Circular RNAs (circRNA) are a class of covalently closed single-stranded RNAs that have been implicated in cancer progression. Here we identify circNDUFB2 to be downregulated in non-small cell lung cancer (NSCLC) tissues, and to negatively correlate with NSCLC malignant features. Elevated circNDUFB2 inhibits growth and metastasis of NSCLC cells. Mechanistically, circNDUFB2 functions as a scaffold to enhance the interaction between TRIM25 and IGF2BPs, a positive regulator of tumor progression and metastasis. This TRIM25/circNDUFB2/IGF2BPs ternary complex facilitates ubiquitination and degradation of IGF2BPs, with this effect enhanced by N6-methyladenosine (m6A) modification of circNDUFB2. Moreover, circNDUFB2 is also recognized by RIG-I to activate RIG-I-MAVS signaling cascades and recruit immune cells into the tumor microenvironment (TME). Our data thus provide evidences that circNDUFB2 participates in the degradation of IGF2BPs and activation of anti-tumor immunity during NSCLC progression via the modulation of both protein ubiquitination and degradation, as well as cellular immune responses.

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Two-step nucleation pathways in which disordered, amorphous, or dense liquid states precede the appearance of crystalline phases have been reported for a wide range of materials, but the dynamics of such pathways are poorly understood. Moreover, whether these pathways are general features of crystallizing systems or a consequence of system-specific structural details that select for direct versus two-step processes is unknown. Using atomic force microscopy to directly observe crystallization of sequence-defined polymers, we show that crystallization pathways are indeed sequence dependent. When a short hydrophobic region is added to a sequence that directly forms crystalline particles, crystallization instead follows a two-step pathway that begins with the creation of disordered clusters of 10-20 molecules and is characterized by highly non-linear crystallization kinetics in which clusters transform into ordered structures that then enter the growth phase. The results shed new light on non-classical crystallization mechanisms and have implications for the design of self-assembling polymer systems.

BACKGROUND Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. Advanced AMD is comprised of geographic atrophy (GA) and choroidal neovascularization (CNV). Specific genetic variants that predispose for GA are largely unknown. METHODS We tested (i) for association between the functional toll-like receptor-3 (TLR3) variant rs3775291 (L412F) and AMD in European Americans and (ii) the effect of TLR3 L and F variants on the viability of human retinal pigment epithelium (RPE) cells in vitro and on RPE cell apoptosis in wildtype and Tlr3−/− mice. RESULTS The F variant (or T allele at single nucleotide polymorphism at rs3775291) was associated with protection against GA (P=0.005); this association was replicated in two independent GA case-control series (P=5.43×10−4 and P=0.002, respectively. We observed no association between TLR3 variants and CNV. The rs377291 variant is probably critical to the function of TLR3, because a prototypic TLR3 ligand induced cell death and apoptosis in human RPE cells with the LL genotype to a greater extent than it did RPE cells with the LF genotype. Moreover, the ligand induced more RPE cell death and apoptosis in wild-type than in Tlr3−/− mice. CONCLUSIONS The TLR3 412F variant confers protection against GA, probably by suppressing RPE cell death. Given that double stranded RNA can activate TLR3-mediated apoptosis, our results suggest a possible role for viral dsRNA transcripts in the development of GA and raise awareness of potential toxicity induced by short interfering RNA (siRNA) therapeutics in the eye.

Metal zinc, with the advantages of low cost, low redox potential, and high capacity, is an ideal anode for aqueous zinc-ion batteries. Nonetheless, the inferior plating/stripping Coulombic efficiency and poor reversibility hinder its practical applications. To address the drawbacks, the zinc nucleation overpotential of different substrates is systematically investigated in asymmetric cells for the first time to confirm the suitable substrate with highly reversible plating/stripping behavior. As a result, Cu foam presents the low zinc nucleation overpotential of 65.2 mV and superior plating/stripping Coulombic efficiency close to 100%. Meanwhile, Cu foam is optimized as the carrier for the deposition of metallic zinc and the preparation of the Zn@Cu foam anode through the electrochemical deposition method. Besides, the Zn@Cu foam anode holds the low initial polarization voltage and stable voltage hysteresis profile with negligible voltage polarization in the symmetric cell. Furthermore, coupled with the β-MnO2 cathode, it could exhibit an outstanding cycling ability with a capacity of 172.8 mA h g–1 after 600 cycles at 1 A g–1 in the full cell, corresponding to an extremely low decay rate of 0.0218% per cycle.

The exploitation of cathode materials with high capacity as well as high operating voltage is extremely important for the development of aqueous zinc‐ion batteries (ZIBs). Yet, the classical high‐capacity materials (e.g., vanadium‐based materials) provide a low discharge voltage, while organic cathodes with high operating voltage generally suffer from a low capacity. In this work, organic (ethylenediamine)–inorganic (vanadium oxide) hybrid cathodes, that is, EDA‐VO, with a dual energy‐storage mechanism, are designed for ultrahigh‐rate and ultralong‐life ZIBs. The embedded ethylenediamine (EDA) can not only increase the layer spacing of the vanadium oxide, with improved mobility of Zn ions in the V–O layered structure, but also act as a bidentate chelating ligand participating in the storage of Zn ions. This hybrid provides a high specific capacity (382.6 mA h g−1 at 0.5 A g−1), elevated voltage (0.82 V) and excellent long‐term cycle stability (over 10 000 cycles at 5 A g−1). Assistant density functional theory (DFT) calculations indicate the cathode has remarkable electronic conductivity, with an ultralow diffusion barrier of 0.78 eV for an optimal Zn‐ion diffusion path in the EDA‐VO. This interesting idea of building organic–inorganic hybrid cathode materials with a dual energy‐storage mechanism opens a new research direction toward high‐energy secondary batteries.

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To colonize surfaces, the bacterium Caulobacter crescentus employs a polar polysaccharide, the holdfast, located at the end of a thin, long stalk protruding from the cell body. Unlike many other bacteria which adhere through an extended extracellular polymeric network, the holdfast footprint area is tens of thousands times smaller than that of the total bacterium cross-sectional surface, making for some very demanding adhesion requirements. At present, the mechanism of holdfast adhesion remains poorly understood. We explore it here along three lines of investigation: a) the impact of environmental conditions on holdfast binding affinity, b) adhesion kinetics by dynamic force spectroscopy, and c) kinetic modeling of the attachment process to interpret the observed time-dependence of the adhesion force at short and long time scales. A picture emerged in which discrete molecular units called adhesins are responsible for initial holdfast adhesion, by acting in a cooperative manner.