Three pairs of weak interactions precisely regulate the G‐loop gate of Kir2.1 channel

Kir2.1 (also known as IRK1) plays key roles in regulation of resting membrane potential and cell excitability. To achieve its physiological roles, Kir2.1 performs a series of conformational transition, named as gating. However, the structural basis of gating is still obscure. Here, we combined site‐directed mutation, two‐electrode voltage clamp with molecular dynamics simulations and determined that H221 regulates the gating process of Kir2.1 by involving a weak interaction network. Our data show that the H221R mutant accelerates the rundown kinetics and decelerates the reactivation kinetics of Kir2.1. Compared with the WT channel, the H221R mutation strengthens the interaction between the CD‐ and G‐loops (E303‐R221) which stabilizes the close state of the G‐loop gate and weakens the interactions between C‐linker and CD‐loop (R221‐R189) and the adjacent G‐loops (E303‐R312) which destabilizes the open state of G‐loop gate. Our data indicate that the three pairs of interactions (E303‐H221, H221‐R189 and E303‐R312) precisely regulate the G‐loop gate by controlling the conformation of G‐loop. Proteins 2016; 84:1929–1937. © 2016 Wiley Periodicals, Inc.     

Insights into IL‐29: Emerging role in inflammatory autoimmune diseases

Interleukin‐29 (IL‐29) is a newly discovered member of type III interferon. It mediates signal transduction via binding to its receptor complex and activates downstream signalling pathways, and therefore induces the generation of inflammatory components. Recent studies reported that expression of IL‐29 is dysregulated in inflammatory autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, Sjögren's syndrome, psoriasis and systemic sclerosis. Furthermore, functional analysis revealed that IL‐29 may involve in the pathogenesis of the inflammatory autoimmune disorders. In this review, we will systematically review the current knowledge about IL‐29. The information collected revealed the regulatory role of IL‐29 and may give important implications for its potential in clinical treatment.     

Nicorandil alleviates apoptosis in diabetic cardiomyopathy through PI3K/Akt pathway

Nicorandil exerts myocardial protection through its antihypoxia and antioxidant effects. Here, we investigated whether it plays an anti‐apoptotic role in diabetic cardiomyopathy. Sprague‐Dawley rats were fed with high‐fat diet; then single intraperitoneal injection of streptozotocin was performed. Rats with fasting blood glucose (FBG) higher than 11.1 mmol/L were selected as models. Eight weeks after the models were built, rats were treated with nicorandil (7.5 mg/kg day and 15 mg/kg day respectively) for 4 weeks. H9c2 cardiomyocytes were treated with nicorandil and then stimulated with high glucose (33.3 mmol/L). TUNEL assay and level of bcl‐2, bax and caspase‐3 were measured. 5‐HD was used to inhibit nicorandil. Also, PI3K inhibitor (Miltefosine) and mTOR inhibitor (rapamycin) were used to inhibit PI3K/Akt pathway. The results revealed that nicorandil (both 7.5 mg/kg day and 15mg/kg day) treatment can increase the level of NO in the serum and eNOS in the heart of diabetic rats compared with the untreated diabetic group. Nicorandil can also improve relieve cardiac dysfunction and reduce the level of apoptosis. In vitro experiments, nicorandil (100 µmol) can attenuate the level of apoptosis stimulated by high glucose significantly in H9C2 cardiomyocyte compared with the untreated group. The effect of nicorandil on apoptosis was blocked by 5‐HD, and it was accompanied with inhibition of the phosphorylation of PI3K, Akt, eNOS, and mTOR. After inhibition of PI3K/Akt pathway, the protective effect of nicorandil is restrained. These results verified that as a NO donor, nicorandil can also inhibit apoptosis in diabetic cardiomyopathy which is mediated by PI3K/Akt pathway.     

LncRNA DUXAP9‐206 directly binds with Cbl‐b to augment EGFR signaling and promotes non‐small cell lung cancer progression

Long noncoding RNAs (lncRNAs) are involved in the pathology of various tumours, including non‐small cell lung cancer (NSCLC). However, the underlying molecular mechanisms of their specific association with NSCLC have not been fully elucidated. Here, we report that a cytoplasmic lncRNA, DUXAP9‐206 is overexpressed in NSCLC cells and closely related to NSCLC clinical features and poor patient survival. We reveal that DUXAP9‐206 induced NSCLC cell proliferation and metastasis by directly interacting with Cbl‐b, an E3 ubiquitin ligase, and reducing the degradation of epidermal growth factor receptor (EGFR) and thereby augmenting EGFR signaling in NSCLC. Notably, correlations between DUXAP9‐206 and activated EGFR signaling were also validated in NSCLC patient specimens. Collectively, our findings reveal the novel molecular mechanisms of DUXAP9‐206 in mediating the progression of NSCLC and DUXAP9‐206 may serve as a potential target for NSCLC therapy.     

