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.     

Decreases in Both the Seroprevalence of Serum Antibodies and Seroprotection against Japanese Encephalitis Virus among Vaccinated Children

The incidence of Japanese encephalitis(JE) has significantly decreased in China due to JE vaccines. In this study, we investigated the post-JE vaccination seroprevalence and protection provided by vaccinated sera against Japanese encephalitis virus(JEV) to elucidate the persistence and waning of antibodies to JEV among JE-SA14-14-2-vaccinated children. A total of 300 serum samples were collected from vaccinated children aged 3–10 years in Zhaotong, Yunnan,China. The seroprevalence of anti-JEV antibodies was determined by enzyme-linked immune sorbent assay and plaque reduction neutralization test. The highest seropositivity of 82% was observed in vaccinated children during the first0.5–1.5 years after booster vaccination. Then, the seropositivity began to decline and remained lower than the original level observed in the 0.5–1.5-year group. An association was found between the waning of seroprevalence and elapsed time of the post-booster vaccination. Similarly, the neutralizing antibody(nAb) titres gradually decreased over time, and the levels showed a positive correlation with the protective efficacy in mice. This finding suggests that nAbs play an important role in the antiviral process and that the nAb titre is an adequately credible parameter for evaluating the protective efficacy induced by the JE vaccine. Our results provide data that clarify the persistence and waning of antibodies to JEV, which may help elucidate the pathogenesis of JE.     

Chromatin interacting factor OsVIL2 increases biomass and rice grain yield

Grain number is an important agronomic trait. We investigated the roles of chromatin interacting factor Oryza sativa VIN3‐LIKE 2 (OsVIL2), which controls plant biomass and yield in rice. Mutations in OsVIL2 led to shorter plants and fewer grains whereas its overexpression (OX) enhanced biomass production and grain numbers when compared with the wild type. RNA‐sequencing analyses revealed that 1958 genes were up‐regulated and 2096 genes were down‐regulated in the region of active division within the first internodes of OX plants. Chromatin immunoprecipitation analysis showed that, among the downregulated genes, OsVIL2 was directly associated with chromatins in the promoter region of CYTOKININ OXIDASE/DEHYDROGENASE2 (OsCKX2), a gene responsible for cytokinin degradation. Likewise, active cytokinin levels were increased in the OX plants. We conclude that OsVIL2 improves the production of biomass and grain by suppressing OsCKX2 chromatin.     

KIN‐4/MAST kinase promotes PTEN‐mediated longevity of Caenorhabditis elegans via binding through a PDZ domain

PDZ domain‐containing proteins (PDZ proteins) act as scaffolds for protein–protein interactions and are crucial for a variety of signal transduction processes. However, the role of PDZ proteins in organismal lifespan and aging remains poorly understood. Here, we demonstrate that KIN‐4, a PDZ domain‐containing microtubule‐associated serine‐threonine (MAST) protein kinase, is a key longevity factor acting through binding PTEN phosphatase in Caenorhabditis elegans. Through a targeted genetic screen for PDZ proteins, we find that kin‐4 is required for the long lifespan of daf‐2/insulin/IGF‐1 receptor mutants. We then show that neurons are crucial tissues for the longevity‐promoting role of kin‐4. We find that the PDZ domain of KIN‐4 binds PTEN, a key factor for the longevity of daf‐2 mutants. Moreover, the interaction between KIN‐4 and PTEN is essential for the extended lifespan of daf‐2 mutants. As many aspects of lifespan regulation in C. elegans are evolutionarily conserved, MAST family kinases may regulate aging and/or age‐related diseases in mammals through their interaction with PTEN.     

Perivascular adipose tissue‐derived stromal cells contribute to vascular remodeling during aging

Aging is an independent risk factor for vascular diseases. Perivascular adipose tissue (PVAT), an active component of the vasculature, contributes to vascular dysfunction during aging. Identification of underlying cell types and their changes during aging may provide meaningful insights regarding the clinical relevance of aging‐related vascular diseases. Here, we take advantage of single‐cell RNA sequence to characterize the resident stromal cells in the PVAT (PVASCs) and identified different clusters between young and aged PVASCs. Bioinformatics analysis revealed decreased endothelial and brown adipogenic differentiation capacities of PVASCs during aging, which contributed to neointimal hyperplasia after perivascular delivery to ligated carotid arteries. Mechanistically, in vitro and in vivo studies both suggested that aging‐induced loss of peroxisome proliferator‐activated receptor‐γ coactivator‐1 α (PGC1α) was a key regulator of decreased brown adipogenic differentiation in senescent PVASCs. We further demonstrated the existence of human PVASCs (hPVASCs) and overexpression of PGC1α improved hPVASC delivery‐induced vascular remodeling. Our finding emphasizes that differentiation capacities of PVASCs alter during aging and loss of PGC1α in aged PVASCs contributes to vascular remodeling via decreased brown adipogenic differentiation.     

Novel monoamine oxidase inhibitors based on the privileged 2-imidazoline molecular framework

Series of structurally diverse 2-imidazoline derivatives have been synthesized by condensation of substituted aldehydes with ethylenediamine, Pd-catalyzed N-arylation of 2-imidazolines and by the formation of 1,2,4-oxadiazoles and benzoxazepines from 2-imidazoline-containing precursors. The 2-imidazoline derivatives were evaluated as potential inhibitors of human monoamine oxidase (MAO) A and B. Among the 2-imidazolines, good potency inhibitors were discovered with compound 9p (IC₅₀?=?0.012?µM) being the most potent MAO-B inhibitor, while compound 9d (IC₅₀?=?0.751?µM) was the most potent MAO-A inhibitor of the series. These potencies are in the same range as those of reference MAO inhibitors used in the clinic. Among 33 compounds evaluated, 13 exhibited IC₅₀ values in the submicromolar range for the inhibition of an MAO isoform. It is postulated that the imidazoline moieties of some of these inhibitors may be recognized by the imidazoline I₂-binding site of MAO. Good potency MAO inhibitors may be useful for the treatment of neuropsychiatric and neurodegenerative disorders such as depression and Parkinson’s disease, and future application for the treatment of prostate cancer, congestive heart failure and Alzheimer’s disease. In addition, high potency 2-imidazoline-derived MAO inhibitors may be used as potential probes for the imidazoline binding sites of the MAOs, as well as to determine alternative binding regions of imidazoline within the MAO active site.