Inhibition of mugineic acid-ferric complex uptake in barley by copper, zinc and cobalt

The interfering effects of copper, zinc, and cobalt on the uptake of mugineic acid-ferric complex were studied in barley ( Hordeum vulgare , cv. Minorimugi) grown in nutrient solution. Short-term uptake experiments of 3 h were performed utilizing both ionic and mugineic acid-complex forms of each metal at two different concentrations. Copper was most effective in decreasing iron uptake when added in an ionic form at either concentration. The inhibition order at higher concentrations followed Cu(II) > Zn(II) ≥ Co(II), Co(III), which is consistent with the stability constants of these metal complexes with mugineic acid. The displacement of iron from its mugineic acid complex by these metals is suggested as a probable explanation for the decreased iron uptake. The inhibitory effect of metal complexes with mugineic acid on iron uptake was only found in cases with higher concentrations of Cu(II) and Zn(II) complexes. Deformation of the specific iron transport system in the plasma membrane due to their adsorption may be responsible for this effect.     

Autophagic flux is essential for the downregulation of <Emphasis Type="Italic">D</Emphasis>-dopachrome tautomerase by atractylenolide I to ameliorate intestinal adenoma formation

Colorectal cancer is generally believed to progress through an adenoma - carcinoma sequence. Adenomatous polyposis coli (APC) mutations serve as the initiating event in adenoma formation. The Apc^Min/+ mouse harbors a mutation in the APC gene, which is similar or identical to the mutation found in individuals with familial adenomatous polyposis and 70% of all sporadic CRC cases. Autophagy is a constitutive process required for proper cellular homeostasis. However, its role in intestinal adenoma formation is still controversial. Atractylenolide I (AT1) is a sesquiterpenoid that possesses various clinically relevant properties such as anti-tumor and anti-inflammatory activities. The role of AT1 on adenoma formation was tested in Apc^Min/+ mice and its underlying mechanism in regulating autophagy was documented. D-dopachrome tautomerase (D-DT) was identified as a potential target of AT1 by an proteomics-based approach. The effects of p53 modification on autophgic flux was monitored in p53^?/? and p53^+/+ HCT116 cells. Small interfering RNA was used to investigate the function of Atg7 and D-DT on autophagy programme induce by AT1. AT1 effectively reduced the formation of adenoma and downregulated the tumorigenic proteins in Apc^Min/+ mice. Importantly, AT1 stimulated autophagic flux through downregulating acetylation of p53. Activation of Sirt1 by AT1 was essential for the deacetylation of p53 and downregulation of D-DT. The lowered expression of COX-2 and β-catenin by AT1 were partly recovered by Atg7 knockdown. AT1 activates autophagy machinery to downregulate D-DT and reduce intestinal adenoma formation. This discovery provides evidence in vivo and in vitro that inducing autophagy by natural products maybe a potential therapy to ameliorate colorectal adenoma formation.     

聚乙二醇沉淀剂有效分离尿外泌体

尿外泌体是病毒大小的胞外囊泡,是非侵入性获得肾及泌尿生殖道细胞生理病理信息的重要靶标。聚乙二醇沉淀 剂可经济高效地分离富集血清等外泌体,但未见用于尿外泌体富集的详细报道。本研究采用聚乙二醇沉淀剂分离鉴定尿外泌体,并对其RNA组分进行检测,以期建立一个经济、高效、简便的尿外泌体分离富集方法。采集10例健康志愿者晨尿20 mL,聚乙二醇沉淀剂分离尿外泌体。透射电镜观察到直径30～100 nm双层膜包绕的囊性小泡,中央有直径5～15 nm高电子密度区。Western印迹检测到外泌体标记蛋白CD63、CD9、TSG101、ADAM10和内标蛋白β-肌动蛋白的表达。纳米粒径仪测定粒子直径介于30～130 nm,并可见25.37 nm和95.07 nm二个粒子峰。qRT-PCR扩增得到β-肌动蛋白和RNU6 RNA产物带。上述结果表明,聚乙二醇沉淀剂可分离富集尿外泌体,该法简单、高效,不需要超速离心机等昂贵设备,且采用该法富集到的外泌体可用于后续蛋白质与核酸分析。该方法可望加速液体活检应用,尤其是肾及泌尿生殖道病变的无创检测。     

All‐Solution‐Processed Silver Nanowire Window Electrode‐Based Flexible Perovskite Solar Cells Enabled with Amorphous Metal Oxide Protection

Silver nanowire (AgNW)‐based transparent electrodes prepared via an all‐solution‐process are proposed as bottom electrodes in flexible perovskite solar cells (PVSCs). To enhance the chemical stability of AgNWs, a pinhole‐free amorphous aluminum doped zinc oxide (a‐AZO) protection layer is deposited on the AgNW network. Compared to its crystalline counterpart (c‐AZO), a‐AZO substantially improves the chemical stability of the AgNW network. For the first time, it is observed that inadequately protected AgNWs can evanesce via diffusion, whereas a‐AZO secures the integrity of AgNWs. When an optimally thick a‐AZO layer is used, the a‐AZO/AgNW/AZO composite electrode exhibits a transmittance of 88.6% at 550 nm and a sheet resistance of 11.86 Ω sq^?1, which is comparable to that of commercial fluorine doped tin oxide. The PVSCs fabricated with a configuration of Au/spiro‐OMeTAD/CH₃NH₃PbI₃/ZnO/AZO/AgNW/AZO on rigid and flexible substrates can achieve power conversion efficiencies (PCEs) of 13.93% and 11.23%, respectively. The PVSC with the a‐AZO/AgNW/AZO composite electrode retains 94% of its initial PCE after 400 bending iterations with a bending radius of 12.5 mm. The results clearly demonstrate the potential of AgNWs as bottom electrodes in flexible PVSCs, which can facilitate the commercialization and large‐scale deployment of PVSCs.     

