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The dynamic arrangement of cortical microtubules (MTs) plays a pivotal role in controlling cell growth and shape formation in plants, but the mechanisms by which cortical MTs are organized to regulate these processes are not well characterized. In particular, the dynamic behavior of cortical MTs is critical for their spatial organization, yet the molecular mechanisms controlling MT dynamics remain poorly understood. In this study, we used the puzzle piece-shaped pavement cells of Arabidopsis () leaves as a model system in which to study cortical MT organization. We isolated an ethyl methanesulfonate mutant with reduced interdigitation of pavement cells in cotyledons. This line carried a mutation in (), which encodes a member of the plant-specific IQ motif protein family. Live-cell imaging and biochemical analyses demonstrated that IQD5 binds to MTs and promotes MT assembly. MT-depolymerizing drug treatment and in vivo MT dynamics assays suggested that IQD5 functions to stabilize MTs. Hence, our findings provide genetic, cell biological, and biochemical evidence that IQD5 regulates MT dynamics that affect MT organization and subsequent cell shape formation.

BackgroundAcetaminophen (APAP) overdose-induced acute liver failure (ALF) is mainly resulted from uncontrolled oxidative stress. Nuclear factor-erythroid 2-related factor 2 (Nrf2), a key antioxidant transcription factor, is essential for alleviating APAP-induced hepatotoxicity. Corilagin (Cori) is a natural polyphenol compound that possesses effective antioxidant activity; however, the protective effect of Cori on APAP-induced hepatotoxicity is still unknown. The current study aimed to explore whether Cori could mitigate hepatotoxicity caused by APAP and the underlying molecular mechanisms of action.MethodsCell counting kit-8 (CCK-8) assays, Western blotting analysis, dual-luciferase reporter assays, a mouse model, CRISPR/Cas9 knockout technology, and hematoxylin-eosin (H & E) staining were employed to explore the mechanisms by which Cori exerts a protective effect on hepatotoxicity in HepG2 cells and in a mouse model.ResultsOur findings suggested that Cori efficiently decreased APAP-triggered the generation of reactive oxygen species (ROS) and cell death in HepG2 cells. Additionally, Cori significantly induced the expression of several antioxidant enzymes, and this induced expression was closely linked to the upregulation of Nrf2, inhibition of Keap1 protein expression, and promotion of antioxidant response element (ARE) activity in HepG2 cells. Moreover, Cori clearly induced the phosphorylation of AMP-activated protein kinase (AMPK), glycogen synthase kinase-3β (GSK3β), liver kinase B1 (LKB1) and acetyl-CoA carboxylase (ACC). Furthermore, Cori-mediated GSK3β inactivation, Nrf2 upregulation and cytoprotection were abolished by an AMPK inhibitor (Compound C) in HepG2 cells. Lastly, we found that Cori inhibited APAP-induced hepatotoxicity and mediated the expression of many antioxidant enzymes; these results were reversed in Nrf2 −/− HepG2 cells. In vivo, Cori significantly protected against APAP-induced ALF by reducing mortality and alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, attenuating histopathological liver changes, inhibiting myeloperoxidase (MPO) and malondialdehyde (MDA) levels, and increasing the superoxide dismutase (SOD) content and GSH-to-GSSG ratio as well as suppressing c-jun N-terminal kinase (JNK) phosphorylation. However, Cori-induced reductions in mortality, AST and ALT levels, and histopathological liver changes induced by APAP were clearly abrogated in Nrf2-deficienct mice.ConclusionsThese findings principally indicated that Cori effectively protects against APAP-induced ALF via the upregulation of the AMPK/GSK3β-Nrf2 signaling pathway.

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Novel sulfonated poly(arylene ether ketones) (SDN-PAEK-x), consisting of dual naphthalene and flexible sulfoalkyl groups, were prepared via polycondensation, demethylation, and sulfobutylation grafting reaction. Among them, SDN-PAEK-1.94 membrane with the highest ion exchange capacity (IEC = 2.46 mequiv·g(-1)) exhibited the highest proton conductivity, which was 0.147 S· cm(-1) at 25 °C and 0.271 S·cm(-1) at 80 °C, respectively. The introduction of dual naphthalene moieties is expected to achieve much enhanced properties compared to those of sulfonated poly(arylene ether ketones) (SNPAEK-x), consisting of single naphthalene and flexible sulfoalkyl groups. Compared with SNPAEK-1.60 with a similar IEC, SDN-PAEK-1.74 membrane showed higher proton conductivity, higher IEC normalized conductivity, and higher effective proton mobility, although it had lower analytical acid concentration. The SDN-PAEK-x membranes with IECs higher than 1.96 mequiv·g(-1) also exhibited higher proton conductivity than that of recast Nafion membrane. Furthermore, SDN-PAEK-1.94 displayed a better single cell performance with a maximum power density of 60 mW·cm(-2) at 80 °C. Considering its high proton conductivity, excellent single cell performance, good mechanical stabilities, low membrane swelling, and methanol permeability, SDN-PAEK-x membranes are promising candidates as alternative polymer electrolyte membranes to Nafion for direct methanol fuel cell applications.

Summary Pulpitis suppressed the level of let‐7c‐5p that promotes osteogenesis and bone formation by repressing HMGA2. In the current study, the function of let‐7c‐5p in the inflammation and osteogenesis in dental pulp stem cells (DPSCs) was explored. The level of let‐7c‐5p in DPSCs was up‐regulated, and the cells were subjected to lipopolysaccharide (LPS) to induce inflammation. The effect of let‐7c‐5p on cell proliferation potential, osteogenic differentiation potential, and activity of HMGA2/PI3K/Akt pathway was detected. The administration of LPS suppressed the cell proliferation of DPSCs and suppressed calcium deposition, activity of alkaline phosphatase (ALP), and levels of OCN, OPN, OSX, MSX2, and RUNX2 in inflamed DPSCs. The impaired osteogenic differentiation of inflamed DPSCs was associated with the increased levels of HMGA2, p‐PI3K, and p‐Akt. In let‐7c‐5p‐overexpressed inflamed DPSCs, the proliferation and osteogenic differentiation potential of DPSCs were restored, and the activation of HMGA2/PI3K/Akt signalling was inhibited. In rat pulpitis models, the injection of let‐7c‐5p agomir restored the osteogenic differentiation potential of dental pulp cells and inhibited HMGA2/PI3K/Akt signalling. The findings demonstrated the anti‐inflammation and pro‐osteogenesis effect of let‐7c‐5p during the attack of pulpitis, which depended on the inhibition of HMGA2/PI3K/Akt signalling.

Purpose High-throughput chemosensitivity testing of low-passage cancer cell lines can be used to prioritize agents for personalized chemotherapy. However, generating cell lines from primary cancers is difficult, because contaminating stromal cells overgrow the malignant cells. Experimental Design We produced a series of hypoxanthine phosphoribosyl transferase (hprt)-null immunodeficient mice. During growth of human cancers in these mice, hprt-null murine stromal cells replace their human counterparts. Results Pancreatic and ovarian cancers explanted from these mice were grown in selection media to produce pure human cancer cell lines. We screened one cell line with a 3,131-drug panel and identified seventy-seven FDA approved drugs with activity, including two novel drugs to which the cell line was uniquely sensitive. Xenografts of this carcinoma were selectively responsive to both drugs. Conclusion Chemotherapy can be personalized using patient-specific cell lines derived in biochemically selectable mice.