2H‐Pyran‐2‐one and 2H‐Furan‐2‐one Derivatives from the Plant Endophytic Fungus Pestalotiopsis fici

Two new α‐pyrones (=2H‐pyran‐2‐ones), ficipyrones A and B ( 1 and 2 , resp.), and two new α‐furanones (=2H‐furan‐2‐ones), ficifuranones A and B ( 3 and 4 , resp.), together with three known metabolites, antibiotic F 0368 ( 5 ), hydroxyseiridin ( 6 ), and hydroxyisoseiridin ( 7 ), were isolated from solid cultures of the plant endophytic fungus Pestalotiopsis fici. Their structures were elucidated primarily by NMR spectroscopy, and the absolute configuration of 1 was deduced from the circular‐dichroism (CD) data. Compound 1 showed antifungal activity against the plant pathogen Gibberella zeae (CGMCC 3.2873) with an IC₅₀ value of 15.9 μM .     

Spermidine oxidase‐derived H2O2 regulates pollen plasma membrane hyperpolarization‐activated Ca2+‐permeable channels and pollen tube growth

Spermidine (Spd) has been correlated with various physiological and developmental processes in plants, including pollen tube growth. In this work, we show that Spd induces an increase in the cytosolic Ca²⁺ concentration that accompanies pollen tube growth. Using the whole‐cell patch clamp and outside‐out single‐channel patch clamp configurations, we show that exogenous Spd induces a hyperpolarization‐activated Ca²⁺ current: the addition of Spd cannot induce the channel open probability increase in excised outside‐out patches, indicating that the effect of Spd in the induction of Ca²⁺ currents is exerted via a second messenger. This messenger is hydrogen peroxide (H₂O₂), and is generated during Spd oxidation, a reaction mediated by polyamine oxidase (PAO). These reactive oxygen species trigger the opening of the hyperpolarization‐activated Ca²⁺‐permeable channels in pollen. To provide further evidence that PAO is in fact responsible for the effect of Spd on the Ca²⁺‐permeable channels, two Arabidopsis mutants lacking expression of the peroxisomal‐encoding AtPAO3 gene, were isolated and characterized. Pollen from these mutants was unable to induce the opening of the Ca²⁺‐permeable channels in the presence of Spd, resulting in reduced pollen tube growth and seed number. However, a high Spd concentration triggers a Ca²⁺ influx beyond the optimal, which has a deleterious effect. These findings strongly suggest that the Spd‐derived H₂O₂ signals Ca²⁺ influx, thereby regulating pollen tube growth.     

Nuclear morphology and c‐Jun N‐terminal kinase 1 expression differentiate serum‐starved oxidative stress signalling from hydrogen peroxide‐induced apoptosis in retinal neuronal cell line

Oxidative stress induced by serum starvation and H₂O₂ exposure, both triggers apoptosis in retinal neuronal cell line RGC‐5 (retinal ganglion cell‐5). We have examined whether, despite excess generation of ROS (reactive oxygen species) and apoptosis induction, there is any dissimilarity in nuclear morphology and apoptotic signalling pathway in RGC‐5 under these conditions. Sub‐confluent cells were treated either with H₂O₂ or maintained in SFM (serum‐free medium). ROS level was detected along with nuclear morphology and ultrastructural analysis. Generation of excess intracellular ROS, nuclear localization of Bax and caspase 3 activation along with decrease of cellular viability, confirmed apoptosis induction in RGC‐5 by 72 h serum starvation and 500 M H₂O₂ exposure for 1 h. Nuclear swelling as supported by nuclear cytoplasmic ratio and conspicuous black spots with nuclear remodelling were observed only upon SFM, but not with H₂O₂ treatment. Serum starvation did not alter JNK1 (c‐Jun N‐terminal kinase 1) expression, although nuclear translocation and higher level of pJNK (phospho‐JNK) was evident. Conversely, H₂O₂ exposure blocked the expression and activation of JNK1 to phospho‐JNK as a negligible level of pJNK was present in the cytoplasm. Despite similar ROS generation in both the conditions, difference in nuclear morphology and JNK1 expression leads to the hypothesis that RGC‐5 cells may follow different signalling pathways when challenged with serum starvation and H₂O₂.     