NFκB mediated elevation of KCNJ11 promotes tumor progression of hepatocellular carcinoma through interaction of lactate dehydrogenase A

It has been well documented that changes in ion fluxes across cellular membranes is fundamental in maintaining cellular homeostasis. Dysregulation and/or malfunction of ion channels are critical events in the pathogenesis of diverse diseases, including cancers. In this study, we focused on the study of K⁺ channels in hepatocellular carcinoma (HCC). By data mining TCGA cohort, the expression of 27 K⁺ channels was investigated and KCNJ11 was identified as a key dysregulated K⁺ channels in HCC. KCNJ11 was differentially expressed in HCC and predicted a poor prognosis in HCC patients. Inhibition of NFκB signaling suppressed KCNJ11 expression in HCC cells. Knockdown of KCNJ11 expression inhibited cell proliferation, promoted cell apoptosis, and reduced cell invasive capacity. Mechanistically, we found that KCNJ11 promotes tumor progression through interaction with LDHA and enhancing its enzymatic activity. Pharmacological inhibition of LDHA largely compromised the oncogenic function of KCNJ11 in cell proliferation, cell apoptosis, and cell invasion. Collectively, our data, as a proof of principle, demonstrate that KCNJ11 acts as an oncogene in HCC though forming a complex with LDHA and suggest that targeting KCNJ11 can be developed as a candidate tool to dampen HCC.     

Intracellular trafficking of planar cell polarity proteins

Background

Planar cell polarity (PCP) is a phenomenon in which epithelial cells are polarized along the plane of a tissue. PCP is critical for a variety of developmental processes and is regulated by a set of evolutionarily conserved PCP signaling proteins. Many of the PCP proteins adopt characteristic asymmetric localizations on the opposing cellular boundaries. Currently, the molecular mechanisms that establish and maintain this PCP asymmetry remain largely unclear. Newly synthesized integral PCP proteins are transported along the secretory transport pathway to the plasma membranes. Once delivered to the plasma membranes, PCP proteins undergo endocytosis. Recent studies reveal insights into the intracellular trafficking of PCP proteins, suggesting that intracellular trafficking of PCP proteins contributes to establishing the PCP asymmetry.

Objective

To understand the intracellular trafficking of planar cell polarity proteins in the secretory transport pathway and endocytic transport pathway.

Methods

This review summarizes our current understanding of the intracellular trafficking of PCP proteins. We highlights the molecular mechanisms that regulate sorting of PCP proteins into transport vesicles and how the intracellular trafficking process regulates the asymmetric localizations of PCP proteins.

Results

Current studies reveal novel insights into the molecular mechanisms mediating intracellular trafficking of PCP proteins. This process is critical for delivering newly synthesized PCP proteins to their specific destinations, removing the unstable or mislocalized PCP proteins from the plasma membranes and preserving tissue polarity during proliferation of mammalian skin cells.

Conclusion

Understanding how PCP proteins are delivered in the secretory and endocytic transport pathway will provide mechanistic insights into how the asymmetric localizations of PCP proteins are established and maintained.

     

A novel podoplanin‐GFPCre mouse strain for gene deletion in lymphatic endothelial cells

The lymphatic vascular system is a one‐direction network of thin‐walled capillaries and larger vessels covered by a continuous layer of endothelial cells responsible for maintaining fluid homeostasis. Some of the main functions of the lymphatic vasculature are to drain fluid from the extracellular spaces and return it back to the blood circulation, lipid absorption from the intestinal tract, and transport of immune cells to lymphoid organs. A number of genes controlling the development of the mammalian lymphatic vasculature have been identified in the last few years, and their functional roles started to be characterized using gene inactivation approaches in mice. Unfortunately, only few mouse Cre strains relatively specific for lymphatic endothelial cells (LECs) are currently available. In this article, we report the generation of a novel Podoplanin (Pdpn) GFPCre transgenic mouse strain using its 5’ regulatory region. Pdpn encodes a transmembrane mucin‐type O‐glycoprotein that is expressed on the surface of embryonic and postnatal LECs, in addition to few other cell types. Our detailed characterization of this novel strain indicates that it will be a valuable additional genetic tool for the analysis of gene function in LECs.     

Spring phenology at different altitudes is becoming more uniform under global warming in Europe

Under current global warming, high‐elevation regions are expected to experience faster warming than low‐elevation regions. However, due to the lack of studies based on long‐term large‐scale data, the relationship between tree spring phenology and the elevation‐dependent warming is unclear. Using 652k records of leaf unfolding of five temperate tree species monitored during 1951–2013 in situ in Europe, we discovered a nonlinear trend in the altitudinal sensitivity (S_A, shifted days per 100 m in altitude) in spring phenology. A delayed leaf unfolding (2.7 ± 0.6 days per decade) was observed at high elevations possibly due to decreased spring forcing between 1951 and 1980. The delayed leaf unfolding at high‐elevation regions was companied by a simultaneous advancing of leaf unfolding at low elevations. These divergent trends contributed to a significant increase in the S_A (0.36 ± 0.07 days 100/m per decade) during 1951–1980. Since 1980, the S_A started to decline with a rate of ?0.32 ± 0.07 days 100/m per decade, possibly due to reduced chilling at low elevations and improved efficiency of spring forcing in advancing the leaf unfolding at high elevations, the latter being caused by increased chilling. Our results suggest that due to both different temperature changes at the different altitudes, and the different tree responses to these changes, the tree phenology has shifted at different rates leading to a more uniform phenology at different altitudes during recent decades.