A mammalian Wnt5a-Ror2-Vangl2 axis controls the cytoskeleton and confers cellular properties required for alveologenesis.

Alveolar formation increases the surface area for gas-exchange and is key to the physiological function of the lung. Alveolar epithelial cells, myofibroblasts and endothelial cells undergo coordinated morphogenesis to generate epithelial folds (secondary septa) to form alveoli. A mechanistic understanding of alveologenesis remains incomplete. We found that the planar cell polarity (PCP) pathway is required in alveolar epithelial cells and myofibroblasts for alveologenesis in mammals. Our studies uncovered a Wnt5a-Ror2-Vangl2 cascade that endows cellular properties and novel mechanisms of alveologenesis. This includes PDGF secretion from alveolar type I and type II cells, cell shape changes of type I cells and migration of myofibroblasts. All these cellular properties are conferred by changes in the cytoskeleton and represent a new facet of PCP function. These results extend our current model of PCP signaling from polarizing a field of epithelial cells to conferring new properties at subcellular levels to regulate collective cell behavior

Hemicentin-1 is an essential extracellular matrix component during tooth root formation by promoting mesenchymal cells differentiation

Introduction: Root dentin formation is an important process in tooth development. We tried to identify potential genes that regulate root dentin formation which could be potentially used for the regeneration and repair of defective or damaged dental roots.Methods: Tissues harvested from the labial and lingual sides of mouse incisors were used for microarray analysis. Gene ontology (GO) analysis of differentially expressed genes indicated the critical role of extracellular matrix in the discrepancy of dentin formation between root and crown, for which hemicentin-1 (Hmcn1) was selected as the target gene. Single-cell RNA sequencing analysis the expression pattern of Hmcn1 at different developmental stages in mouse molars. The spatiotemporal expression of HMCN1 in mouse incisors and molars was detected by immunohistochemical staining. The functions of HMCN1 in human dental pulp cells, including proliferation, differentiation and migration, were examined in vitro by CCK8 assay, BrdU assay, wound-healing assay, ALP staining and alizarin red staining, respectively.Results: It was showed that HMCN1 expression was more pronounced in papilla-pulp on the root than crown side in mouse incisors and molars. In vitro experiments presented inhibited dentinogenesis and migration after HMCN1-knockdown in human dental pulp cells, while there was no significant difference in proliferation between the HMCN1-knockdown group and control group.Discussion: These results indicated that HMCN1 plays an important role in dentinogenesis and migration of pulp cells, contributing to root dentin formation

Trust Region Methods For Nonconvex Stochastic Optimization Beyond Lipschitz Smoothness

In many important machine learning applications, the standard assumption of having a globally Lipschitz continuous gradient may fail to hold. This paper delves into a more general $(L_0, L_1)$-smoothness setting, which gains particular significance within the realms of deep neural networks and distributionally robust optimization (DRO). We demonstrate the significant advantage of trust region methods for stochastic nonconvex optimization under such generalized smoothness assumption. We show that first-order trust region methods can recover the normalized and clipped stochastic gradient as special cases and then provide a unified analysis to show their convergence to first-order stationary conditions. Motivated by the important application of DRO, we propose a generalized high-order smoothness condition, under which second-order trust region methods can achieve a complexity of $\mathcal{O}(\epsilon^{-3.5})$ for convergence to second-order stationary points. By incorporating variance reduction, the second-order trust region method obtains an even better complexity of $\mathcal{O}(\epsilon^{-3})$, matching the optimal bound for standard smooth optimization. To our best knowledge, this is the first work to show convergence beyond the first-order stationary condition for generalized smooth optimization. Preliminary experiments show that our proposed algorithms perform favorably compared with existing methods