Increased 4‐hydroxy‐2‐nonenal‐induced proteasome dysfunction is correlated with cardiac damage in streptozotocin‐injected rats with isoproterenol infusion

Increase in 4‐hydroxy‐2‐nonenal (4HNE) due to oxidative stress has been observed in a variety of cardiac diseases such as diabetic cardiomyopathy. 4HNE exerts a damaging effect in the myocardium by interfering with subcellular organelles like mitochondria by forming adducts. Therefore, we hypothesized that increased 4HNE adduct formation in the heart results in proteasome inactivation in isoproterenol (ISO)‐infused type 1 diabetes mellitus (DM) rats. Eight‐week‐old male Sprague Dawley rats were injected with streptozotocin (STZ, 65 mg kg^?1). The rats were infused with ISO (5 mg kg^?1) for 2 weeks by mini pumps, after 8 weeks of STZ injection. We studied normal control (n = 8) and DM + ISO (n = 10) groups. Cardiac performance was assessed by echocardiography and Millar catheter at the end of the protocol at 20 weeks. Initially, we found an increase in 4HNE adducts in the hearts of the DM + ISO group. There was also a decrease in myocardial proteasomal peptidase (chymotrypsin and trypsin‐like) activity. Increases in cardiomyocyte area (446 ± 32·7 vs 221 ± 10·83) (µm²), per cent area of cardiac fibrosis (7·4 ± 0·7 vs 2·7 ± 0·5) and cardiac dysfunction were also found in DM + ISO (P < 0·05) relative to controls. We also found increased 4HNE adduct formation on proteasomal subunits. Furthermore, reduced aldehyde dehydrogenase 2 activity was observed in the myocardium of the DM + ISO group. Treatment with 4HNE (100 μM) for 4 h on cultured H9c2 cardiomyocytes attenuated proteasome activity. Therefore, we conclude that the 4HNE‐induced decrease in proteasome activity may be involved in the cardiac pathology in STZ‐injected rats infused with ISO. Copyright © 2016 John Wiley & Sons, Ltd.     

Complete Dehydrogenation of N2H4BH3 over Noble‐Metal‐Free Ni0.5Fe0.5–CeOx/MIL‐101 with High Activity and 100% H2 Selectivity

Efficient and selective dehydrogenation of hydrazine borane (HB), a novel hydrogen storage material with very high hydrogen content (HB, 15.4 wt%), is a key challenge for a fuel‐cell‐based hydrogen economy. However, even using the noble metal catalysts for HB decomposition, the activities are still far from satisfying, to say nothing of non‐noble‐metal‐containing catalysts. In response, as a proof‐of‐concept experiment, herein, noble‐metal‐free NiFe–CeO_x nanoparticles are successfully immobilized on an MIL‐101 support without surfactant by a simple liquid impregnation method. Unexpectedly, the resultant Ni_0.5Fe_0.5–CeO_x/MIL‐101 catalyst shows good performance, including 100% H₂ selectivity, 100% conversion, and record catalytic activity (351.3 h^?1) for hydrogen generation at mild temperature, which is even better than most of the noble metal heterogeneous catalysts and might be attributed to the good dispersion and uniform particle size of the Ni_0.5Fe_0.5–CeO_x nanoparticles due to steric restrictions effect of the MIL‐101 support. Additionally, extending MIL‐101 to some other important kinds of metal–organic framework (MOF) structures, the resultant NiFe–CeO_x/MOF catalysts all show good catalytic activity toward HB decomposition, showing the universality of the MOF supported NiFe–CeO_x catalysts.     