One‐Step Controllable Synthesis of Catalytic Ni4Mo/MoOx/Cu Nanointerfaces for Highly Efficient Water Reduction

Currently, in addition to the electroactive non‐noble metal water‐splitting electrocatalysts, a scalable synthetic route and simple activity enhancement strategy is also urgently needed. In particular, the well‐controlled synthesis of the well‐recognized metal–metal nanointer face in a single step remains a key challenge. Here, the synthesis of Cu‐supported Ni₄Mo nanodots on MoO_x nanosheets (Ni₄Mo/MoO_x) with controllable Ni₄Mo particle size and d‐band structure is reported via a facile one‐step electrodeposition process. Density functional theory (DFT) calculations reveal that the active open‐shell effect from Ni‐3d‐band optimizes the electronic configuration. The Cu‐substrate enables the surface Ni–Mo alloy dots to be more electron‐rich, forming a local connected electron‐rich network, which boosts the charge transfer for effective binding of O‐related species and proton–electron charge exchange in the hydrogen evolution reaction. The Cu‐supported Ni₄Mo/MoO_x shows an ultralow overpotential of 16 mV at a current density of 10 mA cm^?2 in 1 m KOH, demonstrating the smallest overpotential, at loadings as low as 0.27 mg cm^?2, among all non‐noble metal catalysts reported to date. Moreover, an overpotential of 105 mV allows it to achieve a current density of 250 mA cm^?2 in 70 °C 30% KOH, a remarkable performance for alkaline hydrogen evolution with competitive potential for applications.     

Enhancing the Open‐Circuit Voltage of Perovskite Solar Cells by up to 120 mV Using π‐Extended Phosphoniumfluorene Electrolytes as Hole Blocking Layers

Four π‐extended phosphoniumfluorene electrolytes (π‐PFEs) are introduced as hole‐blocking layers (HBL) in inverted architecture planar perovskite solar cells with the structure of ITO/PEDOT:PSS/MAPbI₃/PCBM/HBL/Ag. The deep‐lying highest occupied molecular orbital energy level of the π‐PFEs effectively blocks holes, decreasing contact recombination. It is demonstrated that the incorporation of π‐PFEs introduces a dipole moment at the PCBM/Ag interface, resulting in significant enhancement of the built‐in potential of the device. This enhancement results in an increase in the open‐circuit voltage of the device by up to 120 mV, when compared to the commonly used bathocuproine HBL. The results are confirmed both experimentally and by numerical simulation. This work demonstrates that interfacial engineering of the transport layer/contact interface by small molecule electrolytes is a promising route to suppress nonradiative recombination in perovskite devices and compensates for a nonideal energetic alignment at the hole‐transport layer/perovskite interface.     

Same but different–Scale up and numbering up in electrobiotechnology and photobiotechnology

Facing energy problems, there is a strong demand for new technologies dealing with the replacement of fossil fuels. The emerging fields of biotechnology, photobiotechnology and electrobiotechnology, offer solutions for the production of fuels, energy, or chemicals using renewable energy sources (light or electrical current e.g. produced by wind or solar power) or organic (waste) substrates. From an engineering point of view both technologies have analogies and some similar challenges, since both light and electron transfer are primarily surface‐dependent. In contrast to that, bioproduction processes are typically volume dependent. To allow large scale and industrially relevant applications of photobiotechnology and electrobiotechnology, this opinion first gives an overview over the current scales reached in these areas. We then try to point out the challenges and possible methods for the scale up or numbering up of the reactors used. It is shown that the field of photobiotechnology is by now much more advanced than electrobiotechnology and has achieved industrial applications in some cases. We argue that transferring knowledge from photobiotechnology to electrobiotechnology can speed up the development of the emerging field of electrobiotechnology. We believe that a combination of scale up and numbering up, as it has been shown for several photobiotechnological reactors, may well lead to industrially relevant scales in electrobiotechnological processes allowing an industrial application of the technology in near future.