Research on surface roughness of circular arc cut by ASJ

Izrađen je potpuni faktorijalni plan eksperimenata za istraživanje učinaka tlaka mlaza, reznog posmaka i polumjera kružnog luka na površinsku hrapavost kružnog luka rezanog mlazom abrazivne otopine - abrasive suspension jet (ASJ). Ortogonalnim planom eksperimenata analizirala se veličina djelovanja parametara na hrapavost rezne površine na različitim dubinama. Smanjivanje brzine prijelaza je najučinkovitija metoda za smanjenje površinske hrapavosti. Uz to, usporedbom topografije rezne površine s onom pomoću AWJ, ustanovilo se da je površina sastavljena od četiri zone: inicijalna zona, glatka zona, prijelazna zona i gruba zona. Konačno, primijenjena je metoda multipne linearne regresije za postavljanje modela hrapavosti površine na različitim dubinama, što se eksperimentima potvrdilo kao pouzdano. Zaključci mogu poslužiti kao teorijski vodič za poboljšanje učinkovitosti rezanja pomoću ASJ.Full factorial design of experiments was developed in order to investigate the effects of jet pressure, cutting feed, and circular arc radius upon the one response variable surface roughness of circular arc cut by abrasive suspension jet (ASJ). And orthogonal design of experiments was used for analysing the magnitude of effects of parameters on roughness of the cutting surface at different depths. Slowing down the traverse speed is the most effective method to reduce the surface roughness. In addition, comparing the topography of the cutting surface with that by AWJ, it is found that the surface also consists of four zones: initial zone, smooth zone, transition zone and rough zone. Finally, the multiple linear regression was employed to establish the model of cutting surface roughness at different depths, which was proved to be reliable by experiments. The conclusions can provide theoretical guidance for improving the cutting efficiency of ASJ

BHDPC Is a Novel Neuroprotectant That Provides Anti-neuroinflammatory and Neuroprotective Effects by Inactivating NF-κB and Activating PKA/CREB.

Microglia-mediated neuroinflammatory responses are inevitable and important pathological processes in several kinds of disorder of the central nervous system (CNS). Therefore, alleviating activated microglia-induced inflammatory process might be a valuable therapeutic approach to neuroinflammation-related diseases. In the present study, we investigated BHDPC, a novel neuroprotectant discovered in our previous study that had anti-inflammatory effects under neuroinflammatory conditions. First, we found that BHDPC could inhibit neuroinflammatory responses and promote microglial M2 phenotype polarization in both lipopolysaccharide (LPS)-activated BV-2 microglia l cells. Furthermore, BHDPC provided protective actions against neuroinflammation-induced neurotoxicity in HT22 mouse hippocampal cells co-cultured with activated BV-2 microglia. Further experiments demonstrated that BHDPC could suppress LPS-induced activation of transcription factor nuclear factor kappa B (NF-κB) via interfering with the degradation of the inhibitor of kappa B (IκB) and phosphorylation of IκB, the IκB kinase (IKK). Moreover, we also found that BHDPC could induce phosphorylation of cAMP-dependent protein kinase A (PKA) and cAMP-response element-binding protein (CREB) in BV-2 microglial cells. Also, using the PKA-specific inhibitor, we found that BHDPC-induced CREB phosphorylation was dependent on PKA, which also contributed to BHDPC-mediated anti-inflammation and neuroprotection

Diversity of Trichoderma species associated with the black rot disease of Gastrodia elata, including four new species

IntroductionTrichoderma species establish symbiotic relationships with plants through both parasitic and mutualistic mechanisms. While some Trichoderma species act as plant pathogenic fungi, others utilize various strategies to protect and enhance plant growth.MethodsPhylogenetic positions of new species of Trichoderma were determined through multi-gene analysis relying on the internal transcribed spacer (ITS) regions of the ribosomal DNA, the translation elongation factor 1-α (tef1-α) gene, and the RNA polymerase II (rpb2) gene. Additionally, pathogenicity experiments were conducted, and the aggressiveness of each isolate was evaluated based on the area of the cross-section of the infected site.ResultsIn this study, 13 Trichoderma species, including 9 known species and 4 new species, namely, T. delicatum, T. robustum, T. perfasciculatum, and T. subulatum were isolated from the diseased tubers of Gastrodia elata in Yunnan, China. Among the known species, T. hamatum had the highest frequency. T. delicatum belonged to the Koningii clade. T. robustum and T. perfasciculatum were assigned to the Virens clade. T. subulatum emerged as a new member of the Spirale clade. Pathogenicity experiments were conducted on the new species T. robustum, T. delicatum, and T. perfasciculatum, as well as the known species T. hamatum, T. atroviride, and T. harzianum. The infective abilities of different Trichoderma species on G. elata varied, indicating that Trichoderma was a pathogenic fungus causing black rot disease in G. elata.DiscussionThis study provided the morphological characteristics of new species and discussed the morphological differences with phylogenetically proximate species, laying the foundation for research aimed at preventing and managing diseases that affect G. elata