BAPTA‐AM dramatically improves maturation and development of bovine oocytes from grade‐3 cumulus‐oocyte complexes

Intracellular free calcium ([Ca²⁺]_i) is essential for oocyte maturation and early embryonic development. Here, we investigated the role of [Ca²⁺]_i in oocytes from cumulus‐oocyte complexes (COCs) with respect to maturation and early embryonic development, using the calcium‐buffering agent BAPTA‐AM (1,2‐bis[2‐aminophenoxy]ethane‐N,N,N′,N′‐tetraacetic acid tetrakis [acetoxymethyl ester]). COCs were graded based on compactness of the cumulus mass and appearance of the cytoplasm, with Grade 1 indicating higher quality and developmental potential than Grade 3. Results showed that: (i) [Ca²⁺]_i in metaphase‐II (MII) oocytes from Grade‐3 COCs was significantly higher than those from Grade‐1 COCs, and was significantly reduced by BAPTA‐AM; (ii) nuclear maturation of oocytes from Grade‐3 COCs treated with BAPTA‐AM was enhanced compared to untreated COCs; (iii) protein abundance of Cyclin B and oocyte‐specific Histone 1 (H1FOO) was improved in MII oocytes from Grade‐3 COCs treated with BAPTA‐AM; (iv) Ca²⁺ transients were triggered in each group upon fertilization, and the amplitude of [Ca²⁺]_i oscillations increased in the Grade‐3 group upon treatment with BAPTA‐AM, with the magnitude approaching that of the Grade‐1 group; and (v) cleavage rates and blastocyst‐formation rates were improved in the Grade‐3 group treated with BAPTA‐AM compared to untreated controls following in vitro fertilization and parthenogenetic activation. Therefore, BAPTA‐AM dramatically improved oocyte maturation, oocyte quality, and embryonic development of oocytes from Grade‐3 COCs.     

Tim‐2 is the receptor for H‐ferritin on oligodendrocytes

Oligodendrocytes stain more strongly for iron than any other cell in the CNS, and they require iron for the production of myelin. For most cell types transferrin is the major iron delivery protein, yet neither transferrin receptor protein nor mRNA are detectable in mature oligodendrocytes. Thus an alternative iron delivery mechanism must exist. Given the significant long term consequences of developmental iron deficiency and the iron requirements for normal myelination, identification of the iron delivery mechanism for oligodendrocytes is important. Previously we have reported that oligodendrocytes bind H‐ferritin and that H‐ferritin binds to white matter tracts in vivo. Recently, T cell immunoglobulin and mucin domain‐containing protein‐2 (Tim‐2) was shown to bind and internalize H‐ferritin. In the present study we show that Tim‐2 is expressed on oligodendrocytes both in vivo and in vitro. Further, the onset of saturable H‐ferritin binding in CG4 oligodendrocyte cell line is accompanied by Tim‐2 expression. Application of a blocking antibody to the extracellular domain of Tim‐2 significantly reduces H‐ferritin binding to the differentiated CG4 cells and primary oligodendrocytes. Tim‐2 expression on CG4 cells is responsive to iron; decreasing with iron loading and increasing with iron chelation. Taken together, these data provide compelling evidence that Tim‐2 is the H‐ferritin receptor on oligodendrocytes suggesting it is the primary mechanism for iron acquisition by these cells.     

Regulation of basal and oxidative stress‐triggered jasmonic acid‐related gene expression by glutathione

Glutathione is a determinant of cellular redox state with roles in defence and detoxification. Emerging concepts suggest that this compound also has functions in cellular signalling. Here, we report evidence that glutathione plays potentially important roles in setting signalling strength through the jasmonic acid (JA) pathway. Firstly, we show that basal expression of JA‐related genes is correlated with leaf glutathione content when the latter is manipulated either genetically or pharmacologically. Secondly, analyses of an oxidative stress signalling mutant, cat2, reveal that up‐regulation of the JA pathway triggered by intracellular oxidation requires accompanying glutathione accumulation. Genetically blocking this accumulation in a cat2 cad2 line largely annuls H₂O₂‐induced expression of JA‐linked genes, and this effect can be rescued by exogenously supplying glutathione. While most attention on glutathione functions in biotic stress responses has been focused on the thiol‐regulated protein NPR1, a comparison of JA‐linked gene expression in cat2 cad2 and cat2 npr1 double mutants provides evidence that glutathione acts through other components to regulate the response of this pathway to oxidative stress. Our study provides new information implicating glutathione as a factor determining basal JA gene expression and suggests novel glutathione‐dependent control points that regulate JA signalling in response to intracellular oxidation.     

