The glomerular filtration barrier in the kidney is formed in part by a specialized intercellular junction known as the slit diaphragm, which connects adjacent actin-based foot processes of kidney epithelial cells (podocytes). Mutations affecting a number of slit diaphragm proteins, including nephrin (encoded by NPHS1), lead to renal disease owing to disruption of the filtration barrier and rearrangement of the actin cytoskeleton, although the molecular basis for this is unclear. Here we show that nephrin selectively binds the Src homology 2 (SH2)/SH3 domain-containing Nck adaptor proteins, which in turn control the podocyte cytoskeleton in vivo. The cytoplasmic tail of nephrin has multiple YDxV sites that form preferred binding motifs for the Nck SH2 domain once phosphorylated by Src-family kinases. We show that this Nck-nephrin interaction is required for nephrin-dependent actin reorganization. Selective deletion of Nck from podocytes of transgenic mice results in defects in the formation of foot processes and in congenital nephrotic syndrome. Together, these findings identify a physiological signalling pathway in which nephrin is linked through phosphotyrosine-based interactions to Nck adaptors, and thus to the underlying actin cytoskeleton in podocytes. Simple and widely expressed SH2/SH3 adaptor proteins can therefore direct the formation of a specialized cellular morphology in vivo.

The controlled exfoliation of hexagonal boron nitride (h-BN) into single- or few-layered nanosheets remains a grand challenge and becomes the bottleneck to essential studies and applications of h-BN. Here, we present an efficient strategy for the scalable synthesis of few-layered h-BN nanosheets (BNNS) using a novel gas exfoliation of bulk h-BN in liquid N2 (L-N2 ). The essence of this strategy lies in the combination of a high temperature triggered expansion of bulk h-BN and the cryogenic L-N2 gasification to exfoliate the h-BN. The produced BNNS after ten cycles (BNNS-10) consisted primarily of fewer than five atomic layers with a high mass yield of 16-20 %. N2 sorption and desorption isotherms show that the BNNS-10 exhibited a much higher specific surface area of 278 m(2)  g(-1) than that of bulk BN (10 m(2)  g(-1) ). Through the investigation of the exfoliated intermediates combined with a theoretical calculation, we found that the huge temperature variation initiates the expansion and curling of the bulk h-BN. Subseqently, the L-N2 penetrates into the interlayers of h-BN along the curling edge, followed by an immediate drastic gasification of L-N2 , further peeling off h-BN. This novel gas exfoliation of high surface area BNNS not only opens up potential opportunities for wide applications, but also can be extended to produce other layered materials in high yields.

Abstract. Visceral glomerular epithelial cells (GEC) are critical for normal permselectivity of the kidney. Nephrin is a molecule that is expressed specifically in GEC in a structure called the slit diaphragm and is required for normal morphology and permselectivity of GEC. However, the mechanisms of action of nephrin are not understood precisely. The intracellular domain of nephrin has six conserved tyrosine residues. It was hypothesized that these tyrosine residues are phosphorylated by Srcfamily kinases and that this phosphorylation modulates the function of nephrin. A transient transfection system was used to study the role of tyrosine phosphorylation of the cytoplasmic domain of nephrin in its function. When nephrin was cotransfected with Src-family kinases Fyn or Src in Cos-1 cells, nephrin was strongly tyrosine phosphorylated by Fyn and less so by Src. The results with tyrosine-to-phenylalanine mutations suggested that multiple tyrosine residues contribute to phosphorylation mediated by Src-family kinases. The intracellular domain of nephrin is known to interact with another slit diaphragm protein, podocin. When nephrin and podocin were transfected with Fyn, the interaction between nephrin and podocin was augmented significantly. Podocin was not tyrosine phosphorylated by Fyn; thus, the increased interaction is likely to be secondary to tyrosine phosphorylation of nephrin. Fyn also significantly augmented the activation of the AP-1 promoter induced by nephrin and podocin. In summary, Fyn phosphorylates the cytoplasmic domain of nephrin on tyrosine, leading to enhanced association with podocin and downstream signaling of nephrin.

Lithium–sulfur (Li–S) batteries are strong contenders among lithium batteries due to superior capacity and energy density, but the polysulfide shuttling effect limits the cycle life and reduces energy efficiency due to a voltage gap between charge and discharge. Here, we demonstrate that graphene foam impregnated with single-atom catalysts (SACs) can be coated on a commercial polypropylene separator to catalyze polysulfide conversion, leading to a reduced voltage gap and a much improved cycle life. Also, among Fe/Co/Ni SACs, Fe SACs may be a better option to be used in Li–S systems. By deploying SACs in the battery separator, cycling stability improves hugely, especially considering relatively high sulfur loading and ultralow SAC contents. Even at a metal loading of ∼2 μg in the whole cell, an Fe SAC-modified separator delivers superior Li–S battery performance even at high sulfur loading (891.6 mAh g–1, 83.7% retention after 750 cycles at 0.5C). Our work further enriches and expands the application of SACs catalyzing polysulfide blocking and conversion and improving round trip efficiencies in batteries, without side effects such as electrolyte and electrode decomposition.

One-pot extraction combined with the metal-free photochemical aerobic oxidative deep-desulfurization of fuels in deep eutectic solvents was successfully achieved.

15-Deoxy-Δ12,14-PDJ2 (15d-PGJ2) is a degradation product of PGD2 that has been proposed as an anti-inflammatory compound because of its various inhibitory effects, some of which are mediated by peroxisome proliferator-activated receptor-γ. In contrast to its reported inhibitory effects on macrophages and other cells, we found that this compound is a potent activator of eosinophils, inducing calcium mobilization, actin polymerization, and CD11b expression. It is selective for eosinophils, having little or no effect on neutrophils or monocytes. 15d-PGJ2 has an EC50 of ∼10 nM, similar to that of its precursor, PGD2. The concentrations of 15d-PGJ2 required to activate eosinophils are thus much lower than those required for its anti-inflammatory effects (usually micromolar). 15-Deoxy-Δ12,14-prostaglandin D2 (15d-PGD2) is also a potent activator of eosinophils, with an EC50 about the same as that of PGD2, whereas Δ12-PGJ2 is slightly less potent. Eosinophils pretreated with PGD2 no longer respond to 15d-PGJ2, and vice versa, but in both cases the cells still respond to another eicosanoid proinflammatory mediator, 5-oxo-6,8,11,14-eicosatetraenoic acid. This indicates that the effects of 15d-PGJ2 are mediated by the DP2/chemoattractant receptor-homologous molecule expressed on Th2 cells that has recently been identified in eosinophils. 15d-PGJ2 is selective for the DP2 receptor, in that it has no effect on DP1 receptor-mediated adenylyl cyclase activity in platelets. We conclude that 15d-PGJ2 and 15d-PGD2 are selective DP2 receptor agonists that activate human eosinophils with potencies at least 100 times greater than those for the proposed anti-inflammatory effects of 15d-PGJ2 on other cells.

Metal-free graphene-like boron nitride (BN) samples were prepared and applied as adsorbents for removing dibenzothiophene (DBT) in model oil. The results showed that the graphene-like BN exhibited a remarkable adsorption performance. The adsorption capacity could reach 28.17 mg S g −1 adsorbent. Experiments have been carried out to investigate the effects of the number of BN layers, DBT initial concentration, and temperature on DBT adsorption. Langmuir and Freundlich isotherm models were used to study the adsorption of DBT on BN. The kinetic results showed that the adsorption process was best described by the pseudosecond-order kinetic model. Density functional theory (DFT) was employed to prove that the Lewis acidbase interaction plays an important role in removing DBT over graphene-like BN.

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