β2 loop of GAFb as key motifs that have been previously proposed to communicate with the catalytic domains of PDE6. Molecular dynamics (MD) simulations of cone GAFab revealed asymmetry in the two GAFab subunits forming the homodimer and allosteric perturbations on cGMP binding. Cross-linking of Pγ to GAFab in conjunction with solution NMR spectroscopy of isotopically labeled Pγ identified the central polycationic region of Pγ interacting with the GAFb domain. These results provide a mechanistic basis for developing allosteric activators of PDE6 with therapeutic implications for halting the progression of certain retinal degenerative diseases

Determination of the spin axis in quantum spin Hall insulator monolayer WTe2

Evidence for the quantum spin Hall (QSH) effect has been reported in several experimental systems in the form of approximately quantized edge conductance. However, the most fundamental feature of the QSH effect, spin-momentum locking in the edge channels, has never been demonstrated experimentally. Here, we report clear evidence for spin-momentum locking in the edge channels of monolayer WTe2, thought to be a two-dimensional topological insulator (2D TI). We observe that the edge conductance is controlled by the component of an applied magnetic field perpendicular to a particular axis, which we identify as the spin axis. The axis is the same for all edges, situated in the mirror plane perpendicular to the tungsten chains at 40$\pm$2{\deg} to the layer normal, implying that the spin-orbit coupling is inherited from the bulk band structure. We show that this finding is consistent with theory if the band-edge orbitals are taken to have like parity. We conclude that this parity assignment is correct and that both edge states and bulk bands in monolayer WTe2 share the same simple spin structure. Combined with other known features of the edge states this establishes spin-momentum locking, and therefore that monolayer WTe2 is truly a natural 2D TI

The ‘Symbol of Angst’ and the Poetics of Remembrance: Lu Xun and Chinese Literary Modernity

This essay examines a crucial aspect of Lu Xun’s literary thought—namely, his understanding of the relationship between literature and reality. Bringing together a number of reflections on literature Lu Xun made at different moments of his life, including his translation of the concept of the “symbol of angst” and his creation of the image of the grave, the author demonstrates how Lu Xun formulated a notion of literature that conceives of writing not as the symbolic representation of truth, but as the correlative depiction of transitional existence. It argues that Lu Xun’s conception of literature, informed by a strong sense of the lived moment of the historical present, is essentially a modernist attempt to revitalize the Chinese aesthetic tradition’s correlative articulation of the world, for which his encounter with the ontological “spirit” of the West provides a crucial stimulation

A Novel Phishing Website Detection Model Based on LightGBM and Domain Name Features

Phishing attacks have evolved in terms of sophistication and have increased in sheer number in recent years. This has led to corresponding developments in the methods used to evade the detection of phishing attacks, which pose daunting challenges to the privacy and security of the users of smart systems. This study uses LightGBM and features of the domain name to propose a machine-learning-based method to identify phishing websites and maintain the security of smart systems. Domain name features, often known as symmetry, are the property wherein multiple domain-name-generation algorithms remain constant. The proposed model of detection is first used to extract features of the domain name of the given website, including character-level features and information on the domain name. The features are filtered to improve the model’s accuracy and are subsequently used for classification. The results of experimental comparisons showed that the proposed model of detection, which integrates two types of features for training, significantly outperforms the model that uses a single type of feature. The proposed method also has a higher detection accuracy than other methods and is suitable for the real-time detection of many phishing websites

Early Silurian chondrichthyans from the Tarim Basin (Xinjiang, China)

The Sinacanthida ordo nov. and Mongolepidida are spine- and scale-based taxa whose remains encompass some of the earliest reported fossils of chondrichthyan fish. Investigation of fragmentary material from the Early Silurian Tataertag and Ymogantau Formations of the Tarim Basin (Xinjiang Uygur Autonomous Region, China) has revealed a diverse mongolepidid and sinacanthid fauna dominated by mongolepids and sinacanthids in association with abundant dermoskeletal elements of the endemic 'armoured' agnathans known as galeaspids. Micro-computed tomography, scanning electron microscopy and histological sections were used to identify seven mongolepid genera (including Tielikewatielepis sinensis gen. et sp. nov., Xiaohaizilepis liui gen. et sp. nov. and Taklamakanolepis asiaticus gen. et sp. nov.) together with a new chondrichthyan (Yuanolepis bachunensis gen. et sp. nov.) with scale crowns consisting of a mongolepid-type atubular dentine (lamellin). Unlike the more elaborate crown architecture of mongolepids, Yuanolepis gen. nov. exhibits a single row of crown elements consistent with the condition reported in stem chondrichthyans from the Lower Devonian (e.g. in Seretolepis, Parexus). The results corroborate previous work by recognising lamellin as the main component of sinacanthid spines and point to corresponding developmental patterns shared across the dermal skeleton of taxa with lamellin and more derived chondrichthyans (e.g. Doliodus, Kathemacanthus, Seretolepis and Parexus). The Tarim mongolepid fauna is inclusive of coeval taxa from the South China Block and accounts for over two-thirds of the species currently attributed to Mongolepidida. This demonstrates considerable overlap between the Tarim and South China components of the Lower Silurian Zhangjiajie Vertebrate Fauna