3D Graphene‐Based H2‐Production Photocatalyst and Electrocatalyst

Hydrogen (H₂) has been deemed as the most promising and valuable alternative to nonrenewable fossil fuels. Photocatalytic and electrocatalytic water splitting are considered to be the most efficient and environmentally friendly approaches for the sustainable H₂ evolution reaction (HER). Graphene with a 3D framework has been utilized for the HER due to its unique structure and properties, including its hierarchical network, large specific surface area, diverse pore distribution, outstanding light absorption ability, and excellent electrical conductivity. The large specific surface area and hierarchically porous structure of 3D graphene can not only maximize the exposure of active sites but also promote electron transfer and gas product diffusion. In addition, the free‐standing 3D graphene monolith is easily recycled compared with powder phase support, which can prevent the loss of active catalysts. By making full use of the aforementioned merits, 3D graphene‐based composite materials show great promise as high‐performance catalysts toward photocatalytic and electrocatalytic HER. In this review, recent advances in fabricating 3D graphene‐based composite materials and their applications in both photocatalytic and electrocatalytic HER are summarized and discussed. Furthermore, the current challenges and future vision associated with the design, fabrication, and integration of 3D graphene‐based composite materials toward HER are put forward.     

Leaf‐Mosaic‐Inspired Vine‐Like Graphitic Carbon Nitride Showing High Light Absorption and Efficient Photocatalytic Hydrogen Evolution

Green plants use solar energy efficiently in nature. Simulating the exquisite structure of a natural photosynthesis system may open a new approach for the construction of desirable photocatalysts with high light harvesting efficiency and performance. Herein, inspired by the excellent light utilization of “leaf mosaic” in plants, a novel vine‐like g‐C₃N₄ (V‐CN) is synthesized for the first time by copolymerizing urea with dicyandiamide‐formaldehyde (DF) resin. The as‐prepared V‐CN exhibits ultrahigh photocatalytic hydrogen production of 13.6 mmol g^?1 h^?1 under visible light and an apparent quantum yield of 12.7% at 420 nm, which is ≈38 times higher than that of traditional g‐C₃N₄, representing one of the highest‐activity g‐C₃N₄‐based photocatalysts. This super photocatalytic performance is derived from the unique leaf mosaic structure of V‐CN, which effectively improves its light utilization and affords a larger specific surface area. In addition, the introduction of DF resin further optimizes the energy band of V‐CN, extends its light absorption, and improves its crystallinity and interfacial charge transport, resulting in high performance. It is an easy and green strategy for the preparation of broad‐spectrum, high‐performance g‐C₃N₄, which presents significant advancement for the design of other nanophotocatalysts by simulating the fine structure of natural photosynthesis.     

The role of chlorine atom on the binding between 2‐phenyl‐1H‐benzimidazole analogues and fat mass and obesity‐associated protein

In this work, nine 2‐phenyl‐1H‐benzimidazole structural analogues were screened for potential inhibitor of the fat mass and obesity‐associated protein (FTO) by isothermal titration calorimetry (ITC). The results show that the binding between 6‐chloro‐2‐phenyl‐1H‐benzimidazole (1d) and FTO was dominated by entropy. Results of enzymatic activity assays provided an IC₅₀ value of 24.65 μM for 1d. Our previous results and comparison of nine structural analogues indicated that the chlorine atom was crucial for the binding of small molecules with FTO. The identification of novel small molecules may provide information for the design of FTO inhibitors and the treatment of leukemia.     

S‐sulfhydration of MEK1 leads to PARP‐1 activation and DNA damage repair

The repair of DNA damage is fundamental to normal cell development and replication. Hydrogen sulfide (H₂S) is a novel gasotransmitter that has been reported to protect cellular aging. Here, we show that H₂S attenuates DNA damage in human endothelial cells and fibroblasts by S‐sulfhydrating MEK1 at cysteine 341, which leads to PARP‐1 activation. H₂S‐induced MEK1 S‐sulfhydration facilitates the translocation of phosphorylated ERK1/2 into nucleus, where it activates PARP‐1 through direct interaction. Mutation of MEK1 cysteine 341 inhibits ERK phosphorylation and PARP‐1 activation. In the presence of H₂S, activated PARP‐1 recruits XRCC1 and DNA ligase III to DNA breaks to mediate DNA damage repair, and cells are protected from senescence.